Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and Stage II Classical Hodgkin Lymphoma (HL)
Phase: PHASE2
Conditions: Lymphoma
Sponsor: Alliance for Clinical Trials in Oncology



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P H A S E II T RI A L O F R E S P O N S E - AD A P T E D T H E R A P Y B A S E D O N P O SI T R O N E MI S SI O N T O M O G R A P H Y 
( P E T) F O R B U L K Y S T A G E I A N D S T A G E II C L A S SI C A L H O D G KI N L Y M P H O M A  
Sc he m a 
 
Eli gi bilit y Criteri a  
I niti al Re q uire d L a b or at or y V al ues 
Hist ol o gicall y  d oc u me nte d  sta ge  I A,  I B,  II A,  II B  classical 
H o d g ki n l y m p h o ma.  
A N C  
≥ 1 0 0 0/ µ L  
N o d ular  l y m p h oc yte  pre d o mi na nt  H o d g ki n  l y m p h o ma  is 
e xcl u de d. 
Platelet C o u nt  
≥ 1 0 0, 0 0 0/ µ L  
Mass > 1 0 c m or > 0. 3 3 ma xi m u m i ntrat h oracic dia meter (see 
Secti o n 4. 1. 2 ). 
Ser u m Creati ni ne  
≤ 2 m g/ d L  
N o c urre ntl y acti ve sec o n d mali g na nc y ot her t ha n n o n - 
   mela n o ma s ki n  ca ncers.  
Bilir u bi n 1 
≤ 2 x U L N  
A S T  
≤ 2 x U L N  
N o pri or treat me nt f or H o d g ki n l y m p h o ma , a part fr o m o ne 
    c ycle of A B V D (see Secti o n 4. 3 ). 
 
 
E C O G P erf or ma nce Stat us 0 -2.  
 
L V E F b y E C H O or M U G A wit h i n i nstit uti o nal n or mal li mits.2  
D L C O ≥ 6 0 % wit h n o s y m pt o matic p ul m o nar y disease. 2 
 
Patie nts wit h k n o w n HI V m ust ha ve a C D 4 c o u nt >  3 5 0  a n d 
    be o n c o nc urre nt a ntiretr o virals.  
 
 
N o n -pre g na nt a n d n o n -n ursi n g.  
1I n t he a bse nce of Gil bert’s disease 
A ge 1 8 -6 0 years.  
 2U nless t h o u g ht t o be disease relate d  
 
Acc ess t o F D G-P E T/ C T  is a re q uire me nt f or i nstit uti o ns e nr olli n g p atie nts o n t his pr ot oc ol. I nstit uti o ns 
m ust be cre de nti ale d by t he Alli a nce  I m a gi n g C ore L a b at I R O C O hi o pri or t o e nr olli n g p atie nts (see 
Secti o n 8. 1. 1 ). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I F R T (see Secti o n 7. 2)  
P E T/ C T sca n a n d Ce C T sca n  
( Ce C T li mite d t o i n v ol ve d sites at b aseli n e) * 
A B V D x 2 c ycles  
 
A B V D x 4 c ycles  
(t otal of 6 c ycles) 
Escalate d B E A C O P P * * ( x 4 c ycl es) 
 
F oll o w -U p †  
 
R E GI S T R A TI O N  
 
C R, P R, S D: P E T –  
( Secti o n 7. 3. 1 ) 
 
C R, P R, S D: P E T +  
 
 
 
C R, P R, S D: P E T –  
 
C R, P R, S D: P E T +  
 
P E T/ C T sca n,  
C T sca n (li mite d t o i n v ol ve d site at b aseli n e) *  
 
A B V D Tre at me nt  
C ycle = 2 8 d a ys  
Escalate d B E A C O P P 
Treat me nt * *  
C ycle = 2 1 d a ys  
Bi o ps y ‡ 
P ositi ve  
Bi o ps y ‡ 
Ne gati v e  
Bi o ps y 
Deferre d ‡  
See Secti o n 
1 4. 1. 2  
F oll o w -U p †  
 
P E T/ C T 
sca n¥  
 
See Secti o ns 7. 3. 1  a n d 7. 3. 2.  
 

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* 
If t he P E T/ C T sca n was perf or me d pri or t o c o ntrast-e n ha nce d C T ( Ce C T) a n d s h o ws disease c o nfi ne d 
t o a s pecific a nat o mic l ocati o n/s (e. g. nec k, c hest, a b d o me n, pel vis), Ce C T after t w o c ycles of A B V D 
a n d at e n d of treat me nt ca n be li mite d t o t he i n v ol ve d a nat o mic l ocati o n.  
* * F or  HI V  p ositi ve  patie nts,  sta n dar d  B E A C O P P  will  be  use d  i nstea d  of  escalate d  B E A C O P P  (see 
Secti o n 7. 1. 3 ). 
†  F oll o w- u p acc or di n g t o t he p ost- treat me nt sc he d ule i n Secti o n 6. 0 . 
‡ 
Bi o ps y ma y be perf or me d if me dicall y necessar y at t he discreti o n of t he treati n g p h ysicia n. If bi o ps y is 
neit her cli nicall y i n dicate d n or me dicall y a p pr o priate, t he n patie nt s h o ul d u n der g o a re peat P E T/ C T 
t hree m o nt hs l ater as n ote d i n t he f o ot n ote ( ¥) bel o w. 
¥ 
If bi o ps y is neit her cli nicall y feasi ble n or a p pr o priate, t he n re peat P E T/ C T s h o ul d be o btai ne d 3 m o nt hs 
later (see Secti o n  7. 3. 2 ). 
 

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T A B L E O F C O N T E N T S  
 
S E C TI O N  
P A G E  
1. 0  
I N T R O D U C TI O N ........................................................................................................................... 9 
1. 1  
T R E A T M E N T O F B U L K Y E A R L Y  S T A G E H O D G KI N L Y M P H O M A  .................................................... 9 
1. 2  
R O L E O F P E T  S C A N NI N G I N H O D G KI N L Y M P H O M A  ..................................................................... 9 
1. 3  
B E A C O P P  I N H O D G KI N L Y M P H O M A  ......................................................................................... 1 0 
1. 4  
R A TI O N A L E F O R I F R T D O S E  ....................................................................................................... 1 0 
1. 5  
R A TI O N A L E F O R C U R R E N T S T U D Y  .............................................................................................. 1 2 
1. 6  
IN C L U SI O N O F W O M E N &  M I N O RI TI E S ....................................................................................... 1 2 
2. 0  
O B J E C TI V E S  ............................................................................................................................... 1 3 
2. 1  
P RI M A R Y O BJ E C TI V E  .................................................................................................................. 1 3 
2. 2  
S E C O N D A R Y O BJ E C TI V E S  ............................................................................................................ 1 3 
3. 0  
O N -S T U D Y G UI D E LI N E S  .......................................................................................................... 1 4 
4. 0  
E LI GI BI LI T Y C RI T E RI A  .......................................................................................................... 1 4 
4. 1  
D O C U M E N T A TI O N O F D I S E A S E .................................................................................................... 1 4 
4. 2  
S E C O N D M A LI G N A N C Y  ............................................................................................................... 1 4 
4. 3  
P RI O R T H E R A P Y  .......................................................................................................................... 1 4 
4. 4  
E C O G  P E R F O R M A N C E  ................................................................................................................ 1 5 
4. 5  
L V E F  A N D D L C O  ....................................................................................................................... 1 5 
4. 6  
HI V  IN F E C TI O N  ........................................................................................................................... 1 5 
4. 7  
P R E G N A N C Y R E S T RI C TI O N S  ........................................................................................................ 1 5 
4. 8  
A G E R E S T RI CI TI O N S  .................................................................................................................... 1 5 
4. 9  
INI TI A L R E Q UI R E D L A B O R A T O R Y D A T A : ................................................................................... 1 5 
5. 0  
R E GI S T R A TI O N, D A T A S U B MI S SI O N, HI S T O L O GI C R E VI E W, A N D C O R R E L A TI V E 
S CI E N C E S A M P L E P R O C U R E M E N T A N D S U B MI S SI O N ............................................................. 1 6  
5. 1  
R E GI S T R A TI O N  ............................................................................................................................ 1 6 
5. 2  
D A T A S U B MI S SI O N  ...................................................................................................................... 1 9 
5. 3  
H I S T O L O GI C R E VI E W  .................................................................................................................. 2 2 
5. 4  
C O R R E L A TI V E S CI E N C E S A M P L E S U B MI S SI O N ............................................................................ 2 3 
6. 0  
R E Q UI R E D D A T A  ....................................................................................................................... 2 8 
7. 0  
T R E A T M E N T P L A N  ................................................................................................................... 3 0 
7. 1  
C H E M O T H E R A P Y R E GI M E N S  ....................................................................................................... 3 0 
7. 2  
IN V O L V E D - FI E L D R A DI A TI O N T H E R A P Y (I F R T) ......................................................................... 3 1 
7. 3  
T R E A T M E N T D U R A TI O N A N D S T A GI N G ....................................................................................... 3 6 
8. 0  
I M A GI N G ...................................................................................................................................... 3 7 
8. 1  
IN S TI T U TI O N C R E D E N TI A LI N G P R O C E D U R E S F O R F D G -P E T/ C T  IM A GI N G  ................................ 3 7 
8. 2  
P E T/ C T  IM A GI N G T I M E LI N E S ..................................................................................................... 3 9 
8. 3  
C T  D A T A A C Q UI SI TI O N  ............................................................................................................... 4 0 
8. 4  
P E T/ C T  D A T A A C Q UI SI TI O N  ...................................................................................................... 4 0 
8. 5  
E V A L U A TI O N O F P E T/ C T  D A T A  ................................................................................................. 4 2 
8. 6  
P RI M A R Y O BJ E C TI V E / EN D P OI N T : D E FI NI TI O N O F R E S P O N S E B Y M E T A B O LI C C RI T E RI A  ........... 4 3 
8. 7  
S E C O N D A R Y O BJ E C TI V E S / EN D P OI N T S  ........................................................................................ 4 3 
8. 8  
P O S T - TH E R A P Y F O L L O W - UP O F T U M O R S  ................................................................................... 4 4 
8. 9  
P E T  A N D C T  D A T A S U B MI S SI O N  ................................................................................................ 4 4 

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9. 0  
D O S E M O DI FI C A TI O N S A N D M A N A G E M E N T O F T O X I CI T Y ....................................... 4 5 
9. 1  
D O S E M O DI FI C A TI O N S F O R A B V D  ............................................................................................. 4 5 
9. 2  
D O S E M O DI FI C A TI O N S F O R E S C A L A T E D B E A C O P P  .................................................................. 4 7 
9. 3  
D O S E M O DI FI C A TI O N F O R O B E S E P A TI E N T S  ............................................................................... 4 9 
1 0. 0  
C O R R E L A TI V E S CI E N C E C O M P A NI O N S T U DI E S  ............................................................ 4 9 
1 0. 1  
S E R U M M A R K E R S  ........................................................................................................................ 4 9 
1 0. 2  
P L A S M A M A R K E R S  ...................................................................................................................... 5 0 
1 0. 3  
IM M U N O HI S T O C H E MI C A L M A R K E R S  .......................................................................................... 5 1 
1 1. 0  
D R U G F O R M U L A TI O N, A V AI L A BI LI T Y, A N D P R E P A R A TI O N  .................................... 5 2 
1 1. 1  
Q U A LI FI E D P E R S O N N E L ............................................................................................................... 5 2 
1 1. 2  
D I S C A R DI N G U N U S E D A G E N T S  ................................................................................................... 5 2 
1 1. 3  
C A L C U L A T E D D O S E R A N G E  ........................................................................................................ 5 2 
1 1. 4  
D O X O R U BI CI N H C L  .................................................................................................................... 5 2 
1 1. 5  
B L E O M Y CI N  ................................................................................................................................. 5 3 
1 1. 6  
V I N B L A S TIN E S U L F A T E  ............................................................................................................... 5 3 
1 1. 7  
D A C A R B A ZI N E ( D TI C) ................................................................................................................ 5 4 
1 1. 8  
E T O P O SI D E  .................................................................................................................................. 5 5 
1 1. 9  
C Y C L O P H O S P H A MI D E  .................................................................................................................. 5 5 
1 1. 1 0  
V I N C RI S TI N E............................................................................................................................ 5 6 
1 1. 1 1  
P R O C A R B A ZI N E  ....................................................................................................................... 5 7 
1 1. 1 2  
P R E D NI S O N E  ............................................................................................................................ 5 8 
1 2. 0  
A N CI L L A R Y T H E R A P Y  ............................................................................................................ 5 8 
1 2. 1  
S U P P O R TI V E C A R E  ...................................................................................................................... 5 8 
1 2. 2  
C O N DI TI O N S F O R O T H E R T H E R A P Y  ............................................................................................ 5 8 
1 2. 3  
P R O P H Y L A XI S F O R P R E V E N TI O N O F H E M O R R H A GI C C Y S TI TI S  ................................................... 5 8 
1 2. 4  
A N TI E M E TI C T H E R A P Y  ................................................................................................................ 5 8 
1 2. 5  
T R A N S F U SI O N S  ............................................................................................................................ 5 8 
1 3. 0  
C RI T E RI A F O R R E S P O N S E, P R O G R E S SI O N, A N D R E L A P S E  ........................................ 5 9 
1 3. 1  
D E FI NI TI O N S O F R E S P O N S E [ 6 0] .................................................................................................. 5 9 
1 3. 2  
G UI D E LI N E S F O R E V A L U A TI O N O F M E A S U R A B L E D I S E A S E ........................................................ 6 0 
1 3. 3  
R E S P O N S E A S S E S S M E N T T A B L E  .................................................................................................. 6 1 
1 3. 4  
D E FI NI TI O N O F P R O G R E S SI O N - FR E E S U R VI V A L  .......................................................................... 6 1 
1 4. 0  
R E M O V A L O F P A TI E N T S F R O M P R O T O C O L T H E R A P Y ............................................... 6 1  
1 4. 1  
D U R A TI O N O F T R E A T M E N T  ......................................................................................................... 6 1 
1 4. 2  
E X T R A O R DI N A R Y M E DI C A L C I R C U M S T A N C E S: .......................................................................... 6 2 
1 5. 0  
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................................ 6 2 
1 5. 1  
S T U D Y D E SI G N  ............................................................................................................................ 6 2 
1 5. 2  
P RI M A R Y E N D P OI N T  .................................................................................................................... 6 2 
1 5. 3  
A C C R U A L A N D F O L L O W - UP  ........................................................................................................ 6 3 
1 5. 4  
S A M P L E S I Z E M O DI FI C A TI O N  ...................................................................................................... 6 3 
1 5. 5  
IN C L U SI O N O F W O M E N &  M I N O RI TI E S ....................................................................................... 6 4 
1 5. 6  
P R E DI C TI V E V A L U E O F F D G -P E T  .............................................................................................. 6 4 
1 5. 7  
S E C O N D A R Y O BJ E C TI V E S  ............................................................................................................ 6 4 
1 5. 8  
C O R R E L A TI V E E N D P OI N T S  .......................................................................................................... 6 5 
1 6. 0  
A D V E R S E E V E N T R E P O R TI N G ( A E R) .................................................................................. 6 6 
1 6. 1  
C A L G B  5 0 8 0 1  A D V E R S E E V E N T R E P O R TI N G R E Q UI R E M E N T S  .................................................. 6 6 

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1 6. 2  
A D DI TI O N A L IN S T R U C TI O N S O R E X C L U SI O N S T O C T E P -A E R S  E X P E DI T E D R E P O R TI N G 
R E Q UI R E M E N T S F O R C A L G B  5 0 8 0 1: ..................................................................................................... 6 7  
1 7. 0  
R E F E R E N C E S  .............................................................................................................................. 6 9 
A P P E N DI X I  
L O N D O N/ D E A U VI L L E C RI T E RI A  ......................................................................... 7 4 
A P P E N DI X II  
I M M U N O HI S T O C H E MI C A L A N A L Y SI S A N D I M A GI N G  P R O C E D U R E S  . 7 5 
A P P E N DI X III  
 S U M M A R Y O F BI O L O GI C  P R O G N O S TI C M A R K E R S I N C L A S SI C A L H L 
( ≥5 0 P T S)   
7 6 
A P P E N DI X I V  
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S 
F O R M   
7 7 
A P P E N DI X V  
C A L G B 5 0 8 0 1 I M A GI N G SI T E P E R S O N N E L F O R M  ....................................... 8 2 
 

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1. 0  I N T R O D U C TI O N  
1. 1  
Tre at me nt of B ul k y E arl y St a ge H o d g ki n L y m p h o m a 
T he maj orit y of patie nts wit h earl y sta ge H o d g ki n l y m p h o ma ( H L) a n d b ul k y me diasti nal 
disease, t y picall y defi ne d as a mass meas uri n g > 1 0 c m or o ne -t hir d t he ma xi mal dia meter 
of t he t h oracic ca vit y, recei ve c o m bi ne d m o dalit y t hera p y wit h 4 -6 c ycles of c he m ot hera p y 
f oll o we d  b y  i n v ol ve d  fiel d  ra diati o n  [ 1,  2].  M ulti ple  retr os pecti ve  st u dies  ha ve 
de m o nstrate d si g nifica nt l o n g -ter m t o xicities ass ociate d wit h me diasti nal ra di ot hera p y. A 
rece nt a nal ysis i n dicates t hat t here is a c u m ulati ve i nci de nce of sec o n dar y mali g na ncies of 
1 4 % at 5 years a n d 2 3 % at 1 0 years [ 3, 4]. S oli d t u m ors pre d o mi nate, wit h breast ca ncer 
a n d l u n g ca ncer bei n g t he m ost c o m m o n sec o n dar y mali g na ncies. I n w o me n, t he relati ve 
ris k of de vel o pi n g breast ca ncer is relate d t o a ge at treat me nt, wit h patie nts y o u n ger t ha n 
1 5  ha vi n g  t he  hi g hest  relati ve  ris k  ( 1 1 1. 8 -ti mes)  a n d  patie nts  u p  t o  a ge  4 0  ha vi n g  a 
persiste ntl y  hi g her  relati ve  ris k  ( 3. 4 -ti mes) [ 3].  Ot her  t o xicities  of  me diasti nal  ra diati o n 
i ncl u de val v ular da ma ge, accelerate d c or o nar y arter y disease a n d pericar dial fi br osis [ 5, 6]. 
T w o ra n d o mize d st u dies a n d o ne p hase 2 st u d y i n patie nts wit h o ut b ul k y disease s u g gest 
t hat A B V D c he m ot hera p y al o ne res ults i n si milar o verall s ur vi val c o m pare d wit h c o m bi ne d 
m o dalit y  t hera p y  or  ra diati o n  al o ne [ 7- 9].  A  rece nt  st u d y  fr o m  Ital y  ra n d o mize d  1 6 0 
patie nts wit h b ul k y disease, defi ne d as a mass greater t ha n 5 c m i n greatest di me nsi o n w h o 
achie ve d a ne gati ve P E T f oll o wi n g 6 c ycles of V E -B E P ( vi n blasti ne, et o p osi de, ble o m yci n, 
e pir u bici n, a n d pre d nis o ne) t o ra di ot hera p y vers us o bser vati o n [ 1 0]. At a me dia n f oll o w-
u p of 4 0 m o nt hs, 1 4 % of patie nts i n t he c he m ot hera p y o nl y ar m rela pse d c o m pare d t o 4 % 
of patie nts w h o recei ve d c he m ot hera p y pl us ra di ot hera p y ( 2 cases of H L a n d o ne carci n o ma 
i n t he ra diati o n fiel d). All of t he rela pses i n t he c he m ot hera p y o nl y ar m occ urre d i n t he 
b ul k y  site  a n d  c o nti g u o us  n o dal  re gi o ns.  P E T  sca ns  were  n ot  o btai ne d  at  mi d -c ycle 
resta gi n g. 
1. 2 
R ole of P E T Sc a n ni n g i n H o d g ki n L y m p h o m a  
Rece nt e vi de nce s u g gests t hat earl y resta gi n g P E T sca ns are hi g hl y pre dicti ve of o utc o me 
i n  H L [ 1 1- 1 3].  H utc hi n gs  a n d  c ollea g ues  eval uate d  t he  pre dicti ve  val ue  of  P E T  i n  7 7 
patie nts wit h sta ges I -I V H L [ 1 3]. F oll o wi n g 2 c ycles of c he m ot hera p y, 6 1 patie nts were 
P E T ne gati ve a n d 1 6 were P E T p ositi ve. At a me dia n f oll o w -u p of 2 3 m o nt hs, t hree of t he 
P E T ne gati ve patie nts, all of w h o m ha d a d va nce d sta ge disease, rela pse d. El e ve n of 1 6 P E T 
p ositi ve patie nts rec urre d. Of 1 6 P E T p ositi ve patie nts, fi ve ha d earl y sta ge disease a n d 
o nl y  o ne  rela pse d.  All  earl y  sta ge  patie nts  recei ve d  i n v ol ve d  fiel d  ra di ot hera p y  (I F R T) 
f oll o wi n g  c he m ot hera p y.  T he  i m pact  of  b ul k y  disease  i n  earl y  sta ge  patie nts  was  n ot 
s pecificall y a d dresse d. T he ma n uscri pt, t heref ore, c o ncl u de d t hat p ositi ve earl y resta gi n g 
P E T sca ns were hi g hl y pre dicti ve of rec urre nt H L i n patie nts wit h a d va nce d sta ge disease.  
A rece nt st u d y b y Galla mi ni e val uate d 2 6 0 patie nts wit h sta ge II B -I V H L w h o u n der we nt 
P E T sca ns after 2 c ycles of c he m ot hera p y [ 1 1]. T he maj orit y of patie nts recei ve d A B V D 
wit h or wit h o ut ra di ot hera p y. Treat me nt was n ot altere d base d o n res ult of t he P E T. Fift y 
of 2 6 0 patie nts ha d a p ositi ve resta gi n g P E T a n d 2 1 0 were P E T ne gati ve. T he defi niti o n of 
P E T p ositi ve was descri be d as “clearl y i ncrease d ac ti vit y relati ve t o t he bac k gr o u n d.” T w o 
ce ntral ra di ol o gists re vie we d P E T sca ns t hat s h o we d “ mi ni mal resi d ual u pta ke,” a n d sca ns 
wit h sta n dar dize d u pta ke val ues ( S U V) of 2 -3. 5 were c o nsi dere d ne gati ve f or t he a nal ysis. 
At  a  me dia n  f oll o w -u p  of  2  years,  t he  pr o gressi o n -free  s ur vi val  ( P F S)  i n  P E T  ne gati ve 
patie nts was 9 5 %, w hereas o nl y 1 2. 8 % of patie nts wit h a p ositi ve P E T sca n were free fr o m 
disease.  A p pr o xi matel y  o ne -t hir d  of  patie nts  ha d  b ul k y  disease,  w hic h  was  n ot  a n 
i n de pe n de nt pre dict or of o utc o me. 

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C A L G B 5 0 2 0 3 e val uate d earl y resta gi n g P E T sca ns i n patie nts wit h n o n -b ul k y sta ge I a n d 
II H L treate d wit h 6 c ycles of A V G ( A dria m yci n, vi n blasti ne a n d ge mcita bi ne) wit h o ut 
I F R T. T he c o m plete res p o nse rate ( C R/ C R u) was 6 7 % a n d esti mate d 1 a n d 2 year P F S 
rates were  8 1 %  a n d  7 1 %,  res pecti vel y.  T he  st u d y  di d  n ot  meet  its  pri mar y  e n d p oi nt. 
Alt h o u g h  t he  ne gati ve  pre dicti ve  val ue  of  a  p ositi ve  P E T  sca n  after  t w o  c ycles  was 
c o m para ble t o ot her st u dies at 9 1 %, t he p ositi ve pre dicti ve val ue was 4 8 %. It is u nclear 
w het her t his differe nce is relate d t o t he i ncl usi o n of e xcl usi vel y earl y sta ge patie nts, t he 
n o vel c he m ot hera p y re gi me n or p ossi bl y differe nces i n t he defi niti o n of a p ositi ve P E T 
sca n. Earlier st u dies use d less stri n ge nt defi niti o ns, a n d relie d o n S U V’s. C A L G B 50 2 0 3 
was  c o nsiste nt  wit h  rece ntl y  p u blis he d  g ui deli nes  w here  a  ne gati ve  P E T  is  defi ne d  as 
u pta ke l o wer t ha n t hat of me diasti nal bl o o d p o ol str uct ures f or resi d ual n o des ≥ 2 c m. F or 
n o des less t ha n 2 c m, p ositi vit y is defi ne d as u pta ke greater t ha n s urr o u n di n g bac k gr o u n d 
n o dal str uct ures [ 1 4]. 
1. 3 
B E A C O P P i n H o d g ki n L y m p h o m a  
B E A C O P P  ( ble o m yci n,  et o p osi de,  a dria m yci n,  c ycl o p h os p ha mi de,  vi ncristi ne, 
pr ocar bazi ne  a n d  pre d nis o ne)  is  a n  i nte nsi ve  c he m ot hera p y  re gi me n  de vel o pe d  b y  t he 
Ger ma n H o d g ki n L y m p h o ma St u d y Gr o u p ( G H S G).  T he re gi me n, w hic h is gi ve n e ver y 
t hree  wee ks,  s u bstit utes  et o p osi de  f or  dacar bazi ne  a n d  vi ncristi ne  f or  vi n blasti ne  a n d 
i nc or p orates  i ncrease d  d ose  c ycl o p h os p ha mi de.  A  lar ge  ra n d o mize d  st u d y  c o m pare d 
sta n dar d  d ose  B E A C O P P,  d ose  escalate d  B E A C O P P  a n d  C O PP- A B V D [ 1 5].  1, 2 0 1 
patie nts  wit h  sta ge  II B -I V  were  ra n d o mize d.  T he  st u d y  was  cl ose d  earl y  after  i nteri m 
a nal ysis re veale d t he C O P P-A B V D ar m was i nferi or wit h res pect t o P F S a n d O S, c o m pare d 
t o t he ot her t w o ar ms. Wit h l o n g ter m f oll o w-u p of 1 0 years, free d o m fr o m treat me nt fail ure 
rates were 6 4 %, 7 0 %, a n d 8 2 % a n d o verall s ur vi val rates were 7 5 %, 8 0 %, a n d 8 6 % f or 
C O P P -A B V D , sta n dar d B E A C O P P, a n d escalate d B E A C O P P, res pecti vel y ( p < 0. 0 0 1) 
[ 1 6]. He mat ol o gic t o xicit y of escalate d B E A C O P P was si g nifica nt wit h 9 0 % a n d 4 7 % of 
patie nts  de vel o pi n g  gra de  4  le u k o pe nia  a n d  t hr o m b oc yt o pe nia  res pecti vel y. 
M ye l o d ys plasia or sec o n dar y ac ute m yel oi d le u ke mia was see n i n o ne of 2 6 0 e val ua ble 
patie nts  treate d  wit h  C O P P -A B V D  c o m pare d  wit h  4  of  4 6 9  treate d  wit h  sta n dar d 
B E A C O P P  a n d  9  of  4 6 6  wit h  escalate d  B E A C O P P.  I nfertilit y  was  nearl y  u ni versal  i n 
patie nts recei vi n g escalate d B E A C O P P.  
A n  Israeli  st u d y  treate d  6 9  patie nts  wit h  earl y  u nfa v ora ble  sta ge  H L  ( defi ne d  as  B 
s y m pt o ms,  b ul k y  disease,  > 4  i n v ol ve d  n o dal  re gi o ns,  E S R  > 5 0,  l y m p h oc yte  de plete d 
hist ol o g y or e xtra n o dal disease) or a d va nce d sta ge disease wit h a n I nter nati o nal Pr o g n ostic 
I n de x of less t ha n or e q ual t o 2 wit h t w o c ycles of sta n dar d d ose B E A C O P P. 2 7 patie nts 
ha d b ul k y  me diasti nal disease. T h ose w h o were P E T or 6 7 Ga ne gati ve after t w o c ycles 
were c o nti n ue d o n sta n dar d B E A C O P P, w hile t h ose w h o were P E T or 6 7 Ga p ositi ve were 
s witc he d t o escalate d B E A C O P P. T he 5-year P F S a n d O S were si milar f or b ot h gr o u ps at 
8 4 %,  a n d  9 0 %  res pecti vel y. [ 1 7].  I n  a d diti o n,  t he  G H S G  rece ntl y  prese nte d  a n  i nteri m 
a nal ysis of t heir st u d y i n earl y u nfa v ora ble H L. Patie nts were ra n d o mize d t o 2 c ycles of 
escalate d B E A C O P P  f oll o we d b y 2 c ycles of A B V D pl us I F R T c o m pare d t o 4 c ycles of 
A B V D pl us I F R T. 1 1 2 7 of a t otal 1 6 0 0 pla n ne d patie nts were e val ua ble.  Wit h a me dia n 
f oll o w-u p of 3 2 m o nt hs, t he C R rates were 9 3. 7 % a n d 9 5 % a n d O S 9 1 % a n d 9 5 % f or t he 
A B V D a n d escalate d B E A C O P P ar ms, res pecti vel y.  
1. 4 
R ati o n ale f or I F R T D ose  
M ulti ple ra n d o mize d st u dies ha ve s h o w n t hat c o m bi ne d m o dalit y t hera p y pr o vi des s u peri or 
disease c o ntr ol c o m pare d t o ra diati o n t hera p y al o ne [ 2, 1 8, 1 9] or c he m ot hera p y al o ne [ 7, 
2 0, 2 1]  i n earl y sta ge H o d g ki n l y m p h o ma ( H L). H o we ver, t he o pti mal d ose of i n v ol ve d-

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U p date # 1 3  
fiel d  ra diati o n  t hera p y  (I F R T)  i n  c o m bi ne d  m o dalit y  treat me nt  pr o gra ms  is  u n k n o w n. 
P ote ntial car diac a n d p ul m o nar y c o m plicati o ns relate d t o me diasti nal irra diati o n, as well 
as i n d ucti o n of sec o n dar y mali g na ncies, ha ve le d t o trials e xa mi ni n g l o wer I F R T d oses.  
O ne of t he first s uc h  trials was fr o m t he Ger ma n H o d g ki n L y m p h o ma St u d y Gr o u p ( H D 1) 
[ 2 2]. T his trial e nr olle d 1 4 6 patie nts wit h sta ge I-IIIa H L wit h a d verse pr o g n ostic fact ors 
i ncl u di n g lar ge me diasti nal a de n o pat h y ( L M A), massi ve s ple nic i n v ol ve me nt, m ore t ha n 
fi ve  lesi o ns,  a n d/ or  e xtra n o dal i n v ol ve me nt.  All  patie nts  res p o n di n g  t o  4  c ycles  of 
c o m bi nati o n c he m ot hera p y ( C O P P/ A B V D) were ra n d o mize d t o 2 0 G y vers us 4 0 G y I F R T. 
H o we ver,  all  patie nts  wit h  L M A  recei ve d  4 0  G y.  T he  4 -year  free d o m  fr o m  treat me nt 
fail ure di d n ot differ bet wee n t he treat me nt ar ms ( 7 9 % a n d 8 0 %, res pecti vel y). 
T he C hil dre n’s Ca ncer Gr o u p 5 9 4 2 st u d y ra n d o mize d c hil dre n a n d a d olesce nts y o u n ger 
t ha n  2 1  years  of  a ge  t o  I F R T  or  o bser vati o n  after  ac hie vi n g  a  c o m plete  res p o nse  t o 
c he m ot hera p y ( C O P P -A B V) [ 2 1]. L M A was prese nt i n a mi n orit y of patie nts ( 2 5 %). All 
patie nts ra n d o mize d t o I F R T, re gar dless of disease b ul k, recei ve d 2 1 G y. T he 3 -ye ar e ve nt -
free  s ur vi val  was  8 5 %  f or  patie nts  ra n d o mize d  t o o bser vati o n  a n d  9 3 %  f or  patie nts 
recei vi n g I F R T ( p = 0. 0 5 7). O utc o mes f or patie nts wit h L M A were n ot s pecificall y re p orte d. 
F or  patie nts  wit h  fa v ora ble  disease  prese ntati o ns,  preli mi nar y  res ults  fr o m  m ore  rece nt 
st u dies als o s u p p ort a l o wer R T d ose. T he E O R TC H 9 -F c o m pare d 3 6 G y, 2 0 G y, a n d 0 
G y I F R T after 6 c ycles of E B V P [ 2 3]. T he 4-year e ve nt -free s ur vi val was 8 7 %, 8 4 %, a n d 
7 0 %,  res pecti vel y.  T he  o bser vati o n  ar m  was  dr o p pe d  after  a n  i nteri m  re p ort  s h o we d 
i nferi or o utc o mes. T he Ger ma n H o d g ki n L y m p h o ma St u d y Gr o u p trial H D 1 0 ra n d o mize d 
patie nts wit h earl y sta ge, fa v ora ble H L t o 2 vers us 4 c ycles of A B V D wit h a se c o n dar y 
ra n d o mizati o n  t o  2 0  G y  vers us  3 0  G y  of  I F R T [ 2 4].  Preli mi nar y  res ults  s h o we d  n o 
differe nce i n free d o m fr o m treat me nt fail ure bet wee n 3 0 G y a n d 2 0 G y. L o n ger f oll o w- u p 
will be necessar y t o c o nfir m t he fi n di n gs fr o m t hese t w o trials.  
T here are n o p u blis he d ra n d o mize d trials e val uati n g t he o pti mal I F R T d ose f or patie nts 
wit h L M A. A retr os pecti ve a nal ysis fr o m D u ke a n d Yale e xa mi ni n g 8 3 patie nts wit h H L 
wit h L M A  treate d wit h c o m bi ne d m o dalit y t hera p y s u g geste d t hat l o w d ose I F R T ma y be 
a de q uate [ 2 5]. Rela pse-free s ur vi val was 1 0 0 % i n patie nts recei vi n g < 2 0 G y ( n = 1 2), 7 1 % 
after 2 0-2 5 G y ( n = 2 4), 8 3 % after 2 5 -3 0 G y ( n = 3 0) a n d 7 5 % after > 3 0 G y ( n = 1 2). A s maller 
st u d y fr o m t he U ni versit y of Mic hi ga n als o f o u n d e q ui vale nt fail ure rates after l o w d oses 
( 1 9. 8-2 5. 2 G y) c o m pare d wit h hi g her d oses ( 3 0 -4 4 G y) [ 2 6]. H o we ver, fir m c o ncl usi o ns 
ca n n ot be dra w n gi ve n t he retr os pecti ve nat ure of t he a nal yses a n d s mall patie nt n u m bers.  
C o nsi derati o n of treat me nt-relate d t o xicities m ust be ta ke n i nt o acc o u nt w he n f or m ulati n g 
treat me nt  pr o gra ms  f or  patie nts  wit h  H L.  T here  is  i ncreasi n g  data  s u g gesti n g  t hat  R T-
i n d uce d  t o xicities,  i n  partic ular  car diac  c o m plicati o ns  a n d  sec o n dar y  mali g na ncies,  are 
d ose relat e d. I n a retr os pecti ve st u d y fr o m D u ke, t here was a si g nifica nt differe nce i n t he 
i nci de nce of sec o n dar y mali g na ncies bet wee n patie nts treate d wit h R T al o ne ( mea n d ose 
3 7. 9 G y), c o m pare d wit h patie nts treate d wit h c o m bi ne d m o dalit y t hera p y wit h l o w d ose 
I FR T ( mea n d ose 2 5. 5 G y) [ 2 7]. T he 2 0-year act uarial ris k of sec o n dar y mali g na ncies was 
1 6 % wit h R T al o ne c o m pare d wit h 0 % wit h c o m bi ne d m o dalit y utilizi n g l o w d ose I F R T. 
T he R T fiel ds were als o s maller i n t he c o m bi ne d m o dalit y t hera p y gr o u p, w hic h als o li kel y 
c o ntri b ute d  t o  t he  decre ase  i n  sec o n dar y  mali g na ncies.  I n  a  retr os pecti ve  st u d y  fr o m 
Sta nf or d, t he ris k of deat h fr o m heart disease a p peare d t o be d ose relate d. D oses a b o ve 3 0 
G y were ass ociate d wit h a relati ve ris k of 3. 5, w hile d oses less t ha n 3 0 G y c o nferre d n o 
e xcess ris k [ 2 8]. 
I n t he prese nt st u d y of patie nts wit h b ul k y s u pra dia p hra g matic H L, t he use of I F R T will be 
base d  o n  res p o nse  t o  c he m ot hera p y.  Patie nts  w h o  ac hie ve  a  P E T  C R  after  2  c ycles  of 
c he m ot hera p y  will  n ot  recei ve  I F R T.  Patie nts  w h o  res p o n d  sl o wl y  t o  c he m ot hera p y,  or 

