Tumor Ablation in Metastatic Sarcoma Stable on Chemotherapy
Phase: PHASE2
Conditions: Osteosarcoma, Sarcoma
Sponsor: Washington University School of Medicine

Protocol Version: 05/17/17 
 
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Tumor Ablation in Metastatic Sarcoma Stable on Chemotherapy 
 
Washington University School of Medicine 
Division of Oncology 
660 South Euclid Avenue, Campus Box 8056 
St. Louis, MO  63110 
 
Protocol#: 201309108  
Version Date: 05/17/17 
 
Principal Investigator: 
Brian A. Van Tine, M.D., Ph.D. 
 
 
 
 
Phone:  (314) 362-5817 
 
 
 
 
E-mail:  bvantine@wustl.edu 
 
Sub-Investigators 
 
 
Modality 
Angela Hirbe, M.D.  
 
Medical Oncology 
Jack Jennings, M.D.  
 
Radiology 
Ling Chen, Ph.D. 
 
 
Biostatistics 
 
 
Clinical Trials.gov# 
NCT01986829 
 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless law or regulations require such 
disclosure.  Persons to whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them 
 
 

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Tumor Ablation in Metastatic Sarcoma Stable on Chemotherapy 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
09/09/2013 
Amendment #1 Version 
 
 
 
 
 
 
10/06/2014 
Amendment #2 Version 
 
 
 
 
 
 
12/20/2016 
Amendment #3 Version  
 
 
 
 
 
 
05/17/2017 

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Tumor Ablation in Metastatic Sarcoma Stable on Chemotherapy 
 
 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligible Patients 
Patients with high-grade metastatic sarcoma stable on chemotherapy for 6-
12 cycles with 10 or fewer metastatic lesions which are amenable to 
ablation and which are measurable by CT, PET/CT, or MRI 
Treatment Plan 
Chemotherapy stopped at initiation of ablation 
therapy.  All ablation therapy completed within 
3 weeks with CT/PET every 9 weeks for the 
first year, every 12 weeks for the second year, 
and then every 6 months until radiographic 
progression or 5 years 

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Glossary of Abbreviations 
 
AE 
Adverse event 
ALT (SGPT) 
Alanine transaminase (serum glutamate pyruvic transaminase) 
ANC 
Absolute neutrophil count 
AST (SGOT) 
Aspartate transaminase (serum glutamic oxaloacetic transaminase) 
BPI 
Brief Pain Inventory 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CMP 
Complete metabolic panel 
CR 
Complete response 
CRF 
Case report form 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DOB 
Date of birth 
DSM 
Data and Safety Monitoring  
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
HRPO 
Human Research Protection Office (IRB) 
INR 
International normalized ratio 
IR 
Interventional radiology 
IRB 
Institutional Review Board 
IULN 
Institutional upper limit of normal 
MRI 
Magnetic resonance imaging 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
OHRP 
Office of Human Research Protections  
PD 
Progressive disease 
PET 
Positron emission tomography 
PFR 
Progression-free rate 
PFS 
Progression-free survival 
PI 
Principal investigator 
PR 
Partial response 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QASMC 
Quality Assurance and Safety Monitoring Committee 
QOL 
Quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors (Committee) 
SAE 
Serious adverse event 
SCC 
Siteman Cancer Center 

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SD 
Stable disease 
UPN 
Unique patient number 
US 
Ultrasound 
WBC 
White blood cell (count) 
 
 

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Table of Contents 
 
SCHEMA ........................................................................................................................................ 3 
1.0 
BACKGROUND AND RATIONALE ................................................................................ 8 
1.1 
Study Disease ................................................................................................................... 8 
1.2 
Ablation for Sarcoma ....................................................................................................... 8 
2.0 
OBJECTIVES ...................................................................................................................... 9 
2.1 
Primary Objectives ........................................................................................................... 9 
2.2 
Secondary Objectives ....................................................................................................... 9 
3.0 
PATIENT SELECTION ...................................................................................................... 9 
3.1 
Inclusion Criteria .............................................................................................................. 9 
3.2 
Exclusion Criteria ........................................................................................................... 10 
3.3 
Inclusion of Women and Minorities............................................................................... 11 
4.0 
REGISTRATION PROCEDURES ................................................................................... 11 
4.1 
Confirmation of Patient Eligibility ................................................................................. 11 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ........................... 11 
4.3 
Assignment of UPN ....................................................................................................... 11 
5.0 
TREATMENT PLAN ........................................................................................................ 12 
5.1 
Cryoablation ................................................................................................................... 12 
5.2 
Radiofrequency Ablation ............................................................................................... 13 
5.3 
Microwave Ablation ....................................................................................................... 13 
5.4 
Criteria for Ablation ....................................................................................................... 13 
5.5 
Evaluation for Severity of Pain and Quality of Life ...................................................... 14 
5.6 
Evaluability .................................................................................................................... 14 
5.7 
General Concomitant Medication and Supportive Care Guidelines .............................. 14 
5.8 
Women of Childbearing Potential .................................................................................. 14 
5.9 
Duration of Therapy ....................................................................................................... 15 
5.10 Duration of Follow-up .................................................................................................... 15 
6.0 
REGULATORY AND REPORTING REQUIREMENTS ............................................... 15 
6.1 
Definitions ...................................................................................................................... 15 
6.2 
Reporting to the Human Research Protection Office (HRPO) at Washington University
 
