Mometasone Furoate 0.1% Versus Eucerin on Moderate to Severe Skin Toxicities in Breast Cancer Patients Receiving Postmastectomy Radiation:A Randomized Trial, Double Blind Trial
Phase: PHASE3
Conditions: Invasive Breast Cancer
Sponsor: Memorial Sloan Kettering Cancer Center

 
 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Mometasone Furoate 0.1% versus Eucerin on Moderate to Severe Skin Toxicities in 
Breast Cancer Patients Receiving Postmastectomy Radiation: A Randomized, 
Phase III, double-blind Trial 
 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL 
 
 
Principal Investigator/Department: 
Molly Olm-Shipman, R.N. 
Nursing 
Co-Principal 
Investigator(s)/Department: 
Alice Ho, M.D. 
Mario Lacouture, M.D. 
Daphna Gelblum, M.D. 
Radiation Oncology 
Medicine/Dermatology 
Radiation: Commack 
Investigator(s)/Department: 
Beryl McCormick, M.D. 
Simon Powell, M.D., Ph.D. 
Christopher Barker, M.D. 
Gaorav Gupta, M.D., Ph.D. 
Zhigang Zhang, Ph.D. 
Patricia Demarco, R.N. 
Regina Pineda, R.N. 
Melissa O’Dell, R.N. 
Lorraine Kipel, R.N. 
Kathleen Logan, R.N. 
Amanda Hill, R.N. 
Elyse Berrett, R.N. 
Mark Klang, PhD 
Radiation Oncology 
Radiation Oncology 
Radiation Oncology 
Radiation Oncology 
Epidemiology & Biostatistics 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Pharmacy 
Consenting 
Professional(s)/Department: 
Molly Olm-Shipman, R.N. 
Alice Ho, M.D. 
Beryl McCormick, M.D. 
Simon Powell, M.D., Ph.D. 
Christopher Barker, M.D. 
Gaorav Gupta, M.D, Ph.D. 
Patricia Demarco, R.N. 
Regina Pineda, R.N. 
Melissa O’Dell, R.N. 
Lorraine Kipel, R.N. 
Kathleen Logan, R.N. 
Amanda Hill, R.N. 
Elyse Berrett, R.N. 
Nursing 
Radiation Oncology 
Radiation Oncology 
Radiation Oncology 
Radiation Oncology 
Radiation Oncology 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
 
 
 
 
 
Amended: 08/07/13 
Page 1 of 20 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 2 of 20 
Amended: 08/07/13 
 
 
Table of Contents 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ......................................................................... 4 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .................................................................................. 4 
 
3.0 
BACKGROUND AND RATIONALE ....................................................................................... 5 
 
3.1 Benefit of Postmastectomy Radiation ............................................................................................ 5 
 
3.2 Radiation-Induced Dermatitis ....................................................................................................... 5 
 
3.3 Evidence for Topical Agents’ Prevention and Treatment of Radiation-Induced Dermatitis ................... 6 
 
3.4 Patient-Reported Outcomes and Provider Assessment Tools for Radiation Dermatitis ......................... 8 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION................................................................ 8 
 
4.1 
Design................................................................................................................................. 8 
 
4.2 
Intervention ......................................................................................................................... 8 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................... 9 
 
5.1 Mometasone Furoate ................................................................................................................... 9 
 
5.2 Eucerin Original cream ................................................................................................................ 9 
 
5.3 Skindex-16 Assessment Module ................................................................................................... 9 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ............................................................................... 9 
 
6.1 
Subject Inclusion Criteria..................................................................................................... 9 
 
6.2 
Subject Exclusion Criteria ................................................................................................. 10 
 
7.0 
RECRUITMENT PLAN ......................................................................................................... 10 
 
8.0 
PRETREATMENT EVALUATION ........................................................................................ 10 
 
9.0 
TREATMENT/INTERVENTION PLAN.................................................................................. 11 
 
9.2 Chest Wall Radiotherapy ........................................................................................................... 11 
 
10.0 EVALUATION DURING TREATMENT/INTERVENTION ..................................................... 12 
 
11.0 TOXICITIES/SIDE EFFECTS ............................................................................................... 13 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ......................... 13 
 
12.1 Assessment of Primary Objective .............................................................................................. 13 
 
12.2 Assessment of Secondary Objectives ......................................................................................... 13 
 
13.0 CRITERIA FOR REMOVAL FROM STUDY ......................................................................... 13 
 
14.0 BIOSTATISTICS .................................................................................................................. 14 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES... 14 
 
15.1 Research Participant Registration ..................................................................................... 14 
 
15.2 Randomization .................................................................................................................. 15 
 
16.0 DATA MANAGEMENT ISSUES ........................................................................................... 15 
 
16.1 Quality Assurance ............................................................................................................. 15 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 3 of 20 
Amended: 08/07/13 
 
 
16.2 Data and Safety Monitoring ............................................................................................... 16 
 
17.0 PROTECTION OF HUMAN SUBJECTS .............................................................................. 16 
 
17.1 Privacy .............................................................................................................................. 16 
 
17.2 Serious Adverse Event (SAE) Reporting ........................................................................... 17 
 
18.0 INFORMED CONSENT PROCEDURES .............................................................................. 17 
 
19.0 REFERENCES ..................................................................................................................... 18 
 
20.0 APPENDICES ...................................................................................................................... 20 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 4 of 20 
Amended: 08/07/13 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
This is a double-blinded, randomized trial. Its purpose is to compare the steroid cream 
mometasone furoate 0.1% (MF), with standard emollient skin care, Eucerin, on the prevention of 
grade 2 or higher skin toxicities in breast cancer patients receiving PMRT to the chest wall and 
regional lymph nodes. Patients will be stratified based on two variables: the presence of a 
reconstruction in order to achieve a balanced population of patients being treated with either 
photon or electron beams, and body mass index (BMI <30 vs ≥30). 
 
Female breast cancer patients who have received mastectomy + axillary surgery and will undergo 
postmastectomy radiation (PMRT) at our institution are eligible for this study. Enrollment of 143 
patients is expected to take place over 3 years. 
 
