Phase II Study of Stereotactic Body Radiation Therapy and Vertebroplasty for Localized Spinal Metastasis (SBRT Spine)
Phase: PHASE2
Conditions: Metastatic Cancer, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Sponsor: University of Texas Southwestern Medical Center

1 | P a g e  
 
Phase II Study of Stereotactic Body Radiation Therapy  
and Vertebroplasty for Localized Spinal Metastasis  
 
Organizing Institution: 
University of Texas Southwestern Medical Center, Dallas, TX 
 
Principal Investigator (P.I.): Robert Timmerman, M.D. 
 
 
 
 
 
 
 
Department of Radiation Oncology 
 
Co-Investigators:                         David Chason, M.D. 
Department of Radiology 
 
Chuxiong Ding, Ph.D. 
Medical Physics 
 
 
 
Protocol Version 3 
 
Ver.1 1.8.09 
Ver.2 2.17.09 
Ver.3 11.17.09 
Ver.4 02.20.12 
Ver. 5  03.05.12 
Ver. 6   03.08.13 
Ver. 7   06.07.13 
Ver. 8   08.13.13 
Ver. 9   10.26.17

 
2
INDEX 
 
 
Schema  
 
Eligibility Checklist  
 1.0 
Introduction 
 2.0 
Objectives 
 
 3.0 
Patient Selection  
 4.0 
Pretreatment Evaluations/Management 
 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 
14.0 
Data Safety Monitoring Plan 
 
References 
 
 
Appendix I  
- Patient Calendar (Study Parameters)  
 
Appendix II 
- Performance Status Scoring 
 
Appendix II 
- Visual Analog Scoring System (VAS) 
 
Appendix V 
- Brief Pain Inventory (BPI) 
 
Appendix V 
- Functional Assessment Cancer Therapy-General (FACT-G) 
 
Appendix VI 
- EuroQol-5 Dimension (EQ-5D) 

 
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Title:  Phase II Study of Stereotactic Body Radiation Therapy and Vertebroplasty for Localized Spinal 
Metastasis  
 
Schema:  
 
Number of patients: 29 patients for 1 fraction treatment having no prior radiation to the treatment site. 
13 patients for 5 fraction treatment having a history of prior radiation to the 
treatment site. 
 
Follow-up Assessment 
 VAS2 of treated spinal level at 2 weeks, 1, 3, and 6 months and then every 6 months for 3 years. 
 Patient pain diary of maximum VAS of treated spine recorded once a week on the same day of 
radiation treatment for 5 weeks following radiation treatment. 
 Clinical and neurological exams at 1, 3, 6, and then every 6 months for 3 years 
 BPI, Fact-G, and EQ-5D at baseline, 1, 3, 6, and 12 months. 
 MRI at baseline 1, 3, 6 and then every 6 months for 3 years.  
 
Eligibility: 
Inclusion:   
 Patients must have localized spine metastasis (a solitary spine metastasis; two contiguous levels, 
or up to three separate single vertebral levels are permitted) 
 Patients must have a VAS of ≥4 at any of the planned treatment sites 
 Patient with epidural, spinal nerve, and/or cord compression on MRI may be included 
 Histologic confirmation of cancer is required by biopsy, prior surgery, or re-biopsy 
 Narcotic pain prescription and usage information must be available and documented 
 Patients must sign study specific consent 
 Above the age of 18 
 For women of childbearing age a negative pregnancy test is required 
 Patients considered for the retreatment arm, must not of had prior radiation to the proposed 
spinal site within a 3 month interval prior to treatment 
 Zubrod score of 0-2 
 
Exclusion: 
 Patients who have been non-ambulatory for more than 7 days 
 Patients with compression fractures 
Prior 
Eligible
SBRT 1
Follo
Vertebropl
Register and 
No prior 
SBRT 5

 
4
 Spine instability requiring fixation 
 Patients with paraspinal extension 
 Patients with bony fragments 
 Planned systemic treatment within one week after treatment. 
 Absence of pathological diagnosis of cancer 
 Chemotherapy within one week of treatment 
 Patients with Multiple Myeloma, Lymphoma, or Plasmacytoma 
 Patient suffered from unstable angina and/or congestive heart failure requiring hospitalization 
within the last 6 months 
 Patient had a transmural myocardial infarction within the last 6 months 
 Patient has an acute bacterial or fungal infection requiring intravenous antibiotics at the time of 
registration 
 Patient has hepatic insufficiency resulting in clinical jaundice and/or coagulation defects 
 PT is not within normal limits or planned and feasible to be corrected to normal limits prior to 
vertebroplasy 
 PTT is not within normal limits or planned and feasible to be corrected to normal limits prior to 
vertebroplasy 
 Platelet count is < 50,000 
 History of significant psychiatric illness 
 
1Vertebroplasty may not be possible for certain patients due to tumor location or safety.  In such cases, 
patients will omit the vertebroplasty but receive all other protocol care and follow-up. 
2Visual Analog Scoring   

 
5
Phase II Study of Stereotactic Body Radiation Therapy 
and Vertebroplasty for Localized Spinal Metastasis 
 
Patient Initial: ________ 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Checklist: 
____(Y) 1. 
Does patient have localized spine metastasis (a solitary spine metastasis; two contiguous 
levels, or up to three separate single vertebral levels are permitted)? 
____(Y) 2. 
Does patient have a Visual Analog Scoring of pain ≥4 at any of the planned treatment 
sites within 14 days of registration?____(Y) 3. 
Was a MRI or CT done? (Patient 
with epidural, spinal nerve, and/or cord compression on MRI/CT may be included) 
___(N) 4. 
Does patient have paraspinal extension?  
____(Y) 5. 
Did patients sign study specific consent form? 
____(Y) 6. 
Is patient above the age of 18? 
____(Y) 7. 
Does patient have a negative pregnancy test if she is at childbearing age? 
____(Y) 8. 
Does patient have normal vertebral height?  
____(N) 9. 
Did patient have prior radiation to the proposed spinal site within a 3 month interval prior 
to treatment if patient is considered for the retreatment arm? 
____(Y) 10. Is Zubrod performance status 0-2? 
____(N) 11. Has patient been non-ambulatory for more than 7 days? 
____(N) 12. Does patient have spine instability requiring fixation? 
____(N) 13. Is there absence of pathological diagnosis of cancer? 
____(N) 14. Did patient receive chemotherapy within one week of treatment? 
____(N) 15. Does patient have Multiple Myeloma, Lymphoma, or Plasmacytoma? 
____(N) 16. 
Does the patient have a history of significant psychiatric illness? 
____(N) 17. 
Has the patient suffered from unstable angina and/or congestive heart failure requiring  
 
 
hospitalization within the last 6 months? 
____(N) 18. 
Has the patient had a transmural myocardial infarction within the last 6 months? 
____(N) 19. 
Did the patient have an acute bacterial or fungal infection requiring intravenous   
 
 
antibiotics at the time of registration? 
____(N) 20. 
Has the patient had hepatic insufficiency resulting in clinical jaundice and/or  
 
 
 
coagulation defects? 
____(Y) 21. 
Is PT within normal limits or planned and feasible to be corrected to normal limits prior 
 
to vertebroplasy? 
____(Y) 22. 
Is PTT within normal limits or planned and feasible to be corrected to normal limits prior 
 
to vertebroplasy? 
____(Y) 23. 
Is platelet count ≥ 50,000? 
____(Y) 24. 
Is narcotic pain prescription and usage information available? 
 
 
 
The Eligibility Checklist must be completed in its entirely prior to registration.  The completed, signed, 
and dated checklist used at study entry must be retained in the patient’s study file and will be evaluated 
during an audit. 
 
 
Completed by ___________________ 
 
Date ____________ 

 
6
1.0 Introduction: 
1.1 Background: 
Each year, more than 100,000 patients in the U.S. develop bone metastasis from spread of their 
primary cancer [1].  Bone is the third most common site of metastatic disease after liver and 
lung.  While all bones can be affected, the most common site of disease spread is the spine.  
Complications from this metastatic spread include bone pain, pathologic fracture, and spinal cord 
compression which are associated with considerable morbidity.  The incidence of bone 
metastasis is expected to increase over the next decade as patient survival improves due to 
advances in anticancer therapy [2].  This will make the treatment of this problem more important 
in the overall management of the surviving cancer patient. 
 
1.2 Stereotactic Radiation Therapy: 
‘Stereotactic radiosurgery’ generally refers to a radiotherapy procedure designed to treat deep-
seated brain tumors or abnormalities, and is commonly performed on a specialized machine, 
such as the Gamma Knife.  This procedure involves immobilizing the patient (cranial halo), 
affixing a stable 3-D coordinate system (fiducial box and head frame), performing high 
resolution imaging (CT or MRI), registering the images to the coordinate system using a 
computer, virtually simulating delivery of very focal and conformal dose profiles of radiation 
with steep dose gradients toward normal tissue, and finally carrying out the treatment with sub-
millimeter accuracy.  Typically very high doses of radiation (15-40 Gy) are given in a single 
treatment with this technique.  Any adjacent normal tissues that receive this dose may be 
significantly damaged, thus the requirement for very conformal treatments with rapid dose fall-
off.  An alternate strategy has been to divide total radiation dose into 2-5 fractions, still with 
fairly large dose per fraction (5-10 Gy), attempting to decrease adjacent normal tissue toxicity.  
These fractionated techniques are referred to as ‘stereotactic radiotherapy,’ and are carried out 
with hope that surrounding normal tissue will tolerate the treatment as a result of relatively more 
successful sublethal damage repair as compared to tumor. 
 
