NOVEMBER (Novem- (9), BrEast Radiation), A Phase II Trial of a 9 Day Course of Whole Breast Radiotherapy for Early Stage Breast Cancer
Phase: PHASE2
Conditions: Ductal Breast Carcinoma In Situ, Invasive Breast Carcinoma, Stage 0 Breast Cancer, Stage I Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer
Sponsor: University of Utah

 
Protocol name:  NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date:  23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
  
 
NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole 
breast radiotherapy for early stage breast cancer. 
Lead Trial ID: HCI103976/IRB# 103976  
NCT03345420 
 
 
Principal Investigator 
Matthew M. Poppe, MD 
Associate Professor 
Department of Radiation Oncology, Univ. of Utah 
1950 Circle of Hope Dr., RM 1570 
Salt Lake City, UT 84112 
Tel: 801-581-8793 Fax: 801-585-3502 
Matthew.Poppe@hci.utah.edu  
 
 
Medical Monitor  
 
Randa Tao, MD 
Assistant Professor,  
Department of Radiation Oncology, Univ. of Utah 
2000 Circle of Hope Dr.  
Salt Lake City UT, 84112 
Tel: 801-581-8793 
u6007955@umail.utah.edu 
 
Statistician  
Kenneth Boucher, PhD 
Huntsman Cancer Institute/University of Utah 
2000 Circle of Hope 
Salt Lake City, UT 84112 
kenneth.boucher@hci.utah.edu 
 
Investigational agent 
External Beam Radiation Therapy (EBRT)  
 
IND Number 
N/A 
 
 
 
Historical Protocol Versions 
Version 1: 21JUL2017 
Version 2: 12APR2018 
Version 3: 08JUN2018  
Version 4: 03MAY2019 
Version 5: 16AUG2019 
Version 6: 15SEP2020 
Version 7: 23NOV2021 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 2 of 61 
Template version date: 3-5-2015 
TABLE OF CONTENTS 
Page 
LIST OF ABBREVIATIONS ............................................................................................. 4 
PROTOCOL SIGNATURE ................................................................................................ 8 
STUDY SUMMARY.......................................................................................................... 9 
STUDY SCHEMA............................................................................................................ 10 
1 
OBJECTIVES ........................................................................................................... 11 
1.1 
Primary Objectives and Endpoint ...................................................................... 11 
1.2 
Secondary Objectives and Endpoint .................................................................. 11 
2 
BACKGROUND ...................................................................................................... 11 
2.1 
Rationale for the Study ....................................................................................... 11 
2.2 
Baseline Toxicity from whole breast radiation .................................................. 13 
2.3 
Altered Fractionation in Breast Cancer .............................................................. 14 
2.4 
Photographic Cosmetic Assessment................................................................... 15 
2.5 
Patient Satisfaction and Well-being as Patient Reported Outcomes (PROs) ..... 15 
2.6 
Cost Effectiveness .............................................................................................. 16 
3 
STUDY DESIGN...................................................................................................... 16 
3.1 
Description ......................................................................................................... 16 
3.2 
Number of Patients ............................................................................................. 17 
3.3 
Number of Study Centers ................................................................................... 17 
3.4 
Study Duration ................................................................................................... 17 
4 
ELIGIBILITY CRITERIA........................................................................................ 18 
4.1 
Inclusion Criteria ................................................................................................ 18 
4.2 
Exclusion Criteria ............................................................................................... 19 
5 
TREATMENT PLAN ............................................................................................... 20 
5.1 
Surgical Management ......................................................................................... 20 
5.2 
Systemic Therapy ............................................................................................... 20 
5.3 
Radiotherapy ...................................................................................................... 21 
5.4 
Prohibited Concomitant Medications ................................................................. 26 
5.5 
Duration of Therapy ........................................................................................... 26 
6 
TOXICITIES AND DOSEAGE MODIFICATION ................................................. 27 
6.1 
Supportive Care .................................................................................................. 27 
7 
STUDY CALENDAR .............................................................................................. 28 
8 
CRITERIA FOR EVALUATION AND ENDPOINT .............................................. 30 
8.1 
Photographic Assessment ................................................................................... 30 
8.2 
Patient Reported Outcomes ................................................................................ 30 
8.3 
Local and local regional recurrence ................................................................... 31 
8.4 
Economic Analysis ............................................................................................. 32 
8.5 
Safety .................................................................................................................. 33 
8.6 
Stopping Rules ................................................................................................... 33 
9 
STATISTICAL CONSIDERATIONS...................................................................... 34 
9.1 
Primary Objective .............................................................................................. 34 
9.2 
Secondary Objectives ......................................................................................... 34 
10 REGISTRATION GUIDELINES ............................................................................. 36 
11 DATA SUBMISSION SCHEDULE ........................................................................ 36 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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12 ETHICAL AND REGULATORY CONSIDERATIONS ........................................ 36 
12.1 Informed consent ................................................................................................ 36 
12.2 Institutional Review ........................................................................................... 36 
12.3 Data and Safety Monitoring Plan ....................................................................... 36 
12.4 Adverse Events / Serious Adverse Events ......................................................... 37 
12.5 SAE Reporting Requirements ............................................................................ 39 
12.6 Reporting of Pregnancy ...................................................................................... 40 
12.7 Protocol Amendments ........................................................................................ 40 
12.8 Protocol Deviations ............................................................................................ 40 
12.9 FDA Annual Reporting ...................................................................................... 41 
12.10 Clinical Trials Data Bank ................................................................................... 41 
12.11 Record Keeping .................................................................................................. 41 
13 BIBLIOGRAPHY ..................................................................................................... 41 
14 APPENDICES .......................................................................................................... 45 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 4 of 61 
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LIST OF ABBREVIATIONS 
Abbreviation or 
Term1 
Definition/Explanation 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
β-HCG 
Beta-human chorionic gonadotropin 
BID 
Twice daily 
BLQ 
Below limit of quantification 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca++ 
Calcium 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CHF 
Congestive heart failure 
CI 
Confidence interval 
Cl- 
Chloride 
CLcr 
Creatinine clearance 
Cmax 
Maximum observed concentration 
Cmin 
Trough observed concentration 
CNS 
Central nervous system 
CR 
Complete response 
CRF 
Case report form 
CT 
Computed tomography 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Abbreviation or 
Term1 
Definition/Explanation 
CTCAE 
Common Toxicity Criteria for Adverse Events 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
D/C 
Discontinue 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
Eg 
Exempli gratia (for example) 
FACS 
Fluorescence Activated Cell Sorting  
FDA 
Food and Drug Administration 
FDG-PET 
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GLP 
Good laboratory practice  
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCO3- 
Bicarbonate 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
Hr 
Hour or hours 
IC50 
Half maximal inhibitory concentration 
i.e. 
Id est (that is) 
IEC 
Independent ethics committee 
INR 
International normalized ratio 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Template version date: 3-5-2015 
Abbreviation or 
Term1 
Definition/Explanation 
IRB 
Institutional review board 
IU 
International unit 
IV 
Intravenous, intravenously 
LDH 
Lactate dehydrogenase 
LLQ 
Lower limit of quantitation 
MedRA 
Medical Dictionary for Drug Regulatory Activities 
MRI 
Magnetic resonance imaging 
MRSD 
Maximum recommended starting dose 
MTD 
Maximum tolerated dose  
NOAEL 
No-observed-adverse-effect level 
NOEL 
No-observed-effect-level 
PD 
Pharmacodynamic(s) 
PFS 
Progression Free Survival 
PK 
Pharmacokinetic(s) 
PO 
Per os (administered by mouth) 
PR 
Partial response 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QC 
Quality control 
RBC 
Red blood cell 
QD 
Once daily 
QTc 
QT interval corrected  
QTcF 
QT interval corrected using Fredericia equation 
SAE 
Serious adverse event 
SD 
Standard deviation or stable disease 
T1/2 
Terminal elimination half-life 
T3 
Triiodothyronine 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Abbreviation or 
Term1 
Definition/Explanation 
T4 
Thyroxine 
Tmax 
Time of maximum observed concentration 
TID 
Three times daily 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
ULQ 
Upper limit of quantitation 
UV 
Ultraviolet 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
WONCBP 
Women of non-childbearing potential 
All of these abbreviations may or may not be used in protocol.  

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 8 of 61 
Template version date: 3-5-2015 
PROTOCOL SIGNATURE 
 
I confirm that I have read this protocol, and I will conduct the study as outlined herein 
and according to the ethical principles stated in the latest version of the Declaration of 
Helsinki, the applicable ICH guidelines for good clinical practice, and the applicable laws 
and regulations of the federal government. I will promptly submit the protocol to the IRB 
for review and approval. Once the protocol has been approved by the IRB, I understand 
that any modifications made during the course of the study must first be approved by the 
IRB prior to implementation except when such modification is made to remove an 
immediate hazard to the subject. 
 
I will provide copies of the protocol and all pertinent information to all individuals 
responsible to me who assist in the conduct of this study. I will discuss this material with 
them to ensure that they are fully informed regarding the study treatment, the conduct of 
the study, and the obligations of confidentiality. 
 
Note: This document is signed electronically through submission and approval by the 
Principal Investigator in the University of Utah IRB Electronic Research Integrity and 
Compliance Administration (ERICA) system. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 9 of 61 
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STUDY SUMMARY 
 
Title 
NOVEMBER (Novem- (9), BrEast Radiation), 
A Phase II trial of a 9 day course of whole 
breast radiotherapy for early stage breast 
cancer. 
Short Title 
NOVEMBER. 
Protocol Number 
IRB#103976 
IND 
N/A 
Phase 
Phase II 
Design 
Single arm non-inferiority trial 
Study Duration 
8 years (3 years enrollment, 5 years follow-up) 
Study Center(s) 
Single-center at Huntsman Cancer Institute 
Objectives 
Primary objective will be to evaluate 24 month 
breast photographic cosmetic scores with 9 
fraction hypofractionated radiation compared to 
published hypofractionation radiation. 
 
Secondary objectives include evaluation of 
patient reported outcomes, radiation toxicities, 
disease recurrence, and cost effectiveness. 
 
Number of Subjects 
102 enrolled for at least 87 evaluable 
Diagnosis and Main Eligibility Criteria 
Stage 0-IIB breast cancer in the setting of breast 
conservation. 
Exclusion: Prior RT, Recurrent setting, Node 
positive, NO chemo before RT, No pregnancy 
Study Product, Dose, Route, Regimen 
External Beam Radiation Therapy (EBRT) 
Duration of administration 
9 days of Radiation (11-14 calendar days) 
Reference therapy 
Study therapy will be compared with published 
phase III data on 15 day, & 16 day 
hypofractionation breast RT studies from the 
UK and Canada. 
Statistical Methodology 
The primary analysis will be a one sample t-
test. The null hypothesis will be that the true 
rate is good to excellent photographic breast 
cosmetic assessment in ≤70% of patients. The 
one sided alternative hypothesis is a good to 
excellent photographic breast cosmetic 
assessment in > 70% of patients. Assuming the 
true rate is 80% (e.g. exact equivalence), a 
sample of 87 evaluable subjects will provide 
80% power at the alpha = 0.1 significance level. 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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STUDY SCHEMA 
 
 
*Regional Nodes will not be specifically targeted, however some level I/II nodes may be 
incidentally covered. Nodal evaluation requirement waived for selected patients (Section 
5.1). 
 
Patients will be followed with clinical visits for 3 years or until death, whichever comes 
first. Data at 5 years will be by chart review only. 
 
Please refer to the full protocol text for a complete description of the eligibility criteria 
and treatment plan. 
 
 
 
 
Hypofractionated Whole Breast Radiation: 
34.2Gy/3.8Gy (9) fractions to the whole 
breast with simultaneous 39.6Gy/4.4Gy to the 
lumpectomy cavity over 2 weeks. 
Register 
Lumpectomy – 
pathology 
confirmation of 
negative lymph 
nodes and margins. 
(see nodal 
exception*) 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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1 OBJECTIVES 
1.1 Primary Objectives and Endpoint 
 To evaluate 24 month breast photographic cosmetic scores with 9 fraction 
radiation compared to standard hypofractionation. 
 