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2. 0  
O B J E C TI V E S  
2. 1 
P ri m ar y O bjecti ve  
2. 1. 1 
T o deter mi ne t he pr o gressi o n -free s ur vi val ( P F S) at 3 6 m o nt hs fr o m e nr oll me nt 
f or patie nts wit h b ul k y sta ge I a n d II H o d g ki n l y m p h o ma. All patie nts will be gi n 
treat me nt  wit h  A B V D.  Patie nts  w h o  are  P E T  ne gati ve  after  2  c ycles  of 
c he m ot hera p y will recei ve 6 c ycles of A B V D wit h o ut ra di ot hera p y.  Patie nts w h o 
are P E T p ositi ve after 2 c ycles of A B V D will t he n recei ve 4 c ycles of escalate d 
B E A C O P P f oll o we d b y I F R T.  A c o m paris o n will be ma de of t he 3 6-m o nt h P F S 
bet wee n patie nts w h o are P E T p ositi ve a n d t h ose w h o are P E T ne gati ve f oll o wi n g 
2 c ycles of A B V D.  
2. 2 
Sec o n d ar y O bjecti ves  
2. 2. 1 
T o e val uate t he c o m plete res p o nse ( C R) rate of patie nts dia g n os e d wit h b ul k y sta ge 
I a n d II H o d g ki n l y m p h o ma f oll o wi n g P E T res p o nse-a da pte d c he m ot hera p y wit h 
or wit h o ut ra diati o n t hera p y. 
2. 2. 2 
T o deter mi ne t he pre dicti ve val ue of F D G u pta ke usi n g vari o us se mi q ua ntitati ve 
a p pr oac hes, at baseli ne, after 2 c ycles of AB V D a n d at c o m pleti o n of t hera p y. 
2. 2. 3 
T o  deter mi ne  t he  pre dicti ve  val ue  of  v ol u metric  vs.  2  di me nsi o nal  ( 2 -D) 
meas ure me nt c ha n ges o n C T bet wee n baseli ne a n d after 2 c ycles, at t he e n d of 
c he m ot hera p y ( P E T ne gati ve patie nts o nl y) a n d after R T ( P E T p ositi ve patie nts 
o nl y) a n d c o m pare wit h P E T para meters.  
2. 2. 4 
T o  deter mi ne  if  c ha n ges  i n  b ot h  q ualitati ve  a n d  se mi q ua ntitati ve  F D G -P E T 
fi n di n gs bet wee n baseli ne a n d after c ycle 2, at e n d of c he m ot hera p y ( P E T ne gati ve 
patie nts o nl y)  a n d after R T ( P E T p ositi ve patients o nl y) wit h c o m bi nati o n a nal yses 
wit h  i nc or p orati n g  c ha n ges  o btai ne d  fr o m  de dicate d  C T  sca ns,  c orrelate  wit h 
res p o nse a n d P F S. 
2. 2. 5 
T o c o m pare t he pre dicti ve  val ue  of  b ot h  q ualitati ve a n d  se mi q ua ntitati ve  F D G -
P E T  c ha n ges,  2 -D  a n d  v ol u metric  C T  c ha n ges,  a n d  c o m bi nat orial  a nal yses 
( P E T + de dicate d  C T  data)  wit h  m olec ular  para meters,  a n d  c o n ve nti o nal 
para meters, i ncl u di n g I P S.  
2. 2. 6 
T o assess w het her ele vate d baseli ne ser u m s ol u ble C D 3 0 (s C D 3 0), I L 1 0, C C L 1 7, 
a n d C C L 2 2 c orrelate wit h cli nical res p o nse a n d P F S . 
2. 2. 7 
T o assess w het her persiste nt or rec urre nt ele vati o n of serial ser u m s C D 3 0, I L 1 0, 
C C L 1 7, or C C L 2 2 c orrelate wit h rela pse/ pr o gressi o n or P E T sca n res ults.  
2. 2. 8 
T o c o nfir m i n de pe n de ntl y usef ul tiss ue bi o mar kers ( bcl -2, M A L, F O X P 3, C D 6 8, 
Gz B) f or ris k  stratificati o n i n patie nts wit h b ul k y sta ge I a n d II H o d g ki n l y m p h o ma 
treate d wit h t his re gi me n. 
2. 2. 9 
T o  c o m pare  me diasti nal  b ul k  o n  sta n di n g  P A  a n d  lateral  c hest  x -ra y  ( >  0. 3 3 
ma xi m u m c hest dia meter) wit h c hest C T ( mass > 1 0 c m) . 

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3. 0  
O N - ST U D Y  G UI D E LI N E S  
T his cli nic al tri al c a n f ulfill its o bjecti ves o nl y if p atie nts a p pr o pri ate f or t he tri al are e nr olle d.  
All rele va nt me dical a n d ot her c o nsi derati o ns s h o ul d be ta ke n i nt o acc o u nt w he n deci di n g w het her 
t his pr ot oc ol is a p pr o priate f or a partic ular patie nt. T o ma xi mi ze patie nt safet y, patie nts s h o ul d be 
treate d o n t his pr ot oc ol o nl y at ce nters ha vi n g rea d y access t o bl o o d pr o d uct s u p p ort a n d a de q uate 
staff t o care f or t he se verel y ne utr o pe nic patie nt. P h ysicia ns s h o ul d c o nsi der t he ris ks a n d be nef its of 
a n y  t hera p y  a n d  t heref ore  o nl y  e nr oll  patie nts  f or  w h o m  t he  a ge nts  a d mi nistere d  are  a p pr o priate. 
Alt h o u g h t he y will  n ot  be  c o nsi dere d  as f or m al  eli gi bilit y  (e xcl usi o n)  criteri a,  as  p art  of  t he 
decisi o n -m a ki n g pr ocess p h ysici a ns s h o ul d rec o g nize t h at  t he f oll o wi n g m a y i ncre ase t he ris k 
t o t he p atie nt e nteri n g t his pr ot oc ol: 
• 
Seri o us me dical ill ness or ps yc hiatric c o n diti o n t hat c o ul d pre ve nt c o m plia nce wit h treat me nt or 
i nf or me d c o nse nt. 
• 
U nc o ntr olle d  or  se vere  car di o vasc ular  disease  i ncl u di n g  rece n t  ( <  6  m o nt hs)  m y ocar dial 
i nfarcti o n.  Patie nts  wit h  car diac  arr h yt h mias  re q uiri n g  treat me nt  ma y  be  e ntere d  at  t heir 
p h ysicia n’s discreti o n. 
4. 0  
E LI GI BI LI T Y C RI T E RI A  
All q uesti o ns re gar di n g eli gi bilit y criteria s h o ul d be directe d t o t he St u d y C hair. Please n ote t hat t he 
St u d y C hair ca n n ot gra nt wai vers t o eli gi bilit y re q uire me nts.  
I nstit uti o ns m ust be cre de ntiale d b y t he Allia nce  I ma gi n g C ore La b at I R O C O hi o pri or t o e nr olli n g 
patie nts (see Secti o n 8. 1. 1 ). 
4. 1  
D oc u me nt ati o n of Di se ase 
4. 1. 1 
Hist ol o gicall y  d oc u me nte d  H o d g ki n  l y m p h o ma  s u bclassifie d  acc or di n g  t o  t he 
W H O m o dificati o n of t he R ye Classificati o n a n d sta ge d acc or di n g t o t he m o difie d 
A n n Ar b or Sta gi n g Classificati o n s yste m. Patie nts m ust ha ve cli nical sta ge I A, I B, 
II A or II B. Patie nts wit h “ E” e xte nsi o ns will be eli gi ble if all ot her criteria ha ve 
bee n met. N o d ular l y m p h oc yte pre d o mi na nt H o d g ki n l y m p h o ma is e xcl u de d.  
C ore  nee dle  bi o psies  are  acce pta ble  if  t he y  c o ntai n  a de q uate  tiss ue  f or  pri mar y 
dia g n osis  a n d  i m m u n o p he n ot y pi n g.  Fi ne  nee dle  as pirates  are  n ot  acce pta ble.  If 
m ulti ple s peci me ns are a vaila ble, please s u b mit t he m ost rece nt. F ail ure t o s u b mit 
p at h ol o g y m ateri als wit hi n 6 0 d a ys of p atie nt re gistr ati o n will be c o nsi dere d 
a m aj or pr ot oc ol vi ol ati o n (see Secti o n 5. 3 ). 
4. 1. 2 
Patie nts m ust ha ve a me diasti nal mass > 0. 3 3 ma xi m u m i ntrat h oracic dia meter o n 
sta n di n g  p oster o-a nteri or  c hest  x -ra y  or mass meas uri n g  >  1 0  c m  i n  its  lar gest 
dia meter.  
4. 2 
Sec o n d M ali g n a nc y  
N o “c urre ntl y acti ve” sec o n d mali g na nc y ot her t ha n n o n -mela n o ma s ki n ca ncers. Patie nts 
are n ot c o nsi dere d t o ha ve a “c urre ntl y acti ve” mali g na nc y if t he y ha ve c o m plete d t hera p y 
a n d are c o nsi dere d b y t heir p h ysicia n t o be at less t ha n 3 0 % ris k of rela pse. 
4. 3 
P ri or T her a p y  
Patie nt s ma y  ha ve ha d o ne c ycle o nl y of A B V D pri or t o e nr olli n g o n st u d y. N o ot her pri or 
treat me nt (c he m ot hera p y or ra diati o n t hera p y) f or H o d g ki n l y m p h o ma is all o we d. 
If patie nt has ha d o ne c ycle of A B V D, i n or der t o be eli gi ble t o e nr oll o n C A L G B 5 0 8 0 1, 
t he patie nt m ust ha ve ha d all of t he f oll o wi n g tests pri or  t o starti n g t he first c ycle of A B V D: 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
1 5  
U p date # 1 3  
•  
L V E F b y E C H O or M U G A  
•  
P F Ts (i ncl u di n g D L C O/ F V C)  
•  
C T sca n ( nec k *, c hest, a b d o me n, pel vis) 
•  
F D G -P E T/ C T sca n  
•  
C hest X -ra y, P A & Lateral  
•  
C B C, differe ntial, platelets 
•  
E S R  
•  
Ser u m crea ti ni ne  
•  
Gl uc ose 
•  
A S T  
•  
Al kali ne p h os p hatase  
•  
Bilir u bi n  
•  
L D H  
* Patie nts wit h a ne gati ve F D G -P E T/ C T sca n d o n ot nee d t o ha ve ha d a de dicate d nec k C T 
sca n pri or t o starti n g t he pre vi o us c ycle of A B V D. 
4. 4 
E C O G P erf or m a nce  
E C O G p erf or ma nce stat us 0 - 2. 
4. 5 
L V E F a n d D L C O  
L V E F b y E C H O or M U G A wit hi n i nstit uti o nal n or mal li mits u nless t h o u g ht t o be disease 
relate d. D L C O ≥ 6 0 % wit h n o s y m pt o matic p ul m o nar y disease u nless t h o u g ht t o be disease 
relate d. 
4. 6 
HI V I nfecti o n  
Patie nts wit h k n o w n  HI V m ust ha ve a C D 4 c o u nt > 3 5 0  an d be o n c o nc urre nt a ntiretr o virals 
( See Secti o n  1 2. 1 ).  Patie nts  wit h  a  hist or y  of  i ntra ve n o us  dr u g  a b use  or  a n y  be ha vi or 
ass ociate d wit h a n i ncrease d ris k of HI V i nfecti o n s h o ul d be teste d f or e x p os ure t o t he HI V 
vir us. A n HI V t est is n ot re q uire d f or e ntr y o n t his pr ot oc ol, b ut is re q uire d if t he patie nt is 
percei ve d t o be at ris k.  
4. 7 
P re g n a nc y Restricti o ns  
N o n -pre g na nt a n d n o n - n ursi n g. D ue t o t he terat o ge nic p ote ntial of t he a ge nts use d i n t his 
st u d y, pre g na nt or n ursi n g w o me n ma y n ot be e nr olle d. W o me n a n d me n of re pr o d ucti ve 
p ote ntial s h o ul d a gree t o use a n effecti ve mea ns of birt h c o ntr ol.  
4. 8 
A ge Restriciti o ns  
A ge 1 8 – 6 0 years.  
4. 9 
I niti al Re q uire d L a b or at or y D at a: 
A N C  
≥ 1 0 0 0/ µ L  
Platelet c o u nt  
≥ 1 0 0, 0 0 0/ µ L  
Ser u m Creati ni ne  
≤ 2 m g/ d L  
Bilir u bi n *  
≤ 2 x u p per li mit of n or mal  
A S T  
≤ 2 x u p per li mit of n or mal  
* I n t he a bse nce of Gil bert’s disease  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
2 0  
U p date # 1 3  
r ole,  t he  user  m ust  h ol d  a  mi ni mu m  of  a n  A P  re gistrati o n  t y pe. T o  h ol d  t he  Ra ve  Site 
I n vesti gat or r ole, t he i n di vi d ual m ust be re gistere d as a n N PI V R or I V R. Ass ociates ca n 
h ol d  rea d -o nl y  r oles  i n  Ra ve.  T he  Ra ve  s yste m  ca n  be  accesse d  t hr o u g h  t he i Me di data 
p ortal at 
. F or a d diti o nal i nf or mati o n re gar di n g acc o u nt set u p 
or  trai ni n g,  please  visit  t he  trai ni n g  secti o n  of  t he  Allia nce  we bsite.  F or ms  s h o ul d  be 
s u b mitte d i n c o m plia nce wit h t he ta ble bel o w, a n d a c o p y of t he All F or ms Pac ket ca n be 
d o w nl oa de d fr o m t he Allia nce we bsite. 
U p o n i nitial site re gistrati o n a p pr o val f or t he st u d y i n R S S, site pers o n nel wit h Ra ve r oles 
assi g ne d o n t he a p pr o priate r oster ma y recei ve a st u d y i n vitati o n e -mail fr o m i Me di data. 
T o  acce pt  t he  i n vitati o n,  site  users  
m ust  l o g  i nt o  t he  Select  
L o gi n 
 usi n g t heir C T E P-I A M user na me a n d pass w or d, 
a n d clic k o n t he “acce pt” li n k i n t he u p per ri g ht -c or ner of t he i Me di data pa ge. Please n ote, 
site users will n ot be a ble t o access t he st u d y i n Ra ve u ntil all re q uire d Me di data a n d st u d y 
s pecific  trai ni n gs  are  c o m plete d.  Trai ni n gs  will  be  i n  t he  f or m  of  electr o nic  lear ni n gs 
(e Lear ni n gs), a n d ca n be accesse d b y clic ki n g o n t he li n k i n t he u p per ri g ht pa ne of t he 
i Me di data scree n. Pers o n nel w h o di d n ot recei ve a n i n vitati o n s h o ul d c o ntact t he Allia nce 
Ser vice Ce nter.  
Users w h o ha ve n ot pre vi o usl y acti vate d t heir i Me di data/ Ra ve acc o u nt at t he ti me of a n 
i nitial site re gistrati o n a p pr o val f or a st u d y i n R S S will als o recei ve a se parate i n vitati o n 
fr o m i Me di data t o acti vate t heir acc o u nt. Acc o u nt acti vati o n i nstr ucti o ns are l ocate d o n t he 
C T S U we bsite’s Ra ve ta b u n der t he Ra ve Res o urce Materials hea di n g ( Me di data Acc o u nt 
Acti vati o n a n d St u d y I n vitati o n Acce pta nce). A d diti o nal i nf or mati o n o n i Me di data/ Ra ve 
is a vaila ble o n t he C T S U me m bers’ we bsite u n der t he Ra ve ta b at w w w.cts u. or g/ R A V E/ 
or  b y  c o ntacti n g  t he  C T S U  Hel p  Des k  at 
  or  b y  e-mail  at 
. 
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
2 1  
U p date # 1 3  
F or m *  
S u b missi o n Sc he d ule  
B aseli ne  
 
5 0 8 0 1 Re gistrati o n W or ks heet  
Wit hi n o ne m o nt h of re gistrati o n  
 
5 0 8 0 1 Eli gi bilit y C hec klist  
C -1 8 7 7  
5 0 8 0 1 O n -St u d y F or m  
L Y -4  
L y m p h o ma Pre -St u d y Fl o w S heet  
C -1 8 7 8  
5 0 8 0 1 P E T a n d C T Meas ure me nt F or m  
C -1 8 8 3  
5 0 8 0 1 F D G -P E T A dj u ncti ve Data S heet  
Re p ort  
Baseli ne P E T, C T, a n d Pat h ol o g y re p orts  
 
Tre at me nt * * *  
C -1 8 8 0  
5 0 8 0 1 Treat me nt S u m mar y F or m  
S u b mit  after  eac h  c ycle  of  A B V D, 
B E A C O P P, or I F R T  
S -0 6 8  
5 0 8 0 1 Me dicati o n Cale n dar † †  
C -1 8 8 1  
5 0 8 0 1 A d verse E ve nt F or m * *  
L Y -5  
L y m p h o ma Fl o w S heet  
 
 
 
C -1 8 8 2  
5 0 8 0 1 F oll o w -u p F or m  
P E T ne gati ve: S u b mit after c ycle 2 a n d 
c ycle 6 of A B V D 
 
P E T  p ositi ve:  S u b mit  after  c ycle  2  of 
A B V D,  c ycle  6  of  B E A C O P P  ( C - 1 8 8 2 
o nl y), a n d f oll o wi n g I F R T  
C -1 8 7 8  
5 0 8 0 1 P E T a n d C T Meas ure me nt F or m  
C -1 8 8 3  
5 0 8 0 1 F D G -P E T A dj u ncti ve Data S heet  
Re p ort 
C o pies of P E T/ C T sca ns a n d pat h ol o g y re p orts 
 
F oll o w -u p ( P ost -tre at me nt)  
C -1 8 8 2  
5 0 8 0 1 F oll o w -u p F or m  
S u b mit e ver y 3 m o nt hs f or t he first year 
p ost treat me nt, e ver y 6 m o nt hs f or years 
2 a n d 3, a n d a n n uall y at years 4 a n d 5 
C -1 8 7 8  
5 0 8 0 1 P E T a n d C T Meas ure me nt F or m  
C -1 8 8 3  
5 0 8 0 1 F D G -P E T A dj u ncti ve Data S heet †  
Re p ort  
C o pies of P E T/ C T sca ns a n d pat h ol o g y re p orts  
 
 
 
C -4 0 0  
L o n g T er m F oll o w -u p F or m  
S u b mit a n n uall y years 6 -1 0  
 
 
 
Ot her  
R T -1  
Ra diati o n D osi metr y S u m mar y F or m  
S u b mit per Secti o n 7. 2. 1 3  
R T -2  
Ra diati o n T otal D ose Rec or d  
 
C -3 0 0  
Off Treat me nt F or m  
At e n d of all pr ot oc ol treat me nt  
C -1 1 3  
N otificati o n of Deat h  
At ti me of deat h  
C -1 0 0 1  
Ne w Mali g na nc y F or m  
At ti me of dia g n osis of ne w mali g na nc y  
C- 1 8 2 0 
A d verse E ve nts A d de n d u m F or m 
C o m plete if a d diti o nal s pace is nee de d t o 
re p ort  ot her  a d verse  e ve nts.    See  f or m 
f or i nstr ucti o ns.  
C -1 7 4 2  
C A L G B C o nfir mati o n of L ost t o F oll o w U p  
See f or m f or s u b missi o n i nstr ucti o ns  
* 
Use C A L G B Re mar ks  A d de n da ( C -2 6 0) if a d diti o nal c o m me nts are necessar y or a d diti o nal  writi n g  s pace is 
nee de d.   
* *  
S u b mit A E f or m u ntil all pr ot oc ol treat me nt relate d e ve nts ha ve res ol ve d or u ntil n o n -pr ot oc ol treat me nt be gi ns. 
If patie nt deat h is re p orte d vi a C T E P -A E R S , re p ort Gra de 5 e ve nt of A E f or m e ve n if p atie nt is off pr ot oc ol 
treat me nt.   
* * *  If patie nt ne ver starts treat me nt, s u b mit all baseli ne data a n d t he C-3 0 0 Off -Treat me nt F or m.  N o ot her f oll o w -
u p f or ms are re q uire d f or s u b missi o n.  
† 
O nl y s u b mit t hr o u g h year 3.  
† †  
S u b missi o n o nl y f or t h ose pati e nts recei vi n g escalate d B E A C O P P.  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
2 3  
U p date # 1 3  
If patie nt has c o nse nte d t o all o w t heir tiss ue t o be use d f or c urre nt researc h descri be d i n 
Secti o n  1 0. 3  ( m o del  c o nse nt  q uesti o n  # 1)  or  ke pt  f or  f ut ure  researc h  ( m o del  c o nse nt 
q uesti o ns  # 2  a n d  # 3,  o nl y  o ne  tiss ue  bl oc k  nee d  be  s u b mitte d  t o  acc o m m o date  b ot h 
hist ol o gic c o nfir mati o n of dia g n osis a n d c orrelati ve scie nce st u dies (see Secti o n 5. 4. 2 ). 
T he Allia nce/ C A L G B  has  i nstit ute d  s pecial  c o nsi derati o ns  f or  t he  s mall  perce nta ge  of 
i nstit uti o ns w h ose p olicies pr o hi bit release of a n y bl oc ks. If, d ue t o i nstit uti o nal p olic y, a 
bl oc k  ca n n ot  be  se nt,  please  call 
  t o  o btai n  a  pr ot oc ol  f or  s u b missi o n  of 
re prese ntati ve tiss ue fr o m y o ur i nstit uti o n. 
5. 4 
C orrel ati ve Scie nce S a m ple S u b missi o n  
All  partici pati n g  i nstit uti o ns  m ust  as k  patie nts  f or  t heir  c o nse nt  t o  partici pate  i n  t he 
c o m p o ne nts of t he c orrelati ve s u bst u d y ( C A L G B 1 5 0 9 0 3) , alt h o u g h patie nt partici pati o n 
is o pti o nal. Rati o nale a n d met h o ds f or t hese st u dies are descri be d i n Secti o n 1 0. 0 . 
S peci me ns f or patie nts re gistere d o n t his st u d y m ust be l o g ge d a n d s hi p pe d usi n g t he o nli ne 
Allia nce Bi os peci me n M a na ge me nt S yste m ( Bi o M S).  
U S E  O F  T H E  A L LI A N C E  BI O S P E CI M E N  M A N A G E M E N T  S Y S T E M  ( Bi o M S)  I S 
M A N D A T O R Y  A N D  A L L  S P E CI M E N S  M U S T  B E  L O G G E D  A N D  S HI P P E D  VI A 
T HI S S Y S T E M.  
Bi o M S  is  a  we b -base d  s yste m  f or  l o g gi n g  a n d  trac ki n g  all  bi os peci me ns  c ollecte d  o n 
Allia nce / C A L G B trials. A ut h orize d i n di vi d uals ma y access Bi o M S at t he f oll o wi n g U R L: 
, usi n g m ost sta n dar d we b br o wsers ( Safari, Firef o x, I nter net 
E x pl orer).  F or i nf or mati o n o n usi n g t he Bi o M S s yste m, please refer t o t he ‘ Hel p’ li n ks o n 
t he Bi o M S we b pa ge t o access t he o n -li ne user ma n ual, F A Qs, a n d trai ni n g vi de os.  T o 
re p ort tec h nical pr o ble ms, s uc h as l o gi n iss ues or a p plicati o n err ors, please c o ntact: 
  F or  assista nce  i n  usi n g  t he  a p plicati o n  or  q uesti o ns  or  pr o ble ms  rela te d  t o 
s pecific s peci me n l o g gi n g, please c o ntact: 
 
After l o g gi n g c ollecte d s peci me ns i n Bi o M S, t he s yste m will create a s hi p pi n g ma nifest. 
T his  s hi p pi n g  ma nifest  m ust  be  pri nte d  a n d  place d  i n  t he  s hi p me nt  c o ntai ner  wit h  t he 
s peci me ns. 
 
S a m ple T y pe  
S a m ple C ollecti o n Ti me P oi nts 1 
W h ole Bl o o d 
( Ser u m) * 
W h ole Bl o o d 
( Plas ma) * * 
F F P E Tiss ue  
Pri or t o i nitiati o n of t hera p y ( B aseli ne) 
X 
X 
X * * *  
Ti me of 2 n d P E T/ C T sca n ( p ost -c ycle 2)  
X 
X 
 
Ti me of 3r d P E T/ C T sca n  
At c he m o c o m pleti o n f or P E T ne gati ve patie nts  
P ost I F R T c o m pleti o n f or P E T p ositi ve patie nts  
X 
X 
 
D uri n g year 1 f oll o w -u p  
(at 3, 6, 9, a n d 1 2 m o nt hs p ost-t x) 
X 
X 
 
D uri n g year 2 f oll o w -u p  
(at 1 8 a n d 2 4 m o nt hs p ost-t x) 
X 
X 
 
D uri n g year 3 f oll o w -u p  
(at 3 0 a n d 3 6 m o nt hs p ost -t x) 
X 
X 
 
Pr o gressi o n or Rela pse  
 
 
X 2 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
2 4  
U p date # 1 3  
 
(Sec ti o n 5. 4. 3 ) 
* 
W h ole bl o o d f or ser u m ( 1 0 m L) is c ollecte d at t he ti me of eac h P E T/ C T sca n a n d at 
t he ti me of eac h C T sca n d uri n g t he first 3 years of f oll o w- u p. 
* * 
W h ole bl o o d f or plas ma ( 1 0 m L) is c ollecte d at t he ti me of eac h P E T/ C T sca n a n d at 
t he ti me of eac h C T sca n d uri n g t he first 3 years of f oll o w- u p. 
* * * A n F F P E tiss ue bl oc k is ma n dat or y f or hist ol o gic c o nfir mati o n of dia g n osis a n d if 
patie nt has c o nse nte d t o all o w tiss ue t o be ke pt f or c urre nt a n d/ or f ut ure researc h, o nl y 
o ne bl oc k nee ds t o be s u b mitte d. 
1  
Patie nts w h o a ns were d, “ yes” t o m o del c o nse nt q uesti o n # 1. 
2  
Patie nts w h o a ns were d, “ yes” t o m o del c o nse nt q uesti o n # 2 a n d # 3. 
5. 4. 1 
Ser u m a n d Pl as m a S u b missi o n f or t he C orrel ati ve S u bst u d y ( 1 5 0 9 0 3)  
F or patie nts w h o c o nse nt t o partici pate ( m o del c o nse nt q uesti o n # 1), b ot h ser u m 
a n d plas ma will be use d f or t he bi o mar ker a nal yses descri be d i n Secti o n s 1 0. 1 a n d 
1 0. 2 . S u b missi o n of b ot h s peci me n t y pes is re q uire d. 
W h ole bl o o d ( 2 0 m L) will be c ollecte d at baseli ne ( pri or t o i nitiati o n of t hera p y), 
at eac h of t he first t w o P E T/ C T sca ns, a n d at t he ti me of eac h P E T/ C T sca n d uri n g 
t he first 3 years of p ost- treat me nt f oll o w-u p. T hat is, bl o o d will be c ollecte d at t he 
f oll o wi n g 1 1 or 1 2 ti me p oi nts: 
1.  Pri or t o i nitiati o n of t hera p y  
2.  At t he ti me of t he sec o n d P E T/ C T sca n ( p ost c ycle 2)  
3.  At  t he  ti me  of  t he  t hir d  P E T/ C T  sca n  (at  c he m o  c o m pleti o n  f or  P E T 
ne gati ve  patie nts; at p ost I F R T c o m pleti o n f or P E T p ositi ve patie nts)  
4.  3 m o nt hs p ost- treat me nt 
5.  6 m o nt hs p ost- treat me nt 
6.  9 m o nt hs p ost- treat me nt 
7.  1 2 m o nt hs p ost- treat me nt 
8.  1 8 m o nt hs p ost- treat me nt 
9.  2 4 m o nt hs p ost- treat me nt 
1 0.  3 0 m o nt hs p ost- treat me nt 
1 1.  3 6 m o nt hs p ost- treat ment 
5. 4. 1. 1 
Ser u m C ollecti o n Pr oce d ures  
F or patie nts w h o c o nse nt t o partici pate ( m o del c o nse nt q uesti o n # 1), ser u m 
sa m ples will be use d f or t he st u dies descri be d i n Secti o n 1 0. 1 .  
1. 
C ollect  bl o o d  i n  1 0  m L  Re d  T o p  T u be.  After  c ollecti o n,  t u bes 
(“ vac utai ners”)  s h o ul d  sit  u pri g ht  after  t he  bl o o d  is  dra w n  at  r o o m 
te m perat ure f or a mi ni m u m of 3 0 t o a ma xi m u m of 6 0 mi n utes t o all o w 
t he cl ot t o f or m. N ote: Use re d t o p (ser u m) t u bes (silic o n-c oate d) — n o 
a d diti ves a n d n ot S S T (ser u m se parat or t u bes).  
2. 
Ce ntrif u ge  t he  bl o o d  sa m ple  at  t he  e n d  of  t he  cl otti n g  ti me  ( 3 0 - 6 0 
mi n utes) i n a h oriz o ntal r ot or (s wi n g -o ut hea d) f or 2 0 mi n utes at 1 1 0 0 -
1 3 0 0 g at r o o m te m perat ure.   
3. 
Use  a  pi pette  t o  tra nsfer  t he  ser u m  ( Rec o m me n dati o n:  d o  n ot  p o ur). 
Pi p ette ser u m i nt o t he la bele d cr y o vials (rec o m me n de d cr y o vials are 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
2 5  
U p date # 1 3  
descri be d i n Secti o n 5. 4. 1. 3 ). Ali q u ot v ol u me is t o be 5 0 0 µ L. Cl ose 
t he ca ps o n t he vials ti g htl y. T his pr ocess s h o ul d be c o m plete d wit hi n 
1 h o ur of ce ntrif u gati o n. N ote: Be ver y caref ul n ot t o pic k u p re d bl o o d 
cells w he n ali q u oti n g. T his ca n be d o ne b y kee pi n g t he pi pet a b o ve t he 
re d bl o o d cell la yer a n d lea vi n g a s mall a m o u nt of ser u m i n t he t u be.  
4. 
C hec k t hat all ali q u ot vial ca ps are sec ure a n d t hat all vi als are la bele d.  
5. 
Place  all  ali q u ots  u pri g ht  i n  a  s peci me n  b o x  or  rac k  i n  a n -8 0° C  or 
c ol der freezer. All s peci me ns s h o ul d re mai n at -8 0° C or c ol der pri or t o 
s hi p pi n g. T he C A L G B 5 0 8 0 1 sa m ples s h o ul d n ot be t ha we d pri or t o 
s hi p pi n g. Ser u m s h o ul d be s hi p pe d o n dr y ice acc or di n g t o t he s hi p pi n g 
pr oce d ures i n Secti o n 5. 4. 1. 3 . 
5. 4. 1. 2 
Pl as m a C ollecti o n P r oce d ures  
F or patie nts w h o c o nse nt t o partici pate ( m o del c o nse nt q uesti o n # 1), plas ma 
sa m ples will be use d f or t he st u dies descri be d i n Secti o n 1 0. 2 .  
1. 
C ollect bl o o d i n 1 0 m L P ur ple T o p T u be. After c ollecti o n, ge ntl y mi x 
t he bl o o d b y i n verti n g t he t u be 8 t o 1 0 ti mes. St ore vac utai ner t u bes 
u pri g ht  at  4° C  u ntil  ce ntrif u gati o n.  Bl o o d  sa m ples  s h o ul d  be 
ce ntrif u ge d wit hi n f o ur h o urs of bl o o d c ollecti o n.   
2.  
Ce ntrif u ge bl o o d sa m ples i n a h oriz o ntal r ot or (s wi n g- o ut hea d) f or 1 0 
t o 2 0 mi n utes at 1 1 0 0-1 3 0 0 g at r o o m te m perat ure. War ni n g: E xcessi ve 
ce ntrif u ge s pee d ( o ver 2 0 0 0 g) ma y ca use t u be brea ka ge a n d e x p os ure 
t o bl o o d a n d p ossi ble i nj ur y.  If nee de d, R C F f or a ce ntrif u ge ca n be 
calc ulate d.  F or  a n  o n -li ne  calc ulat or  t o ol,  please  refer  t o: 
  
3. 
After  ce ntrif u gati o n,  plas ma  la yer  will  be  at  t he  t o p  of  t he  t u be. 
M o n o n uclear cells a n d platelets will be i n a w hitis h la yer, calle d t he 
“ b uff y c oat”, j ust u n der t he plas ma a n d a b o ve t he re d bl o o d cells.  
4. 
Caref ull y c ollect t he plas ma la yer wit h a n a p pr o priate tra nsfer pi pette 
wit h o ut  dist ur bi n g  t he  b uff y  c oat  la yer.  Pi pette  t he  plas ma  i nt o  t he 
la bele d  cr y o vials  (rec o m me n de d cr y o vials  are  descri be d  i n Secti o n 
5. 4. 1. 3 ). Ali q u ot v ol u me is t o be 5 0 0 µ L. Cl ose t he ca ps ti g htl y a n d 
place  o n  ice.  T his  pr ocess  s h o ul d  be  c o m plete d  wit hi n  1  h o ur  of 
ce ntrif u gati o n.   
5. 
C hec k t hat all ali q u ot vial ca ps are  sec ure an d t hat all vials are la bele d.  
6. 
Place  all  ali q u ots  u pri g ht  i n  a  s peci me n  b o x  or  rac k  i n  a n -8 0° C  or 
c ol der freezer. All s peci me ns s h o ul d re mai n at -8 0° C or c ol der pri or t o 
s hi p pi n g. T he sa m ples s h o ul d n ot be t ha we d pri or t o s hi p pi n g. Plas ma 
s h o ul d be s hi p pe d o n dr y ice acc or di n g t o t he s hi p pi n g pr oce d ures i n 
Secti o n 5. 4. 1. 3 . 

