Pilot Study Evaluating Stereotactic Body Radiation Therapy (SBRT) and Adaptive Radiation Therapy (ART) for Pulmonary Metastases From Soft Tissue Sarcomas
Phase: NA
Conditions: Stage IV Adult Soft Tissue Sarcoma, Sarcoma,Soft Tissue
Sponsor: Medical College of Wisconsin

Protocol Title:  Pilot Study Evaluating Stereotactic Body Radiation Therapy (SBRT) and 
Adaptive Radiation Therapy (ART) for Pulmonary Metastases from Soft Tissue Sarcomas 
 
NCT Number:  NCT01949506 
 
Version Date:  February 24, 2017 

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TITLE 
 
Pilot Study Evaluating Stereotactic Body  Radiation Therapy (SBRT) and Adaptive Radiation Therapy 
(ART) for Pulmonary Metastases from Soft Tissue Sarcomas 
 
 
 
Principle Investigator/Radiation Oncology: 
M. Bedi, MD 
E. Gore, MD (Co-PI) 
 
 
Radiation Oncology Co-Chairs: 
C. Johnstone, MD 
 
 
Medical Oncology Chair: 
J. Charlson, MD 
 
 
Physics Chair 
X. Allen Li, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version Date:  
February 24, 2017  
 
 
 

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INDEX 
 
 
 
Schema  
 
Eligibility Checklist  
 1.0 
Introduction 
 2.0 
Objectives 
 
 3.0 
Patient Selection  
 4.0 
Recommended Pretreatment Evaluations 
 5.0 
Registration Procedures 
 6.0 
Radiation Therapy 
 7.0 
Drug Therapy 
 8.0 
Surgery 
 9.0 
Other Therapy 
10.0 
Tissue/Specimen Submission 
11.0 
Patient Assessments 
12.0 
Data Collection 
13.0 
Statistical Considerations 
 
References 
 
 
Appendix I 
-Performance Status Scoring 
 
Appendix II  
-Staging System 
 
Appendix III 
-Toxicity Scoring 
 
Appendix IV 
-QoL Scoring 
 
 
 
 

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TITLE 
Pilot Study Evaluating Stereotactic Body  Radiation Therapy (SBRT) and Adaptive Radiation Therapy 
(ART) for Pulmonary Metastases from Soft Tissue Sarcomas 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Population:   
 
 
Accrual goal is 20 patients with pulmonary metastatic disease from soft tissue sarcoma primaries.  A reasonable 
estimate for accrual at the Medical College of Wisconsin is 5 patients per year and 5 patients per year at Kraemer 
Cancer Center, West Bend with a conservative estimate of 40 tumors.  The estimated duration of the study is 2 
years. 
 
 
Required Sample Size: 20 
Primary Soft Tissue 
Sarcoma (STS) 
1-5 Pulmonary Metastases 
(Histologic confirmation or radiologic 
characteristics c/w pulmonary 
metastases) 
Register 
SBRT 

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4
 
 
ELIGIBILITY CHECKLIST 
_____ (Y) 
1. Does the patient have a pathologically (histologically or cytologically) proven diagnosis  
 
    of a soft tissue sarcoma? 
 
_____ (Y) 
2. Has the patient had a history and physical within 4 weeks of registration? 
 
_____ (Y) 
3. Was the patient deemed inoperable by cardiothoracic surgery, declined surgery, or surgery not 
recommended by the multidisciplinary tumor board? 
 
_____ (Y) 
4. Was pre-treatment imaging done within 6-8 weeks prior to registration? 
 
_____ (Y) 
5. Is the patient at least 18 years of age? 
 
_____ (Y) 
6. Was the Zubrod performance scale 0-2 4 weeks prior to registration? 
 
_____ (Y) 
7. Did the patient sign a study-approved informed consent? 
 
_____ (N) 
8. Does the patient have >5 pulmonary metastases disease?     
                                
_____ (N) 
9. Does the patient have disease progression outside of the lungs within 3 months of  
                                enrollment? 
 
 
 

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1.0 
INTRODUCTION 
 
Management for patients with distant metastatic disease from solid tumors is usually conducted with 
palliative intent.  Pulmonary tissue is a common site for metastatic seeding, in particular for sarcomatoid 
tumors (1).  Historically, metastatic disease to the lungs from a primary sarcoma has traditionally been by 
surgical means in conjunction with the use of chemotherapy (2-6). 
 
Recently, however, a multimodality approach to treatment for pulmonary metastatic lesions from various 
malignancies, including sarcoma, has been employed at this institution.  NCCN guidelines for single 
organ and limited tumor bulk metastases recommend an approach of metastectomy +/- post-operative 
chemotherapy +/-post-operative RT, interventional techniques such as RFA or cryoablation, or SBRT/RT 
methods. 
 
Patients with metastatic soft tissue sarcoma to any site often undergo chemotherapy.   However, it is 
often difficult to determine whether the chemotherapy alone is effective treating widespread disease (7, 
8). 
In a study done by Canter, et al, those that were administered perioperative chemotherapy had a median 
post-metastasis disease-specific survival of 24 months vs. 33 months in those those that underwent both 
surgery and chemotherapy. (9).    Thus, the need for local therapy in conjunction with chemotherapy may 
be warranted.  Recently, less invasive techniques, such as SBRT and RFA have been employed in 
treating oligometastatic disease. 
 
Radiation has typically been reserved for palliation.  Hypofractionated sterotactic body radiation therapy 
(SBRT) is an emerging method of treatment for oligometastatic disease in the lungs.  SBRT has become 
standard of care for stage I lung cancer in medically inoperable patients with local control rates exceeding 
90% with minimal toxicity (10). 
 
SBRT is increasingly being used to treat pulmonary metastases (11-17).  This is particularly appealing as 
the toxicity is low, control rates are high and in many cases invasive procedures can be avoided. 
Large hypofractionated doses are used to treat metastatic lesions.  SBRT can be safely administered 
because the volume of each lesion is small with tight margins.  Moreover, many beams are utilized, so 
that a small fraction of the total dose is administered through each beam, thereby effectively minimizing 
toxicity through the trajectory of the beam.  However, all beams coalesce at the target and result in a 
larger, summed, dose (11, 20-21).  Many studies have evaluated outcomes and toxicity in patients who 
have undergone SBRT for pulmonary oligometastasis from various tumor primaries (12).  Lesions are 
usually central or peripherally located and a small proportion is comprised of sarcoma primaries.  
Nonetheless, crude local control rates when utilizing this method of treatment are between 67-100% and 
2-year survival ranging between 32-87% (11, 13-19).  Toxicity was acceptable with very few developing 
grade 3 or 4 complications. 
 
Although local control of pulmonary metastases with SBRT is high, there is no prospective data 
evaluating control with SBRT for pulmonary metastases from soft tissue sarcomas.  This is a prospective 
study to document the local control rates with SBRT specifically for pulmonary metastases from soft 
tissue sarcoma.  This study will prospectively document acute and late toxicity, quality of life (QoL), tumor 
control, and survival.   
 
