Whole Lung IMRT in Children and Adults With Synovial Sarcoma and Lung Metastases
Phase: PHASE2
Conditions: Synovial Sarcoma, Single or Multiple Lung Metastases
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
Page 1 of 22 
 
 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Whole Lung IMRT in Children and Adults with Synovial Sarcom 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUTIC/DIAGNOSTIC PRO 
Principal Investigator/Department: 
Suzanne Wolden, MD 
a and Lung Metastases 
TOCOL 
Radiation Oncology 
Co-Principal 
Leonard Wexler, MD 
Investigator(s)/Department: 
Kaled M. Alektiar, MD 
Pediatrics 
Radiation Oncology 
Investigator(s)/Department: 
Paul A. Meyers, MD 
Samuel Singer, MD 
Michael P. LaQuaglia, MD 
William Tap, MD 
Mary Louise Keohan, MD 
Sandra D’Angelo, MD 
Mark Dickson, MD 
Ping Chi, MD 
Mrinal Gounder, MD 
Anita Price, MD 
Robert Lefkowitz, MD 
Neeta Pandit-Taskar, MD 
Daphna Gelblum, MD 
Melissa Remis Zinovoy, MD 
Boris Mueller, MD 
Borys Mychalczak, MD 
Pinaki Dutta, MD 
Richard Gewanter, MD 
Karen Borofsky, MD 
Preeti Parhar, MD 
Karen Schupak, MD 
Annemarie F. Shepherd, MD 
John Cuaron, MD 
Marsha Reyngold, MD, PhD 
Jillian Tsai, MD, PhD 
Carla Hajj, MD 
Ellen Yorke, PhD 
Sean Berry, PhD 
Zhigang Zhang, PhD 
Dana Casey, MD 
Pediatrics 
Surgery 
Pediatric Surgery 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Radiology 
Radiology 
Radiology 
Radiation Oncology 
Radiation Oncology 
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Radiation Oncology 
Radiation Oncology 
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Radiation Oncology 
Medical Physics 
Medical Physics 
Epidemiology and Biostatistics 
Radiation Onocology 
Consenting  Professional(s)/Department: 
Suzanne Wolden, MD 
Kaled M. Alektiar, MD 
Daphna Gelblum, MD 
Melissa Remis Zinovoy, MD 
James Lee, MD 
Boris Mueller, MD 
Borys Mychalczak, MD 
Pinaki Dutta, MD 
Richard Gewanter, MD 
Karen Borofsky, MD 
Preeti Parhar, MD 
Karen Schupak, MD 
Annemarie F. Shepherd, MD 
John Cuaron, MD 
Marsha Reyngold, MD, PhD 
Radiation Oncology 
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Page 2 of 22 
Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
 
 
 
 
 
Jillian Tsai, MD, PhD 
Carla Hajj, MD 
Radiation Oncology 
Radiation Oncology 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
OneMSK Sites 
Manhattan 
Rock ville Centre 
Westchester 
Basking Ridge 
Commack 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 3 of 22 
 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ...................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS ............................................................................... 3 
3.0 
BACKGROUND AND RATIONALE ..................................................................................... 3 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ................................................................... 6 
4.1 Design .................................................................................................................................. 6 
4.2 Intervention .................................................................................................................................7 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................. 7 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ................................................................................ 7 
6.1 Subject Inclusion Criteria ...................................................................................................... 7 
6.2 Subject Exclusion Criteria ..................................................................................................... 7 
7.0 
RECRUITMENT PLAN ...................................................................................................................... 8 
8.0 
PRETREATMENT EVALUATION ........................................................................................ 9 
9.0 
TREATMENT/INTERVENTION PLAN ................................................................................. 9 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION .................................................... 13 
11.0 
TOXICITIES/SIDE EFFECTS .................................................................................................... 14 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ........................ 15 
13.0 
CRITERIA FOR REMOVAL FROM STUDY ....................................................................... 16 
14.0 
BIOSTATISTICS ............................................................................................................... 16 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES17 
15.1 Research Participant Registration ......................................................................................... 17 
15.2 
Randomization ................................................................................................................... 17 
16.0 
DAT A M ANAGEMENT ISSUES ........................................................................................ 18 
16.1 
Quality Assurance ........................................................................................................ 18 
16.2 
Data and Safety Monitoring .............................................................................................. 19 
17.0 
PROTECTION OF HUMAN SUBJECTS ............................................................................ 19 
17.1 
Privacy .......................................................................................................................... 19 
17.2 
Serious Adverse Event (SAE) Reporting ......................................................................... 19 
17.2.1.........................................................................................................................................18 
18.0 
INFORMED CONSENT PROCEDURES .................................................................................. 18 
19.0 
REFERENCES ...................................................................................................................... 19 
20.0 
APPENDICES ................................................................................................................... 21 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 4 of 22 
 
 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
This is a safety study to evaluate toxicity and other clinical outcomes of whole lung intensity- 
modulated radiation therapy (IMRT) following standard treatment in patients with synovial sarcoma 
and lung metastases. Patients who received standard therapy for synovial sarcoma will be assessed 
for residual disease in the lungs by post-therapy imaging. Patients with pulmonary metastases <2 
cm will then be eligible to receive Whole Lung Irradiation (WLI).  The treatment plan will involve 1500 
cGy of radiation delivered using IMRT in 150 cGy fractions. 
 
Following completion of treatment, patients will have CT chest, physical exams, and toxicity 
assessments at 3, 6, 12, 18, and 24 months (+/-3 weeks for 3 and 6 months and +/-6 weeks for 12, 
18, and 24 months), an echocardiogram at 6, 12, and 24 months, and pulmonary function tests at 6 
and 24 months. 
 