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6. 0  
R E Q UI R E D D A T A  
G ui deli nes F or Pre- St u d y Testi n g 
T o be c o m plete d wit hi n 1 6 D A Y S bef ore re gistrati o n: 
-  All bl o o d w or k 
- Hist or y a n d p h ysical e xa mi nati o n 
T o be c o m plete d wit hi n 2 8 D A Y S bef ore re gistrati o n: 
-  A n y sca n of a n y t y pe (e. g., P E T, C T, or M RI) t hat is utilize d f or t u m or meas ure me nt 
T o be c o m plete d wit hi n 4 2 D A Y S bef ore re gistrati o n: 
- A n y baseli ne e xa ms use d f or scree ni n g (i.e., M U G A, P F Ts)  
- A n y sca n of a n y t y pe, or ultras o u n d of u ni n v ol ve d or ga ns t hat is n ot utilize d f or t u m or meas ure me nt  
Tests & O bser vati o ns  
Pri or  
t o St u d y  
D a y 1 of  
E ac h 
C y cle *  
D a y 1 5 of  
E ac h 
C y cle * *  
Ti me of 
Rest a gi n g  
 
P ost Tre at me nt F oll o w -u p  
( after c y cle 2 of A B V D a n d 
f oll o wi n g eit her c y cle 6 of 
A B V D or I F R T) * * *  
Hist or y a n d Pr o gress N otes  
X  
X  
 
 
X  
P h ysical E xa mi n ati o n  
X  
X  
 
 
X  
Hei g ht/ Wei g ht/ B S A  
X  
 
 
 
 
P erf or ma nce Stat us  
X  
X  
 
 
 
T u m or Meas ure me nts  
X  
A  
 
X  
X  
Dr u g T o xicit y Ass ess me nt  
 
X  
X  
X  
X  
L a b or at or y St u dies  
 
 
 
 
 
C B C, Differe ntial, Platelets  
G  
X  
X * *  
X  
 
E S R  
G  
 
 
X  
 
Ser u m Creati ni n e  
G  
X  
 
X  
 
Gl uc ose  
G  
 
 
X  
 
A S T, Al kali ne P h os p h atase, Bilir u bi n  
G  
X  
 
X  
 
Ser u m or uri ne β H C G  
X 
 
 
 
 
L D H  
G 
 
 
 
 
L V E F b y E C H O or M U G A  
F  
 
 
 
P R N  
P F Ts (i ncl u di n g D L C O/ F V C)  
F 
 
 
 
P R N 
HI V (if re q uire d, see secti o n 4. 5) 
B 
 
 
 
 
St a gi n g  
 
 
 
 
 
C T sca n ( nec k, c h est, a b d o me n/ p el vis)  
F , H  
 
 
X  
D  
F D G -P E T/ C T sc a n †  
E , F 
 
 
C 1 -3  
 
C hest X -ra y, P A & Lateral  
F 
 
 
 
 
Hist ol o gic Re vie w (s ee S ecti o n 5. 3 ) 
X 
 
 
 
 
C A L G B 1 5 0 9 0 3 (c o nse nti n g p atie nts)  
F F P E tiss ue  
At b aseli n e a n d at t h e ti me of pr o gressi o n / rela pse.  
W h ole bl o o d f or mar ker a n al ysis  
Pri or  t o  re gistrati o n;  at  t h e  ti me  of  t h e  p ost -c ycle  2  P E T/ C T  sca n,  c he m o 
c o m pleti o n P E T/ C T sca n; p ost I F R T P E T/ C T sc a n (if p ost -c ycle 2 P E T/ C T sc a n 
is p ositi ve); at 3, 6, 9, 1 2, 1 8, 2 4, 3 0 a n d 3 6 m o nt hs p ost-treat me nt f oll o w-u p.  
†  I nstit uti o ns m ust be cre de ntiale d b y t he Allia nce  I ma gi n g C ore La b at I R O C O hi o  pri or t o e nr olli n g 
patie nts (see  Secti o n 8. 1. 1 ). It is critical t hat all F D G-P E T/ C T sca ns be perf or me d i n a n i de ntical wa y 

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t o t he baseli ne sca n, wit h t he sa me sca n ner, sa me sca n directi o n, a n d c o nsiste nt ar m p ositi o ni n g. T he 
i nter val bet wee n F D G i njecti o n a n d i nitiati o n of e missi o n sca n ni n g s h o ul d be t he sa me or si milar t o 
t he baseli ne sca n. 
* Wit hi n 4 8 h o urs pri or t o da y 1 of A B V D or B E A C O P P. 
* *  
Wit hi n 4 8 h o urs pri or t o da y 1 5 of eac h treat me nt c ycle of A B V D. 
* * * 
E ver y 3 m o nt hs  f or o ne year fr o m t he res p o nse assess me nt at t he c o m pleti o n of t hera p y, 
t he n e ver y 6 m o nt hs f or years 2 a n d 3, a n d t he n a n n uall y f or a ma xi m u m of te n years fr o m st u d y 
e ntr y.  
A If accessi ble t o p h ysical e xa mi nati o n, rec or d meas ure me nts o n da y 1 of eac h c ycle. 
B A n HI V test is n ot re q uire d f or e ntr y o n t his pr ot oc ol, b ut is re q uire d if t he patie nt is percei ve d t o 
be at ris k.  
C 1 
P ost -c ycle 2 F D G-P E T/ C T sca ns m ust be perf or me d 8 -1 0 da ys after t he Da y -1 5 d ose of 
A B V D  d uri n g  c ycle  2. (i.e. o n  da y  2 3,  2 4 or 2 5  o f  c ycle  2, see Secti o n  8. 2  f or  acce pta ble  F D G-
P E T/ C T sca n c o m pleti o n da ys).   
C 2 
F or  patie nts  w h o  are  P E T ne gati ve  after  2  c ycles  of  A B V D,  p ost -treat me nt  c o m pleti o n 
F D G -P E T/ C T will be perf or me d ≥ 3 a n d ≤ 8 wee ks after c o m pleti o n o f c he m ot hera p y. 
C 3 
F or patie nts w h o are P E T p ositi ve after 2 c ycles of A B V D, p ost -I F R T F D G-P E T/ C T sca ns 
m ust be perf or me d ≥1 2 wee ks a n d ≤1 6 wee ks after c o m pleti o n of I F R T. 
D C o ntrast- e n ha nce d helical/s piral C T sca ns of t he c hest, a b d o me n, a n d pel vis will be o btai ne d e ver y 
3 m o nt hs f or year o ne a n d e ver y 6 m o nt hs f or years 2 -3 a n d a n n uall y f or years 4 - 5. F oll o w-u p r o uti ne 
C Ts of t he nec k will n ot us uall y be necessar y, si nce m ost rec urre nces i n t he nec k will be f o u n d b y 
p h ysical e xa mi nati o n. 
E Baseli ne F D G - P E T/ C T will be o btai ne d ≤ 2 8 da ys pri or t o re gistrati o n. See S ecti o n 5. 1. 2  i n t he 
case of a patie nt w h o has alrea d y ha d a baseli ne sca n at a n ot her facilit y.  
F If a patie nt has ha d o ne pre vi o us c ycle of A B V D pri or t o e nr olli n g o n st u d y, t he patie nt m ust ha ve 
ha d t he f oll o wi n g tests pri or t o starti n g t he pre vi o us c ycle of A B V D: L V E F, P F Ts, C T sca n, F D G -
P E T/ C T sca n, a n d c hest x -ra y. T hese tests d o n ot nee d t o be re peate d pri or t o st u d y i n t h ose patie nts 
wit h a pre vi o us c ycle of A B V D.  
G If a patie nt has ha d o ne pre vi o us c ycle of A B V D pri or t o e nr olli n g o n st u d y, t he patie nt m ust ha ve 
ha d t he f oll o wi n g tests pri or t o starti n g t he pre vi o us c ycle of A B V D: C B C, differe ntial, platelets; 
E S R; ser u m creati ni ne; gl uc ose; A S T, al kali ne p h os p hatase, bilir u bi n; a n d L D H. T hese tests d o n ot 
nee d t o be re peate d pri or t o st u d y i n t h ose patie nts wit h a pre vi o us c ycle of A B V D.  
H Patie nts wit h a ne gati ve F D G - P E T/ C T sca n d o n ot nee d t o ha ve a de dicate d nec k C T sca n pri or t o 
st u d y. 
P R N As cli nicall y i n dicate d.  

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7. 0  
T R E A T M E N T P L A N  
I nstit uti o ns m ust be cre de ntiale d b y t he Allia nce  I ma gi n g C ore La b at I R O C Ohi o pri or t o e nr olli n g 
patie nts (see Secti o n 8. 1. 1 ). 
Patie nts m ust be gi n treat me nt wit hi n 7 da ys of re gistrati o n. Q uesti o ns re gar di n g treat me nt ma y be 
directe d t o t he St u d y C hair. 
A misse d or v o mite d d ose of oral a ge nt s h o ul d n ot be ma de u p.  
7. 1 
C he m ot her a p y Re gi me ns  
M o n da ys  a n d  T ues da ys  are  rec o m me n de d  as  t hera p y  i nitiati o n  da ys  t o  ass ure  a  ti mel y 
ce ntral P E T rea di n g.  
7. 1. 1 
A B V D  
T hera p y will c o nsist of d o x or u bici n, ble o m yci n, vi n blasti ne, a n d dacar bazi ne o n 
Da ys 1 a n d 1 5 of eac h c ycle. A c ycle will be c o nsi dere d 2 8 da ys. 
D o x or u bici n 2 5 m g/ m 2 I V o n Da ys 1 a n d 1 5 of eac h c ycle 
Ble o m yci n 1 0 u nits/ m 2 I V o n Da ys 1 a n d 1 5 of eac h c ycle 
Vi n blasti ne 6 m g/ m 2 I V o n Da ys 1 a n d 1 5 of eac h c ycle 
Dacar bazi ne 3 7 5 m g/ m 2 I V i nf usi o n o n Da ys 1 a n d 1 5 of eac h c ycle 
All  patie nts  will  recei ve  2  c ycles  of  A B V D. F or  patie nts  w h o  ha ve  ha d  o ne 
pre vi o us c ycle of A B V D pri or t o re gistrati o n, t he pre vi o us c ycle will be c o nsi dere d 
c ycle 1. Patie nts w h o ac hie ve a C R, P R, or S D a n d w h ose P E T sca ns are ne g ati v e 
after  t w o  c ycles  of  A B V D  (see Secti o n  8. 2  f or  ti mi n g  of  i ma gi n g  st u dies)  will 
recei ve f o ur m ore c ycles of A B V D (a t otal of si x c ycles). 
See Secti o n 9. 0  f or d ose m o dificati o ns a n d ma na ge me nt of t o xicit y. See Secti o n 
1 2. 0  f or a ncillar y t hera p y. 
7. 1. 2 
Esc al ate d B E A C O P P  
Patie nts w h o ac hie ve a C R, P R, or S D a n d w h ose P E T sca ns are p ositi ve  after t w o 
c ycles  of  A B V D  will  recei ve  f o ur  c ycles  of  escalate d  B E A C O P P  f oll o we d  b y 
i n v ol ve d-fiel d ra di ot hera p y (see secti o n 7. 2): 
Ble o m yci n 1 0 u nits/ m 2 I V o n Da y 8 of eac h c ycle 
Et o p osi de 2 0 0 m g/ m 2 I V o ver 6 0 mi n utes o n Da ys 1, 2 a n d 3 of eac h c ycle 
D o x or u bici n 3 5 m g/ m 2 I V o n Da y 1 of eac h c ycle 
C ycl o p h os p ha mi de 1 2 5 0 m g/ m 2 I V o ver 6 0 mi n utes o n Da y 1 of eac h c ycle 
Vi ncristi ne 1. 4 m g/ m 2 ( ma xi m u m 2 m g) I V o n Da y 8 of eac h c ycle 
Pr ocar bazi ne *  1 0 0 m g/ m 2 (r o u n de d t o nearest 5 0 m g) orall y o n Da ys 1-7 of eac h 
c ycle 
Pre d nis o ne *  4 0 m g/ m 2 (r o u n de d t o nearest 5 m g) orall y o n Da ys 1- 1 4 of eac h c ycle  
Re peat escalate d B E A C O P P treat me nt e ver y 2 1 da ys f or f o ur c ycles.  
Fil grasti m ( G -C S F) *  5 mc g/ k g s u bc uta ne o usl y o n Da ys 8 -1 4 of eac h c ycle. G -
C S F ma y be disc o nti n ue d w he n, after reac hi n g t he na dir, t he ne utr o p hil c o u nt has 
re mai ne d o ver 1, 0 0 0/ m m3 o n 3 s uccessi ve da ys. D o n ot gi ve escalate d B E A C O P P 
wit hi n 4 8 h o urs of fil grasti m. 

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A nti bi otic pr o p h yla xis * wit h c otri m o xaz ole, o ne d o u ble stre n gt h ta blet t wice dail y 
is  re q uire d  o n  da ys  8-1 5  of  eac h  c ycle.  Da ps o ne  ( 5 0  m g  orall y  t wice  dail y)  or 
pe nta mi di ne ma y be s u bstit ute d f or P ne u m oc ystis pr o p h yla xis i n s u bjects aller gic 
t o c otri m o xaz ole. 
See Secti o n 9. 0  f or d ose m o dificati o ns a n d ma na ge me nt of t o xicit y. See Secti o n 
1 2. 0  f or a ncillar y t hera p y. 
* Patie nts s h o ul d rec or d t he d oses of pr ocar bazi ne, pre d nis o ne a n d a nti bi otic ta ke n, 
as well as t he da y i n w hic h G -C S F i nj ecti o n is gi ve n o n t he C A L G B f or m S - 0 6 8 
( 5 0 8 0 1 Me dicati o n Cale n dar). ( See Secti o n 5. 2 ) 
7. 1. 3 
St a n d ar d B E A C O P P  
Patie nts w h o are HI V -p ositi ve a n d w h ose P E T sca ns are p ositi ve  after t w o c ycles 
of A B V D will recei ve f o ur c ycles of sta n dar d B E A C O P P f oll o we d b y i n v ol ve d -
fiel d ra di ot hera p y (see secti o n 7. 2). 
Ble o m yci n 1 0 u nits/ m 2 I V o n Da y 8 of e ac h c ycle 
Et o p osi de 1 0 0 m g/ m 2 I V o ver 6 0 mi n utes o n Da ys 1, 2 a n d 3 of eac h c ycle 
D o x or u bici n 2 5 m g/ m 2 b y I V o n Da y 1 of eac h c ycle 
C ycl o p h os p ha mi de 6 5 0 m g/ m 2 I V o ver 6 0 mi n utes o n Da y 1 of eac h c ycle 
Vi ncristi ne 1. 4 m g/ m 2 ( ma xi m u m 2 m g) I V o n Da y 8 of eac h c ycle  
Pr ocar bazi ne * 1 0 0 m g/ m 2 (r o u n de d t o nearest 5 0 m g) orall y o n Da ys 1 -7 of eac h 
c ycle 
Pre d nis o ne * 4 0 m g/ m 2 (r o u n de d t o nearest 5 m g) orall y o n Da ys 1 -1 4 of eac h c ycle
  
 
Re peat sta n dar d B E A C O P P treat me nt e ver y 2 1 da ys f or f o ur c ycles.  
Fil grasti m ( G -C S F ) * 5 mc g/ k g s u bc uta ne o usl y o n Da ys 8 -1 4 of eac h c ycle. G -
C S F ma y be disc o nti n ue d w he n, after reac hi n g t he na dir, t he ne utr o p hil c o u nt has 
re mai ne d o ver 1, 0 0 0/ m m 3 o n 3 s uccessi ve da ys. D o n ot gi ve sta n dar d B E A C O P P 
wit hi n 4 8 h o urs of fil grasti m. 
A nti bi otic pr o p h yla xis * wit h c otri m o xaz ole, o ne d o u ble stre n gt h ta blet t wice dail y 
is  re q uire d  o n  da ys  8-1 5  of  eac h  c ycle.  Da ps o ne  ( 5 0  m g  orall y  t wice  dail y)  or 
pe nta mi di ne ma y be s u bstit ute d f or P ne u m oc ystis pr o p h yla xis i n s u bjects aller gic 
t o c otri m o xaz ole. 
See Secti o n 9. 0  f or d ose m o dificati o ns a n d ma na ge me nt of t o xicit y. See Secti o n 
1 2. 0  f or a ncillar y t hera p y. 
* Patie nts s h o ul d rec or d t he d oses of pr ocar bazi ne, pre d nis o ne a n d a nti bi otic ta ke n, 
as well as t he da y i n w hic h G-C S F i nj ecti o n is gi ve n o n t he C A L G B f or m S - 0 6 8 
( 5 0 8 0 1 Me dicati o n Cale n dar). ( See Secti o n 5. 2 ) 
7. 2  
I n v ol ve d- Fiel d R a di ati o n T her a p y (I F R T)  
7. 2. 1 
A d mi nistr ati o n of I F R T  
A d mi nistrati o n  of  i n v ol ve d -fiel d  ra diati o n  t hera p y (I F R T)  will  de pe n d  o n  P E T 
res p o nse (see Secti o n 8. 0 ) after 2 c ycles of A B V D as f oll o ws: 
1.  Patie nts w h o are P E T ne gati ve after 2 c ycles of A B V D will n ot  recei ve 
I F R T. 