Skin toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) v.4 scale 
will be scored by evaluating RN or MD . Assessments will be completed at baseline, weekly 
during radiation therapy (RT), and 10-14 days following the completion of RT. Patient-reported 
skin symptoms will also be assessed at baseline, at week 5 of RT, and 10-14 days following 
completion of RT. 
 
Screening 
Randomization 
Pre-RT 
Weekly 
During RT (5 
weeks, 50 Gy) 
Follow-up 
(10-14 Days 
Post-RT) 
143 breast cancer 
patients status post 
mastectomy + axillary 
surgery, ± 
chemotherapy 
•  Stratifications: 
–Reconstruction 
Yes vs no 
–Body Mass Index 
<30 vs ≥30 
Eucerin BID 
or 
mometasone 
furoate 0.1% BID 
• Baseline H and P 
• Baseline Provider 
Skin Toxicity 
Assessment 
• Baseline Skindex- 
16 questionnaire 
• Patient education 
on topical cream 
usage 
• Weekly status 
checks 
• Weekly skin 
cream 
compliance 
assessed 
• Weekly 
Provider Skin 
Toxicity 
• Skindex 
Questionnaire 
during Week 5 
of RT 
• Skin cream 
compliance 
assessed 
• Provider Skin 
Toxicity 
Assessment 
• Skindex-16 
questionnaire 
 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary Objective 
• 
To determine if MF, as compared to Eucerin, is effective in preventing grade 2 or higher 
radiation dermatitis, particularly moist desquamation and/or moderate to brisk erythema 
in women receiving PMRT 
Secondary Objectives 
• 
To compare patient-reported skin symptoms between interventions 
• 
To determine maximum reported skin toxicity and the time to occurrence 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 5 of 20 
Amended: 08/07/13 
 
 
3.0 
BACKGROUND AND RATIONALE 
 
3.1 Benefit of Postmastectomy Radiation 
 
 
PMRT is an essential component of treatment for locally advanced breast cancer. The publication 
of the Oxford Overview meta-analyses of randomized clinical trials in 2005 showed that, 
compared with surgery alone, the addition of PMRT after mastectomy both reduced the rate of 
local cancer recurrence and improved 15-year breast cancer mortality by 5% (Clarke, Collins et 
al. 2005). Although the clinical benefits of PMRT are well established, there is a paucity of data 
available on the acute toxicities of PMRT, namely, skin toxicities. The majority of studies that 
examine quality of life after mastectomy focus primarily on cosmetic and psychosocial issues. 
 
3.2 Radiation-Induced Dermatitis 
 
 
A variety of patient and treatment-related factors such as fractionation schedules, dose, size of 
the treatment field, concurrent chemotherapy, use of bolus or other beam-modifying devices, 
and individual genetic variation can affect the intensity of the skin reaction to radiation 
(Tucker, Turesson et al. 1992). The majority of data available regarding side effects are 
generated from patients receiving radiation to the intact breast, not the chest wall after 
mastectomy. Side effects are generally categorized as acute if occurring during or within 6 
weeks of radiation treatment and late if occurring >6 weeks after completion of treatment. A 
common acute toxicity is dermatitis within the irradiated volume. Typically, the skin becomes 
erythematous and/or hyperpigmented, and may desquamate, in particular in the area of skin 
folds such as the axilla, supraclavicular fossa, or inframammary fold. Desquamation may be 
dry  or  moist.  Progressive  erythema  may  be  seen  after  10-20  Gy,  depending  on  the 
fractionation schedule (Turesson and Notter 1975), and reaches maximal intensity 
approximately 1-2 weeks following the completion of treatment. An example of the 
development of moist desquamation and grade 2 erythema in a woman 1 week post- 
completion of PMRT to an unreconstructed chest wall is illustrated in Appendix 3. 
 
Factors contributing to variation in the severity of dermatitis in patients receiving PMRT have 
not been well studied. Acute skin toxicities are generally more severe in the setting of PMRT 
than breast conservation therapy (BCT), as the skin itself is considered part of the radiation 
target with PMRT. There are remarkably little data available on the incidence of radiation 
dermatitis in the post-mastectomy chest wall setting. The three large randomized trials 
investigating the use of PMRT either do not report toxicity or report late toxicity excluding skin 
toxicities (Overgaard, Hansen et al. 1997; Overgaard, Jensen et al. 1999; Ragaz, Olivotto et al. 
2005). One small retrospective series of 89 patients receiving PMRT using an electron technique 
reported that 19 patients developed dry desquamation, and only five developed moist 
desquamation (Hehr, Budach et al. 1999). In contrast, a series of 118 patients treated with a 
similar technique reported that 52% of patients developed grade 3-4 skin toxicity by Radiation 
Therapy Oncology Group (RTOG) criteria, and 31% of patients required an unplanned treatment 
break to recover from early radiation-induced skin toxicities (Spierer, Hong et al. 2004). 
 
The  development  of  normal  tissue  toxicities  in  breast  cancer  patients  receiving  adjuvant 
external beam RT demonstrates significant heterogeneity among individuals (Twardella, Popanda 
et  al.  2003),  which  can  be  attributed  to  a  variety of  individual,  tumor  stage,  cellular,  and 
molecular factors. Increasing evidence suggests that individual genetic variations may also play a 
significant role in the development of adverse radiation responses (De Ruyck, Van Eijkeren et al. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 6 of 20 
Amended: 08/07/13 
 
 
2005; Andreassen, Alsner et al. 2006; Alsbeih, El-Sebaie et al. 2007), but these remain poorly 
understood. Existing estimates on rates of radiation dermatitis are extrapolated from patients with 
intact breasts, who have been treated with a variety of techniques that affect the development of 
dermatitis. A  randomized  trial  investigating  the  use  of   intensity-modulated  RT  (IMRT)  in 
the setting  of  BCT  demonstrated  moist  desquamation  in  31.2% receiving IMRT and 47.8% 
with standard treatment, respectively (Pignol, Olivotto et al. 2008). The primary factor that 
predisposed to moist desquamation was large breast size; race-ethnicity and genetic factors were 
not assessed in this Canadian study.  In Table 1, we summarize the results from the few studies 
that  have  specifically evaluated  skin  toxicities  in  breast  cancer  patients  who  have  received 
PMRT. 
 