Translation of the stereotactic radiosurgery and radiotherapy concepts to extracranial sites has 
not been straightforward[4-6].  With brain treatments, the skull serves as an excellent surface to 
rigidly couple the immobilization frame using stainless steel pins under local anesthesia.  Once 
the skull is immobilized, targets within the skull are likewise immobilized in that there is very 
little movement of intracranial structures outside of fluid waves around the ventricles.  Such is 
not the case for extracranial soft tissue sites.  Inherent motion, such as the heart beating, lungs 
expanding and emptying, and bowels churning results in movement of potential targets.  In 
addition, the external surface anatomy does not have structures amenable to rigid fixation to a 
frame.  In 1994, Lax, et al, from the Karolinska Hospital in Sweden reported on the development 
and testing of an extracranial frame that incorporated a fiducial stereotactic coordinate system 
along its side panels[6].  The system used vacuum pillows to make contact with three sides of the 
patient (maximizing surface area of contact) and correlation of external anatomical reference 
points on the sternum and calf.  The spine is an ideal site for extracranial stereotactic 
radiosurgery in one fraction or stereotactic radiotherapy in 3-5 fractions.  The bony anatomy of 
the spine can be visualized with kV imaging such as orthogonal pair x-rays or cone beam CT on 
today modern radiation treatment machines.  The vertebral bones can serve as an internal fiducial 
for highly precise treatments.  The spine is also not prone to movement when immobilization 
devices are used and the patient is positioned supine [7-10]. 
 
Stereotactic body radiation therapy (SBRT) is a new therapeutic paradigm for treating localized 
tumors outside of the central nervous system and involves delivering very high doses of focused 

 
7
radiation using unique beam arrangements and special immobilization equipment[11].  As 
already demonstrated in lung and liver cancers, these treatments offer hope for improved local 
control of cancers that may translate into gains in survival especially for smaller early stage 
lesions.  SBRT employs daily treatment doses dramatically higher than typical for 
conventionally fractionated radiation therapy (CFRT).  In turn, it is incorrect to assume that 
SBRT radiobiology is similar to historical CFRT.  Indeed, a unique biology of radiation response 
for very large dose per fraction treatments is being appreciated both in terms of tumor control as 
well as normal tissue consequences translating into unique clinical outcomes.  For example, local 
control with CFRT in early stage lung cancer is consistently reported below 50% while several 
series using SBRT show local control around 90%[19, 20]. Similarly, high control rates with 
SBRT for spinal metastases have been demonstrated in large series from Memorial Sloan 
Kettering, University of Pittsburg, and Henry Ford Hospital [14-16].  The University of Pittsburg 
has the largest published series of 500 patients treated with single fraction stereotactic 
radiotherapy for spinal metastasis with local tumor control rates of 90% and long term pain 
improvement rates of 86% [15]. 
 
The radiation dose that can be delivered stereotactically to vertebral body metastasis is limited by 
the surrounding normal tissues.  The spinal cord is the most important organ to consider.  Henry 
Ford Hospital treated 49 patients with spine metastases on a dose escalation protocol allowing a 
maximum of 10 Gy in a single fraction to 10% of the cord defined 6mm above and below the 
vertebral body[16].  This was found to be a well tolerated and safe constraint.  A radiation dose-
response relationship for pain control has not been clearly established.  Large radiosurgical 
experiences have been reported with improved control with higher doses regardless of histology.  
Both large series from Henry Ford Hospital and University of Pittsburg have shown excellent 
results with minimal toxicity up to 20 Gy in a single fraction[15, 16].   In patients that have 
received prior radiation to the spine less is known about the optimal tolerated dose.  Bilsky et al. 
has reported safely giving 20 Gy separated over 4-5 treatments[14].  This protocol will deliver 
14-20 Gy in a single fraction to patients that have not received prior radiation in the area and 14-
20 Gy in 5 fractions to patients that have received prior radiation treatment to the affected level.   
 
1.3 Vertebroplasty: 
Currently, the management of metastatic spinal tumors in the neurologically intact patient 
includes radiotherapy alone or a combination of surgery and radiotherapy for tumor suppression, 
pain reduction, and spinal stabilization[17]. Extensive surgical treatment is often limited by a 
patient’s poor general condition, the multifocal nature of the disease, or the patient’s short life 
expectancy. Radiation therapy alone does not impart early spinal stability and, frequently, 
patients progress to develop further vertebral body height loss or progressive deformity[18].  
Percutaneous vertebral augmentation procedures can be effective in preventing further vertebral 
body collapse and in improving pain relief. 
 
Percutaneous Vertebroplasty (PV) is a minimally invasive fluoroscopically guided procedure 
aimed at augmenting the vertebral body by injection of  polymethyl methacrylate (PMMA) 
Initially developed in France in the late 1980’s to treat aggressive vertebral angiomas, 
vertebroplasty has gained widespread acceptance worldwide[19]. In the United States, it is 
predominantly used to treat osteoporotic compression fractures. Percutaneous kyphoplasty is a 
modification of PV. It involves the percutaneous placement of balloons into the vertebral body, 
followed by an inflation/deflation sequence to create a cavity prior to the cement injection. The 
PK procedure may restore VB height and reduce kyphotic angulation  prior to PMMA 
injection[20]. 

 
8
Vertebroplasty has been shown to be effective in controlling pain secondary to compression 
fractures in over 90% of patients in prospective studies[21]. Significant improvement in quality 
of life and decreased oral analgesic usage has also been shown. Although not widely used in the 
United States, vertebroplasty for metastatic spine disease has been shown in multiple studies to 
be effective in controlling pain and improving quality of life. In one study, 97% of patients 
experienced decrease in pain within 48 hours of the procedure. In another study 73% of patients 
decreased their oral analgesic dose by 50% or more[22-25]. 
 
The initial complication rate of vertebroplasty in patients with metastatic disease is reported to be 
approximately 10%[23]. This is significantly higher that observed when the procedure is done 
for osteoporotic compression fractures (2-5%). This is likely secondary to increased bony 
destruction in the cancer patient. Reported complications include cement leakage into the spinal 
canal, neural foramina or paraspinous soft tissue. Notably, most cement leaks are asymptomatic 
and the long term complication rate is reported to be 1.7%. Cement leakage into the neural 
foramina can cause a painful radiculopathy which typically improves spontaneously in most 
patients. Extravasation into the spinal canal can cause spinal cord compression. In some 
instances surgery to decompress the neural structures was necessary. Extravasation into the 
epidural venous plexus or inferior vena cava can result in pulmonary embolism[26]. Increased 
back pain after the procedure has also been reported and is thought to be secondary to local 
irritation from the PMMA. This typically responds well to a short course of non-steroidal anti-
inflammatory medications[25].  
 
1.4 Rationale for Current Protocol 
Spinal metastases are a common problem with unique clinical considerations.  Indications for 
treatment of spinal metastases include pain, spinal cord compression, fracture, and spinal 
instability.  The most common is pain.  Conventional palliative radiation treatments to the spine 
gave a pain response rate of approximately 50% at one month according to RTOG 97-14[27].  
Stereotactic radiation treatment of spinal metastases has demonstrated a pain response of 
approximately 80% at one month and has shown tumor control of 88% in the largest single 
series[15].  This improved local control could be the reason for the durable pain responses.  
Tumor control has even translated to improvement of neurological symptoms as seen in the trial 
done at Henry Ford Hospital[28].  
 
The rational for stereotactic radiotherapy of the spine goes beyond the excellent pain response 
rates and neurological improvement.  The primary treatment for patients with metastatic disease 
is systemic therapy.  This therapy often decreases blood counts necessitating expensive 
supportive measures.  Stereotactic radiotherapy can spare spinal bone marrow where much of an 
adult’s blood products are made.  This is done by only treating the involved vertebral bone.  It 
has been shown with this method that the risk of failure in adjacent vertebral bones is less than 
5%[29].  Next the treatment is convenient and quick allowing patients to come for 1-4 treatments 
instead of 10-15 treatments.  While the patients like this, it is also to their benefit because they 
can return to systemic therapy quicker.  Lastly, stereotactic radiation treatment is non-invasive.  
Recovery time from stereotactic radiation treatment is short and patients are often able to 
continue with their daily routines after treatment or the next day. 
 
Radiation causes osteopenia and bone loss [30-33].  While disruption of the destructive growth 
potential of malignant spinal lesions afforded by radiotherapy is at first helpful, this radiation 
induced osteopenia becomes counterproductive, especially with time from treatment.  
Vertebroplasty is a minimally invasive procedure that fortifies bone by injection of polymethyl 

 
9
methacrylate and is indicated in patients with pain from benign and malignant compression.  
Since radiation to the spine contributes to osteopenia that could lead to destabilization or 
fracture, vertebroplasty may prevent this late radiation effect.  Unfortunately, vertebroplasty may 
not be technically possible in certain patients due to inability to safely inject the cement.  For 
example, in some cervical spine locations, the vertebral arteries prohibit an approach through the 
pedicles.  Such levels, however, are less likely to undergo post radiation collapse.  As such, if it 
is not technically feasible to perform vertebroplasty, patients may still benefit from SBRT. 
 
This study proposes combining stereotactic body radiation with vertebroplasty to provide both 
durable local tumor control and pain control while preventing fracture, spinal destabilization, or 
spinal cord compression. 
 
The hypothesis of this study is stereotactic radiation treatments combined with vertebroplasty 
will increase pain relief at one month to 80% compared with conventional historical controls of 
approximately 50% in the setting of patients with no prior radiation treatments and for the group 
of patients with a history of prior radiation stereotactic radiation combined with vertebroplasty 
will increase the pain relief at one month to 75% compared with conventional historical 
retreatment control of approximately 35% .  
 