17 
6.3 
Reporting to the Quality Assurance and Safety Monitoring Committee (QASMC) at 
Washington University .............................................................................................................. 18 
6.4 
Timeframe for Reporting Required Events .................................................................... 18 
7.0 
STUDY CALENDAR ....................................................................................................... 19 
8.0 
DATA SUBMISSION SCHEDULE ................................................................................. 20 
9.0 
MEASUREMENT OF EFFECT........................................................................................ 20 
9.1 
Antitumor Effect – Solid Tumors................................................................................... 20 
9.2 
Disease Parameters ......................................................................................................... 21 
9.3 
Methods for Evaluation of Measurable Disease ............................................................ 22 
9.4 
Response Criteria ........................................................................................................... 24 
10.0 DATA AND SAFETY MONITORING ............................................................................ 27 
11.0 STATISTICAL CONSIDERATIONS............................................................................... 27 
11.1 Power .............................................................................................................................. 27 
11.2 Data Analysis ................................................................................................................. 28 

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12.0 REFERENCES .................................................................................................................. 29 
APPENDIX A: ECOG Performance Status Scale ........................................................................ 30 
APPENDIX B: Brief Pain Inventory ............................................................................................ 31 
APPENDIX C: FACT-G7............................................................................................................. 33 
 
 

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1.0 
BACKGROUND AND RATIONALE 
 
1.1 
Study Disease 
 
Sarcomas encompass a group of an estimated 70 different histologic subtypes with 
varying biology (1).  There are approximately 13,000 new cases of sarcoma per year in 
the United States, accounting for about 1% of adult malignancies (2).  Prognosis is poor 
for patients with metastatic disease, with only a median survival of 12 months.  Given the 
biological diversity of these tumors, a single drug therapy is not likely to be successful 
across all subtypes. As such, novel and multidisciplinary approaches will likely be 
needed to improve survival. 
 
1.2 
Ablation for Sarcoma 
 
Cytotoxic chemotherapy is the mainstay of therapy for metastatic sarcoma.  This alone, 
however, is very unlikely to result in a durable remission or cure.  There is data 
demonstrating increased survival following surgical removal of pulmonary metastases in 
the setting of osteosarcoma.  The combination of chemotherapy with resection of 
pulmonary metastases has been shown to increase the 3-year survival in metastatic 
osteosarcoma from approximately 5% to 65% (3).  An alternative procedural approach to 
treating metastatic cancer includes ablation therapy.  We hypothesize that we can use 
ablation therapy as a form of maintenance therapy in this patient population. 
 
There is retrospective data that radiofrequency ablation is safe in sarcoma patients with 
lung metastases with a 3-year survival of 65%, similar to what is quoted in surgical 
studies (4).  Given these data, we propose this single arm prospective phase II trial of 
ablation therapy in metastatic sarcoma patients that have less than 10 lesions that are 
stable on chemotherapy.  These patients must be stable on 6-12 cycles of either cytotoxic 
or biologic chemotherapy as this is the natural stopping point for Adriamycin-based 
chemotherapy, which is the standard treatment in soft tissue sarcoma.  Ablation therapy 
will then substitute as a form of maintenance therapy.   
 
Tumor ablation will include radiofrequency ablation, cryoablation, or microwave 
ablation, and will include vertebral augmentation/cementoplasty of metastases with 
pathologic fracture or impending risk of fracture in the axial-loading bones including 
vertebral bodies and pelvis.  These techniques are thought to be equivalent and the choice 
of which type of ablation to use is based on the performing radiologist and the site of 
metastasis.  Others have validated the use of progression-free rate (PFR) as a surrogate 
for activity in phase II sarcoma studies (5).  We hypothesize that there will be at least a 
40% 3-month PFR indicating a significant response to ablation therapy.  
 
 
 

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2.0 
OBJECTIVES 
 
2.1 
Primary Objectives 
 
To determine the progression-free rate at 3 months in patients with metastatic sarcoma 
stable on chemotherapy whose lesions have undergone ablation.  PFR is defined as the 
percentage of patients with no progression (local recurrence of an ablated lesion or the 
appearance of a new lesion) at 3 months after ablation.  
 
2.2 
Secondary Objectives 
 
1. To determine the rate of overall survival of patients with metastatic sarcoma stable on 
chemotherapy whose lesions have undergone ablation.  Overall survival is defined as 
the time from diagnosis of metastatic disease to the time of death. 
2. To determine the effects of ablation on quality of life (QOL) as measured with the 
FACT-G7 validated survey. 
3. To determine the effects of ablation on pain as measured by the Brief Pain Inventory 
(BPI)-Short form, a validated scale for assessment of pain. 
 
 
3.0 
PATIENT SELECTION 
 
3.1 
Inclusion Criteria 
 
1. Histologically or cytologically confirmed high-grade metastatic sarcoma that has 
been stable on 6-12 cycles of one chemotherapeutic regimen (cytotoxic or biologic) 
although a change in chemotherapy is allowed if it is a result of toxicity/tolerability 
rather than progression.  A patient must not have evidence of progression at any time 
while on chemotherapy in order to be eligible for this trial. 
 
2. Measurable disease defined as lesions that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as >10 mm with CT scan, PET CT, or 
MRI exam. 
 
3. At least 18 years of age. 
 
4. ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)  
 
5. Normal bone marrow and organ function as defined below: 
a. Leukocytes ≥ 3,000/mcL 
b. Absolute neutrophil count ≥ 1,500/mcl 
c. Platelets ≥ 100,000/mcl 
d. Total bilirubin ≤ 1.5 x IULN or 3x IULN with normal ALT and AST in patients 
with Gilbert’s disease 
e. AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN 

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f. Creatinine less than the institutional upper limit of normal         
OR 
Creatinine clearance ≥ 50 mL/min/1.73 m2  
g. INR<1.5 or patient off Coumadin at the time of ablation 
 
6. No more than 10 treatable lesions as evaluated by an experienced interventional 
oncologic radiologist for eligibility and lesion accessibility as the ablation of more 
than 10 lesions becomes technically infeasible.  These lesions must be treated in a 
two- to three-week time period from initial interventional radiology evaluation.  Lung 
and liver lesions can range from 1 cm to 7 cm for a single lesion and no greater than 5 
cm for multiple lesions. There are no size criteria for the osseous lesions.  
 
