A Pilot Study of Image-Guided Navigation for High Dose Rate Temporary Interstitial Brachytherapy in the Palliative Management of Previously Treated Tumors of the Spine and Pelvis
Phase: NA
Conditions: Metastatic or Recurrent Lesions in the Spine, Metastatic or Recurrent Lesions in the Pelvis
Sponsor: Memorial Sloan Kettering Cancer Center

 
 
MEMOR IAL SLOAN-KETTER ING C ANCER CENTER 
IRB PROTOCOL #: 12-260 A(4) 
 
 
 
 
A Pilot Study of Image-Guided Nav igation for High D ose Rate Tempor ar y Interstitial 
Brachytherapy in the Palliative Manage ment of Previously Treated Tumor s of the 
Spine and Pelv is 
 
 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUT IC/DIAG NOSTIC PROTOCOL 
 
 
Principal Investigator/Department: 
Yoshiya Yamada, MD 
Radiation Oncology 
Co-Principal 
Investigator(s)/Department: 
Mark H. Bilsky, MD 
Neurosurgery 
Investigator(s)/Department: 
Ilya Laufer, MD 
Eric Lis, MD 
George Krol, MD 
Joan M. Zatck y, NP 
Gil’ad N. Cohen, MS 
Marco Zaider, PhD 
Laszlo Voros, MS 
Patrick Boland, MD 
Zhigang Zhang, PhD 
Neurosurgery 
Radiology 
Radiology 
Radiation Oncology 
Medical Physics 
Medical Physics 
Medical Physics 
Surgery 
Epidemiology & Biostatistics 
Consenting Professional(s)/Department: 
Yoshiya Yamada, MD 
Mark Bilsky, MD 
Ilya Laufer, MD 
Eric Lis, MD George 
Krol, MD Joan M. 
Zatck y, NP 
Radiation Oncology 
Neurosurgery 
Neurosurgery 
Radiology 
Radiology 
Radiation Oncology 
 
 
Please Note : A Conse nting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
Ne w York, New York 10065 
 
 
 
 
 
 
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Table of Contents 
 
1.0 
PROTOCOL SUMM ARY AND/OR SCHEM A........................................................................3 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIM S ................................................................................3 
 
3.0 
BACKGROUND AND RATIONALE ......................................................................................4 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION...............................................................7 
 
4.1 
Design..............................................................................................................................7 
 
4.2 
Intervention.......................................................................................................................7 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ..............................................................................8 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ..............................................................................8 
 
6.1 
Subject Inclusion Criteria...................................................................................................8 
 
6.2 
Subject Exclusion Criteria .................................................................................................9 
 
7.0 
RECRUITM ENT PLAN with limited waiver of authorization...............................................9 
 
8.0 
PRETREATM ENT EVALUATION....................................................................................... 10 
 
9.0 
TREATM ENT/INTERVENTION PLAN ................................................................................ 10 
 
10.0 EVALUATION DURING TREATM ENT/INTERVENTION..................................................... 12 
 
11.0 TOXICITIES/SIDE EFFECTS ............................................................................................. 13 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOM E ASSESSM ENT ......................... 14 
 
13.0 CRITERIA FOR REM OVAL FROM STUDY ........................................................................ 15 
 
14.0 BIOSTATISTICS ................................................................................................................ 16 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOM IZATION PROCEDURES ... 16 
 
15.1 Research Participant Registration ................................................................................... 16 
 
16.0 DATA M ANAGEM ENT ISSUES ......................................................................................... 17 
 
16.1 Quality Assurance........................................................................................................... 17 
 
16.2 Data and Safety Monitoring............................................................................................. 17 
 
17.0 PROTECTION OF HUM AN SUBJECTS............................................................................. 18 
 
17.1 Privacy ........................................................................................................................... 18 
 
17.2 Serious Adverse Event (SAE) Reporting.......................................................................... 18 
 
18.0 INFORMED CONSENT PROCEDURES............................................................................. 19 
 
19.0 REFERENCES................................................................................................................... 20 
 
20.0 APPENDICES .................................................................................................................... 21 

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1.0 
PROTOCOL SUMMARY AND/OR SCHEM A 
 
This pilot s tudy is an invest igation into the use of Ir -192 h igh dose rate ( HDR) 
afterloader-based brachytherapy with catheter place ment us ing image-guided surgica l 
navigation techn iques for patients with pa inful/s ymp tomat ic metastat ic or recurrent 
lesions in the spine and/or pe lvis that have been ma ximally treated with e xternal beam 
radiation therapy.  This study will assess the feasibilit y of this approach in ter ms of 
appropriate dosimetr ic coverage of the target volu me with sparing of tis sues/organs at 
risk fro m e xcess ive radiat ion dose. 
 
Patients enrolled on this study will undergo HDR brachytherapy using the same eq uipment, 
techniques and treatment planning aspects as currently practiced at MSKCC, with the 
exception of the incorporation of image-guided surgical navigation equipment into the HDR 
catheter placement procedure. 
 
Patients will be followed at 2 months (+/- 2 weeks) post-treatment and then approximately 
every 3 months (+/- 2 weeks) until approximately 11 months of follow up. They will be 
evaluated for pain referable to the treated site, clinical and radiographic evidence of local 
progression, and treatment related toxicity.  Thereafter, patients will be followed as clinically 
indicated. 
 
Twenty patients will be entered into this protocol which is expected to take 4 years to 
complete. 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
 
The objective of this study is to validate methods of delivering adequate conformal dose to 
spinal and pelvic targets with HDR catheters using image-guided navigational techniques. 
 