1.5 Quality of Life (QOL) measurements: 
Patients with spinal metastasis have unique clinical considerations.  Focal treatments such as 
radiation are often used to palliate or prevent symptoms such as pain, decreased mobility, 
fracture, and spinal cord compression.  QOL measurements have very important clinical 
implications since our therapy is directed at improving subjective symptoms such as pain.  
Improved understanding of patient’s symptoms and perceptions of treatment will guide what 
treatments are most advantageous in the future. 
 
1.5.1  Visual Analogue Scoring System (VAS):  
The VAS is a simple measure of pain in 11 scales (0-10).  In the study comparing the 
reliability and validity of several measures of pain intensity, the composites of 0-10 ratings 
was useful practically when maximal reliability is necessary in studies with relatively small 
sample sizes or in clinical settings where monitoring of changes in pain intensity in 
individuals is needed[34]. 
 
1.5.2  Brief Pain Inventory (BPI): 
Pain originating form the spine affects a patient’s quality of life, because the spine is the 
major weight-bearing area.  The BPI is a 17 item patient self rating scale assessing 
demographic, medication, and pain data.  The BPI includes items that will address 
components of sensory pain including severity, location, chronicity, and degree of relief 
due to therapy.  The BPI includes items that will address components of reactive pain such 
as depression, suffering, and the perceived ability of relief.  The scale is from 0-10, mild 
pain correlates with scores of 1-4, moderate pain with 5-6, and severe pain with scores of 
7-10.  Reliability has been demonstrated using the test retest item correlation (eg., for worst 
pain r = 0.93).  As these patients disease progresses, the BPI will be a valuable tool to 
access the general pain status.  Issues of the BPI validity and reliability have been 
examined in detail[34, 35].  The BPI’s ease of translation and brief administration (5 min) 
have made it a frequent used clinical tool in clinical trials where reduction or prevention of 
pain are the outcomes measured. 
 

 
10
1.5.3  Functional Assessment of Cancer Therapy (FACT-G, version 4.0): 
The FACT-G is a commonly used tool for measuring the multidimensional components of 
health related quality of life (HRQOL) over four scales: physical well being (7 items), 
social/family well-being (7 items), emotional well being (6 items), and functional well 
being (7 items)[36].  FACT developed by Cella et al., is a five point self rating scale (from 
“not at all” to “very much”).  Test-retest reliability is high for the subscales with correlation 
coefficients ranging from a high of .88 for physical well being to .82 for social and 
emotional well being.  It is written at the 4th grade reading level, all patients can complete 
the FACT-G in 5-10 minutes.  The FACT has been translated into more than 25 different 
languages. 
 
1.5.4  EuroQol – 5 Dimension (EQ-5D): 
The EQ-5D is a method for obtaining evaluations of health related QOL, preference and 
utility scores to be used as an adjustment to survival, and may be used in future cost-utility 
analysis.  It is a two-part questionnaire that takes approximately 5 minutes to complete[37].  
The first part consists of 5 dimensions including mobility, self care, usual activities, 
pain/discomfort, and anxiety/depression.  Each dimension can be graded on 3 levels 
including: 1-no problems, 2-moderate problems, and 3-extreme problems.  Health states are 
defined by the combination of the leveled responses to the five dimensions, generating 243 
(35) health states to which unconsciousness and death are added[38].  The second part is a 
visual analogue scale valuing current health state measured on a 20 cm 10 point-interval 
scale.  Best imaginable health state is scored as 100 at the top.  Both the five-item index 
score and the Visual analogue scale are transformed into a utility score between 0 “worst 
health state” and 1 “best health state”.  Either the index score or the visual analogue score 
can be used in the quality adjusted survival analysis, or enter the cost utility equation, 
depending on the health state(s) of interest[39].  Quality-adjusted survival time [U=sum of 
quality (qi) of health states K times the duration (si) spent in each health state][40].  The 
EQ-5D has been translated into multiple languages which are available at 
http://www.euroqol.org/.  
 
2.0 Objectives: 
2.1  Primary:   To determine the efficacy of stereotactic body radiation for spinal metastasis in reduction 
of pain at one month.  Both partial and complete response will be measured by the visual analogue 
system (VAS).  Partial relief equals an improvement of 2 points on the VAS and complete pain response 
is defined by a score of 0-1 on the VAS with no increase in narcotic requirement. 
 
2.2 Secondary:   
2.2.1 To determine the duration of pain response at the treated site(s) scored as the time of 
maximal pain relief to an increase of 2 on the VAS 
2.2.2 To determine the functional preservation of improvement using the Brief Pain Inventory 
(BPI) 
 
2.2.3 To prospectively assess patients quality of life (QOL) using the Functional Assessment of 
Cancer Therapy – General (FACT-G) and patients utilities using the EuroQol (EQ-5D) 
2.2.4 To determine the long term stability of the treated vertebral bone (such as fracture, sclerotic 
change, vertebral body height or mal alignment) by MRI, CT scan and plain radiographs. 
 
3.0 Patient Selection: 
3.1 
All patients must be willing and capable to provide informed consent to participate in the 
protocol. 

 
11
3.2 
Histologic confirmation of cancer will be required by biopsy, prior surgery, and re-biopsy at the 
discretion of the treating physician. 
3.3 
The patient’s Zubrod performance status must be 0-2 
3.4 
Patients must be or have been ambulatory within a week prior to treatment. 
3.5 
Patients with instability of the spine requiring instrumentation as judged by a neurosurgeon are 
not eligible. 
3.6 
No planned systemic treatment is allowed within one week after treatment. 
3.7 
Patients must have localized spinal metastasis.  This includes patients with a solitary lesion, a 
lesion that spans two contiguous levels, a lesion with a para-spinal component, and up to three 
separate single vertebral levels.  
3.8 
Patients with loss of normal vertebral height, due to for example compression fracture or other 
process, prior to treatment are not allowed. Patients with normal height and compression fracture 
are allowed. 
3.9 
Patients with prior fractionated radiation to the treated site are allowed.  Their prior treatment 
plan with date, fractionation, dose and treatment fields must be obtained. There must be at least a 
three month interval elapsed from the prior radiation to the treated site and enrollment. 
3.10 
Patients must have had a visual analog scoring of pain ≥4 at the planned treated site within 14 
days of registration.  Pain must be ongoing or require narcotic pain medicine to control. 
3.11 
Narcotic pain prescription and usage information must be available and documented. 
3.12 
Radiation sensitive histology such as lymphoma, myoloma, or plasmacytoma are not allowed. 
3.13 
Patients must be past their 18th birthday at time of registration. 
3.14 
Women of childbearing age must have documentation of a negative pregnancy test and agreed 
that they or their partner use an effective contraceptive method such as condom/diaphragm and 
spermacidal foam, non-stainless-steel intrauterine device, or prescription birth control pills. 
3.15 
Patients should not have a history of significant psychiatric illness. 
3.16 
Patients should not have severe, active co-morbidity that would preclude vertebroplasty or 
stereotactic radiotherapy, defined as follows: 
3.16.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 
months. 
3.16.2 Transmural myocardial infarction within the last 6 months. 
3.16.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of 
registration. 
3.16.4 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. 
 
3.17 
Laboratory entry criteria: 
 
3.17.1 PT within normal limits or planned and feasible to be corrected to normal limits prior to 
vertebroplasy. 
 
3.17.2 PTT within normal limits or planned and feasible to be corrected to normal limits prior to 
vertebroplasy. 
 
3.17.3  Platelet count must be ≥ 50,000. 
3.18 
Patient with epidural, spinal nerve, and/or cord compression on MRI may be included. 
 
4.0 Pretreatment Evaluations / Management: 
Note: This section lists baseline evaluations needed before the initiation of protocol treatment that do not 
affect eligibility. 
4.1  Required Evaluations/Management  
4.1.1 History and physical exam to include: determination and description of pain from spine 
metastasis and full neurological exam, VAS for given painful area, BPI, FACT-G, and EQ-
5D. 

 
12
4.1.2 Zubrod performance status (Appendix III). 
4.1.3 Imaging studies to include: complete spine MRI and plain radiographs of involved areas 
4.1.4 Laboratory work to include: complete blood count with platelets and differential within 30 
days or after last round of chemotherapy, Electrolytes, BUN and creatinine as appropriate for 
histology 
4.2  Highly Recommended Evaluations/Management 
4.2.1 Dedicated spine CT if clinically indicated or radiographic correlation is needed to evaluate 
the vertebral body cortex and look for bone fragments within the spinal canal. 
 
5.0 REGISTRATION PROCEDURES 
5.1.1 Preregistration Requirements for diagnostic pathology review 
There are no requirements for central review of pathology used for initial diagnosis. 
5.1.2 Pre-Registration Requirements for SBRT Treatment Approach 
In order to utilize SBRT in this protocol, the institution must have met technology requirements 
and have provided a description of techniques, methods, training, and experience showing 
competency to the study PIs.  
5.2 
Registration 
5.2.1 
Fax Registration 
Prior to registration, participating investigators and institutions should review the 
eligibility checklist and confirm eligibility. Patients can be registered only after 
eligibility criteria are met.  To register a patient, the site should fax the Enrollment 
Form to the Project Manager (fax #: 214-648-5923).  A unique, participant ID number 
will then be assigned.  
5.3 
Accreditation 
5.3.1 Institutional Processes 
Prior to treating patients on protocol, the institution’s specific methods for 
immobilization (e.g., frame vs. frameless), targeting, dose construction, daily verification 
of accuracy, ongoing assessment of accuracy and Quality Assurance policies must be 
described to and approved by the study PI and other approved institutional PIs.  The 
primary purpose of accreditation will be to insure that dose is delivered to the targets and 
avoiding normal tissues according to protocol criteria.  This accreditation may be 
assessed by written documentation, conference calls, or direct observation via site visits.  
Additional data may be required of institutions to verify that techniques are performing as 
intended. 
 
