Phase IV Trial Evaluating the Use of Stereotactic Body Radiotherapy for the Treatment of Spine Metastases and Primary Spine Tumors
Phase: NA
Conditions: Spinal Metastases, Vertebral Metastases, Benign Spinal Tumors, Chordoma, Meningioma, Schwannoma, Neurofibroma, Paragangliomas, Arteriovenous Malformations
Sponsor: Mercy Research

 
 
 
 
 
 
 
 
 
 
 
PHASE IV TRIAL EVALUATING THE USE OF STEREOTACTIC 
BODY RADIOTHERAPY FOR THE TREATMENT OF  
SPINE METASTASES AND PRIMARY SPINE TUMORS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigators 
 
 
 
Radiation Oncology 
Robert Frazier, M.D. 
 
 
Kathy Baglan, M.D. 
 
 
Jeffrey Craft, M.D. 
 
 
Julie Mai, M.D. 
 
 
Jaymeson Stroud, M.D.  
 
 
David C. Pratt Cancer Center 
 
 
(314) 251-6844 
 
 
Fax (314) 251-4337 
 
 
Oncology Research 
Bethany Sleckman, M.D. 
 
 
David C. Pratt Cancer Center 
 
 
(314) 251-7057 
 
 
Fax (314) 251-5665 
 
 
Activation Date: 
August 1, 2008 
 
Amendment 1: 
February 26, 2009 
 
Amendment 2:  
February 4, 2013 

 
Amendment 1: February 26, 2009 
1
Index 
 
1   Introduction/Background ……………………………………………………………………………3 
2 
Objectives 
 
2.1 
Hypothesis ………………………….………………………………………………………. 6 
 
2.2 
Study Design ……………………………………………….………………………………..6 
 
2.3 
Endpoints ………………………….………………………………………………………... 7 
3 
Patient Selection  
 
3.1 
Eligibility Criteria …………………………………………………………………………... 7 
 
3.2 
Exclusion Criteria …………………………………………………………………………... 7 
4 
Pretreatment Evaluation ……………………………………………………………………………. 8 
5 
Simulation ……………………………………………………………………………………….…..8 
6 
Radiation Treatment Planning 
 
6.1 
Target Definition …………………………………………………………………………… 8 
 
6.2 
Normal Tissue Definition …………………………………………………………………... 9 
 
6.3 
Dose Specification …………………………………….……………………………………. 9 
 
6.4 
Normal Tissue Dose Constraints ………………………………………………………….…10 
7 
Stereotactic Body Radiotherapy Treatment Delivery 
 
7.1 
Premedication ………………………………………………………………………………. 11 
 
7.2 
Treatment ……………………………………………………………………………………11 
8 
Drug Therapy ………………………………………………………………………………………. 12 
9 
Patient Assessment 
 
9.1 
Study Parameters …………………………………………………………………………… 12 
 
9.2 
Response Evaluation ……………………………………………………………………….. 13 
 
9.3 
Toxicity ……………………………………………………………………………………... 13 
 
9.4 
Patient Withdrawal …………………………………………………………………………. 14 
10 Risk/Benefit Analysis 
 
 
10.1 
Risk associated with SBRT for Spine Metastases and Primary Spine Tumors ……….…. 
14 
 
10.2 
Minimization of Risks ……………………………………………………………………… 14 
 
10.3 
Potential Patient Benefits …………………………………………………………………... 14 
 
10.4 
Justification of the Study …………………………………………………………………… 14 
 
10.5 
Statistical Analysis …………………………………………………………………………. 15 
11 References ………………………………………………………………………………………….. 15 
12 Appendices 
 
12.1 
Appendix I - Sample Informed Consent ……………………………..….………………….. 16 
 
12.2 
Appendix II - Performance Status …………………………………..….…………………... 21 
 
12.3 
Appendix III - Toxicity Score ……………………………….…...………………………… 22 
 
12.4 
Appendix IV - Neurologic Impairment Scale ……………………………………………… 25 
 
12.5 
Appendix V - Pain Scale ……………………………………………….…………………... 26 
 
12.6 
Appendix VI - Patient Demographic Form ……………………..…..…….…………….….. 27 
 
12.7 
Appendix VII - Treatment Form ………………………………………………………….... 28 
 
12.8 
Appendix VIIII - Patient Follow-up Form ……….…………..………………………….…. 30 
 
 
 
 
 
 
 
 

 
Amendment 1: February 26, 2009 
2
PHASE IV TRIAL EVALUATING THE USE OF STEREOTACTIC 
BODY RADIOTHERAPY FOR THE TREATMENT OF SPINE 
METASTASES AND BENIGN SPINE TUMORS 
 
 
SCHEMA 
 
 
R  
 
Stereotactic Body Radiotherapy (SBRT) 
 
 
 
 
 
E 
      Patient Groups: 
 
 
Vertebral Metastasis - not previously irradiated 
 
 
 
 
Vertebral Metastasis - previously irradiated cord 
 
G 
 
 
Intramedullary Spinal Metastasis 
 
 
I 
Suggested Dose-Fractionation: 
14-25 Gy / 1 fraction 
 
  
 
 
21-27 Gy / 3 fractions (7-9 Gy per fraction) 
 
S 
 
 
25-30 Gy / 5 fractions (5-6 Gy per fraction) 
 
  
 
 
 
 
  
 
 
T 
Patient Group: 
Benign Extradural Spinal Tumor 
 
  
 
E 
Suggested Dose-Fractionation:  
12-16 Gy / 1 fraction 
 
 
 
 
21-27 Gy / 3 fractions (7-9 Gy per fraction) 
 
R 
 
 
25-30 Gy / 5 fractions (5-6 Gy per fraction) 
 
 
  
 
 
 
 
 
 
 
 
 
Chemotherapy 
Chemotherapy may be given at the discretion of the patient’s medical oncologist.  However, ideally 
chemotherapy should not have been given within 30 days of starting radiation and should not resume until 
at least 2 weeks after completing radiation.  In addition, it is not recommended to perform SBRT when 
targeted anti-angiogenesis therapy is planned within 2 months of the procedure.  
 
 
Eligibility 
- Patient age > 18 years 
- Zubrod performance status of 0-3 
-  Vertebral and/or paraspinal metastases, with or without prior surgery and/or fractionated radiotherapy 
- Benign extradural spine tumors, such as chordomas, meningiomas, schwannomas, neurofibromas,  
 paragangliomas, and arteriovenous malformations (AVMs). 
-  Established histologic diagnosis of a benign or malignant tumor of the spine.  For patients with  
   malignant spine tumors, the histologic diagnosis may come from biopsy of the primary tumor site or an  
   elsewhere metastatic site.  If this represents the first appearance of metastatic disease, however, the  
   diagnosis of metastasis should be histologically confirmed, when possible 
-  Arteriovenous malformation (AVM) of the spine identified radiographically (no biopsy required) 
- Well-defined lesion involving no more than 2 adjacent vertebral levels or spinal segments 
-  No overt spinal instability 
-  Neurologic deficit is unrelated to bony fragments/bony compression of neural structures 
-  No previous radiation therapy at the involved level(s) within 3 months of radiosurgery 
-  Minimal spinal canal compromise that is not rapidly progressive 
- No pregnant or lactating women (negative pregnancy test for women of child-bearing age) 
- Signed study-specific consent form 

 
Amendment 1: February 26, 2009 
3
1.0   Introduction 
 
 
       Spine metastases are a common pattern of spread for many different malignancies, especially prostate 
cancer, breast cancer, lung cancer, renal cancer, melanoma, and colorectal cancer.  Treatment of 
symptomatic spine metastases typically consists of radiation therapy, sometimes following surgical 
decompression of the spine.  Radiation therapy has been used to improve tumor control, alleviate tumor-
related pain, prevent pathologic fractures, and improve neurologic symptoms such as weakness, 
numbness, and paresthesias.  The traditional radiation therapy course consists of daily treatment, Monday 
through Friday, for a period of approximately 2-5 weeks.  A prolonged course of radiation therapy can 
affect quality of life, particularly if life expectancy is limited.  In addition, patients with spinal metastases 
often have other sites of disease, and a more rapid radiation course may allow more timely administration 
of systemic chemotherapy to address these other disease sites.  Recent technological advancements allow 
high-dose precisely targeted radiation treatments to be delivered in only 1-5 sessions.  A more rapid 
radiation course may positively affect quality of life.  This radiation procedure is called stereotactic body 
radiotherapy (SBRT).  Traditional radiation therapy usually includes at least 1-2 vertebral levels proximal 
and distal to the affected spine.  SBRT limits the amount of normal tissue irradiated, and this sparing of 
bone marrow may facilitate continued delivery of intensive systemic chemotherapy with less delays for 
management of myelosuppression.  Radiosurgery may also result in better long-term local control than 
standard radiation therapy thus obviating the ultimate need for extensive spine surgery for decompression 
and fixation, and may provide potentially more rapid onset of clinical response such as pain improvement 
or amelioration of neurologic deficits. 
 