1.2 Secondary Objectives and Endpoint 
 To evaluate Breast-Q Patient Reported Outcomes (PROs) compared to historical 
control in breast conservation. 
 To evaluate the incidence of acute and late radiation complications, based on 
CTCAE 4.0 toxicity. 
 To evaluate the local and local regional recurrence rate. 
 To compare the direct and indirect patient costs for radiation therapy compared to 
historical controls as well as quality adjusted life years, utilizing the Breast-Q 
Patient Reported Outcomes (PROs) and the EQ-5D. 
 
2 BACKGROUND 
2.1 Rationale for the Study 
 
Adjuvant radiation therapy (RT) plays an important role in successful breast conservation 
in early stage breast cancer, and has been shown to significantly reduce the risk of breast 
cancer recurrence over surgery alone1-4. Adding breast radiation to lumpectomy has 
allowed women to keep their natural breast, as multiple randomized trials have 
demonstrated equivalent overall and disease free survival compared to a mastectomy.4-7 
Meta-analyses have concluded that post lumpectomy radiation improves breast cancer 
survival, with an estimated 1 life saved for every 4 recurrences prevented.8 An important 
component of radiation therapy is the time-dose-fractionation schedule. Up until the last 
decade, the standard radiation schedule in North America involved 6-8 weeks of daily 
radiation.  
In 1986 Royal Marsden Hospital and the Gloucestershire Oncology Centre collaborated 
in a prospective trial evaluating 3 breast fractionations: 50Gy in 25 fractions, 39Gy in 13 
fractions (3.0Gy/fx), or 42.9Gy in 13 fractions (3.3Gy/fx) all over 5 weeks 9. In 1999, 
after over 1400 patients had been enrolled the trial design was expanded into a multi-
institutional trial and patient data from the earlier study was rolled into what became 
START A, with the 13 fraction regimen changed to 3.2Gy/day for 41.6Gy. A total of 
2236 women were randomized to one of three arms between 1986 and 1999, treating 
patients with 2D planning and Cobalt-60. The overall treatment time of 5 weeks was kept 
constant in all three arms. The primary endpoint was late breast change. Local control 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 12 of 61 
Template version date: 3-5-2015 
was a secondary endpoint. Locoregional relapse was non-significantly different in the 3 
arms at 10 years at 7.4%, 6.3% and 8.8%.10 Fourteen percent of patients received CMF 
chemotherapy. Running in parallel to STARTA, the UK STARTB trial was an 
accelerated hypofractionation trial comparing 50Gy in 2Gy daily fractions for 5 weeks 
versus 40Gy delivered in 2.67Gy daily for 15 days.11 This trial accrued 2215 stage I and 
II breast cancer patient between 1999 and 2001, treating patients with Cobalt-60, utilizing 
2D planning. 23% of patients received chemotherapy +/- tamoxifen. In 1993, shortly after 
the RMH began their prospective trial, researchers with the National Cancer Institute of 
Canada (NCIC) and Ontario Clinical Oncology Group conducted a similar 
hypofractionated randomized trial comparing whole breast radiation of 50 Gy in 25 
fractions versus a hypofractionated regimen 42.5 Gy in 16 fractions. 10 year data was 
published by Whelan et al in 2010 revealing equivalent outcomes in terms of cancer 
control and toxicity.12,13 Cosmesis was identical with excellent or good scores at 3 and 5 
years in 77% of patients in both groups. Toxicities were comparable. Grade 2 and 3 
toxicities were negligible. At 5 years, 87% of women in the experimental arm had no skin 
toxicity, and 66% of women had no subcutaneous toxicity, compared with 82% and 60% 
in the control arm, respectively. A major limitation of the Canadian study is the lack of a 
lumpectomy boost. The addition of an extra dose of radiation to the lumpectomy cavity, 
called a boost, has been shown in 2 randomized trials to significantly reduce further the 
risk of a local breast recurrence.14,15 Women in the NCIC study were not allowed a breast 
lumpectomy boost, but the UK start trials allowed an optional boost of 14Gy in 5 daily 
fractions. This occurred in 61% of patients in STARTA and 43% in STARTB.  
Adding a lumpectomy cavity boost in a sequential manner, adds an additional 5-8 
treatment days of radiation, significantly increasing treatment burden. Several institutions 
have published results suggesting the safety of delivering the lumpectomy cavity boost 
concurrent with the whole breast radiation.16-19 From 2011-2015, the Radiation Therapy 
Oncology Group (RTOG) moved this single institution data into the phase III randomized 
trial 1005, randomizing women with a sequential vs. concurrent lumpectomy cavity 
boost.20 In this trial, the whole breast radiation could be administered in 15 vs. 25 
fractions, at the discretion of the treating physician. In the concurrent arm, the breast 
received the UK START dose of 40Gy (2.66/day) while the lumpectomy cavity received 
an additional daily dose, resulting in a total of 48Gy delivered, 3.2Gy/day. In the 
conventional arm, the breast received the boost delivered over an additional 6-7 daily 
treatments as the treating physician discretion.  
The UK has tried to advance the hypofractionation concept further with the UK Fast trial. 
This trial enrolled 915 patients from 2004 to 2007 into one of three treatment arms: 50Gy 
in 25 fractions, 28.5Gy in 5 fractions or 30Gy in 5 fractions, all delivered over 5 weeks. 
The primary endpoint for the trial is change in photographic breast appearance. Initial 
publication in 2011, with a mean follow up of 3 years, has shown all arms acceptable in 
regards to conventional toxicity. The 50Gy and 28.5Gy arms appear to be similar in 2 
year photographic appearance, however the 30Gy arms appears to be inferior with a risk 
ratio of mild to marked change in appearance 1.7:1 (1.26-2.29, p<0.001).21 There are two 
potential problems with this hypofractionation model. The radiobiology is not well 
understood when taking 6 days off between each treatment fractions, therefore the long 
term disease control outcomes will need to be carefully followed over the next 5-10 years 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 13 of 61 
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to ensure equivalent cancer control. Additionally, for women residing a long distance 
from the nearest treatment facility, this results in additional burden for housing and 
transportation. 
With the publishing of the hypofractionated data from the UK and Canada, there has been 
an increasing adoption rate of short course radiation here in the US, despite some 
reluctance.22-25 This is likely due to the difficulty some physicians have with changing 
30+ years of tradition, as well as the decreased reimbursement rates that come with 
hypofractionation, given the current fee for service payment model.  
We feel our proposed fractionation will provide a significant improvement in 
convenience and cost effectiveness, while delivering equivalent cancer control.  
2.2 Baseline Toxicity from whole breast radiation 
In reviewing toxicity data from previous hypofractionation trials, the UK STARTB 40Gy 
in 15 fraction treatment arm (majority received an optional 10Gy boost) reported a 5 and 
10 year local recurrence rate of 2% and 3.8% (respectively), and 10 year 4.3% local-
regional relapse (3.2-5.2%, CI). Reported toxicities are shown in the table below. Cosmetic 
results overall were better in the 3 week 40Gy hypofractionation arm compared to the 5 
week 50Gy standard arm.10,11 
 
 
Symptomatic rib 
fracture  
2.2% 
Lung fibrosis 
1.7% 
Ischemic heart disease 
1.5% 
Breast edema 
5% 
Telangiectasia  
4.2% 
Breast shrinkage 
26% 
Breast induration 
14% 
 
In the NCIC hypofractionation randomized study the local recurrence rate (invasive only) 
at 5 and 10 years was 2.8% and 6.2%. Grade 3 RT associated morbidity was 4%. 30% of 
women had less than an excellent or good cosmetic result (grade 2 or 3 on the EORTC 
photographic assessment).12,13 This slight higher recurrence rate compared to the UK start 
data may reflect a higher risk group or the fact the NCIC patients did not receive a 
lumpectomy cavity boost.  
Based on this information, we feel that a reasonable expected combined radiation grade 2 
or greater non-acute toxicity rate (non-cosmetic) would be 7-10%, a conservative estimate 
from several prospective trials. 
Also based on this information, we feel that a reasonable expected local recurrence rate 
would be 5-6%, with an upper limit of 10% acceptable.  

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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2.3  Altered Fractionation in Breast Cancer 
In standard breast irradiation, daily fraction sizes of 180 cGy or 200 cGy are commonly 
used and are described as conventional or standard. The rationale for conventional 
fractionation and the relationship between fraction size and tissue response is well 
described by the α/β ratio in the linear quadratic model of fractionation sensitivity.26 In this 
empiric model, “late-reacting” normal tissues such as fibroblasts and neurons have a low 
α/β ratio (2-5 Gy) and are very responsive to increases in fraction size, while “acutely-
reacting” normal tissues such as intestinal epithelium have a high α/β ratio (>7 Gy) and are 
less responsive to changes in fraction size. The biological effect of a given fractionation 
scheme size is related to the α/β ratio by the equation:  
Biological Effective Dose = BED = 𝑛𝑛𝑛𝑛 (1 +
𝑛𝑛
𝛼𝛼
𝛽𝛽
) where 
d = dose/fraction 
n = # of fractions 
Although relatively high cumulative doses of radiation are needed for tumor control, the 
daily fraction size has to be respectful of the fraction sensitivity of normal tissues in the 
treated volume. Accounting for these assumptions, increases in fraction size have to be 
compensated for by reductions in cumulative radiation dose, which typically are 
insufficient for tumor control. As a result, daily fractions of 1.8 to 2 Gy are delivered over 
4-6 weeks to reach a cumulative dose of 45-60 Gy. In vitro experiments in human breast 
carcinoma cell lines have suggested an α/β ratio of about 4 Gy.27,28  
This 9 day radiation treatment design is supported in its safety and efficacy through similar 
randomized trials in early stage breast conservation, confirming the BED modeling.  
Table of Biological Effective doses from different radiation fractionations 
Biological Effective Dose 
Total dose/fx size 
α/β=2 (normal 
tissue) 
α/β =4 (breast 
cancer) 
Whole Breast 
NSABP-B06 
50Gy/2 
100 
75 
NCIC 
42.56Gy/2.66 
100 
71.2 
UK Start B 
40Gy/2.66 
93 
66.4 
UK FAST 
30Gy/6 (5 wks) 
120 
75 
UK FAST 
30Gy/5.8 (5 wks) 
110 
69 
November 
34.2Gy/3.8 
99.2 
66.7 
With Lump Boost 
Lyon Boost 
60Gy/2 
120 
90 
EORTC Boost 
66Gy/2 
132 
99 
UK Start w/Boost 
40Gy/2.66 + 10Gy/2 
113 
81.4 
RTOG 1005 SIB 
48Gy/3.2 
125 
86 
November 
39.6Gy/4.4 
126.7 
83.2 
 