7. The 
lesions 
will 
be 
amenable 
to 
a 
safe, 
ultrasound/computed 
tomographic/fluoroscopic guided percutaneous approach. The targeted metastases 
must be sufficiently separateable from the central nervous system, major peripheral 
motor nerves, bowel, and bladder.  All lesions must be amenable to treatment. 
 
8. If patients have received radiation therapy, there must be a one-month washout 
period. 
 
9. Women of childbearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control, abstinence) prior to study entry and for 
the duration of ablation.  Should a woman become pregnant or suspect she is pregnant 
while participating in this study, she must inform her treating physician immediately. 
 
10. Patient (or legally authorized representative if applicable) must be able to understand 
and willing to sign an IRB approved written informed consent document. 
 
3.2 
Exclusion Criteria 
 
1. History of other malignancy ≤ 5 years previous with the exception of basal cell or 
squamous cell carcinoma of the skin which were treated with local resection only, 
carcinoma in situ of the cervix, or localized prostate cancer. 
 
2. Receiving any other investigational agents simultaneously or within 3 weeks 
following ablation procedure. 
 
3. Known brain metastases.  Patients with known brain metastases must be excluded 
from this clinical trial because of their poor prognosis and because they often develop 
progressive neurologic dysfunction that would confound the evaluation of neurologic 
and other adverse events. 
 
4. Intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance with study 
requirements.  

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5. Pregnant and/or breastfeeding. 
 
6. Patients whose treatment plans include continuing chemotherapy after ablation as per 
the treating physician, as ablation therapy is meant to serve as maintenance therapy in 
lieu of chemotherapy. 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this 
trial.   
 
 
4.0 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility 
2. Registration of patient in the Siteman Cancer Center OnCore database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility collecting the information listed below: 
 
1. Registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form 
5. Completed eligibility checklist, signed and dated by a member of the study team 
6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must be registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All 
data will be recorded with this identification number on the appropriate CRFs. 
 
 
 

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5.0 
TREATMENT PLAN 
 
Eligible patients will have their lesions ablated using any one or more of the procedures 
described below.  The choice of the procedure will be based on the expertise of the interventional 
oncologic radiologist and the site of metastasis.  These techniques are thought to be equivalent. 
 
Pre-and post procedure, patients must fill out a QOL survey and Brief Pain Inventory (BPI)-
Short form, which is a validated visual analog scale for assessment of patient pain asking the 
patient to rate his/her worst pain in 24 hours.  These surveys can be done over the phone. 
 
5.1 
Cryoablation 
 
Cryoablation is performed under ultrasound, CT and occasional fluoroscopic guidance 
with CT fluoroscopy available for intermittent use in cyroprobe placement and CT 
monitoring of ablation. Procedures will be performed on an outpatient basis, but patients 
can be admitted for observation post-procedure as deemed appropriate by the treating 
interventional radiologist.  Patients are generally under moderate conscious sedation with 
midazolam and fentanyl with continuous nurse monitoring of pulse oximetry, blood 
pressure, cardiac rhythm and rate, and respirations. General endotracheal anesthesia is 
allowed in cases felt clinically appropriate as deemed by the interventional radiologist.   
One percent lidocaine alone or a 1:1 mixture of 1% lidocaine and 0.25% bupivicaine or 
0.5% ropivicaine is used for local and periosteal anesthesia.  
 
Cryoprobes from Endocare Inc. (Irvine CA) or Galil Medical (Arden Hills MN) are either 
introduced into the lesion co-axially through a bone biopsy needle or directly into the 
lesions that are amenable to such, i.e., soft tissue, lung, liver, and large lytic lesions with 
extensive bone destruction. For blastic lesions, a hand drill may be needed for bone 
access.  For larger lesions, additional cryoprobes are placed in parallel arrangement 
approximately 1.0 cm apart. The Cryocare Surgical System allows the operation of up to 
twenty-five cryoprobes at a time through 5 controllable channels. The Endocare system 
allows for the independent operation of up to 16 cryoprobes at a time. Cryoprobe 
positioning and adequate coverage of bone-tumor interface is confirmed with CT 
imaging.  When necessary thermal protection and temperature monitoring of neural 
structures is performed and includes placement of thermocouples in the neural foramen 
and epidural space at the level of the lesion and injection of warm saline or carbon 
dioxide for thermal insulation.  Bowel protection with balloon interposition or with 
carbon dioxide dissection will be used if necessary. 
 
A single freeze-thaw-freeze cycle is performed for each lesion at 10 minutes, 8 minutes, 
and 10 minutes, respectively.  The freezing portions of the cycle may vary depending on 
size of the ice-ball and adequacy of coverage and proximity to adjacent critical structures.  
Non-enhanced computed tomography is performed every 3 to 5 minutes with soft tissue 
windows (400 HU window, 40 HU level) throughout the freezing cycle to monitor 
growth of the ice ball.  After completion of the final freeze cycle of the cryoablation 
procedure, the cryoprobes are actively heated with helium until temperature is above 20 
degrees Celsius and then the probe is withdrawn.   

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5.2 
Radiofrequency Ablation 
 
Radiofrequency ablation will be predominantly used on metastatic spine lesions and will 
include use of the Dfine STAR ablation probe.  This probe will be placed coaxially 
through an introducer needle into the spinal metastatic lesion.  Time and area of kill is 
based on temperatures measured at both proximal and distal thermocouples on the probe.  
The ablation will usually be followed by placement of high viscosity cement for 
treatment of a fracture or lesions at risk. 
 