       Treatment of recurrent spine metastases is often challenging.  With the advent of more effective 
chemotherapy and targeted therapy agents, many patients with metastatic cancer are surviving longer than 
has traditionally been seen in the past.  Although patients often have significant improvement in pain 
and/or neurologic symptoms with traditional radiation therapy, as survival rates have improved patients 
are at risk of developing recurrent symptomatic disease.  Traditional radiation therapy cannot be repeated 
at the same site in the spine, due to the increased risk of injury to normal tissue.  Spinal surgery is often 
difficult and can be associated with significant risk, or may not be an option due to prior surgery, other 
medical conditions or limited life expectancy.  Stereotactic body radiotherapy offers an alternative to 
surgery for management of recurrent disease, which can be delivered in an outpatient setting with low risk 
of side effects.   
      
 
Treatment of primary spine tumors may consist of surgery, radiation therapy, or a combination of 
surgery followed by radiation therapy.  As with spine metastases, radiation therapy has been used to 
achieve tumor control, alleviate tumor-related pain, and improve neurologic symptoms such as weakness, 
numbness, and paresthesias.  The traditional radiation therapy course consists of daily treatment, Monday 
through Friday, for a period of approximately 3-6 weeks.  This prolonged course of radiation can affect 
quality of life.  Stereotactic body radiotherapy (SBRT) allows the delivery of highly precise radiation in 
only 1-5 treatments.  Surgical management of patients with primary spine tumors can be associated with 
significant risk of morbidity.  Some patients are not surgical candidates due to other serious medical 
conditions.  The advantage of SBRT over surgery is that it is not painful, and does not require anesthesia 
or hospitalization.  In addition, some of these benign tumors, such as meningiomas and schwannomas, 
also occur in the brain where radiosurgery has been proven to produce local control rates similar to 
surgical resection.   
 
       Traditional fractionated radiation therapy for spine metastases has been studied extensively.  A meta-
analysis of 16 randomized trials comparing various schedules of fractionated radiation therapy over 1-2 
weeks to single fraction radiotherapy demonstrated unsatisfactory complete pain relief rates of less than 
30%.  Most studies analyzed used a single fraction of 8 Gy.  There was no difference between single 
fraction and multi-fraction radiotherapy in overall response rate or complete response rate; however, the 

 
Amendment 1: February 26, 2009 
4
re-treatment rate was 2.5 fold higher for single fraction radiation therapy (1).  The dose that can be 
delivered safely in a single fraction of radiation to the spine is limited by the tolerance of the spinal cord.  
Standard radiation therapy commonly includes a relatively long length of spinal cord, and delivers the full 
prescription dose to the cord. 
 
     Recent technological advances have made it possible to deliver high doses of radiation therapy with 
high precision over just a few days, while preserving function of surrounding critical structures.  This 
treatment modality, termed stereotactic body radiotherapy (SBRT), is emerging as an expedient, safe, and 
effective radiation modality for a variety of malignancies.  SBRT was recently defined by the American 
Society for Therapeutic Radiology and Oncology (ASTRO) as a “treatment method to deliver a high dose 
of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of 
precision within the body” (2).  Stereotactic radiosurgery is a well-established treatment for intracranial 
metastases with local control rates of 80-90%.  Several institutions have investigated the use of SBRT for 
the treatment of spine metastases and primary spine tumors, and have reported excellent local tumor 
control, onset of pain relief and neurologic improvement at least as rapid as traditional radiation therapy, 
with fairly low toxicity risk.  Many phase I and II trials of SBRT have now been published demonstrating 
its efficacy and safety.  Although follow-up is variable, the local control rates for metastatic disease have 
generally been in the range of 81-95%, at least partial pain relief of 67-100%, and rates of late 
myelopathy of 0-4%.  No grade 3-5 late toxicity has been reported with respect to other organs such as the 
kidneys, lungs, bowel, and esophagus (3). 
 
       Gerszten and colleagues from the University of Pittsburgh published a series of 393 patients with 500 
spine metastases treated with Cyberknife stereotactic radiosurgery to a maximum dose of 12.5-25 Gy 
(mean 20 Gy, or 16 Gy to the 80% isodose line) in a single fraction.  344 tumor sites had received prior 
fractionated radiation therapy (30 Gy in 10 fractions or 35 Gy in 14 fractions).  With a median follow-up 
of 21 months, 86% had significant long-term pain improvement and 88% had long-term tumor control.  
The rate of neurologic deficit improvement was 84%.   No tumor progression at immediately adjacent 
spine levels was seen.  There were no cases of treatment-related myelopathy (4).   
 
       Some tumor histologies, such as renal cell carcinomas and malignant melanoma, are known to be 
relatively radioresistant, and thus standard RT may provide less than optimal clinical response.  The 
University of Pittsburgh experience treating spine metastases from renal cell cancer and malignant 
melanoma was reported by Gerszten in 2005.  Forty-eight patients with 60 renal cell metastases were 
treated to 14-20 Gy (mean 16 Gy) prescribed to the 80% isodose line (maximum dose 17.5-25 Gy) in a 
single fraction.  Most patients had previously been treated with fractionated external-beam radiation 
therapy.  With a median follow-up of 37 months, 89% of patients had durable pain improvement and 
there were no cases of radiation myelopathy or radiculopathy (5).  Thirty-six melanoma spine metastases 
in 28 patients were treated with single fraction SBRT using the same dose regimen.  With a median 
follow-up of 13 months, 96% of patients had long-term pain improvement and there were no cases of 
neural toxicity (6). 
 
       Chang and colleagues published MD Anderson Cancer Center’s phase I/II experience using SBRT 
for spine metastases.  Seventy-four tumors in 63 patients were treated to 30 Gy in 5 fractions or 27 Gy in 
3 fractions delivered every 2 days, with typically 80-90% of the target volume receiving at least the 
prescription dose.  Thirty-five patients had previously received in-field radiation therapy, with the cord 
dose limited to < 45 Gy.  No chemotherapy was given within 30 days of radiosurgery.  With a median 
follow-up of 21.3 months, the 1-year local control rate based on MRI imaging was 84%, and narcotic use 
decreased from 60% to 36% at six months.  Twenty-three percent of patients progressed radiographically, 
and the pattern of failure suggested that the pedicles and posterior elements using a wide bone margin 
posterior to the involved vertebrae should be routinely included in the planning target volume.  The spinal 

 
Amendment 1: February 26, 2009 
5
cord was limited to 10 Gy in 5 fractions or 9 Gy in 3 fractions.  No patient developed grade 3 or 4 
neurologic toxicity (7). 
 
       Yamada and colleagues from Memorial Sloan-Kettering Cancer Center treated 103 spinal metastases 
in 93 patients with SBRT to a median dose of 24 Gy (range 18-24 Gy), with the median percentage of the 
PTV receiving at least 95% of the dose being 95% (82-100%).  No patient had received prior RT to the 
region of interest.  The maximum spinal cord dose was limited to 14 Gy and the cauda equina dose was 
limited to 16 Gy.  With a median follow-up of 15 months, 90% of patients experienced durable pain 
control and local control.  The median time to local failure was 9 months.  Local control was dose-related:  
95% for 24 Gy compared to 80% for < 24 Gy (mean 20.8 Gy).  Treatment failure was defined as disease 
progression on MRI.  Acute toxicity was generally mild (grade 1-2), and there were not cases of late 
myelopathy or radiculopathy (8). 
 