Table 1. Incidence of RT-Related Adverse Reactions in PMRT Patients 
 
Sample Size 
Skin Toxicities 
Study Variables 
References 
41 PMRT 
patients 
Late tissue fibrosis and 
telangiectasias 
XRCC1&3, 
TGFB1, SOD2, 
APEX SNPs 
Andreassen et al., 
2003 
118 PMRT 
patients 
52% grade 3-4 acute skin 
toxicity 
- 
Spierer et al., 
2004 
89 PMRT 
patients 
19 dry desquamation; 5 
moist desquamation 
- 
Hehr et al., 1999 
 
 
3.3 Evidence for Topical Agents’ Prevention and Treatment of Radiation-Induced Dermatitis 
 
 
Acute  radiation  dermatitis  has  been  attributed  to  the  combined  result  of  a  decrease  in 
functional stem cells, changes in the skin’s endothelial cells, inflammation, cell necrosis, and 
death (Hymes et al. 2006). Proposed mechanisms for the anti-inflammatory effect of 
corticosteroids include vasoconstriction, decreased capillary permeability, and inhibition of 
leukocyte proliferation and migration (Yohn,1990). However, all mechanisms are not fully 
elucidated. 
 
At the present time, there are no established standards for either the prevention or management 
of radiation-induced skin reactions. Intervention is primarily based on clinician experience. 
Numerous products are used by various radiation oncology departments throughout the world. 
Biafene cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, USA) was evaluated in a 
multicenter randomized trial conducted by the RTOG and was not found to be superior to 
standard regimens in the prevention of radiation-induced skin reactions (Fisher, Scott et al. 
2000). Generally, it is agreed that a key element of the prevention of radiation dermatitis is 
moisturizing the irradiated area with Eucerin, Aquaphor, aloe vera, or other hydrophilic products 
(Maddocks-Jennings, Wilkinson et al. 2005). The emphasis has been on teaching self care to 
minimize skin trauma, irritation, and or/infection. In our department, we recommend the 
application of Eucerin BID to the breast or chest wall as standard care for our breast cancer 
patients. Moist desquamation is treated with Silvadene cream or hydrocolloid dressings. 
 
To  date,  five  trials  have  evaluated  topical  corticosteroids  for  the  prevention  of  acute  skin 
reactions in patients receiving radiation (Bostrom, Lindman et al. 2001; Schmuth, Wimmer et al. 
2002; Shukla, Gairola et al. 2006; Omidvari, Saboori et al. 2007; Miller, Schwartz et al. 2011). 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 7 of 20 
Amended: 08/07/13 
 
 
The details and results of these studies are summarized in Table 2; however, these studies 
collectively demonstrated that topical corticosteroid agents used as the sole skin care regimen 
during irradiation reduced the severity of skin reactions following RT. 
 
Table 2. Select Trials of Topical Steroidal Creams in Breast Cancer Patients Receiving 
Radiation Therapy 
 
Study (Year) 
Study 
Population, 
Targeted 
Corticosteroid Agent 
Outcomes 
Bostrom et 
al, 2001 
N=49, whole 
breast 
Mometasone furoate 
0.1% vs Placebo 
MMF group with 
significantly decreased 
acute radiation 
dermatitis (P=0.0033). 
Schmuth et 
al, 2002 
N=36 ,whole 
breast 
0.1%methylprednisolone cream 
vs 0.5% dexpanthenol cream vs 
no intervention 
No significant 
difference in mean 
severity scores of 
radiation dermatitis 
Shukla et 
al, 
2006 
N=60, 
whole 
breast 
Beclomethasone dipropionate spray 
vs no intervention 
Corticosteroid group 
with significantly 
reduced 
incidence of moist 
desquamation 
Omidvari 
et al, 2001 
N=51, 
chest wall 
Betamethasone 0.1% vs placebo vs 
no intervention 
Steroid arm with 
significantly delayed 
occurrence of ARD 
Miller et 
al, 
2011 
N=176; 140, 
whole breast; 
29, chest 
wall 
Mometasone Furoate 
0.1% vs Placebo 
No difference in the 
mean maximum grade 
of radiation dermatitis 
 
 
Mometasone furoate is a medium-strength topical steroid that has a low atrophogenic potential, 
and has demonstrated greater anti-inflammatory activity and a longer duration of action than 
other medium-strength topical steroids such as betamethasone (Prakash & Benfield, 1998).  MF 
has  been  shown  to  be  effective  in  reducing  clinically  appreciated  radiation  dermatitis  and 
pruritus in patients who are receiving whole breast radiotherapy in several randomized trials 
comparing MF with a placebo emollient (Bostrom, Lindman et al. 2001; Miller, Schwartz et al. 
2011). However, its applicability in patients who have undergone mastectomy and receive 
irradiation of the chest wall has not been established. Only one of these studies included patients 
who received chest wall radiotherapy but, because the sample size was so small, they were 
unable to draw definitive conclusions regarding the benefit of MF in this population (Miller et 
al., 2011). The aim of this study is to elucidate the effect of mometasone furoate versus 
standard of care on patients receiving post-mastectomy irradiation, specifically. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 8 of 20 
Amended: 08/07/13 
 
 
3.4 Patient-Reported Outcomes and Provider Assessment Tools for Radiation Dermatitis 
 
 
Currently, the most widely used standardized method of recording provider-assessed toxicities 
is the CTCAE version 4. CTCAE has been shown to result in stable assessments of toxicities 
among practitioners (Trotti, 2003). Using this assessment tool, grade ≥2 radiation dermatitis 
encompasses an assessment of both the degree of erythema and desquamation, as gauged by the 
provider. Grade 2 erythema is defined as “moderate to brisk,” and grade 2 
MD is defined as “patchy, mostly confined to skin folds and creases” (CTCAE v4.03, 2009). 
 