6.0  RADIATION THERAPY 
6.1 DOSE SPECIFICATIONS 
6.1.1 Stereotactic Targeting and Treatment 
The term “stereotactic” for the purposes of this protocol implies the targeting, planning, and 
directing of therapy using beams of radiation along any trajectory in 3-D space guided by one 
or several fiducials of known 3-D coordinates.  This differs from conventional radiation 
therapy in which therapy is directed toward skin marks or bony landmarks and assumed to 
correlate to the actual tumor target based on a historical simulation.  It should be understood 
that Stereotactic Body Radiation Therapy (SBRT) has become a treatment that is well 
beyond just stereotactic targeting.   Indeed SBRT is mostly about ablative range dose per 
fraction, accounting properly for errors including motion, careful construction of dosimetry 
that delivers high dose to the tumor and not normal tissues, and extra careful treatment 
delivery.  This protocol will require treatments to be conducted with the use of a fixed 3-D 
coordinate system defined by fiducials.  The coordinate system defined by the fiducials 

 
13
should be directly related to the radiation producing device (e.g., couch and gantry) in a 
reproducible and secure fashion.   Capability should exist to define the position of targets 
within the patient according to this same 3-D coordinate system.  As such, the patient is set 
up for each treatment with the intention of directing the radiation toward a target according to 
the known 3-D coordinates as determined in the process of treatment planning.  The nature of 
the fiducials themselves may include radio-opaque markers or rods placed at known locations 
in a frame or fixed structure adjacent to the patient as well as use of the tumor/spine itself as 
a fiducial (e.g. acquiring tomographic views of the tumor simultaneously with the treatment).   
6.1.2 Dose Fractionation 
Patients will be treated by two different dose fractionation schedules decided by a prior 
history of radiation to the treated area.  Patients with no prior treatment will receive a single 
fraction of radiation.  Each patient will have two target volumes of interest regardless of 
fractionation, a Planning Treatment Volume (PTV) and a Gross Tumor Volume (GTV) 
defined below.  Minimum prescription dose for the single fraction treatment will be 14 Gy to 
at least 95% of the PTV and 20 Gy to at least 90% of the GTV.  The plans overall maximum 
dose must occur within the GTV and be no greater than 25 Gy.  For the single dose regimen, 
the spinal cord will receive no greater than 14 Gy to a point, 10 Gy to no more than 0.25 cc 
of spinal cord volume, and 7 Gy to no more than 0.5 cc of spinal cord volume.  Patients with 
prior radiation treatment will be treated with 5 fractions of radiation. A minimum of 14 hours 
and a maximum of 7 days should separate each treatment.  Minimum prescription dose for 
the five fraction treatment will be 2.8 Gy per fraction to at least 95% of the PTV for a total 
dose of 14 Gy and 4 Gy per fraction to at least 90% of the GTV for a total dose of 20 Gy.  
The plan’s overall maximum dose must occur within the GTV and be no greater than 5 Gy 
per fraction for a total dose of 25 Gy.   For the five fraction retreatment regimen, the spinal 
cord will receive no greater than 14 Gy (2.8 Gy per fraction) to a point, 10 Gy (2 Gy per 
fraction) to no more than 0.25 cc of spinal cord volume, and 7 Gy (1.4 Gy per fraction) to no 
more than 0.5 cc of spinal cord volume. Treatment dose will prescribed typically to the 70-90 
percent isodose line for each fractionation scheme. 
 
Total doses will be the same for the single fraction and five fraction treatments 
Structure 
Dose 
Required 
Volume 
Minor Volume 
Variation 
Major Volume 
Variation 
Required 
Conformality 
index (CI) 
PTV 
≥ 14 Gy 
≥ 95% 
90% - 95% 
< 90% 
1.3 
≥ 12.6 Gy 
≥ 99% 
95% - 99% 
< 95% 
 
GTV 
20 Gy 
≥ 90% 
85% - 90% 
< 85% 
 
 
6.1.3 Premedications 
Unless contraindicated, it is recommended but not required that all patients receive 
corticosteroid premedication (e.g. Decadron 4 mg p.o. in a single dose, or equivalent) 15-60 
minutes prior to each of the five treatments for the intended purpose of modulating 
immediate acute inflammatory effects.  Analgesic premedication to avoid general discomfort 
during long treatment durations is also recommended when appropriate. 
6.1.4 Supportive medicines 
Are allowed as medically indicated. 
 
6.2 Technical Factors 
6.2.1 Physical Factors 

 
14
Only photon (x-ray) beams produced by linear accelerators with photon energies 6-21 MV 
will be allowed.  Cobalt-60 and charged particle beams (including electrons, protons, and 
heavier ions) are not allowed.  
6.2.2 Dose Verification at Treatment 
Personal dosimeter measurements (e.g. diode, TLD, etc.) may be obtained for surface dose 
verification for accessible beams as per institutional preference.  This information is not 
required by the protocol. 
 
6.3 Localization, Simulation, and Immobilization 
6.3.1 Patient Positioning 
Patients will be positioned supine in a stable position capable of allowing accurate 
reproducibility of the target position from treatment to treatment.  Positions uncomfortable 
for the patient should be avoided so as to prevent uncontrolled movement during treatments.  
A variety of immobilization systems may be utilized including stereotactic frames that 
surround the patient on three sides and large rigid pillows (conforming to patients external 
contours) with reference to the stereotactic coordinate system.  All positioning systems must 
be validated and accredited by the Study Committee (Principal Investigator and Institutional 
PIs) prior to enrolling or treating patients on this trial.  Patient immobilization must be 
reliable enough to insure that the Gross Tumor Volume (GTV) does not deviate beyond the 
confines of the Planning Treatment Volume (PTV) as defined in Section 6.4 with any 
significant probability (i.e., < 5%). 
6.3.2 Inhibition of Effects of Internal Organ Motion 
Special considerations must be made to account for the effect of internal organ motion (i.e., 
breathing, etc.) on target positioning and reproducibility.  In some cases, the intrafractional 
tumor motion is small and no special maneuvers are required to achieve motion limits (as is 
true with most spinal metastasis treated in the supine position).  Treating in the prone 
position will accentuate internal organ motion problems related to breathing and should be 
avoided unless special measures are taken to account for this motion.  When accounting for 
intrafractional motion, acceptable maneuvers including accelerator beam gating or tracking 
with the respiratory cycle, and active breath-holding techniques. Internal organ inhibition 
maneuvers must be reliable enough to insure that the Gross Tumor Volume (GTV) does not 
deviate beyond the confines of the Planning Treatment Volume (PTV) as defined in Section 
6.4 with any significant probability (i.e., < 5%).  Assessment of this motion will be left to the 
institution.  This type of interfractional motion analysis with correction is only required by 
protocol just prior to each separate treatment.  Intrafraction assessment during the course of 
each treatment (dynamic and adaptive maneuvers) is allowed and encouraged especially if 
treatment times are long. 
6.3.3 Localization and treatment maneuvers 
A direct method of localization of the spine on the day of treatment must be used in this 
protocol.  Acceptable methods would include placing a radio-opaque seed or marker that can 
be visualized and triangulated using dual imaging prior to simulation and planning.  Also, it 
would be acceptable to perform computed tomography such as axial, spiral or conebeam CT 
prior to each treatment in the treatment position to identify the tumor target directly.  
Orthogonal kv or mv x-ray images (or patients should undergo a tomographic imaging study 
utilizing the linear accelerator couch, if available) should be obtained on the day of treatment 
and compared to digitally reconstructed images from simulation to ensure proper alignment. 
 
6.4 Treatment Planning/Target Volumes 
6.4.1 Image Acquisition 

 
15
Computed Tomography (CT) will be the primary image platform for targeting and treatment 
planning.  The planning CT scans must allow simultaneous view of the patient anatomy and 
fiducial system for stereotactic targeting.  Treatment planning images should be performed in 
the treatment position using all aids/maneuvers described above.  Axial acquisitions with 
gantry 0 degrees will be required with spacing ≤ 2.0 mm between scans.  Images will be 
transferred to the treatment planning computers via direct lines, disc, or tape. 
 
Image fusion with other imaging modalities such as MRI that might be useful in delineating 
the target and normal tissues is encouraged.  MRI is to be done in the treatment position to 
allow for precise fusion. 
 
6.4.2 Target Volumes 
The GTV (gross tumor volume) will be defined as gross tumor visualized on CT/MRI scan in 
the vertebral body, para-spinal recess, or in the spinal canal.  The CTV (clinical target 
volume) will include the GTV and contiguous bone marrow cavity adjacent to the tumor.  
The posterior elements of the vertebra will be included in the CTV only when directly 
involved by gross tumor.  GTV and CTV target volume will be outlined by an appropriately 
trained physician.  The target will generally be drawn using CT soft tissue/bone windows and 
from fused MRI.  Since the spine is very stable and daily image guidance is used there will 
be no expansion from CTV to PTV.  That is, the CTV will also be the PTV (planned target 
volume).    
6.4.3 Dosimetry 
Three-dimensional coplanar or non-coplanar beam, arc rotation, or Intensity Modulated 
Radiotherapy (IMRT) beam arrangements will be custom designed for each case to deliver 
highly conformal prescription dose distributions.  Non-opposing, non-coplanar beams are 
preferable.  Typically, 10-15 beams of radiation will be used with roughly equal weighting 
for conventional linac treatments.  When static beams are used, a minimum of 10 non-
opposing beams should be used.  For arc rotation techniques, a minimum of 300 degrees 
(cumulative for all beams) should be utilized.  For CyberKnife treatments many more beams 
may be utilized depending on the size and the location.  For this protocol, the isocenter is 
defined as the common point of gantry and couch rotation for the treatment unit. Field 
aperture size and shape should correspond nearly identically to the projection of the PTV 
along a beam’s eye view (i.e. no additional “margin” for dose build up at the edges of the 
blocks or MLC jaws beyond the PTV).  As such, prescription lines covering the PTV will 
typically be the 70-90% line (rather than 95-100%); however, higher isodoses (hotspots) 
must be manipulated to occur within the target and not in adjacent normal tissue.  The 
isocenter in stereotactic coordinates will be determined from system fiducials (or directly 
from the tumor) and translated to the treatment record. 
 