       The Stanford University experience was reported by Gibbs and colleagues.  Seventy-four patients 
with 102 spinal metastases were treated with Cyberknife.  The majority (50 patients) had prior radiation 
therapy within or adjacent to the treatment site.  Patients were treated to 16-25 Gy in 1-5 fractions, with 
fractionated treatment used when single-fraction SBRT would give a cord Dmax > 10 Gy.  With a mean 
follow-up of 9 months, 84% had improvement or resolution of their symptoms and 3 patients (4%) 
developed clinical or radiographic signs of spinal cord injury at 6-10 months after treatment.   There were 
no clear spinal cord total dose or average dose that predicted these complications.  Two of three patients 
had received anti-angiogenic or epidermal growth factor inhibitor-targeted therapy within 2 months of 
developing clinical myelopathy.  No complications occurred when the volume of cord receiving a 
biological equivalent dose of 12 Gy in a single fraction (BED3 of 58 Gy) was less than 0.15 cm3.  Acute 
toxicity was uncommon and limited to nausea. They recommended using SBRT treatment schedules that 
limited the spinal cord biologic equivalent dose to 10 Gy to < 0.3 cc and 12 Gy to < 0.15 cc in 1 fraction 
(9). 
 
       The Stanford University experience in treating benign tumors of the spine has been reported.  Fifty-
one patients with 55 benign extra-axial, intradural spinal tumors were treated with Cyberknife stereotactic 
radiosurgery, including 30 schwannomas, 9 neurofibromas, and 16 meningiomas.  Only 4 patients were 
previously irradiated.  Eligibility criteria were contraindications for surgery due to medical co-
morbidities, underlying Neurofibromatosis I (7 patients) or II (10 patients) resulting in multiple lesions 
developing over time, or patient preference, with well-circumscribed lesions, no evidence of spinal 
instability and minimal compression of the spinal cord.   The most common presenting symptom was 
pain, followed by radiculopathy and myelopathy.  Patients were treated to 16-30 Gy in 1-5 fractions 
typically to the 80% IDL (most received 1-2 fractions).  The median follow-up time was 23 months.  Of 
the 28 patients with greater than 24 months follow-up, all have stabilized (61%) or decreased (39%) in 
size.  Radiosurgery was not very effective at reversing mass effect.  Three tumors enlarged by < 10% at 6-
12 months, two were transient and one underwent surgery for worsening pre-existing meylopathy.  
Schwannoma patients experienced 96% local control, with 56% stable and 40% decreased in size on 
imaging.  The majority experienced stabilized clinical symptoms, 50% had significant pain improvement, 
and 40% had decreased weakness or improved sensation; 18% experienced clinical worsening.  
Meningioma patients experienced 100% local control, with 67% stable and 33% decreased in size on 
imaging.  Approximately 70% significant improvement in pain and 50% had improved strength, but 
without improvement in sensory loss.  Thirty percent experienced minor worsening pain, numbness, or 
weakness.  Only 50% of neurofibroma patients were symptomatically stable, and none had improved 
clinical symptoms.  However, 6 of 7 patients who underwent follow-up imaging had stable disease.  
Interesting, the surgical literature also reports poor symptomatic control.  One patient with a meningioma 
(2%) experienced presumed radiation myelopathy 8 months after SBRT to a dose of 24 Gy in 3 fractions 
(maximum dose 3435 cGy); the volume of cord irradiated to 18 Gy was 1.7 cm3 (9,10).  
 

 
Amendment 1: February 26, 2009 
6
     Intramedullary spinal cord AVMs have also been treated with SBRT.  A report from Stanford 
University on 15 patients treated to a mean prescription dose of 20 Gy in 2-5 fractions.  With mean 
follow-up of 28 months, only 1 of 8 patients with follow-up angiography at 3 years showed complete 
obliteration; however, there were no further hemorrhages or neurologic deterioration. The authors 
recommended not treating intramedullary lesions greater than 1.5 cm3 in volume, to minimize the chance 
of neural toxicity (9).   
 
       Sohn (from Korea) reported results at the International Stereotactic Radiosurgery Society Meeting in 
July 2007 on the use of SBRT for 33 patients with schwannoma or meningioma of the spine treated with 
the Novalis system.  Patients received a single fraction of 13 Gy (schwannoma) or 15 Gy (meningioma) 
prescribed to the 80% isodose line.  For patients with spinal cord compression, fractionated stereotactic 
radiosurgery was utilized (24 Gy in 3 fractions).  With a mean follow-up of two years, there were no late 
toxicities. 
 
       Also at the International Stereotactic Radiosurgery Society Meeting in July 2007, Sahgal (UCSF) 
reported the results of 16 patients with benign spinal tumors treated with Cyberknife radiosurgery.  Doses 
ranged from 12 Gy in 1 fraction to 5 Gy in 5 fractions.  With a median follow-up of 25 months, there 
were no late toxicities.  Three patients with Neurofibromatosis I progressed.  The one year freedom from 
progression rate was 89%.   
 
 
St. John’s Mercy has installed an Elekta Synergy-S® linear accelerator at the David C. Pratt Cancer 
Center that is specifically designed to deliver highly-precise SBRT treatments.  It has a tightened 
isocenter accuracy calibrated to a precision of within 1.5 mm diameter, a micro-MLC for treatment of 
small radiation ports, a specially designed Hexapod® table top that can correct for patient misalignment in 
both translational and rotational directions, an onboard cone-beam kV CT for precise tumor localization 
immediately prior to treatment, four-dimensional CT (4D-CT) and 3D Line® which together allow for 
accurate monitoring of and compensation for tumor motion during respiration, active breathing control for 
respiratory gating, and real-time continuous fluoroscopic capability for visual confirmation that the target 
remains in the treatment field. 
 
2.0 Objectives 
 
 
This study will evaluate the local control rate as well as acute and late toxicity rates of stereotactic 
body radiotherapy (SBRT) for the treatment of spine metastases and benign spine tumors. 
 
 
2.1 Hypothesis 
 
 
2.1.1 For selected patients with spine metastases or benign spine tumors, stereotactic body  
 
 
 
radiotherapy (SBRT) is technically feasible with acceptable complication rates. 
 
 
2.1.2 Local tumor control rate with stereotactic body radiotherapy (SBRT) will be at least as  
 
 
 
good as standard fractionation radiation therapy. 
 
 
2.2 Study Design 
 
 
2.2.1 Single site, non-randomized, prospective, phase IV trial 
  
2.2.2 Composed of 2 patient groups: 
  
 
     Spine Metastases 
  
 
     Benign Spine Tumors 
 
 
2.2.3 Data collected will include patient demographics, pathology data, tumor stage,  
 
 
 
SBRT dose fractionation scheme, dose received by adjacent critical normal tissues,  
 
 
 
tumor recurrence data, and acute and late toxicities.   
 
 
2.2.4 Follow up data will be collected during the patient’s standard office visits.  The 
 
  
 
anticipated duration of this study is 5 years. 

 
Amendment 1: February 26, 2009 
7
 
2.3 End Points 
 
 
2.3.1 Primary endpoints will be symptom control and local tumor recurrence rate.   
 
 
 
-  Evaluation of pain relief will be assessed using a 10-point visual analog scale 
 
 
 
-  Analgesic use will be documented to ensure that pain improvement is not due to an  
 
 
 
    increase in the amount of analgesic usage.  
 
 
 
-  Evaluation of neurologic improvement will be assessed by physical exam using the  
 
 
 
   ASIA Impairment Scale 
 
 
 
- Local recurrence is defined as tumor recurrence or progression within the planning  
 
 
 
 target volume.  
- Local control rate will be evaluated by imaging techniques and/or clinical symptoms  
 (worsening or no improvement in pain or neurologic compromise).  If follow-up  
   imaging is available, a local recurrence will be defined as an increase of > 20% in  
   tumor size.   
 