There is evidence that patients and clinicians differ in their assessment of the severity of 
subjective skin toxicities (such as pruritus) during radiation (Neben-Wittich M. A., 2011). The 
Skindex-16 is a tool designed to capture patient-reported assessments of subjective adverse 
effects. Skindex-16 is comprised of sixteen questions, which are sub-categorized into an 
emotional subscale (six questions), a functional subscale (five questions), and a symptom 
subscale (five questions). Rankings of the questionnaire are then averaged to obtain a score of 
severity of patient-reported outcomes. This allows providers to gauge which aspects of the 
patient’s experience are most affected by the treatment. 
 
The Fitzpatrick Skin Classification is a well-recognized tool for patients’ initial assessment of 
their general level of skin sensitivity. The scale ranges from category I to VI, representing a range 
from pale skin/always burns to dark skin/never burns (Fitzpatrick TB, 1988). 
 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.1 
Design 
 
This is a Phase III double-blinded, randomized trial. Its purpose is to compare MF 0.1%, a 
steroid cream, with standard emollient skin care, Eucerin, on the prevention of acute grade 2 
or higher skin toxicities in breast cancer patients receiving PMRT to the chest wall and 
regional lymph nodes. We hypothesize that MF will prevent moderate to severe radiation 
dermatitis in women undergoing chest wall irradiation for breast cancer. 
 
4.2 
Intervention 
 
Eligible patients will receive skin care according to their randomization assignment during 
radiation therapy. Skin toxicity assessments and assessment of patient-reported compliance 
will be done on a weekly basis while the patient is receiving RT, by the RN or physician 
utilizing CTCAE 4.0 and the weekly status check form, as per current standard practice. 
Patient-reported skin toxicities will be measured using the Skindex-16 assessment tool. 
Patients will report Fitzpatrick Skin Category at the time of the History and Physical. 
 
Patients will be followed at 10-14 days after the completion of treatment during which time 
they will have a provider skin assessment and they will complete an additional Skindex-16 
Assessment. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 9 of 20 
Amended: 08/07/13 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
5.1 Mometasone Furoate 
 
 
Class: Anti-inflammatory agents 
ATC Class: D07AC13 
VA Class: DE200 
Chemical Name: 9α,21-dichloro-11β,17-dihydroxy-16α-methyl-17(2-furanylcarbonyl)pregna- 
1,4-diene-3,20-dione 
Molecular Formula: C27H30Cl2O6 
CAS Number: 83919-23-7 
Brands: Elocon 
 
Topical MF is a medium-potency corticosteroid that modifies the body's immune response by 
suppressing the formation, release, and activity of endogenous mediators of inflammation, 
including prostaglandins, kinins, histamines, liposomal enzymes, and the complement system. It 
is available in a 0.1% cream, lotion or ointment form. Indications for topical use include relief of 
inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.  MF has a low 
atrophogenic potential, and a longer duration of action than other topical steroids in its class. 
 
5.2 Eucerin Original cream 
Eucerin Original is a hydrous lanolin emollient skin cream, which is used to soften and moisturize 
the skin. Emollients may be used as lubricants to treat or prevent dry, itchy skin, and minor skin 
irritations. 
 
5.3 Skindex-16 Assessment Module 
The usefulness of patient-reported outcomes as an alternate means to measure side effects has 
been reported in the literature (Huschka, Mandrekar et al. 2007). The Skindex-16 is an analog 
scale  of  symptoms  and  functional  endpoints  related  to  skin  toxicity that  can  occur  in  the 
treatment area, and has been assessed for reliability: scale scores were reproducible after 72 
hours, and demonstrate both content and construct validity (Chren, Lasek et al. 2001). It has 
been used for patients to rate skin conditions that have occurred within the previous week. It 
consists of a short 16-item assessment completed by the patient, using numerical analogue scales 
(0 = never bothered to 6 = always bothered). Responses to the Skindex-16 are categorized into 
three subscales: symptom, emotional, and functional (Appendix 1). 
 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.1 
Subject Inclusion Criteria 
 
• Age ≥18 years 
• Stage 1-3 invasive breast cancer that is histologically confirmed at MSKCC 
• Status post mastectomy with axillary exploration (sentinel node biopsy and/or 
axillary lymph node dissection) to receive PMRT 
• ECOG Performance Status of 0 or 1 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 10 of 20 
Amended: 08/07/13 
 
 
6.2 
Subject Exclusion Criteria 
 
• Male 
• Patients with distant metastasis or locally recurrent breast cancer 
• Patients who are pregnant or breastfeeding 
• Prior radiation therapy to the ipsilateral chest wall or thorax 
• Patients requiring a chest wall boost 
• Concurrent chemotherapy (biologic agents are allowed) 
• Psychiatric illness that would prevent the patient from giving informed consent 
• Inability or unwillingness to comply with skin care instructions and follow-up 
• Allergy to either Eucerin or MF• 
Residual grade >1  skin toxicity, cellulitis, 
or incompletely healed wound(s) at intended site of study drug application at 
simulation 
• Medical  condition  such  as  uncontrolled  infection  (including  HIV),  uncontrolled 
diabetes mellitus, or connective tissue diseases (lupus, systemic sclerosis, or other 
collagen vascular diseases) 
• Treatment with non-standard, inverse-planned Intensity Modulated Radiation Therapy 
(IMRT), palliative or pre-operative radiation 
 
7.0 
RECRUITMENT PLAN 
 
All female patients who received a mastectomy and plan to receive PMRT at MSKCC 
will be eligible for screening. Potential participants will be identified by the protocol 
investigators or the departmental breast research team. 
 
Approximately 120-150 breast cancer patients receive PMRT in the Department of Radiation 
Oncology in the Main Campus per year. On average, 15-20 mastectomy patients are under 
treatment at any moment, thus providing a large pool of patients who could be eligible for this 
study. We estimate treating 70-80 eligible patients at the Main Campus per year, which would 
enable us to reach our accrual goal of 143 patients within 3years. 
 