The treatment dose plan will be made up of multiple static beams or arcs as described above.  
The plan should be normalized to a defined point corresponding closely to the center of mass 
of the GTV (COMGTV).  Typically, this point will be the isocenter of the beam rotation; 
however, it is not a protocol requirement for this point to be the isocenter.  Regardless, the 
point identified as COMGTV must have defined stereotactic coordinates and receive 100% of 
the normalized dose.  Because the beam apertures coincide nearly directly with the edge of 
the PTV (little or no added margin), the external border of the PTV will be covered by a 
lower isodose surface than usually used in conventional radiotherapy planning, typically 
around 80% but ranging from 70-90%.  The prescription dose in both the single fraction and 
five fraction treatments will be delivered to the margin of the GTV and fulfill the 

 
16
requirements below.  As such, a “hot spot” will exist within the GTV centrally at the 
COMGTV with a magnitude of the prescription dose times the reciprocal of the chosen 
prescription isodose line (i.e., 70-90%). 
 
For purposes of dose planning and calculation of monitor units for actual treatment, all 
tissues within the body should be modeled in the planning system as to their electron density.  
Proper heterogeneity correction algorithms should be approved by the PI. 
  
Successful treatment planning will require accomplishment of all of the following criteria: 
1) 
Normalization  
The treatment plan should be normalized such that 100% corresponds to the 
center of mass of the GTV (COMGTV).  This point will typically also correspond 
(but is not required to correspond) to the isocenter of the treatment beams.  
2) 
Prescription Isodose Surface Coverage 
The prescription isodose surface will be chosen such that ≥95% of the target 
volume (PTV) is covered by the minimum prescription isodose surface (see 
section 6.1.2) and 99% of the target volume (PTV) receives a minimum of 90% of 
the minimum prescription dose.  However, the spinal tolerance limits in section 
6.5 should not be exceeded, even if the goals of target coverage remain unmet.  In 
such a case, the treatment should proceed at the attainable dose without exceeding 
spinal cord tolerance with a potential protocol violation for target coverage. 
3) 
Target Dose Heterogeneity 
The prescription isodose surface selected in number 2 (above) must be ≥ 60% of 
the dose at the center of mass of the GTV (COMGTV) and ≤ 90% of the dose at the 
center of mass of the GTV (COMGTV). The COMGTV corresponds to the 
normalization point (100%) of the plan as noted in 1) above. 
4) 
High Dose Spillage 
a. Location 
Any dose greater than 105% of the prescription dose should occur primarily 
within the PTV itself and not within the normal tissues outside of the PTV.  
Therefore, the cumulative volume of all tissue outside of the PTV receiving a 
dose greater than 105% of prescription dose should be no more than 15% of 
the PTV volume.  Ideally, these hot spots will be manipulated to occur within 
the gross tumor volume.  IMRT and other techniques will be encouraged to 
accomplish this goal.  
b. Volume 
Conformality of PTV coverage will be judged such that the ratio of the 
volume of the prescription isodose meeting criteria 1) through 4) to the 
volume of the PTV is less than 1.3. 
 
6.5 Critical Structures 
6.5.1 Critical Organ Dose-Volume Limits 
The following tables lists maximum dose limits to a point or volume within several critical 
organs.  These are absolute limits, and dose that exceeds these limits by 5% will constitute a 
major protocol violation. 
 
These limits were formulated with the approval of the study committee using known 
tolerance data, radiobiological conversion models, norms used in current practice at 
academic centers.  Participating centers are encouraged to observe prudent treatment 

 
17
planning principles in avoiding unnecessary radiation exposure to critical normal structures 
irrespective of these limits.  The tables list limits for previously non-irradiated tissues.  
Previous radiation dose should be quantified.  Clinicians should factor in previous radiation 
by modifying the actual dose tolerance limits employed in a given patient on a case by case 
basis. 
 
In order to verify each of these limits, the organs must be contoured such that appropriate 
dose volume histograms can be generated.  Instruction for the contouring of these organs will 
follow below. 
 
6.5.2One Fraction 
 
 
 
 
 
 
 
 
Serial Tissue 
Volume 
Volume Max 
(Gy) 
Max Point Dose 
(Gy) 
Endpoint (≥Grade 3) 
Brainstem 
<1 cc 
10 Gy 
15 Gy 
cranial neuropathy 
Spinal Cord 
See section 
6.1.2 
 
 
myelitis 
Cauda Equina 
<5 cc 
14 Gy 
16 Gy 
neuritis 
Esophagus* 
<5 cc 
14.5 Gy 
19 Gy 
stenosis/fistula 
Ipsilateral 
Brachial 
Plexus 
<3 cc 
14.4 Gy 
16 Gy 
neuropathy 
Heart/Pericard
ium 
<15 cc 
16 Gy 
22 Gy 
pericarditis 
Great vessels 
<10 cc 
31 Gy 
37 Gy 
aneurysm 
Trachea and 
Ipsilateral 
Bronchus* 
<4 cc 
8.8 Gy 
22 Gy 
stenosis/fistula 
Skin 
<10 cc 
14.4 Gy 
16 Gy 
ulceration 
Stomach 
<10 cc 
13 Gy 
16 Gy 
ulceration/fistula 
Duodenum* 
<5 cc 
8.8 Gy 
16 Gy 
ulceration 
Jejunum/Ileu
m* 
<5 cc 
9.8 Gy 
19 Gy 
enteritis/obstruction 
Colon* 
<20cc 
11 Gy 
22 Gy 
colitis/fistula 
Renal 
hilum/vascula
r trunk 
<2/3 volume 10.6 Gy 
 
malignant hypertension 
 
 
 
 
 
Parallel 
Tissue 
Critical 
Volume (cc) 
Critical 
Volume Dose 
Max (Gy) 
 
Endpoint (≥Grade 3) 
Lung (Right 
& Left) 
1500 cc 
7 Gy 
 
Basic Lung Function 
Lung (Right 
& Left) 
1000 cc 
7.4 Gy 
 
Pneumonitis 
Liver 
700 cc 
9.1 Gy 
 
Basic Liver Function 
Renal cortex 
(Right & Left) 
200 cc 
8.4 Gy 
 
Basic renal function 
 
 

 
18
 
 
Five Fractions – These limits for non-irradiated tissues.  Clinician must account for 
previous dose to normal structures using clinical judgement on a case by case basis. 
 
 
 
Serial Tissue 
Volume 
Volume Max 
(Gy) 
Max Point Dose 
(Gy) 
Endpoint (≥Grade 3) 
Brainstem 
<1 cc 
26 Gy (5.2 
Gy/fx) 
31 Gy (6.2 Gy/fx) 
cranial neuropathy 
Spinal Cord 
See section 
6.1.2 
 
 
myelitis 
Cauda Equina 
<5 cc 
30 Gy (6 
Gy/fx) 
34 Gy (6.4 Gy/fx) 
neuritis 
Esophagus* 
<5 cc 
27.5 Gy (5.5 
Gy/fx) 
35 Gy (7 Gy/fx) 
stenosis/fistula 
Ipsilateral 
Brachial 
Plexus 
<3 cc 
30 Gy (6 
Gy/fx) 
32 Gy (6.4 Gy/fx) 
neuropathy 
Heart/Pericard
ium 
<15 cc 
32 Gy (6.4 
Gy/fx) 
38 Gy (7.6 Gy/fx) 
pericarditis 
Great vessels 
<10 cc 
47 Gy (9.4 
Gy/fx) 
53 Gy (10.6 Gy/fx) 
aneurysm 
Trachea and 
Ipsilateral 
Bronchus* 
<4 cc 
18 Gy (3.6 
Gy/fx) 
38 Gy (7.6 Gy/fx) 
stenosis/fistula 
Skin 
<10 cc 
30 Gy (6 
Gy/fx) 
32 Gy (6.4 Gy/fx) 
ulceration 
Stomach 
<10 cc 
28 Gy (5.6 
Gy/fx) 
32 Gy (6.4 Gy/fx) 
ulceration/fistula 
Duodenum* 
<5 cc 
18 Gy (3.6 
Gy/fx) 
32 Gy (6.4 Gy/fx) 
ulceration 
Jejunum/Ileu
m* 
<5 cc 
19.5 Gy (3.9 
Gy/fx) 
35 Gy (7 Gy/fx) 
enteritis/obstruction 
Colon* 
<20cc 
25 Gy (5 
Gy/fx) 
38 Gy (7.6 Gy/fx) 
colitis/fistula 
Renal 
hilum/vascula
r trunk 
<2/3 volume 23 Gy (4.6 
Gy/fx) 
 
malignant hypertension 
 
 
 
 
 
Parallel 
Tissue 
Critical 
Volume (cc) 
Critical 
Volume Dose 
Max (Gy) 
 
Endpoint (≥Grade 3) 
Lung (Right 
& Left) 
1500 cc 
12.5 Gy (2.5 
Gy/fx) 
 
Basic Lung Function 
Lung (Right 
& Left) 
1000 cc 
13.5 Gy (2.7 
Gy/fx) 
 
Pneumonitis 
Liver 
700 cc 
21 Gy (4.2 
Gy/fx) 
 