Fifteen patients will be enrolled in 6 years. The duration of the study will be 6 years. 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary objective 
 
• 
To assess the overall toxicity rate at 1 year after whole lung IMRT in this patient population 
Secondary objectives 
• 
To determine rates of pulmonary failure-free survival after completion of whole lung IMRT. 
• 
To determine rates of overall survival (OS) after completion of whole lung IMRT. 
• Assessment of toxicity and response to treatment. 
• Patients complete standard therapy as determined by disease 
management team (e.g. surgery +/- radiation to the primary site) +/- any 
adjuvant chemotherapy.  Patients are eligible for this protocol if they 
have lung metastases present at diagnosis or develop lung metastases 
over the course of standard therapy. 
• After the completion of all planned therapy, patients will be assessed 
with imaging of their lungs. If there is no residual pulmonary disease or 
lung metastases are <2cm, patients are eligibile to participate on 
protocol. 
• Whole lung irradiation using IMRT on protocol. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 5 of 22 
 
 
 
 
3.0 
BACKGROUND AND RATIONALE 
 
3.1 The usage of whole lung irradiation in the management of pulmonary metastases 
 
Whole lung irradiation (WLI) is standard of care in the treatment of patients with pulmonary 
metastases from rhabdomyosarcoma (RMS), Ewing Sarcoma, and Wilms Tumor
1-3. The 
dose of WLI in modern Children’s Oncology Group (COG) protocols is 15Gy for RMS and 
Ewing Sarcoma and 12 Gy for Wilms tumor. WLI reduces the rates of lung recurrences in 
patients with RMS1 .  In the European Intergroup Cooperative Ewing’s Sarcoma Study 
(EICESS), WLI was associated with a trend to improved overall survival (OS),4  reduced 
pulmonary relapses and improved event-free survival (EFS)5. Similarly, patients with Wilms 
tumor with lung metastases at diagnosis demonstrate reduced pulmonary relapse when 
treated with WLI as demonstrated in both the UK Children’s Cancer Study Group (UKCCSG) 
6  and the National Wilms Tumor Study Group (NWTSG)3. The UKCCSG also demonstrated 
an association between EFS with the use of WLI. Taken together, these studies demonstrate 
that WLI is an accepted and efficacious treatment in the management of pulmonary 
metastases from RMS, Ewing Sarcoma, and Wilms Tumor. 
 
3.2 Rationale for using whole lung irradiation in synovial sarcoma 
 
Synovial sarcoma comprises approximately 8% of all soft tissue sarcomas (STS) and is the 
third most common extremity STS7. Synovial sarcoma is frequently a disease of young adults 
with a mean age of 30-40 years
8. About 6-18% of patients have distant metastases at 
presentation and the lungs are the most common site of metastases. In one series of  
patients <21 years of age with synovial sarcoma, rates of metastases at diagnosis are about 
6% with the vast majority of metastases (86%) located in the lungs9. An adult series reported 
18% of patients with metastatic disease at time of presentation with 78% of metastases 
located in the lungs10. In a Surveillance, Epidemiology and End Result (SEER) database 
study of 1,268 adult and pediatric patients with synovial sarcoma, the rate of distant disease 
at presentations was 13%11. 
In contrast to RMS, Ewing Sarcoma, and Wilms tumor, the use of WLI in patients with 
synovial sarcoma and lung metastases is not standard of care. In the recently closed COG 
phase III ARST0332 trial for non-rhabdomyosarcoma soft tissue sarcoma, which included 
synovial sarcomas, the use of WLI or focal radiation to the lungs was not allowed.  However, 
like RMS and Ewing sarcoma, synovial sarcoma is a radiosensitive histology
8. In the non- 
metastatic setting, the use of radiotherapy has been shown in large series to be associated 
with local control
12  and EFS in patients with localized disease
10. 
 
Data indicate that local control of pulmonary metastases is associated with improved 
survival. In a study from this institution that included 41 pediatric patients <22 years old with 
synovial sarcoma, patients who underwent pulmonary metastasectomy had a 2-year OS of 
65% compared to 0% among patients who did not undergo pulmonary metastasectomy
13. In 
this series, 10 of 41 patients could not undergo pulmonary metastasectomy due to diffuse 
non-resectable disease. A larger series examining pulmonary metastasectomy in all patients 
at this institution with soft tissue sarcoma (STS) and pulmonary metastases showed a 3-year 
overall survival rate of 46% in those patients who underwent complete resection of 
pulmonary metastases compared to 17% in patients with no resection. Of note, of the 20 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 6 of 22 
 
 
 
 
patients in this series with long term survival, 13 relapsed in the lungs requiring repeat 
resections leading the authors to conclude that “pulmonary metastases frequently represent 
diffuse involvement of the lung parenchyma. As such, it is difficult to eradicate all foci of 
metastatic disease with resection14.”  A series from Japan that included pediatric and adult 
patients with STS demonstrated a 2-year actuarial survival rate of 49.7% from time of first 
pulmonary resection with the use of aggressive pulmonary metastasectomy15. 
In addition to metastasectomy, local therapy to the lung in the form of radiation has been 
shown to provide excellent local control and improved OS. A series from the University of 
Rochester using stereotactic body radiotherapy (SBRT) for pulmonary metastases from STS 
showed an 82% rate of local control at three years and an improvement in OS from .6 years 
to 2.1 years with the use of SBRT16. Synovial sarcoma comprised 15% of the patient 
population in this study. A German study investigated the use of WLI to 12Gy with a boost of 
50-60 Gy to the single metastases in eight patients. Complete remissions were achieved in 6 
of 8 patients
17. 
3.3 Delivering whole lung irradiation utilizing IMRT 
 