 
2.3.2 Secondary endpoint will be late toxicity rate.  
 
 
 
- Grading of acute and late complications is defined in Section 12.3 (Appendix III)  
 
3.0 Patient Selection 
 
 
3.1 Eligibility Criteria 
 
 
3.1.1 
Patient age of at least 18 years 
 
 
3.1.2 
Zubrod performance status of 0-3 
 
 
3.1.3 
Vertebral and/or paraspinal metastases, with or without prior surgery and/or  
 
 
 
fractionated radiotherapy 
  
 
 
3.1.4 
Benign extradural spine tumors such as chordomas, meningiomas, schwannomas,  
 
 
 
neurofibromas, paragangliomas, and arteriovenous malformations (AVMs). 
3.1.5 
Established histologic diagnosis of a benign or malignant tumor of the spine.  For  
 
 
 
patients with malignant spine tumors, the histologic diagnosis may come from biopsy  
 
 
 
of the primary tumor site or an elsewhere metastatic site.  If this represents the first  
 
 
 
appearance of metastatic disease, however, the diagnosis of metastasis should be  
 
 
 
histologically confirmed, when possible. 
 
 
3.1.7 
Arteriovenous malformation of the spine identified radiographically (no biopsy) 
 
 
3.1.8 
Well-defined lesion involving no more than 2 adjacent vertebral levels or spinal  
 
 
 
segment 
 
 
3.1.9 
No overt spinal instability 
 
 
3.1.10 
Neurologic deficit is unrelated to bony fragments/bony compression of neural  
 
 
 
structures 
 
 
3.1.11 
No previous radiation therapy at the involved level(s) within 3 months of radiosurgery  
 
 
3.1.12 
Minimal spinal canal compromise that is not rapidly progressive.  Ideally, the tumor  
 
 
 
should not be within 5 mm of the spinal cord. 
 
 
3.1.13 
No pregnant or lactating women (negative serum pregnancy test for pre-menopausal  
 
 
 
women performed within 72 hours of registration) 
 
 
3.1.14 
If chemotherapy is planned, ideally it should not have been given within 30 days of  
 
 
 
starting radiation and should not resume until at least 2 weeks after completing  
 
     radiation.  In addition, it is not recommended to perform SBRT when targeted anti- 
 
     angiogenesis therapy is planned within 2 months of the procedure.  
 
 
3.1.15 
Signed study-specific consent form 
 
 
3.2 Exclusion Criteria 
 
 
3.2.1 
Lesion involving > 3 adjacent vertebral levels 
 
 
3.2.2  
Overt spinal instability 
 
 
3.2.3 
Neurologic deficit due to bony fragments/bony compression of neural structures 

 
Amendment 1: February 26, 2009 
8
 
 
3.2.4 
Prior radiotherapy at the involved level(s) within 3 months of radiosurgery, more than 
 
 
 
one prior course of radiotherapy at the involved level(s), or more than 45 Gy previous  
 
 
 
radiation exposure at the involved level(s) 
 
 
3.2.5 
Rapidly progressive spinal cord compromise or neurological deficit 
 
 
3.2.6 
Paralysis, or otherwise compromised motor function due to radiographically  
 
 
 
confirmed cord compression 
 
 
3.2.7 
Patient unable to undergo an MRI 
 
 
3.2.8 
Pregnant or lactating women, due to potential exposure of the fetus to RT and  
 
 
 
unknown effects of RT on lactating females  
 
 
3.2.9 
Patients with psychiatric or addictive disorder that would preclude obtaining informed  
 
 
 
consent 
 
4.0 Pretreatment Evaluation 
 
 
4.1 Patient history, including prior radiation and chemotherapy treatments 
 
4.2 Physical examination  
 
4.3 Assessment of neurological function using the ASIA Impairment Score (Appendix IV) 
 
4.4 Assessment of pain using a 10-point visual analogue scale (Appendix V) 
 
4.5 Evaulation by an experience neurosurgeon that must include (1) an assessment of spinal  
 
 
stability, (2) an assessment of both medical and surgical operability 
 
4.6 MRI of the affected spine 
 
4.7 Tissue biopsy confirming a diagnosis of malignancy (may be at the primary site, another  
 
 
metastatic site, or the spinal metastatic site dependent on the clinical situation) in the case of  
 
 
metastatic tumors.  Primary tumors should also be biopsy confirmed, except in the case of  
 
 
vascular malformations. 
4.8 CBC, platelets, bilirubin, AST, ALT, alkaline phosphatase, renal panel within 1 month of  
 
planned radiosurgery, if clinically indicated 
 
5.0 Simulation 
 
 
5.1 
Custom Mask and Bite Block Device, such as the HeadFix or Esarte frame, (for C-spine) or  
 
 
Body Fix (for TLS-spine) immobilization device 
 
5.2 
CT simulation without IV contrast with 1-2 mm slice thickness, including the treatment 
 
 
volume and at least 3 vertebral bodies above and below the target area.  When necessary, the  
 
 
planning CT scan will be performed with intravenous contrast and/or oral contrast to aid in  
 
 
target and normal tissue definition. 
 
5.3 
3-point leveling tattoos 
 
5.4  Contrast enhanced MRI with 1-3 mm slice thickness through the involved spine levels 
performed without the immobilization device, to allow for CT-MRI fusion for target volume 
and normal tissue delineation 
 
6.0  Radiation Treatment Planning 
 
 
6.1 
Target Definition 
 
 
6.1.1 
Gross tumor volume (GTV) is contoured on the planning CT scan.  MRI images  
 
 
 
will be registered to the planning CT dataset to assist in constructing the GTV.   
 
 
6.1.2 
Clinical target volume (CTV) will be equal to the GTV  
 
 
6.1.3 
Planning target volume (PTV) for vertebral metastases will be defined as the CTV    
 
 
 
plus a 2-5 mm margin, at the discretion of the treating radiation oncologist.  It is  
 
 
 
recommended that consideration be given to including the entire involved vertebral  
 
 
 
body plus the pedicles and posterior elements of the involved vertebral bodies.   

 
Amendment 1: February 26, 2009 
9
 
 
6.1.4 
The PTV for benign tumors will be defined as the CTV plus a 2-5 mm margin, at the  
 
 
 
discretion of the treating radiation oncologist.  The PTV may be modified to exclude  
 
 
 
the spinal cord and cauda equina volumes. 
 
 
 
6.2 
Normal Tissue Definition 
 
 
6.2.1 
Required normal tissue contours will vary according to the level of spinal irradiation  
 
 
 
and corresponding organs at risk.  The spinal cord (including the cauda equina when  
 
 
 
appropriate) will be contoured for all cases.  The esophagus, stomach, bowel, kidneys,  
 
 
 
liver, larynx, lungs, and heart will be contoured when appropriate. 
 
 
6.2.2 
Spinal cord – Contours should extend from the superior slice of the planning CT scan  
 
 
 
or the foramen magnum (whichever is most caudad) to the inferior slice of the  
 
 
 
planning CT scan or the terminal end of the spinal cord (whichever is most cephalad).  
 
 
 
The volume may be expanded by 1-2 mm for setup uncertainty. 
 
 
6.2.3 
Cauda Equina – Contours should extend from the superior slice of the planning CT  
 
 
 
scan or the terminal end of the spinal cord (whichever is most caudad) to the inferior  
 
 
 
slice of the planning CT scan or the terminal end of the cauda equina (which is most  
 
 
 
cephalad), and includes the entire thecal sac.  The volume may be expanded by  
 
 
 
1-2 mm for setup uncertainty. 
6.2.4 
Esophagus – Contours should include the entire esophagus, from 2 cm above the  
 
manubrium to the level of the gastroesophageal (GE) junction.  When possible, oral  
 
contrast should be utilized to aid in volume definition. 
6.2.5 
Stomach – Contours should include the entire stomach, with the proximal limit at the  
 
 
 
GE junction.  When possible, oral contrast should be utilized to aid in volume  
 
 
 
definition. 
 