The Specific Aims of this study are to: 
 
1.  Verify feasibility of HDR treatment of spinal and/or pelvic lesions using catheters placed 
under image-guided navigational techniques, to provide improved dosimetric coverage of 
lesions such that 
a.  Gross Target Volume (GTV) D90 
 80% 
b.  Cord/Cauda max dose (Cord/Cauda Dmax) of < 8 Gy 
 
Secondary objectives: 
 
1.  Demonstrate safety of HDR brachytherapy for previously irradiated lesions of the spine 
and/or pelvis, defined as an acceptable level of severe toxicity (both acute and late 
effects) in the setting of HDR brachytherapy treatment.  Severe toxicity will be defined as 
≥ grade 3 NCI CTCAE v 4.0 toxicity that is at least possibly related to treatment (see 
Appendix 2). 
2.  Assess patient pain scores referable to the treatment site using the standardized 11-point 
pain scale. 
3.  Assess patients for duration of in-field progression-free survival at the treatment site. 

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3.0 
B ACKGROUND AND R ATION ALE 
 
Current treatment regimens at MSKCC for metastatic and primary lesions in the spine and 
paraspinal lesions of the pelvis include a range of external beam fractionation schedules, 
ranging from conventional low-dose-per-fraction (high total dose) treatments extending over 
many weeks to high dose single-fraction treatments delivered in a single day.  Conventional 
external beam therapy has been shown to achieve local control rates range less than 50%. 
[Greenberg 1980, Maranzano 1998, Klekamp 1998 ]  In contrast, advances in stereotactic 
external beam radiation therapy have improved local control of lesions in the spine to >90% 
using high-dose single fraction treatments as initial therapy. [Yamada 2008, Moulding 2010] 
For the subset of patients who progress locally after optimal treatment, local control may be 
difficult or impossible to salvage with additional external beam radiation therapy due to limits 
of normal tissue tolerance to radiation, particularly that of the spinal cord. 
 
The generally accepted dose limit for the spinal cord is 45 Gy at 1.8 -2.0 Gy/fraction 
(Schultheiss 1995); 50 Gy is observed in otherwise healthy patient s treated with curative 
intent where the tumor location prohibits limiting the cord to a lower dose, with an attendant 
5% risk of myelopathy at 5 years. [Emami 1991, Schultheiss 1995] For patients undergoing 
high-dose spinal cord radiosurgical procedures, spinal cord tolerance is defined as a cord 
maximal dose of 14 Gy, or less than 10 Gy to 10% volume of the spinal cord per level . [Ryu 
2007, Yamada 2008] In the event of failure, these limitations may preclude or impair the 
ability of radiation oncologists to offer effective salvage therapy with external beam 
techniques. Toxicity resulting from repeat irradiation is a subject of open investigation, with 
thresholds of 100-135 BED Gy equivalent proposed for late complications due to repeat 
irradiation of the spinal cord. [Rades 2005, Nieder 2005, Sahgal 2012] (BED Gy equivalent is 
determined by the biological equivalent dose (BED) calculation; BED = nd(1 + d/α/β), where 
n = number of fractions and d = dose per fraction; α/β is the constant for spinal cord late 
effect and equals 2.) 
 
Intraoperative and percutaneous high-dose rate brachytherapy techniques may address this 
issue to improve local control, pain control, and prevent progressive neurological deficit. At 
our institution, 5 patients have undergone placement of high-dose-rate brachytherapy 
catheters; 2 patients using intraoperative techniques and 3 patients using percutaneous 
techniques; treatment delivery has not yet been standardized and we have not determined 
the optimal techniques for placement of HDR catheters. 
 
As proposed, we will use HDR brachytherapy (Ir -192) to provide tumoricidal doses of 
radiation directly to lesions in the vertebral bodies and paraspinal tissues through 
brachytherapy catheters placed using advanced image -guided surgical navigation techniques.   
The penetration characteristics of Ir -192 are well suited to delivering a conformal therapeutic 
dose of radiation to the region of catheter placement and sparing critical nearby structures 
including the spinal cord, cauda, bowel, etc. This makes it possible to give an extremely high 
dose of radiation to the spine lesion and a margin of surrounding tissues over a short period 
of time as an outpatient procedure, with t he source placed temporarily into the target vertebral 
body and/or paravertebral tissues.  However, to achieve this type of dose distribution, proper 
catheter placement is essential.  Use of image-guided surgical navigation will allow pre-
planned catheter trajectories to be optimized as well as reproducibly executed, providing 
improved delivery of radiation dose. Patients will be treated 

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in a shielded treatment room by passing an Ir -192 source through the transcutaneous 
catheters which have been placed dir ectly into the vertebral body and/or paravertebral 
tissues. 
 
3.1 Adv antages of brachytherapy over external beam radiotherapy 
 
Brachytherapy techniques provide a superior means of delivering high doses of radiation to 
localized targets than external beam radiation.  Dose delivery from radiation is dependent 
upon the inverse square law, which states that the radiation delivered to a point is proportional 
to the inverse square of the distance between the point and the source of radiation.  By taking 
advantage of this law, when brachytherapy sources are placed within lesions in the spine and 
pelvis, very high doses of radiation are absorbed by malignant tissue physically near the 
source while doses to normal tissues outside the target receive doses of radiation much lower 
relative to that within the target. The converse is true of external beam radiotherapy; because 
the difference in the distance between the source and the lesion vs. surrounding normal 
tissues is not significantly different, the dose of radiation absorbed by the target lesion and 
nearby normal tissue may be nearly the same.  External radiation beams must therefore be 
specifically shaped and meticulously planned and placed in order to minimize the dose to 
critical normal structures.  However, since patient motion and setup uncertainties exist 
between the target lesion and the radiation beam, and since many photon beams will have 
some degree exit dose through the spine lesion, there will always be a significant dose of 
radiation absorbed by any structure in the path of the exiting megavoltage photon beam.  
Although the same is true of radiation from brachytherapy sources, the dose 
of radiation absorbed by nearby critical structures is significantly less, and minimizing 
treatment uncertainty permits precise dose localization and delivery of a more 
radiobiologically effective treatment in a single fraction.  Coupled with computer optimized 
inverse treatment planning algorithms, brachytherapy is well suited to deliver high doses of 
radiation to the spine lesion while limiting doses to nearby sensitive normal structures such 
as the spinal cord, cauda equina, bowel, and other nearby tissues. 
 