3.3.1 Cardiac complications associated with thoracic radiation 
 
Cardiac morbidity is well-recognized sequelae of radiation therapy. Irradiation of the 
heart can affect the coronary arteries, cardiac valves, pericardium, myocardium, and 
endocardium
18. The complications can ensue while the patient is receiving radiation 
though many of the effects of radiation on the heart are not seen until years after the 
completion of radiation. With regard to late toxicity, the rates of radiation-induced 
cardiac disease are between 10-30% with the onset of symptoms ranging from 5-10 
years post-treatment19. 
In an analysis of the Childhood Cancer Survivor Study cohort which included 14,358 
five year survivors of cancer diagnosed under the age of 21, a dose-response 
relationship was seen with regard to rates of congestive heart failure (CHF), 
myocardial infarction, pericardial disease, and valvular disease with a significant 
increase in these late complications when cardiac radiation exposure exceeded 
15Gy20 . Another study of childhood cancer survivors showed that the risk of dying as 
a result of cardiac disease was significantly higher in patients who had received an 
average radiation dose greater than 5Gy to the heart (RR 12.5) and was further 
increased at doses exceeding 15 Gy (RR 25.1). There was a linear relationship 
between radiation dose and risk of cardiac mortality
21. 
 
The NWTSG reported the rates of congestive heart failure in a cohort of patients 
treated on NWTS 1-4. The RR of CHF was increased in females, by cumulative 
doxorubicin dose, lung irradiation, and abdominal irradiation. The risk of CHF 
increased by a factor of 1.6 for every 10Gy of lung irradiation
22. 
3.3.2 The use of IMRT to reduce the cardiotoxicity of WLI 
 
A dosimetry study performed at Northwestern University, compared WLI plans for 22 
patients using standard anteroposterior-posteroanterior (S-RT) technique and 
cardiac-sparing IMRT (CS-IMRT)23. Dosimetric parameters were calculated for the 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 7 of 22 
 
 
 
 
whole heart, right atrium, left atrium, right ventricle, left ventricle, liver and thyroid 
gland. The volume of the heart receiving 6Gy, 8Gy, 10Gy and 11.4Gy was 
significantly lower in the CS-IMRT plans as compared to the S-RT plans. This was 
also true for the left ventricle, right ventricle and myocardium. The volume of left 
atrium and right atrium receiving 10Gy or above was significantly less in the IMRT 
plans. Similarly, the volume of coronary vessels receiving ≥11.4Gy was lower in the 
IMRT plans. 
 
There is a recently completed multi-institutional protocol (IRB# 11-100), including this 
institution, investigating the feasibility of cardiac-sparing whole lung IMRT in children 
and young adults (<30 years old) with a diagnosis of Wilms tumor, Ewing Sarcoma or 
RMS and lung metastases. 
3.3.3 Pulmonary toxicity following WLI 
 
There is no data on pulmonary toxicity following WLI delivered with IMRT. However, 
there have been studies examining acute and late toxicity in patients who received 
WLI delivered with conventional fractionation. Lung irradiation at higher doses is 
correlated with adverse events including pneumonitis, pneumonia, chronic cough, 
dyspnea, chest wall deformity, interstitial lung disease, and supplemental oxygen 
requirement
24. This study included patients who received up to 64.8 Gy of radiation. 
The mean lung irradiation dose was significant associated with adverse pulmonary 
outcome. In studies that examine patients treated with low-dose whole lung irradiation 
exclusively, there are often mild reductions in pulmonary function abnormalities with 
low rates of clinically symptomatic moderate or severe pulmonary symptoms on 
follow-up4,25,26, In one study that examined patients with osteogenic sarcoma treated 
with 16Gy WLI, restrictive pulmonary function abnormalities present at 6 and 12 
months post-irradiation resolved by 2 years and no patients reported any significant 
pulmonary symptoms or decrease in exercise tolerance26. A second study of patients 
with Ewing Sarcoma treated with WLI showed a rate of late lung toxicity of .6 (on a 0- 
3 scale with 0 indicating no toxicity) and no severe pulmonary function test 
abnormalities among patients treated with WLI and no thoracic surgery. An additional 
study showed reductions in FEV1 in 50% of patients, reductions in total lung capacity 
in 60% of patients, and reductions in diffusing capacity in 81% of patients, but all but 
one patient had none or mild self-reported respiratory symptoms in follow-up25. In one 
study of patients treated with WLI for Wilms Tumor, a failure of chest wall growth was 
thought to contribute to late effects on pulmonary function though the mean age of 
patients was young (3 years and 9 months) and the radiation dose delivered was 
20Gy
27 . Taken together, these results indicate that while pulmonary function test 
abnormalities are often seen after whole lung irradiation, the incidence of clinically 
significant pulmonary toxicity is low, particularly at low-doses of 15Gy, which is the 
dose prescribed in this protocol. 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 8 of 22 
 
 
 
 
This is a single institution study involving patients with synovial sarcoma who have  
completed all standard therapy (e.g. surgery +/- radiation to the primary site) +/- any adjuvant 
chemotherapy. The sequence and types of therapy offered prior to WLI will likely vary based 
on primary tumor site, tumor resectability, extent of metastatic disease, performance status, 
and comorbidity. Each patient’s therapy will be determined by the disease management team 
irrespective of participation on this protocol. 
 