 
6.2.6 
Bowel – Contours should include both small and large bowel.  When possible, oral  
 
 
 
contrast should be utilized to aid in volume definition. 
 
 
6.2.7 
Kidneys – Contours should include the entire left and right kidneys, including the  
 
 
 
renal parenchama and adjacent proximal collecting system. 
 
 
6.2.8 
Liver – Contours should include the entire liver, from the hepatic dome to its inferior  
 
 
 
border.  
 
 
6.2.9 
Larynx – Contours should include the entire larynx, from the hyoid bone through the  
 
 
 
cricoid cartilage 
 
 
6.2.10 Lungs – Contours should include the entire left lung, right lung, and both lungs. 
 
 
6.2.11 Heart – Contours should include the entire heart along with the pericardial sac, from  
 
 
 
the upper limit of the right atrium and right ventricle (excluding the pulmonary trunk,  
 
 
 
ascending aorta, and SVC) to the inferior extent of the myocardium. 
 
 
6.2.12 Skin – Contour should include a 5 mm thick volume beneath the skin surface. 
 
 
6.3 
Dose-Specification 
 
 
6.3.1 
Radiation beams will conform to the PTV outline without additional margin and the  
 
 
 
dose will be prescribed to the isodose line (IDL) that covers at least 95% of the PTV, 
 
 
 
which is typically around 80%.  
 
 
6.3.2 
SBRT dose-fractionation scheme will be chosen at the discretion of the treating  
 
 
 
radiation oncologist, but the normal tissue dose constraints must be maintained. 
 
 
 
Suggested dose-fractionation schemes, derived from the available literature, are listed 
 
 
 
below.  Also included are the corresponding biologic equivalent dose (BED) for each 
 
 
 
based on the linear-quadratic model: 
 
 
 
 

 
Amendment 1: February 26, 2009 
10
 
 
 
 
SBRT scheme 
BED1 
(/=10) 
BED2 
(/=3) 
Equivalent 
2 Gy/Fx 
Dose1 
(/=10) 
Equivalent 
2 Gy/Fx 
Dose2 
(/=3) 
 
Vertebral 
Metastases  
 
 
 
 
25 Gy x 1 
24 Gy x 1 
23 Gy x 1 
22 Gy x 1 
21 Gy x 1 
20 Gy x 1 
19 Gy x 1 
18 Gy x 1 
17 Gy x 1 
16 Gy x 1 
15 Gy x 1 
14 Gy x 1 
9 Gy x 3 
8 Gy x 3 
7 Gy x 3 
6 Gy x 5 
5 Gy x 5 
 
87.5 Gy 
81.6 Gy 
75.9 Gy 
70.4 Gy 
65.1 Gy 
60 Gy 
55.1 Gy 
50.4 Gy 
45.9 Gy 
41.6 Gy 
37.5 Gy 
33.6 Gy 
51.3 Gy 
43.2 Gy 
35.7 Gy 
48 Gy 
37.5 Gy 
233.3 Gy 
216 Gy 
199.3 Gy 
183.3 Gy 
168 Gy 
153.3 Gy 
139.3 Gy 
126 Gy 
113.3 Gy 
101.3 Gy 
90 Gy 
79.3 Gy 
108 Gy 
88 Gy 
70 Gy 
90 Gy 
66.7 Gy 
 
72.9 Gy 
68 Gy 
63.25 Gy 
58.7 Gy 
54.25 Gy 
50 Gy 
45.9 Gy 
42 Gy 
38.25 Gy 
34.7 Gy 
31.25 Gy 
28 Gy 
42.75 Gy 
36 Gy 
29.75 Gy 
40 Gy 
31.25 Gy 
 
140 Gy 
129.6 Gy 
119.6 Gy 
110 Gy 
100.8 Gy 
92 Gy 
83.6 Gy 
75.6 Gy 
68 Gy 
60.8 Gy 
54 Gy 
47.6 Gy 
64.8 Gy 
52.8 Gy 
42 Gy 
54 Gy 
40 Gy 
Intrameduallary  
Spinal 
Metastases 
 
5 Gy x 5 
 
37.5 Gy 
 
66.7 Gy 
 
31.25 Gy 
40 Gy 
 
 
Benign 
Extradural Spine 
Tumors 
 
 
 
16 Gy x 1 
15 Gy x 1 
14 Gy x 1 
13 Gy x 1 
12 Gy x 1 
9 Gy x 3 
8 Gy x 3 
7 Gy x 3 
6 Gy x 5 
5 Gy x 5 
 
41.6 Gy 
37.5 Gy 
33.6 Gy 
29.9 Gy 
24.6 Gy 
51.3 Gy 
43.2 Gy 
35.7 Gy 
48 Gy 
37.5 Gy 
 
101.3 Gy 
90 Gy 
79.3 Gy 
69.3 Gy 
60 Gy 
108 Gy 
88 Gy 
70 Gy 
90 Gy 
66.7 Gy 
 
34.7 Gy 
31.25 Gy 
28 Gy 
24.9 Gy 
22 Gy 
42.75 Gy 
36 Gy 
29.75 Gy 
40 Gy 
31.25 Gy 
 
60.8 Gy 
54 Gy 
47.6 Gy 
41.6 Gy 
36 Gy 
64.8 Gy 
52.8 Gy 
42 Gy 
54 Gy 
40 Gy 
 
 
 
 
1Cancers are assumed to have an / ratio of approximately 10 
 
 
 
 
2Normal tissues are assumed to have an / ratio of approximately 3 
 
 
6.4 
Normal Tissue Dose Constraints    
 
 
6.4.1 
Tissues arranged in series, where the function of each subunit is vital for organ  
 
 
 
 
function, include the gastrointestinal tract and spinal cord 
 
 
 
 
6.4.1.1 
Esophagus, Stomach 
 
 
 
 
 
 
- Maximum point dose, Dmax < 15 Gy in 1 fraction (< 1 cc to > 10 Gy) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 24 Gy in 3 fractions (8 Gy per fraction) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 30 Gy in 5 fractions (6 Gy per fraction) 
 
 

 
Amendment 1: February 26, 2009 
11
 
 
 
 
6.4.1.2 
Bowel 
 
 
 
 
 
 
- Maximum point dose, Dmax < 15 Gy in 1 fraction 
 
 
 
 
 
 
- Maximum point dose, Dmax < 24 Gy in 3 fractions (8 Gy per fraction) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 30 Gy in 5 fractions (6 Gy per fraction) 
 
 
 
 
6.4.1.3 
Spinal Cord 
 
 
 
 
 
 
- < 0.5 cc to 8 Gy in 1 fraction  
 
 
 
 
 
 
- < 0.3 cc to 10 Gy in 1 fraction 
 
 
 
 
 
 
- < 0.15 cc to 12 Gy in 1 fraction 
 
 
 
 
 
 
- Maximum point dose, Dmax < 18 Gy in 3 fractions (6 Gy per fraction) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 22.5 Gy in 5 fractions (4.5 Gy per fraction) 
 
 
 
 
6.4.1.4 
Cauda Equina 
 
 
 
 
 
 
- Maximum point dose, Dmax < 13 Gy in 1 fraction  
 
 
 
 
 
 
- Maximum point dose, Dmax < 21 Gy in 5 fractions (7 Gy per fraction) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 25 Gy in 5 fractions (5 Gy per fraction) 
 
 
6.4.2 
Tissues arranged in parallel includes the liver parenchyma, kidneys, skin, and lungs  
 
 
 
 
6.4.2.1 
Liver critical volume model 
 
 
 
 
 
 
- Maximum point dose, Dmax < 15 Gy in 1 fraction 
 
 
 
 
 
 
- At least 700 cc of normal liver volume must receive < 15 Gy in  
 
 
 
 
 
 
  3 fractions (9.5 Gy in 1 fraction; 18 Gy in 5 fractions), which has a  
 
 
 
 
 