3.2 Use of image-guided surgical navigation systems 
 
Our current experience with HDR brachytherapy for lesions of the spine and pelvis requires 
placement of the catheters under either direct visualization or fluoroscopic guidance, and has 
not been optimized to ensure that the catheter placement provides the best possible coverage 
of the target lesion while sparing critical dose-limiting structures.  Using a pre- implant CT 
would allow us to determine the optimal configuration of brachytherapy catheter placement in 
prior to surgery, improving target coverage and reducing procedure time; 
image-guided surgical navigation systems would then allow us to precisely track their 
surgical instruments in relation to patient anatomy and place the brachytherapy catheters 
along the pre-planned trajectories. 
 
The Medtronic O-arm surgical imaging system and STEALTH® surgical navigation system 
(Medtronic Inc., Minneapolis MN USA) has been proposed as the platform for image -guided 
navigation of brachytherapy catheters along these pre-planned trajectories.  This system is a 
multi-dimensional surgical imaging platform that is designed for use in s pine, orthopaedic, 
and trauma-related surgeries and approved for clinical use for applications such as pedicle 
preparation and screw placement; it provides real-time, intra-operative imaging of a patient's 

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anatomy with high quality images and a large field -of-view in both two and three dimensions. 
Integration of this platform into our procedures may improve catheter placement accuracy, 
reduce the total time for treatment, improve target coverage and help meet dose constraints 
for critical structures such as the spinal cord/cauda equina. 
 
3.3 Published Outcome s with HDR brachytherapy for spine lesions 
 
HDR brachytherapy for spine lesions is a novel technique developed at Memorial Sloan - 
Kettering Cancer Center; previous techniques have used either electron cone applicators 
requiring an invasive open procedure with poor conformality (Seichi 1999); the INTRABEAM 
electron applicator (XRS 4, Carl Zeiss Surgical Oberkochen, Germany) which delivers a non - 
conformal dose via a percutaneous technique (Schnieder 2011), and injection of samarium- 
153 during kyphoplasty, again with limited conformality (Cardoso 2009). 
 
We have presented on our own limited experience in HDR brachytherapy for palliation of 
previously treated lesions in the spine at the World Congress of Brachyth erapy in May of 
2012. [Yamada 2012]  In our experience, 5 patients were identified with progressive disease 
at multiply irradiated sites in the spine; 2 patients subsequently received HDR brachytherapy 
using catheters placed intraoperatively in the vertebral bodies during surgery and 3 patients 
have been treated using percutaneously implanted catheters with the assistance of 
interventional radiology.  All treatments were performed using a two -stage interstitial catheter 
system (Mick Radionuclear, Mt. Vernon NY) and GammaMed Plus HDR afterloaders (Varian 
Medical Systems).  In all cases treatment was successfully delivered with no brachytherapy- 
related complications.  At a median followup of 4.8 months, there has been no local 
progression of disease.  Median dose delivered was 14 Gy (range 12-18 Gy) with a median 
GTV V90 of 77% (range 40-89%) and median GTV D90 of 75% (range 31-94%). (Appendix 
3, figures 1 and 2 show a representative plan). In all cases the spinal cord/cauda maximum 
dose constraints were met.  No significant difference was noted between the intraoperative 
or percutaneous approach.  3 patients (60.0%) had pain relief 1 -4 weeks following treatment. 
It was noted that patients with lower D90 coverage had suboptimal HDR brachytherapy 
catheter placement, and coverage improved rapidly with experience. 
 
3.4 Expected Toxicity from HDR brachytherapy for spine and pelv ic lesions 
 
Expected toxicities are limited to tissues within close proximity to the treated spine or pelvic 
lesions, where the highest doses of radiation are absorbed.  We would expect that the 
toxicities resulting from treatment would be similar to those experienced with any 
percutaneous procedure (biopsy or kyphoplasty), including standard risks of anesthesia, 
bleeding, and infection.  Mild fatigue and irritation at the sites of catheter insertion are also 
likely. For patients who have received previous treatment to the spine using external beam 
treatment techniques, they will be at increased risk of neurologic injury (due to repeat 
radiation exposure to the spinal cord and/or cauda equina and exiting peripheral nerves) and 
musculoskeletal injury (due to treatment effect on paraspinal musculature and the vertebral 
bodies themselves).  Based on the experience of Seichi et al [Seichi 1999], where 37 patients 
received intraoperative radiation therapy to the spine (22 of 37 had additional radiation 
therapy), only 1 patient (2.7%) developed radiation myelopathy of the spine.  In our own 
limited series, there have been no treatment related comp lications and no late effects 

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observed.  As such, we would expect that the likelihood of neurological toxicity would be on 
the order of 5%. 
 
3.5 Benefits to Patients 
 
While high-dose single fraction radiosurgical techniques have reduced the risk of local fai lure 
to less than 10%, for patients who have local progression after maximal external beam 
radiation for lesions in the spine and pelvis, the only options are aggressive surgical 
intervention, protracted courses of steroid therapy, or systemic chemotherapy ; unfortunately 
these alternatives come at the price of high morbidity, and often these patients are poor 
surgical candidates or have already failed multiple lines of chemotherapy and as such have no 
further systemic options available.  This protocol will allow for the possibility of retreatment in 
the setting of multiply irradiated lesions of the spine and pelvis, with the potential of improved 
local control, prevention of progressive neurological benefit, and alleviation of symptoms. 
 
4.0 
OVER VIEW OF STUDY DESIGN/INTERVENTION 
 
4.1 
Design 
 
The objective of this study is to validate methods of delivering adequate conformal dose to 
previously treated spinal and pelvic targets with HDR catheters using image-guided 
navigational techniques 
 
Patients enrolled on this study will undergo HDR brachytherapy using the same equipment, 
techniques and treatment planning aspects as currently practiced at MSKCC, with the 
exception of the incorporation of image-guided surgical navigation equipment into the HDR 
catheter placement procedure.  The prescribed dose of radiation will be 14 Gy in a single 
fraction. 
 