Siva, et al reported a literature review to critically review the effects of SBRT for treatment of pulmonary 
metastases.  Data from 334 patients combined from 13 publications reported a 2 year weighted local 
control of 77.9% (12).   Rusthoven et al conducted a multi-institutional Phase I/II trial of SBRT for patients 
with 1-3 lung metastases up to 7cm.  Two year local control was 96% (19). 
 
The University of Rochester retrospectively reviewed control rates of 74 sarcoma pulmonary metastases 
in 52 patients from 1990-2006 (22).  Sixteen patients had surgical procedures for management.  Fifteen 
patients were treated to 74 lesions with SBRT. The preferred dose was 50 Gy in 5 fractions.  Two-year 
local control was 88% for all patients treated with radiation although with exclusion of one patient’s lesion 
treated with 30 GY in 10 fractions, local control was 97%.   There was no ≥ grade 3 pulmonary toxicity. 
 
 

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Daily treatment uncertainties include set-up error, internal organ motion, tumor size, patient position, and 
patient external contour (23-25).  The precision of radiation depends on the consistency of these planning 
variables.  Changes in these variables may change the dose to the tumor and organs at risk.  In order to 
ensure coverage of the target during organ movement, conventionally margins have been added to the 
clinical target volume (CTV) to form a planning target volume (PTV).  However, increasing the margin 
size leads to increased radiation dose to adjacent organs at risk.  As such, adaptive radiation therapy 
(ART) has been done to decrease the effects of treatment deviation for each patient.  This allows a re-
optimization of the treatment plans in regards to dose distribution and delivery of radiation with each 
fraction (23-25).    
 
In the lung, delineation of the target (tumor) for planning is critical (26).  This is especially important when 
delivering radiation in a stereotactic manner, where margins are smaller compared to conventional 3D 
conformal radiation therapy.  In the lung, target delineation may be confounded by respiratory motion and 
breathing patterns and changes in the position and shape of the target lesion.  Respiratory cycle issues 
can be taken into consideration with a 4D CT scan, however, changes in breathing patterns of the patient 
and tumor changes need image guidance as well (26).  Ramsey et al, showed that image-guided and 
ART in patients with lung cancer lead to a decrease of 21% of lung volume being treated receiving ≥ 20 
Gy (27).    
 
The primary goal of this study is to assess the local management with SBRT for patients with pulmonary 
oligometastatic disease from a sarcoma primary using ART.  Toxicity, quality of life, progression and 
survival rates will be obtained for each method.  The goal is to improve the care of metastatic sarcoma 
patients by employing techniques that are standard of care to treat oligometastatic disease.  This study, 
however, will assess patients who have metastatic disease from a primary sarcoma, which has not yet 
been prospectively studied. 
 
 
 
 
 
Studies and Publications Supporting SBRT for Pulmonary Metastatses Including Sarcoma: 
 
 
1. Wulf, et al.  Dose-response in stereotactic irradiation of lung tumors. Radiother Oncol. 2005  
Oct;77(1):83-7. 
a. Conclusions: When normalization to a biologically effective dose (BED) is used a dose of 94 Gy 
at the isocenter and 50 Gy at the PTV margin are demonstrated to give 50% probability of tumor 
control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only 
significant factor for local control. 
 
2. Le QT, et al. Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for 
lung tumors. J of Thorac Oncol, 2006 Oct;1(8):802-9.   
a. Conclusions: Single-fraction stereotactic RT is feasible for selected patients with lung tumors. For 
those with prior thoracic RT, 25 Gy may be too toxic. Higher dose was associated with improved 
local control. Longer follow-up is necessary to determine the treatment efficacy and toxicity. 
 
3. Uematsu, et al. Focal, high dose, and fractionated modified stereotactic radiation therapy for lung 
carcinoma patients: a preliminary experience. Cancer 1998; 15;82(6):1062-70. 
a. Conclusions: With this unit and procedure, focal radiation therapy similar to stereotactic radiation 
therapy is possible for extracranial sites. The preliminary experience appeared safe and 
promising, and further exploration of this approach is warranted. 
 
4. Nagata Y, et al. Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for 
one or two lung tumors using a stereotactic body frame. Int J Radiat Oncol Biol Phys  2001;51:352–353. 
a. Conclusions: 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions 
using a stereotactic body frame was useful for the treatment of lung tumors. 
 
5. Song DY, Benedict SH, Cardinale RM, et al. Stereotactic body radiation therapy of lung tumors: 
preliminary experience using normal tissue complication probability-based dose limits. Am J Clin Oncol 
2005;28: 591–596. 

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a. Conclusions: SBRT prescribed within the confines of NTCP-restricted dosing on this protocol 
resulted in no radiation pneumonitis. Tissues other than lung parenchyma which are unaccounted 
for by NTCP may be dose-limiting when performing hypofractionated SBRT in the lung. 
 
6. Norihisa Y, et al. Stereotactic body radiotherapy for oligometastatic lung tumors. Int J Radiat Oncol Biol 
Phys 2008; 72:398–403. 
a. Conclusions: The clinical result of SBRT for oligometastatic lung tumors in our institute was 
comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of 
pulmonary oligometastases 
 
7. Brown W, Wu X, Fowler J, et al. Lung metastases treated by CyberKnife image-guided robotic 
stereotactic radiosurgery at 41 months. South Med J 2008;101:376–382 
a. Conclusions: The delivery of precisely targeted radiation doses to lung tumors in a 
hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of 
pulmonary metastases with the CyberKnife achieves good rates of local disease control with 
limited toxicity to surrounding tissues and in many cases may be beneficial for patients for whom 
surgery is not an option. 
 
8. Rusthoven KE, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung 
metastases. J Clin Oncol 2009; 27:1579 –1584. 
a. Conclusions: This multi-institutional phase I/II trial demonstrates that high-dose SBRT is safe and 
effective for the treatment of patients with one to three lung metastases. 
 
Studies and Publications Supporting Adaptive Radiation Therapy: 
 
1. Wu, et al.  Online Re-optimization of Prostate IMRT Plans for Adaptive Radiation Therapy.  Phys. Med. 
Biol. 2008;  53: 673–691  
a. Conclusions:  The feasibility of this technique is demonstrated with a clinical case with large 
deformation.  Such on-line ART process can be highly valuable with hypo-fractionated prostate 
IMRT treatment. 
 
 
2.  Ahn, et al.  Adaptive Planning in Intensity-Modulated Radiation Therapy in Head and Neck Cancers: 
Single Institution Experience and Clinical Implications.  Int. J. Radiation Oncology Biol. Phys. 2011; 80:  
677–685. 
a. Conclusions: Variations in patient positioning and anatomy changes during IMRT for head and 
neck cancer can 
affect dosimetric parameters and have wide-ranging clinical implications. The interplay between 
random positional 
variability and gradual anatomic changes requires careful clinical monitoring and frequent use of CT- 
based image-guided radiation therapy, which should determine variations necessitating new plans. 
 
3. Yan, et al.  The Us e of Adaptive Radiation Therapy to Reduce Set-Up Error:  A Prospective Clinical 
Study.  Int. J. Radiation Oncology Biol. Phys 1998;  41: 715–720. 
a. Conclusions:  The prospective study demonstrates that the ART process can be effectively 
implemented in routine 
clinical practice to improve treatment accuracy. This process is also ready to be further extended to 
reoptimize the treatment plan by incorporating the predicted patient specific setup variation.  
 