Hopefully, this short treatment schedule will reduce cost while likely improving patient 
satisfaction for women. The promise of short-course radiation lies in the added 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Template version date: 3-5-2015 
convenience it may offer to patients who otherwise may not be able to receive radiation, 
and it may also allow earlier sequencing of radiation with systemic chemotherapy. 
Although sequencing seems to be unimportant in the context of breast preservation, it 
may be important in women at higher risk for locoregional recurrence. In this trial, we 
will require adjuvant chemotherapy to be delivered after radiation. Given the excellent 
cure rates and low morbidity with current adjuvant radiation therapy technique and 
fractionation, it is only natural that subsequent improvements in the field take 
convenience and economic impact into account. 
2.4 Photographic Cosmetic Assessment 
The EORTC Breast Cosmetic Rating system is a blinded digital photographic method that 
has been utilized in prior radiation studies and shown to be reliable and valid in detecting 
effects of radiation morbidity.10,15,21,36,37 This method compares the radiated breast with the 
contralateral untreated side and evaluates: Size, shape, location of the areola/nipple, 
appearance of the surgical scar, skin pigmentation changes, presence of telangiectasia and 
a global cosmetic score based on all of the factors. Characteristics are graded on a four-
point scale: 0, excellent or no difference; 1, good or small difference; 2, fair or moderate 
difference; and 3, poor or large difference. In the UK Start B analysis of more than 900 
patients, the rate of good/excellent photographic cosmetic assessment was 80% at 2 years.2 
In the NCIC analysis of over 1200 patients the 3 year rate of good/excellent cosmetic 
assessment was 77% (no 2 yr rate given).4 Based on the NCIC and UK start photographic 
assessment, we anticipate that our patients will have an overall good-excellent cosmetic 
score in ≥ 70% of patients, when compared to their baseline. 
2.5 Patient Satisfaction and Well-being as Patient Reported Outcomes (PROs) 
The assessment of patient-reported outcomes (PROs) in clinical research provides 
important insight into how therapies impact the daily lives of patients. There is a growing 
recognition that patient-reported endpoints are critical in oncology trials, particularly when 
cosmesis and toxicity are likely to be different in the treatment arms. Patient-reported 
adverse event collection has been shown to be more thorough than collection by provider-
report, with consistent underreporting of side effects by providers.29 Patient-reporting of 
health-related quality of life has become the gold standard in part because providers have 
been found to underestimate the pain and distress their patients are experiencing.30,31 
In a trial of different radiation schedules, in which cosmesis may be substantially different 
in the two arms of the study, patient-reported satisfaction and well-being are particularly 
important. Although short-term differences between the treatment arms may be 
momentarily relevant to patients, the long-term cosmetic outcomes are most critical, so we 
have chosen to collect this data at 24 months (and compare to historical controls). In order 
to avoid burdening patients, we will only administer the Breast-Q survey to patients at 
baseline, 6, and 24 months. The EQ-5D-3L will be administered at baseline and 2-8 weeks 
post radiation therapy. 
We will be using the Breast Q survey tool to assess patient satisfaction and well-being.32,33 
This tool has been validated for use in patients after breast conserving therapy to assess 
well-being and patient satisfaction with results, and is provided free of charge for academic 
research.34 Domains for the survey include: satisfaction with breast, adverse effects of 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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radiation, psychosocial well-being, physical well-being and satisfaction with information. 
Cronbach’s alphas for the scale range from 0.81 to 0.98, and the BREAST-Q has test-retest 
reliability, demonstrated by an intra-class correlation coefficient ranging from 0.85 to 
0.987.35 The electronic 2.0 version we will be using was given retrospectively to 3497 
women who had undergone a lumpectomy (1622 with adjuvant radiation) and determined 
to be a reliable and validated survey tool, with median score for Satisfaction with Breast to 
be 62 (44-77), and no significant difference in the radiated cohort.  
We will be using the EQ-5D-3L survey tool. The 3-level version of EQ-5D (EQ-5D-3L) 
was introduced in 1990 by the EuroQol Group. The EQ-5D-3L essentially consists of 2 
pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). 
The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 
levels: no problems, some problems, and extreme problems. The patient is asked to 
indicate her health state by ticking the box next to the most appropriate statement in each 
of the five dimensions. This decision results into a 1-digit number that expresses the level 
selected for that dimension. The digits for the five dimensions can be combined into a 5-
digit number that describes the patient’s health state. 
The EQ VAS records the patient’s self-rated health on a vertical visual analogue scale 
where the endpoints are labelled ‘Best imaginable health state’ and ‘Worst imaginable 
health state’. The VAS can be used as a quantitative measure of health outcome that 
reflects the patient’s own judgement. 
2.6 Cost Effectiveness 
We hypothesize that a 9 fraction course will be more cost effective. Costs will be 
compared to 45 de-identified patients that were treated with a standard hypofractionated 
regimen of 19 treatments. Direct costs of medical care to each patient will be estimated 
using utilization information from HCI financial/claims data. Generalized linear models 
will then be used to model these costs as a function of treatment, time on study, and all 
available baseline patient characteristics to assess the extent to which estimated direct 
cost is impacted by the type of radiation dosing. Given the well-known fact that 
healthcare costs are typically highly skewed, regression models will employ the 
appropriate distribution and transformation link. 
3 STUDY DESIGN 
3.1 Description 
This will be a phase II single arm non-inferiority trial. Trial patients will receive 9 
fractions hypofractionated radiation. Patients will be evaluated for breast photographic 
cosmetic scores with hypofractionated radiation compared to standard fractionation 24 
months after radiation. Secondary objectives include evaluation of toxicities, recurrence, 
patient reported outcomes and cost effectiveness. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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3.2 Number of Patients 
87 Analyzable patients. Plan for 15% drop out rate, therefore plan to enroll 102 patients 
3.3 Number of Study Centers 
At this time, Huntsman Cancer Hospital is the only planned enrolling institution. 
3.4 Study Duration  
We anticipate enrolling 30 patients per year on this trial with 3 years of clinical follow 
up. We plan to do a chart review at 5 years for any long-term toxicities or evidence of 
late breast cancer recurrences. 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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4 ELIGIBILITY CRITERIA 
This eligibility checklist is used to determine patient eligibility and filed with enrolling 
investigators signature in the patient research chart. 
 
Patient No. ______________________ 
Patient’s Initials: (L, F, M) _________________ 
4.1 Inclusion Criteria 
Yes/No  (Response of “no” = patient ineligible) 
 _____ Histologically confirmed invasive carcinoma and/or Ductal Carcinoma In 
Situ (DCIS) of the breast. 
 _____ Final pathologic Tis, T1-T3, all must be N0 and M0 status). 
 _____ Negative inked histologic margins from lumpectomy, with the exception of 
a focus of positive margin at the pectoralis fascia. 
 _____ Radiation oncologist does not plan to treat regional lymph nodes beyond 
standard whole breast tangent fields. 
 _____ Lumpectomy with negative lymph node on surgical evaluation (Isolated 
tumor cells in lymph nodes will be permitted). Patients with invasive carcinoma 
≥ 70 yrs and with ER+ positive tumor ≤ 2.0cm may enroll without surgical 
lymph node evaluation, per section 5.1. Patients with Ductal Carcinoma In Situ 
(DCIS) of the breast only may enroll without surgical lymph node evaluation. 
 _____ Negative serum or urine β-HCG in women of child-bearing potential ≤ 7 
days prior to registration. 
A female of childbearing potential is a sexually mature female who 
has not undergone a hysterectomy or bilateral oophorectomy and 
has not been naturally postmenopausal for at least 12 consecutive 
months. 
 _____ Women of child-bearing potential must agree to utilize a form of birth 
control or agree to undergo sexual abstinence during radiation therapy. 
 _____ ECOG (Zubrod) Performance Status 0-1. 
 _____ Patient ≥ 18 years of age. 
 _____ Able to provide informed consent and willing to sign an approved 
consent form that conforms to federal and institutional guidelines. 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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4.2 Exclusion Criteria 
Yes/No (Response of “yes” = patient ineligible) 
 _____ Prior radiation therapy to the chest, neck or axilla. 
 _____ Prior history of ipsilateral breast cancer (invasive disease or DCIS). LCIS 
and benign breast disease is allowed. 
 _____ History of prior or concurrent contralateral invasive breast cancer. Benign 
breast disease, LCIS or DCIS of contralateral breast is allowed. 
 _____ Active collagen vascular diseases, such as: systemic lupus erythematous, 
scleroderma, or dermatomyositis. 
 _____ Significant post lumpectomy complications requiring an unplanned re-
operation or admission for IV antibiotics. Re-operation for margins evaluation 
or nodal evaluation is acceptable. 
 _____ Co-existing medical conditions with life expectancy < 5 years. 
 _____ Other malignancy within 5 years of registration with the exception of basal 
cell or squamous cell carcinoma of the skin treated with local resection only or 
carcinoma in situ of the cervix. 
 _____ Neoadjuvant chemotherapy or adjuvant chemotherapy delivered before 
radiation. 
 _____ Neuroendocrine carcinoma or sarcoma histology. 
 
4.2.10 ____ Concurrent radiation sensitizing medications concurrent with radiation, per 
treatment physician. 
 
I certify that this patient meets all inclusion and exclusion criteria for enrollment 
onto this study.  
 
______________________________ 
 
_________ 
_______ 
Investigator Signature  
 
 
 