Patients will be followed at 2 months post-treatment and then approximately every 3 months 
until approximately 11 months of follow up. They will be evaluated for pain referable to the 
treated site, clinical and radiographic evidence of local progression, and treatment related 
toxicity.  Thereafter, patients will be followed as clinically indicated. 
 
Any severe toxicities (defined as ≥ NCI CTCAE v4.0 grade 3) will be carefully evaluated (see 
Section 11) case by case. Further accrual will be stopped if the level of toxicity is higher than 
expected (grade 3 toxicity ≥ 10%). The protocol may then be terminated or modifications 
submitted to the IRB for review, as determined by the principal investigator. 
 
Patients with previously treated malignant lesions of the spine and/or pelvis will be eligible for 
this study (see section on Patient Eligibility). 
 
4.2 
Intervention 
 
The Spine Tumor service at MSKCC has extensive experience with all aspects of HDR 
brachytherapy.  The treatment will be performed utilizing the same equipment and software 
currently used in standard HDR treatments for sarcoma, prostate, and other malignanc ies, 
with the exception of the incorporation of Medtronic STEALTH® applications for guided 
placement of brachytherapy catheters.  Otherwise, all other aspects of the treatment are as 
currently practiced. 

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All procedural aspects of HDR brachytherapy will be performed as currently practiced by the 
brachytherapy service at MSKCC. The technical aspects of intraoperative HDR treatment 
planning (equipment used, acquiring images, computer optimized treatment planning, 
treatment delivery) will otherwise be no different than those currently employed. As part of 
the intervention, patients will undergo a minimum of 2 cone -beam CT scans, with an effective 
dose of 10 mSv per scan. Operator doses will be monitored as per institutional standards 
and will be carefully controlled during catheter placement. 
 
All other aspects of treatment followup will be no different from the current standard of care 
for stereotactic external beam radiation therapy for spinal lesions. The patient will be 
followed at two months and then approximately every three months thereafter with clinical 
examination and spinal imaging (preferably MRI unless otherwise contraindicated), as per 
routine until approximately 11 months of follow up. After 1 year, patients will be followed as 
per standard clinical practice. 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
The major components required for this study are the HDR catheters and remote afterloader, 
the off-line treatment planning software, and the Medtronic O -arm imaging / STEALTH 
surgical navigation systems. 
 
All treatments will be performed using a two-stage interstitial catheter system (Mick 
Radionuclear, Mt. Vernon NY) and GammaMed Plus HDR afterloaders (Varian Medical 
Systems, Palo Alto CA). 
 
The Medtronic STEALTH® surgical navigation system (Medtronic Inc ., Minneapolis MN USA) 
integrates an O-arm cone-beam CT scan taken in the operative room to a set of optically 
tracked tools (drills and probes); the system is in regular use by our orthopedic and 
neurosurgical services at MSKCC. The STEALTH® system is FDA approved for procedures 
in the spine, including surgery, biopsy, and the placement of hardware or other devices in or 
near the spinal column. While this is not an investigational device, its application in this 
protocol is off labelIt will be used to assist in the guidance of brachytherapy catheters into 
pre-planned positions within the vertebral body and/or paravertebral tissues in which the lesion 
of concern is located; while this system is not marketed for use in placement of HDR 
brachytherapy catheters, it is approved for use in spine applications including placement of 
hardware such as pedicle screws into the vertebral pedicles and bodies.  We would also 
investigate integration of the Medtronic Synergy Cranial application to improve workflow in an 
off-label use to assist in automated image fusion of the pre-planning CT scan and 
intraoperative imaging, a process that is currently performed manually in our treatment 
planning system. Synergy Cranial is a software package used to register and fuse CNS CT 
and/or MRI images; while it has additional functionality for interventional use, we would only 
plan to take advantage of the image fusion capability. Image fusion in our treatment planning 
system may take several minutes, while automated image fusion is prac tically instantaneous; 
all fused images would still be reviewed by the clinician to ensure adequacy. 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.1 
Subject Inclusion Criteria 
 
 
Patients must have histologic proof of a malignancy suitable for radiation therapy . 
 
Patients must have received prior external beam radiation therapy to the region 
proposed for HDR brachytherapy treatment; evaluation of doses previously delivered 
to spinal cord/cauda equina, pelvis, and other critical structures (bowel, kidneys, 
rectum) will be taken into consideration. 

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o  If repeat irradiation would exceed any normal tissue constraint set by MSKCC 
Radiation Oncology Department dose constraint criteria, the patient will 
potentially be eligible. 
o If the total prior radiation dose to the cord or pelvis exceeds 100 Gy BED 
equivalent, the patient will be potentially eligible, where a total of 100 BED Gy 
equivalent is determined by the biological equivalent dose (BED) calculation; 
BED = nd(1 + d/α/β), where n = number of fractions and d = dose per fraction; 
α/β is the constant for spinal cord late effect and equals 2. [Rades 2005, 
Nieder 2005, Sahgal 2012] 
 
KPS ≥ 60 (See Appendix 1). 
 
Age ≥ 18 years old 
 
6.2 
Subject Exclusion Criteria 
 
 
Patients who may receive therapeutically effective doses via an external beam 
approach to the lesion of interest as specified by MSKCC Radiation Oncology 
Department dose constraint criteria. 
 
Patients with kyphoplasty cement or hardware that would preclude effective catheter 
placement 
 
Patients with paraspinal extension of disease with visceral involvement. 
 