Patients are eligible for this protocol if their pulmonary metastases are present at diagnosis  
or develop over the course of treatment. After completion of all planned therapy, patients will 
be assessed with a CT scan of their lungs and a PET scan if the CT scan shows residual 
lung metastases. Assuming there is no residual pulmonary disease or that any remaining 
pulmonary metastases are <2 cm, patients will proceed to WLI. If there is gross disease in 
the lung >2 cm, patients will be evaluated for metastasectomy. If they undergo 
metastasectomy and subsequently have no residual pulmonary disease or have pulmonary 
metastases <2 cm, they are eligible to receive WLI on this protocol. Patients will also have an 
echocardiogram and pulmonary function tests (PFTs) prior to initiation of whole lung 
irradiation to assess baseline cardiac and pulmonary function. Patients will be simulated for 
external beam radiation with the use of a 4D CT to account for respiratory motion, as per 
standard practice. Patients will be treated with IMRT to 1500cGy in 150cGy fractions. 
 
After completion of WLI, patients will be followed by members of the Radiation Oncology 
department for toxicity evaluations and will be evaluated by physical exams and chest CT 
scans at 3, 6, 12, 18, and 24 months (+/-3-6 weeks depending on timepoint). Patients will 
also have echocardiograms at 6 months (+/- 3 weeks) and 12, and 24 months (+/- 6 weeks). 
Patients will also undergo pulmonary function tests (PFTs) at 6 months (+/- 3 weeks) and 24 
months (+/- 6 weeks). Any severe toxicity due to radiation will be carefully evaluated and 
further accrual will be terminated if the level of toxicity is greater than expected. The protocol 
may be terminated or modified as determined by the principal investigator. Please see 
section 11.0 regarding specific dose limiting toxicities and stopping rules for the protocol. 
 
4.3 
Intervention 
 
External beam radiation therapy will be administered on an outpatient basis, once daily 
(except weekends and holidays) for approximately two weeks. Patients will undergo a 
simulation prior to initiation of radiation. Once an IMRT plan is generated which meets all 
dose constraints specified in section 9.3.3, patients will be treated with 6MV photons for 10 
treatments. Any pediatric patients who are too young to lay still on a daily basis will receive 
general anesthesia per department practice. 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
IMRT is a sophisticated technique that uses a computer controlled multileaf collimator to shape the 
intensity of each treatment beam to optimally deliver the dose to the tumor and protect normal 
tissue.  IMRT is being used to deliver WLI in order to minimize the dose to the heart as explained in 
section 3.3.2. 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 9 of 22 
 
 
 
 
6.2 
Subject Inclusion Criteria 
 
• 
Patients with synovial sarcoma confirmed by MSKCC pathological review 
• 
Patients with single or multiple lung metastases at diagnosis or that develop over the 
course of treatment. 
• 
After completion of all chemotherapy, lung metastases must be <2 cm. 
• 
Age  ≥12 months of age 
• 
Karnofsky performance status (KPS) must be ≥ 70 for patients ≥ 16 years of age and 
Lansky performance status must be ≥ 70 for patients < 16 years of age. 
• 
Normal cardiac function 
o No active coronary artery disease; 
o No New York Heart Association class II, III or IV disease; 
o No arrhythmia requiring treatment. 
o Baseline echocardiogram with a shortening fraction of ≥ 27% or an ejection 
fraction ≥ 50%. 
• 
Female patients of childbearing potential must have a negative pregnancy test within 
14 days of radiation start. 
• 
Female patients who are lactating must agree to stop breast-feeding. 
• 
Sexually active patients of childbearing potential must agree to use effective 
contraception. 
 
6.3 
Subject Exclusion Criteria 
 
• 
Patients with a history of prior radiation therapy to the thorax. 
• 
Patients requiring a field size >40 cm as IMRT cannot be performed at extended 
SSDs. 
• 
Patients with any concurrent medical or psychiatric condition or disease which, in the 
investigator’s judgment, would make them inappropriate candidates for entry into this 
study. 
 
 
7.0 
RECRUITMENT PLAN with recruitment plan addendum 
 
All patients meeting the eligibility requirements will be considered for enrollment regardless of 
gender, race, or religion.  Patients will be made aware of the protocol, its specific aims and 
objectives, and the potential risks and benefits that the patient may incur.  Patients will be consented 
by the treating radiation oncologist at MSKCC.  They will be required to agree to and sign an IRB- 
approved informed consent form prior to registration. There will be no financial compensation for 
patients enrolling in this protocol. 
 
As a comprehensive cancer center, MSKCC is in a unique position to recruit patients for this  
protocol as we are hoping to recruit both pediatric and adult patients and MSKCC has high-volume 
adult and pediatric sarcoma services. This study mirrors the national trend of including both pediatric 
and adult patients on sarcoma protocols. The soon to open ARST 1321-RTOG 1313 is a joint 
protocol sponsored by the COG and RTOG to study non-rhabdomyosarcoma soft tissue sarcoma 
across the age spectrum. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 10 of 22 
 
 
 
 
Potential research subjects will be identified by a member of the patient’s treatment team, the 
protocol investigator, or research team at Memorial Sloan-Kettering Cancer Center (MSKCC).  If the 
investigator is a member of the treatment team, s/he will screen their patient’s medical records for 
suitable research study participants and discuss the study and their potential for enrolling in the 
research study.  Potential subjects contacted by their treating physician will be referred to the 
investigator/research staff of the study. 
 