Date  
Time 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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5 TREATMENT PLAN 
Initial surgery is defined as lumpectomy and any subsequent surgeries related to the 
initial lumpectomy, including additional margin resection, or lymph node removal. 
Radiation treatment may begin no later than 84 days after initial surgery. 
Chemotherapy must be delivered after (NOT BEFORE) radiation. 
Chemotherapy is defined as cytotoxic chemotherapy, not biological therapy, such as 
trastuzumab, pertuzumab, etc. 
5.1 Surgical Management 
Lumpectomy 
Margins should be negative, defined as no tumor on ink. A focally positive deep margin 
will be considered a negative margin if the deep margin is the pectoralis fascia. This is 
provided there is no evidence of pectoralis fascia invasion by imaging or pathological 
evaluation.  
Lymph nodes must be evaluated by sentinel node biopsy or axillary dissection. The 
exception, per the CALGB 9343 criteria is patients who are ≥ age 70 and have ER 
positive tumors ≤ 2.0cm.38 These patients will not require lymph node evaluation. This 
protocol does not stipulate sentinel node versus axillary dissection, but does require 
lymph node management per standard of care. Patients will be recorded as having 
undergone a sentinel node only procedure or an axillary dissection. A sentinel node 
procedure will be considered an axillary dissection if more than 5 lymph nodes are 
removed. 
5.2 Systemic Therapy 
Any adjuvant hormonal therapy is allowed. It may begin any time relative to the 
radiation, at the discretion of the treating physician. 
Chemotherapy is allowed, but must be delivered after radiation therapy. Neoadjuvant 
chemotherapy is not allowed. Patients may be co-enrolled on systemic therapy trials, if 
there is no contraindication on the other trial. 
Cytotoxic systemic therapy may not be used concurrently with radiation; however, 
trastuzumab, pertuzumab or other biological therapy may be given concurrently per 
standard of care. 
If cytotoxic chemotherapy is started after radiation, a minimum of 10 days must pass 
after the last fraction of radiation before beginning chemotherapy. If a patient is 
experiencing a CTCAE Grade 2 or higher skin reaction, it is recommended that this be 
extended to 21 days, or until the skin reaction has resolved.  
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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5.3 Radiotherapy 
Radiation therapy treatment planning should begin after consultation with the radiation 
oncologist and prior to radiation treatment. 
 Technical Factors 
3-dimentional CT based treatment planning is required. Megavoltage photon beam 
energies with energies ≥ 4 MV are required. Electron beams require megavoltage 
energies, if utilized. Proton beams are not allowed on this trial. 
Localization, simulation and immobilization 
Simulation and treatment must be performed with the patient in the supine or prone 
position. Patients should be optimally positioned with alpha cradle casts, vac fix, breast 
boards, wing boards and/or other methods of immobilization at the discretion of the 
treating physician. 
Methods to minimize the cardiac exposure to RT such as a heart block, gating or breath-
hold are allowed at the discretion of the treating physician. 
A treatment planning CT scan in the treatment position will be required to define the 
clinical target volumes (CTV), planning target volumes (PTV), and Organs at Risk 
(OAR). 
Radio-opaque markers are to be placed on the patient’s skin in the treatment position as 
external landmarks at the acquisition of the CT scan to facilitate contouring segmentation 
of the CT data-set. 
The CT scan should extend cephalad to start at or above the mandible and extend 
sufficiently caudally (or inferiorly) to the inframammary fold to encompass the entire 
lung volume. A CT scan image thickness of < 0.5 cm should be employed. 
External skin localizing marks, which may include permanent tattoos, are recommended 
for radiation daily localization and set-up accuracy. 
Use of IMRT is allowed. Please see the section below for IMRT guidelines. 
Calculations shall take into account the effect of tissue heterogeneities. 
Each of the following volumes and normal structures must be delineated on each 
slice of the planning CT:  
Post Lumpectomy Volumes: Ipsilateral and Contralateral Breast and Lumpectomy 
Cavity. 
Normal tissue: Right and left lung, contralateral breast, heart, thyroid. 
Normal tissues should be delineated as follows: 
Breast: Breast CTV. Includes the palpable breast tissue demarcated with radio-opaque 
markers at CT simulation, the apparent CT glandular breast tissue visualized by CT, 
consensus definitions of anatomical borders, and the Lumpectomy CTV from the RTOG 
breast cancer atlas. The breast CTV is limited anteriorly within 5 mm from the skin and 
posteriorly to the anterior surface of the pectoralis, serratus anterior muscle excluding 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
Page 22 of 61 
Template version date: 3-5-2015 
chest wall, boney thorax and lung. In general, the pectoralis and/or serratus anterior 
muscles are excluded from the breast CTV unless clinically warranted by the patient’s 
pathology. The breast CT should generally follow consensus guidelines 
Contralateral breast: Includes the apparent CT glandular breast tissue visualized by CT 
and consensus definitions of anatomical borders from the RTOG Breast Atlas.  
In general the borders are: 
• 
Posterior border: At the anterior surface of the pectoralis, serratus anterior 
muscles excluding Breast, ribs, boney thorax, and lung/heart.  
• 
Medial border: The sternal-costal junction. 
• 
Lateral border: Varies based on the size of the breast, but typically is at the mid-
axillary line and excludes the ipsilateral lattismus dorsi muscle. 
• 
Cephalad border: Should be similar to that of the ipsilateral breast CTV. 
• 
Anterior border: Skin minus 5 mm to minimize inaccuracy of dose calculation at 
the skin surface. 
Ipsilateral and contralateral lung: These may be contoured with auto-segmentation with 
manual verification. 
Heart: This is to be contoured on all cases – not just the left sided cases. The heart should 
be contoured beginning just inferior to the level in which the pulmonary trunk branches 
into the left and right pulmonary arteries (pa). Above the pa, none of the heart’s 4 
chambers are present. The heart should be contoured on every contiguous slice thereafter 
to its inferior most extent near the diaphragm. The following structures, if identifiable, 
should be excluded from the heart contour: esophagus, great vessels (ascending and 
descending aorta, inferior vena cava). One need not include pericardial fat, if present. 
Contouring along the pericardium itself, when visible, is appropriate. 
Thyroid: The thyroid is easily visible on a non-contrast CT due to its preferential 
absorption of iodine, rendering it “brighter” or denser than the surrounding neck soft 
tissues. The left and right lobes of the thyroid are somewhat triangular in shape and often 
do not converge anteriorly at mid-line. All “bright” thyroid tissue should be contoured. 
For patients who have undergone total thyroidectomy, there may be no thyroid tissue to 
contour. 
IMRT 
The following definitions and conditions are applied concerning IMRT in this protocol: 
1) 
The treatment plan will be considered IMRT for the purposes of this protocol if an 
inverse planned optimization is used to determine the beam weights to meet the target 
and critical structure dose-volume constraints. 
2) 
A plan generated by direct aperture optimization that employs an inverse planning 
algorithm is considered as IMRT when the target and critical structure dose-volume 
constraints are met and at least 3 apertures for each beam direction are used. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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3) 
If IMRT is combined with the standard open medial and lateral tangential fields 
for whole breast irradiation, the IMRT beam, as described in number 1) above, should 
deliver > 50% of the total number of monitor units for the beam orientation. 
4) 
If an IMRT plan is used with another IMRT plan, forward-planning photon 
beams, and/or electron beam, the composite dose distribution and DVHs should be 
generated.  
5) 
All standard IMRT planning and delivery systems using MLC (step-and-shoot, 
dynamic MLC, slide-and shoot, VMAT, tomotherapy) are allowed and classified as 
IMRT as long as target and critical structure dose-volume constraints are met. 
6) 
IMRT planning and delivery systems using physical beam-intensity compensators 
designed by an inverse algorithm to modulate beam intensity so that the required dose 
constraints are met are also accepted as IMRT. 
All plans that are not fit into the above definitions and conditions are classified as 
3DCRT plans. Specifically: 
• 
The plans generated using forward-planning methods or segmental techniques 
such as “field-in-field” to meet dose-volume constraints are considered as 3DCRT plans. 
These forward-planned or segmental treatment techniques are those intended mainly to 
improve the uniformity of the dose distribution, but not to produce steep dose gradients to 
protect critical structures (e.g. heart or lung). 
• 
The plans with the number of apertures < 3 for each beam direction are 
considered 3DCRT plans even if they were generated with inverse planning algorithms. 
 Treatment Planning 
The goals of treatment planning in this study in both arms are to encompass the breast 
and minimize inclusion of the heart and lung. 
Field arrangements for 3D conformal and IMRT of the breast are defined below with 
some discretion of the treating physician. Multiple beam arrangements are to be designed 
during the treatment planning process to produce an optimal plan that meets the dose-
volume constraints on the target volumes and normal tissues outlined below. This trial is 
specifically evaluating toxicity and cosmesis; therefore we have set tight constraints on 
maximum doses. 
Treatment plans must meet Dose Volume Constraints for the contoured targets and 
normal structures. Various treatment approaches may be used to develop treatment plans. 
Ipsilateral Breast CTV to PTV expansion is a range of 5-7mm, based on practice and 
technical capabilities. 
The following volumes are to be delineated: 
Lumpectomy GTV: Contour using all available clinical and radiographic information 
including the excision cavity volume, architectural distortion, lumpectomy scar, seroma 
and/or extent of surgical clips (clips are strongly recommended). Patients without a 
clearly identifiable lumpectomy bed are not eligible for protocol participation. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Lumpectomy CTV: Lumpectomy GTV + 1 cm 3D expansion. Limit the CTV posteriorly 
at anterior surface of the pectoralis major and anterolaterally 5 mm from skin and should 
not cross midline. In general, the pectoralis and/or serratus anterior muscles are excluded 
from the lumpectomy CTV unless clinically warranted by the patient’s pathology. The 
Lumpectomy CTV should not extend outside of the Breast CTV and should be trimmed if 
necessary to accomplish this. 
Lumpectomy PTV: Lumpectomy CTV + 5 mm 3D expansion (excludes heart). 
Lumpectomy PTV Eval: Since a substantial part of the Lumpectomy PTV often extends 
outside the patient (especially for superficial cavities), the Lumpectomy PTV is then 
copied to a Lumpectomy PTV Eval which is edited. This Lumpectomy PTV EvaL is 
limited to exclude the part outside the ipsilateral breast and the first 5 mm of tissue under 
the skin (in order to remove most of the build up region for the DVH analysis) and 
excluding the Lumpectomy PTV expansion beyond the posterior extent of breast tissue 
(Breast, pectoralis muscles and lung) when pertinent. The lumpectomy PTV should not 
cross midline. This Lumpectomy PTV Eval is the structure used for DVH constraints and 
analysis. This Lumpectomy PTV Eval cannot be use for beam aperture generation. 
Breast CTV: Includes the palpable breast tissue demarcated with radio-opaque markers at 
CT simulation (see section 5.3.1), the apparent CT glandular breast tissue visualized by 
CT, consensus definitions of anatomical borders, and the Lumpectomy CTV from the 
breast cancer atlas (section 5.3.1). The breast CTV is limited anteriorly within 5 mm from 
the skin and posteriorly to the anterior surface of the pectoralis, serratous anterior muscle 
excluding chest wall, boney thorax and lung. In general, the pectoralis and/or serratous 
anterior muscles are excluded from the breast CTV unless clinically warranted by the 
patient’s pathology. The breast CT should generally follow consensus guidelines 
Breast PTV: Breast CTV + 5-7 mm 3D expansion (exclude heart and do not cross 
midline). 
Breast PTV Eval: As a part of the Breast PTV often extends outside the patient, the 
Breast PTV is then copied to a Breast PTV Eval, which is edited. This Breast PTV Eval 
is limited anteriorly to exclude the part outside the patient and the first 5 mm of tissue 
under the skin (in order to remove most of the buildup region for the DVH analysis) and 
posteriorly is limited to no deeper than the posterior rib surface and excludes lung and 
heart. This Breast PTV Eval is the structure used for DVH constraints and analysis and 
not for beam aperture generation. 
 
Ribs: The ribs within the Breast PTV need to be contoured as a structure. 
 Dose-Volume Histogram (DVH) Analysis.  
Breast:  
** These are calculated by evaluating the whole breast plan before the summation of the 
lumpectomy cavity boost. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Preferred: ≥ 95% of the Breast PTV Eval contour that falls within the tangential 
treatment fields will receive 32.5Gy, 95% of the Breast prescribed dose of 
34.2Gy. Acceptable: ≥ 90% of the Breast PTV Eval contour that falls within the 
tangential treatment fields will receive > 30.8Gy Gy which is ≥ 90% of the whole 
breast prescribed dose of 34.2 Gy. 
Maximum Dose to Breast: Less than 10cc of PTV Eval will receive > 107% dose 
or 36.6 Gy for a prescribed breast/Breast dose of 34.2 Gy. Less than 0.03cc can 
receive > 115% of dose, 39.3Gy. 
** These are calculated by evaluating the entire plan sum, inclusive of the lumpectomy 
cavity integrated boost. 
Preferred: ≤ 30% of the breast PTV Eval will receive > 100% of the boost 
prescribed dose of 39.6Gy. Acceptable ≤ 35% of the breast PTV Eval will receive 
> 100% of the boost prescribed dose of 39.6Gy.  
Preferred: ≤ 50% of the breast PTV Eval will receive > 37Gy. Acceptable: ≤ 50% 
of the breast PTV Eval will receive > 38.3Gy.  
Lumpectomy: 
** These are calculated by evaluating the entire plan sum, inclusive of the lumpectomy 
cavity integrated boost. 
Preferred: ≥ 95% of the Lumpectomy PTV Eval contour will receive 37.6Gy, 95% of the 
Lumpectomy prescribed dose of 39.6Gy. Acceptable: ≥ 90% of the Lumpectomy or 
Lumpectomy PTV Eval contour that falls within the tangential treatment fields will 
receive > 35.6Gy Gy which is ≥ 90% of the whole Lumpectomy prescribed dose of 39.6 
Gy. 
Preferred: ≤ 5% of the Lumpectomy PTV Eval will receive > 43.5Gy, 110% of the boost 
prescribed dose of 39.6Gy. Acceptable ≤ 10% of the Lumpectomy PTV Eval will receive 
> 43.5Gy 
Preferred: Maximal dose to greater than 0.03 cc will be 45.5 Gy. Acceptable is maximal 
dose no greater than 47.5 Gy. 
Contralateral Breast:  
Preferred: Less than 10% of the contralateral Breast or breast receives > 2 Gy. 
Acceptable: Less than 10% of the contralateral Breast or breast receives 4 Gy or more. 
Ipsilateral Lung: 
Preferred: ≤ 35% of the ipsilateral lung should receive ≥ 14.5 Gy. 
Acceptable: ≤ 40 % of the ipsilateral lung should receive ≥ 14.5 Gy. 
Contralateral Lung: 
Preferred: ≤ 10% of the contralateral lung should receive 4 Gy or more. 
Acceptable is ≤ 15% of the contralateral lung should receive 4 Gy or more. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Heart: 
Preferred ≤ 10% of the whole heart should receive ≥ 18 Gy for left-sided breast cancers, 
and < 2% of the heart should receive ≥ 18 Gy for right-sided breast cancers.  
Acceptable: ≤ 10% of the whole heart should receive ≥ 22 Gy for left-sided breast 
cancers, and < 2% of the heart should receive ≥ 22 Gy for right-sided breast cancers. 
Preferred: Mean heart dose should be ≤ 1.5 Gy. 
Acceptable is a mean heart dose ≤ 2.5 Gy.  
Every attempt should be made to make the cardiac exposure to radiation as low as 
possible. 
Ribs:  
The max rib dose for the entire plan sum is 36Gy.  Blocking the ribs from the boost field 
will likely be necessary.  If the lump PTV_eval cannot be adequately covered by a 
minimum dose (90% volume to 90% dose), consider taking the patient off protocol. 
5.4 Prohibited Concomitant Medications 
No potential radio-sensitizers may be used concurrent with radiation therapy. 
5.5 Duration of Therapy 
Subjects must be withdrawn from the study treatment for the following reasons:  
 
•    Subject withdraws consent from the study treatment and/or study procedures. A 
subject must be removed from the trial at his/her own request or at the request of 
his/her legally acceptable representative. At any time during the trial and without 
giving reasons, a subject may decline to participate further. The subject will not 
suffer any disadvantage as a result. 
•    Subject is lost to follow-up. 
• The development of a second cancer or recurrent disease. 
•    Death. 
 