5.3 
Microwave Ablation 
   
Microwave ablation will be predominantly used on metastatic soft tissue lesions and will 
include use of Covidien’s Evident™ MWA System. Microwave ablation is performed 
under ultrasound, CT, and occasional fluoroscopic guidance with CT fluoroscopy 
available for intermittent use in probe placement and CT monitoring of ablation. 
Procedures will be performed on an outpatient basis, but patients can be admitted for 
observation post-procedure as deemed appropriate by the treating interventional 
radiologist.  Patients are generally under moderate conscious sedation with midazolam 
and fentanyl with continuous nurse monitoring of pulse oximetry, blood pressure, cardiac 
rhythm and rate, and respirations. General endotracheal anesthesia is allowed in cases felt 
clinically appropriate as deemed by the interventional radiologist.   One percent lidocaine 
alone or a 1:1 mixture of 1% lidocaine and 0.25% bupivicaine or 0.5% ropivicaine is 
used for local and periosteal anesthesia.  
 
Microwave antennae from Covidien (Mansfield, MA) are either introduced into the lesion 
co-axially through a bone biopsy needle or directly into the lesions that are amenable to 
such, i.e., soft tissue, lung, liver, and large lytic lesions with extensive bone destruction. 
For blastic lesions, a hand drill may be needed for bone access.  For larger lesions, 
additional antennae are placed in parallel arrangement approximately 1.0 cm apart. 
Antenna positioning and adequate coverage of the tumor is confirmed with CT imaging.  
When necessary, thermal protection and bowel protection with balloon interposition or 
with carbon dioxide dissection or hydrodissection will be used. 
 
Ablations will be performed according to the manufacturer’s recommendations in the 
package insert.  After completion of ablation, tract ablation is performed as the probe is 
withdrawn.   
 
5.4 
Criteria for Ablation 
 
Ablation will be postponed for ANC<1500 or platelets <100,000.  Ablation will also be 
postponed if the creatinine or bilirubin are elevated above baseline until those lab values 
normalize. 
 
 
 

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5.5 
Evaluation for Severity of Pain and Quality of Life 
 
Patients will be evaluated for severity of pain using the BPI-Short Form (Appendix B) 
with the assistance of a study coordinator at the following time points: 
 Prior to ablation 
 1 day post-ablation 
 1 month post-ablation – from first procedure if more than 1 is done 
 Time of disease progression 
 
The patients are asked to answer the questions with respect to the lesion(s) treated.  They 
are not given a copy of the BPI-Short Form and no prior responses are available to review 
on subsequent visits to minimize bias.  Analgesic use following the tumor ablation will 
be recorded as well.   
 
 
Patients will be evaluated on quality of life based on the FACT-G7 survey (Appendix C) 
with the assistance of the study coordinator at the following time points: 
 Prior to ablation 
 1 day post-ablation 
 1 month post-ablation – from first procedure if more than 1 done 
 Time of disease progression 
 
They are not given a copy of the FACT-G7 form and no prior responses are available to 
review on subsequent visits to minimize bias. 
 
These surveys may be administered over the phone. 
 
5.6 
Evaluability 
 
All patients who undergo ablation are evaluable for toxicity.  Patients are evaluated from 
date of first procedure and for 30 days thereafter. 
 
All patients who undergo ablation are evaluable for disease response provided they have 
had at least one disease assessment. 
 
5.7 
General Concomitant Medication and Supportive Care Guidelines 
 
No restrictions to medications exist with regards to the ablation procedures. However, 
clopidogrel (anti-platelet medication) should be discontinued for 5-7 days pre-procedure, 
unless the risk of discontinuation outweighs the risk of bleeding. Blood thinners such as 
warfarin should be discontinued for 5-7 days prior to the procedure as well. 
 
5.8 
Women of Childbearing Potential 
 
Women of childbearing potential (women with regular menses, women with amenorrhea, 
women with irregular cycles, women using a contraceptive method that precludes 

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withdrawal bleeding, and women who have had a tubal ligation) are required to have a 
negative pregnancy test (serum or urine) within 1 day prior to the ablation procedure. 
 
5.9 
Duration of Therapy 
 
Tumor ablation is a one-time procedure.  If at any time prior to or during ablation, the 
constraints of this protocol are considered to be detrimental to the patient’s health and/or 
the patient no longer wishes to proceed with ablation, this treatment should be 
discontinued and the reason(s) for discontinuation documented in the case report forms. 
 
Because the ablation procedures are intended to replace maintenance chemotherapy, 
chemotherapy should not resume following ablation therapy.  If the treating physician 
feels it is warranted (i.e., the patient develops a lesion that is not amenable to ablation), 
then the patient will be considered to have progressed and will be taken off trial and 
replaced. 
   
5.10 
Duration of Follow-up 
 
Patients will be followed every 9 weeks for the first year, every 12 weeks for the second 
year, and then every 6 months for 5 years or until death, progression, consent is 
withdrawn, or the study is closed, whichever occurs first.  Patients will be followed by 
CT or PET scan and office visits every 9 weeks. CT and PET scans can be performed at 
outside facilities and mailed to us for review by our radiologists. Patients removed from 
study for unacceptable adverse events will be followed until resolution or stabilization of 
the adverse event.  After progression, patients will be followed for survival every 3 
months.  
 
 
6.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outline below. 
 
The Washington University Human Research Protection Office (HRPO) requires that all events 
meeting the definition of unanticipated problem or serious noncompliance be reported as 
outlined in Section 6.2. 
 
 
6.1 
Definitions 
 
6.1.1 
Adverse Events (AEs) 
 
Definition: any unfavorable medical occurrence in a human subject including 
any abnormal sign, symptom, or disease. 
 