The principal investigator may also screen the medical records of patients with whom they do not 
have a treatment relationship for the limited purpose of identifying patients who would be eligible to 
enroll in the study and to record appropriate contact information in order to approach these patients 
regarding the possibility of enrolling in the study. 
 
During the initial conversation between the investigator/research staff and the patient, the patient 
may be asked to provide certain health information that is necessary to the recruitment and 
enrollment process.  The investigator/research staff may also review portions of their medical 
records at MSKCC in order to further assess eligibility.  They will use the information provided by the 
patient and/or medical record to confirm that the patient is eligible and to contact the patient 
regarding study enrollment.  If the patient turns out to be ineligible for the research study, the 
research staff will destroy all information collected on the patient during the initial conversation and 
medical records review, except for any information that must be maintained for screening log 
purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment team. 
The recruitment process outlined presents no more than minimal risk to the privacy of the patients 
who are screened and minimal PHI will be maintained as part of a screening log.  For these reason, 
we seek a limited waiver of authorization for the purposes of (1) reviewing relevant to the enrollment 
process; (2) conversing with patients regarding possible enrollment; (3) handling of PHI contained 
within those records and provided by the potential subjects; and (4) maintaining information in a 
screening log of patients approached (if applicable). 
 
8.1 
PRETREATMENT EVALUATION 
 
Any time prior to treatment start: 
• 
Confirmation of pathology at MSKCC 
 
The following are to be completed within 45 days of registration: 
• 
History and physical exam 
• 
Echocardiogram 
• 
Pulmonary function tests 
 
The following are to be completed within 30 days of registration: 
• 
Chest CT scan with or without contrast to evaluate pulmonary metastases after 
completion of systemic therapy and to serve as a baseline for follow-up scans. To be 
done within 30 days of treatment start. 
• 
If lung metastases are present on Chest CT and are <2 cm, FDG-PET scan to assess 
avidity of pulmonary metastases after completion of systemic therapy 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
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Page 11 of 22 
 
 
 
 
 
 
The following is to be completed within 14 days of treatment start 
• 
Serum pregnancy test (for women of childbearing potential) 
 
9.0 
TREATMENT/INTERVENTION PLAN 
 
9.1 Simulation 
 
These simulation procedures represent our standard simulation procedures for 
comprehensive radiation therapy. 
 
9.1.1 In order to develop a conformal treatment plan, all patients will undergo a CT 
simulation. IV contrast is not necessary for simulation. 
 
9.1.2 All patients will undergo simulation in the treatment position with both upper extremities 
extended above their head using an Alpha Cradle (Alpha Cradle, Smithers Medical Products, 
North Canton, OH) or slant board immobilization. 
9.1.3 Patients will be scanned with 3mm slices from the level of the mandible to the pelvic 
brim. 
9.1.4 A 4D CT will be obtained to capture motion in all phases of the respiratory cycle. A 
free-breathing scan will also be obtained to be used as the planning CT scan. 
9.2 Target Volume Definitions 
 
These procedures generally represent our standard procedures. 
 
9.2.1 Normal structure and treatment volume contours will be delineated on the planning CT 
scan. 
9.2.2. The following normal structures will be contoured. 
 
• 
Heart 
• 
Liver 
• 
Stomach 
• 
Right kidney 
• 
Left kidney 
• 
Esophagus 
• 
Thyroid 
• 
Right and left breast (in female patients only) 
 
9.2.3 The following target structures will be contoured 
 
• 
Target volumes will be defined according to International Commission on 
Radiation Units and Measurements Report-50 and 62 definitions for gross 
tumor volume (GTV), clinical target volume (CTV), internal target volume 
(ITV), and planning target volume (PTV). 
• 
The GTV will include all areas of pre-chemotherapy lung metastases. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 12 of 22 
 
 
 
 
• 
The CTV is the bilateral lung volume including all pleural recesses and 
bilateral hila. 
• 
The ITV is defined as an expansion on the CTV to encompass the bilateral 
lungs on all phases of the respiratory cycle as defined by the 4DCT. Careful 
review of the sagittal and coronal views of the costo-diaphragmatic recesses 
should help determine the inferior extent of the pleural cavity and care must 
be taken to ensure that they are included in the ITV. 
• 
The PTV is defined as a 1 cm expansion on the ITV in order to account for 
spatial uncertainties in patient positioning and treatment delivery. This 1cm 
expansion of the ITV should be made in all dimensions. Compared to the 
standard AP-PA technique using 2-D or 3-D planning, the final PTV for IMRT 
in this protocol will be more accurate because we are utilizing 4-D scanning 
and then giving a dosimetric margin of 1cm beyond the maximum lung 
expansion (ITV). 
 
• 
9.3 Radiation Dose, Fractionation, Energy, and Parameters 
 
9.3.1 The prescribed dose for all patients will be 1500cGy in 10 fractions. 6MV energy 
photons will be used. Multi-beam IMRT plans, utilizing dynamic multileaf collimation, will be 
created based on the target tissue coverage and normal tissue avoidance parameters 
described below.  VMAT plans are also acceptable if all specified dose constraints are 
achieved. 
 
9.3.2 Ninety-five percent of the PTV should receive at least 95% of the prescribed dose. The 
PTV used for the purposes of the DVH is the PTV as drawn by the physician minus 5mm 
from the skin (i.e. the buildup region) as is our departmental practice. No more than 5% of 
the PTV should receive more than 105% of the prescribed dose and no more than 1% of the 
PTV should receive more than 110% of the prescribed dose. For organs at risk (OARs): the 
maximum doses to the spinal cord, breast (in female patients), and liver should be <107%, 
<108%, and <110% respectively of the prescribed dose. For the heart: 
 
1) The maximum dose should be <110%. 
 