4. Ramsey et al.  A Technique for Adaptive Image-Guided Helical Tomotherapy For Lung Cancer.  Int. J. 
Radiation Oncology Biol. Phys.2006; 64: 1237–1244. 
a. Conclusions:  Megavoltage CT-based image guidance can be used to position lung cancer 
patients daily. This has the potential to decrease margins associated with daily setup error. 
Furthermore, the adaptive therapy technique described in this article can decrease the volume of 
healthy lung tissue receiving above 20 Gy. However, further study is needed to determine 
whether adaptive therapy could result in the underdosing of microscopic extension. 
 
 
 
2.0 
OBJECTIVES 

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2.1 
Hypothesis and Specific Aims:  The primary objective of the study is to assess acute toxicity of 
SBRT and adaptive planning for up to 5 pulmonary metastases from STS.   We hypothesize that SBRT 
for pulmonary metastases will result in local control similar to resection with less toxicity.  
2.1.1 Primary Objective: Assess the acute toxicity of SBRT for < 5 pulmonary metastases 
from soft tissue sarcoma. 
2.1.2 Secondary Objectives:  
2.1.2.1.1 
Local control 
2.1.2.1.2 
QoL using FACT-L 
2.1.2.1.3 
Late toxicity 
2.1.2.1.4 
Overall Survival 
 
 
3.0 
PATIENT SELECTION  
3.1 
Conditions for Patient Eligibility 
3.1.1 
≥18 years of age  
3.1.2 
Pathologic confirmation of primary soft tissue sarcoma with pathologic or radiographic 
evidence of pulmonary metastatic disease  
3.1.3 
No evidence of extra pulmonary progression of disease for 3 months prior to enrollment 
on study. 
3.1.4 
1-5 pulmonary lesions all ≤5 cm in size.   
3.1.5 
Medically inoperable or declines surgery 
3.1.6 
Patients may have had previous treatment for pulmonary metastases 
 
3.2 
Conditions for Patient Ineligibility 
3.2.1 
Patients who have uncontrolled extra-pulmonary disease 
3.2.2 
Pregnant women 
3.2.3 
Patients who have greater than 5 pulmonary lesions at the time of study enrollment 
3.2.4 
Patients who have disease progression outside the lungs within 3 months of enrollment 
on the study. 
3.2.5 
Disease pathology other than sarcoma subtypes 
3.2.6 
Patients with a history of metastatic disease from a primary other than sarcoma 
 
 
4.0 
RECOMMENDED PRETREATMENT EVALUATIONS  
4.1 
CT of the chest within 6-8  weeks of study entry 
4.2 
Documentation of extra-thoracic disease control within 6 weeks of study entry 
4.3 
PFTs are recommended, but not required within 3 months study entry 
 
 
5.0 
REGISTRATION PROCEDURES:  Eligible patients will be registered per the CTO standard procedure. 
 
6.0 
RADIATION THERAPY 
 
 
6.1 
Dose Specifications 
The treatment goal for each lesion  peripherally located lesion is 54 Gy in 3 fractions at 18 Gy per 
fraction and for centrally located lesions  50 Gy in 5 fractions at 10 Gy per fraction.  Peripherally 
located lesions are those that are >2cm beyond the proximal bronchial tree.  Centrally located 
lesions are ≤2 cm from the proximal bronchial tree.  Total dose and fractionation modifications 
may be required to meet normal tissue dose constraints.  This will be at the treating physician’s 
discretion based on tumor size, location, organs at risk, patient comorbidities and prior treatment.   
(Table 1). 
 
 
 
 
Tumor Location 
Dose per Fraction 
Total Dose 
> 2cm from proximal bronchial tree 
18 Gy 
54 Gy 

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≤2 cm from proximal bronchial tree 
10 Gy 
50 Gy 
Table 1:  Dose and Fractionation based on Tumor Location 
 
 
 
 
6.2 
Treatment Schedule:  Treatments delivered with > 10 Gy per fraction will have a minimum of 48 
hour interfraction interval.  For treatments with≤10 Gy per fraction will have a minimum 24 hour 
interfraction interval.  Treatments will be ideally completed over 14 days for 3 fraction treatments 
and over 21 days for > 5fraction treatment schedules.   
6.3 
Technical Factors  
Photon (x-ray) beams with photon energies of 6 MV will be used for most beams.  Photon beam 
energies >10 MV will be allowed for beams that must travel more than a cumulative distance of 
10 cm through soft tissue (not lung) to reach the isocenter. A minimum field dimension of 3.5 cm 
is required for any field used for treatment delivery.  
 
6.4 
Simulation, Immobilization, Localization for Treatment Delivery 
 
6.4.1 Patient Positioning:  All extra-cranial SBRT patients should be set-up with an alpha cradle 
or vacuum lock immobilization device.  Multiple immobilization devices as well as 
abdominal compression and/or stereotactic body frames may be used upon physician 
request.  
6.4.2 Image Acquisition:  Unless otherwise instructed by the physician, 4D CT and 3D CT s will 
be acquired. The planning CT scans with IV contrast are recommended.  Axial 
acquisitions with gantry 0 degrees will be required with spacing ≤ 3.0 mm between scans 
in the region of the tumor.  
6.4.3 
Localization for Treatment Delivery: Image Guided Radiation Therapy (IGRT) will be 
used for each fraction with cone-beam CT or CT on rails. The physician will check and 
approve the IGRT alignment along with table shifts prior to each fraction.  When multiple 
lesions are being treated at the same time with more than one isocenter, one isocenter 
will be chosen as the “primary” isocenter for purposes of positioning the patient.  IGRT 
images will be acquired and table shifts made for the “primary” isocenter and the 
corresponding lesion will be treated.  Shifts to the second isocenter will be made and 
orthogonal films acquired and compared to corresponding DRRs.  If shifts are indicated 
they will be made films repeated and reviewed and approved by the MD prior treatment.   
6.4.4 
This will be repeated for each isocenter 
 
6.4 
Treatment Planning/Target Volumes 
6.4.1 
Target volumes: Each target lesion will be outlined uniquely designated GTVx (x=1, 2, 3, 
4, or 5 depending on the number of lesions being treated).  GTVs will include only 
abnormal CT signal consistent with gross tumor (i.e., the GTV and the clinical target 
volume [CTV] are identical). The GTVs will be defined either on MIP (Maximum Intensity 
Projection) images or using GTVs at 3 phases (inspiration, expiration and midphase) of 
the respiratory cycle to create an ITV.   An additional 0.5 cm in the axial plane and 0.5 to 

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1.0 cm in the longitudinal plane (craniocaudal) will be added to the each GTVx (ITVx) to 
create the PTVx  
6.4.2 
Treatment Planning:  Three-dimensional coplanar or non-coplanar beam arrangements 
will be used. Non-opposing, non-coplanar beams are preferable.  A minimum of 7 beams 
will be used although typically, ≥ 10 beams of radiation will be used.   Field aperture size 
and shape should correspond nearly identically to the projection of the PTV along a 
beam’s eye view.  An exception will be when observing the minimum field dimension of 
3.5 cm when treating small lesions. Prescription lines covering the PTV will typically be 
the 60-90%.  Higher isodoses (hotspots) must be within the target and not in adjacent 
normal tissue. The prescription dose will be delivered to the margin of the PTV and fulfill 
the requirements below. 
 