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2.  Patie nts w h o are P E T p ositi ve after 2 c ycles of A B V D, will  recei ve I F R T 
f oll o wi n g  4  c ycles  of  escalate d  B E A C O P P.  T hese  patie nts  will  recei ve 
3 0. 6 G y I F R T. 
A  peri o d  of  3 -6  wee ks  will  ela pse  bet wee n  t he  be gi n ni n g  of  t he  last  d ose  of 
c he m ot hera p y a n d t he be gi n ni n g of ra diati o n t hera p y, I F R T ma y n ot be gi n u ntil 
t he W B C is > 2, 0 0 0/ micr oliter a n d t he platelet c o u nt is > 1 0 0, 0 0 0/ micr oliter. 
7. 2. 2 
E q ui p me nt  
E ner g y :  4-1 0  M V  p h ot o ns  are  re q uire d  f or  all  disease  sites.  C o balt -6 0  is n ot 
all o we d. I M R T is n ot all o we d. Pr ot o n t hera p y is n ot all o we d. 
Ge o metr y : I n ge neral, parallel o p p ose d e q uall y wei g hte d fiel ds ( A P/ P A) are m ost 
a p pr o priate. Is oce ntric tec h ni q ue wit h S A D ≥ 8 0 c m is prefera ble, wit h t he patie nt 
s u pi ne i n t he sa me p ositi o n f or b ot h t he A P a n d P A treat me nts. F or lar ge fiel d sizes 
(e. g., nec k pl us me diasti n u m), e xte n de d dista nce a n d S S D tec h ni q ue are all o we d, 
wit h t he S S D i n t he 1 1 0 -1 2 0 c m ra n ge. I n t his setti n g, S S D tec h ni q ue w here t he 
patie nt t ur ns fr o m s u pi ne t o pr o ne is acce pta ble.  
Si m ul ati o n : C T base d treat me nt pla n ni n g is re q uire d f or all patie nts.  
C ali br ati o n:  All  t hera p y  u nits  use d  f or  t his  pr ot oc ol  s hall  ha ve  cali brati o ns 
verifie d b y t he Ra di ol o gical P h ysics Ce nter. 
7. 2. 3 
Re q uire d Be nc h m ar ks  
Ce nters partici pati n g i n t his pr ot oc ol usi n g 3 D -C R T are re q uire d t o c o m plete t he 
3 D Be nc h mar k. Be nc h mar k materials ma y be o btai ne d fr o m t he Q ualit y Ass ura nce 
Re vie w  Ce nter  ( w w w. qarc. or g )  a n d  m ust  be  s u b mitte d  bef ore  patie nts  o n  t his 
pr ot oc ol ca n be e val uate d.  
7. 2. 4 
Pl a n ni n g T ar get V ol u me  
G ui deli nes f or deli neati n g t he i n v ol ve d fiel d ha ve  bee n pre vi o usl y p u blis he d [ 2 9]. 
Briefl y,  a  re gi o n,  n ot  i n di vi d ual  l y m p h  n o des,  is  treate d.  I n  ge neral,  pre -
c he m ot hera p y v ol u mes are utilize d, wit h t he e xce pti o n of t he tra ns verse dia meter 
of  me diasti nal  disease.  T o  s pare  n or mal  tiss ue,  p ost -c he m ot hera p y  vol u mes  are 
treate d i n t his circ u msta nce. All sites i n v ol ve d at prese ntati o n nee d t o be i ncl u de d 
i n t he  treat me nt  fiel ds. Treat me nt  will  i ncl u de t he  v ol u mes  as  descri be d  bel o w. 
Ori gi nal e xte nt of disease pl us 2. 0 c m mar gi n m ust be i ncl u de d; t his s u perse des all 
ot her  re q uire me nts. T he  o nl y  e xce pti o n  is  f or fiel ds  near critical  or ga ns  (l u n gs) 
w he n a 1- 1. 5 c m mar gi n ma y be acce pta ble (see bel o w).  
T he Gr oss T u m or V ol u me  ( G T V) is defi ne d as t he v ol u me occ u pie d b y visi ble 
or  pal pa ble  disease,  a n d  will  be  li mite d  t o  areas  of  disease  as  defi ne d  at 
prese ntati o n  a n d  i ncl u des  resi d ual  disease  prese nt  after  t he  c o m pleti o n  of 
c he m ot hera p y.  T he Cli nic al  T ar get  V ol u me  ( C T V)  is  t he  a nat o mical 
c o m part me nt(s)  i n  w hic h  t he  G T V  is  l ocate d.  T he Pl a n ni n g  T ar get  V ol u me  
( P T V) is defi ne d as t he mar gi n ar o u n d t he C T V t o acc o u nt f or patie nt m oti o n a n d 
set- u p varia bilit y. T he P T V fiel ds are o utli ne d bel o w. 
•  
U nil ater al Cer vic al/ S u pr acl a vic ul ar Re gi o n:  I n v ol ve me nt at a n y u nilateral 
cer vical  le vel  wit h  or  wit h o ut  i n v ol ve me nt  of  t he  i psilater al  s u pracla vic ular 
( S C L) n o des. Ar ms a ki m b o or at si des. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
3 3  
U p date # 1 3  
U p per B or der:  1-2 c m a b o ve t he l o wer ti p of t he mast oi d pr ocess a n d mi d p oi nt 
t hr o u g h  t he  c hi n.  If  o nl y  t he  S C L  n o des  are  i n v ol ve d  ( n o  cer vical  n o dal 
i n v ol ve me nt), t he u p per b or der s h o ul d be place d at t he t o p of t he lar y n x. 
L o wer B or der:  2 c m bel o w t he b ott o m of t he cla vicle. 
L ater al B or der:  T o i ncl u de t he me dial 2/ 3 of t he cla vicle. 
Me di al B or der:  
( a) If t he s u pracla vic ular n o des are n ot i n v ol ve d, place t he b or der at t he 
i psilateral tra ns verse pr ocesses e xce pt w he n me dial n o des cl ose t o t he 
verte bral b o dies are prese nt o n i nitial sta gi n g, i n w hic h case t he b or der 
s h o ul d all o w 2 c m mar gi n or i ncl u de t he e ntire verte bral b o d y. 
( b) W he n  t he  i psilateral  s u pracla vic ular  n o des  are  i n v ol ve d,  t he  b or der  
s h o ul d be place d at t he c o ntralateral tra ns verse pr ocesses. 
Bl oc ks: 
( a) Mi d -nec k calc ulati o ns s h o ul d be perf or me d t o deter mi ne t he ma xi m u m 
s pi nal c or d d ose. 
( b) A s mall a nteri or lar y n x bl oc k ma y be use d t hr o u g h o ut treat me nt u nless 
t his bl oc k w o ul d s hiel d disease.  
•  
Bil ater al  Cer vic al/ S u pr acl a vic ul ar  Re gi o n:  Treat  b ot h  cer vical  a n d 
s u pracla vic ular re gi o ns as descri be d a b o ve. Use a p osteri or m o ut h bl oc k o n t he 
p osteri or- a nteri or fiel d t o bl oc k t he u p per fiel d di ver gi n g t hr o u g h t he m o ut h. 
Bl oc ks ma y be use d as descri be d a b o ve.  
•  
Me di asti n u m:  I n v ol ve me nt of t he me diasti n u m a n d/ or t he hilar n o des. T he 
fiel d  i ncl u des  als o  t he  bilateral  me dial  S C L  n o des  e ve n  if  n ot  cli nicall y 
i n v ol ve d. Ar ms a ki m b o, at si des, or u p. 
U p per  B or der:  C 5 -C 6  i nters pace  if  t he  S C L  n o des  were  n ot  ori gi nall y 
i n v ol ve d. If S C L n o des were i n v ol ve d, t he u p per b or der s h o ul d be place d at 
t he t o p of t he lar y n x a n d t he lateral b or der s h o ul d be a dj uste d as descri be d i n 
t he secti o n o n treati n g nec k n o des. 
L o wer B or der : 5 c m bel o w t he cari na or 2 c m bel o w t he pre -c he m ot hera p y 
i nferi or b or der, w hic he ver is l o wer. 
L ater al B or der:  P ost -c he m ot hera p y G T V wit h 1. 5 c m mar gi n. 
Hil ar Are a:  T o be i ncl u de d wit h 1 c m mar gi n (e xce pt w here G T V re q uires 1. 5 
c m mar gi n).  
He art:  Treat me nt of t he e ntire pericar di u m s h o ul d be li mite d t o patie nts wit h 
e xte nsi ve pericar dial i n v ol ve me nt; i n t his case, t he w h ole heart ca n be treate d 
t o  1 4. 4  G y.  Selecte d  pericar dial  treat me nt  is  reas o na ble  i n  ot her  cli nical 
sit uati o ns, s uc h as e xte nsi o n of a n i nter nal ma m mar y n o de t o t he pericar di u m, 
or ri g ht -si de d pericar dial fat pa d i n v ol ve me nt a butti n g t he pericar di u m wit h o ut 
eff usi o n. 
•  
Me di asti n u m wit h i n v ol ve me nt of t he cer vic al n o des:  W he n b ot h cer vical 
re gi o ns are i n v ol ve d, t he fiel d is a ma ntle wit h o ut a xillae usi n g t he g ui deli nes 
descri be d a b o ve. If o nl y o ne cer vical c hai n is i n v ol ve d, t he verte bral b o dies, 
c o ntralateral u p per nec k, a n d lar y n x ca n be bl oc ke d as pre vi o usl y descri be d.  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
3 4  
U p date # 1 3  
•  
A xill ar y Re gi o n:  T he i psilateral a xillar y, i nfracla vic ular, a n d s u pracla vic ular 
areas are treate d w he n t he a xilla is i n v ol ve d. W he ne ver p ossi ble use C T -base d 
pla n ni n g f or t his re gi o n.  
U p per B or der : C 5 -C 6 i nters pace or i nferi or b or der of t he lar y n x (if n o S C L 
i n v ol ve me nt; ot her wise m o dif y fiel d as n ote d a b o ve). 
L o wer B or der:  T he ti p of t he sca p ula or 2 c m bel o w t he l o west a xillar y n o de, 
w hic he ver is l o wer.  
Me di al B or der : I psilateral cer vical tra ns verse pr ocess. I ncl u de t he verte bral 
b o dies o nl y if t he S C L is i n v ol ve d. 
L ater al B or der:  Flas h a xilla.  
•  
U n us u al Sites ( W al de yer’s Ri n g):  T o be disc usse d wit h t he C A L G B 5 0 8 0 1 
Ra diati o n O nc ol o g y C o -C h air.  
7. 2. 5 
T ar get D ose  
All fiel ds will be treate d t o a t otal d ose of 3, 0 6 0 c G y, calc ulate d at t he is oce nter or 
at t he ce ntral a xis at mi d pla ne. Eac h dail y fracti o n will be 1 8 0 c G y. 
7. 2. 6 
Ti me -D ose C o nsi der ati o ns  
Prescri be 1 8 0 c G y per fracti o n t o t he prescri pti o n p oi nt. Treat wit h 1 fracti o n/ da y, 
5 fracti o ns/ wee k. Treat all fiel ds eac h da y. N o d ose a dj ust me nts will be ma de  f or 
treat me nt i nterr u pti o ns.  
7. 2. 7 
D ose U nif or mit y a n d Refere nce P oi nts  
E ver y  eff ort  s hall  be  ma de  t o  ma ke  t he  d ose  u nif or m  t hr o u g h o ut  t he  treat me nt 
v ol u me. T he d ose s h o ul d be 3, 0 6 0 c G y ± 7. 5 % t hr o u g h o ut t he treat me nt v ol u me. 
D oses s h o ul d be carrie d at t he ce ntral a xis, 2 c m a b o ve t he i nferi or fiel d e d ge a n d 
2  c m  bel o w  t he  s u peri or  fiel d  e d ge.  Off -a xis  refere nce  p oi nts  s h o ul d  als o  be 
carrie d,  as  a p pr o priate  f or  t he  fiel d  (e. g.,  mi d -nec k,  mi d -a xilla,  S C L). 
C o m pe nsat ors/ b o osti n g/ bl oc ki n g  is  all o we d  w he n  nec essar y  t o  ac hie ve  t he  
± 7. 5 % h o m o ge neit y. 
7. 2. 8 
Heter o ge neit y C orrecti o ns  
Calc ulati o ns t hat ta ke i nt o acc o u nt tiss ue heter o ge neities s hall be use d.  
7. 2. 9 
Tre at me nt Tec h ni q ues  
P atie nt  P ositi o n : S u pi ne  t hr o u g h o ut  is  prefera ble.  Ge nerall y  treat  wit h  ar ms 
a ki mb o ( ha n ds o n hi ps). If a xillar y l y m p h n o des are i n v ol ve d, p ositi o ni n g wit h t he 
ar ms u p is als o acce pta ble. Ot her s pecific p ositi o ni n g rec o m me n dati o ns are n ote d 
a b o ve. A p pr o priate i m m o bilizati o n de vices are hi g hl y rec o m me n de d. 
Fiel d S h a pi n g : Use c ust o m s hie l di n g wit h di ver ge nt a n d i n di vi d uall y c ut bl oc ks 
or m ultileaf c olli mat ors. Treat me nt will be verifie d wit h wee kl y p ortal fil ms.  
7. 2. 1 0 N or m al Tiss ue S p ari n g  
T he ma xi m u m d ose t o a n y p oi nt i n t he s pi nal c or d will be ≤ 4, 0 0 0 c G y. 
T he v ol u me of l u n g recei vi n g o ver 2 0 G y ( V 2 0) will be ≤ 3 5 %. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
3 7  
U p date # 1 3  
P D  at  a n y  ti me  will  be  re m o ve d  fr o m  pr ot oc ol  t hera p y.  Patie nts  will  be  e val uate d  f or 
res p o nse after c ycle 2 a n d after c o m pleti o n of treat me nt c he m ot hera p y. P ost c o m pleti o n of 
treat me nt P E T/ C T sca ns m ust be o btai ne d ≥ 3 wee ks b ut ≤ 8 wee ks fr o m c o m pl eti o n of 
last  c ycle  of  c he m ot hera p y f or  P E T  ne gati ve  patie nts  o nl y.  Patie nts  recei vi n g  escalate d 
B E A C O P P + I F R T will als o u n der g o a P E T/ C T sca n ≥ 1 2 wee ks a n d ≤ 1 6 wee ks after 
c o m pleti o n I F R T. 
7. 3. 1  
C R, P R, or S D a n d P E T Ne g ati ve after C o m pleti o n of Tre at me nt  
Patie nts w h o ac hie ve a C R, P R, or S D a n d w h o are P E T ne gati ve after c o m pleti o n 
of treat me nt will be f oll o we d acc or di n g t o t he p ost -treat me nt f oll o w-u p sc he d ule 
i n Secti o n 6. 0 . 
7. 3. 2  
C R, P R, or S D a n d P E T P osi ti ve after C o m pleti o n of Tre at me nt 
F or patie nts w h o ac hie ve a C R, P R, S D a n d w h o are P E T p ositi ve after c o m pleti o n 
of treat me nt, a bi o ps y ma y be perf or me d at t he discreti o n of t he treati n g p h ysicia n. 
If  bi o ps y  ne gati ve,  t he n  t he  patie nt  s h o ul d  be  f oll o we d acc or di n g  t o  t he  p ost -
treat me nt f oll o w-u p sc he d ule i n Secti o n 6. 0 . If bi o ps y p ositi ve, t he n t he patie nt 
s h o ul d be f oll o we d per Secti o n 1 4. 1. 2 . If a bi o ps y is neit her cli nicall y i n dicate d 
n or  me dicall y  feasi ble,  t he n  t he  patie nt  s h o ul d  u n der g o  re peat  P E T/ C T  a n d  C T 
sca ns t hree m o nt hs later. 
If P E T ne gati ve after t hree m o nt hs, t he n t he patie nt will be f oll o we d acc or di n g t o 
t he p ost-treat me nt f oll o w- u p sc he d ule i n Secti o n 6. 0 . 
If PE T p ositi ve after t hree m o nt hs, t he n at t he discreti o n of t he treati n g p h ysicia n 
t he patie nt ma y u n der g o a bi o ps y if cli nicall y feasi ble a n d a p pr o priate.  
If, at t hree m o nt hs, bi o ps y is neit her cli nicall y a p pr o priate n or me dicall y feasi ble, 
t he n  t he  patie nt  s h o ul d  be  f oll o we d  acc or di n g  t o  t he  p ost-treat me nt  f oll o w- u p 
sc he d ule i n Secti o n 6. 0 . 
8. 0  I M A GI N G  
F D G - P E T I ma gi n g, I nter pretati o n, P E T a n d C T Data S u b missi o n, a n d Se mi q ua ntitati ve A nal ysis. 
8. 1 
I nstit uti o n Cre de nti ali n g P r oce d ures f or F D G-P E T/ C T I m a gi n g  
Pri or t o e nr oll me nt of patie nts, i nstit uti o ns m ust be cre de ntiale d t o partici pate i n t he trial 
b y t he Allia nce  Ima gi n g C ore La b or at or y (I C L) at I R O C O hi o if t he y ha ve n ot pre vi o usl y 
bee n cre de ntiale d f or a n y ot her C A L G B trials (see Secti o n 8. 1. 1 ). T he I ma gi n g C ore La b 
has de vel o pe d a n d will pr o vi de a site ma n ual t hat o utli nes all of t he details as t he y re late t o 
t he i ma ge ac q uisiti o n a n d rec o nstr ucti o n.  
8. 1. 1 
F D G -P E T/ C T Re q uire me nts f or P artici p ati o n  
T he partici pati n g ce nter m ust ha ve, or ha ve access t o, a facilit y wit h a n i nte grate d 
p ositr o n-e missi o n t o m o gra p h y a n d c o m p ute d t o m o gra p h y ( P E T/ C T) sca n ner.  
T he  partici pati n g  ce nter  m ust  ha ve  t he  a bilit y  t o  s u b mit  P E T  a n d  C T  st u dies 
electr o nicall y t o t he I C L i n di gital DI C O M f or mat ( ot her f or mats: BI T M A P, J P G, 
har dc o p y  or  sca n ne d  files  are  n ot  acce pta ble).  See Secti o n  8. 9  f or  s u b missio n 
pr oce d ures. 
Partici pati n g  sites  m ust  be  cre de ntiale d  b y  t he  I C L  s o  t hat  t he  perf or ma nce 
c haracteristics a n d i nfrastr uct ure re q uire me nts are met:  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
3 8  
U p date # 1 3  
If  a  site  has  bee n  cre de ntiale d  b y  t he  I C L  f or  partici pati n g  i n  C A L G B  5 0 3 0 3 
P E T/ C T  i ma gi n g  st u d y,  a  pr ot oc ol  refres h me nt  o nl y  will  be  nee de d f or 
partici pati n g i n C A L G B 5 0 8 0 1. 
If a site has ne ver bee n cre de ntiale d b y t he I C L, h o we ver t he site partici pate d or is 
partici pati n g i n a n y ot her Allia nce/ C A L G B  P E T or C T i ma gi n g trials, a pr ot oc ol 
refres h me nt  (a n d  a  Virt ual  Site  Visit,  if  necessar y)  is  re q uir e d  f or  partici pati n g 
C A L G B 5 0 8 0 1. 
If  a  site  has  neit her  bee n  cre de ntiale d  b y  t he  I C L  n or  partici pate d  i n  a n y 
Allia nce/ C A L G B P E T or C T i ma gi n g trials, t he Allia nce / C A L G B I C L will a d here 
t o t he A C RI N criteria f or P E T i ma gi n g a p pr o val pr oce d ures. C o nsiste nc y i n t he 
ac q uisiti o n  pr ot oc ol  b ot h  fr o m  a  ti me  a n d  a n  ac q uisiti o n  m o de  is  re q uire d.  I n 
a d diti o n, data ma na ge me nt m ust be d o ne i n a sta n dar dize d pr ocess. I n or der f or a n 
instit uti o n t o be a p pr o ve d t o partici pate i n t his st u d y, t he y are re q uire d t o s u b mit 
t he f oll o wi n g f or tec h nical a n d q ualit y re vie w b y t he Allia nce  I ma gi n g C ore La b 
at I R O C O hi o : 
1)  T w o test patie nt st u dies ( F O R A L L P E T/ C T i nstr u me nts utilize d)  
I ma ges of tw o u ni de ntifie d patie nts s hall c o nsist of t hree v ol u me or m ultislice files 
as  f oll o ws:  a)  W h ole  b o d y  C T  fr o m  P E T/ C T  sca n ner;  b)  W h ole  b o d y  (t ors o) 
e missi o n wit h atte n uati o n c orrecti o n ( A/ C); a n d c) W h ole b o d y (t ors o) e missi o n 
wit h o ut A/ C. 4  
2)  U nif or m p ha nt o m data wit h t he S U V meas ure me nt of t he p ha nt o m ( F O R A L L 
P E T/ C T i nstr u me nts utilize d)  
Water -filla ble  u nif or m  p ha nt o m:  T he  p ha nt o m  m ust  be  fille d  wit h  water, a n d a 
k n o w n a m o u nt of F -1 8 (eit her as fl u ori de or as F D G) s h o ul d be i njecte d i nt o t he 
p ha nt o m.  T he acti vit y  i njecte d  s h o ul d  be  deter mi ne d  b y  meas ure me nt  of  t he 
s yri n ge bef ore a n d after t he i njecti o n i n a pr o perl y cali brate d d ose cali brat or. T he 
i njecte d acti vit y s h o ul d be c h ose n t o res ult i n a n acti vit y c o nce ntrati o n si milar t o 
t hat e nc o u ntere d i n cli nical F D G i ma gi n g (i.e., 1-1. 5 m Ci of F -1 8 s h o ul d be a d de d 
t o t he 6, 2 8 3 m L p ha nt o m: 2 m Ci f or t he 9. 2 9 3 m L p ha nt o m). After t h or o u g hl y 
mi xi n g t he p ha nt o m, t he p ha nt o m m ust be sca n ne d wit h t he sa me pr ot oc ol use d 
f or  t he  patie nt  i ma gi n g.  T he  i ma ges  als o  m ust  be rec o nstr ucte d  wit h  t he  sa me 
al g orit h m  a n d  filters use d f or  patie nt  i ma gi n g.  A  circ ular or  elli ptical re gi o n  of 
i nterest ( R OI) c o veri n g m ost of t he i nteri or of t he p ha nt o m m ust be dra w n o ver all 
slices, a n d t he a vera ge S U V a n d sta n dar d de viati o n m ust be meas ure d a n d re p orte d 
i n  t he  P E T/ C T  I nstr u me nt  T ec h nical  S pecificati o ns  F or m  (A p pe n di x  I V ).  T he 
e x pecte d S U V f or t he u nif or m p ha nt o m is 1. 0 a n d t he acce pta ble ra n ge is 0. 9 t o 
1. 1. 
( Alter nati vel y)  Ge- 6 8/ Ga-6 8  cali brati o n  p ha nt o m:  T his  p ha nt o m  ca n  rea dil y  be 
sca n ne d  wit h  t he  sa me  pr ot oc ol  use d  f or  patie nt  i ma gi n g.  T he  assa y  date  a n d 
acti vit y fr o m t he cali brati o n certificate of t his p ha nt o m m ust be re p orte d o n t he 
P E T/ C T  I nstr u me nt  T ec h nical  S pecificati o ns  F or m  ( A p pe n di x  I V ).  T he  i ma ges 
m ust be rec o nstr ucte d wit h t he sa me al g orit h m a n d filters use d f or patie nt i ma gi n g. 
A circ ular or elli ptical R OI c o veri n g m ost of t he i nteri or of t he p ha nt o m m ust be 
dra w n  o ver  all  slices,  a n d  t he  a vera ge  S U V  a n d  sta n dar d  de viati o n  m ust  be 
meas ure d a n d re p orte d i n t he P E T I nstr u me nt T ec h nical S pecificati o n f or m. T he 
e x pecte d S U V f or t he u nif or m p ha nt o m is 1. 0 a n d t he acce pta ble ra n ge is 0. 9 t o 
1. 1. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 0  
U p date # 1 3  
All  p ost -t hera p y  P E T/ C T  a n d  I V  c o ntrast  C T  sca ns  s h o ul d  be  perf or me d  o n  t he  sa me 
sca n ner wit h t he sa me s pecificati o ns as t h ose perf or me d at baseli ne. I deall y, t he I V c o ntrast 
C T sca n s h o ul d be d o ne o n t he sa me da y f oll o wi n g t he P E T/ C T sca n. H o we ver, if t he I V 
c o ntrast C T is o btai ne d o n a se parate da y, t he ti me differe nce bet wee n P E T/ C T a n d I V 
c o ntrast C T s h o ul d n ot e xcee d 1 5 da ys at baseli ne a n d s h o ul d n ot e xcee d 5 da ys after a n y 
c ycle of t hera p y. I n t he case of a p atie nt w h o  has alrea d y ha d a baseli ne F D G -P E T/ C T sca n 
at a n o utsi de facilit y, t he sca n m ust be s u b mitte d t o t he Allia nce I ma gi n g C ore La b at I R O C 
O hi o wit hi n 3 0 da ys of patie nt re gistrati o n . F urt her m ore, t hese patie nts will n ot be i ncl u de d 
i n t he q ua ntitati ve e val uati o ns. 
F or re pr o d uci ble a n d acc urate res ults, p ost -t hera p y P E T/ C T sca ns s h o ul d be ac q uire d usi n g 
t he sa me F D G u pta ke ti me ( p ost-i njecti o n i nter val) as t he pre-t hera p y sca n. T he differe nce 
i n waiti n g peri o d after i njecti o n of F D G bet wee n t he baseli ne a n d p ost-t hera p y (after c ycle 
2 of A B V D a n d f oll o wi n g eit her c ycle 6 of A B V D f or P E T ne gati ve patie nts, or I F R T f or 
P E T  p ositi ve  patie nts )  P E T/ C T  sca ns  s h o ul d  n ot  e xcee d  1 0  mi n utes  f or  mai ntai ni n g 
c o nsiste nc y a n d e ns uri n g acc urac y f or q ua ntitati ve st u dies.  
8. 3 
C T D at a Ac q uisiti o n  
C o ntrast e n ha nce d helical/s piral C T sca ns of t he  c hest, a b d o me n, a n d pel vis ( nec k will be 
i ncl u de d if baseli ne C T d oc u me nts prese nce of disease i n t he nec k) s h o ul d be o btai ne d o n 
all patie nts acc or di n g t o pr ot oc ol re q uire me nts at baseli ne. T he sa me C T sca ns s h o ul d als o 
be perf or me d after 2 c ycles a n d 4 c ycles, eit her c oi nci di n g wit h t he date of t he P E T/ C T or 
wit hi n 5 da ys of t he P E T/ C T.  
D uri n g f urt her f oll o w -u p, c o ntrast e n ha nce d helical/s piral C T sca ns of t he c hest, a b d o me n, 
pel vis, a n d nec k (if i n v ol ve d at baseli ne) e ver y 3 m o nt hs f or t he first year f r o m t he res p o nse 
assess me nt at c o m pleti o n of t hera p y, e ver y 6 m o nt hs f or years 2 a n d 3, a n d t he n a n n uall y 
f or years 4 a n d 5 acc or di n g t o t he p ost-treat me nt f oll o w-u p sc he d ule i n Secti o n 6. 0 . 
Patie nt C T sca ns s h o ul d f oll o w i nstit ut i o nal sta n dar ds wit h f oll o wi n g mi ni m u m criteria: 
•  
Sc a n m o de:  M ulti -detect or a n d/ or helical  
•  
E n h a nce me nt:  I V a n d oral c o ntrast u nless c o ntrai n dicate d  
•  
Secti o n t hic k ness: ma xi m u m 5 m m, prefera ble 2. 5 m m or less  
•  
I ncre me nt: c o nti n u o us or o verla p pi n g secti o ns; n o ga ps  
•  
M atri x size: 5 1 2 × 5 1 2 or better  
•  
Rec o nstr ucti o n ：I nstit uti o nal sta n dar d 
C T sca ns s h o ul d be perf or me d i n a c o nsiste nt ma n ner f or f oll o w -u p fr o m t he baseli ne, wit h 
t he sa me secti o n or slice t hic k ness, i ncre me nt, rec o nstr ucti o n pr ot oc ol a n d i ma ge matri x 
size as well as patie nt p ositi o ni n g. 
8. 4 
P E T/ C T D at a Ac q uisiti o n  
All  data  ac q uisiti o ns  a n d  rec o nstr ucti o ns  will  be  perf or me d  o n  a  P E T/ C T  s yste m.  A 
p ha nt o m st u d y will be perf or me d t o sta n dar dize all P E T/ C T s yste ms pri or t o t he i nitiati o n 
of t he pr ot oc ol. 
8. 4. 1 
P ri or t o F D G I njecti o n a n d D uri n g U pt a ke P eri o d  
Patie nts m ust fast f or at least f o ur h o urs bef ore t he P E T/ C T sca n. Oral h y drati o n 
is str o n gl y e nc o ura ge d pri or t o a n d d uri n g i nj ecti o n of 1 8F- F D G ( 2 5 0 -5 0 0 m L water 
ca n  be  gi ve n  P O  d uri n g  t he  u pta ke  peri o d )  a n d  d uri n g  t he  u pta ke  peri o d  after 
a d mi nistrati o n of 1 8F- F D G. I V f ur ose mi de ( 1 0 m g) ma y be a d mi nistere d ( b ut is 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 1  
U p date # 1 3  
n ot ma n dat or y) t o i ncrease uri nar y eli mi nati o n of t he tracer a n d mi ni mize i ma ge 
artifacts  ca use d  b y  uri nar y  stasis  i n  t he  a b d o me n  a n d  pel vis. I ntra ve n o us  fl ui ds 
c o ntai ni n g de xtr ose or pare nteral fee di n g s h o ul d be wit h hel d f or at least 6 h o urs 
pri or t o t he i njecti o n of 1 8F- F D G. N o ster oi d a d mi nistr ati o n is all o we d f or at 
le ast 7 d a ys pri or t o F D G-P E T i m a gi n g.  Acti ve e xercise s h o ul d be disc o ura ge d  
f or  at  least  2 4  h o urs  pri or  t o  t he  st u d y.  M uscle  stress,  te nsi o n,  c he wi n g,  a n d 
m o ve me nt  d uri n g  t he  u pta ke  peri o d  s h o ul d  be  mi ni mize d  t o  decrease  m uscle 
u pta ke.  Patie nts  s h o ul d  n ot  s pea k  d uri n g  t he  i njecti o n  a n d  u pta ke  peri o d. 
I nter vie ws  wit h  t he  patie nt  sh o ul d  be  wit h hel d  u ntil  after  c o m pleti o n  of  t he 
i ma gi n g st u d y. 
T he bl o o d gl uc ose le vel s h o ul d be c hec ke d bef ore 1 8F- F D G i njecti o n. Bl o o d s u gar 
( meas ure d b y gl uc o meter) m ust be less t ha n 2 0 0 m g/ d L at t he ti me of t he F D G-
P E T/ C T st u d y.  If  t he  bl o o d  gl uc ose le vel is  greater t ha n  2 0 0  m g/ d L,  t he  F D G -
P E T/ C T i ma gi n g s h o ul d be resc he d ule d. If t he bl o o d gl uc ose le vel still e xcee ds 
2 0 0 m g/ d L o n t he f oll o wi n g sc he d ule d da y f or P E T sca n ni n g, t he patie nt will n ot 
be  i ncl u de d  i n  t he  trial.  I ns uli n  a d mi nistrati o n  i m me diate l y  bef ore  t he  P E T/ C T 
st u d y  t o  re d uce t he  gl uc ose  le vels is  n ot  all o we d.  Patie nts  wit h  dia betes s h o ul d 
c o nti n ue  t o  a d here  t o  t heir  oral  a ge nts  or  i ns uli n  r o uti nes.  T hese  me dicati o ns 
s h o ul d n ot be a d mi nistere d near t he 1 8F- F D G i nj ecti o n ti me. I n i ns uli n - de pe n de nt 
patie nts,  i ns uli n  s h o ul d  be  a d mi nistere d  at  least  5  h o urs  pri or  t o  t he 1 8F- F D G 
i njecti o n. Patie nts wit h dia betes w h o are o n dia betic me dicati o n s h o ul d ta ke t heir 
me dicati o n 4 -5 h o urs pri or t o t he test. If bl o o d s u gar e xcee ds 1 5 0 m g/ d L ( b ut less 
t ha n 2 0 0 m g/ d L), a n ote s h o ul d be ma de i n o n t he case re p ort f or m. 
Metallic o bjects s h o ul d be re m o ve d fr o m t he patie nts w he ne ver p ossi ble. Patie nts 
s h o ul d be ke pt i n a war m waiti n g r o o m pri or t o 1 8F- F D G i njecti o n t o a v oi d br o w n 
a di p ose tiss ue  u pta ke.  I n  a n xi o us  a n d cla ustr o p h o bic patie nts,  a d mi nistrati o n of 
oral  diaze pa m  ( 0. 0 6 -0. 1 0  m g/ k g)  is  rec o m me n de d  3 0 -4 0  mi n utes  pri or  t o  t he 
i nitiati o n of t he i ma gi n g st u d y. 
Wei g ht  ( k g),  hei g ht  (c m),  bl o o d  gl uc ose  ( m g/ d L),  a n d  t he  date  a n d  ti me  of 
c he m ot hera p y a n d c ol o n y sti m ulati n g a d mi nistrati o n (e. g., G C S F, G M C S F) will 
be rec or de d pri or t o t he i njecti o n of 1 8F- F D G.  
1 0- 2 0 m Ci of 1 8F- F D G will be a d mi nistere d I V, de pe n di n g o n t he ma n ufact urer’s 
rec o m me n dati o n. A 1 0-2 0 m L sali ne fl us h is rec o m me n de d i n re d uci n g t he ve n o us 
retenti o n of 1 8F- F D G. T he patie nt m ust wait f or at least 6 0 mi n utes pri or t o t he 
i nitiati o n  of  t he  P E T/ C T  ac q uisiti o n  f or  all  P E T/ C T  sca ns  ( b ot h  pre-a n d  p ost -
t hera p y sca ns). T he wait peri o d s h o ul d be ke pt wit hi n a ma xi m u m of 1 0 mi n utes  
a m o n g patie nts. T he wait peri o d m ust n ot e xcee d 8 0  mi n utes at baseli ne. It is N O T 
acce pt a ble  t o  st art  i m a gi n g  wit h  w ait  peri o ds  of  less  t h a n  6 0  mi n utes  a n d 
l o n ger  t h a n  8 0 mi n utes  f or  b ot h  pre- a n d  p ost -t her a p y  P E T/ C T  sc a ns. T he 
ti me differe nce bet wee n baseli ne a n d ot her P E T st u dies (after c ycle 2 of A B V D, 
a n d f oll o wi n g eit her c ycle 6 of A B V D f or P E T ne gati ve patie nts, or I F R T f or P E T 
p ositi ve patie nts ) s h o ul d n ot  be > 1 0 mi n utes. A ti me differe nce of > 1 5 mi n utes 
bet wee n P E T/ C T st u dies is N O T  acce pta ble. 
T he i ma gi n g will start aft er v oi di n g t he bla d der. 1 5 0 -2 0 0 m L of water m ust be 
gi ve n  t o  t he  patie nt  i m me diatel y  pri or  t o  t he  st u d y  ac q uisiti o n  bef ore  t he y  are 
p ositi o ne d o n t he ta ble t o diste n d st o mac h a n d a v oi d p h ysi ol o gic st o mac h u pta ke. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 2  
U p date # 1 3  
8. 4. 2 
P E T/ C T I m a ge Ac q uisiti o n  
Patie nts wil l be p ositi o ne d o n t he ta ble i n a hea dfirst, s u pi ne p ositi o n wit h ar ms 
ele vate d a b o ve t he hea d  t o re d uce bea m-har de ni n g artifacts at t he le vel of t he li ver. 
A se parate hea d a n d nec k i ma gi n g will be p urs ue d f or t h ose w h ose pri mar y disease 
site is i n t he neck wit h t he ar ms p ositi o ne d al o n g t he si de. T he use of oral c o ntrast 
is at t he discreti o n of eac h facilit y. H o we ver, I V-c o ntrast de dicate d C T ac q uisiti o n 
s h o ul d f oll o w P E T i ma gi n g wit h n o n-c o ntrast l o w d ose C T t o a v oi d variati o ns i n 
F D G u pta ke i n t he bl o o d p o ol a n d t he t u m or t hat is ca use d b y t he I V c o ntrast a ge nt. 
T he l o w d ose C T ass ociate d wit h P E T s h o ul d be ac q uire d usi n g a c urre nt of n ot 
less t ha n 8 0 m A/sec o n d. 
It is critical t hat all p ost-t hera p y P E T/ C T sca ns be perf or me d i n a n i de ntical wa y 
t o t he baseli ne sca n wit h t he sa me sca n ner, sa me sca n ni n g directi o n (s k ull t o t hi g hs 
or t hi g hs t o s k ull) a n d c o nsiste nt ar m p ositi o ni n g. 
F or P E T i ma gi n g, si x t o se ve n c o nti g u o us v ol u mes will be c h ose n, de pe n di n g o n 
t he patie nt’s hei g ht, t o e ns ure data ac q uisiti o n of t he e ntire re gi o n of i nterest ( R OI), 
t he le vel of t he s k ull base t o t he 1/ 3 pr o xi mal fe m urs. T he ti me/ be d p ositi o n s h o ul d 
be i n acc or da nce wit h t he ma n ufact urer’s rec o m me n dati o ns f or o pti mal i ma gi n g. 
A djace nt fiel ds of vie w s h o ul d s hare o verla p pi n g slices.  
8. 4. 3 
P E T/ C T I m a ge P r ocessi n g  
F oll o w  t he  ma n ufact urer’s  rec o m me n dati o n  f or  i ma ge  rec o nstr ucti o n.  T he 
e missi o n data will be c orrecte d f or scatter, ra n d o m c oi nci de nce e ve nts, a n d s yste m 
dea d -ti me usi n g pr o vi de d s oft ware. A n iterati ve rec o nstr ucti o n ( or dere d s u bsets 
e x pectati o n ma xi mizati o n) a n d C T -base d atte n uati o n c orrecti o n will be use d f or 
t he  P E T  i ma ges.  Rec o nstr ucti o ns  s h o ul d  be  arc hi ve d  b ot h  wit h  a n d  wit h o ut 
atte n uati o n c orrecti o n t o res ol ve iss ues arisi n g fr o m p ote ntial artifacts ge nerate d 
b y t he C T- base d atte n uati o n c orrecti o n pr oce d ure. 
8. 5 
E v al u ati o n of P E T/ C T D at a  
All i ma ges will be rea d ce ntrall y b y t he Allia nce  I ma gi n g C ore La b orat or y at I R O C O hi o . 
T o e ns ure t he hi g hest sta n dar ds a n d c o nsiste nc y bet wee n differe nt ce nters, all F D G -P E T 
sca ns ( baseli ne, i nteri m, a n d e n d of treat me nt P E T sca ns) m ust be s u b mitte d t o t he Allia nce  
I ma gi n g  C ore  La b  at I R O C  O hi o f or  ce ntralize d  re vie w ( See Secti o n  8. 9 ).  Res p o nse 
deter mi nati o ns  a n d  treat me nt  decisi o ns  (e. g.  c o nti n uati o n  of  A B V D  or s witc h  t o 
B E A C O P P) m ust be base d o n t he ce ntralize d re vie w of t he F D G -P E T sca n a n d N O T o n 
sca n assess me nts b y l ocal p h ysicia ns. The cr ucial F D G -P E T sca n c o n d ucte d after t he 2 n d 
c ycle of A B V D will be 8 -1 0 da ys after t he Da y -1 5 d ose of A B V D d uri n g C ycle 2 (i .e. o n 
da y 2 3 or 2 4 or 2 5 of c ycle 2, see  Secti o n 8. 2  f or acce pta ble F D G-P E T/ C T sca n c o m pleti o n 
da ys). T he sec o n d P E T sca n s h o ul d be sc he d ule d at t he start of C ycle 2 of treat me nt t o 
e ns ure a p pr o priate ti mi n g of res p o nse sca ns.  
Ce ntralize d re vie w will be perf or me d b y a me m ber of a tea m of P E T/ C T rea ders. T here 
will be a n a dj u dicat or fr o m t he sa me p o ol of re vie wers i n t he case of disa gree me nt. T here 
will be o ne re vie wer, Dr. Nat ha n Hall, w h o will pr o vi de bac k -u p P E T/ C T re vie wer ser v ices 
wit hi n t he Allia nce  Ima gi n g C ore La b at I R O C O hi o . T he Allia nce  I ma gi n g C ore La b at 
I R O C O hi o will tra ns mit t he sca ns t o t he e x pert re vie wers f or res p o nse deter mi nati o n a n d 
t he n  will  tra ns mit  t he  res ults t o  t he Allia nce  Statistic s a n d  Data Ce nter  a n d t o  t he  sites 
pri mar y c o ntact wit h 7 2 h o urs of i ma ge recei pt ( n ot i ncl u di n g wee ke n ds).   