Basic Liver Function 
Renal cortex 
200 cc 
17.5 Gy (3.5 
 
Basic renal function 

 
19
(Right & Left) 
Gy/fx) 
 
 
 
 
 
 
 
 
*Avoid circumferential irradiation 
 
6.6 Contouring of Normal Tissue Structures 
6.6.1 Spinal Cord 
The spinal cord will be contoured as multiple structures based on MRI or CT.  Ideally the 
actual spinal cord and not necessarily the entire spinal canal will be contoured if possible.  
For each treated site, the spinal cord should be contoured on axial slices in the region of the 
PTV and extending at least 2.5 cm above and below the PTV.  Each section of contoured 
spinal cord will be evaluated separately. 
6.6.2 Cauda Equina 
The cauda equina will be contoured as multiple structures based on MRI.  For each treated 
site, the cauda equina should be contoured on axial slices if it is within 5 cm of the PTV.  
The superior aspect of the cauda equina begins at the conus medularis.  The entire spinal 
canal will be contoured to represent the cauda equine extending inferiorly to the end of the 
thecal sac.    
6.6.3 Lungs 
Both the right and left lungs should be contoured as one structure.  Contours should be 
carried out using pulmonary windows on CT.  Any para-spinal gross tumor should not be 
included in this structure. 
6.6.4 Esophagus 
The esophagus will be contoured using mediastinal windowing on CT to correspond to the 
mucosal, submucosa, and all muscular layers out to the fatty adventitia.  The esophagus 
should be contoured 5 cm above the superior extend of the PTV and continued on every 
slice to 5 cm below the inferior extent of the PTV.  
6.6.5 Small Intestine 
Small intestine will be contoured if the PTV is within the range of T10-L5. The small 
intestines should be contoured as a conglomerate of all bowel loops within each CT cut 
starting at the first appearance of small intestine in the pelvis and extending superiorly up 
to the level of the sacral promontory within each cut.  
6.6.6 Kidneys 
Kidneys will be contoured if the PTV is within the range of T10-L5. Each kidney should be 
contoured and evaluated separately.  Kidney should be contoured on abdominal windows 
on CT. 
6.6.7 Heart 
The heart will be contoured along with the pericardial sac.  The superior aspect (or base) 
for the purposes of contouring will begin at the level of the inferior aspect of the aortic arch 
(aorto-pulmonary window) and extend inferiorly to the apex of the heart. 
6.6.8 Skin 
The skin will constitute the external contour minus 5 mm.  The skin within folds, especially 
in the gluteal folds as the skin surfaces make contact, will be contoured as a separate 
structure. 
6.7 Documentation Requirements 
6.7.1 In general, treatment interruptions should be avoided by preventative medical measures and 
nutritional, psychological, and emotional counseling.  Treatment breaks, including 
indications, must be clearly documented on the treatment record. 
 
6.8 Compliance Criteria 

 
20
6.8.1 Accreditation Compliance 
 
All criteria listed in Section 5 must be completed to the satisfaction of the study committee 
in order to be accredited.  Upon completion of the criteria, a letter will be sent to 
institutions’ PIs informing them of accreditation for the study. No institution will be 
allowed to enroll patients without accreditation. 
6.8.2 Dosimetry Compliance 
 
Section 6 describes appropriate conduct for treatment planning dosimetry.  The table 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 and should be strictly avoided. 
6.8.3 Treatment Delivery Compliance 
Set-up films will be compared to digitally reconstructed radiographs from the same beam’s 
eye view.  Deviations of less than 0.3 cm will be considered compliant.  Deviations from 
0.3-0.5 cm will be considered minor protocol deviations.  Deviations greater than those 
listed as minor will be considered major protocol deviations. 
6.8.4 Target Coverage Compliance 
As listed in sections 6.1.2 and 6.4.3, the protocol requires that 95% of the PTV volume be 
given the protocol dose while 99% of the PTV volume should get 90% of the prescribed 
dose.  A minor violation would be issued for PTV prescription dose coverage of 90-95% 
while and a major violation for <90%.  A minor violation will be issued if between 95-99% 
of the target volume receives 90% of the prescribed dose, while a major violation for <95% 
of the volume.  In regard to the GTV coverage, a minor violation will be issued for 
coverage of 85-90% of the volume by the prescription dose, while a major violation for 
<85% of the volume.  
 
6.9 R.T. Quality Assurance Reviews 
Dr. Timmerman will perform an RT Quality Assurance Review after complete data for the first 9 
cases enrolled into the single fraction group and 6 patients enrolled into the four fraction group have 
been received at the University of Texas Southwestern. Dr. Timmerman will perform the next 
review after complete data for the next and subsequent 15 cases enrolled has been received at the 
University of Texas Southwestern. The final cases will be reviewed within 3 months after this study 
has reached the target accrual or as soon as complete data for all cases enrolled has been received, 
whichever occurs first. 
 
6.10 Radiation Adverse Events 
6.10.1 Neurology 
Monitored treatment related toxicity associated with neurology function will include 
myelitis, motor and sensory neuropathy, plexopathy, and pain.  The consequences of 
neurology toxicity should all be graded according to the Common Terminology Criteria 
For Adverse Events (CTCAE). 
6.10.2 Blood/Bone Marrow 
Monitored treatment related toxicity associated with blood and bone marrow function will 
include anemia, leukocytopenia, thrombocytopenia, and myelodysplasia.  The 
consequences of blood and bone marrow toxicity should all be graded according to the 
Common Terminology Criteria For Adverse Events (CTCAE). 
6.10.3 Constitutional Symptoms 
Monitored treatment related toxicity associated with constitutional function will include 
fatigue, fever, and weight loss.  The consequences of constitutional toxicity should all be 
graded according to the Common Terminology Criteria For Adverse Events (CTCAE). 

 
21
6.10.4 Skin 
Monitored treatment related toxicity associated with skin function will include fibrosis, 
rash (desquamation), ulceration, and telangiectasia.  The consequences of skin toxicity 
should all be graded according to the Common Terminology Criteria For Adverse Events 
(CTCAE). 
6.10.5 Gastro-intestinal 
Monitored treatment related toxicity associated with gastrointestinal function will include 
colitis, dehydration, diarrhea, enteritis, fistula, nausea, vomiting, obstruction, proctitis, 
fecal incontinence, stricture/stenosis, hemorrhage, and ulcer.  The consequences of gastro-
intestinal toxicity should all be graded according to the Common Terminology Criteria For 
Adverse Events (CTCAE). 
6.10.6 Renal/Genitourinary 
Monitored treatment related toxicity associated with renal and genito-urinary function will 
include cystitis, fistula, urinary incontinence, urinary obstruction, hemorrhage, and urinary 
retention.  The consequences of renal/genitourinary toxicity should all be graded according 
to the Common Terminology Criteria For Adverse Events (CTCAE).   
6.10.7 Quality of Life and Other Toxicities 
Other treatment related toxicity attributed to the therapy will be captured, recorded and the 
consequences of should all be graded according to the Common Terminology Criteria For 
Adverse Events (CTCAE).  VAS, BPI, FACT-G and EQ-5D 
 
6.11 Serious Adverse Event Reporting 
6.11.1 ERGO 
Electronic Research Grant Organizer (ERGO) constitutes a mechanism for reporting 
serious adverse events to the UTSW IRB for reporting purposes.   
 
Any adverse event equivalent to CTCAE V.3 grade 3, 4, or 5 or which precipitates 
hospitalization or prolongs an existing hospitalization must be reported regardless of 
designation (expected or unexpected) along with the attribution. This includes all deaths 
that occur within 30 days after the patient was discontinued from the study regardless of 
attribution AND any events that occur beyond 30 days and are considered probably related 
to treatment. 
 
Participating sub-sites must file an SAE report (the CRF plus information describing the 
event, the grade, and the attribution) within 48 hours of the investigator’s awareness of the 
occurrence of the event.  
Attribution of an event can be categorized as:  
 Not Related 
 Possibly Related 
 Likely Related 
 
Adverse events (below grade 3) do not need to be submitted immediately.  Rather, they 
should be documented in the Adverse Events CRF along with a brief description of the 
event, grade, and attribution). 
 
 
 
 
 

 
22
 
All SAE reports should be made via FAX transmission to: 
 
Department of Radiation Oncology 
Clinical Research Office 
The University of Texas Southwestern Medical Center 
Attention:  Jean Wu, Project Manager 
FAX #: 214-648-5923 
 
7.0 Drug Therapy:   
Chemotherapy will be held 1 week prior to radiation and may be continued one week after treatment. 
 
8.0 Surgery: 
8.1 Vertebroplasty 
Vertebroplasty will be performed within one month of start of radiation therapy in the standard 
angiography suite or in the operating room depending on individual patient needs.  C-arm 
fluoroscopy will be utilized for localization and visualization throughout the procedure. All patients 
undergo continuous physiologic monitoring and observation by anesthesia provider. In most 
instances the procedure may be completed using conscious sedation with a combination of a short 
acting narcotic and benzodiazepine. Local anesthesia with lidocaine or bupivicaine is also utilized. 
 
The patient will be positioned prone on the operating table, prepped and draped in the usual sterile 
fashion. Under fluoroscopic guidance, the pedicle of the involved vertebral level is localized. The 
skin, soft tissue and periosteum are anesthetized. A standard bone biopsy needle with an outer 
cannula and a central stylet is advanced under fluoroscopic guidance into the vertebral body via the 
pedicle. The stylet is removed and the polymethyl methacrylate (PMMA) mixture is injected into the 
vertebral body through the cannula under continuous fluoroscopy. Careful attention to any 
extravasation is noted. After adequate vertebral body fill, the cannula is withdrawn and a sterile 
dressing applied to the puncture site.  
 