6.4.3 
Dose Calculations: Heterogeneity correction will be used for dose calculations.   
 
6.4.4 
Treatment planning criteria:   
 
Normalization: The treatment plan should be normalized such that 100% 
corresponds to the center of mass of the PTV (COMPTV). This point will typically 
also correspond to the isocenter of the treatment beams. 
 
Prescription Isodose Surface Coverage: 95% of the PTV is covered by the 
prescription isodose surface and 99% of the target volume (PTV) receives a 
minimum of 90% of the prescription dose. 
 
Target Dose Heterogeneity: The prescription isodose surface selected (above) must 
be ≥ 60% of the dose at the center of mass of the PTV (COMPTV) and ≤ 90% of the 
dose at the center of mass of the PTV (COMPTV).  
6.4.5 
High Dose Spillage: 
 
Location:  Any dose > 105% of the prescription dose should occur primarily within the 
PTV itself and not within the normal tissues outside the PTV. Therefore, the 
cumulative volume of all tissue outside the PTV receiving a dose > 105% of 
prescription dose should be no more than 15% of the PTV volume. 
 
Conformality The ratio of the prescription isodose volume to the PTV volume is 
ideally < 1.2.   
6.4.6 
Low Dose Spillage:  
 
Location: The maximum total dose over all fractions in Gray (Gy) to any point 2 cm or 
greater away from the PTV in any direction should be no greater than 50% of the 
prescription dose. 
 
Volume: The ratio 50% of prescription isodose volume to the PTV volume should  be, 
< 6. 
 
6.5 
Critical Structures: 
Critical Organ Dose-Limits:  See Table 3 for dose limits to the point or 
volume. No part of any OAR will receive more than 105% of the prescribed. In addition, the 
volume of the OAR in question will be minimized, both in length and in the width, with efforts 
made to reduce the dose to the contralateral wall of the organ. Maximum point dose limits should  
be respected. The total dose will be adjusted when necessary to meet normal tissue dose 
constraints. (Table 3). 
 
 
OAR 
3 Fractions 
5 Fractions 
Max Dose 
Volume Constraint 
Max Dose 
Volume Constraint 
Spinal Cord 
18 Gy 
(6 Gy/fx) 
12. 3 Gy to < 1.2 cc 
30 Gy 
(6 Gy/fx) 
< 22.5 Gy to  < 0.25 cc 
Esophagus 
30 Gy 
(10 Gy/fx) 
17.7 Gy to < 5 cc 
52.5 Gy 
(10.5 Gy/fx) 
27.5 Gy to < 5cc 
(non-adj wall)   
Brachial 
Plexus 
21 Gy 
(7 Gy/fx) 
20.4 Gy to < 3 cc 
30 Gy 
(6 Gy/fx) 
30 Gy to < 3 cc  
Heart/ 
Pericardium 
30 Gy 
(10 Gy/fx) 
24 Gy to < 15 cc 
52.5 Gy 
(10.5 Gy/fx) 
32 Gy to < 15 cc 
Great 
Vessels 
45 Gy 
(15 Gy/fx) 
39 Gy to < 10 cc 
52.5 Gy 
(10.5 Gy/fx) 
47 Gy to < 10cc 
Trachea & 
30 Gy 
15 Gy to < 4 cc 
52.5 Gy 
18 Gy to < 4 cc 

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Proximal 
Bronchial 
Tree 
(10 Gy/fx) 
(10.5 Gy/fx) 
(non-adj wall) 
Rib* 
36.9 Gy 
(12.3 Gy/fx) 
28.8 to < 1 cc 
52.5 Gy 
(10.5 Gy/fx) 
30 Gy to < 3 cc 
Skin 
33 Gy 
(11 Gy/fx) 
30 Gy to < 10 cc 
40 Gy 
(8 Gy/fx) 
30 Gy to  < 10cc 
Stomach 
27 Gy 
(9 Gy/fx) 
16.5 Gy to < 10 cc 
35 Gy 
(7 Gy/fx) 
 
Lung 
N/A 
10.5 Gy to < 1500 cc
11.4 Gy to < 1000 cc
N/A 
12.5 Gy to 1500 cc  
13.5 Gy to < 1000 cc 
*Rib constraints are not absolute. The max dose for lesions adjacent should be < 105% prescribed dose if at all 
possible. 
 
Table 3:  Volume and Point Dose Maximum for Serial Tissues (28) 
 
 
 
 
6.5.1 
Spinal Cord: The spinal cord will be contoured based on the bony limits of the spinal 
canal on the entire planning scan. 
6.5.2 
Esophagus: The esophagus will be contoured from the cricoid cartilage to the GE 
junction 
6.5.3 
Brachial Plexus:  The brachial plexus will be contoured using the RTOG thoracic 
contouring atlas guidelines 
6.5.4 
Heart: The heart will be contoured along with the pericardial sac. The superior aspect for 
purposes of contouring will begin at the level of the inferior aspect of the aortic arch and 
extend inferiorly to the apex of the heart. 
6.5.5 
Trachea: The trachea will be contoured to 2cm above the carina. 
6.5.6 
Proximal Bronchial Tree:  This will include the most inferior 2 cm of distal trachea and the 
proximal airways on both sides as indicated in Figure 1 using RTOG atlas standard 
6.5.7 
Lung: Both the right and left lungs should be contoured as one structure on pulmonary 
windows 
6.5.8 
Skin:  The skin will be defined as the outer 0.5 cm of the body surface.   
6.5.9 
Great Vessels:  The great vessels (aorta and vena cava, not the pulmonary artery or 
vein) will be contoured using mediastinal windowing on CT.  
6.5.10 Non-adjacent Wall of a Structure: For the esophagus, trachea and proximal bronchial 
tree, and great vessels, the nonadjacent wall corresponds to the half circumference of 
the tubular structure not immediately touching the GTV or PTV, These contours would 
start and stop superiorly and inferiorly just as with the named structure. The half lumen of 
the structure should be included in this contour. (This anatomic association may occur for 
centrally located tumors.  By definition if the GTV or PTIV is touching a central structure it 
is a centrally located tumor and fractionation for centrally located disease will be used) 
6.5.11 Rib: Ribs within 5 cm of the PTV should be individually contoured. 
 
6.6 
Adaptive Planning  
6.6.1 
Patients will be placed a linear accelerator equipped with an EPID, MLCs and adaptive 
planning capabilities.  All patients will treated using the SABR, which is planned as 
explained above in sections 6.1-6.5. Each treatment field will be shaped by the MLCs 
using an in-house MLC preparation system (3) and transferred through the computer 
network to the linear accelerator. The daily portal image of each treatment field was 
aligned off-line to a reference image using a treatment verification tool (6). The reference 
image will be obtained from the simulation film, which will include the planned treatment 
isocenter and delineations of each treatment field. Throughout the study, daily setup 
errors for each treatment field will be delineated separately using the department’s 
adaptive planning software. 
6.7 
Documentation Requirements 
6.7.1 
Treatment interruptions should be avoided when possible by preventative medical 
measures and nutritional and psychological counseling.  Treatment breaks and reasons 
need to be clearly documented. 