Subjects may be withdrawn from the study for the following reasons:  
• The subject is non-compliant with radiation treatments, trial procedures, or 
both; including the use of anti-cancer therapy not prescribed by the study 
protocol. 
• If, in the investigator's opinion, continuation of the trial would be harmful to the 
subject's well-being. 
• Development of an intercurrent illness or situation which would, in the 
judgment of the investigator, significantly affect assessments of clinical status 
and trial endpoints. 
•  Deterioration of ECOG performance status to 4. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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6 TOXICITIES AND DOSEAGE MODIFICATION 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse 
Events) Version 4.0 for adverse event and serious adverse event reporting. Dose 
Modifications 
Radiation doses should not be modified and compliance with the protocol will be 
determined as defined above, by the ideal and acceptable dose constraint criteria. Dose 
deviations outside of the acceptable range will be considered major protocol violations. 
Patients may occasionally require treatment breaks, which should be kept to a minimum. 
Treatment breaks of up to 2 days will be considered acceptable. Treatment breaks of greater 
than 2 days are strongly discouraged. 
6.1 Supportive Care 
 
All supportive measures consistent with optimal patient care will be given throughout the 
study. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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7 STUDY CALENDAR 
Laboratory and clinical parameters during treatment are to be followed using individual institutional guidelines and the best clinical 
judgment of the responsible physician. It is expected that patients on this study will be cared for by physicians experienced in the 
treatment and supportive care of patients on this trial. 
 
Tests & Observations 
Prior to 
Registration 
Before 
RT 
Weekly 
during RT 
2 to 8 
weeks 
post RT 
6 months 
post RT* 
12 
months 
post RT* 
2 years 
post 
RT* 
3 years 
post RT** 
5 years 
Post RT** 
Obtain Informed Consent13 
X 
 
 
 
 
 
 
 
 
H&P 
X3,11 
 
 
 
 
 
 
 
 
Symptom Directed Physical11 
 
 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Score 
X 
 
X 
X 
X 
X 
X 
X 
 
Recurrence Assessment10 
 
 
 
 
X 
X 
X 
X 
X5,10 
Adverse Events Assessment1 
 
 
X 
X 
X 
X 
X 
X 
X1,5 
Photographic Cosmetic 
Assessment6 
 
X 
 
 
 
 
X 
 
 
Serum or Urine HCG 
X2 
 
 
 
 
 
 
 
 
Breast-Q Survey7 
 
X 
 
 
X 
 
X 
 
 
Health Care Expense Diary 
 
 
X4 
 
 
 
 
 
 
Health Care Expense Survey 
 
 
 
X8,12 
 
 
 
 
 
EQ-5D Survey9 
 
X 
 
X 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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*    +/- 6 weeks 
** +/- 3 months  
1. Assessment of side effects related to radiation therapy should be assessed according to the history and physical examination. 
2. For women of childbearing potential. Must be done within 7 days prior to registration. 
3. All screening procedures should be performed within 28 days prior to registration except as otherwise noted. 
4. Health Care Expense Diary should be provided to the patient each week during RT to assist in recall for the Health Care Expense Survey 
after radiation completion. (Appendix III) 
5. Post hoc chart review only for 5 years. 
6. Photographic assessment collection will be done as described in section 8.1. 
7. Breast Q Survey should be completed by the patient prior to radiation therapy and at 6 months post radiation therapy. (Appendix I) 
8. Health Care Expense Survey should be completed using the Health Care Expense Diary worksheet (Appendix III) during the 2-8 week 
window and is found in Appendix II.  
9. EQ-5D Survey should be completed by the patient prior to radiation therapy and during the post radiation therapy 2-8 week window. 
(Appendix IV) 
10. Disease recurrence will be determined by standard of care assessments as described in section 8.3. 
11. Clinical assessments above are a minimum for trial purposes only and do not represent the entirety of necessary medical care. Weekly 
treatment visits occur once every 5 treatment fractions during radiation. Follow up visits should be scheduled per standard of care and 
physician discretion. Per NCCN guidelines, clinical follow up visit should occur 1-4 times per year with continued annual mammograms. 
12. Identified patients who voluntarily agree to complete the Health Care Expense Survey should be provided this survey at 2-8 weeks post 
standard of care hypofractionated radiation. (See section 8.4 Economic Analysis for further instruction) 
13. Patients who volunteer to complete the Health Care Expense Survey must be provided with the Informed Consent Letter prior to 
completing the questionnaire.   

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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8 CRITERIA FOR EVALUATION AND ENDPOINT 
8.1 Photographic Assessment 
The primary outcome of this study is the overall photographic cosmetic outcome of 9 
fraction radiation in NOVEMBER versus published hypofractionation radiation. 
Cosmetic effects of radiation can include telangiectasia, breast fibrosis, scar retraction 
and skin pigmentation changes. As this is not a blinded study, cosmetic assessment will 
be blinded with digital photography reviewed by a 3 unbiased reviewers. Reviewers will 
include a radiation oncologist, surgeon and nurse. 
Confidential bilateral digital photographs (excluding the face) will be taken with a digital 
camera: 
Photo #1) 
Bilateral, standing, anterior photo to show both breasts with the arms at 
45° from the body and 
Photo #2) 
Unilateral, close up of treated area to show the surgical scar at 24 months 
post radiation.  
Photographs will be captured of both breasts at the following time points: 
• 
Before radiation (Post Lumpectomy and before Radiation) 
• 
24 months after the completion of radiation 
Photographs of both breasts will be collected as above and reviewed by a blinded Central 
Adjudication Committee according to the modified EORTC Cosmetic Rating System. An 
on-line training module is available. 
8.2 Patient Reported Outcomes 
We will be using the Breast Q survey tool to assess patient-reported satisfaction with 
breast, well-being, and overall satisfaction. This tool has been validated for use in 
patients before and after mastectomy as well as breast conservation, and is provided free 
of charge for academic research. We will be using the Breast Q Breast Conserving 
Therapy Module at baseline, 6 months and 24 months after radiation finishes. There are 
119 questions with the conceptual framework of the BREAST-Q modules comprised of 
two overarching themes, which are health-related quality of life (QOL) and patient 
satisfaction.  
Within QOL, there are two scales: Physical, Psychosocial and Sexual Well-being. Within 
the Psychosocial Well-being scale for patients, there are items that ask about body and a 
woman’s confidence in social settings. Other items cover emotional health and self-
esteem. Within the Sexual Well-being scale, there are items that ask about feelings of 
sexual attractiveness when clothed and unclothed and sexual confidence as it relates to 
one’s breasts, as well as how comfortable or at ease a woman feels during sexual activity. 
Within the Physical Well-being scales here are questions asking about pain, activity 
limitations, and sleep problems due to discomfort.  

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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Within patient satisfaction, there are three other scales: Satisfaction with Breasts, and 
Satisfaction with Care. “Satisfaction with Breasts,” measures body image in terms of a 
woman’s satisfaction with her breasts and asks questions regarding how comfortably bras 
fit, and how satisfied a woman is with her breast area both clothed and unclothed. 
Postoperative items ask about breast appearance (e.g., size, symmetry, softness) and 
clothing issues (e.g., how bras fit; being able to wear fitted clothes). The preoperative 
modules and the Satisfaction with Care scale will not be included in this study. 
Each scale can be used independently and scored separately. The BREAST-Q scoring 
software, QScore, transforms patient-reported data into summary scores ranging from 0-
100 with a higher number meaning better quality of life or higher satisfaction on the 
various scales.  
BREAST Q questionnaires can be collected with pencil/paper or done electronically. 
8.3 Local and local regional recurrence 
Recurrence data will be collected at 6, 12, 24, and 36 months of follow up and will 
include a 5 year chart review. 
 Criteria for Local and regional recurrence  
 Local Recurrence 
Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive 
breast cancer in the same quadrant as the lumpectomy of ipsilateral reconstructed breast 
or breast. A recurrence elsewhere in the breast is considered a local-regional recurrence. 
 Regional Recurrence 
Regional recurrence is defined as the cytologic or histologic evidence of disease in the 
ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or 
ipsilateral axillary nodes or soft tissue of the ipsilateral axilla. A recurrence in a separate 
quadrant from the initial lumpectomy will also be scored as a regional recurrence. 
 Distant Recurrence 
Distant recurrence is defined as the cytologic, histologic and/or radiographic evidence of 
disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional 
metastasis), lung, bone marrow, central nervous system or histologic and/or radiographic 
evidence of skeletal or liver metastasis. 
 Second Primary Breast Cancer 
Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ 
or invasive breast cancer in the contralateral breast. 
 Second Primary Cancer (Non-breast) 
Any non-breast second primary cancer other than squamous or basal cell carcinoma of 
the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
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be confirmed histologically whenever possible. If this occurs in the breast radiation field, 
it will be scored as a radiation induced secondary malignancy. 
 Death 
Underlying cause of death is to be reported. 
8.4 Economic Analysis 
A reduction in number of radiation treatments and thereby number of visits to the 
radiation therapy department will benefit patients directly, both in terms of reduced direct 
and indirect healthcare costs. Direct healthcare costs are expected to go down because of 
an expected reduction in health care utilizations services (e.g., office visits, emergency 
room visits, inpatient admissions). With short-course treatment patients may be able to 
take less time off from work and/or return to work faster. Potential improvements in 
cosmetic-outcomes and side effects of radiation therapy with short-course therapy could 
also translate into a reduction in utilization of health care services, further enhancing the 
economic impact of hypofractionation. Indirect costs are also expected to be lower for the 
intervention arm because patients in this arm are expected to resume normal activities 
sooner. This in turn would help save family caregiver time as well as the cost of 
dependent care, which will further add to the saving in indirect costs. Therefore, robust 
measurement of the patient resources used to receive radiation therapy and utilization of 
health services is a critical component of this trial. 
Patients will be given a diary with question domains to be filled out weekly during 
radiation therapy in order to help improve recall (Appendix II, III and IV). 
We will utilize available CPT code charges generated from the time of registration to 2-8 
weeks after the completion of radiation therapy. We will utilize the HCI financial data to 
estimate reimbursable charges. 
Questions are adapted from the Medical Expenditure Panel Survey-Household 
Component (MEPS-HC) created by 
AHRQ (https://meps.ahrq.gov/survey_comp/hc_survey/2014/DD111214.pdf). 
For comparison assessment, this survey will be administered to an additional 45 patients 
undergoing standard of care hypofractionated radiation who are otherwise not eligible or 
interested in enrollment on this protocol. The Health Care Expense Survey should be 
provided to the patient and completed by the patient 2-8 weeks post standard of care 
hypofractionated radiation. The comparison group will either receive a $20 meal card or 
be reimbursed for a meal up to $20, with provision of a receipt from the date of the study 
visit, after completion of the Health Care Expense Survey. This comparison cohort will 
be case-matched for distance to treatment facility and employment status. 
Collected 2-8 weeks after the completion of radiation: 
• 
Work status prior to breast cancer diagnosis (job for pay or business owner, not   
including work around the house; including work in a family farm or business 
even if unpaid). 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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• 
If working number of days working per week. 
• 
If working, number of hours working per day. 
• 
Profession and the job title. 
• 
Total number of hours spent for each radiation treatment (time from leaving home 
or work to return to home or work). 
• 
Distance from radiation treatment facility from home or work. 
• 
Means of getting to radiation treatment facility (ask if only one modality used or a 
combination, if a combination record number of days for each modality). 
1) 
Car 
- 
Approximate cost for parking 
- 
Did patient drive, was patient driven, or a combination 
2) 
Shuttle 
- 
Approximate cost 
3) 
Public transportation 
- 
Approximate cost per visit 
4) 
Foot 
5) 
Taxi/car service 
- 
Approximate total cost per visit (both ways) 
• 
Number of radiation treatments during which at least one other person 
accompanied patient 
8.5 Safety 
Routine safety and tolerability will be evaluated from the results of reported signs and 
symptoms, scheduled physical examinations, vital sign measurements, and clinical 
laboratory test results. More frequent safety evaluations may be performed if clinically 
indicated or at the discretion of the investigator.  
Physical Examination 
Complete and symptom-directed physical examinations will be performed by a licensed 
physician (or physician’s assistant or nurse practitioner). 
Vital Signs 
Vital signs (blood pressure, respiratory rate, pulse rate and temperature) will be obtained. 
8.6 Stopping Rules 
After 45 patients have been enrolled and followed for 6 months, an interim analysis will 
be performed of all patients with greater than 6 months of follow up. Based on an 
expected RT toxicity rate of ≤10%, if greater than 20% of our patients are found to have 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
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non-acute grade 2 or 3 RT toxicities ≥ 6 months after the completion of radiation, this 
study will be temporarily halted for interim review. Based on an anticipated recurrence 
rate of < 7%, if ≥ 15% of patients have a documented local recurrence, this study will be 
temporarily halted for interim review. Once temporarily halted, a team of experts will 
review the data to determine if it is safe to proceed with the trial or if the trial should be 
discontinued. 
9 STATISTICAL CONSIDERATIONS 
9.1 Primary Objective 
Overall good to excellent photographic cosmetic of the treated compared to the untreated 
breast, 24 months after radiation in ≥ 70% of patients, when compared to baseline pre-
radiation photographs (See Section 2.4 for data on baseline expected risk). Two year 
photographic cosmetic scores will be scored according to the EORTC and NCIC 
photographic assessment system. The primary analysis will be a one sample t-test. The 
null hypothesis will be that the true rate is good to excellent photographic breast cosmetic 
assessment in ≤ 70% of patients. The one sided alternative hypothesis is a good to 
excellent photographic breast cosmetic assessment in > 70% of patients. Assuming the 
true rate is 80% (e.g. exact equivalence), a sample of 87 evaluable subjects will provide 
80% power at the alpha = 0.1 significance level. 
9.2 Secondary Objectives 
 Patient reported outcomes 
 