8.0 
PRETREATMENT EVALUATION 
 
The History and physical exam in Radiation Oncology w i ll include information on 
race/ethnicity, age, body mass index, chemotherapy status, hormone therapy, smoking 
history/status, diabetes, high blood pressure, Eastern Cooperative Oncology Group (ECOG) 
performance, and reconstruction status. 
 
Radiation Treatment Planning will be approved by the treating MD, in order to determine type 
of chest wall radiotherapy (photons vs electrons) to be administered, as outlined in section 
9.1. 
 
Baseline  Provider  Skin  Toxicity Assessment  will be done within  14  days  prior  to  the 
start  of  RT. 
 
Patients will complete a baseline Skindex-16 Questionnaire and Fitzpatrick Skin 
Classification within 14 days prior to the start of RT (Appendix 1 and 2). 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
status of the patient. Patients without reconstruction reveive electrons directed en face to 
Page 11 of 20 
Amended: 08/07/13 
 
 
9.0 
TREATMENT/INTERVENTION PLAN 
 
9.1 Skin Cream Application 
 
Arm 1 consists of patients randomized to standard of care arm (Eucerin) and Arm 2 is the 
experimental arm (MF 0.1%). Patients will start applying the agent to the chest wall twice 
daily beginning on the first day of radiation treatment and continuing 10-14 days post- 
completion of RT. 
 
Patient education regarding amount to be applied (amount depending on body habitus) and 
area of treatment field will be reinforced by the R.N. prior to the first radiation treatment. 
Patients will be instructed to apply cream to the upper outer quadrant, upper inner quadrant, 
lower outer quadrant, and lower inner quadrant, as well as irradiated nodal fields. They will 
be instructed to apply cream in a thin, uniform layer twice a day, in the morning and 
evening, and not within the immediate 4 hours prior to radiation treatment. Patients will be 
informed that application immediately following radiation treatment is acceptable for those 
scheduled to receive morning treatments. 
 
Patients will be instructed to wash the area daily using a mild soap such as Dove or 
Cetaphil, and to pat skin dry prior to cream application. Patients will be instructed to avoid 
the use of any exfoliating agents, such as loofah, sponges, or scrubs. Skin will not be 
washed for at least 8 hours after each application. 
 
Patients will be instructed to wear soft, loose clothing to cover the treated areas, but not to 
use any occlusive dressings, and to avoid exposure to the sun. The use of sunscreens should 
be discouraged, with a preference to using clothing to cover the treatment area when 
exposure to the sun is expected. Patients will be discouraged from scratching the treated 
area and using possible skin irritants such as aftershaves, colognes, and perfumes. 
Aluminum-free deodorants will be permitted.   Topical and/or systemic treatments for 
prophylaxis of dermatitis other than assigned cream will be prohibited during the study. 
 
The topical agents will be blinded and dispensed after randomization at patient’s simulation 
visit or at the radiation setup in 130 gram jars labelled with patient’s name and MRN by the 
Memorial Sloan-Kettering Cancer Center (MSKCC) pharmacy.  It is estimated that the 
average patient will require approximately 3 grams of cream per application, and will 
require one additional prescription for a jar of study cream during the 7 week trial.  During 
weekly assessment of compliance at routine status check, date of dispensation of second jar 
will be recorded on provider assessment sheet as an additional indicator of compliance. 
 
Patients will return to clinic for a follow up visit at 10-14 days following the completion of 
RT. At this visit the study investigator will perform  a skin assessment and the patient will 
complete the Skindex-16. 
 
9.2 Chest Wall Radiotherapy 
 
 
 
The radiation treatment included in this study represents the institutional standard of care and 
is not influenced by the patient’s decision to participate in this study. Either photons or 
electrons will be used for the primary radiotherapy treatment, depending on reconstruction 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 12 of 20 
Amended: 08/07/13 
 
 
the chest wall with customized bolus, or photon tangents with daily bolus over the chest 
wall.  Patients who have a reconstruction are treated with two tangential photon beams and 
bolus over the reconstructed breast everyday. Treatment breaks necessitated by severe 
toxicities will be recorded and will not be considered deviations. 
 
Concurrent delivery of chemotherapy will not be allowed. Biologic agents and hormonal 
therapy during radiation will be permitted. 
10.0 EVALUATION DURING TREATMENT/INTERVENTION 
 
10.1 Evaluation During Radiation 
Weekly status checks including assessment of patient compliance and Provider Skin Toxicity 
Assessments using CTCAE 4.0 during radiation treatment will be performed according to 
standard practice in the Department of Radiation Oncology. The patient will complete the 
Skindex-16 form during the last week of RT (week 5). The amount of topical agent used will 
be evaluated based on timing of patient’s request for refillby an R.N. in order to assess 
compliance with the treatment regimen and will be documented on the Provider Skin Toxicity 
Assessment form. 
 
10.2 Evaluations After Radiation 
Follow-up visits will be completed 10-14 days after the completion of RT. At this time, 
provider assessment of skin toxicity will be performed by the physician and RN, and the 
patient will complete another Skindex-16 form. 
 
Tests and 
Observations 
Consultation Simulation 
Set-Up/ 
Treatment 
#1 
During 
Treatment 
(5 weeks) 
10-14 Days 
Following 
Completion 
of Treatment 
(CoT) 
History and Physical 
X 
Weekly Status 
checks 
Radiation Treatment 
Plan approval 
X 
Randomization 
X 
Patient Teaching and 
Administration 
of Topical Agent 
X 
X 
Assess 
compliance 
weekly 
Provider 
Assessment of Skin 
Toxicity 
X 
Provider 
assessment 
weekly 
X 
Patient Assessment of 
Fitzpatrick Category 
(Appendix 2) 
X 
Patient Assessment 
of Skin Toxicity 
(Appendix 1) 
X 
Week 5 only 
X 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 13 of 20 
Amended: 08/07/13 
 
 
11.0 TOXICITIES/SIDE EFFECTS 
 
The patient will be monitored for erythema and desquamation in the radiation field, which are 
expected side effects from chest wall radiotherapy. Some patients may develop moist 
desquamation, which usually heals within a few weeks and is treated with Silvadene cream 
and/or hydrocolloid dressings. Treatment breaks secondary to severe acute skin toxicities and/or 
cellulitis during radiation are not anticipated. 
 