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 3  
U p date # 1 3  
T he ce ntral P E T/ C T e x pert re vie w will o nl y f oc us o n t he assess me nt of H o d g ki n l y m p h o ma 
disease sites. T his ce ntral e x pert re vie w will N O T pr o vi de a c o m pre he nsi ve assess me nt of 
t he e ntire P E T/ C T st u d y a n d will t h us N O T rec or d i nci de ntal fi n di n gs a n d a b n or malities 
u nrelate d t o H o d g ki n l y m p h o ma.  Ce ntralize d P E T/ C T is d o ne f or t he p ur p ose of t his trial; 
it d oes N O T relie ve l ocal P E T/ C T rea ders of t heir res p o nsi bilit y t o issue a c o m pre he nsi ve 
P E T/ C T re p ort.  
C ycle 3 of c he m ot hera p y m ust n ot be a d mi nistere d u ntil t he res ults of t he sec o n d P E T sca n 
are a vaila ble. Deter mi nati o n of F D G -P E T p ositi vit y or ne gati vit y will be perf or me d usi n g 
a 5 p oi nt sc ori n g s yste m o n g ui deli nes esta blis he d b y a n i nter nati o nal P E T har m o nizati o n 
c o nfere nce  c o n ve ne d  i n  L o n d o n  i n  Ma y  2 0 0 7  ( See A p pe n di x  I ). Acc or di n g  t o  t hese 
g ui deli nes, sca ns will be j u d ge d t o be p ositi ve if lesi o ns are m ore h y per meta b olic t ha n t he 
li ver b y vis ual, q ualitati ve i ns pecti o n.  B or derli ne meta b olis m i n a lesi o n will be c o nsi dere d 
ne gati ve  i n  c o nc or da nce  wit h  t he  p olicies  of  Galla mi ni  a n d  H utc hi n gs  w h ose  st u dies 
esta blis he d t he val ue of earl y i nteri m F D G -P E T i ma gi n g. [ 1 1- 1 3, 3 0]  
8. 6 
P ri m ar y O bjecti ve/ E n d p oi nt: Defi niti o n of Res p o nse b y Met a b olic Criteri a  
T he pri mar y e n d p oi nt is pr o gressi o n free s ur vi val ( P F S) at 3 6 m o nt hs fr o m e nr oll me nt f or 
patie nts  wit h  b ul k y  sta ge  I  a n d  II  H o d g ki n  l y m p h o ma.  T he  t otal  n u m ber  of  c ycles  of 
c he m ot hera p y ( ±  I F R T) will be deter mi ne d b y meta b olic res p o nse as vis uall y assesse d b y 
P E T/ C T i ma gi n g after 2 c ycles usi n g criteria pr o vi de d  i n A p pe n di x I.   
8. 6. 1 
Ne g ati ve P E T Sc a n ( Met a b olic Res p o n ders)  
All  P E T/ C T  i nter pretati o ns  will  be  perf or me d  o n  b ot h  a xial  a n d  c or o nal  slices. 
Mai nl y, fi n di n gs o n a xial slices s h o ul d be c o nfir me d b y fi n di n gs o n c or o nal slices, 
as c o m paris o n wit h t he li ver is us uall y easier a n d m ore acc urate o n c or o nal slices.  
U p o n q ualitati ve e val uati o n, t u m or F D G u pta ke t hat is less t ha n or e q ual t o t he 
li ver i n tar get or n o n -tar get t u m ors, re gar dless of t heir l ocati o n, a n d a bse nce of 
ne w lesi o ns t hat are dee me d t o be t u m or a n d a bse nce of n o n -tar get t u m ors will be 
c o nsi dere d ne gati ve f or t he prese nce of resi d ual l y m p h o ma  ( A p pe n di x I). 
8. 6. 2 
P ositi ve P E T Sc a n  
U p o n q ualitat i ve e val uati o n, diff use or f ocal u pta ke e xcee di n g t hat see n i n t he li ver 
i n tar get  or  n o n-tar get  t u m ors,  re gar dless  of  t heir  l ocati o n, will  be  c o nsi dere d 
p ositi ve f or resi d ual t u m or.  
8. 7 
Sec o n d ar y O bjecti ves/ E n d p oi nts  
8. 7. 1 
Se mi q u a ntit ati ve A n al ysis: I n patie nts wit h m ulti ple t u m or sites, t he si x sites wit h 
t he hi g hest u pta ke will be desi g nate d as t he tar get sites. F or t hese lesi o ns, S U V 
meas ure me nts  will  be  deter mi ne d  at  baseli ne,  after  c ycle  2,  at  c o m pleti o n  of 
c he m ot hera p y, a n d after I F R T i n res pecti ve patie nt gr o u ps, as o utli ne d bel o w. 
At baseli ne, a 3 D v ol u me of i nterest ( V OI) wil l be ta ke n o ver t he t u m or o n a xial, 
sa gittal, a n d c or o nal m ulti-pla nar ref or matti n g ( M P R) vie ws t hat vis uall y s h o w t he 
m ost  pr o mi ne nt  u pta ke. M a xi m u m  S U V  b o d y  wei g ht  ( S U V b w) , S U V pea k  a n d 
S U V lea n b o d y mass ( S U Vl b m) will be o btai ne d o ver t he lesi o n .  
A si milar V OI will be o btai ne d i n t he:  
1) a dj ace nt  bac k gr o u n d  t hat  d oes  n ot  c orres p o n d  t o  p h ysi ol o gicall y  or 
pat h ol o gicall y acti ve sites a wa y fr o m t he F D G a vi d sites;  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 4  
U p date # 1 3  
2) Me diasti nal  bl o o d p o ol ( M B P) ta ke n i n t he mi d -a ortic le vel  or  wit hi n  2 
slices of t he a ortic arc h; 
3) a p pr o xi matel y mi d -li ver re gi o n or i n secti o ns t hat are wit hi n 3 slices of t he 
p orta he patis re gi o ns .   
I n or der t o ta ke meta b olic varia bilit y i nt o c o nsi derati o n, t w o S U V meas ure me nts 
o n t w o differe nt a xial slices will be o btai ne d f or ite ms 1 -3 a b o ve a n d t he a vera ge 
S U Vs will be use d ( mea n S U V b w a n d mea n S U Vl b m of t w o a xial slices).  
After c ycle  2 of A B V D a n d f oll o wi n g eit her c ycle 6 of A B V D (f or P E T ne gati ve 
patie nts) o r I F R T (f or P E T p ositi ve patie nts), i n patie nts wit h meta b olicall y acti ve 
resi d ual t u m ors, as well as i n t h ose wit h meta b olicall y n o nacti ve C T masses, t he 
sa me ste ps as descri be d a b o ve will be re peate d. 
8. 7. 2 
Usi n g recei ver o perat or c ur ves ( R O C), m ost o pti mal c ut off f or a bs ol ute decrease 
i n ma xi m u m S U V b w, S U V pea k a n d S U Vl b m, a bs ol ute u pta ke i n t he t u m or/s a n d 
relati ve  u pta ke  i n  t u m or/s  vers us  vari o us  refere nce  a nat o mic  sites  (li ver, 
me diasti nal  bl o o d  p o ol,  a n d  bac k gr o u n d),  as  well  as  vari o us  c ut offs  f or  p os t-
t hera p y  ma xi m u m  S U V b w,  S U V pea k  a n d  S U Vl b m,  will  be  deter mi ne d  an d 
c o m pare d after c ycle 2 of A B V D a n d f oll o wi n g eit her c ycle 6 of A B V D (f or P E T 
ne gati ve patie nts) or I F R T (f or P E T p ositi ve patie nts) . 
8. 7. 3 
I n patie nts wit h m ulti ple t u m or sites, t he si x sites c orrelati n g wit h t he P E T tar get 
lesi o ns will be desi g nate d as t he tar get sites.  I n eac h l y m p h n o de re gi o n t he lesi o ns 
wit h  t he  hi g hest  u pta ke  will  be  c h ose n. If  t here  is  a n y  lesi o n  t hat  de m o nstrates 
u pta k e after t hera p y ot her t ha n t he desi g nate d tar get  lesi o ns, t he y will be n o n-tar get 
lesi o ns  a n d  will  be  e val uate d  i n  t he  sa me  fas hi o n  as  tar get  lesi o ns. F or  t hese 
lesi o ns,  v ol u metric  vs.  2  di me nsi o nal  ( 2-D)  meas ure me nt  c ha n ges  bet wee n 
baseli ne  a n d  after c ycle  2  of  A B V D  a n d  f oll o wi n g  eit her  c ycle  6  of  A B V D  or 
I F R T, will be deter mi ne d fr o m de dicate d C T sca ns. Usi n g recei ver o perat or c ur ves 
( R O C), t he m ost o pti mal c ut off f or a bs ol ute decrease a n d perce nt decrease will be 
deter mi ne d. A c o m bi nat orial a nal ysis will be perf or me d i nc or p orati n g t he c ha n ges 
fr o m P E T data a n d de dicate d C T data t o deter mi ne if t his a p pr oac h i ncreases t he 
pre dicti ve val ue of b ot h tests c o m bi ne d c o m pare d t o eac h test al o ne.  
8. 7. 4. 
Q ualitati ve a n d se mi q ua ntitati ve F D G -P E T fi n di n gs/c ha n ges, 2 -D a n d v ol u metric 
C T  c ha n ges,  a n d  c o m bi nat orial  a nal yses  ( P E T + de dicate d  C T  data)  will  be 
c o m pare d wit h m olec ular para meters, a n d c o n ve nti o nal para meters, i ncl u di n g I P S 
i n t he pre dicti o n of res p o nse a n d P F S. 
8. 8 
P ost -T her a p y F oll o w -U p of T u m ors  
At a n y p oi nt after t hera p y, t he decisi o n f or bi o ps y of a n y lesi o n is at t he discreti o n of t he 
treati n g p h ysicia n. After c o m pleti o n of treat me nt, f or t h ose patie nts w h o ac hie ve a C R or 
P R w h o are P E T ne gati ve, C T sca ns will be o btai ne d e ver y 3 m o nt hs f or t he first year, t he n 
e ver y 6 m o nt hs f or years 2 a n d 3, a n d a n n uall y years 4 a n d 5 acc or di n g t o t he p ost -treat me nt 
f oll o w- u p sc he d ule i n Secti o n 6. 0 . 
8. 9 
P E T a n d C T D at a S u b missi o n  
T he c o m plete P E T a n d C T st u dies m ust be electr o nicall y s u b mitte d t o t he Allia nce I ma gi n g 
C ore La b  at I R O C O hi o  i n di gital DI C O M f or mat, a n y ot her f or mats s uc h as Bit ma p, J P G, 
har dc o p y  files  or  sca n ne d  fil ms  are  u nacce pta ble.  De -i de ntif y  t he  patie nt  data  usi n g 
i nstit uti o nal  pr oce d ures  t o  re m o ve  patie nt  na me  a n d  me dical  rec or d  n u m ber  w hile 
preser vi n g t he C A L G B patie nt I D n u m ber a n d C A L G B pr ot oc ol n u m ber se paratel y. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 6  
U p date # 1 3  
vi n blasti ne a n d d o x or u bici n t o 7 5 % of t he last d ose recei ve d f or t he ne xt c ycle (i n 
a d diti o n t o a b o ve a nti bi otic a n d G -C S F s u p p orti ve care meas ures).    Re -escalati o n 
is at t he discreti o n of t he treati n g p h ysicia n. 
9. 1. 2  
T hr o m b oc yt o pe ni a  
F or  platelets  ≥  7 5, 0 0 0  – 1 0 0, 0 0 0  o n  t he  da y  of  treat me nt  ( or  wit hi n  4 8  h o urs), 
c o nti n ue  A B V D  wit h a  decrease i n t he d oses  of  vi n blasti ne  a n d  d o x or u bici n t o 
7 5 % of t he last d ose recei ve d f or t he ne xt c ycle.  Re -escalati o n is at t he discreti o n 
of t he treati n g p h ysicia n. F or platelets < 7 5, 0 0 0 o n t he da y of treat me nt ( or wit hi n 
4 8  h o urs),  dela y  treat me nt  u ntil  platelets  ≥  7 5, 0 0 0,  t he n  res u me  A B V D  wit h  a 
decrease  i n  t he  d oses  of  vi n blasti ne  a n d  d o x or u bici n  t o  7 5 %  of  t he  last  d ose 
recei ve d f or t he ne xt c ycle. 
9. 1. 3 
He p atic D ysf u ncti o n  
All patie nts wit h bilir u bi n ≤ 2 x t he u p per li mit of n or mal ( U L N) will recei ve a f ull 
i nitial d ose of d o x or u bici n a n d vi n blasti ne.  If t he bilir u bi n i ncreases t o > 2 x U L N 
a n d is < 5 x U L N, t he d o x or u bici n a n d vi n blasti ne d oses s h o ul d be re d uce d b y 5 0 % 
of t he last d ose.  F ull d oses s h o ul d be a d mi nistere d if t he bilir u bi n rec o vers t o ≤ 2 
x U L N.  If t he bilir u bi n e xcee ds 5 x U L N, d o x or u bici n a n d vi n blasti ne s h o ul d be 
o mitte d f or t hat c ycle.  If t he bilir u bi n ha s n ot rec o vere d t o ≤ 2 x U L N b y t he ti me 
t he ne xt c ycle is d ue, t he n re m o ve t he patie nt fr o m pr ot oc ol treat me nt.  I n cases of 
biliar y o bstr ucti o n b y a t u m or mass, a biliar y drai na ge ste nt s h o ul d be place d pri or 
t o c he m ot hera p y. 
Bilir u bi n  
D o x or u bici n d ose  
Vi n bl asti ne d ose  
≤ 2 x U L N  
1 0 0 %  
1 0 0 %  
> 2 -5 x U L N  
5 0 % ( of last d ose recei ve d)  
5 0 % ( of last d ose recei ve d)  
> 5 x U L N  
0 %  
0 %  
9. 1. 4  
C ar di ot o xicit y 
F or persiste nt arr h yt h mia (i ncl u di n g si n us tac h ycar dia wit h se vere s y m pt o ms a n d 
wit h n o  de m o nstra ble  ca use); c o n gesti ve  heart  fail ure;  or  a  decrease  i n  ejecti o n 
fracti o n b y ≥ 1 5 % (a bs ol ute perce nta ge p oi nts) fr o m baseli ne or t o less t ha n 4 5 %, 
disc o nti n ue pr ot oc ol t hera p y.  
9. 1. 5 
S ki n T o xicit y  
Vi n blasti ne  a n d  d o x or u bici n  are  vesica nts;  st o p  i nf usi o n  i m me diatel y  if 
e xtra vasati o n  is  s us pecte d  a n d  a d mi nister  t he  dr u g  at  a n ot her  site.  I nstit uti o nal 
sta n dar d meas ures f or treat me nt of e xtra vasati o n s h o ul d be e m pl o ye d. 
9. 1. 6  
Ne ur ot o xicit y 
F or gra de 3 se ns or y ne ur o pat h y, or f or se vere c o nsti pati o n wit h ile us, re d uce d ose 
of vi n blasti ne b y 5 0 % f or all s u bse q ue nt d oses. 
F or gra de 4 se ns or y ne ur o pat h y, vi n blasti ne will be o mitte d fr o m all f ut ure d oses. 
9. 1. 7  
P ul m o n ar y T o xicit y 
Ble o m yci n i n d uce d p ne u m o nitis ma y be diffic ult t o dia g n ose cli nicall y.  A hi g h 
res ol uti o n C T sca n of t he c hest a n d p ul m o nar y f u ncti o n tests s h o ul d be perf or me d 
at  t he  sli g htest  s us pici o n.    As  t here  are  n o  re pr o d uci ble  cli nical  or  hist ol o gic 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 7  
U p date # 1 3  
fi n di n gs  f or  ble o m yci n -i n d uce d  p ne u m o nitis,  t he  dia g n osis  m ust  be  ma de  o n 
cli nical, ra di ol o gic, a n d/ or hist ol o gic fi n di n gs after e xcl u di n g ot her eti ol o gies.  If 
t hese st u dies s u g gest ble o m yci n t o xicit y, ble o m yci n s h o ul d be disc o nti n ue d.  Later 
res u m pti o n  s h o ul d  o nl y  be  c o nsi dere d  if  t he  s us pici o n  f or  ble o m yci n-i n d uce d 
t o xicit y has pr o ve d u nf o u n de d. 
9. 2 
D ose M o dific ati o ns f or esc al ate d B E A C O P P  
9. 2. 1 
A c ycle of B E A C O P P s h o ul d n ot be gi n u ntil le u k oc ytes > 2, 5 0 0 a n d platelets > 
8 0, 0 0 0.  If  le u k oc ytes  <  2, 5 0 0  or  platelets  <  8 0 , 0 0 0  o n  da y  1  of  a  c ycle  of 
B E A C O P P, dela y treat me nt u ntil le u k oc ytes ≥ 2, 5 0 0 a n d platelets ≥ 8 0, 0 0 0. C B C 
s h o ul d be rec hec ke d after 3, 7, 1 0 a n d 1 4 da ys. T he first c ycle  of B E A C O P P  ma y 
be gi n t w o wee ks after c ycle 2 of A B V D i n patie nts wit h a p ositi ve i nteri m P E T 
sca n, re gar dless of le u k oc yte c o u nt. 
9. 2. 2 
D ose re d ucti o ns f or escalate d B E A C O P P f oll o w a defi ne d de -escalati o n sc he me 
base d o n t he occ urre nce of t o xic e ve nts i n t he pre vi o us c ycle. T here are n o d ose 
re-escalati o ns. 
9. 2. 3  
T he f oll o wi n g are c o nsi dere d d ose re d ucti o n e ve nts o n B E A C O P P:  
Decrease d w hile bl o o d cells/ Le u k o pe nia: gra de 4 (le u k oc ytes < 1 0 0 0) f or > 4 da ys.  
Platelet c o u nt decrease/ T hr o m b oc yt o pe nia: gra de 4 ( platelets < 2 5, 0 0 0) o n o ne or 
m ore da ys.  
I nfecti o n: gra de 4. 
Ot her t o xicit y: gra de 4 (e . g. m uc ositis);(see bel o w f or d ose re d ucti o ns f or bilir u bi n 
a n d p ul m o n dar y). 
P ost p o ne me nt of treat me nt f or m ore t ha n 2 wee ks d ue t o i na de q uate rec o ver y of 
bl o o d val ues. 
9. 2. 4 
S h o ul d o ne or m ore d ose -re d ucti o n e ve nts occ ur i n a gi ve n c ycle, t he d ose i n all 
f oll o wi n g c ycles will be re d uce d b y o ne d ose le vel.  If a n y t o xic e ve nt occ urs i n 2 
s uccessi ve  c ycles,  t he  f oll o wi n g  c ycle  is  a d mi nistere d  at  sta n dar d  B E A C O P P 
d oses.  N o re d ucti o n is ma de f or treat me nt p ost p o ne me nt of u p t o 2 wee ks.   
9. 2. 5 
All patie nts wit h bilir u bi n ≤ 2 x t he u p per li mit of n or mal ( U L N) will recei ve a f ull 
i nitial d ose of d o x or u bici n a n d vi ncristi ne . If t he bilir u bi n i ncreases t o > 2 x U L N 
a n d is < 5 x U L N, t he d o x or u bici n a n d vi ncristi ne d oses s h o ul d be re d uce d b y 5 0 % 
of  t he  last  d ose.  If  t he  bilir u bi n  e xcee ds  5  x  U L N,  d o x or u bici n  a n d vi ncristi ne 
s h o ul d be o mitte d f or t hat c ycle.  If t he bilir u bi n has n ot rec o vere d t o ≤ 2 x U L N 
b y t he ti me t he ne xt c ycle is d ue, t he n re m o ve t he patie nt fr o m pr ot oc ol treat me nt.  
I n cases of biliar y o bstr ucti o n b y a t u m or mass, a biliar y drai na ge ste nt s h o ul d be 
place d pri or t o c he m ot hera p y.  
Bilir u bi n  
D o x or u bici n d ose  
Vi ncristi ne d ose  
≤ 2 x U L N  
1 0 0 %  
1 0 0 %  
> 2 -5 x U L N  
5 0 % ( of last d ose recei ve d)  
5 0 % ( of last d ose recei ve d)  
> 5 x U L N  
0 %  
0 %  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 8  
U p date # 1 3  
9. 2. 6  
P ul m o n ar y T o xicit y  
Ble o m yci n i n d uce d p ne u m o nitis ma y be diffic ult t o dia g n ose cli nicall y.  A hi g h 
res ol uti o n C T sca n of t he c hest a n d p ul m o nar y f u ncti o n tests s h o ul d be perf or me d 
at  t he  sli g htest  s us pici o n.    As  t here  are  n o  re pr o d uci ble  cli nical  or  hist ol o gic 
fi n di ngs  f or  ble o m yci n -i n d uce d  p ne u m o nitis,  t he  dia g n osis  m ust  be  ma de  o n 
cli nical, ra di ol o gic, a n d/ or hist ol o gic fi n di n gs after e xcl u di n g ot her eti ol o gies.  If 
t hese st u dies s u g gest ble o m yci n t o xicit y, ble o m yci n s h o ul d be disc o nti n ue d.  Later 
res u m pti o n  s h o ul d  o nl y  be  c o nsi dere d  if  t he  s us pici o n  f or  ble o m yci n-i n d uce d 
t o xicit y has pr o ve d u nf o u n de d 
9. 2. 7 
I nt oler a nce n ot q u alif yi n g as a d ose re d ucti o n e ve nt 
I n  case  of  dr u g  s pecific  i nt olera nce  (e. g.  vi ncristi ne  ne ur o pat h y,  pr ocar bazi ne 
aller g y), si n gle dr u gs ma y be  dr o p pe d fr o m t he re gi me n wit h o ut s u bstit uti o n.  T he 
reas o n f or a de viati o n s h o ul d al wa ys be rec or de d o n t he c orres p o n di n g treat me nt 
f or ms. 
9. 2. 8 
D ose Le vels of Esc al ate d B E A C O P P  
Treat me nt  al wa ys  be gi ns  wit h  D ose  Le vel  0. D oses  of  ble o m yci n,  vi ncristi ne, 
pr ocar bazi ne a n d pre d nis o ne are n ot re d uce d. 
D ose Le vel 0  
D ose  
R o ute  
Sc he d ule  
C ycl o p h os p ha mi de  
1 2 5 0 m g/ m 2 
I V 
Da y 1  
D o x or u bici n  
3 5 m g/ m 2 
I V 
Da y 1  
Et o p osi de  
2 0 0 m g/ m 2 
I V 
Da ys 1 -3  
 
D ose Le vel -1  
D ose  
R o ute  
Sc he d ule  
C ycl o p h os p ha mi de  
1 1 5 0 m g/ m 2 
I V 
Da y 1  
D o x or u bici n  
3 5 m g/ m 2 
I V 
Da y 1  
Et o p osi de  
1 7 5 m g/ m 2 
I V 
Da ys 1 -3  
 
D ose Le vel -2  
D ose  
R o ute  
Sc he d ule  
C ycl o p h os p ha mi de  
9 5 0 m g/ m 2 
I V 
Da y 1  
D o x or u bici n  
3 5 m g/ m 2 
I V 
Da y 1  
Et o p osi de  
1 5 0 m g/ m 2 
I V 
Da ys 1 -3  
 
D ose Le vel -3  
D ose  
R o ute  
Sc he d ule  
C ycl o p h os p ha mi de  
8 0 0 m g/ m 2 
I V 
Da y 1  
D o x or u bici n  
3 5 m g/ m 2 
I V 
Da y 1  
Et o p osi de  
1 2 5 m g/ m 2 
I V 
Da ys 1 -3  
 