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6.8 
Compliance Criteria  
6.8.1 
Section 6 describes appropriate conduct for treatment planning dosimetry. Criteria for 
both major and minor deviations are provided in Section 6.4. In addition to the criteria in 
Section 6.4, table 3 in Section 6.5 lists dose volume limits for specific organs and 
structures. Exceeding these limits by more than 2.5% constitutes a minor protocol 
violation. Exceeding these limits by more than 5% constitutes a major protocol violation. 
 
6.9 
Radiation Toxicity:  All acute and late toxicity related to SBRT will be reported.  Study accrual 
will be suspended for and Grade 4 or 5 events possibly related to study treatment. 
 
6.8.1 
Toxicities related to Stereotactic Body Radiation Therapy (24): 
Cough, pneumonitis, atelectasis, bronchial obstruction, bronchial stricture, 
bronchopleural fistula, chest wall pain, fracture, changes in pulmonary function tests (see 
below), pulmonary fibrosis, radiation skin changes, including dermatitis from radiation, 
alopecia, dyspnea, fever, fatigue, pericarditis, pericardial effusion, chest pain – cardiac, 
palpitations, heart failure, myocardial infarction, paresthesias.  All of these toxicities will 
be graded based on CTCAE 4.0 (Appendix III) 
6.8.2 
Lung Injury: Radiation pneumonitis is a subacute (weeks to months from treatment) 
inflammation of the end bronchioles and alveoli. Patients reporting symptoms as above 
will be promptly evaluated and treated. Mild radiation pneumonitis may be treated with 
nonsteroidal anti-inflammatory agents or steroid inhalers. More significant pneumonitis 
will be treated with systemic steroids, bronchodilators, and pulmonary toilet. It is unlikely 
that symptomatic pneumonitis will occur during the weeks radiation is actually delivered 
to the patients. However, if a patient experiences pneumonitis before completing therapy, 
therapy will be put on hold until symptoms resolve.  All patients who have pneumonitis 
will be graded and documented 
6.8.3 
Bronchial Injury (e.g., bronchial obstruction; bronchial stricture; bronchopleural fistula): 
Focal collapse of lung secondary to bronchial injury may impair overall pulmonary status. 
It also makes further assessment of tumor response more difficult as the collapsed lung 
approximates the treated tumor. Because atelectatic lung and tumor have similar imaging 
characteristics, radiology reports will often describe the overall process as progressive 
disease while the actual tumor may be stable or shrinking.  
6.8.4 
Chest Wall Pain and/or Fracture (Rib): Some patients will experience chest wall pain 
either as a result of intercostal neuropathy or rib fracture. Focal radiation induced 
osteoporosis can result in both occult and obvious rib fractures generally propagated by 
severe coughing/sneezing episodes or chest wall trauma/ The pain typically occurs 
several months after treatment and may last several more months.  
6.8.5 
Changes in Pulmonary Function Tests: Patients enrolled to this study may have some 
degree of impaired pulmonary function as measured by pulmonary function tests (PFTs), 
including Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), 
and Diffusing Capacity for Carbon Monoxide (DLCO).  In order to monitor changes in 
lung function from baseline, a protocol-specific toxicity classification for PFTs has been 
developed for use with this study. PFTs will be coded for all patients in both treatment 
groups using this scale. The RTOG Pulmonary Function Test Toxicity Scale is below.  
PFT acquisition, however, is suggested and not required for this study.   
 
 
 
Adverse 
Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 
5 
FEV1 
Decline 
0.90-0.75 times 
the patient’s 
baseline value 
<0.75-0.50 
times the 
patient’s 
baseline value 
<0.50-0.25 times 
the patient’s 
baseline value 
 
<0.25 times 
the patient’s 
baseline value 
Death 
FVC Decline 
0.90-0.75 times 
the patient’s 
baseline value 
<0.75-0.50 
times the 
patient’s 
baseline value 
 
<0.50-0.25 times 
the patient’s 
baseline value 
 
<0.25 times 
the patient’s 
baseline value 
Death 

IIT-Bedi-SBRT v2-24-17 
 
13
 
DLCO 
Decline 
0.90-0.75 times 
the patient’s 
baseline value 
<0.75-0.50 
times the 
patient’s 
baseline value 
 
<0.50-0.25 times 
the patient’s 
baseline value 
 
<0.25 times 
the patient’s 
baseline value 
Death 
Table 4:  RTOG Pulmonary Toxicity Scale (24) 
 
 
 
 
 
7.0 
DRUG THERAPY 
 
NOT APPLICABLE TO THIS STUDY 
 
8.0 
SURGERY  
 
NOT APPLICABLE TO THIS STUDY 
 
9.0 
OTHER THERAPY 
9.1 Supportive Therapy 
9.1.1 All supportive therapy for optimal medical care will be given during the study period at the discretion   
         of the attending physician(s). 
 
 
10.0 
TISSUE/SPECIMEN SUBMISSION 
NOT APPLICABLE TO THIS STUDY 
 
 
11.0 
PATIENT ASSESSMENTS 
11.1 
Study Parameters  
 
 
 
 
Assessments 
Pre-Study 
Entry 
 
 
During 
Therapy 
(each fraction)
At 4-6 
Weeks (+/- 1 
month) after 
SBRT 
Every -6 
months (+/- 
1 month) 
after RT for 
12years 
History/physical, 
X 
 
X 
X 
Zubrod PS 
X 
X 
X 
X 
Toxicity Evaluation 
 
X 
X 
X 
QoL (FACT-L) 
X 
 
 
X 
CT of the Chest 
X* 
 
 
X 
PET/CT 
 X** 
 
 
If Needed*** 
PFTs 
   X (not 
required) 
 
 
X** (not 
required) 
 
 
PFTs are not required for this protocol. PFTs may be done pre-treatment and  3 months after 
therapy and as clinically indicated.   
*CT scan- within 6-8 weeks of study entry 
** PET/CT -may be omitted if not covered by insurance although is recommended to assist in 
treatment planning and to assess the appropriateness of study therapy.  
***PET/CT-to be done at discretion of physician 
 
 
11.2 
PATIENT ASSESSMENTS 
11.2.1 Patients will be seen 4 to 6 weeks after the last fraction of radiation therapy, every 6 
months for 2 years. 

IIT-Bedi-SBRT v2-24-17 
 
14
 
11.2.2 Prior to each visit, a CT of the chest with contrast will be obtained for disease 
assessment.  If there is deemed to be progressive disease, a PET scan will be obtained 
per discretion of the physician.  Biopsy is recommended although will be at the discretion 
of treating physician. Treatment after failure will be at the treating teams discretion and 
documented.    
11.2.3 QOL assessments will be made using the FACT-L questionnaire.  Questionnaires will be 
given every 6 months for 2 years. 
 