An important secondary objective will be one of patient reported outcomes. We’ve 
chosen to use the validated Breast-Q breast conservation survey. 
Physical well-being, psychosocial well-being, sexual well-being, satisfaction with breast, 
and satisfaction with overall outcome at 6 months and 24 months after radiation will be 
evaluated. Scores at 6 months and 24 months post-radiation (relative to pre-RT) will be 
summarized and compared to prior published data, utilizing a two-sample t-test with a 
two-sided alternative. 
 Radiation Toxicity:  
Incidence of acute and late radiation complications based on CTCAE 4.0 toxicity. The 
proportion of patients with acute or late radiation complications, will be estimated. Any 
event longer than 3 months will be considered a late effect. 
 
The Clinical Cancer Research (CCR) database or data warehouse (as applicable) will be 
utilized to identify comparison group patients. Fisher’s Exact test will be used to compare 
the rate of toxicity of study participants and comparison groups. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
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 Local and local regional recurrence rate: 
The cumulative incidence of local and local regional recurrence will be estimated using 
the cumulative incidence function treating death as the competing risk. In addition, local 
and local regional recurrence free survival will be summarized using the Kaplan-Meier 
estimators. The Clinical Cancer Research (CCR) database or data warehouse (as 
applicable) will be utilized to identify comparison group patients. The Cox proportional 
hazards model may be used to compare recurrence of study participants and comparison 
groups. Follow up time will be censored at the time of a competing event. 
 Economic Analysis:  
Cost-effectiveness (CE) analysis of hypofractionated radiation versus standard 
fractionation will be explored using cost data and quality adjusted life years (QALYs) (i.e. 
effectiveness side). A societal perspective will be applied for the analysis because the direct 
costs (i.e. resource used) relevant to treatments/intervention, indirect costs (i.e. resource 
lost such as travel time, lost productivity) and side-effects related costs will be considered. 
Cost for the intervention will be measured for the cost of therapy, medications, 
hospitalization and medical visits. Costs for treatments due to side effects will be collected. 
Patient times spent for treatment, travel and lost productivity will be converted to costs 
using year 2022 mean adult US wage rate. Because costs related to the intervention will be 
occurred in different years (for example, 2018~2022), they will be adjusted to year 2022 
US dollars using the medical component of the Consumer Price Index. If charged amounts 
relevant to the treatments are available only (i.e. plan paid amounts or reimbursed amounts 
are not available), they will be converted to costs by using cost-to-charge ratios. We will 
not compare charges or costs between institutions. The quality of life (QoL) measures will 
be based on the BREAST-Q and EQ-5D survey and will be used to calculate Quality 
Adjusted Life Years (QALYs) for the effectiveness side. Because costs and effects will be 
measured over multiple years, both costs and effects will be discounted at the rate of 
3.5%40. We will utilize the EQ-5D and Breast-Q to assist in the QALY analysis.  See 
appendix IV.  Once parameters are computed: 1) mean differences in cost and effect 
between treatments, 2) variances for differences in costs and effects, and 3) covariance 
between effectiveness and cost difference, the incremental cost-effectiveness ratio (ICER) 
or incremental net benefits summarizing the monetary value of the intervention will be 
calculated. 
 
A CE acceptability curve will be used to quantify and graphically depict uncertainty in 
the analysis. To consider uncertainty in parameters, probabilistic sensitivity analysis 
utilizing Monte Carlo simulation (i.e. second-order simulation) will be conducted. To 
reflect the uncertainties in costs and in effects, a gamma distribution for costs and a 
normal distribution for effects will be adopted. And one-way sensitivity analyses will be 
conducted to consider an uncertainty of one parameter at a time over a range of 95% 
confidence interval in cost and effectiveness measures.  
ion
Fractionat
 
Standard
Radiation 
 
onated
Hypofracti
ion
Fractionat
 
Standard
Radiation 
 
onated
Hypofracti
Effect
Effect
Cost
Cost
ICER
−
−
=

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
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10 REGISTRATION GUIDELINES 
Patients must meet all of the eligibility requirements listed in Section 4 prior to 
registration.  
 
Study related screening procedures can only begin once the patient has signed a 
consent form. Patients must not begin protocol treatment prior to registration. 
 
Treatment should start within five working days after registration. 
 
To register eligible patients on study, complete a Clinical Trials Office Patient Registration 
Form and submit to: CTORegistrations@hci.utah.edu.  
11 DATA SUBMISSION SCHEDULE 
The Case Report Forms (CRFs) are a set of (electronic or paper) forms for each patient 
that provides a record of the data generated according to the protocol. CRF’s should be 
created prior to the study being initiated and updated (if applicable) when amendments to 
the protocol are IRB approved. Data capture should be restricted to endpoints and 
relevant patient information required for planned manuscripts. These forms will be 
completed on an on-going basis during the study. The medical records will be source of 
verification of the data. During the study, the CRFs will be monitored for completeness, 
accuracy, legibility and attention to detail by a member of the Research Compliance 
Office. The CRFs will be completed by the Investigator or a member of the study team as 
listed on the Delegation of Duties Log. The data will be reviewed no less than annually 
by the Data and Safety Monitoring Committee. The Investigator will allow the Data and 
Safety Monitoring Committee or Research Compliance Office personnel access to the 
patient source documents, clinical supplies dispensing and storage area, and study 
documentation for the above-mentioned purpose. The Investigator further agrees to assist 
the site visitors in their activities. 
12 ETHICAL AND REGULATORY CONSIDERATIONS 
12.1 Informed consent  
Informed consent will be obtained from all research participants prior to performing 
any study procedures using the most recent IRB approved version. Patients who 
volunteer to complete the Health Care Expense Survey must be provided with the Informed 
Consent Letter prior to completing the questionnaire.     
12.2 Institutional Review 
Study will be approved by the Institutional Review Board of University of Utah. 
12.3  Data and Safety Monitoring Plan 
A Data and Safety Monitoring Committee (DSMC) is established at Huntsman 
Cancer Institute (HCI) and approved by the NCI to assure the well-being of patients 
enrolled on Investigator Initiated Trials that do not have an outside monitoring 
review. Roles and responsibilities of the DSMC are set forth in the NCI approved 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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plan. The activities of this committee include a quarterly review of adverse events 
including SAEs, important medical events, significant revisions or amendments to the 
protocol, and approval of cohort/dose escalations. If the DSMC and/or the PI have 
concerns about unexpected safety issues, the study will be stopped and will not be 
resumed until the issues are resolved. The DSMC also reviews and approves audit 
reports generated by the Research Compliance Office.  
All phase II studies are reviewed by the full committee at each quarterly DSMC 
meeting. This includes a review of all serious adverse events (SAEs) occurring in 
patients treated at HCI or its affiliates as well as all grade 3 or greater toxicities for 
patients on treatment and within 30 day follow-up window (only if possibly, probably 
or definitely related).  
12.4 Adverse Events / Serious Adverse Events 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse 
Events) Version 4.0 for AE and SAE reporting.  
 Adverse Events (AE) 
An adverse event is the appearance or worsening of any undesirable sign, 
symptom, or medical condition occurring after starting the study treatment even if 
the event is not considered to be related to study treatment. For the purposes of 
this study, the terms toxicity and adverse event are used interchangeably. Medical 
conditions/diseases present before starting study treatment are only considered 
adverse events if they worsen after starting study treatment. Abnormal laboratory 
values or test results constitute adverse events only if they induce clinical signs or 
symptoms, are considered clinically significant, or require therapy. Events that 
occur ≤3 months after radiation will be considered early toxicities while events 
occurring or persisting ≥ 6 months will be considered late toxicities. 
 
Adverse events will be recorded after the start of radiation therapy. All events, 
even grade 1 will be recorded. AEs recorded until year 3. 
 
Information about all adverse events, whether volunteered by the subject, 
discovered by investigator questioning, or detected through physical examination, 
laboratory test or other means, will be collected and recorded and followed as 
appropriate. 
 
The occurrence of adverse events should be sought by non-directive questioning 
of the patient at each visit or phone contact during the study. Adverse events also 
may be detected when they are volunteered by the patient during or between visits 
or through physical examination, laboratory test, or other assessments. As far as 
possible, each adverse event should be evaluated to determine: 
1. the severity grade based on CTCAE v.4 (grade 1-5) 
2. its relationship to the study treatment (definite, probable, possible, 
unlikely, not related)  
3. its duration (start and end dates or if continuing at final exam) 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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4. action taken (no action taken; study treatment dosage adjusted/temporarily 
interrupted; study treatment permanently discontinued due to this adverse 
event; concomitant medication taken; non-drug therapy given; 
hospitalization/prolonged hospitalization) 
5. whether it constitutes an SAE 
 
All adverse events will be treated appropriately. Such treatment may include 
changes in study treatment as listed in the dose modification section of this 
protocol (see section 6 for guidance). Once an adverse event is detected, it should 
be followed until its resolution, and assessment should be made at each visit (or 
more frequently, if necessary) of any changes in severity, the suspected 
relationship to the study treatment, the interventions required to treat it, and the 
outcome. 
 
Information about common side effects already known about the treatment is 
discussed in section 2. This information will be included in the patient informed 
consent and will be discussed with the patient during the study as needed. 
 
All adverse events will be immediately recorded in the patient research chart.  
 Serious Adverse Event (SAE) 
Information about all serious adverse events will be collected and recorded. A 
serious adverse event is an undesirable sign, symptom or medical condition 
which: 
• is fatal or life-threatening 
• results in persistent or significant disability/incapacity 
• is medically significant, i.e., defined as an event that jeopardizes the 
patient or may require medical or surgical intervention to prevent one of 
the outcomes listed above 
• causes congenital anomaly or birth defect 
• requires inpatient hospitalization or prolongation of existing 
hospitalization, unless hospitalization is for: 
o routine treatment or monitoring of the studied indication, not 
associated with any deterioration in condition (procedures such as 
central line placements, paracentesis, pain control) 
o elective or pre-planned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since the 
start of study treatment 
o treatment on an emergency outpatient basis for an event not fulfilling 
any of the definitions of a SAE given above and not resulting in 
hospital admission 
o social reasons and respite care in the absence of any deterioration in 
the patient’s general condition 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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Serious adverse events will be recorded after the start of radiation therapy until 
year 3. 
 