St a n d ar d B E A C O P P  
D ose  
R o ute  
Sc he d ule  
C ycl o p h os p ha mi de  
6 5 0 m g/ m 2 
I V 
Da y 1  
D o x or u bici n  
2 5 m g/ m 2 
I V 
Da y 1  
Et o p osi de  
1 0 0 m g/ m 2 
I V 
Da ys 1 -3  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
4 9  
U p date # 1 3  
9. 2. 9 
Tre at me nt P ost p o ne me nt a n d D ose M o dific ati o ns f or st a n d ar d B E A C O P P  
A c ycle of B E A C O P P s h o ul d n ot be gi n u ntil le u k oc ytes  > 2, 5 0 0 a n d platelets > 
8 0, 0 0 0.  If  le u k oc ytes  <  2, 5 0 0  or  platelets  <  8 0, 0 0 0  o n  da y  1  of  a  c ycle  of 
B E A C O P P, dela y treat me nt u ntil le u k oc ytes ≥ 2, 5 0 0 a n d platelets ≥ 8 0, 0 0 0. C B C 
s h o ul d be rec hec ke d after 3, 7, 1 0 a n d 1 4 da ys. T he first c ycle of B E A C O P P ma y 
be gi n t w o wee ks after c ycle 2 of A B V D i n patie nts wit h a p ositi ve i nteri m P E T 
sca n, re gar dless of le u k oc yte c o u nt. 
Tre at me nt Del a y  
D ose M o dific ati o n  
< 1 wee k *  
N o d ose re d ucti o n  
1- 2 wee ks  
2 5 % d ose re d ucti o n f or c ycl o p h os p ha mi de, d o x or u bici n , 
pr ocar bazi ne a n d et o p osi de  
> 2 wee ks  
5 0 % d ose re d ucti o n f or c ycl o p h os p ha mi de, d o x or u bici n , 
pr ocar bazi ne a n d et o p osi de  
* N o d ose re d ucti o ns will be perf or me d if dela ys of le u k oc yte or platelet rec o ver y 
are  less  t ha n  o ne  wee k.  Ot her wise  d ose  re d ucti o ns  will  f oll o w  t he  sc he ma 
descri be d b y t he Ger ma n H o d g ki n Disease St u d y Gr o u p. [ 3 1] 
9. 3 
D ose M o dific ati o n f or O bese P atie nts  
T here is n o clearl y d oc u me nte d a d verse i m pact of treat me nt of o bese patie nts w he n d osi n g 
is perf or me d acc or di n g t o act ual b o d y wei g ht. T heref ore, all d osi n g is t o be deter mi ne d 
s olel y b y ( 1) t he p atie nt’s B S A as c alc ul ate d fr o m act u al wei g ht or ( 2) act u al wei g ht 
wit h o ut  a n y  m o dific ati o n  ( wit h  t he  e xce pti o n  of  t he  c a p  o n  vi ncristi n e  d oses  i n 
B E A C O P P as n ot e d i n S ecti o n 7. 1). T his will eli mi nate t he ris k of calc ulati o n err or a n d 
t he p ossi ble i ntr o d ucti o n of varia bilit y i n d ose a d mi nistrati o n. F ail ure t o use act u al b o d y 
wei g ht  i n  t he  c alc ul ati o n  of  dr u g  d os a ges  will  be  c o nsi dere d  a  m aj or  pr ot oc ol 
de vi ati o n.  P h ysicia ns w h o are u nc o mf orta ble wit h a d mi nisteri n g c he m ot hera p y d ose base d 
o n act ual b o d y wei g ht s h o ul d n ot e nr oll o bese patie nts o n C A L G B pr ot oc ols.  
1 0. 0  C O R R E L A TI V E S CI E N C E C O M P A NI O N S T U DI E S  
T here  is  o ne  c orrelati ve  scie nce  c o m pa ni o n  c o m prise d  of  t w o  st u d y  c o m p o ne nts  t hat  m ust  be 
prese nte d t o all patie nts, t h o u g h patie nts ma y o pt n ot t o partici pate. T he first c o m p o ne nt will be t o 
e val uate ser u m a n d plas ma mar kers a n d t o c orrelate wit h cli nical o utc o mes. T he sec o n d c o m p o ne nt 
will  be t o e val uate i m m u n o hist oc he mical mar kers f or pr o g n osis. B ot h c o m p o ne nts will c o m prise t he 
c o m pa ni o n st u d y C A L G B 1 5 0 9 0 3 . 
1 0. 1 
Ser u m M ar kers  
1 0. 1. 1  B ac k gr o u n d 
Se veral ser u m mar kers ha ve bee n s u g geste d t o be of pre dicti ve val ue wit h re gar d 
t o  pr o gressi o n-free  a n d  o verall  s ur vi val.  A m o n g  t he  m ost  pr o misi n g  are  I L 1 0, 
s ol u ble  C D 3 0  (s C D 3 0),  C C L 1 7,  a n d  C C L 2 2 [ 3 2].  Ele vate d  s C D 3 0  has  bee n 
ass ociate d  wit h  p o or  e ve nt -free  s ur vi val [ 3 3- 3 5] a n d  ele vate d  I L 1 0  has  bee n 
ass ociate d  wit h  p o or  fail ure -free  s ur vi val  i n  m ulti varia ble  a nal yses [ 3 6,  3 7].  I n 
a d diti o n,  c he m o ki nes  C C L 1 7  ( T A R C)  a n d  C C L 2 2  ( M D C)  are  ele vate d  i n 
a p pr o xi matel y 7 5 % of patie nts wit h H o d g ki n l y m p h o ma a n d ha ve bee n s h o w n t o 
fall wit h s uccessf ul treat me nt [ 3 8- 4 0]. F urt her m ore, ele vate d T A R C at dia g n osis 
has bee n s h o w n t o c orrelate wit h p o or o verall s ur vi val [ 4 0]. T hese ha ve n ot bee n 
well st u die d pr os pecti vel y a n d t heir c orrelati o n wit h P E T sca n res ults a n d a bilit y 
t o pre dict rela pse after re missi o n i n d ucti o n are u n k n o w n. T heref ore, we pr o p ose 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 0  
U p date # 1 3  
t o assess t hese pr o misi n g bi ol o gic ser u m mar kers b y E LI S A t o pre dict o utc o me at 
dia g n osis a n d t o f oll o w serial le vels at t he ti me of i ma gi n g st u dies i n or der t o assess 
w het her t hese mar kers ca n pre dict rela pse.  
1 0. 1. 2 O bjecti ves  
1 0. 1. 2. 1 
T o  assess  w het her  ele vate d  baseli ne  ser u m  s ol u ble  C D 3 0  (s C D 3 0), 
I L 1 0, C C L 1 7, a n d C C L 2 2 c orrelate wit h cli nical res p o nse a n d P F S.  
1 0. 1. 2. 2 
T o assess w het her lac k of n or malizati o n or rec urre nt ele vati o n of serial 
ser u m  s C D 3 0,  I L 1 0,  
C C L 1 7,  or  
C C L 2 2  c orrelate  
wit h 
rela pse/ pr o gressi o n or P E T sca n res ults. 
1 0. 1. 3 Met h o ds  
S a m ple C ollecti o n a n d L a b or at or y Met h o ds: I n patie nts w h o c o nse nt, 1 0 m L 
peri p heral ve n o us bl o o d f or plas ma a n d ser u m will be c ollecte d at baseli ne ( pri or 
t o i nitiati o n of t hera p y), after c ycle 2 of A B V D a n d f oll o wi n g eit her c ycle 6 of 
A B V D (f or P E T ne gati ve patie nts) or I F R T (f or P E T p ositi ve patie nts) , a n d at 3, 
6, 9, 1 2, 1 8, 2 4, 3 0 a n d 3 6 m o nt hs d uri n g p ost -treat me nt f oll o w-u p. E LI S A assa ys 
will  be  perf or me d  acc or di n g  t o  ma n ufact ure  pr ot oc ol  at  Cle vela n d  Cli nic 
Refere nce La b orat or y usi n g c o m merciall y a vaila ble E LI S A kits ( R & D s yste ms). 
Res ults will be re p orte d t o t he Allia nce  Statistics a n d Data  Ce nter i n pic o gra ms/ m L 
via a c o de d e xcel s prea ds heet f or mat. N or mal ra n ges ha ve bee n esta blis he d b y t he 
ma n ufact urer.  
1 0. 2 
Pl as m a M ar kers  
1 0. 2. 1 B ac k gr o u n d  
O ne  of  t he  stri ki n g  his t ol o gic  feat ures  of  c H L  is  t he  d o mi na nt  i nfla m mat or y 
bac k gr o u n d prese nt i n m ost cases. We are n o w be gi n ni n g t o rec o g nize t hat t hese 
cells  pr o vi de  a  c o m ple x  net w or k  of  c yt o ki nes  a n d  c he m o ki nes  t hat  pr o vi de  a 
per missi ve  micr oe n vir o n me nt.  T he  T -cell  hea v y  i nfiltrate  of  c H L  is  hea vil y 
s ke we d  t o war ds  a T h 2  a n d  re g ulat or y  T-cell ( Tre g)  c o m p ositi o n [ 4 1,  4 2].  H R S 
cells secrete n u mer o us c yt o ki nes a n d c he m o ki nes s uc h as  I L-5, I L -6, I L -8, I L - 9, 
I L- 1 0, I L-1 3,  T G F ß ,  A P RI L,  B A F F,  C C L 2 8, I P 1 0/ C X C L 1 0,  R A N T E S/ C C L 5), 
M C P 4 ( C C L 1 3), T A R C/ C C L 1 7, a n d M D C/ C C L 2 2 [ 4 1- 4 5]. W hile s o me ma y act 
as a ut ocri ne gr o wt h fact ors f or H R S cells t he msel ves (I L -1 3, A P RI L, B A F F ) [ 4 3, 
4 6] ,  ot hers  a p pear  t o  attract  a n d  s ha pe  t he  i m m u n e  micr oe n vir o n me nt.    F or 
e xa m ple,  I L -5  a n d  C C L 2 8  ser ve  t o  attract  e osi n o p hils,  w hile  I L -6  a n d  C C L 2 8 
attract  plas ma  cells [ 4 1,  4 2,  4 4,  4 5].  I L-1 0  pr o m otes  a  T h 2  res p o nse  a n d  a n 
i m m u n os u p presse d micr oe n vir o n me nt [ 4 5]. T A R C a n d M D C pr o d ucti o n b y H R S 
cells  als o  pr o m ote  a  T h 2  e n vir o n me nt [ 4 2].  Li ke wise,  galecti n  1  secreti o n 
pr o m otes a n i m m u ne pri vile ge d micr oe n vir o n me nt b y pr o m oti n g a T h 2 res p o nse 
a n d  e x pa nsi o n  of  Tre gs [ 4 7].  T hese  s ol u ble  fact ors  ha ve  bee n  e xa mi ne d  as 
pr o g n ostic  fact ors  i n  H L.  Se veral  of  t hese  fact ors  ha ve  bee n  s h o w n  t o  be  of 
p ote ntial pr o g n ostic si g nifica nce i n H L. I n partic ular s ol u ble C D 3 0 (s C D 3 0) a n d 
I L 1 0  ha ve  bee n  s h o w n  i n  se veral  st u dies  t o  be  of  pr o g n ostic  si g nifica nce  at 
baseli ne ( A p pe n di x III ). T A R C a n d M D C, hi g hl y e x presse d i n H R S cells, are als o 
ele vate d  i n  ser u m  of  H L  patie nts [ 3 9,  4 8,  4 9].  T h us,  t hese  mar kers  ma y  be 
i n dicati ve of t u m or b ur de n a n d, i n t he case of T A R C, ma y als o be of pr o g n ostic 
si g nifica nce.    I m p orta ntl y,  t hese  mar kers,  c haracteristicall y  pr o d uce d  b y  H R S 
cells, ma y als o be i n dicati ve of rela pse. We pr o p ose st u d yi n g plas ma le vels of t hese 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 1  
U p date # 1 3  
I L 1 0, s C D 3 0, T A R C, a n d M D C i n patie nts at baseli ne, at ti me of P E T sca ns a n d 
selecte d ti me p oi nts d uri n g f oll o w-u p i n or der t o deter mi ne w het her t hese mar kers 
ha ve pr o g n ostic val ue i n t he c o o perati ve gr o u ps setti n g.  
1 0. 2. 2 O bjecti ves  
1 0. 2. 2. 1 
T o  assess  w het her  ele vate d  baseli n e  plas ma  s ol u ble  C D 3 0  (s C D 3 0), 
I L 1 0, C C L 1 7, a n d C C L 2 2 c orrelate wit h cli nical res p o nse a n d E F S. 
1 0. 2. 2. 2 
T o  assess  w het her  lac k  of  n or malizati o n  or  rec urre nt  ele vate d  serial 
plas ma  s C D 3 0,  I L 1 0,  
C C L 1 7,  or  
C C L 2 2  c orrelate  
wit h 
rela pse/ pr o gressi o n. 
1 0. 2. 2. 3 
T o  assess w het her  ele vate d  plas ma  bi o mar ker  le vels  c orrelate  wit h 
a b n or mal P E T sca n res ults.  
1 0. 2. 3 Met h o ds  
S a m ple C ollecti o n a n d L a b or at or y Met h o ds: I n patie nts w h o c o nse nt, 1 0 m L 
peri p heral ve n o us bl o o d f or plas ma will be c ollecte d at baseli ne ( pri or t o i nitiati o n  
of t hera p y), after c ycle 2 of A B V D, a n d f oll o wi n g eit her c ycle 6 (f or P E T ne gati ve 
patie nts) or I F R T (f or P E T p ositi ve patie nts), a n d  at 3, 6, 9, 1 2, 1 8, 2 4, 3 0 a n d 3 6 
m o nt hs  d uri n g  p ost -treat me nt  f oll o w-u p.  E LI S A  assa ys  will  be  perf or me d 
acc or di n g t o ma n ufact ure pr ot oc ol at Cle vela n d Cli nic Refere nce La b orat or y usi n g 
c o m merciall y  a vaila ble  E LI S A  kits  ( T A R C,  M D C,  I L 1 0  fr o m  R & D  s yste ms, 
Mi n nea p olis,  M N  a n d  s C D 3 0  Ale xis  Bi oc he micals,  Pl y m o ut h  Meeti n g,  P A).   
Sa m ples will be r u n i n d u plicate a n d c orrelate d wi t h cli nical o utc o mes. 
1 0. 3 
I m m u n o hist oc he mic al M ar kers 
1 0. 3. 1  B ac k gr o u n d 
Rece nt  data  s u g gest  t hat  t here  are  bi ol o gic  pre dict ors  of  o utc o me  i n  H o d g ki n 
l y m p h o ma.  Pre dict ors  of  p o or  o utc o me  i n  si n gle  i nstit uti o n  series  i n 
heter o ge ne o usl y  treate d  patie nts  i ncl u de  Bcl -2  a n d  M A L  e x pressi o n  i n  t he 
H o d g ki n  l y m p h o ma  cells [ 5 0- 5 3].  I n  a d diti o n,  F O X P 3 +  cells  (as  a  mar ker  of 
re g ulat or y T-cells wit hi n t he n o n -ne o plastic l y m p h oc ytes) ha ve bee n re p orte d t o 
be a mar ker of fa v ora b le o utc o me [ 5 4]. M A L a n d F O X P 3 ha ve n ot bee n vali date d 
i n ot her series a n d n o ne of t hese mar kers ha ve bee n teste d s pecificall y i n patie nts 
wit h earl y sta ge H L or i n p atie nts treate d wit h t his re gi me n. I n a d diti o n t o F O X P 3, 
mar kers of effect or T -cells, s uc h as gra nz y me B ( Gz B; acti vate d c yt ot o xic T -cells) 
[ 5 5, 5 6] a n d mast cells (tr y ptase/ C D 1 1 7) [ 5 7] will be assesse d as a c o m ple me nt t o 
t he s u p pressi ve re g ulat or y T- cells. B ot h Gz B + T -cells a n d mast cells ha ve bee n 
ass ociate d  wit h  p o or  o utc o me  i n  H L [ 5 5- 5 8]. C D 6 8 +  macr o p ha ges  ha ve  als o 
e mer ge d as a n i m p orta nt micr oe n v ir on me ntal fact or  wit h cases s h o wi n g less t ha n 
5 % C D 6 8 + cells ha vi n g a fa v ora ble pr o g n osis c o m pare d t o t h ose wit h ≥ 5 %. 
1 0. 3. 2 O bjecti ve  
T o deter mi ne w het her t hese tiss ue bi o mar kers c orrelate wit h cli nical o utc o me i n 
patie nts wit h b ul k y sta ge I a n d II H o d g ki n l y m p h o ma treate d wit h t his re gi me n. 
1 0. 3. 3 Met h o ds  
S a m ple C ollecti o n a n d L a b or at or y Met h o ds: I n patie nts w h o c o nse nt, T M As 
will be c o nstr ucte d fr o m f or mali n -fi xe d, paraffi n-e m b e d de d tiss ue c ollecte d pri or 
t o i nitiati o n of t hera p y. M o n ocl o nal a nti b o dies t o Gz B ( Ve nta na), F O X P 3 ( A bca m, 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 2  
U p date # 1 3  
Ca m bri d ge,  U K),  C D 1 1 7  ( Ve nta na),  C D 6 8  ( K P 1,  D A K O), a n d  M A L  ( Dr.  M. 
Al o ns o, C NI O) will be use d t o perf or m a ut o mate d i m m u n o hist oc he mistr y at t he 
Allia nce Bi ore p osit or y at O hi o State  acc or di n g t o sta n dar d pr ot oc ols. N u m bers of 
Gz B, F O X P 3, a n d C D 1 1 7 will be sc ore d as n u m ber of p ositi ve cells/ 5 h pf. M A L 
will be c o nsi dere d p ositi ve if > 2 0 % of H R S cells e x press t his mar ker [ 5 1]. Bcl- 2 
will be c o nsi dere d p ositi ve if > 1 0 % of H R S cells s h o w str o n g Bcl -2 e x pressi o n 
c o m pare d t o a n i nter nal T -cell c o ntr ol  ( A p pe n di x II). C D 6 8 will b e assesse d b y 
ma n ual c o u nti n g as < 5 %, 5- 2 5 %, 2 6- 5 0 %, a n d > 5 0 % [ 5 9]. 
1 1. 0  D R U G F O R M U L A TI O N , A V AI L A BI LI T Y , A N D P R E P A R A TI O N  
1 1. 1 
Q u alifie d Pers o n nel  
Q ualifie d  pers o n nel  w h o  are  fa miliar  wit h  pr oce d ures  t hat  mi ni mize  u n d ue  e x p os ure  t o 
t he msel ves a n d t o t he e n vir o n me nt s h o ul d u n derta ke t he pre parati o n, ha n dli n g, a n d safe 
dis p osal of c he m ot hera pe utic a ge nts i n a self -c o ntai ne d, pr otecti ve e n vir o n me nt. 
1 1. 2 
Disc ar di n g U n use d A ge nts  
Discar d  u n use d  p orti o ns  of  i njecta ble  c he m ot hera pe utic  a ge nts  t hat  d o  n ot  c o ntai n  a 
bacteri ostatic  a ge nt  or  are  pre pare d  wit h  u n preser ve d  dil ue nts  (i.e.,  Sterile  Water  f or 
I nj ecti o n U S P or 0. 9 % S o di u m C hl ori de f or I nj ecti o n U S P) wit hi n ei g ht h o urs of vial e ntr y 
t o mi ni mize t he ris k of bacterial c o nta mi nati o n. 
1 1. 3 
C alc ul ate d D ose R a n ge  
T he t otal a d mi ni stere d d ose of c he m ot hera p y ma y be r o u n de d u p or d o w n wit hi n a ra n ge 
of 5 % of t he act ual calc ulate d d ose. 
1 1. 4 
D o x or u bici n H C L  
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or d o x or u bici n f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d  a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
D o x or u bici n is c o m merciall y a vaila ble as a l y o p hilize d p o w der f or rec o nstit uti o n i n 1 0, 2 0, 
5 0, a n d 1 5 0 m g vials. Als o a vaila ble are 2 m g/ m L s ol uti o n f or i njecti o n i n 1 0, 2 0, 5 0, 7 5, 
a n d 2 0 0 m g vials of d o x or u bici n i n s ol uti o n. 
S T O R A G E &  S T A BI LI T Y  
I ntact  vials  of  d o x or u bici n  s ol uti o n  s h o ul d  be  st ore d  i n  t he  refri gerat or.  I ntact  vials  of 
p o w der f or rec o nstit uti o n s h o ul d be st ore d at r o o m te m perat ure. Rec o nstit ute d s ol uti o ns 
are sta ble f or 7 da ys at r o o m t e m perat ure a n d 1 5 da ys u n der refri gerati o n w he n pr otecte d 
fr o m li g ht. C o m merciall y a vaila ble s ol uti o ns la bele d as s uc h are i nte n de d t o be m ulti d ose 
vials.  
P R E P A R A TI O N  
Rec o nstit ute  t he  vials  wit h  5,  1 0,  2 5,  or  5 0  m L,  res pecti vel y,  of  s o di u m  c hl ori de  f or 
i njecti o n, U S P, res ulti n g i n a c o nce ntrati o n of 2 m g/ m L. 
A D MI NI S T R A TI O N  
D o x or u bici n  is  a d mi nistere d  i ntra ve n o usl y  o ver  3 -5  mi n utes.  A v oi d  e xtra vasati o n,  as 
se vere l ocal tiss ue necr osis ma y res ult. 
T O XI CI TI E S  
He mat ol o gic:  le u k o pe nia ( d ose-li miti n g), t hr o m b oc yto pe nia, a ne mia. Na dir i n 1 0 -1 4 da ys 
wit h rec o ver y us uall y i n 2 1 da ys.  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 3  
U p date # 1 3  
Der mat ol o gic:  al o pecia ( us uall y c o m plete; re versi ble) ra diati o n recall reacti o ns; i ncrease d 
se nsiti vit y t o s u nli g ht. 
Gastr oi ntesti nal:  na usea a n d v o miti n g ( d o x or u bici n is ge nerall y c o nsi dere d m o deratel y t o 
hi g hl y e met o ge nic), a n ore xia, diarr hea, m uc ositis (st o matitis, es o p ha gitis).  
Car di o vasc ular:  car di o m y o pat h y ma y occ ur a n d is relate d t o t otal c u m ulati ve lifeti me d ose. 
T he ris k f or car di o m y o pat h y i ncreases wit h t otal d oses > 4 5 0 m g/ m 2. E C G c ha n ges a n d 
less ofte n, arr h yt h mias, are see n. Rarel y, s u d de n deat h has occ urre d. 
Ot her:  re d disc ol orati o n of uri ne f or 2 4- 4 8 h o urs after dr u g a d mi nistrati o n. D o x or u bici n is 
a vesica nt a n d ca n ca use tiss ue necr osis if e xtra vasate d.  
1 1. 5 
Ble o m yci n  
Pleas e refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or ble o m yci n f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Ble o m yci n  is  c o m merciall y  a vaila ble  i n  vials  c o ntai ni n g  1 5  or  3 0  u nits  of l y o p hilize d 
p o w der f or rec o nstit uti o n. ( 1 u nit = 1 m g) 
S T O R A G E &  S T A BI LI T Y  
I ntact  vials  s h o ul d  be  st ore d  i n  t he  refri gerat or.  Rec o nstit ute d  s ol uti o ns  pre pare d  wit h 
bacteri ostatic dil ue nts are sta ble f or 2 8 da ys at r o o m te m perat ure or u n der refri gerati o n.  
P R E P A R A TI O N  
Rec o nstit ute  t he  vial  wit h  1 -5  m L  of  water  f or  i njecti o n  or  0. 9 %  s o di u m  c hl ori de  wit h 
bacteri ostat res ulti n g i n a c o nce ntrati o n of 3 -1 5 u nits/ ml ( 1 5 u nit vial) or 6 -3 0 u nits/ ml ( 3 0 
u nit vial).  
A D MI NI S T R A TI O N  
Ble o m yci n is a d mi nistere d I V.  
T O XI CI TI E S  
Der mat ol o gic :  s ki n  reacti o ns  are  c o m m o n  ( 5 0 %)  a n d  ma y  i ncl u de,  h y per pi g me ntati o n, 
e de ma, er yt he ma, t hic ke ni n g of nail be ds, a n d al o pecia. Ble o m yci n is n ot a vesica nt a n d 
has bee n a d mi nistere d b y S Q or I M i nj ecti o n. 
P ul m o nar y :  i nterstitial  p ne u m o nitis, p ul m o nar y  fi br osis.  P ne u m o nitis  is  relate d  t o  t otal 
c u m ulati ve  d ose  (e. g.,  it  is  m ore  li kel y  t o  occ ur  wit h  c u m ulati ve  d oses  >  4 0 0  u nits). 
H o we ver,  t he  occ urre nce  i n  i n di vi d ual  patie nts  is  s o me w hat  u n pre dicta ble.  Si g ns  a n d 
s y m pt o ms  i ncl u de  d ys p nea,  c o u g h,  fi ne  rales,  ra di o gra p hic  fi n di n gs  rese m bli n g 
p ne u m o nia, a n d altere d p ul m o nar y f u ncti o n stat us. 
H y perse nsiti vit y : a na p h ylact oi d reacti o ns are re p orte d t o occ ur i n a b o ut 1 % of l y m p h o ma 
patie nts.  T he  reacti o n  is  c haracterize d  b y  se vere  h y per p yre xia,  wit h  s u bse q ue nt 
car di o vasc ular c olla pse. 
Ot her :  Fe ver  wit h  or  wit h o ut  c hills  is  ofte n  see n  ( u p  t o  5 0 %  of  patie nts)  s o o n  after 
a d mi nistrati o n  a n d  ma y  last  f or  4 -1 2  h o urs.  Pre  treat me nt  wit h  aceta mi n o p he n  ma y 
decrease t he li keli h o o d or se verit y of fe ver  
1 1. 6 
Vi n bl asti ne S ulf ate  
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or vi n blasti ne f or pr o d uct i nf or mati o n, 
pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 4  
U p date # 1 3  
A V AI L A BI LI T Y  
Vi n blasti ne is c o m merciall y a vaila ble i n vials of 1 0 m g as a p o w der f or rec o nstit uti o n.  
S T O R A G E &  S T A BI LI T Y  
St ore  i ntact  vials  u n der  refri gerati o n.  O nce  rec o nstit ute d  wit h  bacteri ostatic  dil ue nt, 
s ol uti o ns are sta ble f or 2 1 da ys at r o o m te m perat ure or u n der refri gerati o n. 
P R E P A R A TI O N  
Rec o nstit ute wit h 1 0 m L bacteri ostatic H 2O or 0. 9 % Na Cl, or 0. 9 % Na Cl or sterile H 20 f or 
i njecti o n, t o yiel d a c o nce ntrati o n of 1 m g/ m L. Bacteri ostatic dil ue nt s h o ul d be use d w he n 
vials will be st ore d as descri be d i n “ St ora ge & Sta bilit y.”  
A D MI NI S T R A TI O N  
I V o ver 3-5 mi n utes.  
T O XI CI TI E S  
He mat ol o gic : m yel os u p pressi o n is a m o n g t he m ost c o m m o n si de effects, a n d ma y be d ose 
li miti n g. 
Gastr oi ntesti nal:  na usea a n d v o miti n g ma y occ ur, b ut vi n blasti ne is ge nerall y c o nsi dere d 
mil dl y e met o ge nic w he n use d as a si n gle a ge nt.  
Ne ur ot o xicit y: vi n blasti ne is ass oc iate d wit h q ualitati vel y t he sa me ne ur ot o xicit y as is see n 
wit h  vi ncristi ne  (e. g.,  peri p heral  ne ur o pat h y,  a ut o n o mic  d ysf u ncti o n,  e ve n  ile us),  b ut 
q ua ntitati vel y, vi n blasti ne is m uc h less ne ur ot o xic t ha n vi ncristi ne. Hi g her d oses are m ore 
li kel y t o ca use neur ot o xicit y.  
Vesica nt : vi n blasti ne is a vesica nt a n d ma y ca use tiss ue da ma ge u p o n e xtra vasati o n. 
Ot her:  al o pecia; vi n blasti ne has bee n ass ociate d wit h Ra y na u d’s p he n o me n o n.  
1 1. 7 
D ac ar b azi ne ( D TI C)  
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or dacar bazi ne f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Dacar bazi ne is c o m merciall y a vaila ble i n vials c o ntai ni n g 1 0 0 m g, 2 0 0 m g, or 5 0 0 m g of 
l y o p hilize d p o w der f or rec o nstit uti o n. 
S T O R A G E &  S T A BI LI T Y  
I ntact vials s h o ul d be u n der refri gerati o n a n d pr otecte d fr o m li g ht. T he y are re p orte d t o be 
sta ble f or 4 wee ks at r o o m te m perat ure. O nce rec o nstit ute d, vials are sta ble f or 4 h o urs at 
r o o m te m perat ure or 9 6 h o urs u n der refri gerati o n. F urt her dil ute d s ol uti o ns f or i nf usi o ns 
are sta ble f or 2 4 h o urs at r o o m te m perat ure a n d pr otecte d fr o m li g ht. 
N ote : A c ha n ge i n c ol or of s ol uti o n fr o m pale yell o w t o pi n k is i n dicati ve of dec o m p ositi o n 
of t he dr u g. 
P R E P A R A TI O N  
T he 1 0 0 m g, 2 0 0 m g, a n d 5 0 0 m g  vials s h o ul d be rec o nstit ute d wit h 9. 9 m L, 1 9. 7 m L, a n d 
4 9. 5  m L  of  sterile  water,  res pecti vel y,  res ulti n g  i n  a  c o nce ntrati o n  of  1 0  m g/ m L.  M ore 
c o nce ntrate d s ol uti o ns (e. g. 2 0 m g/ m L) ma y als o be use d. T he desire d v ol u me s h o ul d t he n 
be wit h dra w n a n d i njecte d i nt o 1 5 0 - 1 0 0 0 m L D 5 W or 0. 9 % Na C L, f or I V i nf usi o n. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 5  
U p date # 1 3  
A D MI NI S T R A TI O N  
Dacar bazi ne s h o ul d be a d mi nistere d b y I V i nf usi o n o ver 3 0 mi n utes or l o n ger. Dacar bazi ne 
a d mi nistrati o n ma y be ass ociate d wit h pai n/irritati o n. Pai nf ul a d mi nistrati o n is mi ni mize d 
wit h t h e use of sl o w a n d dil ute i nf usi o ns. 
T O XI CI TI E S  
He mat ol o gic :  m yel os u p pressi o n;  na dir  of  W B C  a n d  platelet  de pressi o n  occ urs 
a p pr o xi matel y 7-1 0 da ys after treat me nt.  
Der mat ol o gic :  al o pecia,  p h ot ose nsiti vit y.  Dacar bazi ne  is  c o nsi dere d  a n  irrita nt. 
E xtra vasati o n ma y res ult i n pai n, b ut is n ot ass ociate d wit h tiss ue da ma ge.  
Gastr oi ntesti nal : na usea a n d v o miti n g. Dacar bazi ne is c o nsi dere d hi g hl y e met o ge nic. 
Ot her :  fl u-li ke  s y n dr o me  ( wit h  fe ver,  malaise,  m yal gia)  ma y  occ ur  wit hi n  7  da ys  of 
treat me nt. 
1 1. 8 
Et o p osi de   
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or et o p osi de f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Et o p osi de  is  c o m merciall y  a vaila ble  i n  5  m L,  2 5  m L,  a n d  5 0  m L  vials  c o ntai ni n g  2 0 
m g/ m L. S ol uti o ns c o ntai n p ol ys or bate 8 0.  
S T O R A G E &  S T A BI LI T Y  
U n o pe ne d vials s h o ul d be st ore d at r o o m te m perat ure a n d pr otecte d fr o m li g ht. S ol uti o ns 
dil ute d t o a c o nce ntrati o n of 0. 2 a n d 0. 4 m g/ m L (i n D 5 W or N S) are sta ble f or 9 6 a n d 4 8 
h o urs, res p ecti vel y, at r o o m te m perat ure u n der n or mal li g ht. 
P R E P A R A TI O N  
T he d ose of et o p osi de s h o ul d be f urt her dil ute d wit h D 5 W or n or mal sali ne f or i njecti o n t o 
a fi nal c o nce ntrati o n of less t ha n or e q ual t o 0. 4 m g/ m L. 
A D MI NI S T R A TI O N  
Et o p osi de is deli vere d b y I V i nf usi o n o ver at least 4 5 -6 0 mi n utes; a d mi nistrati o n t hat is t o o 
ra pi d ma y be ass ociate d wit h h y p ote nsi o n. 
T O XI CI TI E S  
He mat ol o gic : m yel os u p pressi o n. 
Gastr oi ntesti nal :  a n ore xia,  na usea  a n d  v o miti n g  (et o p osi de  is  c o nsi dere d  mil dl y 
e met o ge nic). 
Der mat ol o gic: al o pecia. 
Ot her :  h y perse nsiti vit y  reacti o ns  i ncl u di n g  c hills,  fe ver,  tac h ycar dia,  br o nc h os pas m, 
d ys p nea a n d h y p ote nsi o n are re p orte d rarel y.  
1 1. 9 
C ycl o p h os p h a mi de  
Please  refer  t o  t he  F D A -a p pr o ve d  pac ka ge  i nsert  f or  c ycl o p h os p ha mi de  f or  pr o d uct 
i nf or mati o n, e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts. 
A V AI L A BI LI T Y  
C o m merciall y a vaila ble as a p o w der f or rec o nstit uti o n i n vials c o ntai ni n g 1 0 0, 2 0 0, 5 0 0, 
1 0 0 0, a n d 2 0 0 0 m g. 
St ora ge & Sta bilit y  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 6  
U p date # 1 3  
I ntact vials s h o ul d be st ore d at r o o m te m perat ure. Rec o nstit ute d s ol uti o ns are sta ble f or 2 4 
h o urs at r o o m te m perat ure a n d 6 da ys i n a refri gerat or. F urt her dil ute d s ol uti o ns are als o 
sta ble f or 2 4 h o urs at r o o m te m perat ure a n d 6 da ys u n der refri gerati o n. 
P R E P A R A TI O N  
Rec o nstit ute 1 0 0 m g, 2 0 0 m g, 5 0 0 m g, 1 g a n d 2 g vi als wit h 5, 1 0, 2 5, 5 0, or 1 0 0 m L of 
S WI or N S t o gi ve a fi nal c o nce ntrati o n of 2 0 m g/ m L. Vi g or o us s ha ki n g ma y be n ecessar y 
f or n o n-l y o p h ylize d pre parati o ns. Bacteri ostatic water f or i njecti o n ( para be n pre parati o ns 
o nl y) ma y b e use d; be nz yl alc o h ol deri vati ves ma y N O T be use d. S ol uti o ns ma y b e f urt her 
dil ute d i n D 5 W or N S f or I V i nf usi o n. 
A D MI NI S T R A TI O N  
C ycl o p h os p ha mi de ma y be a d mi nistere d as a n I V b ol us or I V i nf usi o n. 
T O XI CI T Y  
He mat ol o gic : m yel os u p pressi o n; e x pecte d na dir f or ne utr o pe nia is a p pr o xi matel y 1 0 da ys.  
Gastr oi ntesti nal :  na usea  a n d  v o miti n g;  t he  d ose  of  c ycl o p h os p ha mi de  i n  escalate d  d ose 
B E A C O P P is c o nsi dere d hi g hl y e met o ge nic. T he c ycl o p h os p ha mi de d ose i n sta n dar d d ose 
B E A C O P P is c o nsi dere d m o deratel y e met o ge nic ( w h e n a d mi nistere d as a si n gle a ge nt).  
Der mat ol o gic: al o pecia.  
Ge nit o uri nar y :  he m orr ha gic  c ystitis  is  t h o u g ht  t o  be  d ue  t o  t he  prese nce  of  t he 
c ycl o p h os p ha mi de  meta b olite,  acr olei n,  i n  t he  bla d der.  H y drati o n  a n d  fre q ue nt  v oi di n g 
hel p t o mi ni mize t he occ urre nce of he m orr ha gic c ystitis. I n a d diti o n, i n t his st u d y, mes na 
ma y  be  a d mi nistere d  wit h  c ycl o p h os p ha mi de.  SI A D H  is  see n  less  fre q ue ntl y  t ha n 
he m orr ha gic c ystitis. SI A D H ge nerall y res ol ves wit hi n 2 4 h o urs wit h fl ui d restricti o n.  
Ot her : heart fail ure a n d cardiac necr osis occ ur rarel y after hi g h d ose c ycl o p h os p ha mi de. 
( d oses hi g her t ha n t h ose use d i n t his st u d y) 
1 1. 1 0 Vi ncristi ne  
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or vi ncristi ne f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Vi ncristi ne is c o m merciall y a vaila ble as a s ol uti o n 1 a n d 2 m g vials at a c o nce ntrati o n of 1 
m g/ m L.  
S T O R A G E &  S T A BI LI T Y  
I ntact vials s h o ul d be st ore d u n der refri gerati o n. T he y are re p orte d t o be sta ble f or u p t o 3 0 
da ys at r o o m te m perat ure. M ost vials are i nte n de d t o be m ulti -d ose vials. S ol uti o ns f urt her 
dil ute d f or I V i nf usi o n i n D 5 W or N S are sta ble f or 7 da ys or u n der refri gerati o n or 2 da ys 
at r o o m te m perat ure. 
A D MI NI S T R A TI O N  
Vi ncristi ne  is  a d mi nistere d  i ntra ve n o usl y.  N u mer o us  re p orts  of  fatalities  f oll o wi n g 
i na d verte nt  i ntrat hecal  a d mi nistrati o n  of  vi ncristi ne  u n derlie  t he  rec o m me n dati o n  f or 
a d mi nistrati o n as a s h ort I V i nf usi o n rat her t ha n a b ol us I V i nj ecti o n. 
T O XI CI T Y  
T he  d ose  li miti n g  t o xicit y  of  vi ncristi ne  is  ne ur ot o xicit y.  B ot h  se ns or y  a n d  m ot or 
ne ur o pat hies  are  c o m m o n.  Ot her  ma nifestati o ns  of  ne ur ot o xicit y  i ncl u de  cra nial  ner ve 
palsies,  c o nsti pati o n  a n d  ile us,  a n d  ort h ostatic  h y p ote nsi o n.  Al o pecia  is  als o  c o m m o n. 
F atalities ha ve bee n re p orte d f oll o wi n g i na d verte nt i ntrat hecal a d mi nistrati o n of vi ncristi ne 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 7  
U p date # 1 3  
a n d  care  s h o ul d  be  ta ke n  t o  a v oi d  t his  err or.  Vi ncristi ne  is  c o nsi dere d  a  vesica nt  a n d 
ulcerati o n ca n occ ur u p o n e xtra vasati o n. 
1 1. 1 1 P r oc ar b azi ne  
Please refer t o t he F D A-a p pr o ve d pac ka ge i nsert f or pr ocar bazi ne f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Pr ocar bazi ne is c o m merciall y a vaila ble as 5 0 m g ca ps ules f or oral a d mi nistrati o n.  
S T O R A G E  &  S T A BI LI T Y  
Pr ocar bazi ne ca ps ules s h o ul d be st ore d at r o o m te m perat ure a n d sta bilit y is as n ote d b y t he 
ma n ufact urer(s).  
A D MI NI S T R A TI O N  
Pr ocar bazi ne  s h o ul d  be  a d mi nistere d  orall y,  o nce  dail y.  A d mi nistrati o n  at  be dti me  ma y 
hel p t o mi ni mize na usea. 
T O XI CI T Y  
Ce ntral ner v o us s yste m : ne ur ot o xicit y i ncl u di n g m o o d dis or ders a n d C N S de pressi o n is 
c o m m o nl y  s u g geste d  t o  occ ur  wit h  pr ocar bazi ne,  alt h o u g h  t he  i nci de nce  is  n ot  well 
d oc u me nte d.  I n  t he  Ger ma n  H o d g ki n’s  L y m p h o ma  St u d y  Gr o u p  st u d y  ( N EJ M  2 0 0 3; 
3 4 8: 2 3 8 6) t he  fre q ue nc y of gra de 3 or 4 ne ur ol o gic a d verse e ve nts was 5 % wit h sta n dar d 
d ose  B E A C O P P,  4 %  wit h  escalate d  d ose  B E A C O P P  a n d  4 %  wit h  C O P P -A B V D.  All 
re gi me ns als o i ncl u de d vi ncristi ne a n d t he details of ne ur ot o xicit y are n ot descri be d. 
He mat ol o gic : m yel os u p pressi o n, he m ol ysis i n patie nts wit h G- 6-P D deficie nc y.  
Gastr oi ntesti nal :  na usea  a n d  v o miti n g  ( pr ocar bazi ne  is  c o nsi dere d  m o deratel y 
e met o ge nic); i ncreasi n g t he d ose i n a ste p wise fas hi o n o ver se veral da ys ma y  mi ni mize 
t his, as ma y a d mi nistrati o n of e ntire d ose at be dti me. 
Ge nit o uri nar y: re pr o d ucti ve d ysf u ncti o n > 1 0 %. 
Ot her :  sec o n d  mali g na ncies  (c u m ulati ve  i nci de nce  2 %  t o  1 5 %  re p orte d  wit h  M O P P 
c o m bi nati o n t hera p y). 
IN T E R A C TI O N S  
Pr ocar bazi ne  is  a  wea k  m o n oa mi ne  o xi dase  ( M A O)  i n hi bit or.  Us ual  ca uti o ns  re gar di n g 
a v oi da nce of t yra mi ne -c o ntai ni n g f o o ds are c o m m o nl y e xercise d t o a v oi d t he p ossi bilit y 
of  h y perte nsi ve  crisis.  F o o ds  wit h  t he  hi g hest  a m o u nts  of  t yra mi ne  i ncl u de  b o ursa ult, 
ca me m bert, c he d dar, e m me nt haler, a n d stilt o n c heese; ca viar; pic kle d herri n g; fer me nte d 
sa usa ges ( b ol o g na, pe p per o ni, sala mi, s u m mer sa usa ge); C hia nti wi ne; fa va bea ns (c o ntai n 
d o pa mi ne); yeast e xtract ( ba ke d g o o ds, h o we ver, d o n ot c o ntai n hi g h a m o u nts of t yra mi ne). 
T here  are  n o  re p orts  i n  h u ma ns  of  h y perte nsi ve  crisis  f oll o wi n g  i n gest i o n  of  t yra mi ne-
c o ntai ni n g  f o o ds  i n  w hic h  pr ocar bazi ne  was  t he  M A O  i n hi bit or.  T he  sa me  ca uti o n  is 
a p plie d f or tric yclic a nti de pressa nts a n d s y m pat h o mi metic a ge nts.  
Pr ocar bazi ne is c o m m o nl y sai d t o res ult i n a dis ulfira m reacti o n w he n ta ke n wit h alc o h ol. 
T h e re p orte d reacti o n c o nsiste d of facial fl us hi n g (re d, h ot).  
C N S  de pressi o n:  See  disc ussi o n  of  ner v o us  s yste m  t o xicit y  a b o ve.  Pr ocar bazi ne  is 
s u g geste d t o a d d t o t he effects of ot her C N S de pressa nts. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 8  
U p date # 1 3  
1 1. 1 2 P re d nis o ne  
Please refer t o t he F D A -a p pr o ve d pac ka ge i nsert f or pre d nis o ne f or pr o d uct i nf or mati o n, 
e xte nsi ve pre parati o n i nstr ucti o ns, a n d a c o m pre he nsi ve list of a d verse e ve nts.  
A V AI L A BI LI T Y  
Pre d nis o ne is c o m merciall y a vaila ble i n 1, 2. 5, 5, 1 0, 2 0, a n d 5 0 m g ta blets a n d i n a n oral 
s ol uti o n (c o ntai ni n g alc o h ol) i n c o nce ntrati o ns of 1 m g or 5 m g of pre d nis o ne/ m L. 
S T O R A G E &  S T A BI LI T Y  
Pre d nis o ne s h o ul d be st ore d at r o o m te m perat ure. 
A D MI NI S T R A TI O N  
Pre d nis o ne is a d mi nistere d orall y.  
T O XI CI T Y  
S h ort- ter m use of pre d nis o ne (e. g., ≤ 4 wee ks) ma y be ass ociate d wit h gastr oi ntesti nal si de 
effects  ( d ys pe psia,  ulcerati o n); i ns o m nia,  ner v o us ness,  a n d  occasi o nall y,  ps yc h osis;  a n d 
h y per gl yce mia. I m m u n os u p pressi o n wit h a n i ncreasi n g ris k of i nfecti o n is als o see n. 
1 2. 0  A N CI L L A R Y T H E R A P Y  
1 2. 1 
S u p p orti ve C are  
Patie nts  s h o ul d  recei ve  f ull  s u p p orti ve  care,  i ncl u di n g  tra nsf usi o ns  of  bl o o d  a n d  bl o o d 
pr o d ucts,  a nti bi otics,  a ntie metics,  etc.,  w he n  a p pr o priate.  T he  reas o n(s)  f or  treat me nt, 
d osa ge, a n d t he dates of treat me nt s h o ul d be rec or de d o n t he fl o w s heets. HI V p ositi ve 
pati e nt s h o ul d be ma na ge d acc or di n g t o i nstit uti o nal g ui deli nes. Zi d o v u di ne a n d sta v u di ne 
ma y n ot be a d mi nistere d as part of t he a ntiretr o viral t hera p y f or HI V p ositi ve patie nts. See 
S ecti o ns 7. 1. 2 , 7. 1. 3  a n d 9. 1. 1 . 
1 2. 2 
C o n diti o ns f or Ot her T her a p y  
Treat me nt  wit h  h or m o nes  or  ot her  c he m ot hera pe utic  a ge nts  ma y  n ot  be  a d mi nistere d 
e xce pt i n t he f oll o wi n g circ u msta nces: Ster oi ds ma y be a d mi nistere d f or a dre nal fail ure. 
H or m o nes  ma y  be  a d mi nistere d  f or  n o n -disease -relate d  c o n diti o ns  (e. g.,  i ns uli n  f or 
dia betes). De xa met has o ne ma y be a d mi nistere d o n t he da y of c he m ot hera p y f or (ac ute) 
c he m ot hera p y-i n d uce d na usea or v o miti n g. 
1 2. 3 
P r o p h yl a xis f or Pre ve nti o n of He m orr h a gic C ystitis  
Mes n a  ma y  be  a d mi nistere d  f or patie nts  getti n g  c ycl o p h os p ha mi de  t o  pre ve nt/ mi ni mize 
t he  occ urre nce  of  he m orr ha gic  c ystitis.  If  use d,  mes na  s h o ul d  be  gi ve n  acc or di n g  t o 
i nstit uti o nal g ui deli nes. 
1 2. 4 
A ntie metic T her a p y  
A ntie metic  t hera p y  s h o ul d  i ncl u de  5 -H T 3  re ce pt or  a nta g o nists  (e. g.  o n da nsetr o n, 
gra nisetr o n).  
1 2. 5 
Tr a nsf usi o ns  
Er yt hr oc yte a n d platelet tra nsf usi o ns ma y be a d mi nistere d as necessar y at t he discreti o n of 
t he treati n g p h ysicia n. 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
5 9  
U p date # 1 3  
1 3. 0  C RI T E RI A F O R R E S P O N S E , P R O G R E S SI O N , A N D R E L A P S E  
F or t he p ur p oses  of t his st u d y, patie nts will be re -e val uate d after t w o ( 2) c ycles of A B V D t hera p y. 
Patie nts  wit h  a  ne gati ve  P E T  sca n  will  be  re -e val uate d  after  6  c ycles  of  A B V D.  Patie nts  wit h  a 
p ositi ve P E T sca n will be re -e val uate d f oll o wi n g I F R T. Res p o nse assess me nts must be perf or me d 
usi n g t he sa me i ma gi n g m o dalit y ( P E T) as use d at t he ti me of pre -st u d y e val uati o n. 
1 3. 1 
Defi niti o ns of Res p o nse [ 6 0] 
1 3. 1. 1 C o m plete Res p o nse ( C R)  
C o m plete disa p peara nce of all detecta ble cli nical e vi de nce of disease a n d disease -
relate d s y m pt o ms if prese nt bef ore t hera p y. 
T he s plee n a n d/ or li ver, if c o nsi dere d e nlar ge d pri or t o t hera p y o n t he basis of a 
p h ysical e xa mi nati o n or C T sca n, s h o ul d n ot be pal pa ble o n p h ysical e xa mi nati o n 
a n d s h o ul d be c o nsi dere d n or mal size b y i ma gi n g st u dies, a n d n o d ules relate d t o 
l y m p h oma  s h o ul d  disa p pear.  H o we ver,  deter mi nati o n  of  s ple nic  i n v ol ve me nt  is 
n ot al wa ys relia ble beca use a s plee n c o nsi dere d n or mal i n size ma y still c o ntai n 
l y m p h o ma, w hereas a n e nlar ge d s plee n ma y reflect variati o ns i n a nat o m y, bl o o d 
v ol u me, t he use of he mat o p oietic gr o wt h fact ors, or ca uses ot her t ha n l y m p h o ma. 
1 3. 1. 2 P arti al Res p o nse ( P R)  
At least a 5 0 % decrease i n t he s u m of t he pr o d uct of t he dia meters ( S P D) of u p t o 
si x of t he lar gest d o mi na nt n o des or n o dal masses. T hese n o des or masses s h o ul d 
be selecte d  acc or di n g t o all of t he f oll o wi n g: a) t he y s h o ul d be clearl y meas ura ble 
i n  at  least  t w o  per pe n dic ular  di me nsi o ns;  b)  if  p ossi ble,  t he y  s h o ul d  be  fr o m 
dis parate  re gi o ns  of  t he  b o d y;  a n d  c)  t he y  s h o ul d  i ncl u de  me diasti nal  a n d 
retr o perit o neal areas of disease w he ne ver t hese sites are i n v ol ve d. 
N o i ncrease s h o ul d be o bser ve d i n t he size of ot her n o des, li ver, or s plee n. 
S ple nic n o d ules m ust re gress b y ≥ 5 0 % i n t heir S P D, or, f or si n gle n o d ules, i n t he 
greatest tra ns verse dia meter.  
Wit h  t he  e xce pti o n  of  s ple nic  n o d ules,  i n v ol ve me nt  of  ot her  or ga ns  is  us uall y 
assessa ble a n d n o meas ura ble disease s h o ul d be prese nt.  
N o ne w sites of disease s h o ul d be o bser ve d.  
If  t he  P E T  sca n  was  p ositi ve  bef ore  t hera p y,  t he  p ost-treat me nt  P E T  s h o ul d  be 
p ositi ve i n at least o ne pre vi o usl y i n v ol ve d site.  
1 3. 1. 3 St a ble Dise ase ( S D): P atie nt f ails t o att ai n t he criteri a nee de d f or a C R or P R, 
b ut d oes n ot f ulfill t h ose f or pr o gressi ve dise ase (see bel o w). T he P E T s h o ul d 
be p ositi ve at pri or sites of dise ase, wit h n o ne w are as of i n v ol ve me nt o n t he 
p ost -tre at me nt C T or P E T. 
1 3. 1. 4 P r o gressi o n ( P D) or Rel a pse  
L y m p h  n o des  s h o ul d  be  c o nsi dere d  a b n or mal  if  t he  l o n g  a xis  is  >  1. 5  c m, 
re gar dless of t he s h ort a xis. If a l y m p h n o de has a l o n g a xis of 1. 1 t o 1. 5 c m, it 
s h o ul d o nl y be c o nsi dere d a b n or mal if its s h ort a xis is > 1. 0. L y m p h n o des ≤ 1. 0 
c m  b y  ≤  1. 0  c m  will  n ot  be  c o nsi dere d  as  a b n or mal  f or  rela pse  or  pr o gressi ve 
disease.  
A p peara nce of a n y ne w lesi o n > 1. 5 c m i n a n y a xis d uri n g or at t he e n d of t hera p y, 
e ve n if ot her lesi o ns are decreasi n g i n size. I ncrease d F D G u pta ke i n a pre vi o usl y 

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u naffecte d  site  s h o ul d  o nl y  be  c o nsi dere d  rela pse d  or  pr o gressi ve  disease  after 
c o nfir mati o n wit h ot her m o dalities. I n patie nts wit h n o pri or hist or y of p ul m o nar y 
l y m p h o ma,  ne w  l u n g  n o d ules  i de ntifie d b y  C T  are  m ostl y  be ni g n.  T h us,  a 
t hera pe utic decisi o n s h o ul d n ot be ma de s olel y o n t he basis of t he P E T wit h o ut 
hist ol o gic c o nfir mati o n.  
At least a 5 0 % i ncrease fr o m na dir i n t he S P D of a n y pre vi o usl y i n v ol ve d n o des, 
or i n a si n gle i n v ol ve d n o de, or t he size of ot her lesi o ns (e. g., s ple nic or he patic 
n o d ules). T o be c o nsi dere d pr o gressi ve disease, a l y m p h n o de wit h a dia meter of 
t he s h ort a xis of < 1. 0 c m m ust i ncrease b y ≥ 5 0 % a n d t o a size of 1. 5 x 1. 5 c m, or 
> 1. 5 c m i n t he l o n g a xis. 
At least a 5 0 % i nc rease i n t he l o n gest dia meter of a n y si n gle pre vi o usl y i de ntifie d 
n o de > 1. 0 c m i n its s h ort a xis. 
Lesi o ns s h o ul d be P E T -p ositi ve if a t y pical F D G -a vi d l y m p h o ma or t he lesi o n was 
P E T -p ositi ve  pri or  t o  t hera p y  u nless  t he  lesi o n  is  t o o  s mall  t o  be  detecte d  w it h 
c urre nt P E T s yste ms ( < 1. 5 c m i n its l o n g a xis b y C T).  
1 3. 2 
G ui deli nes f or E v al u ati o n of Me as ur a ble Dise ase  
Meas ura ble  e xtra n o dal  disease  s h o ul d be assesse d i n  a  ma n ner si milar t o t hat f or  n o dal 
disease. F or t hese rec o m me n dati o ns, t he s plee n is c o nsi dere d n o dal disease. Disease t hat is 
o nl y assessa ble (e. g., ple ural eff usi o ns, b o ne lesi o ns) will be rec or de d as prese nt or a bse nt 
o nl y, u nless, w hile a n a b n or malit y is still n ote d b y i ma gi n g st u dies or p h ysical e xa mi nati o n, 
it is f o u n d t o be hist ol o gicall y ne gati ve.  
1 3. 2. 1 Cli nical  Lesi o ns  will  o nl y  be  c o nsi dere d  meas ura ble  w he n  t he y  are  s u perficial 
(e. g., s ki n n o d ules, pal pa ble l y m p h n o des). 
1 3. 2. 2 C hest X -ra y: Lesi o ns o n c hest X-ra y are acce pta ble as meas ura ble lesi o ns w he n 
t he y  are  clearl y  defi ne d  a n d  s urr o u n de d  b y  aerate d  l u n g.  H o we ver,  C T  is 
prefera ble.  
1 3. 2. 3 C o n ve nti o nal C T a n d M RI s h o ul d be perf or me d wit h c uts of 1 0 m m or less i n slice 
t hic k ness c o nti g u o usl y. S piral C T s h o ul d be perf or me d usi n g a 5 m m c o nti g u o us 
rec o nstr ucti o n al g orit h m. T his a p plies t o t he c hest, a b d o me n, a n d pel vis. Hea d & 
nec k a n d e xtre mities us uall y re q uire s pecific pr ot oc ols.  
1 3. 2. 4 Ultras o u n d ( U S) s h o ul d n ot be use d t o meas ure t u m or lesi o ns t hat are cli nicall y 
n ot easil y accessi ble w he n t he pri mar y e n d p oi nt of t he st u d y is o bject i ve res p o nse 
e val uati o n.  It  is  a  p ossi ble  alter nati ve  t o  cli nical  meas ure me nts  of  s u perficial 
pal pa ble  n o des,  s u bc uta ne o us  lesi o ns,  a n d  t h yr oi d  n o d ules.  U S  mi g ht  als o  be 
usef ul  t o  c o nfir m  t he  c o m plete  disa p peara nce  of  s u perficial  lesi o ns  us uall y 
assesse d b y cli nical e xa mi nati o n.  