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Grading: the descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will 
be utilized for all toxicity reporting.  A copy of the CTCAE version 4.0 can be 
downloaded from the CTEP website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions 
for the terms listed that should be used are those provided by the Department 
of Health and Human Services’ Office for Human Research Protections 
(OHRP).  A copy of this guidance can be found on OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
Only AEs that are related to the ablation procedure should be reported 
for study data.  
 
6.1.2 
Serious Adverse Event (SAE) 
 
Definition:  any adverse event related to the ablation procedure that results in 
any of the following outcomes: 
 Death 
 A life-threatening adverse drug experience 
 Inpatient hospitalization or prolongation of existing hospitalization 
 A persistent or significant disability/incapacity (i.e., a substantial 
disruption of a person’s ability to conduct normal life functions) 
 A congenital anomaly/birth defect 
 Any other experience which, based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above 
 
6.1.3 
Unexpected Adverse Experience  
 
Definition: any adverse experience related to the ablation procedure, the 
specificity or severity of which is not consistent with the current investigator 
brochure (or risk information, if an IB is not required or available). 
 
 
6.1.4 
Life-Threatening Adverse Experience  
 
Definition: any adverse experience, related to the ablation procedure, that 
places the subject (in the view of the investigator) at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction that, had it 
occurred in a more severe form, might have caused death. 
 
 
 
 
 

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6.1.5 
Unanticipated Problems 
 
Definition: 
 
 unexpected (in terms of nature, severity, or frequency) given (a) the 
research procedures that are described in the protocol-related 
documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population 
being studied; 
 related or possibly related to participation in the research (in this 
guidance document, possibly related means there is a reasonable 
possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
 suggests that the research places subjects or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) 
than was previously known or recognized. 
 
6.1.6 
Noncompliance 
 
Definition: failure to follow any applicable regulation or institutional policies 
that govern human subjects research or failure to follow the determinations of 
the IRB.  Noncompliance may occur due to lack of knowledge or due to 
deliberate choice to ignore regulations, institutional policies, or determinations 
of the IRB. 
 
6.1.7 
Serious Noncompliance 
 
Definition: noncompliance that materially increases risks, that results in 
substantial harm to subjects or others, or that materially compromises the 
rights or welfare of participants. 
 
6.1.8 
Protocol Exceptions 
 
Definition: A planned deviation from the approved protocol that are under the 
research team’s control. Exceptions apply only to a single participant or a 
singular situation. 
 
Pre-approval of all protocol exceptions must be obtained prior to the event.   
 
6.2 
Reporting to the Human Research Protection Office (HRPO) at Washington 
University 
 
The PI is required to promptly notify the IRB of the following events: 
 

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 Any unanticipated problems involving risks to participants or others which occur 
at WU, any BJH or SLCH institution, or that impacts participants or the conduct 
of the study. 
 Noncompliance with federal regulations or the requirements or determinations of 
the IRB. 
 Receipt of new information that may impact the willingness of participants to 
participate or continue participation in the research study. 
 
These events must be reported to the IRB within 10 working days of the occurrence of 
the event or notification to the PI of the event.  The death of a research participant that 
qualifies as a reportable event should be reported within 1 working day of the occurrence 
of the event or notification to the PI of the event. 
 
6.3 
Reporting to the Quality Assurance and Safety Monitoring Committee 
(QASMC) at Washington University 
 
The PI is required to notify the QASMC of any unanticipated problem occurring at WU 
or any BJH or SLCH institution that has been reported to and acknowledged by HRPO as 
reportable.  (Unanticipated problems reported to HRPO and withdrawn during the review 
process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via email to 
a QASMC auditor. 
 
6.4 
Timeframe for Reporting Required Events  
 
Reportable adverse events will be tracked for 30 days following ablation. Only AEs that 
are related to the ablation procedure should be reported for study data. 
 
Deaths 
Any reportable death while on study or within 30 days of 
study 
Immediately, within 24 hours, 
to PI and the IRB 
Any reportable death while off study  
Immediately, within 24 hours, 
to PI and the IRB 
Adverse Events/Unanticipated Problems 
Any reportable adverse events as described in Sections 6.1.1 
and 6.1.2 (other than death) 
Immediately, within 24 hours 
to PI and within 10 working 
days to the IRB  
All adverse events regardless of grade and attribution should 
be submitted cumulatively  
Include in DSM report 
Noncompliance and Serious Noncompliance 
All noncompliance and serious noncompliance as described in 
Sections 6.1.6 and 6.1.7 
Immediately, within 24 hours, 
to PI and within 10 working 
days to the IRB 
 
 

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7.0 
STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 3 weeks prior to start of protocol therapy.  Scans 
and x-rays must be done no more than 3 weeks prior to the start of ablation. 
 
 
Baseline Ablation 1 day after 
ablation 
1 month after 
ablation 
Follow-
upd 
Progression 
Physical exam, incl. medical 
history, weight, VS, PS 
X 
 
 
 
 
 
CBC 
X 
 
 
 
 
 
CMP 
X 
 
 
 
 
 
PT/PTT and INR 
X 
 
 
 
 
 
Pregnancy testa 
X 
 
 
 
 
 
IR evaluationb 
X 
 
 
 
 
 
CT or PET scan 
 
 
 
 
Xd 
 
FACT-G7 
X 
 
X 
X 
 
X 
BPI short form 
X 
 
X 
X 
 
X 
Adverse events 
 
Xc 
 
 
 
 
Survival follow-up 
 
 
 
 
 
Xe 
a: Women of childbearing potential only 
b: Patients must have 10 or fewer treatable lesions when enrolled in the study and will be seen in consultation by an 
experienced interventional oncologic radiologist with evaluation of available PET, CT, MR, and US images for 
eligibility and lesion accessibility 
c: Tracked for 30 days following ablation 
d: The patients will be imaged as per routine care at the following time points: 6 weeks post first-procedure, every 9 
weeks for the first year, every 12 weeks for the second year, and every 6 months for 5 years or until death or 
radiographic progression, whichever comes first.  
e. After progression, patients will be followed every 3 months for survival only. 
 