 
  BED2Gy (/=3) of 40 Gy (equivalent to 24 Gy in 2 Gy fractions) 
 
 
 
 
 
 
- At least 35% of normal liver must receive < 15 Gy in 3 fractions 
 
 
 
 
6.4.2.2 
Kidneys 
 
 
 
 
 
 
 
- mean dose < 3 Gy 
 
 
 
 
 
 
 
- V10 < 10% 
 
 
 
 
6.4.2.3  
Skin 
 
 
 
 
 
 
- Maximum point dose, Dmax < 15 Gy in 1 fraction  
 
 
 
 
 
 
- Maximum point dose, Dmax < 24 Gy in 3 fractions (8 Gy per fraction) 
 
 
 
 
 
 
- Maximum point dose, Dmax < 30 Gy in 5 fractions (6 Gy per fraction) 
 
 
 
 
6.4.2.4 
Lungs 
 
 
 
 
- < 10% of total lung volume receiving > 20 Gy (V20)  
 
 
 
 
- < 40% of total lung volume receiving > 5 Gy (V5) 
 
7.0 Stereotactic Body Radiotherapy Treatment Delivery 
 
 
7.1 
Premedication 
 
 
The decision to premedicate a patient prior to spine SBRT is at the discretion of the  
 
 
radiation oncologist and/or neurosurgeon.  While there is no universal agreement, the  
 
 
following are a list of agents that have been suggested by some investigators to potentially  
 
 
reduce patient discomfort, and possibly prevent acute and/or late toxicity if used as  
 
 
premedication prior to spine SBRT.  
 
 
7.1.1 
Corticosteroids (Decadron 4-10 mg PO or equivalent) 15-60 minutes prior to each  
 
 
 
fraction for the intended purpose of modulating immediate inflammatory effects.   
 
 
7.1.2 
Analgesic premedication to avoid general discomfort during long treatment durations.  
 
 
7.1.3 
Prophylactic antiemetics (Zofran 4-8 mg PO or Kytril 2 mg PO) 45-60 minutes prior  
 
 
 
to each fraction to possibly prevent acute nausea 
 
 
7.1.4 
Anti-anxiety medication for patient comfort during long treatment duration 
 
 
7.2 
Treatment 
 
 
7.2.1 
The medical physics staff will perform routine quality assurance checks on the  
 
 
 
treatment machine to ensure that the mechanical isocenter stability is within  
 
 
 
specification (ie. diameter < 1.5 mm).  

 
Amendment 1: February 26, 2009 
12
 
 
7.2.2 
The medical physics staff will perform patient-specific quality assurance  
 
 
 
measurements to ensure that the treatment plan is deliverable and that the dose  
 
 
 
distribution is accurate.  
 
 
7.2.3 
The patient will be positioned in the custom immobilization device on the Hexapod®  
 
 
 
treatment couch and aligned to 3-point setup points with the in-room lasers. 
 
 
7.2.4 
Daily CT localization of the GTV isocenter is required prior to each fraction.  Once  
 
 
 
the patient is properly positioned, a cone-beam CT of the treatment area is acquired,  
 
 
 
fused, and aligned to the treatment planning CT.  Translational and rotational  
 
 
 
adjustments of patient positioning are performed as indicated.  If adjustments are  
 
 
 
required, an orthogonal (ex. AP and LATERAL) set of electron portal images or a  
 
 
 
second cone-beam CT of the treatment area will be obtained prior to treatment 
 
 
 
to confirm proper alignment of the isocenter.  A third cone-beam CT may be  
 
 
 
obtained following treatment delivery to assess for intra-fraction motion.   
 
 
 
Depending on the overall treatment time, an additional cone-beam CT scan may be  
 
 
 
obtained during treatment at the discretion of the treating radiation oncologist to  
 
 
 
ensure accuracy of the isocenter alignment and target localization. 
 
 
7.2.5 
Either multiple coplanar or noncoplanar static gantry angle intensity-modulated fields  
 
 
 
or rotational arcs will be utilized. 
 
 
7.2.6 
Only photon (x-ray) beams will be used, preferably in energies of 6-18 MV. 
 
8.0 Drug Therapy 
 
 
8.1 
The use of chemotherapy is left to the discretion of the medical oncologist. 
 
8.2 
Chemotherapy agents during radiation is not allowed.  Ideally, chemotherapy should not have  
 
 
been given within 30 days of starting radiation and should not resume until at least 2 weeks  
 
 
after completing radiation.  In addition, it is not recommended to perform SBRT when  
 
 
targeted anti-angiogenesis therapy is planned within 2 months of the procedure.  
 
9.0 
Patient Assessment 
 
 
9.1 
Study Parameters 
 
 
The following are suggested patient follow-up intervals and evaluations that may be  
 
 
performed to either assess for treatment toxicity or tumor response to SBRT: 
Assessment 
Pre-
Rx 
Post-Rx
6 wk 
Post-Rx 
3 mo 
Post-Rx
6 mo 
Post-Rx 
9 mo 
Post-Rx
1 yr 
H&P / Weight 
X
X
X
X
X 
Xb
Disease status 
X
X
X
X
X 
Xb
Neurologic Function 
X
X
X
X
X 
Xb
Pain Score 
X
X
X
X
X 
Xb
Toxicity Assessment 
X
X
X
X 
Xb
AST / ALT / Alk Phos 
Xa
 
 
Total Bilirubin 
Xa
 
 
Creatinine 
Xa
 
 
CBC with Platelets 
X
 
 
Pregnancy test 
Xa
 
 
MRI of affected spine 
    X
Xc
   Xc
Xc
Xc 
    Xc
PET/CT 
Xc
Xc
   Xc
Xc
Xc 
    Xc
 
 
 
a 
if clinically appropriate  
 
 
 
b 
clinical examination, neurologic function, pain score, late toxicity, and disease status assessment at  
 
 
 
 
3 month intervals for first year, then at the discretion of the treating radiation oncologist 
 
 
 
c 
at the discretion of the treating radiation oncologist 

 
Amendment 1: February 26, 2009 
13
 
9.2 Response Evaluation 
 
 
 
9.2.1       It is recognized that many patients will not undergo follow-up imaging.  Evaluation  
 
 
 
 
        of treatment response in these patients will be clinical.   
 
 
 
 
        -  Local recurrence will be defined as worsening or no improvement in pain or  
 
 
 
 
           neurologic compromise.   
 
 
 
9.2.2 
MRI scan of the affected spine with IV contrast 
   - Local recurrence will be defined as tumor recurrence or progression within  
       the planning target volume with an increase of > 20% in tumor size.   
 
 
 9.2.3  
PET/CT scan 
 
 
 
 
- May be obtained at the discretion of the treating radiation oncologist if there is  
 
 
 
 
  uncertainty on the diagnostic MRI scan as to the disease status 
 
 
9.3 
Toxicity 
 
 
9.3.1 
The investigator will report and record all serious adverse events that occur.  Adverse  
 
 
 
events should be reported using the CTC grading system (Appendix III).   
 
 
9.3.2 
Examples of anticipated acute adverse events include: 
 
 
 
 
- General malaise 
 
 
 
 
- Nausea occurring within a few hours of treatment 
 
 
 
 
- Anorexia 
 
 
 
 
- Radiation dermatitis – dryness, tanning, redness, itching 
 
 
 
 
- Localized hair loss 
 
 
 
 
- Musculoskeletal pain 
 
 
 
 
- Dysphagia / Esophagitis 
 
 
 
 
- Hoarseness 
 
 
 
 
- Pneumonitis 
 
 
 
 
- Diarrhea 
 
 
 
 
- Neurologic changes including motor weakness, numbness, and/or paresthesias 
 
 
9.3.3 
Examples of anticipated late adverse events include:   
 
 
 
 
- Myelopathy resulting in motor weakness, numbness, and/or paresthesias 
 
 
 
 
- Vertebral body collapse 
 
 
 
 
- Persistent dysphagia, or esophageal stricture 
 
 
 
 
- GI toxicity may consist of bleeding, ulceration and/or perforation of the  
 
 
 
 
  esophagus, stomach, duodenum, or bowel.   
 