If a patient develops grade 2 or greater moist desquamation, or adverse reaction to the topical 
agent, she will be instructed to discontinue study cream and will receive standard of care 
management as determined by the patient’s provider.  These patients will continue to be evaluated 
according to study guidelines, and intervention will be noted on the Provider Skin Toxicity 
Assessment form.   Patients who develop grade 2 erythema without the presence of moist 
desquamation will continue to use study cream without deviation from protocol guidelines. 
 
Side effects from MF are uncommon. In controlled clinical studies of MF, the incidence of 
adverse reactions of burning, pruritus, and skin atrophy was 1.6%. Infrequent side effects 
include irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, 
allergic contact dermatitis, secondary infection, striae, and miliaria. Systemic absorption may 
produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of 
Cushing syndrome, hyperglycemia, and glycosuria. 
 
Eucerin Original side effects are rare but include skin redness, irritation, and itching. 
 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
12.1 Assessment of Primary Objective 
The grading of skin toxicity will be based on the CTCAE version 4.0 scale as defined in section 
3.4. To ensure unbiased skin toxicity measurement, both the  clinical team and patient will be 
blinded to the treatment assignment. The type of skin toxicity (moist desquamation or grade ≥2 
erythema), maximal score, its location within the target (chest wall or axilla), and time to 
occurrence will be recorded weekly during RT and at week 2 follow-up on the Provider Skin 
Toxicity Assessment Form. Following the post-treatment visit, the patient will not need to return 
to the clinic for other follow-up visits unless otherwise specified by the treating physician. 
 
 
12.2 Assessment of Secondary Objectives 
The Skindex-16 module score will be utilized to assess patient-reported toxicities at baseline, 
during week 5 of RT, and 10-14 days post-RT. 
 
The maximal reported toxicity score and time to occurrence will be assessed weekly and at 
the two week follow up. 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
It will be made clear to all participants that they are allowed to withdraw from the study at any 
time. If at any time the patient is found to be ineligible from the protocol as designated in the 
section on Criteria for Patient/Subject Eligibility, the patient will be removed from the study. 

Page 14 of 20 
Amended: 08/07/13 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
 
 
14.0 
BIOSTATISTICS 
 
This is a double-blinded, randomized trial (see Section 15.2 for details of randomization) to 
compare MF 0.1% cream with standard skin care (Eucerin) on the prevention of moderate to 
severe skin toxicities in breast cancer patients receiving post-mastectomy radiation to the chest 
wall and regional lymph nodes. A patient is deemed to have developed skin toxicity if she has a 
grade ≥2 skin toxicity as defined in Section 3.4 within 7 weeks from the beginning of radiation. 
 
Based on estimates provided by radiation oncologists at our institution, the rate of grade ≥2 
toxicity using Eucerin as skin care for chest wall radiation is ≈ 50%. This estimate is slightly 
lower than the findings from the Spierer study cited in section 3.2, to reflect this study’s 
inclusion of patients treated with photons (in the presence of reconstruction) as well as 
electrons.  We expect that the usage of MF can reduce this rate to 25%. 124 evaluable patients 
are needed for the comparison, with 62 patients in each arm. Two-sample, two-sided 
proportion tests will be used to derive the statistical significance. One interim analysis will be 
conducted when 31 patients in each arm have been enrolled and evaluated using the O’Brien- 
Flemming procedure, which will declare significance if the test p-value is less than 0.005. 
Correspondingly the final analysis will declare significance if the test p-value is less than 0.048. 
This design has a power of approximately 0.83 (i.e., detecting the true toxicity rate of 25% or 
lower) at the type I error (i.e., declaring MF more effective while it yields the same toxicity 
rate as Eucerin) rate of 0.05 based on 100000 statistical simulations. 
 
All deaths unrelated to the toxicities, and patients lost to follow-up (before toxicities can be 
evaluated), will be excluded from the comparison and new patients will be accrued for 
replacement. To this end we plan to enroll an additional 15% of patients. Therefore our final 
proposed accrual is about 143 patients, which is expected to be done in 3 years. 
 
Patient-reported skin symptoms will be scored from the Skindex-16 surveys and compared 
between interventions using Wilcoxon tests at each separate assessment time point. Analysis of 
covariance  may  also  be  used  when  the  baseline  information  is  taken  into  account  as  a 
covariate. Multiple comparison tools will be employed to adjust for statistical significance 
levels. Maximum reported skin toxicities will be tabulated and summary statistics will be 
provided. Time to occurrence of skin toxicity will be handled by routine survival analysis such 
as Kaplan-Meier estimation, log-rank tests, and/or Cox regression models when comparisons 
are needed. 
 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.1 
Research Participant Registration 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a protocol 
specific Eligibility Checklist. 

Page 15 of 20 
Amended: 08/07/13 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
 
 
All participants must be registered through the Protocol Participant Registration (PPR) Office 
at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through Friday from 
8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the PPR Electronic 
Registration System (http://ppr/).  The completed signature page of the written consent/RA or 
verbal script/RA, a completed Eligibility Checklist and other relevant documents must be 
uploaded via the PPR Electronic Registration System. 
 
15.2 
Randomization 
 
Randomization will be done at MSKCC. Patients will be randomized to the MF 0.1% cream 
arm or the standard skin care arm with Eucerin at the ratio of 1:1.  For patients enrolled at 
MSKCC, after eligibility is established and immediately after consent is obtained, the RSA 
will register participants in the PPR system and randomize participants using the Clinical 
Research Database (CRDB), by calling the MSKCC PPR Office at 646-735-8000 between the 
hours of 8:30 am and 5:30 pm, Monday to Friday. Randomization will be accomplished by the 
method of random permuted block, and will be stratified by the presence of breast 
reconstruction and BMI. After treatment arm is determined by randomization, RSAs at 
MSKCC will notify the research staff of the participant ID via email within 24 hours of 
randomization. Since this is a double blind study, the research participants’ treatment 
assignments can be viewed in the CRDB only by the hospital pharmacists who are dispensing 
the study drugs. 
 