Abnormal complete blood count.  Any of the following: 

 
Platelet count < 75,000/ml 

 
Hb level < 9gm/dl 

 
WBC <  3.5/ml 
 
Abnormal coagulation profile: INR > 2.5 and/or PTT > 80 

 
Patients who are on anticoagulation medication that may not be safely held for 
the procedure (≥ 5 days for antiplatelet agents and warfarin; ≥ 24 hours for 
low-molecular weight heparin formulations) will be excluded. 
 
Contraindications to general anesthesia 
 
7.0 
RECRUITMENT PLAN with limited waiver of authorization 
 
We have taken notice of NIH/ADAMHA policies concerning the inclusion of women and 
minorities in clinical research populations.  We expect that the study population will be fully 
representative of the range of patients seen at MSKCC without exclusion to age (> 18 years), 
or ethnic background.   Given the limited number of subjects to be entered onto the study, no 
specific outreach efforts are planned. 
 
Potential research subjects will be identified by a member of the pat ient’s treatment team, the 
protocol investigator, or research team at Memorial Sloan -Kettering Cancer Center 
(MSKCC).  If the investigator is a member of the treatment team, s/he will screen their 
patient’s medical records for suitable research study participants and discuss the study and 
their potential for enrolling in the research study.  Potential subjects contacted by their 
treating physician will be referred to the investigator/research staff of the study. 
 
The principal investigator may also screen the medical records of patients with whom they do 
not have a treatment relationship for the limited purpose of identifying patients who would be 
eligible to enroll in the study and to record appropriate contact information in order to 
approach these patients regarding the possibility of enrolling in the study. Those patients 
who are screened will be recorded on the protocol screening log. 

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During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the 
recruitment and enrollment process. The investigator/research staff may also review portions 
of their medical records at MSKCC in order to further assess e ligibility. They will use the 
information provided by the patient and/or medical record to confirm that the patient is eligible 
and to contact the patient regarding study enrollment.  If the patient turns out to be 
ineligible for the research study, the r esearch staff will destroy all information collected on the 
patient during the initial conversation and medical records review, except for any information 
that must be maintained for screening log purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reason, we seek a limited waiver of authorization for the purposes of (1) reviewing 
relevant to the enrollment process; (2) conversing with patients regarding possible enrollment; 
(3) handling of PHI contained within those records and provided by the potential subjects; and 
(4) maintaining information in a screening log of patients approached (if applicable). 
 
8.0 
PRETREATMENT EVALU ATION 
 
Any time prior to treatment start 
 
 
Review of all prior external beam radiation therapy (dose volume histograms, 
beam arrangement, and port films required) 
 
MSKCC pathology review 
 
Within 3 months prior to treatment start 
 
 
History and physical 
 
KPS 
 
Baseline pain assessment 
 
Assessment of baseline comorbidities 
 
Conmed review 
 
Within 30 days prior to treatment start 
 
 
CBC, Comprehensive Serum Chemistry, INR/PTT 
 
MRI if not otherwise contraindicated 
 
CT scan without contrast in the prone position (optional if supine CT already 
performed) 
 
Standard preoperative workup 
 
Within 2 weeks prior to treatment start 
 
 
Pregnancy test for women of childbearing potential 
 
 
9.0 
TREATMENT/INTERVENTION PLAN 
 
All eligible patients will be approached for enrollment.  Patients enrolled on the protocol will 
be scheduled for brachytherapy as per routine, including all necessary laboratory tests for 
preadmission testing as currently practiced. 

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Prior to procedure : 
 
1.  Patient radiographic scans (CT and/or MRI) will be reviewe d by the physicians prior to 
the HDR catheter placement procedure to determine the optimal catheter placement 
trajectories. 
 
HDR Catheter Place ment using image -guided navigation: 
 
The procedure is as currently performed with the addition of the optical fiducial placement 
and registration to the Medtronic STEALTH® system; fiducial placement, image acquisition, 
and image registration is expected to add 10-20 minutes to the procedure. 
 
1.  The patient will be intubated following induction of anesthesia. 
2.  The patient will be positioned in the prone position and prepped. 
3.  An optical fiducial will be placed in the patient for registration with the Medtronic 
STEALTH system (either mounted on a spinous process near the treatment site or 
on a post fixed to the iliac crest through a stab incision). 
4.  A fine-slice (~1mm thick slices with 1mm spacing) cone-beam/O-arm CT scan will be 
obtained and registered to the Medtronic STEALTH® system. 
5.  Catheters will be placed under Medtronic STEALTH® guidance, eitherinto the 
vertebral bodies/ paravertebral tissues or pelvic tissues. Placement will be based 
upon size and location of the lesion, proximity to critical structures, and hardware 
already present in the patient (i.e.: post-surgical fixation and stabilization). Where 
possible, it is preferred to keep the catheters at least 5mm apart. Catheters will be 
placed such that they will extend to the anterior portion of the vertebral body where 
applicable; spatial information of all catheters will be used to avoid overlap and/or 
collision during placement. 
6.  Depth of placement will be verified with fluoroscopic images and a repeat O-arm CT 
scan will be taken. 
a.  As with the pre-placement CT scan, image slices should be ~1mm thick with 
1mm spacing. 
b.  Field of view of the CT scan must encompass the tips of each catheter as well 
as the buttons used to secure the catheters to the skin; Teflon filaments will be 
left in the brachytherapy catheters during the scan. 
c.  Each catheter filament will be marked and labeled with depth of insertion into 
the catheter. 
d.  Final setup picture with catheters in place will be taken and placed in the 
patient’s treatment chart. 
 
Tre atment planning: as currently performed without new devices or techniques. 
 