 
 

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8.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
Registration Form 
Eligibility Form 
On-Study Form 
Prior to starting treatment 
Ablation Form 
After treatment 
Toxicity Form 
30 days following ablation 
Tumor Measurement 
Form 
Follow Up Form 
Baseline 
6 weeks after ablation 
Every 9 weeks during Year 1 
Every 12 weeks during Year 2 
Every 6 months for all subsequent years 
for 5 years or until progression or death 
Every 3 months after progression 
(survival only) 
QOL Form 
Baseline 
1 day after ablation 
1 month after ablation 
Progression 
 
 
9.0 
MEASUREMENT OF EFFECT 
 
9.1 
Antitumor Effect – Solid Tumors 
 
There will be another PET/CT at 42 +/- 3 days following the last procedure 
(approximately 6 weeks post-procedure) and one every 9 weeks thereafter until 
progression of disease.  All imaging is standard of care. 
 
For the purposes of this study, patients should be re-evaluated for response every 9 
weeks.  In addition to a baseline scan, confirmatory scans should also be obtained 4 
weeks (not less than 4) weeks following initial documentation of objective response. 
 
Response and progression will be evaluated in this study using the new international 
criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) 
guideline (version 1.1) [Eur J Ca 45:228-247, 2009].  Changes in the largest diameter 
(unidimensional measurement) of the tumor lesions and the shortest diameter in the case 
of malignant lymph nodes are used in the RECIST criteria. 
 
 

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9.2 
Disease Parameters 
 
Measurable disease:  Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as >20 mm by chest 
x-ray, as >10 mm with CT scan, or >10 mm with calipers by clinical exam.  All tumor 
measurements must be recorded in millimeters (or decimal fractions of centimeters). 
 
Note:  Tumor lesions that are situated in a previously irradiated area might or might not 
be considered measurable.  If the investigator thinks it appropriate to include them, the 
conditions under which such lesions should be considered must be defined in the 
protocol. 
 
Malignant lymph nodes:  To be considered pathologically enlarged and measurable, a 
lymph node must be >15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm).  At baseline and in follow-up, only 
the short axis will be measured and followed. 
 
Non-measurable disease:  All other lesions (or sites of disease), including small lesions 
(longest diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short axis), 
are considered non-measurable disease.  Bone lesions, leptomeningeal disease, ascites, 
pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, 
and abdominal masses (not followed by CT or MRI), are considered as non-measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts 
should not be considered as malignant lesions (neither measurable nor non-measurable) 
since they are, by definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-
cystic lesions are present in the same patient, these are preferred for selection as target 
lesions. 
 
Target lesions:  All measurable lesions up to a maximum of 2 lesions per organ and 5 
lesions in total, representative of all involved organs, should be identified as target 
lesions and recorded and measured at baseline.  Target lesions should be selected on the 
basis of their size (lesions with the longest diameter), be representative of all involved 
organs, but in addition should be those that lend themselves to reproducible repeated 
measurements.  It may be the case that, on occasion, the largest lesion does not lend itself 
to reproducible measurement in which circumstance the next largest lesion which can be 
measured reproducibly should be selected.  A sum of the diameters (longest for non-
nodal lesions, short axis for nodal lesions) for all target lesions will be calculated and 
reported as the baseline sum diameters.  If lymph nodes are to be included in the sum, 
then only the short axis is added into the sum.  The baseline sum diameters will be used 
as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
 

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Non-target lesions:  All other lesions (or sites of disease) including any measurable 
lesions over and above the 5 target lesions should be identified as non-target lesions and 
should also be recorded at baseline.  Measurements of these lesions are not required, but 
the presence, absence, or in rare cases unequivocal progression of each should be noted 
throughout follow-up.  
 
9.3 
Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers.  All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks before the beginning of the 
treatment. 
 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up. Imaging-based 
evaluation is preferred to evaluation by clinical examination unless the lesion(s) being 
followed cannot be imaged but are assessable by clinical exam. 
 
Clinical lesions:  Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and 10 mm diameter as 
assessed using calipers (e.g., skin nodules).  In the case of skin lesions, documentation by 
color photography, including a ruler to estimate the size of the lesion, is recommended.  
 
Chest x-ray:  Lesions on chest x-ray are acceptable as measurable lesions when they are 
clearly defined and surrounded by aerated lung.  However, CT is preferable.  
 
Conventional CT and MRI:  This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5 mm or less.  If CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be 
twice the slice thickness.  MRI is also acceptable in certain situations (e.g. for body 
scans).   
 
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal 
resolution; however, there are many image acquisition variables involved in MRI, which 
greatly impact image quality, lesion conspicuity, and measurement.  Furthermore, the 
availability of MRI is variable globally.  As with CT, if an MRI is performed, the 
technical specifications of the scanning sequences used should be optimized for the 
evaluation of the type and site of disease.  Furthermore, as with CT, the modality used at 
follow-up should be the same as was used at baseline and the lesions should be 
measured/assessed on the same pulse sequence.  It is beyond the scope of the RECIST 
guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body 
parts, and diseases.  Ideally, the same type of scanner should be used and the image 
acquisition protocol should be followed as closely as possible to prior scans.  Body scans 
should be performed with breath-hold scanning techniques, if possible. 
 