15.3 
Blinding 
 
Study drug containers will appear identical with assigned numbers divided evenly between 
study drug and control. Details of which drug is associated with each number will be recorded 
in a logbook. When a patient is assigned to a treatment arm based on the process outlined in 
section 15.2, the pharmacist will obtain a number assignment from CRDB, re-label the cream 
and keep a log recording the number of the jar dispensed. 
 
16.0 
DATA MANAGEMENT ISSUES 
 
An RSA will be assigned to the study, whose responsibilities will include project compliance, 
data collection, abstraction and entry, data reporting, regulatory monitoring, problem resolution 
and prioritization, and coordinating the activities of the protocol study team. 
 
The data collected for this study will be entered into a secure database. Source documentation 
will be available to support the computerized patient record. 
 
 
 
16.1 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness 
of registration data. Routine data quality reports will be generated to assess missing data 
and inconsistencies. Accrual rates, and extent and accuracy of evaluations and follow-up, 
will be monitored periodically throughout the study period and potential problems will be 
brought to the attention of the study team for discussion and action. 

Page 16 of 20 
Amended: 08/07/13 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
 
 
16.2    Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at MSKCC were approved by the National 
Cancer Institute (NCI) in September 2001. The plans address the new policies set forth by 
the NCI in the document entitled “Policy of the National Cancer Institute for Data and 
Safety 
Monitoring 
of 
Clinical 
Trials,” 
which 
can 
be 
found 
at 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. The DSM Plans at MSKCC were 
established and are monitored by the Office of Clinical Research. The MSKCC DSM Plans 
can be found on the MSKCC Intranet at http://mskweb2.mskcc.org/irb/index.htm. 
 
There are several different mechanisms by which clinical trials are monitored for data, 
safety, and quality. There are institutional processes in place for quality assurance (e.g., 
protocol monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research quality assurance) and departmental procedures for quality 
control, plus there are two institutional committees that are responsible for monitoring the 
activities of our clinical trials programs: the Data and Safety Monitoring Committee for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board for Phase III clinical 
trials, reporting to the Center’s Research Council and Institutional Review Board (IRB). 
 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. Every type of protocol (e.g., National 
Institutes of Health sponsored, in-house sponsored, industrial sponsored, NCI cooperative 
group, etc.) will be addressed and the monitoring procedures will be established at the time 
of protocol activation. 
 
 
17.0 
PROTECTION OF HUMAN SUBJECTS 
 
The procedures involved in this study are felt to be of minimal risk, meaning that the probability 
and magnitude of harm or discomfort anticipated in the research are not greater in and of 
themselves than those ordinarily encountered in daily life or during the performance of routine 
physical or psychological examinations or tests. The benefit derived from the study would be 
prevention of moderate to severe skin toxicities in breast cancer patients undergoing chest wall 
radiation.  Patients  or  their  legal  guardians  will  receive  comprehensive  explanation  of  the 
proposed treatment options being offered on this protocol, including the nature of the 
investigation, rationale, alternative treatments and any known previously observed side effects, 
the investigational nature of the study, and the potential benefits and risks of the intervention. 
Participation in this trial is voluntary.  All patients will be required to sign  a statement of 
informed consent, which must conform to IRB guidelines. 
 
 
17.1    Privacy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 17 of 20 
Amended: 08/07/13 
 
 
17.2 
Serious Adverse Event (SAE) Reporting 
 
Any SAE must be reported to the IRB/PB as soon as possible but no later than 5 calendar 
days. The IRB/PB requires a Clinical Research Database (CRDB) SAE report be submitted 
electronically to the SAE Office at sae@mskcc.org.  The report should contain the following 
information: 
 
Fields populated from CRDB: 
 
• Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
• Medical record number 
• Disease/histology (if applicable) 
• Protocol number and title 
 
Data needing to be entered: 
 
• The date the adverse event occurred 
• The adverse event 
• Relationship of the adverse event to the treatment (drug, device, or intervention) 
• If the AE was expected 
• The severity of the AE 
• The intervention 
• Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form. 
The PI’s signature and the date it was signed are required on the completed report. 
 
 
 
18.0 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain full 
details of the protocol and study procedures as well as the risks involved to participants prior 
to their inclusion in the study. Participants will also be informed that they are free to withdraw 
from the study at any time. All participants must sign an IRB/PB-approved consent form 
indicating their consent to participate. This consent form meets the requirements of the Code 
of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. The 
consent form will include the following: 
 
1.   The nature and objectives, potential risks and benefits of the intended study. 
2.   The length of study and the likely follow-up required. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 18 of 20 
Amended: 08/07/13 
 
 
3.   Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4.   The name of the investigator(s) responsible for the protocol. 
5.   The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
19.0 
REFERENCES 
 
Alsbeih, G., M. El-Sebaie, et al. (2007). "Radiosensitivity of human fibroblasts is associated with 
amino acid substitution variants in susceptible genes and correlates with the number of risk alleles." Int 
J Radiat Oncol Biol Phys 68(1): 229-235. 
 
Andreassen, C. N., J. Alsner, et al. (2003). "Prediction of normal tissue radiosensitivity from 
polymorphisms in candidate genes." Radiother Oncol 69(2): 127-135. 
 
Andreassen, C. N., J. Alsner, et al. (2006). "Risk of radiation-induced subcutaneous fibrosis in 
relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM--a 
study based on DNA from formalin fixed paraffin embedded tissue samples." Int J Radiat Biol 82(8): 577- 
586. 
 
Bese, N. S., P. A. Sut, et al. (2007). "The impact of treatment interruptions on locoregional control 
during postoperative breast irradiation." J BUON 12(3): 353-359. 
 
Bostrom, A., H. Lindman, et al. (2001). "Potent corticosteroid cream (mometasone furoate) 
significantly reduces acute radiation dermatitis: results from a double-blind, randomized 
study." Radiother Oncol 59(3): 257-265. 
 