9.0 Other Therapy: 
9.1 Permitted Supportive Therapy 
All supportive therapy for optimal medical care will be given during the study period at the 
discretion of the attending physician(s) within the parameters of the protocol and documented on 
each site’s source documents as concomitant medication. 
9.1.1 Antiemetics 
9.1.2 Anticoagulants 
9.1.3 Antidiarrheals 
9.1.4 Analgesics 
9.1.5 Hematopoietic Growth Factors 
9.1.6 Herbal products 
9.1.7 Nutritional supplementation 
 
10.0 TISSUE/SPECIMEN SUBMISSION 
10.1 Specimen Collection For Central Review For Eligibility 
Central review of pathology is not required for entry on to this study.   
 
11.0 PATIENT ASSESSMENTS 
11.1 Study Parameters: See Appendix II. 

 
23
 
11.2  Follow-up Schedule 
11.2.1  Initial follow-up visit at 2 weeks then 1, 3 and 6 months from start of treatment. 
11.2.2 
VAS will be measured at 2 weeks, 1, 3, and 6 months and then every 6 months for 3 
years by research staff.  VAS will be measured on the day of treatment and weekly 
there after for 5 weeks by patient diary. 
11.2.3 
BPI, Fact-G, and EQ-5D will be done at baseline, 1, 3, 6, and 12 months post therapy. 
11.2.4  After initial follow-up visits, follow-up will be done at 6 month intervals post therapy 
for 3 years. 
11.2.5  MRI at baseline, 1, 3, 6 and then every 6 months for three years.  These MRI are to be 
done of the treated level and a complete whole spine MRI will be done when clinically 
indicated based on pain or other new neurological symptom. 
 
11.3  Criteria for Toxicity 
11.3.1  All acute and late adverse events from protocol radiation therapy will be reported and 
scored for severity using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 3.0. A copy of the CTCAE v3.0 can be downloaded from the CTEP 
home page (http://ctep.info.nih.gov). 
 
Please note that this study will not be using separate toxicity scales for acute and 
late radiation adverse events. 
 
11.4 Measurement of Pain Response 
11.4.1 
Pain as the primary endpoint of the study will be assessed by VAS at 1 month by 
research staff. 
11.4.2 
Pain will also be assessed by VAS at 2 weeks, 1, 3, and 6 months and then every 6 
months for 3 years post therapy by research staff.   A patient pain diary of maximum 
VAS of treated spine recorded on the same day of radiation treatment and then weekly 
for 5 weeks following radiation treatment. 
11.4.2.1 Response to pain will be scored as Complete Response (CR), Partial Response 
(PR), or other. 
11.4.2.2 Complete response (CR): defined as a score of 0 on the VAS at the treated site 
with no increase in narcotic requirements 
11.4.2.3 Partial response (PR):  defined as an improvement of at least two points on the 
VAS with no increase in narcotic requirement. 
11.4.2.4 Other will include people with stable pain, increasing narcotic requirements, and 
progressive pain 
 
11.5  Measurement of Tumor Response 
11.5.1  Spinal metastasis dimensions in centimeters must be recorded on the data collection 
forms for the initial and follow-up evaluations of the patient. 
11.5.2  After study entry, disease evaluations will be made and recorded using the following 
Response Evaluation Criteria in Solid Tumors (RECIST): 
11.5.2.1 Complete Response (CR): No clinical evidence of disease on CT or MRI imaging. 
11.5.2.2 Partial Response (PR): This rating will be assigned when at least a 30% decrease 
in the maximum single dimension of the target lesion has occurred, taking as 
reference the baseline maximum dimension of the target lesion 

 
24
11.5.2.3 Stable Disease (SD)[46]:  This rating will be assigned when neither sufficient 
shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as 
reference the smallest single dimension measurement since treatment started. 
11.5.2.4 Progressive Disease (PD): Progressive disease will be declared when at least a 
20% increase in maximum dimension of the target lesion, taking as reference the 
smallest single dimension measurement since treatment started. 
 
11.6 
Other Response Parameters 
11.6.1 
Duration of Pain Response: The duration of pain response will be measure from the 
date that CR or PR was recorded to the date of increase in the VAS at the treated site to 
a score 2 points higher than the lowest VAS score recorded. 
11.6.2 
Time to Functional Decline:  Time from study entry to a Zubrod PS ≤ 3 
11.6.3  Overall Survival: The survival time will be measured from the date of accession to the 
date of death. All patients will be followed for survival. Every effort should be made to 
document the cause of death. 
 
11.7 
Removal of Subject from Study 
We will be following the patients for 3 years. Subjects can be taken off the study treatment and/or 
study at any time at their own request, or they may be withdrawn at the discretion of the 
investigator for safety, behavioral or administrative reasons. The reason(s) for discontinuation will 
be documented and may include: 
11.7.1 Subject voluntarily withdraws from consent   
11.7.2 Subject is unable to comply with protocol requirements.   
11.7.3 Subject demonstrates disease progression to targeted site.  
11.7.4 Subject experiences toxicity that makes continuation in the protocol unsafe.  
11.7.5 Development of second malignancy that requires treatment, which would interfere with 
this study.  
11.7.6 Treating physician judges continuation on the study would not be in the subject’s best 
interest.  
11.7.8. Subject becomes pregnant.   
11.7.9  If a research subject cannot be located to document survival after a period of 2 years, the 
subject may be considered “lost to follow-up”. All attempts to contact the subject during 
the two years must be documented and approved by the Data Monitoring Committee.    
 
12.0 DATA COLLECTION 
Data should be submitted to: 
Department of Radiation Oncology 
Clinical Research Office 
The University of Texas Southwestern Medical Center 
Attention: Jean Wu, Project Manager                      
5801 Forest Park Road 
Dallas, Texas  75390-9183 
FAX #: 214-648-5923 
Patients will be identified only by initials (first middle last) and a unique study ID number 
assigned to each study participant; if there is no middle initial, a hyphen will be used (first-last). 
Last names with apostrophes will be identified by the first letter of the last name. Participating 
sub-sites must remove or black-out identifiers from source documentation that is sent to UTSW. 
 

 
25
Study-related data will be stored for 5 years after termination of the study when accrual is no 
longer taking place and all patients have discontinued follow-up procedures. 
 
12.1 
Summary of Data Submission 
 
 
 
 
Item 
Recommended Submission Timeline 
Demographics 
Within 2 weeks of study entry 
Eligibility and Entry Characteristics including 
baseline H&P 
Within 2 weeks of study entry 
Pathology Report  
Within 2 weeks of study entry 
QOL studies 
Within 2 weeks of study entry 
SBRT dosimetry information 
Within 1 week after completion of SBRT 
Follow-up H&P data 
After last SBRT treatment, post SBRT 
follow-up at 2 weeks, 1, 3, 6, then every 6 
months to 3 years 
QOL forms post treatment 
After last SBRT treatment, post SBRT 
follow-up at 2 weeks, 1, 3, 6, then every 6 
months to 3 years 
 
 Adverse Event assessment 
 
 
After last SBRT treatment, post SBRT 
follow-up at 2 weeks, 1, 3, 6, then every 6 
months to 3 years 
 
 
12.2 
Procedures to Maintain Confidentiality 
Patient medical information obtained as a result of this study is considered confidential. Patient 
data will be kept in a locked file in the Clinical Research Office, and all electronic data will be 
password protected. All reports and communications related to subjects in this study will identify 
patients only by his/her initials/number. Organizations that may look at and/or copy medical 
records for research, for quality assurance, and data analysis include:  the Institutional Review 
Board (IRB – a group of people who review the study to protect patient rights), the FDA, the 
Office for Human Research Protections (OHRP). These agencies may review the research to 
ensure that it is done safely and correctly.  Patient confidentiality will be maintained at all times 
unless government regulation or applicable law requires disclosure. The investigators are 
obtaining a Certificate of Confidentiality from the U.S. Department of Health and Human 
Services (DHHS).  This Certificate adds special protections for research information that 
identifies participants and will help researchers protect subject privacy.   
 
13.0 Statistical Consideration: 
13.1  Single Fraction Treatment Group 
Two-Stage Design and Sample Size Justification 
The planned sample size of 29 total eligible subjects is based on Simon two-stage optimal design 
with an overall significance level of 0.05 and power of 90% (Simon R, 1989).  The concept of this 
design is to permit early stopping when a moderately long sequence of initial failure occurs. The 
historical response rate to conventional radiation treatments is 50%[27].  This response rate comes 
from the RTOG 9714 trial which looked at 800 cGy in one fraction vs 3000 cGy in ten fractions.  
It represents combined complete and partial responses.  This trial set the standard of care for 

 
26
palliation of pain bone metastasis in previously unirradiated patients and thus is used as the 
historical control for this group.  The statistical hypothesis tested is as follows: 
 
H0: p≤50% vs. HA: p≥80%, where p is one month pain response rate 
 
Rejection of H0 means that further study of the test treatment should be carried out.  Under the 
above hypotheses, the type I error is the false-positive rate in accepting an ineffective treatment 
and type II error is the false-negative rate in rejecting a promising treatment.  
 
Stage 1 of the study will include 9 eligible subjects. If at least 6 of 9 eligible subjects respond, an 
additional 20 subjects will be enrolled into stage 2 of the study. If the total number of patients who 
respond (among the 29 patients) is 19 or more, the null hypothesis above will be rejected in favor 
of the alternate hypothesis.  
 
Under the null hypothesis (p≤50%), the expected sample size of the trial is only 14. 
 