1.   Intraoperative CT scans will be transferred to our treatment planning system 
(Brachyvision) with the assistance of Brachytherapy Physics: 
a.  Catheter positions will be digitized for planning by Brachytherapy Physics. 
b.  The vertebral body/paraspinal tissue and/or pelvic lesion will be contoured to 
provide the gross target volume (GTV), as well as a clinical target volume 
(CTV) to encompass potential microscopic disease; in some cases the GTV = 
CTV, at the discretion of the planning radiation oncologist. 
c.  Associated critical structures that have received sign ificant prior radiation dose 
such as esophagus, bowel, kidneys, and rectum will be contoured and 
appropriate dose constraints will be applied as per standard practice. In all 
cases the spinal canal, cord and/or cauda will be contoured. 
2.   The final treatment plan will be generated by Brachytherapy physics based on the 
post-placement images utilizing computer optimized three dimensional treatment 
planning. 

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a.  The following dose constraints will be used for treatment planning: 
i. 
Prescribed dose is 14 Gy to the periphery of the GTV. 
ii. 
GTV coverage by the prescription dose will at least be 80% (D90 
≥80%). 
iii. 
Maximu m cord dose (cord Dmax) will be 8 Gy. 
iv. 
For lesions in close proximity (<5cm) to visceral organs, the relevant 
constraints will be applied: 
1.  Esophagus max dose (esophagus Dmax) will be 9 Gy. 
2.  Kidney max dose (kidney Dmax) will be 11 Gy. 
3.  Bowel/Rectum max dose (bowel/rectum Dmax) will be a BED Gy 
equivalent of 85 Gy in 2 Gy fractions (accounting for all prior 
treatment). 
 
3.   Plan will be reviewed and approved by the radiation oncologist. 
i.  If the target dose of 14 Gy to the GTV cannot be met without exceeding dose 
constraints to the cord and other organs-at-risk, the highest achievable dose 
will be delivered that does not exceed dose constraints to orga ns at risk 
(spinal cord/cauda, esophagus, kidney, or bowel). 
4.   The treatment plan will undergo quality assurance procedures as per routine. 
 
Tre atment delivery and completion of care : as currently performed without new devices or 
techniques. 
 
1.  The HDR unit is attached to the brachytherapy catheters and catheter positioning is 
verified using a combination of KV fluoroscopic images as well as checking individual 
catheter depths with marked filaments. 
2.  HDR brachytherapy is delivered in the HDR procedure room as per routine. 
3.  After completion of treatment, all HDR catheters will be removed with the assistance 
of Neurosurgery and bandages will be applied. 
4.  Patient will be monitored for a minimum of 1 hour after catheter removal and then 
discharged home if appropriate. 
5.  Patients will undergo deep venous prophylaxis and pain management throughout the 
course of treatment as per routine. 
 
10.0 EVALU ATION DURING TREATMENT/INTERVENTION 
 
Dosimetric planning will be performed on pre -implantation planning CT and then merged with 
post-implant CT images obtained following catheter placement.  Specific dosimetric 
parameters will include GTV V90, V100, V150, V200, D90, and cord/cauda dose volume 
histograms.  Treatment complications will be monitored in terms of radiation related toxic ity 
during post-procedure recovery and during followup visits; all patients treated on this protocol 
will be evaluated regardless of whether dosimetric goals were met . 
 
Regular follow up visits will be scheduled at 2 months (+/- 2 weeks) and then at 3 month (+/- 
2 weeks) intervals until approximately 11 months of follow up. During these follow up visits, 
standard evaluations currently performed on all spine and/or pelvic radiation therapy patients 
(physical examination and imaging) will be performed.  Thu s, no activities that are not 
currently billed will be necessary.  Follow up after 1 year will be performed as per standard 
clinical practice with no further protocol obligations. 
 
If after the 2 month follow up a patient is not available to come in for a follow up visit, a 
telephone follow up by a clinical investigator will be allowed for up to two of the remaining 
follow up visits. If a phone call follow up is used, the physical exam will be foregone. Outside 
imaging studies are also allowed but must be reviewed at MSKCC. 

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Screening 
Treatment 
Follow up 
(2 months post-treatment, then 
every 3 months until 
approximately 11 months of follow 
up) 
Review of pathology 
X 
Review of prior treatment 
X 
Medical history 
X 
Physical Exam, including 
neurological assessment 
and ambulation 
assessment 
X 
X 
KPS 
X 
CBC 
X 
Comprehensive Serum 
Chemistry 
X 
INR/PTT 
X 
CT spine or pelvis1 (without 
contrast) 
X2 
X 
X3 
MRI spine or pelvis 1 
(unless contraindicated) 
X 
X 
Pre-operative workup 
X 
AE assessment 
Baseline 
comorbidities 
X 
Pain assessment 
X 
X 
Review of Conmeds 
X 
Pregnancy test 
X 
HDR 
X 
 
 
1 Imaging location will be dependent on the lesion site of interest 
 
2 CT scan in prone position is required unless a supine CT has already been performed 
within 30 days of planned treatment 
 
3 Optional if MRI is performed 
 
 
 
11.0 TOXICITIES/SIDE EFFECTS 
 
For non-serious adverse events, we will only be capturing the toxicities that are possibly 
related to protocol treatment. The National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0 will be used as an instrument to evaluate 
toxicities, discussed in section 12. 
 
The toxicities associated with radiation therapy to the spine or pelvis can be classified as 
either early (occurring within 90 days of the treatment) or late toxicities (after 90 days to 1 
year).  Mild acute toxicities that are expected from treatment include Grade 1 -2 fatigue and 
irritation at the sites of catheter insertion, as well as a generally transient pain flare in the 
treated bone site. Less likely (<5% of the time) would be infection or bleeding at the sites of 
catheter insertion.  Rare but serious (<1%) acute toxicities could include complications such 

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as perforation of a visceral organ during catheter p lacement (lung, bowel, or kidney) or 
fractures in the bones of the spine. 
 
There are two types of toxicity which will be considered as potentially serious adverse events 
from the brachytherapy treatment:  neurologic and musculoskeletal.  These generally occur 
late and include myelitis or pathologic fractures of the bones of the spine and/or pelvis. 
Neurologic and musculoskeletal toxicities will be evaluated with the National Cancer Institute 
(NCI) Common Toxicity Criteria v4.0 (discussed in section 12, also see Appendix 2 for 
specifics).  The probability of severe (≥ grade 3) neurologic and musculoskeletal toxicity is 
expected to be less than 10%, which is below the currently observed rate of severe toxicity 
reported by patients who undergo standard radiatio n therapy for lesions of the spine at 
MSKCC. 
 