2) The planner should reduce the mean heart dose until the specified PTV coverage 
constraints are approached (i.e. until the planner gets close to the D95, D05, D01 PTV 
limits). 
9.4 Treatment Plan Evaluation 
 
The treatment plan will be evaluated by the treating physician prior to treatment to ensure 
that all treatment parameters have been met. Isodose curves and dose volume histograms 
(DVH) will be analyzed. Evaluation criteria will include. 
 
1. Isodose curves: 
a. The 95% isodose line must generally conform to the PTV with visually acceptable 
target volume coverage and visually acceptable critical structure avoidance. 
2. Dose-Volume Histogram (DVH): 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 13 of 22 
 
 
 
 
a. The maximum allowed heterogeneity will be limited to less than 5% of the PTV 
receiving more than 105% of the prescribed dose. 
b. The DVH must include all normal structures listed in section 9.2.2 
c. PTV DVH must meet all prescription parameters. 
d. Critical structure DVH should meet constraint parameters (described in 9.3.2). 
 
9.5 Radiation Therapy Daily Treatments and Quality Assurance 
 
Patients will receive external beam treatment once a day, 5 days a week (except weekends 
and holidays) for 10 treatments. Any missed radiation days will be recorded and made up. 
Set-up error will be minimized by weekly orthogonal pair films per departmental guidelines. 
These films will be checked by an attending physician weekly. 
9.6 Treatment Interruptions 
 
In the event that a patient must miss a scheduled treatment for non-toxicity related reasons 
(ie: weather, sickness, family emergencies, etc), the treatment visit will be made up at the 
end. If the patient misses more than 3 consecutive treatments, they will be removed from the 
protocol and considered inevaluable. 
 
 
 
 
 
 
 
 
 
 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION 
 
Pre- 
treatment 
During 
WLI 
3 mo 
post- 
WLI 
6 mo 
post- 
WLI 
12 mo 
post- 
WLI 
18 mo 
post- 
WLI 
24 mo 
post- 
WLI 
Follow 
up 
years 
2-5 
History 
x 
x 
x 
x 
x 
x 
Physical 
x 
x 
(weekly) 
x 
x 
x 
x 
x 
Feasible Plan 
Generated 
x 
Weekly Setup 
Data 
x 
CT chest 
x 
x 
x 
x 
x 
x 
PET scan 
x 
(If CT chest 
shows mets 
< 2 cm) 
Echocardiogram 
x 
x 
x 
x 
PFTs 
X 
X 
x 
TSH 
x 
x 
Pregnancy test 
x 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 14 of 22 
 
 
 
 
 
(if relevant) 
Toxicity 
assessment 
x 
x 
(weekly) 
x 
x 
x 
x 
x 
Chart review for 
overall survival 
x 
 
 
10.1 Evaluations During Treatment 
 
All patients will undergo a routine status check visit approximately weekly during treatment. 
The maximum RT related toxicities graded by CTCAE version 4.0 will be submitted to the 
Research Study Assistant at the completion of WLI. 
10.2 Evaluations After Treatment 
 
Patients will have follow-up visits with physical examinations at 3 and 6 months (+/- 3 weeks) 
and at 12, 18, and 24 months (+/-6 weeks) following the completion of radiation therapy. CT 
scans of the chest will be obtained at 3 and 6 months (+/- 3 weeks) and at 12, 18, and 24 
months (+/- 6 weeks). Echocardiograms will be obtained at 6 months (+/- 3 weeks) and at 12, 
and 24 months (+/- 6 weeks). PFTs will be obtained at 6 months (+/- 3 weeks) and at 24 
months (+/- 6 weeks). TSH levels will be obtained at 12 and 24 months (+/- 6 weeks). 
In order to obtain data on overall survival, routine chart reviews will be conducted until 5 
years following the completion of treatment. 
 
 
 
 
10.3 Evaluations of Early and Late Toxicity 
 
The CTCAE version 4.0 scale will be used. Early toxicities are those toxicities that occur 
within 3 months of the completion of treatment. Late toxicities are those that occur after 3 
months following the completion of treatment. 
11.0 
TOXICITIES/SIDE EFFECTS 
 
Adverse events from WLI 
Likely 
• 
Nausea 
• 
Emesis 
• 
Skin erythema 
• 
Low blood counts 
• 
Esophagitis 
 
Less Likely 
 
• 
Thyroid dysfunction 
• 
Pericarditis 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 15 of 22 
 
 
 
 
• 
Cardiac dysfunction 
 
Rare but serious 
 
• 
Pneumonitis 
• 
Increased risk of secondary cancer 
• 
Pulmonary fibrosis 
 
Reproductive risks: Treatment on this study can affect an unborn child. Patients should not 
become pregnant or breastfeed a baby while being treated on this study. Sexually active 
patients who are at risk of getting pregnant or fathering a baby must use an effective method 
of contraception to avoid pregnancy while on treatment and for at least 3 months thereafter. 
Definition of a Serious Adverse Events (SAE): 
 
• 
A Serious Adverse Event is an adverse experience that: 
o Is fatal or life-threatening 
o Is disabling 
o Results in hospitalization or prolongation of hospitalization 
o Results in a congenital anomaly or occurrence of malignancy 
o Any adverse event that is possibly related to WLI that is grade 3 or higher will 
be considered an adverse event. 
 