 
 
 
- Impaired liver function 
 
 
 
 
- Reduction in kidney function 
 
 
 
 
- Reduction in lung function 
 
 
 
 
- Decrease in thyroid function 
 
 
 
 
- Persistent hoarseness 
 
 
 
 
- Localized skin fibrosis, edema, and/or ulceration 
 
 
 
      - Radiation-induced secondary malignancy 
 
 
9.3.4 
Reporting of unanticipated or serious adverse events will be reported according to the  
 
 
 
institutions IRB policy.  An unanticipated adverse effect is defined as follows: 
 
 
 
 
Any serious adverse effect on health or safety or any life-threatening problem or  
 
 
 
 
death caused by, or associated with, stereotactic body radiotherapy, if that effect,  
 
 
 
 
problem, or death was not previously identified in nature, severity, or degree of  
 
 
 
 
incidence in the investigational plan or application (including a supplementary  
 
 
 
 
plan or application), or any other unanticipated serious problem associated with a  
 
 
 
 
treatment that relates to the rights, safety, or welfare of subjects. 
  
 
 

 
Amendment 1: February 26, 2009 
14
 
9.4 
Patient Withdrawal from Study 
 
 
During the course of the study, it is possible that patients may withdraw or be withdrawn from  
 
 
the study.  Factors that may lead to a withdrawal from the study may include, but are not  
 
 
limited to the following: 
 
 
 
Patient Withdrawal……………At any time a patient may voluntarily withdraw from the  
 
 
 
 
 
 
study.  This withdrawal will not affect their future medical  
 
 
 
 
 
 
treatment or benefits.   
 
 
 
Patient Lost to Follow-Up…….Should a patient be classified as lost to follow-up, efforts  
 
 
 
 
 
 
to contact the patient should be made.  
 
 
 
Physician Decision……………Should a physician decide that continuing in the study is  
 
 
 
 
 
 
detrimental to the health and welfare of the patient, the  
 
 
 
 
 
 
patient may be withdrawn from the study.   
 
 
 
Medical Reason……………….Should the patient condition deteriorate the patient may be  
 
 
 
 
 
 
withdrawn from the study to allow for proper medical care.   
 
10.0 Risk/Benefit Analysis 
 
 
10.1 
Risk associated with SBRT for spine metastases and primary spine tumors 
 
 
10.1.1 Acute toxicities reported to occur as a result of SBRT for spine metastases and  
 
 
 
benign spine tumors include, but are not limited to:  general malaise, nausea,  
 
 
 
anorexia, radiation dermatitis, local hair loss, local musculoskeletal pain,  
 
 
 
dysphagia/esophagitis, hoarseness, diarrhea, and neurologic changes including motor  
 
 
 
weakness, numbness, and/or paresthesias 
 
 
10.1.2 Late toxicities reported to occur as a result of SBRT for spine metastases and benign 
spine tumors are uncommon and primarily neurologic, consisting of motor weakness, 
numbness, and/or paresthesias.  Other serious late toxicities are rare and may include 
vertebral body collapse, persistent dysphagia, esophageal stricture, bowel ulceration 
and/or perforation, impaired liver function, reduction in kidney function, reduction in 
lung function, hypothyroidism, persistent hoarseness, and localized skin fibrosis 
edema and/or ulceration. 
 
 
10.2 
Minimization of Risks 
 
 
Although the risks outlined in Section 9.3 may occur, the likelihood of serious events  
 
 
occurring is considered uncommon as long as certain precautions are taken.  The potential  
 
 
risks have been minimized by: 
 
 
- Premedication as described in Section 7.1 
 
 
- Strict compliance with normal tissue dose constraints as described in Sections 6.4 
 
 
10.3 
Potential Patient Benefits 
 
 
10.3.1 Ability to offer effective and expedient local therapy to patients with limited life  
 
 
 
expectancy from spine metastases 
 
 
10.3.2 Reduction in amount of radiation delivered to adjacent normal structures compared to  
 
 
 
standard-fractionation radiation therapy 
10.3.3 Reduced treatment duration compared to standard-fractionation radiation therapy 
10.3.4 Ability to avoid surgery potentially associated with significant risk of morbidity 
 
 
10.4 
Justification of the Study 
 
 
Patients who have spine metastases are not curable and often have a limited life expectancy.   
 
 
Local tumor control is important for prevention of tumor-related pain, pathologic fractures,  
 
 
and neurologic deterioration due to spinal cord / cauda equina compression.  Standard  
 
 
fractionation radiation therapy consists of a daily treatment regimen for approximately 2-3  

 
Amendment 1: February 26, 2009 
15
 
 
weeks, and has demonstrated unsatisfactory complete pain relief rates and tumor control rates.   
 
 
Stereotactic body radiotherapy shortens the radiation course to only 1-5 sessions.  Non- 
 
 
surgical treatment for recurrent spine metastases is very limited.  Traditional radiation therapy  
 
 
cannot be repeated at the same site in the spine, due to the increased risk of injury to normal  
 
 
tissue.  Spinal surgery is often difficult and can be associated with significant risk, or may not  
 
 
be an option due to prior surgery, other medical conditions or limited life expectancy.   
 
 
Stereotactic body radiotherapy offers an alternative to surgery for management of recurrent  
 
 
disease.  Recent phase I/II trials of SBRT for spine metastases have reported local tumor  
 
 
control rates of 81-95%, durable improvement in pain of 67-100%, and improvement in  
 
 
neurologic function of 84%, with low toxicity rates.  Surgical management of patients with  
 
 
benign spine tumors can be associated with significant risk of morbidity.  The advantage of  
 
 
stereotactic body radiotherapy is that it is not painful, and does not require anesthesia or  
 
 
hospitalization.     
  
 
 
10.5 
Statistical Analysis 
 
 
10.5.1 The overall survival and local control rates will be analyzed. 
 
 
10.5.2 
The incidence rate for any serious adverse events will be calculated. 
 
11.0 References 
 
(1) Chow E.  Palliative radiotherapy trials for bone metastases:  A systematic review.  J Clin Oncol.  
25:1423-1436, 2007. 
 
(2) Potters L.  American Society for Therapeutic Radiology and Oncology and American College of 
Radiology practice guidelines for the performance of stereotactic body radiation therapy.  Int J 
Radiat Oncol Biol Phys.  60:1026-1032, 2004. 
 
(3) Sahgal A.  Stereotactic body radiosurgery for spinal metastases:  A critical review.  Int J Radiat 
Oncol Biol Phys.  71(3):652-665, 2008.   
 
(4) Gerszten PC.  Radiosurgery for spinal metastases:  Clinical experience in 500 cases from a single 
institution.  Spine 32:193-199, 2007. 
 
(5) Gerszten PC.  Stereotactic radiosurgery for spinal metastases from renal cell carcinoma.  J 
Neurosurg Spine.  3:288-295, 2005. 
 
(6) Gerszten PC.  Radiosurgery for the treatment of spinal melanoma metastases.  Stereotac Func 
Neurosurg.  83:213-221, 2005. 
 
(7) Chang EL.  Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of 
failure.  J Neurosurg Spine 7:151-160, 2007. 
 
(8) Yamada PC.  High-dose single-fraction image-guided intensity-modulated radiotherapy for 
metastatic spinal lesions.  Int J Radiat Oncol Biol Phys.  71(2):484-490, 2008. 
 
(9) Gibbs IC.  Spinal and paraspinal lesions:  The role of stereotactic body radiotherapy.  Fron Radiat 
Ther Oncol 40: 407-414, 2007 
 
(10) Dodd RL.  CyberKnife radiosurgery for benign intradural extramedullary spinal tumors.  
Neurosurgery 58:674-685, 2006. 
 