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PET-CT:  At present, the low dose or attenuation correction CT portion of a combined 
PET-CT is not always of optimal diagnostic CT quality for use with RECIST 
measurements.  However, if the site can document that the CT performed as part of a 
PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), 
then the CT portion of the PET-CT can be used for RECIST measurements and can be 
used interchangeably with conventional CT in accurately measuring cancer lesions over 
time.  Note, however, that the PET portion of the CT introduces additional data which 
may bias an investigator if it is not routinely or serially performed.   
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used 
as a method of measurement.  Ultrasound examinations cannot be reproduced in their 
entirety for independent review at a later date and, because they are operator dependent, it 
cannot be guaranteed that the same technique and measurements will be taken from one 
assessment to the next.  If new lesions are identified by ultrasound in the course of the 
study, confirmation by CT or MRI is advised.  If there is concern about radiation 
exposure at CT, MRI may be used instead of CT in selected instances. 
 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor 
evaluation is not advised.  However, such techniques may be useful to confirm complete 
pathological response when biopsies are obtained or to determine relapse in trials where 
recurrence following complete response (CR) or surgical resection is an endpoint. 
 
Tumor markers:  Tumor markers alone cannot be used to assess response.  If markers 
are initially above the upper normal limit, they must normalize for a patient to be 
considered in complete clinical response 
 
Cytology, Histology:  These techniques can be used to differentiate between partial 
responses (PR) and complete responses (CR) in rare cases (e.g., residual lesions in tumor 
types, such as germ cell tumors, where known residual benign tumors can remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment when the measurable tumor has met criteria for response or 
stable disease is mandatory to differentiate between response or stable disease (an 
effusion may be a side effect of the treatment) and progressive disease. 
 
FDG-PET: While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in 
assessment of progression (particularly possible 'new' disease).  New lesions on the basis 
of FDG-PET imaging can be identified according to the following algorithm:  
 
 Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
PD based on a new lesion. 
 No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive 
FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this 
is PD.  If the positive FDG-PET at follow-up is not confirmed as a new site of 
disease on CT, additional follow-up CT  scans are needed to determine if there is 

Protocol Version: 05/17/17 
 
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truly progression occurring at that site (if so, the date of PD will be the date of the 
initial abnormal FDG-PET scan).  If the positive FDG-PET at follow-up 
corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD. 
 FDG-PET may be used to upgrade a response to a CR in a manner similar to a 
biopsy in cases where a residual radiographic abnormality is thought to represent 
fibrosis or scarring.  The use of FDG-PET in this circumstance should be 
prospectively described in the protocol and supported by disease-specific medical 
literature for the indication.  However, it must be acknowledged that both 
approaches may lead to false positive CR due to limitations of FDG-PET and 
biopsy resolution/sensitivity. 
  
Note:  A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image. 
 
9.4 
Response Criteria 
 
9.4.1 Evaluation of Target Lesions 
 
Complete Response (CR):  Disappearance of all target lesions.  Any pathological 
lymph nodes (whether target or non-target) must have reduction in short axis to 
<10 mm. 
 
Partial Response (PR):  At least a 30% decrease in the sum of the diameters of 
target lesions, taking as reference the baseline sum diameters. 
 
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters 
of target lesions, taking as reference the smallest sum on study (this includes the 
baseline sum if that is the smallest on study).  In addition to the relative increase 
of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.  
(Note:  the appearance of one or more new lesions is also considered 
progressions). 
 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while 
on study. 
 
9.4.2 Evaluation of Non-Target Lesions 
 
Complete Response (CR):  Disappearance of all non-target lesions and 
normalization of tumor marker level.  All lymph nodes must be non-pathological 
in size (<10 mm short axis). 
 
Note:  If tumor markers are initially above the upper normal limit, they must 
normalize for a patient to be considered in complete clinical response. 
 

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Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or 
maintenance of tumor marker level above the normal limits. 
 
Progressive Disease (PD):  Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesions.  Unequivocal progression 
should not normally trump target lesion status.  It must be representative of 
overall disease status change, not a single lesion increase.     
 
Although a clear progression of “non-target” lesions only is exceptional, the 
opinion of the treating physician should prevail in such circumstances, and the 
progression status should be confirmed at a later time by the review panel (or 
Principal Investigator). 
 
9.4.3 Evaluation of Best Overall Response 
 
The best overall response is the best response recorded from the start of the 
treatment until disease progression/recurrence (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started).  The 
patient's best response assignment will depend on the achievement of both 
measurement and confirmation criteria. 
    
For Patients with Measurable Disease (i.e., Target Disease) 
Target Lesions Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR/Non-
PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not 
evaluated 
No 
PR 
SD 
Non-CR/Non-
PD/not 
evaluated 
No 
SD 
Documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** 
Only for non-randomized trials with response as primary endpoint. 
*** 
In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
Note: Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be reported 
as “symptomatic deterioration.”  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
 
 

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                                      For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since 
SD is increasingly used as an endpoint for assessment of efficacy in some trials so to 
assign this category when no lesions can be measured is not advised 
 
 
9.4.4 Duration of Response 
 
Duration of overall response:  The duration of overall response is measured 
from the time measurement criteria are met for CR or PR (whichever is first 
recorded) until the first date that recurrent or progressive disease is objectively 
documented (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are 
first met for CR until the first date that progressive disease is objectively 
documented.  
 
Duration of stable disease:  Stable disease is measured from the start of the 
treatment until the criteria for progression are met, taking as reference the 
smallest measurements recorded since the treatment started, including the baseline 
measurements. 
 
9.4.5 Other Definitions 
 
Progression-free rate: PFR is defined as the percentage of patients with no 
progression (local recurrence of an ablated lesion or the appearance of a new 
lesion) at 3 months after ablation. 
 
Overall survival: OS is defined as the time from diagnosis of metastatic disease 
to the time of death.  
 
9.4.6 Response Review 
 
For trials where the response rate is the primary endpoint, all responses will be 
reviewed by an expert independent of the study at the study’s completion.  
Simultaneous review of the patients’ files and radiological images is the best 
approach.  
 