Any death from any cause while a patient is receiving treatment on this protocol 
or up to 30 days after the last dose of protocol treatment, or any death which 
occurs more than 30 days after protocol treatment has ended but which is felt to 
be treatment related, must be reported. 
 
Toxicities which fall within the definitions listed above must be reported as an SAE 
regardless if they are felt to be treatment related or not. Toxicities unrelated to 
treatment that do NOT fall within the definitions above, must simply be 
documented as AEs in the patient research chart.  
12.5 SAE Reporting Requirements 
SAEs must be reported to the DSMC, the FDA, and the IRB, according to the 
requirements described below: 
 
A MedWatch 3500A form must be completed and submitted to HCI-RCO@utah.edu 
as soon as possible, but no later than 1 business day of first knowledge or notification 
of event. 
 
DSMC Notifications: 
• An HCI Research Compliance Officer (RCO) will process and submit the 
MedWatch form to the proper DSMC member as necessary for this study. 
• The RCO will summarize and present all reported SAEs according to the Data 
and Safety Monitoring Plan at the quarterly DSMC meeting. 
FDA Notifications: 
• Adverse events occurring during the course of a clinical study that meet the 
following criteria will be promptly reported to the FDA: 
• Serious 
• Unexpected 
• Definitely, Probably or Possibly Related to the investigational treatment. 
• Fatal or life-threatening events that meet the criteria above will be reported 
within 7 calendar days after first knowledge of the event by the investigator; 
followed by as complete a report as possible within 8 additional calendar 
days. 
• All other events that meet the criteria above will be reported within 15 
calendar days after first knowledge of the event by the investigator. 
• The RCO will review the MedWatch report for completeness, accuracy and 
applicability to the regulatory reporting requirements. 
• The RCO will ensure the complete, accurate and timely reporting of the event 
to the FDA. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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• The MedWatch report will be submitted to the FDA through the voluntary 
reporting method by the Regulatory Coordinator. 
 
IRB Notification: 
• Events meeting the University of Utah IRB reporting requirements will be 
reported per local guidelines within 10 working days. 
• *MedWatch 3500A form can be found on line at the FDA website.  
12.6 Reporting of Pregnancy  
Although pregnancy is not considered an adverse event, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject, 
including the pregnancy of a male subjects’ female partner as an SAE. Pregnancies or 
lactation that occurs during the course of the trial or with 30 days of completing the 
trial or starting another new anticancer therapy, whichever is earlier, must be reported 
to the DSMC, IRB, FDA, and the sponsor as applicable. All subjects and female 
partners who become pregnant must be followed to the completion/termination of the 
pregnancy. Pregnancy outcomes of spontaneous abortion, missed abortion, fetal 
death, intrauterine death, miscarriage and stillbirth must be reported as serious events.  
12.7 Protocol Amendments 
Any amendments or administrative changes in the research protocol during the 
period, for which the IRB approval has already been given, will not be initiated 
without submission of an amendment for IRB review and approval.  
 
These requirements for approval will in no way prevent any immediate action 
from being taken by the investigator in the interests of preserving the safety of 
all patients included in the trial.  
12.8 Protocol Deviations 
A protocol deviation (or violation) is any departure from the defined procedures and 
treatment plans as outlined in the protocol version submitted and previously approved 
by the IRB. Protocol deviations have the potential to place participants at risk and can 
also undermine the scientific integrity of the study thus jeopardizing the justification 
for the research. Protocol deviations are unplanned and unintentional events.  
 
Because some protocol deviations pose no conceivable threat to participant safety or 
scientific integrity, reporting is left to the discretion of the PI within the context of the 
guidelines below. The IRB requires the prompt reporting of protocol deviations 
which are: 
• 
Exceptions to eligibility criteria. 
• 
Intended to eliminate apparent immediate hazard to a research participant 
or  
• 
Harmful (caused harm to participants or others, or place them at 
increased risk of harm - including physical, psychological, economic, or 
social harm), or  

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
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• 
Possible serious or continued noncompliance  
12.9 FDA Annual Reporting  
This study is IND exempt therefore there are no annual reporting requirements to 
the FDA.  
12.10 Clinical Trials Data Bank  
      
The study will be registered on http://clinicaltrials.gov and the NCI CTRP    
      
(Clinical Trials Reporting Program) by the Clinical Trials Office. 
12.11 Record Keeping 
Per 21 CFR 312.57, Investigator records shall be maintained for a period of 2 years 
following the date a marketing application is approved; or, if no application is filed or 
the application is not approved, until 2 years after the investigation is discontinued 
and the FDA is notified. 
13 BIBLIOGRAPHY 
1. 
Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in 
the extent of surgery for early breast cancer on local recurrence and 15-year 
survival: an overview of the randomised trials. Lancet 2005;366:2087-106. 
2. 
Early Breast Cancer Trialists' Collaborative G. Effects of radiotherapy and 
surgery in early breast cancer. An overview of the randomized trials. The New 
England journal of medicine 1995;333:1444-55. 
3. 
Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without 
radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and 
mortality. J Natl Cancer Inst 2004;96:115-21. 
4. 
Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized 
trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation 
for the treatment of invasive breast cancer. The New England journal of 
medicine 2002;347:1233-41. 
5. 
van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a 
randomized trial comparing breast-conserving therapy with mastectomy: 
European Organization for Research and Treatment of Cancer 10801 trial. J Natl 
Cancer Inst 2000;92:1143-50. 
6. 
Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a 
randomized study comparing breast-conserving surgery with radical mastectomy 
for early breast cancer. The New England journal of medicine 2002;347:1227-
32. 
7. 
Frandsen J, Ly D, Cannon G, et al. In the Modern Treatment Era, Is Breast 
Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of 
Age? A Multi-Institution Study. International journal of radiation oncology, 
biology, physics 2015;93:1096-103. 
8. 
Effects of radiotherapy and of differences in the extent of surgery for early breast 
cancer on local recurrence and 15-year survival: an overview of the randomised 
trials. The Lancet 2005;366:2087-106. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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9. 
Owen JR, Ashton A, Bliss JM, et al. Effect of radiotherapy fraction size on 
tumour control in patients with early-stage breast cancer after local tumour 
excision: long-term results of a randomised trial. The lancet oncology 
2006;7:467-71. 
10. 
Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast 
Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of 
early breast cancer: 10-year follow-up results of two randomised controlled 
trials. The lancet oncology 2013;14:1086-94. 
11. 
Group ST, Bentzen SM, Agrawal RK, et al. The UK Standardisation of Breast 
Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment 
of early breast cancer: a randomised trial. Lancet 2008;371:1098-107. 
12. 
Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation 
schedules after lumpectomy for women with lymph node-negative breast cancer. 
J Natl Cancer Inst 2002;94:1143-50. 
13. 
Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated 
radiation therapy for breast cancer. The New England journal of medicine 
2010;362:513-20. 
14. 
Romestaing P, Lehingue Y, Carrie C, et al. Role of a 10-Gy boost in the 
conservative treatment of early breast cancer: results of a randomized clinical 
trial in Lyon, France. J Clin Oncol 1997;15:963-8. 
15. 
Vrieling C, Collette L, Fourquet A, et al. The influence of the boost in breast-
conserving therapy on cosmetic outcome in the EORTC "boost versus no boost" 
trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European 
Organization for Research and Treatment of Cancer. Int J Radiat Oncol Biol 
Phys 1999;45:677-85. 
16. 
Cante D, Franco P, Sciacero P, et al. Hypofractionated whole-breast radiotherapy 
and concomitant boost after breast conservation in elderly patients. Tumori 
2016;102:196-202. 
17. 
Franco P, Zeverino M, Migliaccio F, et al. Intensity-modulated and 
hypofractionated simultaneous integrated boost adjuvant breast radiation 
employing statics ports of tomotherapy (TomoDirect): a prospective phase II 
trial. Journal of cancer research and clinical oncology 2014;140:167-77. 
18. 
Ghannam AA, Khedr RA. An accelerated hypofractionated schedule with a daily 
concomitant boost after breast conservation surgery: the feasibility and toxicity. 
Journal of the Egyptian National Cancer Institute 2016;28:39-44. 
19. 
Mondal D, Julka PK, Sharma DN, et al. Accelerated hypofractionated adjuvant 
whole breast radiation with simultaneous integrated boost using volumetric 
modulated arc therapy for early breast cancer: A phase I/II dosimetric and 
clinical feasibility study from a tertiary cancer care centre of India. Journal of the 
Egyptian National Cancer Institute 2017;29:39-45. 
20. 
Freedman GM, White JR, Arthur DW, Allen Li X, Vicini FA. Accelerated 
fractionation with a concurrent boost for early stage breast cancer. Radiotherapy 
and oncology : journal of the European Society for Therapeutic Radiology and 
Oncology 2013;106:15-20. 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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21. 
Group FT, Agrawal RK, Alhasso A, et al. First results of the randomised UK 
FAST Trial of radiotherapy hypofractionation for treatment of early breast 
cancer (CRUKE/04/015). Radiother Oncol 2011;100:93-100. 
22. 
Bekelman JE, Sylwestrzak G, Barron J, et al. Uptake and costs of 
hypofractionated vs conventional whole breast irradiation after breast conserving 
surgery in the United States, 2008-2013. Jama 2014;312:2542-50. 
23. 
Haffty BG, Buchholz TA. Hypofractionated breast radiation: preferred standard 
of care? The lancet oncology 2013;14:1032-4. 
24. 
Rajagopalan MS, Flickinger JC, Heron DE, Beriwal S. Changing practice 
patterns for breast cancer radiation therapy with clinical pathways: An analysis 
of hypofractionation in a large, integrated cancer center network. Practical 
radiation oncology 2015;5:63-9. 
25. 
Wang EH, Mougalian SS, Soulos PR, et al. Adoption of Hypofractionated 
Whole-Breast Irradiation for Early-Stage Breast Cancer: A National Cancer Data 
Base Analysis. Int J Radiat Oncol Biol Phys 2014. 
26. 
Fowler J. The linear-quadratic formula and progress in fractionated radiotherapy. 
British Journal of Radiology 1989;62:679-94. 
27. 
Matthews J, Meeker B, Chapman J. Response of human tumor cell lines in vitro 
to fractionated irradiation. International Journal of Radiation Oncology Biology 
and Physics 1989;16:133-8. 
28. 
Steel G, Deacon J, Duschesne G. The dose-rate effect in human tumour cells. 
Radiotherapy and Oncology 1987;9:299-310. 
29. 
Falchook AD, Green R, Knowles ME, et al. Comparison of Patient- and 
Practitioner-Reported Toxic Effects Associated With Chemoradiotherapy for 
Head and Neck Cancer. JAMA otolaryngology-- head & neck surgery 2016. 
30. 
Kanatas A, Velikova G, Roe B, et al. Patient-reported outcomes in breast 
oncology: a review of validated outcome instruments. Tumori 2012;98:678-88. 
31. 
Oberguggenberger A, Hubalek M, Sztankay M, et al. Is the toxicity of adjuvant 
aromatase inhibitor therapy underestimated? Complementary information from 
patient-reported outcomes (PROs). Breast Cancer Res Treat 2011;128:553-61. 
32. 
Koslow S, Pharmer LA, Scott AM, et al. Long-term patient-reported satisfaction 
after contralateral prophylactic mastectomy and implant reconstruction. Annals 
of surgical oncology 2013;20:3422-9. 
33. 
Rosson GD, Shridharani SM, Magarakis M, et al. Quality of life before 
reconstructive breast surgery: A preoperative comparison of patients with 
immediate, delayed, and major revision reconstruction. Microsurgery 
2013;33:253-8. 
34. 
Fuzesi S, Cano SJ, Klassen AF, Atisha D, Pusic AL. Validation of the electronic 
version of the BREAST-Q in the army of women study. Breast 2017;33:44-9. 
35. 
Pusic AL, Klassen AF, Scott AM, Klok JA, Cordeiro PG, Cano SJ. Development 
of a new patient-reported outcome measure for breast surgery: the BREAST-Q. 
Plastic and reconstructive surgery 2009;124:345-53. 
36. 
Olivotto IA, Whelan TJ, Parpia S, et al. Interim cosmetic and toxicity results 
from RAPID: a randomized trial of accelerated partial breast irradiation using 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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three-dimensional conformal external beam radiation therapy. J Clin Oncol 
2013;31:4038-45. 
37. 
Vrieling C, Collette L, Bartelink E, et al. Validation of the methods of cosmetic 
assessment after breast-conserving therapy in the EORTC "boost versus no 
boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. 
European Organization for Research and Treatment of Cancer. Int J Radiat 
Oncol Biol Phys 1999;45:667-76. 
38. 
Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or 
without irradiation in women age 70 years or older with early breast cancer: 
long-term follow-up of CALGB 9343. J Clin Oncol 2013;31:2382-7. 
39. 
Mundy LR, Homa K, Klassen AF, Pusic AL, Kerrigan CL. Breast Cancer and 
Reconstruction: Normative Data for Interpreting the BREAST-Q. Plastic and 
reconstructive surgery 2017;139:1046e-55e. 
40.  
National Institute for Health and Care Excellence (NICE), Guide to the methods 
of technology appraisal, 2013. Available at 
http://www.nice.org.uk/article/pmg9/chapter/1-Introduction 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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14 APPENDICES 
Appendix I: 
Breast-Q Breast Conservation Module 
 
 
NOVEMBER 
 
BREAST-QTM- BREAST CONSERVING THERAPY 
MODULE (POSTOPERATIVE) 2.0 
 
Patient Study ID: 103976-01-___ ___ ___ 
 
Patient Initials: ___ ___ ___ 
 
Date of Completion: ____ / ____ / ______ 
 
All applicable Breast Conserving modules should be completed at the indicated time points in 
the study calendar.  
 