Evaluation of SAE: 
 
Review of the patient record including the treatment dosimetry will be undertaken by the 
principal investigator and investigators of the study. The principal investigator in conjunction 
with the investigators of the study may decide to continue the protocol without modification, 
discontinue the study altogether, or to modify the protocol prior to enrolling more patients 
pending the results of the review. 
Unacceptable Toxicity: 
 
Enrollment on the protocol will be suspended for WLI related acute toxicities ≥ grade 4 
radiation pneumonitis, esophagitis, pericarditis, cardiac dysfunction, and acute chest wall 
pain. If one of these events is observed in one patient, then the protocol will be closed to 
further accrual until review by the principal investigator in conjunction with the investigators of 
the study. 
 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
12.1 Assessment of Primary Objectives 
 
12.1.1 Assessment of the overall toxicity rate will occur at the pre-specified follow-up 
time-points using the CTCAE version 4.0 grading system. The radiation oncologist will 
score toxicity at each visit. Any toxicity recorded within three months of completion of 
radiation will be considered acute. Any toxicity after three months from completion of 
radiation will be considered late toxicity. 
12.2 Assessment of Secondary Objectives 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 16 of 22 
 
 
 
 
12.2.1 Assessment of Pulmonary Failure-Free Survival 
 
A CT scan of the chest will be obtained at 3 and 6 months (+/- 3 weeks) and at 12, 18, and 
24 months (+/- 6 weeks) post-treatment. This study will use a modified Response Evaluation 
Criteria in Solid Tumor (RECIST) for assessment of tumor response. The baseline scan will 
be the pre-irradiation CT scan. 
 
All patients will be assessed as failure or failure free as defined below. Pulmonary failure-free 
survival will be defined as survival with no progressive disease in the lungs. CR, PR, and SD 
will be considered failure-free. 
 
For patients with measurable (≥5mm but <10mm) lung lesions at the time of study entry: 
 
a. The investigator will identify up to 5 measurable lung lesions to be followed for 
response. The sum of the longest diameter (LD) for all target lesions will be 
calculated and reported as the disease measurement. 
b. Complete response (CR) is defined as the disappearance of all target lesions. 
c. Partial response (PR) is defined as at least a 30% decrease in the disease 
measurement, taking as reference the pre-irradiation CT scan. 
d. Progressive disease (PD) is defined as at least a 20% increase in the disease 
measurement, taking as reference the smallest disease measurement recorded 
since start of treatment, or the appearance of one or more new lung lesions. 
e. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD. 
 
For patients with no measurable disease present at baseline: 
a. Stable disease (SD) is defined as no appearance of measurable lesions in the 
treated area 
 
b. Progressive disease (PD) is defined as the appearance of measurable lesions on 
post-treatment scans and will be considered failure-free if no measurable lesions 
develop. 
 
12.2.2 Assessment of overall survival will be performed for each patient using clinical data 
and information from the social security database. 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
If at any time the patient desires to quit participation in the study or if the treating physician 
determines study participation is no longer appropriate, the patient will be removed from the study. 
 
Toxicity will be evaluated in all patients enrolled who receive any whole-lung irradiation. Pulmonary 
progression free survival will only be evaluated in patients who complete all radiation treatments and 
have at least 1 follow-up chest CT. 
 
14.0 
BIOSTATISTICS 
 
The primary objective of this protocol is to assess the safety of whole lung IMRT following standard 
treatment in patients with synovial sarcoma and lung metastases. To this end we will enroll 15 
eligible patients which will take about 6 years. Due to this long enrollment time the safety endpoint 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 17 of 22 
 
 
 
 
will include both acute (<=3 months from the end of WLI) and late toxicities (>3 months from the end 
of WLI). Namely, we will evaluate the rate of any grade 3 toxicities (including pneumonitis, 
esophagitis, pericarditis and cardiac dysfunction) by using Kaplan-Meier estimation. If a patient 
withdraws from the protocol (expected to be 10% within 1 year), or dies without any grade 3  
toxicities (expected to be 50% at 1 year) he/she will be regarded as a censoring at such time points. 
We will not use a competing risks analysis because it is expected that the withdrawal and death are 
independent from toxicities, and the actuarial estimate is believe to be more illustrative of the toxicity 
profile than the cumulative incidence rate by regarding death as a competing risk. For the decision 
rule we will look at the 1-year toxicity rate. If, the higher bound of the 85%, 1-sided confidence 
interval of the 1-year toxicity rate based on the (one minus) Kaplan-Meier estimate is lower than 0.25 
than we will declare the whole lung IMRT procedure safe. This unusually high type 1 error rate, 15%, 
is used due to the rareness of such patients and the high progression/mortality rate without WLI. To 
roughly assess the power of the study with 15 patients, we simulated 10,000 datasets based on the 
above assumptions and examine the 1-year toxicity rate by Kaplan-Meier method. The following 
table shows probabilities of claiming whole lung IMRT safety under various values of the true 1-year 
toxicity rate. 
 
True 1-year toxicity rate 
0.05 
0.10 
0.15 
0.20 
0.25 
0.30 
0.35 
Probability of claiming whole 
lung IMRT safe 
0.894 
0.712 
0.536 
0.364 
0.243 
0.154 
0.094 
 
 
As mentioned in Section 11.0, this study is also subject to early stopping if any radiation-related 
acute toxicities of grade 4 or higher are observed among the patients. If one of these events is 
observed in one patient, then the protocol will be closed to further accrual until reviewed by the 
principal investigator in conjunction with the investigators of the study. 
Rates of pulmonary failure-free survival will be assessed by cumulative incidence functions. To this 
end pulmonary failure is the event of interest and other progressions and death are considered as 
the competing risks. Overall survival rates will be estimated by the Kaplan-Meier method. 
 