DEFINITIONS 
 
1.  Definition of an Adverse Event (AE) 
a.  An Adverse Event is defined by the GCP (Guide to Good Clinical Practice) as 
any undesirable experience occurring to a subject during a clinical trial, 
whether or not it is considered related to the investigational product(s). In this 
trial we will only document those AEs that are at least possibly related to 
protocol therapy. 
2.  Definition of a Serious Adverse Event (SAE) 
a.  A Serious Adverse Event is an adverse experience that: 
i.  is fatal or life-threatening 
ii.  is disabling 
iii.  results in hospitalization or prolongation of hospitalization , with the 
exception of an overnight admission following the procedure. 
iv.  results in a congenital anomaly or occurrence of malignancy 
b.  Any neurologic and musculoskeletal toxicity that is grade 3 or higher will be 
considered a serious adverse event. 
3.  Definition of an Unexpected Adverse Event 
a.  An Unexpected AE is an experience not previously reported (in nature, 
severity, or incidence) in the current Investigator's Brochure or general 
investigational plan. 
 
Evaluation of SAE: 
 
Review of the patient record including the treatment dosimetry will be undertaken by the 
principal investigator with the assistance of the co-principal investigator and at least one 
investigator from both Medical Physics and Radiology. The principal investigator may decide 
to continue the protocol without modification, discontinue the study altogether, or to modify 
the protocol prior to enrolling more patients pending th e results of the review. 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
Review of dosimetric characteristics of the patients’ treatment plans will be performed to 
determine if the treatments were able to adequately meet determined parameters. 
 
The primary objective of the study is to validate the feasibility of HDR treatment of spine and 
pelvic lesions using catheters placed under image-guided navigational techniques: 
 
1.  This will be accomplished by the following criteria: We consider a D90 of ≥ 80% for 
the lesion GTV with cord and/or cauda equina maximum doses ≤ 8 Gy as acceptable 
dosimetric endpoints.  Dosimetry will be evaluated following implantation of 

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brachytherapy catheters and prior to patient treatment. 
 
The secondary objectives concern toxicity and clinical outcomes, and will be evaluated 
regardless of whether the primary objective was met : 
 
1.  Demonstration of the safety of HDR brachytherapy for previously irradiated lesions of 
the spine and pelvis. 
a.  Both acute and late (1 year post-treatment) toxicity will be evaluated. 
Neurological evaluation and ambulation assessment will be carried out prior to 
treatment to serve as a baseline.  During each subsequent follow up visit, 
patients will be asked to provide evaluations of their symptoms.  The primary 
expected toxicities are musculoskeletal and neurological.   Grade 2 toxicity is 
almost always self limiting and by definition manageable with medications, not 
requiring invasive procedures.  Thus grade 2 toxicities will not be considered 
as serious adverse events. 
2.  Efficacy of HDR brachytherapy for relief of pain 
a.  Patients will be assessed prior to treatment and at each followup visit using 
the standardized 11-point (0-10) Numeric Rating Scale (NRS-11). Descriptive 
statistics regarding time to, degree of, and duration of relief from pain (if any) 
will be reported in summary form. 
3.  Disease-free progression at the treatment site. 
a.  Imaging studies and clinical assessment performed at each followup date will 
be used to assess degree of response; tumor control will be defined for this 
study as the lack of tumor progression at the treated site , where progression 
may consist of an increase in maximal dimension of the tumor by ≥20%, 
compromise of the spinal cord/cauda equina and/or exiting spinal nerves 
(assessed clinically or radiographically), or both. 
 
The following instruments will be used in the evaluation of toxicities: 
 
NCI Common Toxicity Criteria. The NCI scales are simple to complete and provide a means 
for assessing patient symptoms.  For the purp oses of this study, the musculoskeletal panel of 
questions will be limited to those pertaining to back pain and myositis (see Appendix 2). To 
evaluate neurological toxicities, the categories will be limited to cerebrospinal fluid leak and 
myelitis (see Appendix 2).  Only the CTCAE v4.0 will be used in toxicity grading. 
 
Numeric Rating Scale (NRS-11).  The NRS-11 numeric rating scale is a validated tool for 
discriminating pain level, in which patients rank their “pain score” on a scale of 0 to 10, where 
0 is equivalent to “no pain,” and 10 is “unbearable pain.” [Downie 1978, Paice 1997] 
 
 
13.0 
CRITERIA FOR REM OVAL FROM STUDY 
 
The study subject will be removed from the study for any of the following after review by the 
primary investigator: 
 
1.  If a change in the patient’s medical status unrelated to HDR brachytherapy results in 
the patient being unable to comply with the protocol. 
2.  Patient is unable to comply with the follow up requirements of the protocol. 
3.  Patient request.  Patients will be able to withdraw at any time without cause or 
reason. 

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4.  If the attending radiation oncologist believes that the patient will be adversely affected 
by any aspect of the treatment. 
 
14. 
BIOSTATISTICS 
 
This is a pilot interventional study to evaluate the feasibility of high dose rate ( HDR) 
brachytherapy using image-guided navigational techniques as salvage therapy for previously 
treated lesions of the spine. The primary outcome that we wish to assess is the 
reproducibility of the treatment plan parameters; secondary outcomes include to xicity, relief of 
pain, and local disease progression. 
 