 
• 
Satisfaction with Breasts 
• 
Adverse Effects of Radiation (to be completed post radiation only) 
• 
Psychosocial Well-Being 
• 
Physical Well-Being: Chest 
• 
Sexual Well-Being 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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BREAST-QTM - BREAST CONSERVING THERAPY MODULE (POSTOPERATIVE) 2.0 
SATISFACTION WITH BREASTS 
 
The following questions are about your breasts and your breast cancer treatment (by 
treatment, we mean lumpectomy with or without radiation).  If you have had a 
lumpectomy and radiation of both breasts, answer these questions thinking of the 
breast you are least satisfied with.  
 
With your breasts in mind, in the past week, how satisfied or dissatisfied have 
you been with: 
 
 
 
Very 
Dissatisfied 
Somewhat 
Dissatisfied 
Somewhat  
Satisfied 
Very  
Satisfied 
a. 
How you look in the mirror clothed? 
1 
2 
3 
4 
b. 
The shape of your lumpectomy breast when you 
are wearing a bra? 
1 
2 
3 
4 
c. 
How normal you feel in your clothes? 
1 
2 
3 
4 
d. 
Being able to wear clothing that is more fitted? 
1 
2 
3 
4 
e. 
How your lumpectomy breast sits/hangs? 
1 
2 
3 
4 
f. 
How smoothly shaped your lumpectomy breast 
looks? 
1 
2 
3 
4 
g. 
The contour (outline) of your lumpectomy 
breast? 
1 
2 
3 
4 
h. 
How equal in size your breasts are to each other? 
1 
2 
3 
4 
i. 
How normal your lumpectomy breast looks? 
1 
2 
3 
4 
j. 
How much your breasts look the same? 
1 
2 
3 
4 
k. 
How you look in the mirror unclothed? 
1 
2 
3 
4 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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BREAST-QTM - BREAST CONSERVING THERAPY MODULE (POSTOPERATIVE) 2.0 ADVERSE 
EFFECTS OF RADIATION 
 
If you have had radiation on both breasts, answer these questions thinking of the breast 
you are least satisfied with. 
 
With your radiated breast(s) in mind, in the past week, how much have you been 
bothered by: 
 
Not at 
all 
A little 
A lot 
a. Your radiated breast skin looking different (e.g. too dark or too light)? 
1 
2 
3 
b. Marks on your breast skin caused by radiation (e.g. small visible blood 
vessels)? 
1 
2 
3 
c. Your radiated breast skin feeling dry? 
1 
2 
3 
d. Your radiated breast skin feeling sore (sensitive) when touched (e.g. changes 
in water temperature when you bathe/shower)? 
1 
2 
3 
e. Your radiated breast skin feeling unnaturally thick (rough, tough) when you 
touch it? 
1 
2 
3 
f. Your radiated breast skin feeling irritated by clothing that you wear? 
1 
2 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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BREAST-QTM - BREAST CONSERVING THERAPY MODULE (POSTOPERATIVE) 2.0 
PSYCHOSOCIAL WELL-BEING 
 
With your breasts in mind, in the past week, how often have you felt: 
 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
a. Confident in a social setting? 
1 
2 
3 
4 
5 
b. Emotionally able to do the things that you want to do? 
1 
2 
3 
4 
5 
c. Emotionally healthy? 
1 
2 
3 
4 
5 
d. Of equal worth to other women? 
1 
2 
3 
4 
5 
e. Self-confident? 
1 
2 
3 
4 
5 
f. Feminine in your clothes? 
1 
2 
3 
4 
5 
g. Accepting of your body? 
1 
2 
3 
4 
5 
h. Normal?  
1 
2 
3 
4 
5 
i. 
Like other women? 
1 
2 
3 
4 
5 
j. Attractive? 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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BREAST-QTM - BREAST CONSERVING THERAPY MODULE (POSTOPERATIVE) 2.0 
PHYSICAL WELL-BEING: CHEST 
 
In the past week, how often have you experienced: 
 
 
None of 
the time 
Some of 
the time 
All of  
the time 
a. Difficulty lifting or moving your arms? 
1 
2 
3 
b. Difficulty sleeping because of discomfort in your breast area? 
1 
2 
3 
c. Tightness in your breast area? 
1 
2 
3 
d. Pulling in your breast area?  
1 
2 
3 
e. Tenderness in your breast area? 
1 
2 
3 
f. Sharp pains in your breast area? 
1 
2 
3 
g. Aching feeling in your breast area? 
1 
2 
3 
h. Difficulty laying on the side of your lumpectomy breast? 
1 
2 
3 
i. Swelling of the arm (lymphedema) on the side(s) that you had your 
breast surgery? 
1 
2 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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BREAST-QTM - BREAST CONSERVING THERAPY MODULE (POSTOPERATIVE) 2.0 SEXUAL 
WELL-BEING 
 
Thinking of your sexuality, since your lumpectomy surgery, how often do you generally feel: 
 
 
None of 
the time 
A little 
of the 
time 
Some of 
the time 
Most of 
the time 
All of 
the time 
a. 
Sexually attractive in your clothes? 
1 
2 
3 
4 
5 
b. 
Comfortable/at ease during sexual activity? 
1 
2 
3 
4 
5 
c. 
Confident sexually? 
1 
2 
3 
4 
5 
d. 
Satisfied with your sex-life? 
1 
2 
3 
4 
5 
e. 
Confident sexually about how your breast(s) look 
when unclothed? 
1 
2 
3 
4 
5 
f. 
Sexually attractive when unclothed? 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Appendix II – Health Care Expense Survey 
 
 
 
NOVEMBER 
 
Health Care Expense Survey 
 
Patient Study ID: 103976-01-____ ____ ____ 
 
Patient Initials: ____ ____ ____ 
 
Date of Completion: ____ / ____ / ______ 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Health Care Expense Survey 
 
Before you were diagnosed with breast cancer, did you do paid or unpaid work outside 
the home?  
Yes     
No 
 
If you worked outside the home, which of the following best applies to you? 
Paid work outside the home 
Yes     
No 
Unpaid work outside the home 
Yes     
No (including work in a family farm or 
business). 
Self-employed / business owner 
Yes     
No 
 
If you worked outside the home:  
How many days per week did you work? __ (days) 
How many hours per day did you work? __ __ (hours) 
What is your profession? 
_____________________________________________________ 
In what industry do you work?  
________________________________________________ 
What is / was your job title? 
___________________________________________________ 
 
NOTE: This section is designed to capture the out of pocket expenses associated with 
radiation therapy. 
How many hours were spent in total for each radiation treatment (time from leaving 
home/other accommodation or work to return to home/other accommodation or work)?  
__ __ (hours) 
What is the distance from the radiation treatment facility from home/other 
accommodation or work? __ __ __ (miles) 
 
Did you commute daily to radiation treatment from your home? 
Yes     
No 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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(If yes), method of transport used to get to the radiation therapy facility (Check all that 
apply)  
 
Car   
Yes     
No  
 
(If yes) approximate cost for parking per visit $__ __.__ __ 
 
Did you drive yourself? 
Yes     
No 
 
Were you driven? 
Yes     
No 
 
 
Was it a combination of driving yourself or being driven  
Yes     
No 
 
Shuttle  
Yes     
No  
 
(If yes) Approximate cost per visit $__ __.__ __ 
Public transport 
Yes     
No  
 
(If yes) Approximate cost per visit $__ __.__ __ 
On foot 
Yes     
No  
Taxi/car service 
Yes     
No 
(If yes) Approximate cost per visit (both ways) $__ __ __    
 
(If no), which of the follow apply (check one): 
 
  I was in a health care facility during radiation 
 
  I was living with a friend/family member during radiation (answer the 
commuting questions above) 
  I stayed hotel, apartment, or similar facility during radiation (answer the 
commuting questions above) 
If hotel, apartment or similar facility, estimated cost of lodging during your 
radiation treatment $__ __ __ __   
 
Number of radiation treatments during which at least one other person accompanied 
patient __ __ 
Number of visits to radiation treatment facility since completing radiation therapy (follow 
up visits) __ __ 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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From the 1st day of starting radiation, until 40 days after the completion of radiation: 
Number of days the patient was unable to go to work at all __ __ 
Number of days the patient went to work part-time __ __ 
If part time, number of hours reduced from typical work day __ __ 
Estimate child care costs due to radiation therapy $__ , __ __ __   
Estimate wages lost due to radiation therapy $__ __ , __ __ __ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Appendix III - HEALTH CARE EXPENSE DIARY FOR SURVEY COMPLETION 
 
Use this diary to record your health care-related expenses from the time you start 
radiation therapy until 6 to 10 weeks after you have completed radiation therapy. A copy 
of the survey questions is included with this diary for your reference. 
 
Date 
Type of expense 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Appendix IV – EQ-5D-3L  
 
 
NOVEMBER 
 
EQ-5D-3L 
 
Patient Study ID: 103976-01-____ ____ ____ 
 
Patient Initials: ____ ____ ____ 
 
Date of Completion: ____ / ____ / ______ 
 
 

Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Protocol name: NOVEMBER (Novem- (9), BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for 
early stage breast cancer. 
Version Date: 23NOV2021 
Principal Investigator: Matthew M. Poppe, MD 
 
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Appendix V – ECOG/KPS Conversion 
ECOG PERFORMANCE STATUS 
KARNOFSKY PERFORMANCE STATUS 
0—Fully active, able to carry on all pre-disease 
performance without restriction 
100—Normal, no complaints; no evidence of 
disease  
 
90—Able to carry on normal activity; minor signs 
or symptoms of disease 
1—Restricted in physically strenuous activity but 
ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work 
80—Normal activity with effort, some signs or 
symptoms of disease  
 
70—Cares for self but unable to carry on normal 
activity or to do active work 
2—Ambulatory and capable of all selfcare but unable to 
carry out any work activities; up and about more than 50% 
of waking hours 
60—Requires occasional assistance but is able 
to care for most of personal needs  
 
50—Requires considerable assistance and 
frequent medical care 
3—Capable of only limited selfcare; confined to bed or 
chair more than 50% of waking hours 
40—Disabled; requires special care and 
assistance  
 
30—Severely disabled; hospitalization is 
indicated although death not imminent 
4—Completely disabled; cannot carry on any selfcare; 
totally confined to bed or chair 
20—Very ill; hospitalization and active 
supportive care necessary  
 
10—Moribund 
5—Dead 
0—Dead 
*Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, 
ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205. 
**Zubrod C, et al. Appraisal of methods for the study of chemotherapy in man: Comparative therapeutic 
trial of nitrogen mustard and thiophosphoramide. Journal of Chronic Diseases; 1960:11:7-33.