11.3 
Measurement of Response 
11.3.1 Baseline Documentation of Target lesions 
All treated tumors (GTV1-5) should be identified as the target lesions and recorded and 
measured at baseline and with each follow-up imaging evaluation. The longest diameter 
(LD) for the target lesion will be calculated from the treatment planning CT scan using 
pulmonary windowing and reported as the baseline LD.  For follow-up assessment, 
diagnostic CT scans pulmonary windows are preferred as the method of evaluation for 
response.  Cases in which it is indeterminate whether consolidation represents residual 
tumor or treatment effect, it should be assumed that abnormalities are residual tumor 
11.3.2 Evaluation of Target and Involved Lobe Lesions 
 
Complete 
Response(CR) 
Disappearance of the target lesion; ideally, this determination will be made based on 
CT image evaluation. 
Partial Response(PR) 
At least a 30% decrease in the LD of the target lesion, taking as reference the 
baseline LD; ideally, this determination will be made based on CT image evaluation. 
Stable Disease  (SD)  
Neither sufficient shrinkage to qualify for CR/PR above nor sufficient increase to 
qualify for LE below, taking as reference the smallest LD since the treatment started 
Local Enlargement(LE) 
At least a 20% increase in the LD of target lesion, taking as reference the smallest LD 
recorded since the treatment started; Ideally, this determination will be made based 
on CT image evaluation. 
Primary Tumor Failure  
(PTF) 
Refers to the primary treated tumor after protocol therapy and corresponds to meeting 
both of the following two criteria: 1) Increase in tumor dimension of 20% as defined 
above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE 
should be avid on Positron Emission Tomography (PET) imaging with uptake of a 
similar intensity as the pretreatment staging PET, OR the measurable tumor should 
be biopsied confirming viable carcinoma. For outcome analysis, Marginal Failures 
(MF; see below) will also be counted as PTF; however, they should be distinguished 
specifically as MF, not PTF, on all report forms. The EORTC criteria for post-
treatment PET evaluation will be used as a basis for evaluation in cases more difficult 
to assign as to whether the uptake is pathological for cancer recurrence vs. 
inflammation.46 
Marginal Failure (MF) 
Refers to the appearance after protocol therapy of a measurable tumor appearing 
since treatment within 1.0 cm of the treated PTV (see Section 6.4) and meeting the 
following two criteria: 1) Enlarging tumor dimensions corresponding to a 20% increase 
in the longest diameter compared to initial appearance on imaging evaluation. Ideally, 
this determination will be made based on CT image evaluation; 2) The measurable 
tumor within 1.0 cm of the treated PTV should be avid on Positron Emission 
Tomography (PET) imaging with uptake of a similar intensity as the pre-treatment 
staging PET, OR the measurable tumor should be biopsied confirming viable 
carcinoma. 
Primary Tumor Control  
The absence of Primary Tumor Failure. 

IIT-Bedi-SBRT v2-24-17 
 
15
 
(PTC) 
Involved Lobe Failure 
Refers to the appearance of lung cancer after protocol therapy within the anatomical 
boundaries of the lobe in which the primary tumor arose (involved lobe). The 
measurable tumor apart from the primary tumor but within the involved lobe should 
meet criteria for LE, should be avid on Positron Emission Tomography (PET) imaging 
with uptake highly suspicious for cancer (e.g., SUV>3-5), OR the measurable tumor 
should be biopsied confirming viable carcinoma. Failure outside of the involved lobe 
(uninvolved lobes) will be considered metastatic disseminated (distant) failures. Local 
Failure Refers to either primary tumor failure or involved lobe failure or both. 
Local Control  (LC) 
The absence of Local Failure 
 
 
12. DATA COLLECTION 
 
12.1. Study Design:   
This is a non-randomized Phase II pilot protocol to determine the feasibility, toxicity, and disease 
control (overall and progression-free survival) using SBRT in patients with pulmonary 
oligometastatic disease from soft tissue sarcoma primaries. 
  
12.2. Primary Endpoint:   
The primary aim of this study is to assess toxicity and quality of life from SBRT.  All patients will 
be followed for the primary endpoint for a minimum of 3 years.  Based on historical data, we 
expect there will be minimal toxicity, both acute and long term. Adverse event rates will be 
compared at specific time points (3, 6 and 12 months after completion of SBRT).  Quality of life 
will be measured with the FACT-L questionnaire (Appendix IV). 
 
12.3. Secondary Endpoint:   
The secondary objective of this study is to assess local and regional control, progression-free 
survival and overall survival. Local and regional recurrence will be defined for each lesion per 
criteria in section 11.3.2  Disease-free survival is defined as the time from randomization until 
documented disease-recurrence or death, whichever occurs first. Patients who are disease-free 
and alive at the time of analysis will be censored at the time of their last follow-up. Patients will be 
followed for disease-free survival for a minimum of 3 years.  
 
12.4. Endpoint Analysis:   
Crude rates of locoregional recurrences will be documented as well as the time to development 
of recurrence or relapse.  Time of last follow-up or death will also be noted.  This will allow us to 
calculate progression free and overall survival rates.   
 
 
 
13.0 Statistical Considerations 
13.1 PRIMARY ENDPOINTS: Assess the acute and late toxicity of SBRT for < 5 pulmonary metastases 
from soft tissue sarcoma. 
13.1.1 Toxicity for various sub-sites are based on the CTC v 4.0 scale (see Appendix III) 
13.2 SECONDARY ENDPOINTS:  Local and regional control, QoL, and overall survival (see Section 12 
and Appendix IV) 
 
 
 
 
 
 
 
 
 

IIT-Bedi-SBRT v2-24-17 
 
16
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Putnam JB, Jr., Roth JA, Wesley MN, et al. Analysis of prognostic factors in patients undergoing 
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Jablons D, Steinberg SM, Roth J, et al. Metastasectomy for soft tissue sarcoma. Further evidence for 
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Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of 
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van Geel AN, Pastorino U, Jauch KW, et al. Surgical treatment of lung metastases: The European 
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Lanza LA, Putnam JB, Jr., Benjamin RS, et al. Response to chemotherapy does not predict survival after 
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Casper ES, Gaynor JJ, Harrison LB, et al. Preoperative and postoperative adjuvant combination 
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Canter RJ, Qin LX, Downey RJ, et al. Perioperative chemotherapy in patients undergoing pulmonary 
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Timmerman R, Paulus R, Galvin J.  Stereotactic body radiation therapy for inoperable early stage lung 
cancer.  Jama 2010; 303 (11): 1070-6 
11. 
Le QT, Loo BW, Ho A, et al. Results of a phase I dose-escalation study using single-fraction stereotactic 
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Siva S, MacManus M, Ball D. Stereotactic radiotherapy for pulmonary oligometastases: a systematic 
review. J Thorac Oncol 2010;5:1091-1099. 
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Wulf J, Baier K, Mueller G, et al. Dose-response in stereotactic irradiation of lung tumors. Radiother 
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Nagata Y, Negoro Y, Aoki T, et al. Clinical outcomes of 3D conformal hypofractionated single high-dose 
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Uematsu M, Shioda A, Tahara K, et al. Focal, high dose, and fractionated modified stereotactic radiation 
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16. 
Song DY, Benedict SH, Cardinale RM, et al. Stereotactic body radiation therapy of lung tumors: 
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Norihisa Y, Nagata Y, Takayama K, et al. Stereotactic body radiotherapy for oligometastatic lung tumors. 
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18. 
Brown WT, Wu X, Fowler JF, et al. Lung metastases treated by CyberKnife image-guided robotic 
stereotactic radiosurgery at 41 months. South Med J 2008;101:376-382. 
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Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body 
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Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951;102:316319.  
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Lax I, Blomgren H, Naslund I, et al. Stereotactic radiotherapy of malignancies in the abdomen. 
Methodological aspects. Acta Oncol 1994;33: 677- 683. 
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Dhakal S, Corbin KS, Milano MT, et al. Stereotactic body radiotherapy for pulmonary metastases from 
soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol 
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23.   
Wu QJ, Thongphiew D, Wang Z, et al.  Online Re-optimization of Prostate IMRT Plans for Adaptive   
             Radiation Therapy.  Phys. Med. Biol. 2008;  53: 673–691  
24.        Ahn PH, Chen CC, Ahn AI, et al.  Adaptive Planning in Intensity-Modulated Radiation Therapy in Head 
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             Neck Cancers: Single Institution Experience and Clinical Implications.  Int. J. Radiation Oncology Biol. 
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25.       Yan D, Ziaja E, Jaffray D, et al.  The Us e of Adaptive Radiation Therapy to Reduce Set-Up Error:  A 
            Prospective Clinical Study.  Int. J. Radiation Oncology Biol. Phys 1998;  41: 715–720. 
26.       Hasbeek CJ, Langerwaard FJ, Cuijpers JP, et al.  Is Adaptive Treatment Planning Required For Steotactic 
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27.       Ramsey CR, Langen KM, Kupelian PA, et al.  A Technique for Adaptive Image-Guided Helical   
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28.       Radiation Therapy Oncology Group 0618, 0813, 0915, & 1015. 
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Study Chair: Hiran Fernando 
 