In terms of technical feasibility, a patient is regarded as being successfully treated if the 
target D90 is ≥ 80% AND the cord/cauda max dose is 8 Gy. To this end we will enroll 20 
patients and declare the procedure feasible if at least 15 patients can be successfully 
treated. For this decision rule we have the following probability table: 
 
True 
feasibility 
rate 
55% 
60% 
65% 
70% 
75% 
80% 
85% 
90% 
Probability 
of declaring 
feasible 
0.055 
0.126 
0.245 
0.416 
0.617 
0.804 
0.933 
0.989 
 
 
We believe this procedure will be quite safe for patients; a previous study from Japan [Seichi 
1999] showed serious toxicity rates of approximately 3%, and we anticipate ours will be even 
lower. Among the 20 patients we expect to see less than 2 adverse events.  In the event that 
a second serious adverse event (≥ Grade 3, or as otherwise defined above in Section 11.0) 
occurs, this protocol will be immediately halted and the investigator will carefully examine the 
cases with the assistance of the co-principal investigator and at least one investigator from 
both Medical Physics and Radiology and review the protocol (to be either terminated or 
modified in order to proceed further). Self-reported pain scores will be recorded and 
descriptive statistics regarding time to, degree of, and duration of relief from pain (if any) will 
be summarized numerically and/or graphically. In-field progression-free probability will be 
estimated using Kaplan-Meier estimation. 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOM IZATION PROCEDURES 
 
15.1 
Rese arch Participant Registration 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a protocol 
specific Eligibility Checklist. 
 
All participants must be registered through the Protocol Participant Registration (PPR) Office 
at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through Friday from 
8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the PPR Electronic 
Registration System (http://ppr/).  The completed signature page of the written consent/RA or 
verbal script/RA, a completed Eligibility Checklist and other relevant documents mus t be 

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uploaded via the PPR Electronic Registration System. 
 
16.0 
DATA M ANAGEM ENT ISSUES 
 
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of the 
RSA include protocol compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordinate the activities of 
the protocol study team. 
 
Research material from this study will be handled with the same confidentiality as patients’ 
other medical data. The data collected for this study will be entered into a secure database. 
Source documentation will be available to support the computerized patient record. 
 
16.1 
Quality Assurance 
 
Eligibility of patients will be verified with the principal investigator.  Only the designated 
investigators will obtain informed consent. An assigned RSA will work with the principal 
investigators to ensure proper adherence to the protocol, eligibility verification, informed 
consent and data accuracy. 
 
Routine data quality reports will be generated to assess missing data and inconsistencies. 
Accrual rates and accuracy of evaluations and follow-up will be monitored periodically 
throughout the study period and potential problems will be brought to the attention of the 
study team for discussion and action. 
 
16.2 
Data and Safe ty Monitoring 
 
With the help of the RSA, the principal investigators will review each case at the time of 
enrollment to verify eligibility. The RSA will work with the principal investigators to ensure 
that the protocol is followed carefully. 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer Center 
were approved by the National Cancer Institute in September 2001. The plans address the 
new policies set forth by the NCI in the document entitled “Policy of the National Cancer 
Institute for Data and Safety Monitoring of Clinical Trials” which can be found at: 
http://cancertrials.nci.nih.gov/researchers/dsm/index.html.   The DSM Plans at MSKCC were 
established and are monitored by the Office of Clinical Research.  The MSKCC Data and 
Safety Monitoring Plans can be found on the MSKCC Intranet at: 
http://mskweb2.mskcc.org/irb/index.htm. 
 
There are several different mechanisms by which clinical trials are monitored for data, safety 
and quality. There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research QA and departmental procedures for quality control, plus there 
are two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs.  The committees: Data and Safety Monitoring Committee (DSMC) for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) Institutional 
Review Board. 
 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. Every type of protocol (e.g., NIH sponsored, 
in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed 
and the monitoring procedures will be established at the time of protocol activation. 

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17.0 
PROTECTION OF HUM AN SUBJECTS 
 
There are no foreseen additional risks to the patients from this study.  Every effort will be 
made to protect the rights of human subjects as per in stitutional policy. A full discussion of 
risk, benefits, expected toxicities/side effects, alternatives/options for treatment will be 
undertaken.  No additional financial costs or burdens will result as a consequence of joining 
this study.  Informed consent is a prerequisite to enrollment on the study. 
 
In accordance with institutional policy, privacy and confidentiality of medical records will be 
strictly observed.  All data pertaining to the study will also be likewise protected.  The study is 
entirely voluntary.  Patients who do not wish to participate in the study will be offered all 
treatment options including but not limited to those considered to be the standard of care. 
 
17.1 
Priv acy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form.  The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form.  A Research Authorization form mu st be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
 
17.2 
Serious Adverse Event (SAE) Re porting 
 
Any SAE must be reported to the IRB/PB as soon as possible but no later than 5 calendar 
days. The IRB/PB requires a Clinical Research Database (CRDB) SAE report be submitted 
electronically to the SAE Office at  sae@mskcc.org.  The report should contain the following 
information: 
 
Fields populated from CRDB: 
 
 
Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
 
Medical record number 
 
Disease/histology (if applicable) 
 
Protocol number and title 
 
Data needing to be entered: 
 
 
The date the adverse event occurred 
 
The adverse event 
 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
 
If the AE was expected 
 
The severity of the AE 
 
The intervention 
 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form. 

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The PI’s signature and the date it was signed are required on the completed report. 
 
18.0 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants’ consent should be obtained prior to 
treatment planning being completed.  Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 
 
1.  The nature and objectives, potential risks and benefits of the intended study. 
2.  The length of study and the likely follow-up required. 
3.  Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4.  The name of the investigator(s) responsible for the protocol. 
5.  The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 

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19.0 
REFERENCES 
 
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4.  Moulding HD, Elder JB, Lis E, et al. Local disease control after decompressive surgery and 
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6.  Seichi A, Kondoh T, Hozumi, T, Karasawa, K. Intraoperative Radiation Therapy for 
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7961, pp. 79613G-6 ( 2011). 
 
 
 
 
20.0 
APPENDICES 
 
1.  Karnofsky Performance Status 
2.  National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 
3.  HDR Treatment planning