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1 3. 3 
Res p o nse Assess me nt T a ble  
Res p o nse Cate g or y  
Defi niti o n  
N o dal Masses  
S plee n  
C R  
Disa p peara nce of 
all e vi de nce of 
disease  
a) P E T p ositi ve at baseli ne; mass of a n y size 
per mitte d if P E T ne gati ve  
b) Varia bl y P E T ne gati ve at baseli ne; 
re gressi o n t o n or mal size C T 
N ot pal pa ble, 
n o d ules disa p peare d  
P R  
Re gressi o n of 
meas ura ble 
disease, n o ne w 
sites 
≥ 5 0 % decrease i n S P D of u p t o 6 lar gest 
d o mi na nt masses; n o i ncrease i n size of ot her 
n o des  
a) P E T p ositi ve at baseli ne; o ne or m or e P E T 
p ositi ve at pre vi o usl y i n v ol ve d site  
b) Varia bl y P E T ne gati ve at baseli ne; 
re gressi o n o n C T 
≥ 5 0 % decrease i n 
S P D of n o d ules (f or 
si n gle n o d ule i n 
greatest tra ns verse 
dia meter); n o 
i ncrease i n size of 
s plee n 
S D  
Fail ure t o attai n 
C R, P R, or P D  
a) P E T  p ositi ve at baseli ne; P E T p ositi ve at 
pri or sites of disease a n d n o ne w sites o n  C T 
or P E T  
b) Varia bl y P E T ne gati ve at baseli ne; n o 
c ha n ge i n size of pre vi o us lesi o ns o n C T  
 
P D  
A n y ne w lesi o n 
i ncrease b y ≥ 5 0 % 
of pre vi o usl y 
i n v ol ve d disease 
sites 
A p peara nce of a ne w lesi o n(s) > 1. 5 c m i n 
a n y a xis, ≥5 0 % i ncrease i n S P D of m ore t ha n 
o ne n o de, or ≥5 0 % i ncrease i n l o n gest 
dia meter of a pre vi o usl y i de ntifie d n o de > 1 
c m i n s h ort a xis. Lesi o ns P E T p ositi ve if 
F D G -a vi d l y m p h o ma or P E T p ositi ve pri or 
t hera p y. 
≥ 5 0 % i ncrease 
fr o m na dir i n t he 
S P D of a n y pre vi o us 
lesi o ns 
1 3. 4 
Defi niti o n of P r o gressi o n -F ree S ur vi v al  
Pr o gressi o n- free  s ur vi val  ( P F S)  is  meas ure d  as  t he  ti me  fr o m  st u d y  e ntr y  t o  disease 
pr o gressi o n or deat h. 
1 4. 0  R E M O V A L O F P A TI E N T S F R O M P R O T O C O L T H E R A P Y  
1 4. 1  D ur ati o n of Tre at me nt 
1 4. 1. 1 C o nti n ue treat me nt at t he hi g hest t olera ble d ose f or a t otal of 6 c ycles +/ - I F R T or 
u ntil t he a p peara nce of disease pr o gressi o n or u nacce pta ble t o xicit y. Re m o ve fr o m 
pr ot oc ol t hera p y a n y patie nt wit h ra pi d or d oc u me nte d disease pr o gressi o n.  
1 4. 1. 2 P ost -Tre at me nt P atie nt F oll o w -U p: After c ycle 6 wit h or wit h o ut I F R T, patie nts 
will be m o nit ore d de pe n di n g o n res p o nse ac hie ve d, P E T sca ns, a n d, if perf or me d, 
bi o ps y res ults as f oll o ws:  
C R,  P R  a n d  P E T  ne g ati ve:  Patie nts  wil l  be  f oll o we d  acc or di n g  t o  t he  p ost-
treat me nt f oll o w- u p sc he d ule i n Secti o n 6. 0 . 
C R,  P R,  P E T  p ositi ve,  a n d  bi o ps y  p ositi ve:  Patie nts  ma y  be  treate d  at 
i n vesti gat or  discreti o n  a n d  will  be  f oll o we d  f or  s ur vi val  a n d  sec o n dar y 
mali g na ncies or ne w pri maries.  
C R,  P R,  or  S D, P E T  p ositi ve,  a n d  bi o ps y  n ot  perf or me d:  Patie nts  will  ha ve 
re peat P E T/ C T a n d C T sca ns perf or me d t hree m o nt hs later. If P E T sca n bec o mes 
ne gati ve,  patie nts  will  be  f oll o we d  acc or di n g  t o  t he  p ost -treat me nt  f oll o w- u p 
sc he d ule i n Secti o n 6. 0 . If P E T re mai ns p ositi ve, t he n a bi o ps y ma y be perf or me d 
if  me dicall y  a p pr o priate  or  cli nicall y  feasi ble  at  t he  discreti o n  of  t he  treati n g 
p h ysicia n.  If  bi o ps y  is  p ositi ve,  patie nts  will  be  f oll o we d  f or  s ur vi v al  a n d 

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sec o n dar y mali g na ncies or ne w pri maries. If bi o ps y is ne gati ve, patie nts will be 
f oll o we d acc or di n g t o t he p ost-treat me nt f oll o w- u p sc he d ule i n Secti o n 6. 0 . 
1 4. 2 
E xtr a or di n ar y Me dic al Circ u mst a nces :  
If, at a n y ti me t he c o nstrai nts of t his pr ot oc ol are detri me ntal t o t he patie nt’s healt h a n d/ or 
t he  patie nt  n o  l o n ger  wis hes  t o  c o nti n ue  pr ot oc ol  t hera p y,  pr ot oc ol  t hera p y  s hall  be 
disc o nti n ue d. I n t his e ve nt: 
•  
N otif y t he St u d y C hair. 
•  
D oc u me nt t he reas o n(s) f or disc o nti n uati o n  of t hera p y o n fl o w s heets. 
•  
F oll o w  t he  patie nt  f or  rela pse,  pr o gressi o n,  a n d  sec o n dar y  mali g na nc y  or  ne w 
pri maries.  
1 5. 0  S T A TI S TI C A L C O N SI D E R A TI O N S  
1 5. 1 
St u d y Desi g n  
T his  is  si n gle -ar m  p hase  II  cli nical  trial  of  res p o nse -a da pte d  t hera p y  base d  o n  P E T  f or 
b ul k y sta ge I a n d sta ge II H o d g ki n l y m p h o ma. A ma xi m u m of 1 2 3 patie nts will be e ntere d 
t o t he st u d y. 
1 5. 2 
P ri m ar y E n d p oi nt  
T he pri mar y o utc o me of t his st u d y is pr o gressi o n -free s ur vi val ( P F S), defi ne d as t he ti me 
fr o m st u d y e ntr y t o disease pr o gressi o n or deat h.  
1 5. 2. 1 A n al ysis Pl a n  
T he p atie nts w h o ha ve C R, P R or S D after 2 c ycles of A B V D  will u n der g o t he first 
P E T/ C T sca n . We wa nt t o s h o w t hat  b y recei vi n g 4 c ycles of escalate d B E A C O P P 
a n d I F R T, t he P F S of P E T + patie nts will ha ve a P F S t hat is  cl ose t o t hat of P E T - 
patie nts recei vi n g 4 a d diti o nal A B V D. Let λ +  a n d λ - de n ote t he a n n ual hazar d rates 
of P F S f or P E T + a n d P E T - patie nt gr o u ps, res pecti vel y, a n d ∆= λ + / λ- t heir hazar d 
rati o. Base d o n t he pr ojecte d hazar d rates f or P E T + a n d P E T - patie nt gr o u ps as 
di sc usse d  i n Secti o n  1 5. 2. 2 ,  we  wa nt  t o  test H 0:  ∆= 4. 1  vs.  H1:  ∆< 4. 1  usi n g 
u ni variate C o x re gressi o n met h o d wit h o ne -si de d α = 0. 1 5 [ 6 1]. T he fi nal a nal ysis 
will be c o n d ucte d w he n 4 4 e ve nts ( pr o gressi o ns or deat hs) are o bser ve d, w hic h is 
e x pecte d t o occ ur a b o ut 3 years after t he c o m pleti o n of patie nt accr ual.  Ka pla n -
Meier c ur ves of P F S will be esti mate d f or t he t w o patie nt gr o u ps.   
T he u ni variate C o x re gressi o n tests o n t he hazar d rati o bet wee n t w o patie nt gr o u ps, 
s o t hat it d oes n ot re q uire s pecificati o n of t he P F S f or eac h gr o u p. Let S + ( 3) a n d S- 
( 3) de n ote t he 3 year P F S f or P E T + a n d P E T- patie nt gr o u ps, res pecti vel y. F or 
vari o us P F S le vels a n d b y ass u mi n g e x p o ne ntial P F S m o dels, t he 3 year P F S f or 
t w o patie nt gr o u ps u n der H0: ∆= 4. 1 a n d H1: ∆= 2. 2 9 are re prese nte d as f oll o ws:  
S -( 3) 
7 5 %  
8 0 %  
8 5 %  
9 0 %  
S + ( 3) u n der H 0 
3 1 %  
4 0 %  
5 1 %  
6 5 %  
S + ( 3) u n der  H 1 
5 2 %  
6 0 %  
6 9 %  
7 9 %  
As a sec o n dar y a nal ysis, we will test H 0: S+ ( 3)= 4 0 % vs. H 1: S+ ( 3) > 4 0 % usi n g t he 
as y m pt otic res ult of t he Ka pla n -Meier esti mat or of S + ( 3) wit h o ne-si de d α = 0. 1 5  

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1 5. 2. 2 S a m ple Size C alc ul ati o n  
Picar di  et  al. [ 1 0],  usi n g  a  s maller  size  li mit  t o  defi ne  b ul k y  disease  ( >  5  c m 
c o m pare d t o > 1 0 c m i n t his st u d y), o bser ve d a 3 year P F S of a b o ut 8 6 % i n patie nts 
recei vi n g c he m ot hera p y o nl y. Base d o n literat ure i ncl u di n g t his data, we e x pect 
t hat, f oll o wi n g 6 c ycles of A B V D wit h o ut ra di ot hera p y, t he 3-year P F S f or P E T - 
a n d  P E T+ patie nts  (after  2  c ycles  of  A B V D)  will  be  a b o ut  8 0 %  a n d  4 0 %, 
res pecti vel y. We  e x pect 
t hat f or  P E T +  patie nts,  t he  a g gressi ve  treat me nt  b y 4 
c ycles of escalate d B E A C O P P f oll o we d b y ra di ot hera p y f or P E T + patie nts  will 
i ncrease t he 3- year P F S pr o ba bilit y fr o m 4 0 % t o 6 0 %. 
Ass u mi n g e x p o ne ntial distri b uti o ns f or P F S, t hese h y p ot heses i m pl y H 0: ∆= 4. 1 a n d 
H 1: ∆< 4. 1. Ass u mi n g a n a n n ual accr ual of 2 5 patie nts, 3 years of a d diti o nal f oll o w -
u p a n d 3 0 % of P E T p ositi vit y after t w o c ycles of A B V D, a sa m ple size of N = 1 1 0 
eli gi ble patie nts (a b o ut 3 4 P E T + a n d 7 6 P E T - patie nts) g uara ntees 8 0 % of p o wer 
b y t he l o g -ra n k test statistic f or n o n -u nit y hazar d rati o u n der H 0 [ 6 1] wit h o ne -si de d 
α = 0. 1 5 a n d H 0: ∆= 4. 1 ( base d o n S-( 3) = 0. 8, S+ ( 3) = 0. 4) a gai nst H1: ∆= 2. 2 9 ( base d 
o n S -( 3) = 0. 8, S+ ( 3) = 0. 6). 
U n der  t hese  ass u m pti o ns,  wit h  t he  e x pecte d  3 4  P E T +  patie nts,  t he  sec o n dar y 
a nal ysis  f or  testi n g H 0:  S+ ( 3)= 4 0 %  vs. H 1:  S+ ( 3) > 4 0 % usi n g  t he  Ka pla n -Meier 
esti mat or of S + ( 3) wit h o ne -si de d α = 0. 1 5  will ha ve a b o ut 9 0 % p o wer  t o detect H 1: 
S + ( 3) = 6 0 %. 
1 5. 3 
Accr u al a n d F oll o w -U p  
Ass u mi n g  u p  t o  1 0 % of dr o p o ut,  i neli gi b ilit y, or  pr o gressi ve  disease  after  2  c ycles  of 
A B V D (t he latter e x pecte d t o be less t ha n 5 %), we will accr ue  a ma xi m u m of  1 2 3 patie nts.  
T he e x pecte d accr ual is a p pr o xi matel y 2 5 patie nts per year, s o t hat  it will ta ke a b o ut 6 0 
m o nt hs f or patie nt accr ual .  Patie nts will be f oll o we d f or u p t o 1 0 years f or s ur vi val data . 
1 5. 4 
S a m ple Size M o dific ati o n  
D ue t o t he l o wer accr ual rate t ha n e x pecte d, t he accr ual g oal is l o were d fr o m 1 2 3 t o 1 0 0 i n 
A pril  2 0 1 7, w he n a b o ut 9 5 patie nts ha ve re gistere d a n d t he real accr ual rate has bee n o nl y 
a b o ut 1 4 patie nts per year, c o m pare d t o 2 5 patie nts per year e x pecte d at t he de vel o p me nt 
of t his st u d y. I n t his sa m ple size recalc ulati o n, w e ass u me (i) a n a n n ual accr ual rate of 1 4 
patie nts a n d (ii) 7 % of attriti o n d ue t o dr o p o ut, i neli gi bilit y, or pr o gressi ve disease after 2 
c ycles of A B V D, w hile ass u mi n g ot her desi g n para meters t he sa me as bef ore (as i n  secti o n 
1 5. 2. 2 ). Wit h n = 9 3 ( = 1 0 0 x 0. 9 3) eli gi ble a n d e val ua ble patie nts, (a b o ut 2 8 P E T + a n d 6 5 
P E T - patie nts), we ha ve 8 0 % of p o wer b y t he l o g -ra n k test statistic f or n o n-u nit y hazar d 
rati o u n der H0 [ 6 1] wit h o ne-si de d α = 0. 1 5 a n d H0: ∆= 4. 1 ( base d o n S-( 3) = 0. 8, S+ ( 3) = 0. 4) 
a gai nst H 1: ∆= 2. 2 9 ( base d o n S-( 3) = 0. 8, S+ ( 3) = 0. 6). 
U n der t hese ass u m pti o ns, wit h t he e x pecte d 2 8 P E T + patie nts, t he sec o n dar y a nal ysis f or 
testi n g H0: S+ ( 3) = 4 0 % vs. H1: S+ ( 3) > 4 0 % usi n g t he Ka pla n-Meier esti mat or of S
+ ( 3) wit h 
o ne- si de d α = 0. 1 5 will ha ve a b o ut 9 0 % p o wer t o detect H 1: S+ ( 3) = 6 0 %. 
T he  fi nal  a nal ysis  will  be  c o n d ucte d  w he n  D = 4 2  e ve nts  ( pr o gressi o ns  or  deat hs)  are 
o bser ve d, w hic h is e x pecte d t o occ ur after a p pr o xi matel y 3 years of a d diti o nal f oll o w - u p.  
T he st u d y will ta ke a b o ut 1 2 2 m o nt hs  ( 8 6 m o nt hs f or patie nt accr ual a n d 3 6 m o nt hs f or 
a d diti o nal f oll o w- u p). 
T he p o wer a nal ysis f or t he sec o n dar y o bjecti ves a n d c orrelati ve e n d p oi nts is u nc ha n ge d 
(i.e. base d o n n = 1 1 0 eli gi ble a n d e val ua ble patie nts).  

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As of pr ot oc ol U p d ate # 1 3, t he f oll o wi n g  c h a n ge h as bee n m a de:  
Re vise d fi n al a n al ysis ti mi n g d ue t o l o w e ve nt r ate:  
T his st u d y cl ose d t o accr ual i n Se pte m ber 2 0 1 7, ha vi n g re gistere d 1 0 1 patie nts. A t otal of 
9 4 patie nts were eli gi ble, ha d a P E T/ C T sca n after c ycle 2, a n d will be i ncl u de d i n t he 
p ri mar y e n d p oi nt a nal ysis ( 2 5 P E T + a n d 6 9 P E T-). As of Se pte m ber 2 0 1 9, t he p o ole d e ve nt 
rate was m uc h l o wer t ha n t hat s pecifie d b y t he st u d y desi g n. Wit h a me dia n f oll o w-u p of 
3. 6 years (I Q R 2. 5 t o 5. 5), t he o bser ve d n u m ber of e ve nts at t his ti me was 9 ( bas e d  o n 
pr ot oc ol  ass u m pti o ns,  we  w o ul d  ha ve  e x pecte d  a p pr o xi matel y  3 3  e ve nts).  I n  or der  t o 
pr o vi de a ti mel y fi nal a nal ysis, t he fi nal a nal ysis will be perf or me d w he n all patie nts ha ve 
bee n f oll o we d f or at least 3 years, w hic h is e x pecte d i n Se pte m ber 2 0 2 0.  
1 5. 5 
I ncl usi o n of W o me n & Mi n orities 
Alt h o u g h t here is n o e vi de nce t o s u g gest t hat t he o utc o me will differ b y ge n der or et h nicit y 
a n d t here is i ns ufficie nt p o wer t o detect s mall or m o derate effects, we will, i n a sec o n dar y 
a nal ysis, re p ort t he res ults b y g e n der a n d et h nicit y. 
1 5. 6 
P re dicti ve V al ue of F D G -P E T  
I n a nal ysis, t he rati o bet wee n t he S U V ma x after t w o c ycles a n d t he S U V ma x at baseli ne 
will be use d as t he o bser vati o n f or eac h patie nt. ( A rati o s maller t ha n 1 mea ns decrease i n 
p ost- t hera p y S U V ma x fr o m t he baseli ne.) We e x pect t hat a b o ut 3 0 % of patie nts will be 
P E T p ositi ve after c ycle 2 . 
1 5. 7 
Sec o n d ar y O bjecti ves  
P F S a n d C R rate will be esti mate d f or P E T p ositi ve a n d ne gati ve patie nt  gr o u ps after 2 
c ycles  of  A B V D.  P F S f or  eac h  gr o u p will be esti mated b y  Ka pla n -Meier  met h o d.  T he 
c o nfi de nce i nter val ( CI) f or C R rate will be base d o n e xact bi n o mial distri b uti o n. T he p oi nt -
wise CI’s f or P F S will be esti mate d base d o n t he n or mal distri b uti o n a p pr o xi mati o ns. 
Pre dicti ve val ues, se nsiti vit y a n d s pecificit y of  se mi q ua ntitati ve e val uati o n of F D G u pta ke 
will be esti mate d wit h res pect t o P F S a n d C R usi n g vari o us a p pr oac hes, i ncl u di n g recei ver 
o perati n g c haracteristic ( R O C) c ur ves f or differe nt c ut off val ues, perce nt decrease i n S U V, 
a n d  a bs ol ute  S U Vs  after  2  a n d  6  c ycles  i n P E T - patie nt  gr o u p  a n d after  2 c ycles  of 
c he m ot hera p y a n d I F R T i n P E T +  patie nt  gr o u p.  F or P F S,  ti me -de pe n de nt R O C met h o d 
(Hea gert y  et  al.  2 0 0 4)  will  be  use d  i n  t he  prese nce  of  ce ns ori n g  wit hi n  3  years.  T he 
e x pecte d sa m ple size is 1 1 0 f or b ot h c ycle 2 data a nal ysis a n d c ycle 6  (f or P E T- gr o u p) or 
p ost I F R T (f or P E T + gr o u p)  data a nal ysis. Ass u mi n g 8 0 % O R rate ( or 8 0 % e ve nt free at 
year  3),  t he  esti mate d  se nsiti vit y  ( N = 1 1 0 x 0. 2 = 2 2)  will  ha ve  a  sta n dar d  err or  ( S E)  of 
ma xi m u m  0. 1 0 7  a n d  t he  esti mate d  s pecificit y  ( N = 1 1 0 x 0. 8 = 8 8)  will  ha ve  a  varia nce  of 
ma xi m u m  0. 0 5 3.  F urt her,  ass u mi n g  3 0 %  of  P E T  p ositi vit y  after  c ycle  2,  t he  esti mate d 
p ositi ve  pre dicti ve  val ue  ( N = 1 1 0 x 0. 3 = 3 3)  will  ha ve  a  sta n dar d  err or  ( S E)  of  ma xi m u m 
0. 0 8 7 a n d t he esti mate d ne gati ve pre dic ti ve val ue ( N = 1 1 0 x 0. 7 = 7 7) will ha ve a varia nce of 
ma xi m u m a b o ut 0. 0 5 7. Si milar a nal ysis will be c o n d ucte d f or P E T data after R T fr o m t he 
patie nts wit h p ositi ve P E T o utc o me after 2 c ycles of c he m ot hera p y.  
Pre dicti ve val ues, se nsiti vit y a n d s pecificit y of v ol u metric c ha n ges o n C T will be esti mate d 
wit h res pect t o P F S a n d C R after 2 a n d 6 c ycles (f or P E T- gr o u p) or p ost I F R T (f or P E T + 
gr o u p) i n res pecti ve patie nt gr o u ps. F or P F S, ti me- de pe n de nt R O C met h o d will be use d i n 
t he prese nce of ce ns ori n g wit hi n 3 year s [ 6 2]. Si milar a nal ysis will be c o n d ucte d f or P E T 
data after R T fr o m t he patie nts wit h p ositi ve P E T o utc o me after 2 c ycles of c h e m ot hera p y. 
Pre dicti ve val ues, se nsiti vit y a n d s pecificit y of F D G -P E T i ma gi n g will be esti mate d usi n g 
a m ore li beral q ualitati ve rea di n g scale b y usi n g t he li ver as a refere nce bac k gr o u n d. T he 

C A L G B 5 0 8 0 1  
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U p date # 1 3  
sa me  a nal yses  as  i n Secti o n  1 5. 6  wil l  be  c o n d ucte d  usi n g  li ver-base d  P E T  data. F or 
se mi q ua ntitati ve  P E T  data,  t he  c ha n ge  bet wee n  baseli ne  a n d  after  c ycle  2,  a n d  after 
c he m ot hera p y (f or P E T - gr o u p) or after I F R T (f or P E T + gr o u p) will be c orrelate d wit h O R 
a n d P F S. Si milar a nal ysis will be c o n d ucte d f or t he c ha n ge bet wee n baseli ne a n d after R T 
f or t he patie nts wit h p ositi ve P E T o utc o me after 2 c ycles of c he m ot hera p y. 
Pre dicti ve  val ue  will  be  c o m pare d  a m o n g  meta b olic  para meters  ( b ot h  vis ual  a n d 
q ua ntitati ve  c ha n ges),  v ol u metric  C T  c ha n ges,  a n d  m olec ular  para meters.  R O C  c ur ves 
fr o m c orrelate d mar kers will be c o m pare d usi n g t he met h o d b y Del o n g et al [ 6 3]. 
1 5. 8 
C orrel ati v e E n d p oi nts 
All  eli gi ble  patie nts  w h o  c o nse nt  t o  t he  c orrelati ve  scie nce  sa m ple  c ollecti o n  will  be 
i ncl u de d  i n  t he  c orrelati ve  st u dies.  Base d  o n  o ur  e x perie nce  fr o m  pre vi o us  st u dies,  we 
ass u me 7 0 % of patie nts will c o nse nt ( 7 0 % of 1 1 0 eli gi ble patie nts, n = 7 7 ) t o t he c orrelati ve 
scie nce sa m ple c ollecti o n. 
1 5. 8. 1 Ser u m a n d Pl as m a M ar kers  
Ser u m  mar kers  will  be  a nal yze d  as  a  c o nti n u o us  varia ble  as  well  as  a  bi nar y 
(ele vate d vers us n ot ele vate d) varia ble. 
Baseli ne ser u m mar ker val ues will be c orrelate d wit h res p o nse ( o verall res p o nse 
vs.  n o  res p o nse)  at  t he  e n d  of  treat me nt.  Ass u mi n g  8 0 %  of  o verall  res p o nse 
( O R = C R + P R), a t w o-sa m ple t-test wit h t w o-si de d α= 0. 0 5 has 8 0 % p o wer t o detect 
a  sta n dar dize d  effect  size  of  0. 8 usi n g  c o nti n u o us  ser u m  mar ker  val ues.  F or  a 
dic h ot o m o us ser u m mar ker, we ass u me t hat t he baseli ne ser u m mar ker val ue will 
be  ele vate d  f or  a b o ut  6 0 %  of  patie nts.  T he n,  a  c hi -s q uare d  test  wit h  t w o-si de d 
α = 0. 0 5 has 8 9 % p o wer w he n t he pr o ba bilities of ele vati o n i n ser u m mar ker are 
5 0 % f or O R a n d 9 0 % f or n o n- O R.  
Baseli ne ser u m mar ker val ues will be c orrelate d wit h P F S usi n g C o x re gressi o n 
met h o d.  S u p p ose t hat t he 3 -year  P F S  is  8 5 %  f or t he  w h ole  p o p ulati o n,  a n d  we 
ass u me 4 years of accr ual a n d 3 years of a d diti o nal f oll o w- u p after c o m pleti o n of 
accr ual. Usi n g a c o nti n u o us ser u m mar ker, a C o x re gressi o n wit h t w o -si de d α= 0. 0 5 
has 8 4 % p o wer t o detect a l o g hazar d rati o (l o g -H R) of 0. 7 bet wee n t w o patie nt 
gr o u ps  wit h  mar ker  val ues  o ne  sta n dar d  de viati o n  a wa y.  We  ass u me  t hat  t he 
mar ker  val ue  ( or  its  tra nsf or mati o n)  f oll o ws  a  n or mal  distri b uti o n.  F or  a 
dic h ot o m o us  ser u m  mar ker,  t he  l o g -ra n k  test  wit h  t w o-si de d  α= 0. 0 5  has  8 7 % 
p o wer w he n t he pr o ba bilit y of ele vate d ser u m mar ker is a b o ut 6 0 % a n d t he 3 -year 
P F S is 7 5 % f or t he patie nt gr o u p wit h a n ele vate d ser u m mar ker a n d 9 3 % f or t he 
ot her gr o u p. 
We will c o n d uct m ulti variate re gressi o n a nal yses (l o gistic re gressi o n f or res p o nse 
a n d C o x re gressi o n f or P F S), i ncl u di n g treat me nt i n dicat or, differe nt mar kers, a n d 
k n o w n  pre dict o rs.  T hese  m ulti variate  a nal yses  are  t o  test  if  a  baseli ne  ser u m 
mar ker  is  a n  i n de pe n de nt  pre dict or  after  a dj usti n g  f or  ot her  pre dict ors,  or  a 
s urr o gate mar ker wit h res pect t o res p o nse or P F S. 
T he  ser u m  mar ker  val ues  at  eac h  P E T  sca n  will  be  c orrelate d  wit h  t he  P E T 
o utc o me usi n g a n R O C met h o d. We will c o m pare t he areas u n der t he R O C c ur ves 
a m o n g differe nt ser u m mar kers b y c o m bi ni n g t he data fr o m t w o P E T sca ns usi n g 
E mir et al. [ 6 4]. Pr o ba bilit y of p ositi ve P E T o utc o me will be c o m pare d a m o n g t he 
gr o u ps defi ne d b y t he tre n d of mar ker val ues ar o u n d eac h P E T sca n.  
Si milar a nal yses will be c o n d ucte d f or plas ma mar ker data.  

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U p date # 1 3  
•  
T he re p orti n g of a d verse e ve nts descri be d i n t he ta ble a b o ve is i n a d diti o n t o a n d 
d oes n ot s u p pla nt t he re p orti n g of a d verse e ve nts as part of t he re p ort of t he res ults 
of t he cli nical trial, e. g., st u d y s u m mar y f or ms or c o o perati ve gr o u p data re p orti n g 
f or ms (see Secti o n 5. 2  f or re q uire d C A L G B f or ms). 
•  
Sec o n d ar y m ali g n a nc y:  A sec o n dar y mali g na nc y is a ca ncer ca use d b y treat me nt 
f or  a  pre vi o us  mali g na nc y  (e. g.,  treat me nt  wit h i n vesti gati o nal  a ge nt/i nter ve nti o n, 
ra diati o n or c he m ot hera p y). A sec o n dar y mali g na nc y is n ot c o nsi dere d a metastasis 
of t he i nitial ne o plas m.  
C T E P re q uires all sec o n dar y mali g na ncies t hat occ ur f oll o wi n g treat me nt wit h a n 
a ge nt u n der a n N CI I N D/I D E be re p orte d via C T E P -A E R S. I n C T C A E versi o n 5. 0, 
t hree o pti o ns are a vaila ble t o descri be t he e ve nt:  
-Le u ke mia sec o n dar y t o o nc ol o g y c he m ot hera p y (e. g., ac ute m yel oc ytic le u ke mia 
[ A M L])  
- M yel o d ys plastic s y n dr o me ( M D S)  
-Treat me nt -relate d sec o n dar y mali g na nc y  
A n y mali g na nc y p ossi bl y relate d t o ca ncer treat me nt (i ncl u di n g A M L/ M D S) s h o ul d 
als o be re p orte d via t he r o uti ne re p orti n g mec ha nis ms o utli ne d i n eac h pr ot oc ol. 
Sec o n d m ali g n a nc y:  A sec o n d mali g na nc y is o ne u nrelate d t o t he treat me nt of a 
pri or  mali g na nc y  (a n d  is  N O T  a metastasis  fr o m  t he  i nitial  mali g na nc y).  Sec o n d 
mali g na ncies re q uire O N L Y r o uti ne re p orti n g u nless ot her wise s pecifie d.  
•  
P re g na nc y  l oss is  defi ne d as  “ Deat h  i n  uter o,” a n d  a n y  pre g na nc y  l oss  s h o ul d be 
re p orte d  e x pe diti o usl y  as  Gra de  4  “ Pre g na nc y  l oss”  u n der  t he  Pre g na nc y, 
p uer peri u m a n d peri natal c o n diti o ns S O C. A pre g na nc y l oss s h o ul d N O T be re p orte d 
as a Gra de 5 e ve nt u n der  t he Pre g na nc y, p uer peri u m a n d peri natal c o n diti o ns S O C 
as c urre ntl y C T E P -A E R S r ec o g nizes t his e ve nt as a patie nt deat h.  
A  ne o natal  deat h  s h o ul d  be  re p orte d  e x pe diti o usl y  as  Gra de  4,  “ Deat h  ne o natal” 
u n der t he Ge neral dis or ders a n d a d mi nistrati o n S O C. 
•  
Dea t h  d ue  t o  pr o gressi ve  disease  s h o ul d  be  re p orte d  as  Gra de  5  “ Disease 
pr o gressi o n” i n t he s yste m or ga n class ( S O C) “ Ge neral dis or ders a n d a d mi nistrati o n 
site c o n diti o ns.” E vi de nce t hat t he deat h was a ma nifestati o n of u n derl yi n g disease 
(e. g., ra di ol o gical c ha n ges  s u g gesti n g  t u m or  gr o wt h  or  pr o gressi o n:  cli nical 
deteri orati o n ass ociate d wit h a disease pr ocess) s h o ul d be s u b mitte d.  
 