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. 
For patients enrolled, immediately after consent is obtained, the RSA at MSKCC will regis ter 
participants in the Clinical Trial Management System (CTMS). Once the participant’s 
eligibility is established, the registration will be finalized and the participants will be 
randomized using the Clinical Research Database (CRDB). 
15.2 
Randomization 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 18 of 22 
 
 
 
 
This is not a randomized study. 
 
16.1 
DATA MANAGEMENT ISSUES 
 
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of the RSA 
include project compliance, data collection, abstraction and entry, data reporting, regulatory 
monitoring, problem resolution and prioritization, and coordinati ng the activities of the protocol study 
team. 
 
The data collected from this study will be entered into a secure Clinical Research Database (CRDB). 
Source documentation will be available to support the computerized patient record. 
 
Data collection will principally assess: 
• 
Adherence to informed consent procedures. The informed consent must contain a full 
explanation of the possible advantages, benefits, risks, alternative treatment options, and 
availability of treatment in the case of injury, in accordance with Federal Regulations as 
detailed in 21CFR50.  The investigator is responsible for obtaining written informed consent 
from potential patients.  A copy of the signed document will be given to the patient, and the 
original will be retained by the investigator with his/her copy of the record forms. 
 
• 
Adherence to eligibility criteria. The study RSA will ensure that documentation exists for all 
eligibility criteria and that the checklist is complete and signed by the consenting 
professional, prior to initiation of treatment. All supporting source documentation must be 
maintained in the patient’s research file. 
 
• 
Safety Evaluation: Radiation related toxicities will be recorded as they occur, and graded 
according to the CTCAE Version 4.0.  Toxicities that cannot be graded using the CTCAE will 
be graded as grade 1 (mildly symptomatic), grade 2 (moderately symptomatic but not 
interfering significantly with function), grade 3 (causing significant interference with function), 
or grade 4 (life-threatening). All SAEs will be recorded, whether or not related to study 
treatment. 
 
• 
The occurrence of unacceptable toxicity indicating the need for cessation of treatment will 
require mandatory reporting to the IRB. In this circumstance, the IRB will be consulted before 
a patient is removed from therapy. If the physician feels it is in the best interests of the  
patient to stop treatment, the IRB will be consulted. 
 
• 
We expect to enroll 15 patients in 6 years. Since we are assessing two-year follow-up, we 
estimate that it will take 6 years to complete the study. 
 
 
16.1 
Quality Assurance 
 
Regular 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.  Random-sample data 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 19 of 22 
 
 
 
 
quality and protocol compliance audits will be conducted by the study team at a minimum of 
twice per year, or more frequently if indicated. 
 
16.2 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer Center 
were approved by the National Cancer Institute in September 2001. These 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”.  This document is available at:  
http://cancertrials.nci.nih.gov/researchers/dsm/index.html. The DSM Plans at MSKCC were 
established and are monitored by the Office of Clinical Research. The MSKCC Data and 
Safety Monitoring Plans can be found on the MSKCC Intranet at:  
http://mskweb2.mskcc.org/irb/index.htm There are several different mechanisms by which 
clinical trials are monitored for data, safety and quality. Institutional processes are in place for 
quality assurance (e.g., protocol monitoring, compliance and data verification audits, 
therapeutic response, and staff education on clinical research QA) and departmental 
procedures for quality control.  Additionally, there are two institutional committees that are 
responsible for monitoring the activities of our clinical trials programs. The Data and Safety 
Monitoring Committee (DSMC) for phase I and II clinical trials, and the Data and Safety 
Monitoring Board (DSMB) for phase III clinical trials, report to the MSKCC Research Council 
and Institutional Review Board. During the protocol development and review process, each 
protocol will be assessed for its level of risk and the degree of monitoring required. Every  
type of protocol (e.g., NIH sponsored, in-house sponsored, industrial sponsored, NCI 
cooperative group, etc.) will be addressed, and monitoring procedures will be established at 
the time of protocol activation. 
 
 
17.1 
PROTECTION OF HUMAN SUBJECTS 
 
Participation in this trial is voluntary. All patients will be required to sign a statement of informed 
consent, which must conform to MSKCC 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). 
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: 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 20 of 22 
 
 
 
 
• 
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. 
 
17.2.1 
 
This protocol is not an Industry or Cooperative group protocol. 
 
18.1 
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. 
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. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-075 A(6) 
Approval date: 29-Aug-2018 
Page 21 of 22 
 
 
 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
19.0 
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Bolling T, Schuck A, Paulussen M, et al. Whole lung irradiation in patients with exclusively 
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DeVita VT, Hellman S, Rosenberg SA. Cancer, principles & practice of oncology. 7th ed. 
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Stanelle EJ, Christison-Lagay ER, Wolden SL, Meyers PA, La Quaglia MP. Pulmonary 
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Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: 
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Ueda T, Uchida A, Kodama K, et al. Aggressive pulmonary metastasectomy for soft tissue 
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Dhakal S, Corbin KS, Milano MT, et al. Stereotactic body radiotherapy for pulmonary 
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Zamboglou N, Furst G, Pape H, Bannach B, Molls M, Schmitt G. [Results of whole lung 
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Yeh ET, Tong AT, Lenihan DJ, et al. Cardiovascular complications of cancer therapy: 
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20.0 
APPENDICES 
 
Not applicable