 
 

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10.0 
DATA AND SAFETY MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, 
the Principal Investigator will provide a Data and Safety Monitoring (DSM) report to the 
Washington University Quality Assurance and Safety Monitoring Committee (QASMC) semi-
annually beginning six months after accrual has opened (if at least five patients have been 
enrolled) or one year after accrual has opened (if fewer than five patients have been enrolled at 
the six-month mark). 
 
The Principal Investigator will review all patient data at least every six months, and provide a 
semi-annual report to the QASMC. This report will include: 
 
 HRPO protocol number, protocol title, Principal Investigator name, data coordinator 
name, regulatory coordinator name, and statistician 
 Date of initial HRPO approval, date of most recent consent HRPO approval/revision, 
date of HRPO expiration, date of most recent QA audit, study status, and phase of 
study 
 History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol 
exceptions, error, or breach of confidentiality including start/stop dates and reason 
 Study-wide target accrual and study-wide actual accrual 
 Protocol activation date  
 Average rate of accrual observed in year 1, year 2, and subsequent years 
 Expected accrual end date  
 Objectives of protocol with supporting data and list the number of participants who 
have met each objective 
 Measures of efficacy 
 Early stopping rules with supporting data and list the number of participants who 
have met the early stopping rules 
 Summary of toxicities  
 Abstract submissions/publications 
 Summary of any recent literature that may affect the safety or ethics of the study  
 
The study principal investigator and Research Patient Coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator 
becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC 
according to institutional guidelines. 
 
 
11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
Power 
 
Our power analysis is based on the following hypotheses. The null hypothesis assumes 
that the 3-month progression-free survival (PFS) for treatment with ablation therapy is 

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overall 20% for patients with metastatic sarcoma. We hypothesize in the alternative 
hypothesis that the 3-month PFS  will be at least  40%  with ablation therapy.  This is 
based on data from a clinical trials database used to provide reference values for 
conducting phase II studies in sarcoma with PFR as the principal endpoint (5).  An 
enrollment of 36 patients can achieve at least 80% power to conclude that the alternative 
hypothesis is true based on a two-sided test of one-sample proportion at a significance 
level of 0.05.  
 
11.2 
Data Analysis 
 
Possible covariates in the analysis include sex, age, number of lesions and total diameter 
of all ablated lesions. Descriptive statistics (mean, median, range and standard deviation) 
will be provided for continuous variables and frequencies will be tabulated for categorical 
variables for the patients. Kaplan-Meier survival estimates will be obtained for 3-month 
PFS for patients with ablation therapy. For categorical covariates such as sex, number of 
lesions (<5 vs. >=5) and total diameter of all ablated lesions (10cm vs. >=10cm), if there 
are sufficient number of patients in each stratum, Kaplan-Meier survival curves will be 
plotted for each stratum and log-rank test will be performed to test if 3-month PFS is 
significantly different across strata. Overall survival will be analyzed with the same 
strategy as for 3-month PFS.  
 
To determine whether or not there is an improvement in quality of life (QOL), since the 
variables related to QOL are in ordinal scale and will be measured at baseline, one day 
post ablation, one month post ablation and at time of disease progression, the GEE 
analysis implemented in SAS PROC GENMOD will be used to take into account the 
correlation of repeated measures from the same subject. Contrast statements will be used 
to compare mean QOL scores between any two times.  The same  analysis strategy will 
be performed to determine if BPI changes over time.   
 
All analyses will be two-sided at a significance level of 0.05 and will be performed with 
statistical software SAS 9.3. 
 
 
 

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12.0 
REFERENCES 
 
1. 
Wardelmann E, Schildhaus HU, Merkelbach-Bruse S, Hartmann W, Reichardt P, 
Hohenberger P, et al. Soft tissue sarcoma: from molecular diagnosis to selection of 
treatment. Pathological diagnosis of soft tissue sarcoma amid molecular biology and 
targeted therapies. Ann Oncol;21 Suppl 7:vii265-9. 
2. 
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J 
Clin. 2009;59(4):225-49. 
3. 
Carter SR, Grimer RJ, Sneath RS, Matthews HR. Results of thoracotomy in osteogenic 
sarcoma with pulmonary metastases. Thorax. 1991;46(10):727-31. 
4. 
Palussiere J, Italiano A, Descat E, Ferron S, Cornelis F, Avril A, et al. Sarcoma lung 
metastases treated with percutaneous radiofrequency ablation: results from 29 patients. 
Ann Surg Oncol;18(13):3771-7. 
5. 
Van Glabbeke M, Verweij J, Judson I, Nielsen OS. Progression-free rate as the principal 
end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002;38(4):543-9. 
 
 

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APPENDIX A: ECOG Performance Status Scale 
 
 
Grade 
 
 
Description 
0 
Normal activity.  Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., 
light housework, office work). 
2 
In bed <50% of the time.  Ambulatory and capable of all self-care, but unable 
to carry out any work activities.  Up and about more than 50% of waking 
hours. 
3 
 
In bed >50% of the time.  Capable of only limited self-care, confined to bed 
or chair more than 50% of waking hours. 
 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
 
Dead. 
 
 
 
 

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APPENDIX B: Brief Pain Inventory 
 
 
 

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APPENDIX C: FACT-G7 
 
 
 
Below is a list of statements that other people with your illness have said are important. 
Please circle or mark one number per line to indicate your response as it applies to 
the past 7 days. 
 
 
GE6 
I worry that my condition will get worse ............................
0 
1 
2 
3 
4 
GF5 
I am sleeping well ................................................................
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life ..........................................................
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now .............
0 
1 
2 
3 
4 
 
 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
GP1 
I have a lack of energy ........................................................
0 
1 
2 
3 
4 
GP4 
I have pain ..........................................................................
0 
1 
2 
3 
4 
GP2 
I have nausea ......................................................................
0 
1 
2 
3 
4