Chren, M. M., R. J. Lasek, et al. (2001). "Measurement properties of Skindex-16: a brief 
quality-of-life measure for patients with skin diseases." J Cutan Med Surg 5(2): 105-110. 
 
Clarke, M., R. Collins, et al. (2005). "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 366(9503): 2087-2106. 
 
De Ruyck, K., M. Van Eijkeren, et al. (2005). "Radiation-induced damage to normal tissues after 
radiotherapy in patients treated for gynecologic tumors: association with single nucleotide 
polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in 
lymphocytes." Int J Radiat Oncol Biol Phys 62(4): 1140-1149. 
 
Delaloye, J. F., P. A. Coucke, et al. (1997). "Radiation therapy duration influences overall survival in 
patients with cervical carcinoma." Int J Gynaecol Obstet 57(3): 295-303. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 19 of 20 
Amended: 08/07/13 
 
 
 
Fisher, J., C. Scott, et al. (2000). "Randomized phase III study comparing best supportive care to Biafine as 
a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation 
Therapy Oncology Group (RTOG) 97-13." Int J Radiat Oncol Biol Phys 48(5): 1307-1310. 
 
Fitzpatrick TB. The validity and practicality of sun-reaction skin types I through VI. Arch Dermatol 1988; 
124:869–71. 
 
Hehr, T., W. Budach, et al. (1999). "Evaluation of predictive factors for local tumour control after 
electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer." Radiother 
Oncol 50(3): 283-289. 
 
Huschka, M. M., S. J. Mandrekar, et al. (2007). "A pooled analysis of quality of life measures and 
adverse events data in north central cancer treatment group lung cancer clinical trials." Cancer 109(4): 
787-795. 
 
Hymes, S. R., E. A. Strom, et al. (2006). "Radiation dermatitis: clinical presentation, 
pathophysiology, and treatment 2006." J Am Acad Dermatol 54(1): 28-46. 
 
Maddocks-Jennings, W., J. M. Wilkinson, et al. (2005). "Novel approaches to radiotherapy-induced skin 
reactions: a literature review." Complement Ther Clin Pract 11(4): 224-231. 
 
McCloskey, S. A., W. Jaggernauth, et al. (2009). "Radiation treatment interruptions greater than one week 
and low hemoglobin levels (12 g/dL) are predictors of local regional failure after definitive concurrent 
chemotherapy and intensity-modulated radiation therapy for squamous cell carcinoma of the head and 
neck." Am J Clin Oncol. 32(6): 587-591. 
 
Miller, R. C., D. J. Schwartz, et al. (2011). "Mometasone furoate effect on acute skin toxicity in breast 
cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central 
Cancer Treatment Group N06C4." Int J Radiat Oncol Biol Phys 79(5): 1460-1466. 
 
Omidvari, S., H. Saboori, et al. (2007). "Topical betamethasone for prevention of radiation 
dermatitis." Indian J Dermatol Venereol Leprol 73(3): 209. 
 
Overgaard, M., P. S. Hansen, et al. (1997). "Postoperative radiotherapy in high-risk 
premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast 
Cancer Cooperative Group 82b Trial." N Engl J Med 337(14): 949-955. 
 
Overgaard, M., M. B. Jensen, et al. (1999). "Postoperative radiotherapy in high-risk 
postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer 
Cooperative Group DBCG 82c randomised trial." Lancet 353(9165): 1641-1648. 
 
Pignol, J. P., I. Olivotto, et al. (2008). "A multicenter randomized trial of breast intensity- modulated 
radiation therapy to reduce acute radiation dermatitis." J Clin Oncol 26(13): 2085-2092. 
 
Ragaz, J., I. A. Olivotto, et al. (2005). "Locoregional radiation therapy in patients with high-risk 
breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized 
trial." J Natl Cancer Inst 97(2): 116-126. 
 
Schmuth, M., M. A. Wimmer, et al. (2002). "Topical corticosteroid therapy for acute radiation dermatitis: 
a prospective, randomized, double-blind study." Br J Dermatol 146(6): 983- 
991. 

MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 13-069 A(1) 
Page 20 of 20 
Amended: 08/07/13 
 
 
Shukla, P. N., M. Gairola, et al. (2006). "Prophylactic beclomethasone spray to the skin during 
postoperative radiotherapy of carcinoma breast: a prospective randomized study." Indian J Cancer 43(4): 
180-184. 
Spierer, M. M., L. X. Hong, et al. (2004). "Postmastectomy CT-based electron beam radiotherapy: 
dosimetry, efficacy, and toxicity in 118 patients." Int J Radiat Oncol Biol 
Phys 60(4): 1182-1189. 
 
Suwinski, R., A. Sowa, et al. (2003). "Time factor in postoperative radiotherapy: a multivariate 
locoregional control analysis in 868 patients." Int J Radiat Oncol Biol Phys 56(2): 399-412. 
 
Tucker, S. L., I. Turesson, et al. (1992). "Evidence for individual differences in the 
radiosensitivity of human skin." Eur J Cancer 28A(11): 1783-1791. 
 
Turesson, I., G. Notter (1975). "Skin reactions after different fractionation schedules giving the same 
cumulative radiation effect." Acta Radiol Ther Phys Biol 14(5): 475-484. 
 
Twardella, D., O. Popanda, et al. (2003). "Personal characteristics, therapy modalities and individual 
DNA repair capacity as predictive factors of acute skin toxicity in an unselected cohort of breast 
cancer patients receiving radiotherapy." Radiother Oncol 69(2): 145-153. 
 
Yamazaki, H., K. Nishiyama, et al. (2006). "Radiotherapy for early glottic carcinoma (T1N0M0): 
results of prospective randomized study of radiation fraction size and overall treatment time." 
Int J Radiat Oncol Biol Phys 64(1): 77-82. 
 
Yohn, J., Weston WL (1990). Current Problems in Dermatology, Year Book Medical. 
 
 
20.0 
APPENDICES 
 
1.   Skindex-16 Form 
2.   Fitzpatrick Skin Classification System and CTCAE Version 4 Scoring Schema 
3.   Digital Photographs