 
 
 
 

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18
 
 
 
 
APPENDIX I 
 
KARNOFSKY PERFORMANCE SCALE 
 
 
100 
Normal; no complaints; no evidence of disease 
 
90 
Able to carry on normal activity; minor signs or symptoms of disease 
 
80 
Normal activity with effort; some sign or symptoms of disease 
 
70 
Cares for self; unable to carry on normal activity or do active work 
 
60 
Requires occasional assistance, but is able to care for most personal needs 
 
50 
Requires considerable assistance and frequent medical care 
 
40 
Disabled; requires special care and assistance 
 
30 
Severely disabled; hospitalization is indicated, although death not imminent 
 
20 
Very sick; hospitalization necessary; active support treatment is necessary 
 
10 
Moribund; fatal processes progressing rapidly 
 
0 
Dead  
 
 
 
ZUBROD PERFORMANCE SCALE 
 
 
 
0 
Fully active, able to carry on all predisease activities without restriction   
 
 
 
(Karnofsky 90-100). 
 
 
 
 
 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out  
 
 
 
work of a light or sedentary nature.  For example, light housework, office work  
 
 
 
(Karnofsky 70-80). 
 
 
 
 
 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours (Karnofsky 50-60). 
 
 
 
 
 
3 
Capable of only limited self-care, confined to bed or chair 50% or more of waking 
hours (Karnofsky 30-40). 
 
 
 
 
 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or 
chair (Karnofsky 10-20). 

IIT-Bedi-SBRT v2-24-17 
 
19
 
APPENDIX II 
 
STAGING SYSTEM 
 
AJCC 7th Edition (2009) 
Primary Tumor: 
 
T1 - less than or equal to 5cm  
o T1a - superficial 
o T1b - deep 
 
T2 - greater than 5cm  
o T2a - superficial 
o T2b - deep 
Regional Lymph Nodes: 
 
N0 - no 
 
N1 - yes 
Distant Metastases: 
 
M0 - none 
 
M1 - yes 
 
Stage Grouping: 
 
IA - T1a/b N0 G1 - low grade (grade 1), small 
 
IB - T2a/b N0 G1 - low grade (grade 1), large 
 
IIA - T1a/b N0 G2-3 - mod/high grade (grade 2-3), small 
 
IIB - T2a/b N0 G2 - mod grade (grade 2), large 
 
III - T2a/b G3, or N1 - high grade (grade 3), large; or node positive 
 
IV - M1 - metastatic 
 
 
 
 
 
 
 
 
 
 
 
 

IIT-Bedi-SBRT v2-24-17 
 
20
 
APPENDIX III 
 
 
 
CTCAE 4.0 Toxicity Grading 
Cough 
Grade 
Description 
1 
Mild symptoms; nonprescription intervention indicated 
2 
Moderate symptoms, medical intervention indicated; limiting instrumental ADL 
3 
Severe symptoms; limiting self care ADL 
 
Pneumonitis 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic; medical intervention indicated; limiting instrumental ADL 
3 
Severe symptoms; limiting self care ADL; oxygen indicated 
4 
Life-threatening respiratory compromise; urgent intervention indicated (e.g., 
tracheotomy or intubation) 
5 
Death 
 
 
Pneumonitis 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic; medical intervention indicated; limiting instrumental ADL 
3 
Severe symptoms; limiting self care ADL; oxygen indicated 
4 
Life-threatening respiratory compromise; urgent intervention indicated (e.g., 
tracheotomy or intubation) 
5 
Death 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic; medical intervention indicated; limiting instrumental ADL 
3 
Severe symptoms; limiting self care ADL; oxygen indicated 
4 
Life-threatening respiratory compromise; urgent intervention indicated (e.g., 
tracheotomy or intubation) 
5 
Death 

IIT-Bedi-SBRT v2-24-17 
 
21
 
 
Atelectasis 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic (e.g., dyspnea, cough); medical intervention indicated (e.g., chest 
physiotherapy, suctioning); bronchoscopic suctioning 
3 
Oxygen indicated; hospitalization or elective operative intervention indicated (e.g., stent, 
laser) 
4 
Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention 
indicated 
5 
Death 
 
 
Bronchial Obstruction 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic (e.g., mild wheezing); endoscopic evaluation indicated; radiographic 
evidence of atelectasis/lobar collapse; medical management indicated (e.g., steroids, 
bronchodilators) 
3 
Shortness of breath with stridor; endoscopic intervention indicated (e.g., laser, stent 
placement) 
4 
Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention 
indicated 
 
5 
Death 
 
 
Bronchial Fistula 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic; tube thoracostomy or medical management indicated; limiting instrumental 
ADL 
3 
Severe symptoms; limiting self care ADL; endoscopic or operative intervention indicated 
(e.g., stent or primary closure) 
4 
Life-threatening consequences; urgent operative intervention with thoracoplasty, chronic 
open drainage or multiple thoracotomies indicated 
5 
Death 
 

IIT-Bedi-SBRT v2-24-17 
 
22
 
 
Bronchial Stricture 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic (e.g., rhonchi or wheezing) but without respiratory distress; medical 
intervention indicated (e.g., steroids, bronchodilators) 
3 
Shortness of breath with stridor; endoscopic intervention indicated (e.g., laser, stent 
placement) 
4 
Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention 
indicated 
5 
Death 
 
 
 
 
 
Chest-wall Pain 
Grade 
Description 
1 
Mild 
2 
Moderate pain; limiting instrumental ADL 
3 
Severe pain; limiting self care ADL 
 
 
Fracture 
Grade 
Description 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic but non-displaced; immobilization indicated 
3 
Severe symptoms; displaced or open wound with bone exposure; disabling; operative 
intervention indicated 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death 
 