The assumptions and specifications for Simon’s two-stage design are detailed in the following 
table 1 
Alpha --------------------------------------------> 0.05 
Beta ---------------------------------------------> 0.10 
Response Probability of Historical Conventional Radiation Treatment (P0) ---> 0.5 
Response Probability of Stereotactic Radiation Treatment (P1) ---> 0.8 
 
Table 1.  Power Calculation and Sample Size Calculation Table 
 
Optimal Two Stage Design 
Optimum Design 
First Stage Sample Size (n1) 
9 
Upper Limit For 1st Stage Rejection of Stereotactic 
Radiation Treatment (r1) 
5 
Maximum Sample Size (n) 
29 
Upper Limit for 2nd Stage Rejection of Stereotactic 
Radiation Treatment (r) 
18 
Expected Sample Size If Response Probability = P0 
14.08 
Probability of Early Termination at P0 
0.75 
13.2  Five Fraction Treatment Group 
Two-Stage Design and Sample Size Justification  
The planned sample size of 13 total eligible subjects is based on Simon two-stage optimal design 
with an overall significance level of 0.05 and power of 90% (Simon R, 1989).  The concept of this 
design is to permit early stopping when a moderately long sequence of initial failure occurs. The 
historical response rate to conventional radiation treatments is 35%[42].  This response rate comes 
from a subsequent analysis of the Dutch Bone Metastasis Study which looked at 800 cGy in one 
fraction vs 2400 cGy in multiple fractions.  It represents combined complete and partial responses.  
This analysis details what the response rate to conventional radiation retreatment in the setting of 
prior irradiation to the treated area and thus is used as the historical control for this group.  The 
statistical hypothesis tested is as follows: 
 
H0: p≤35% vs. HA: p≥75%, where p is response rate 

 
27
 
Rejection of H0 means that further study of the test treatment should be carried out.  Under the 
above hypotheses, the type I error is the false-positive rate in accepting an ineffective treatment 
and type II error is the false-negative rate in rejecting a promising treatment.  
 
Stage 1 of the study will include 6 eligible subjects. If at least 3 of 6 eligible subjects respond, 
additional 7 subjects will be enrolled into stage 2 of the study. If the total number of patients who 
respond (among the 13 patients) is 8 or more, the null hypothesis above will be rejected in favor of 
the alternate hypothesis.  
 
Under the null hypothesis (p≤35%), the expected sample size of the trial is only 9. 
 
The assumptions and specifications for Simon’s two-stage design are detailed in the following 
table 2 
Alpha --------------------------------------------> 0.05 
Beta ---------------------------------------------> 0.10 
Response Probability of Historical Conventional Radiation Treatment (P0) ---> 0.35 
Response Probability of Stereotactic Radiation Treatment (P1) ---> 0.75 
 
Table 2.  Power Calculation and Sample Size Calculation Table 
 
Optimal Two Stage Design 
Optimum Design 
First Stage Sample Size (n1) 
6 
Upper Limit For 1st Stage Rejection of Stereotactic 
Radiation Treatment (r1) 
2 
Maximum Sample Size (n) 
13 
Upper Limit for 2nd Stage Rejection of Stereotactic 
Radiation Treatment (r) 
7 
Expected Sample Size If Response Probability = P0 
8.47 
Probability of Early Termination at P0 
0.65 
 
13.3 Secondary Endpoints 
Secondary endpoints will be analyzed by the following methods.  For overall survival Kaplan-
Meier plots and median times will be reported.  Time to functional decline will me measured with 
Kaplan-Meier plots and median times will be reported. Duration of pain response will be measured 
with Kaplan-Meier plots and median duration of pain response will be reported.  
 
14.0 Data Safety Monitoring Plan 
A data safety monitoring committee including radiation oncologists not participating in this trial 
will be formed to review toxicity endpoints and efficacy data. The data safety monitoring 
committee will review and verify all reported AE. In particular, this committee will scrutinize the 
grading of adverse events and the attribution to therapy previously assigned by the investigators.  
This panel will have access to patient information so as to have the ability to critically review 
toxicity events.  This study will use this committee to perform ongoing safety assessment.  
Toxicities will be reported to the treating center’s IRB and also to the University of Texas 
Southwestern IRB. 
 
15.0 References: 

 
28
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Blomgren, H., et al., Stereotactic high dose fraction radiation therapy of extracranial tumors 
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5. 
Uematsu, M., et al., Computed tomography-guided frameless stereotactic radiotherapy for stage 
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Murphy, M.J., et al., Image-guided radiosurgery in the treatment of spinal metastases. 
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Yu, C., et al., An anthropomorphic phantom study of the accuracy of Cyberknife spinal 
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Baltimore, MD: Lippincott, Williams, and Wilkins. 
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preliminary report. Neurosurgery, 2004. 54(4): p. 823-30; discussion 830-1. 
15. 
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compression caused by metastatic cancer: a randomised trial. Lancet, 2005. 366(9486): p. 643-
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18. 
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of life. AJR Am J Roentgenol, 1977. 129(6): p. 1095-6. 
19. 
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Lieberman, I.H., et al., Initial outcome and efficacy of "kyphoplasty" in the treatment of painful 
osteoporotic vertebral compression fractures. Spine, 2001. 26(14): p. 1631-8. 
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23. 
Deramond, H., et al., Percutaneous vertebroplasty with polymethylmethacrylate. Technique, 
indications, and results. Radiol Clin North Am, 1998. 36(3): p. 533-46. 

 
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24. 
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lesions. N Engl J Med, 1989. 321(2): p. 121. 
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Padovani, B., et al., Pulmonary embolism caused by acrylic cement: a rare complication of 
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of painful bone metastases. J Natl Cancer Inst, 2005. 97(11): p. 798-804. 
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epidural spinal cord compression: Tumor control and neurologic outcome. Proc Am Soc Clin 
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Ryu, S., et al., Patterns of failure after single-dose radiosurgery for spinal metastasis. J 
Neurosurg, 2004. 101 Suppl 3: p. 402-5. 
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Radiat Res, 1988. 116(2): p. 263-82. 
31. 
Martinez Caballero, A., et al., [Bone metastasis versus insufficiency fractures due to pelvic 
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Theriault, R.L., Pathophysiology and implications of cancer treatment-induced bone loss. 
Oncology (Williston Park), 2004. 18(5 Suppl 3): p. 11-5. 
34. 
Jensen, M.P., et al., Comparative reliability and validity of chronic pain intensity measures. 
Pain, 1999. 83(2): p. 157-62. 
35. 
Daut, R.L., C.S. Cleeland, and R.C. Flanery, Development of the Wisconsin Brief Pain 
Questionnaire to assess pain in cancer and other diseases. Pain, 1983. 17(2): p. 197-210. 
36. 
Cella, D.F., et al., The Functional Assessment of Cancer Therapy scale: development and 
validation of the general measure. J Clin Oncol, 1993. 11(3): p. 570-9. 
37. 
Schulz, M.W., et al., A comparison of techniques for eliciting patient preferences in patients with 
benign prostatic hyperplasia. J Urol, 2002. 168(1): p. 155-9. 
38. 
Badia, X., M. Herdman, and P. Kind, The influence of ill-health experience on the valuation of 
health. Pharmacoeconomics, 1998. 13(6): p. 687-96. 
39. 
Marcus, C.S., et al., Lack of effect of a bisphosphonate (pamidronate disodium) infusion on 
subsequent skeletal uptake of Sm-153 EDTMP. Clin Nucl Med, 2002. 27(6): p. 427-30. 
40. 
Glasziou, P.P., R.J. Simes, and R.D. Gelber, Quality adjusted survival analysis. Stat Med, 1990. 
9(11): p. 1259-76. 
41. 
Degen, J.W., et al., CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain 
control and quality of life. J Neurosurg Spine, 2005. 2(5): p. 540-9. 
42. 
van der Linden, Y.M., et al., Single fraction radiotherapy is efficacious: a further analysis of the 
Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol 
Phys, 2004. 59(2): p. 528-37. 
 

 
30
  

 
31
Appendix I 
STUDY PARAMETER TABLE 
 
 
PreTreatment 
During 
Treatment 
Follow-Up (months after 
therapy) 
  
Within 30 days of 
study entry 
With each 
treatment 
After last 
treatment 
1 
3 
6 
Every 6 months for 
three years 
Confirmation of 
Pathology 
X 
  
  
  
  
  
  
History/physical 
X 
X 
X 
X 
X 
X 
X 
Performance 
Status 
X 
  
  
X 
X 
X 
X 
MRI spine* 
X1 
  
  
X1 
X1 
X1 
X1 
CT spine* 
X1 
  
  
X1 
X1 
X1 
X1 
BUN, 
creatinine, CBC 
w/ platelets, 
PT/PTT INR 
X 
  
  
  
  
  
  
Informed 
consent 
X 
  
  
  
  
  
  
Tumor response 
evaluation 
X 
  
  
X 
X 
X 
X 
VAS at treated 
Site 
X 
  
X 
X 
X 
X 
X 
Adverse event 
evaluation 
  
X 
X 
X 
X 
X 
X 
QOL Studies 
 
X 
  
 X 
X 
X 
X 
X 
(BPI, Fact-G, 
EQ-5D) 
X 
 
 
X 
X 
X 
(12 months only) 
Vertebroplasty 
 
X2 
 
 
 
 
 
 
 
 
*X1: Per physician's discretion 
X2 : within one month of start of radiation treatment. 
 

 
32
Appendix II 
 
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 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 self-care. Totally confined to 
bed or (Karnofsky 10-20). 
 
5 
Death (Karnofsky 0). 
 

 
33
Appendix III 
Visual Analog Scoring System (VAS) 

 
34
Appendix IV 
Brief Pain Inventory 
 

 
35

 
36
Appendix V 
 
 

 
37

 
38
Appendix VI 
 
 

 
39
 
 
 

 
40