 
 

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Versi o n date: 0 5 /1 1 / 2 02 0  
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U p date # 1 3  
1 7. 0  R E F E R E N C E S  
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vi n blasti ne, a n d dacar bazi ne ( A B V D) f oll o we d b y ra diati o n t hera p y ( R T) vers us A B V D al o ne f or 
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1 0. 
Picar di, M., et al., Ra n d o mize d c o m paris o n of c o ns oli dati o n ra diati o n vers us o bser vati o n i n b ul k y 
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1 1. 
Galla mi ni, A., et al., Earl y i nteri m 2 -[ 1 8 F]fl u or o- 2- de o x y- D-gl uc ose p ositr o n e missi o n t o m o gra p h y 
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1 2. 
Galla mi ni, A., et al., T he pre dicti ve val ue of p ositr o n e missi o n t o m o gra p h y sca n ni n g perf or me d after 
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1 3. 
H utc hi n gs,  M.,  et  al.,  F D G -P E T  after  t w o  c ycles  of  c he m ot hera p y  pre dicts  treat me nt  fail ure  a n d 
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1 4. 
J u wei d, M. E., et al., Use of p ositr o n e missi o n t o m o gra p h y f or res p o nse assess me nt of l y m p h o ma: 
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1 5. 
Die hl,  V., et  al.,  Sta n dar d  a n d  i ncrease d -d ose  B E A C O P P  c he m ot hera p y  c o m pare d  wit h  C O P P -
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1 6. 
E n gert, A., J. Fra n kli n, a n d V. Die hl, L o n g -ter m f oll o w-u p of B E A C O P P escalate d c he m ot hera p y i n 
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Bl o o d, 2 0 0 7. 1 1 0 ( 7 0a). 

C A L G B 5 0 8 0 1  
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7 0  
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1 7. 
Da n n, E.J., et al., Ris k -a da pte d B E A C O P P re gi me n ca n re d uce t he c u m ulati ve d ose of c he m ot hera p y 
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1 8. 
E n gert, A., et al., T w o c ycles of d o x or u bici n, ble o m yci n, vi n blasti ne, a n d dacar bazi ne pl us e xte n de d -
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2 0. 
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2 1. 
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Pr ocee di n gs of A S C O, 2 0 0 5. 2 3 (J u ne 1 S u p ple me nt): p. 6 5 0 5. 
2 4. 
Eic h, H., M ueller, R. E n gert, A., et al., C o m paris o n of 3 0 G y vers us 2 0 G y i n v ol ve d fiel d ra di ot hera p y 
after  t w o  vers us  f o ur  c ycles  A B V D  i n  earl y  sta ge  H o d g ki n's  l y m p h o ma:  I nteri m  a nal ysis  of  t he 
Ger ma n H o d g ki n St u d y Gr o u p Trial H D 1 0. Pr ocee di n gs of A S T R O, 2 0 0 5. 6 3 ( S u p ple me nt 1): p. S 1.  
2 5. 
Elc o ni n, J. H., et al., Ra diati o n d ose selecti o n i n H o d g ki n's disease patie nts wit h lar ge me diasti nal 
a de n o pat h y treate d wit h c o m bi ne d m o dalit y t hera p y. I nt J Ra diat O nc ol Bi ol P h ys, 2 0 0 0. 4 8 ( 4): p. 
1 0 9 7- 1 0 5. 
2 6. 
Eis br uc h,  A.,  et  al.,  Ra diati o n  f oll o wi n g  c he m ot hera p y  f or  me diasti nal  H o d g ki n's  disease:  t he 
o utc o me of vari o us d oses f or b ul k y t u m ors. Ra di ot her O nc ol, 1 9 9 8. 4 6 ( 1): p. 4 7-9.  
2 7. 
K o o ntz, B. F., et al., C o m bi ne d -m o dalit y t hera p y vers us ra di ot hera p y al o ne f or treat me nt of earl y -
sta ge H o d g ki n's disease: c ure bala nce d a gai nst c o m plicati o ns. J Cli n O nc ol, 2 0 0 6. 2 4 ( 4): p. 6 0 5- 1 1. 
2 8. 
Ha nc oc k, S. L., M. A. T uc ker, a n d R. T. H o p pe, Fact ors aff ecti n g late m ortalit y fr o m heart disease 
after treat me nt of H o d g ki n's disease. J a ma, 1 9 9 3. 2 7 0 ( 1 6): p. 1 9 4 9- 5 5. 
2 9. 
Ya hal o m, J. a n d P. Ma uc h, T he i n v ol ve d fiel d is bac k: iss ues i n deli neati n g t he ra diati o n fiel d i n 
H o d g ki n's disease. A n n O nc ol, 2 0 0 2. 1 3 S u p pl 1 : p. 7 9- 8 3. 
3 0. 
H utc hi n gs, M., et al., Pr o g n ostic val ue of i nteri m F D G -P E T after t w o or t hree c ycles of c he m ot hera p y 
i n H o d g ki n l y m p h o ma. A n n O nc ol, 2 0 0 5. 1 6 ( 7): p. 1 1 6 0- 8. 
3 1. 
Die hl, V., et al., B E A C O P P: a n i nte nsifie d c he m ot hera p y re gi me n i n a d va nce d H o d g ki n's disease. 
T he Ger ma n H o d g ki n's L y m p h o ma St u d y Gr o u p. A n n O nc ol, 1 9 9 7. 8 ( 2): p. 1 4 3- 8. 
3 2. 
Hsi,  E. D.,  Bi ol o gic  feat ures  of  H o d g ki n  l y m p h o ma  a n d  t he  de vel o p me nt  of  bi ol o gic  pr o g n ostic 
fact ors i n H o d g ki n l y m p h o ma: T u m or a n d micr oe n vir o n me nt. Le u k L y m p h o ma, I n Press. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 1  
U p date # 1 3  
3 3. 
Casas n o vas, R. O., et al., Plas ma c yt o ki ne a n d s ol u ble rece pt or si g nat ure pre dicts o utc o me of patie nts 
wit h classical H o d g ki n's l y m p h o ma: a st u d y fr o m t he Gr o u pe d' Et u de des L y m p h o mes de l' A d ulte. J 
Cli n O nc ol, 2 0 0 7. 2 5 ( 1 3): p. 1 7 3 2- 4 0. 
3 4. 
Na dali, G., et al., Ser u m le vels of s ol u ble C D 3 0 are ele vate d i n t he maj orit y of u ntreate d patie nts 
wit h H o d g ki n's disease a n d c orrelate wit h cli nical feat ures a n d pr o g n osis. J Cli n O nc ol, 1 9 9 4. 1 2 ( 4): 
p. 7 9 3- 7. 
3 5. 
Visc o, C., et al., Ver y hi g h le ve ls of s ol u ble C D 3 0 rec o g nize t he patie nts wit h classical H o d g ki n's 
l y m p h o ma retai ni n g a ver y p o or pr o g n osis. E ur J Hae mat ol, 2 0 0 6. 7 7 ( 5): p. 3 8 7- 9 4. 
3 6. 
Sarris, A. H., et al., I nterle u ki n -1 0 le vels are ofte n ele vate d i n ser u m of a d ults wit h H o d g ki n's diseas e 
a n d are ass ociate d wit h i nferi or fail ure -free s ur vi val. A n n O nc ol, 1 9 9 9. 1 0 ( 4): p. 4 3 3- 4 0. 
3 7. 
Vassila k o p o ul os, T. P., et al., Ser u m i nterle u ki n -1 0 le vels are a n i n de pe n de nt pr o g n ostic fact or f or 
patie nts wit h H o d g ki n's l y m p h o ma. Hae mat ol o gica, 2 0 0 1. 8 6 ( 3): p. 2 7 4- 8 1. 
3 8. 
Nie ns, M., et al., Ser u m c he m o ki ne le vels i n H o d g ki n l y m p h o ma patie nts: hi g hl y i ncrease d le vels of 
C C L 1 7 a n d C C L 2 2. Br J Hae mat ol, 2 0 0 8. 1 4 0 ( 5): p. 5 2 7- 3 6. 
3 9. 
va n de n Ber g, A., L. Visser, a n d S. P o p pe ma, Hi g h e x pressi o n of t he C C c he m o ki n e T A R C i n Ree d -
Ster n ber g cells. A p ossi ble e x pla nati o n f or t he c haracteristic T -cell i nfiltratei n H o d g ki n's l y m p h o ma. 
A m J Pat h ol, 1 9 9 9. 1 5 4 ( 6): p. 1 6 8 5- 9 1. 
4 0. 
Wei hra uc h,  M. R.,  et  al.,  Ele vate d  ser u m  le vels  of  C C  t h y m us  a n d  acti vati o n -relate d  c he m o ki ne 
( T A R C) i n pri mar y H o d g ki n's disease: p ote ntial f or a pr o g n ostic fact or. Ca ncer Res, 2 0 0 5. 6 5 ( 1 3): 
p. 5 5 1 6- 9. 
4 1. 
Ma g gi o, E., et al., C he m o ki nes, c yt o ki nes a n d t heir rece pt ors i n H o d g ki n's l y m p h o ma cell li nes a n d 
tiss ues. A n n O nc ol, 2 0 0 2. 1 3 S u p pl 1 : p. 5 2- 6. 
4 2. 
P o p pe ma, S.,  I m m u n o bi ol o g y a n d pat h o p h ysi ol o g y of h o d g ki n l y m p h o mas. He mat ol o g y  A m S oc 
He mat ol E d uc Pr o gra m, 2 0 0 5: p. 2 3 1- 8. 
4 3. 
C hi u, A., et al., H o d g ki n l y m p h o ma cells e x press T A CI a n d B C M A rece pt ors a n d ge nerate s ur vi val 
a n d pr oliferati o n si g nals i n res p o nse t o B A F F a n d A P RI L. Bl o o d, 2 0 0 7. 1 0 9 ( 2): p. 7 2 9- 3 9. 
4 4. 
Ha na m ot o,  H.,  et  al.,  E x pressi o n  of  C C L 2 8  b y  Ree d -Ster n ber g  cells  defi nes  a  maj or  s u bt y pe  of 
classical H o d g ki n's disease wit h fre q ue nt i nfiltrati o n of e osi n o p hils a n d/ or plas ma cells. A m J Pat h ol, 
2 0 0 4. 1 6 4 ( 3): p. 9 9 7- 1 0 0 6. 
4 5. 
S ki n ni der, B. F. a n d T. W. Ma k, T he r ole of c yt o ki nes i n classical H o d g ki n l y m p h o ma. Bl o o d, 2 0 0 2. 
9 9 ( 1 2): p. 4 2 8 3- 9 7. 
4 6. 
S ki n ni der, B. F., U. Ka p p, a n d T. W. Ma k, T he r ole of i nterle u ki n 1 3 i n classical H o d g ki n l y m p h o ma. 
Le u k L y m p h o ma, 2 0 0 2. 4 3 ( 6): p. 1 2 0 3- 1 0. 
4 7. 
J uszcz y ns ki, P., et al., T he A P 1-de pe n de nt secreti o n of galecti n -1 b y Ree d Ster n ber g cells f osters 
i m m u ne  pri vile ge  in classical  H o d g ki n  l y m p h o ma.  Pr oc  Natl  Aca d  Sci  U  S  A, 2 0 0 7. 1 0 4 ( 3 2):  p. 
1 3 1 3 4- 9. 
4 8. 
He d vat, C. V., et al., Macr o p ha ge -deri ve d c he m o ki ne e x pressi o n i n classical H o d g ki n's l y m p h o ma: 
a p plicati o n of tiss ue micr oarra ys. M o d Pat h ol, 2 0 0 1. 1 4 ( 1 2): p. 1 2 7 0- 6. 
4 9. 
Pe h, S. C., L. H. Ki m, a n d S. P o p pe ma, T A R C, a C C c he m o ki ne, is fre q ue ntl y e x presse d i n classic 
H o d g ki n's l y m p h o ma b ut n ot i n N L P H o d g ki n's l y m p h o ma, T -cell-ric h B-cell l y m p h o ma, a n d m ost 
cases of a na plastic lar ge cell l y m p h o ma. A m J S ur g Pat h ol, 2 0 0 1. 2 5 ( 7): p. 9 2 5- 9. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 2  
U p date # 1 3  
5 0.  
Bri n k, A. A., et al., L o w p 5 3 a n d hi g h bcl- 2 e x pressi o n i n Ree d -Ster n ber g cells pre dicts p o or cli nical 
o utc o me f or H o d g ki n's disease: i n v ol ve me nt of a p o pt osis resista nce? M o d Pat h ol, 1 9 9 8. 1 1 ( 4): p. 
3 7 6- 8 3. 
5 1. 
Hsi, E. D., et al., M A L is e x presse d i n a s u bset of H o d g ki n l y m p h o ma a n d i de ntifies a p o p ulati o n of 
patie nts wit h p o or pr o g n osis. A m J Cli n Pat h ol, 2 0 0 6. 1 2 5 ( 5): p. 7 7 6- 8 2. 
5 2. 
Rassi da kis, G. Z., et al., B C L -2 e x pressi o n i n H o d g ki n a n d Ree d -Ster n ber g cells of classical H o d g ki n 
disease pre dicts a p o orer pr o g n osis i n patie nts treate d wit h A B V D or e q ui vale nt re gi me ns. Bl o o d, 
2 0 0 2. 1 0 0 ( 1 2): p. 3 9 3 5- 4 1. 
5 3. 
S u p, S.J., et al., E x pressi o n of bcl -2 i n classical H o d g ki n's l y m p h o ma: a n i n de pe n de nt pre dict or of 
p o or o utc o me. J Cli n O nc ol, 2 0 0 5. 2 3 ( 1 6): p. 3 7 7 3- 9. 
5 4. 
Al var o,  T.,  et  al.,  O utc o me  i n  H o d g ki n's  l y m p h o ma  ca n  be  pre dicte d  fr o m  t he  prese nce  of 
acc o m pa n yi n g c yt ot o xic a n d re g ulat or y T cells. Cli n Ca ncer Res, 2 0 0 5. 1 1 ( 4): p. 1 4 6 7- 7 3. 
5 5. 
Al var o -Nara nj o, T., et al., T u m or -i nfiltrati n g cells as a pr o g n ostic fact or i n H o d g ki n's l y m p h o ma: a 
q ua ntitati ve tiss ue micr oarra y st u d y i n a lar ge retr os pecti ve c o h ort of 2 6 7 patie nts. Le u k L y m p h o ma, 
2 0 0 5. 4 6 ( 1 1): p. 1 5 8 1- 9 1. 
5 6. 
Kelle y, T. W., et al., T he rati o of F O X P 3 + re g ulat or y T cells t o gra nz y me B + c yt ot o xic T/ N K cells 
pre dicts pr o g n osis i n classical H o d g ki n l y m p h o ma a n d is i n de pe n de nt of bcl -2 a n d M A L e x pressi o n. 
A m J Cli n Pat h ol, 2 0 0 7. 1 2 8 ( 6): p. 9 5 8- 6 5. 
5 7. 
M oli n, D., et al., Mast cell i nfiltrati o n c orrelates wit h p o or pr o g n osis i n H o d g ki n's l y m p h o ma. Br J 
Hae mat ol, 2 0 0 2. 1 1 9 ( 1): p. 1 2 2- 4. 
5 8. 
O u dej a ns, J.J., et al., Acti vate d c yt ot o xic T cells as pr o g n ostic mar ker i n H o d g ki n's disease. Bl o o d, 
1 9 9 7. 8 9 ( 4): p. 1 3 7 6- 8 2. 
5 9.  
S tei dl, C., et al., T u m or-ass ociate d macr o p ha ges a n d s ur vi val i n classic H o d g ki n's l y m p h o ma. N E n gl 
J Me d, 2 0 1 0. 3 6 2 ( 1 0): p. 8 7 5- 8 5. 
6 0. 
C hes o n, B. D., et al., Re vise d res p o nse criteria f or mali g na nt l y m p h o ma. J Cli n O nc ol, 2 0 0 7. 2 5 ( 5): 
p. 5 7 9- 8 6. 
6 1. 
J u n g, S. H., et al., Sa m ple size c o m p utati o n f or t w o -sa m ple n o ni nferi orit y l o g-ra n k test. J Bi o p har m 
Stat, 2 0 0 5. 1 5 ( 6): p. 9 6 9- 7 9. 
6 2. 
Hea gert y, P.J., T. L u mle y, a n d M. S. Pe pe, Ti me -de pe n de nt R O C c ur ves f or ce ns ore d s ur vi val data 
a n d a dia g n ostic mar ker. Bi o metri cs, 2 0 0 0. 5 6 ( 2): p. 3 3 7- 4 4. 
6 3. 
De L o n g,  E. R.,  D. M.  De L o n g,  a n d  D. L.  Clar ke -Pears o n,  C o m pari n g  t he  areas  u n der  t w o  or  m ore 
c orrelate d  recei ver  o perati n g  c haracteristic  c ur ves:  a  n o n para metric  a p pr oac h.  Bi o metrics,  1 9 8 8. 
4 4 ( 3): p. 8 3 7- 4 5. 
6 4. 
E mir, B., et al., C o m paris o n of dia g n ostic mar kers wit h re peate d meas ure me nts: a n o n -para metric 
R O C c ur ve a p pr oac h. Stat Me d, 2 0 0 0. 1 9 ( 4): p. 5 1 1- 2 3. 
6 5.  
Ga use, A., et al., Cli nical si g nifica nce of s ol u ble C D 3 0 a nti ge n i n t he sera of patie nts wit h u ntreate d 
H o d g ki n's disease. Bl o o d, 1 9 9 1. 7 7 ( 9): p. 1 9 8 3- 8. 
6 6. 
Za n otti, R., et al., Ser u m le vels of s ol u ble C D 3 0 i m pr o ve I nter nati o nal Pr o g n ostic Sc ore i n pre dicti n g 
t he o utc o me of a d va nce d H o d g ki n's l y m p h o ma. A n n O nc ol, 2 0 0 2. 1 3 ( 1 2): p. 1 9 0 8- 1 4. 
6 7. 
A x d or p h,  U.,  et  al.,  Bi ol o gical  mar kers  ma y  a d d  t o  pre dicti o n  of  o utc o me  ac hie ve d  b y  t he 
I nter nati o nal Pr o g n ostic Sc ore i n H o d g ki n's disease. A n n O nc ol, 2 0 0 0. 1 1 ( 1 1): p. 1 4 0 5- 1 1. 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 3  
U p date # 1 3  
6 8. 
B o hle n, H., et al., P o or cli nical o utc o me of patie nts wit h H o d g ki n's disease a n d ele v ate d i nterle u ki n -
1 0  ser u m  le vels.  Cli nical  si g nifica nce  of  i nterle u ki n -1 0  ser u m  le vels  f or  H o d g ki n's  disease.  A n n 
He mat ol, 2 0 0 0. 7 9 ( 3): p. 1 1 0- 3. 
6 9. 
Visc o, C., et al., Ele vate d ser u m le vels of I L -1 0 are ass ociate d wit h i nferi or pr o gressi o n -free s ur vi val 
in patie nts wit h H o d g ki n's disease treate d wit h ra di ot hera p y. Le u k L y m p h o ma, 2 0 0 4. 4 5 ( 1 0): p. 2 0 8 5-
9 2. 
7 0. 
Vi via ni, S., et al., Ele vate d pretreat me nt ser u m le vels of Il -1 0 are ass ociate d wit h a p o or pr o g n osis i n 
H o d g ki n's disease, t he mila n ca ncer i nstit ute e x perie nce. Me d O nc ol, 2 0 0 0. 1 7 ( 1): p. 5 9- 6 3. 
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 4  
U p date # 1 3  
 
A P P E N DI X  I  LO N D O N / DE A U VI L L E C RI T E RI A  
 
Ne g ati ve Sc a n 
•  
Sc ore 1   
 n o u pta ke 
•  
Sc ore 2   
 u pta ke ≤ me diasti n u m 
•  
Sc ore 3   
 u p date > me diasti n u m a n d ≤ li ver 
 
P ositi ve Sc a n 
•  
Sc ore 4   
 m o deratel y  > li ver  
•  
Sc ore 5  
mar ke dl y  u pta ke > > li ver  
 
Sc ore X:  
Ne w are as of u p d ate u nlikely t o be rel ate d t o ly m p h o m a. 
 
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 5  
U p date # 1 3  
A P P E N DI X  II  IM M U N O HI S T O C H E MI C A L A N A L Y SI S A N D IM A GI N G P R O C E D U R E S  
 
I m m u n o hist oc he mical stai ns will be perf or me d usi n g a ut o mate d i m m u n ostai ns f or B C L 2, F O X P 3, Gz B, 
t yr ptase,  a n d  M A L  o n  a  Ve nta na  Be nc h mar k  stai ner  ( Ve nta na,  T ucs o n  A Z)  wit h  I VI E WT M   
dia mi n o be nza di ne  detecti o n  i n  t he  C LI A -certifie d  la b orat or y  of  t he  Cle vela n d  Cli nic  Pat h ol o g y  a n d 
La b orat or y Me dici ne I nstit ute.  Stai ni n g c o n diti o ns are s u m marize d i n T a ble A 1 .   
 
Stai ns  will  be  q ua ntitate d  b y  ma n ual  c o u nti n g  per  5/ hi g h  p o wer  oil  o bjecti ve  fiel ds.    T he  wit hi n  r u n 
re pr o d uci bilit y  of  ma n ual  T M A  i m m u n ostai ni n g  c o u nti n g  b y  Dr  Hsi  (ra n d o m  rec o u nti n g)  f or  m ulti ple 
mar kers  is  e xcel le nt  wit h  Pears o n  c orrelati o n  c oefficie nts  of  0. 8 2  or  greater  ( P <. 0 0 1).    S pecific  assa y 
precisi o n acr oss i m m u n ostai ni n g r u ns has bee n c haracterize d b y re petiti ve c o nsec uti ve r u ns of c o ntr ol tiss ue 
wit h  q ua ntitati o n  of serial secti o ns.  T he  c oefficie nt of  v ariati o n  ta ki n g  i nt o acc o u nt  b ot h tec h nical  a n d 
c o u nti n g varia bilit y f or B C L 2, F O X P 3, Gz B a n d tr y pase is 5 %, 7 %, 8 %, a n d 5 % res pecti vel y.  Precisi o n 
f or M A L has n ot yet bee n c haracterize d b ut will be perf or me d pri or t o st u d y a n d is a ntici pate d t o be less 
t ha n 1 0 %. 
T a ble A 1:  I m m u n o hist oc he mistr y  
A nti b o d y  
Cl o ne  
Ve n d or  
A nti ge n retrie v al  
B C L 2 cl o ne  
1 2 4  
Ve nta na  
HI E R *  
M A L  
6 D 9  
M. Al o ns o  
HI E R  
F O X P 3  
2 2 5 1 0  
A bca m  
Pr otease 2  
Gz B  
Gr B -7  
Acc urate  
HI E R  
Tr y ptase  
A A 1  
D A K O  
Pr otease 2  
* hea d i n d uce d e pit o pe retrie val, C C 1 sta n dar d 
 
I m a gi n g: 
I ma ge a nal ysis of t he i m m u n ostai ns will als o be perf or me d f or c o m paris o n t o t he ma n ual met h o ds.  Sli des 
will a nal yze d usi n g t he Ari ol S L -5 0 a ut o mate d sli de sca n ner ( A p plie d I ma gi n g, Sa n J ose, C A) t o q ua ntitate 
t he a m o u nt of p ositi ve stai ni n g f or eac h area of i nterest. T hres h ol ds f or eac h i ma ge are a p plie d base d o n 
m ulti ple para meters: R G B al g orit h m, s ha pe, a n d size. P ositi ve stai ni n g is calc ulate d b y a p pl yi n g t w o c ol or 
t hres h ol ds,  wit h  o ne  rec o g nizi n g  bl ue  bac k gr o u n d  c o u nterstai n  ( he mat o x yli n)  a n d  a n ot her  rec o g nizi n g 
br o w n i m m u n ostai n p ositi ve cells. I n di vi d ual cells were discri mi nate d b y i nc or p orati n g t he s ha pe a n d size 
t hres h ol ds, pr o vi di n g, wit h t he c ol or t hres h ol ds, a n d act ual cell c o u nts. F or n uclear a nti ge ns t he perce nta ge 
of p ositi vit y is t he cell n u m ber detecte d b y t he br o w n t hres h ol d di vi de d b y t he t otal cell n u m ber, detecte d 
b y t he br o w n a n d bl ue t hres h ol ds. T otal tiss ue area a nal yze d ma y als o be i ncl u de d i n t he fi nal a nal ysis. 
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 6  
U p date # 1 3  
A P P E N DI X  III  
SU M M A R Y O F B I O L O GI C P R O G N O S TI C M A R K E R S I N C L A S SI C A L H L  ( ≥5 0  P T S) 
 
Ser u m M ar kers  
N  
I m p act 
E n d p oi nt  
Si g nific a nt  o n  M ulti v ari a ble 
A n al ysis  
s C D 3 0 
 
 
 
 
Cassa n o vas 2 0 0 7 [ 3 3] 
5 1 9  
a d verse 
E F S  
Y E S  
Ga use 1 9 9 1 [ 6 5] 
9 0  
a d verse 
T T F  
N O  
Na dali 1 9 9 4 [ 3 4] 
1 1 7  
a d verse 
E F S  
Y E S  
Visc o 2 0 0 6 [ 3 5] 
3 2 1  
a d verse 
F F S  
Y E S  
Za n otti 2 0 0 2 [ 6 6] 
1 0 1  
a d verse 
F F S  
Y E S  
A x d or p h 2 0 0 0 [ 6 7] 
9 3  
a d verse 
C S S  
Y E S  
 
 
 
 
 
I L-1 0  
 
 
 
 
Cassa n o vas 2 0 0 7  [ 3 3] 
5 1 9  
a d verse 
E F S  
N O  
A x d or p h 2 0 0 0 [ 6 7] 
1 2 3  
a d verse 
C S S  
Y E S  
B o hle n 2 0 0 0 [ 6 8] 
6 4  
a d verse 
F F T F  
Y E S  
Sarris 1 9 9 9 [ 3 6] 
1 0 1  
a d verse 
F F S  
Y E S  
Vassila k o p o ul os 2 0 0 1 [ 3 7] 
1 2 2  
a d verse 
F F S  
Y E S  
Visc o 2 0 0 4  [ 6 9] 
6 9  
a d verse 
P F S  
Y E S  
Vi via ni 2 0 0 0  [ 7 0] 
7 3  
a d verse 
F F P  
Y E S  
 
 
 
 
 
T A R C  
 
 
 
 
Wei hra uc h 2 0 0 5  [ 4 0] 
6 3  
a d verse 
O S  
N O  
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 7  
U p date # 1 3  
A P P E N DI X  I V C A L G B  5 0 8 0 1  P E T/ C T  IN S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S F O R M  
 
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S F O R M  
(Fr o m A C RI N  Cre de ntiali n g A p plicati o n, 2 0 0 5) 
 
P a ge 1 of 5 
 
I nstit uti o n:  
  
  
  
  
  
 
D ate:  
 
I nstit uti o n A d dress: 
 
 
I nstit uti o n C o nt act N a me a n d Tele p h o ne N u m ber: 
 
E- m ail:   
  
  
  
  
 
F a x:  
 
P E T Ce nter N a me:   
  
  
  
  
 
D ate:  
 
P E T Ce nter A d dress:  
 
 
 
P E T Ce nter C o nt act N a me a n d Tele p h o ne N u m ber:  
 
E- m ail:   
  
  
  
  
 
F a x:  
 
T y pe of Sc a n ner:   
(e. g., G E Disc overy S T, Sie me ns Bi o gr a p h, P hili ps Ge mi ni, G E A dv a nce, Sie me ns/ C TI E C A T, etc.) 
 
 
Tr a ns missi o n S o urce:  
(e. g., 6 8G E -r o ds, 1 3 7Cs - p oi nt, C T) 
 
 
Met h o d of Atte n u ati o n C orrecti o n:  
(e. g., se g me nt ati o n, s u btr acti o n of e missi o n c o ntri b uti o n t o tr a ns missi o n sc a n, C T A C) 
 
 
R o ut i ne Q C Testi n g P erf or me d 
 
D ail y:  
 
M o nt hl y: 
 
Q u arterl y:  
 
Ye arl y:  
 
Ot her:  
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 8  
U p date # 1 3  
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S F O R M  
(Fr o m A C RI N  Cre de ntiali n g A p plicati o n, 2 0 0 5) 
 
P a ge 2 of 5  
 
U NI F O R M P H A N T O M S C A N  I N F O R M A TI O N 
 
P h a nt o m Le n gt h:  
  
  
  
P h a nt o m Di a meter:  
 
P h a nt o m V ol u me: 
 
R a di o n ucli de:  
 
F or W ater- Fill a ble P h a nt o ms, Pr o vi de t he F oll o wi n g Data : 
 
Ass a ye d Acti vit y i n S yri n ge bef ore  i njecti o n: 
m Ci   
 
Ti me:  
 
Ass a ye d Acti vit y i n S yri n ge after  i njecti o n: 
m Ci   
 
Ti me:  
 
 
F or Ge -6 8/ G a -6 8 C ali br ati o n P h a nt o ms, Pr o vi de t he F oll o wi n g Data : 
 
C ali br ati o n D ate:  
  
  
 
Ti me:  
 
C ali br ati o n Acti vit y:  
m Ci    
Ti me:  
 
  
  
  
  
  
  
  
  
  
  
 
St d De v of S U V  
N u m ber of Pi xels i n  
Slice #  
A ver a ge S U V i n R OI 1    
  (if a v ail a ble) 
R OI:  
  
 
1    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
2    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
3    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
4    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
5    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
6    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
7    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
8    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
Re p ort i nf o f or E V E R Y   
9    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
slice of t he p ha nt o m 
1 0    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 1    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 2    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 3    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 4    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 5    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 6    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 7    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 8    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
1 9    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
  
 
2 0    
  
_ _ _ _ _ _ _ _  
  
     _ _ _ _ _ _ _ _ 
1 A circ ular or elli ptical re gi o n of i nterest ( R OI) c o veri n g m ost of t he i nteri or of t he p ha nt o m.  

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
7 9  
U p date # 1 3  
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L  S P E CI FI C A TI O N S F O R M  
(Fr o m A C RI N  Cre de ntiali n g A p plicati o n, 2 0 0 5) 
 
P a ge 3 of 5  
 
 
F O R I M A GI N G C O R E L A B O R T O R Y U S E O N L Y:  
 
P h a nt o m I m a ges Re vie w: 
 
D ate:  
C o m me nts:  
 
 
 
 
 
 
        A p pr o ve d  
 
        Dis a p pr o ve d 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _        _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 Si g nat ure                                                            Date  
 
 
 
 
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
8 0  
U p date # 1 3  
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S F O R M  
(Fr o m A C RI N  Cre de ntiali n g A p plicati o n, 2 0 0 5) 
 
P a ge 4 of 5  
 
W H O L E B O D Y F D G -P E T T E S T P A TI E N T # 1 : 
 
File N a me:   
  
  
 
P atie nt Hei g ht:  
P atie nt Wei g ht:  
 
F D G D ose ( m Ci):   
  
 
D ose Ass a y Ti me:  
 
Bl o o d gl uc ose pri or t o F D G a d mi nistr ati o n ( m g/ d L):  
 
I njecti o n Ti me:  
  
 
St art Ti me of E missi o n Sc a n:  
 
A C Q UI SI TI O N  N o. of B e d P ositi o ns: 
 
 
E MI S SI O N TI M E ( MI N/ B E D):   
 
T R A N S MI S SI O N TI M E ( MI N/ B E D):  
 
 
R E C O N S T R U C TI O N A L G O RI T H M:  
(e. g., 2 D F B P, 2 D O S E M, 3 D F O R E/ O S E M, 
3 D R A M L A)  
PI X E L SI Z E ( m m)  
X -Y:  
 
Z:  
 
Sc atter C orrecti o n A p plie d:    
Yes   
 
N o  
 
(Incl u de al g orit h m t y pe, e. g., m o del - b ase d, t ail-fit, B er gstr o m): 
 
R a n d o ms C orrecti o n A p plie d:   
O nli ne    
S m o ot he d R a n d o ms ( offli ne)    
N o ne  
 
 
F O R I M A GI N G C O R E L A B O R T O R Y U S E O N L Y:  
 
Test P atie nt # 1  Re vie w:  
 
D ate:  
C o m me nts:  
 
 
 
        A p pr o ve d  
 
        Dis a p pr o ve d 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _        _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 Si g nat ure                                                            Date  
 

C A L G B 5 0 8 0 1  
Versi o n date: 0 5 /1 1 / 2 02 0  
8 1  
U p date # 1 3  
C A L G B 5 0 8 0 1 P E T/ C T I N S T R U M E N T T E C H NI C A L S P E CI FI C A TI O N S F O R M  
(Fr o m A C RI N  Cre de ntiali n g A p plicati o n, 2 0 0 5) 
 
P a ge 5 of 5  
 
W H O L E B O D Y F D G -P E T T E S T P A TI E N T # 2 : 
 
File N a me:   
  
  
 
P atie nt Hei g ht:  
P atie nt Wei g ht:  
 
F D G D ose ( m Ci):   
  
 
D ose Ass a y Ti me:  
 
Bl o o d gl uc ose pri or t o F D G a d mi nistr ati o n ( m g/ d L):  
 
I njecti o n Ti me:  
  
 
St art Ti me of E missi o n Sc a n:  
 
A C Q UI SI TI O N  N o. of B e d P ositi o ns: 
 
 
E MI S SI O N TI M E ( MI N/ B E D):   
 
T R A N S MI S SI O N TI M E ( MI N/ B E D):  
 
R E C O N S T R U C TI O N A L G O RI T H M:  
(e. g., 2 D F B P, 2 D O S E M, 3 D F O R E/ O S E M, 
3 D R A M L A)  
PI X E L SI Z E ( m m)  
X -Y:  
 
Z:  
 
 
Sc atter C orrecti o n A p plie d:     
  Yes    
N o  
 
(Incl u de al g orit h m t y pe, e. g., m o del - b ase d, t ail-fit, B er gstr o m): 
 
R a n d o ms C orrecti o n A p plie d:   
O nli ne    
S m o ot he d R a n d o ms ( offli ne)    
N o ne  
 
 
F O R I M A GI N G C O R E L A B O R T O R Y U S E O N L Y:  
 
Test P atie nt # 2  Re vie w:  
 
D ate:  
C o m me nts:  
 
 
 
        A p pr o ve d  
 
        Dis a p pr o ve d 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _        _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 Si g nat ure                                                            Date