Pulmonary Fibrosis 
Grade 
Description 
1 
Mild hypoxemia; radiologic pulmonary fibrosis <25% of lung volume 
2 
Moderate hypoxemia; evidence of pulmonary hypertension; radiographic pulmonary 
fibrosis 25 – 50% 
3 
Severe hypoxemia; evidence of right-sided heart failure; radiographic pulmonary fibrosis 

IIT-Bedi-SBRT v2-24-17 
 
23
 
>50 - 75% 
4 
Life-threatening consequences (e.g., hemodynamic/pulmonary complications); intubation 
with ventilatory support indicated; radiographic pulmonary fibrosis >75% with severe 
honeycombing 
5 
Death 
 
 
 
Radiation Dermatitis 
Grade 
Description 
1 
Faint erythema or dry desquamation 
2 
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and 
creases; moderate edema 
3 
Moist desquamation in areas other than skin folds and creases; bleeding induced by minor 
trauma or abrasion 
4 
Life-threatening consequences; skin necrosis or ulceration of full thickness dermis; 
spontaneous bleeding from involved site; skin graft indicated 
5 
Death 
 
Dyspnea 
Grade 
Description 
1 
Shortness of breath with moderate exertion 
2 
Shortness of breath with minimal exertion; limiting instrumental ADL 
3 
Shortness of breath at rest; limiting self care ADL 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death 
 
Fever 
Grade 
Description 
1 
38.0 - 39.0 degrees C (100.4 - 102.2 degrees F) 
2 
>39.0 - 40.0 degrees C (102.3 - 104.0 degrees F) 
3 
>40.0 degrees C (>104.0 degrees F) for < =24 hrs 
4 
40.0 degrees C (>104.0 degrees F) for >24 hrs 
5 
Death 
 
 
 

IIT-Bedi-SBRT v2-24-17 
 
24
 
 
 
Fatigue 
Grade 
Description 
1 
Fatigue relieved by rest 
2 
Fatigue not relieved by rest; limiting instrumental ADL 
3 
Fatigue not relieved by rest, limiting self care ADL 
 
 
Pericarditis 
Grade 
Description 
1 
Asymptomatic, ECG or physical findings (e.g., rub) consistent with pericarditis 
2 
Symptomatic pericarditis 
3 
Pericarditis with physiologic consequences (e.g., pericardial constriction) 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death 
 
 
Pericardial Effusion 
Grade 
Description 
2 
Asymptomatic effusion size small to moderate 
3 
Effusion with physiologic consequences 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death 
 
 
 
 
Chest Pain 
Grade 
Description 
1 
Mild pain 
2 
Moderate pain; limiting instrumental ADL 
3 
Pain at rest; limiting self care ADL 
 
 
Palpitations 
Grade 
Description 

IIT-Bedi-SBRT v2-24-17 
 
25
 
1 
Mild symptoms; intervention not indicated 
2 
Intervention indicated 
 
 
Heart Failure 
Grade 
Description 
1 
Asymptomatic with laboratory (e.g., BNP [B-Natriuretic Peptide ]) or cardiac imaging 
abnormalities 
2 
Symptoms with mild to moderate activity or exertion 
3 
Severe with symptoms at rest or with minimal activity or exertion; intervention indicated 
4 
Life-threatening consequences; urgent intervention indicated (e.g., continuous IV therapy 
or mechanical hemodynamic support) 
5 
Death 
 
 
 
 
 
 
Myocardial Infarction 
Grade 
Description 
2 
Asymptomatic and cardiac enzymes minimally abnormal and no evidence of ischemic ECG 
changes 
3 
Severe symptoms; cardiac enzymes abnormal; hemodynamically stable; ECG changes 
consistent with infarction 
4 
Life-threatening consequences; hemodynamically unstable 
5 
Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IIT-Bedi-SBRT v2-24-17 
 
26
 
 
 
 
 
 
APPENDIX IV 
 
 
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. 
 
 

IIT-Bedi-SBRT v2-24-17 
 
27
 
 
 
PHYSICAL WELL-BEING 
 
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 
GP2 
I have nausea ............................................................
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have trouble 
meeting the needs of my family .................................
 
0 
 
1 
 
2 
 
3 
 
4 
GP4 
I have pain .................................................................
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment ................
0 
1 
2 
3 
4 
GP6 
I feel ill .......................................................................
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed ...............................
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not 
at all 
A little 
bit 
Some
-what 
Quite
a bit 
Very 
much 
 
GS1 
I feel close to my friends ............................................
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family ......................
0 
1 
2 
3 
4 
GS3 
I get support from my friends .....................................
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness ............................
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication about my 
illness ........................................................................
 
0 
 
1 
 
2 
 
3 
 
4 
GS6 
I feel close to my partner (or the person who is my 
main support) .............................................................
 
0 
 
1 
 
2 
 
3 
 
4 
Q1 
Regardless of your current level of sexual activity, please 
answer the following question. If you prefer not to answer it, 
please mark this box           and go to the next section. 
 
 
 
 
 
GS7 
I am satisfied with my sex life ....................................
0 
1 
2 
3 
4 

IIT-Bedi-SBRT v2-24-17 
 
28
 
 
 
Please circle or mark one number per line to indicate your response as it applies 
to the past 7 days. 
 
 
 
EMOTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some
-what 
Quite
a bit 
Very 
much 
 
GE1 
I feel sad ....................................................................
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my illness ...
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my illness ..........
0 
1 
2 
3 
4 
GE4 
I feel nervous .............................................................
0 
1 
2 
3 
4 
GE5 
I worry about dying ....................................................
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse .....................
0 
1 
2 
3 
4 
 
 
 
 
FUNCTIONAL WELL-BEING 
 
Not 
at all 
A little 
bit 
Some
-what 
Quite
a bit 
Very 
much 
 
GF1 
I am able to work (include work at home) ..................
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is fulfilling ................
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life .................................................
0 
1 
2 
3 
4 
GF4 
I have accepted my illness .........................................
0 
1 
2 
3 
4 
GF5 
I am sleeping well ......................................................
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun...............
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now .......
0 
1 
2 
3 
4 
 

IIT-Bedi-SBRT v2-24-17 
 
29
 
 
 
Please circle or mark one number per line to indicate your response as it applies 
to the past 7 days. 
 
 
 
ADDITIONAL CONCERNS 
 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
B1 
I have been short of breath ........................................
0 
1 
2 
3 
4 
C2 
I am losing weight ......................................................
0 
1 
2 
3 
4 
L1 
My thinking is clear ....................................................
0 
1 
2 
3 
4 
L2 
I have been coughing ................................................
0 
1 
2 
3 
4 
B5 
I am bothered by hair loss .........................................
0 
1 
2 
3 
4 
C6 
I have a good appetite ...............................................
0 
1 
2 
3 
4 
L3 
I feel tightness in my chest ........................................
0 
1 
2 
3 
4 
L4 
Breathing is easy for me ............................................
0 
1 
2 
3 
4 
Q3 
Have you ever smoked?  
No ___  Yes ___  If yes: 
L5 
I regret my smoking ...................................................
0 
1 
2 
3 
4