 
Amendment 1: February 26, 2009 
16
12.0 Appendices 
 
 
12.1 
Appendix I 
 
St. John’s Mercy Medical Center 
Informed Consent for a Clinical Research Study 
 
STUDY TITLE: 
PHASE IV TRIAL EVALUATING THE USE OF STEREOTACTIC BODY  
 
RADIOTHERAPY FOR THE TREATMENT OF SPINE METASTASES AND  
 
PRIMARY SPINE TUMORS 
 
This is a clinical trial (type of research study).  Clinical trials include only patients who choose to take 
part.  This consent form may contain words that you do not understand.  Please ask the study doctor or the 
study staff to explain any words or information that you do not clearly understand.  You may take home 
an unsigned copy of this consent form to think about or discuss with family and friends before making 
your decision.   
 
WHAT SHOULD YOU KNOW ABOUT THE RESEARCH DOCTOR? 
 
You should know that your relationship with a research doctor is different from your relationship with 
your personal doctor.  Your personal doctor is treating your specific problem with the hope of a benefit 
for you.  When a doctor is your research doctor, he/she is treating all subjects under a specific protocol to 
learn about the results of a treatment, and with the understanding that you may or may not benefit from 
your participation in the study.  Be sure to ask questions of the study doctor if you want more information 
about this relationship. 
 
WHY IS THIS STUDY BEING PERFORMED?  
 
Treatment of cancer that has spread to the spine (metastases) and tumors that begin in the spine (primary 
tumors) is challenging and the outcome is often disappointing.  Treatment may consist of surgery, 
radiation therapy, or a combination of surgery followed by radiation therapy.  Radiation therapy has been 
used to improve local tumor control, alleviate tumor-related pain, prevent spine fractures, and improve 
neurologic symptoms such as weakness and numbness. Spinal surgery is often difficult and can be 
associated with significant risk, or may not be an option due to prior surgery or other medical conditions.  
While a standard course of radiation therapy may take 2-6 weeks of daily treatment to complete, recent 
technological advancements allow high-dose precisely targeted radiation treatment to be delivered in only 
1-5 sessions.  This technique is called stereotactic body radiotherapy.  The advantage of stereotactic 
radiotherapy over surgery is that it is not painful, and does not require anesthesia or hospitalization.  
Several institutions have reported excellent local tumor control, pain relief, and neurologic improvement, 
with low toxicity risk.  The purpose of this study is to collect additional data on the effectiveness of 
stereotactic body radiotherapy for spine metastases and primary spine tumors.   
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
Approximately 50 people are expected to participate in this clinical study. 
 
WHAT IS INVOLVED IN THE STUDY? 
 
If you wish to take part in this study, a series of tests will be performed to determine if you qualify for 
participation in the clinical study.  Your physician will ask you a series of questions regarding your 

 
Amendment 1: February 26, 2009 
17
medical history and a standard physical exam will be performed.  If you are a woman of childbearing age, 
you may be asked to give a urine or blood specimen so that a pregnancy test can be performed.  
 
If you qualify for the study, you will undergo a radiation treatment planning session called a simulation.  
At this visit, a custom rigid foam device will be fabricated to immobilize your body in the correct position 
for treatment.  A CT scan and an MRI scan will be obtained to plan your treatment.  Permanent small 
tattoos may be applied to your skin to aid in positioning your body on the treatment table. 
 
There may be several days between the simulation and the day you begin radiation.  During this time, 
complex radiation treatment planning will be performed by your radiation oncologist and their medical 
physics staff.  You will receive between 1-5 radiation treatments.  Your physician will explain your 
treatment in more detail.  Each radiation session may take an hour or longer to complete.  After the entire 
radiation course is complete, you will be given follow-up instructions.    
 
HOW LONG WILL I BE IN THE STUDY? 
 
We anticipate that you will remain in the study for approximately 5 years.  After treatment is completed 
routine follow-up visits will be conducted, typically at 3 month intervals for the first year, then less 
frequently. 
 
Your physician may decide stop your treatment if: 1) your disease becomes worse, or 2) side effects 
become very severe, or 3) new scientific developments occur that indicate the treatment is not in your best 
interest, or 4) your physician believes that this treatment is no longer in your best interest.  If your 
treatment is stopped, your doctor will discuss further treatment options with you.  
 
WHAT ARE THE RISKS OF THE STUDY? 
 
By participating in this study, you are at risk for several possible expected and unexpected side effects 
associated with stereotactic body radiotherapy to the spine.  Some of these are described below; however, 
there also may be other side effects that we cannot predict.  Most side effects go away shortly after the 
radiation therapy is stopped, but in some cases side effects can be serious, long-lasting, or permanent.  
 
Risks arising from the delivery of stereotactic radiotherapy to the spine which may occur shortly after 
completing treatment may include, but are not limited to:  
 
• 
Fatigue 
 
• 
Nausea occurring within a few hours of treatment 
 
• 
Loss of appetite 
 
• 
Hair loss over the treatment area 
 
• 
Skin redness over the treatment area 
 
• 
Skin tanning over the treatment area 
 
• 
Dry peeling of skin over the treatment area 
 
• 
Moist desquamation over the treatment area 
 
• 
Dry itchy skin 
 
• 
Muscular pain over the treatment area 
 
• 
Dysphagia (difficulty swallowing) 
 
• 
Dyspnea (shortness of breath) 
 
• 
Hoarseness 
 
• 
Diarrhea 
• 
Neurologic changes including motor weakness, numbness, and/or paresthesias  
 

 
Amendment 1: February 26, 2009 
18
Risks arising from the delivery of stereotactic radiotherapy to the spine which may develop several 
months to years after completing treatment may include, but are not limited to:  
 
• 
Bleeding ulceration and/or perforation (hole) in the stomach, duodenum, and/or small bowel 
 
• 
Scarring, swelling, and/or ulceration of the skin over the treatment area 
 
• 
Persistent dysphagia (difficulty swallowing) or esophageal stricture 
 
• 
Persistent hoarseness 
 
• 
Decrease in liver function 
 
• 
Decrease in kidney function 
 
• 
Dyspnea (shortness of breath) due to decrease in lung function 
 
• 
Decrease in thyroid function 
 
• 
Vertebral body collapse / fracture 
• 
Neurologic changes including motor weakness, numbness, and/or paresthesias 
 
I understand that all these side effects are possible.  I may experience no side effects, some of them, or 
most of them.  Although I will be closely monitored, not all side effects can be predicated and unforeseen 
problems can arise.  I understand that there may be some unknown or unanticipated risks or discomforts 
in addition to those specified here. 
 
Reproductive risks:  Because even very small doses of radiation can affect an unborn baby, you should 
not become pregnant while receiving radiation treatment.  You should also not nurse a baby while 
receiving radiation treatment.  
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
 
If you agree to take part in this study, there may or may not be a direct medical benefit to you.  However, 
there have been several trials completed at other institutions that have shown high local control rates, 
improvement in pain and neurologic symptoms after stereotactic body radiotherapy for spine metastases 
and primary spine tumors.  It is also convenient, requiring only 1-5 radiation sessions and no anesthesia or 
hospitalization.  Toxicity risk has been reported to be fairly low. 
 
WHAT OTHER OPTIONS ARE THERE? 
 
Other treatment options may include surgery, chemotherapy, standard-fractionation radiation therapy, or 
other investigational procedures or medications.  Another option is no further therapy.  Your doctor can 
provide information about your disease and the benefits of the different treatments for you.  You should 
feel free to talk with your doctor about your disease and expected outcomes.  The doctor involved in your 
care will be available to answer any questions you have about this program.  You are free to ask your 
doctor any questions concerning this program now or in the future.  
 
You are free to seek care from a doctor of your choice at any time.  If you do not take part in, or withdraw 
from, the study you will continue to receive alternate care.   
 
WHAT ABOUT CONFIDENTIALITY? 
 
Efforts will be made to keep your personal information confidential.  We cannot guarantee absolute 
confidentiality.  This Informed Consent and another document called an “Authorization to Use and 
Disclose Health Information” control how your health information may be used and disclosed during and 
after this study.  The results of this study may be published or presented at meetings but will not include 
your name or reveal your identity.  To participate in this study, you must sign both the Informed Consent 
and the Authorization to Use and Disclose Health Information.  Your personal information may be 
disclosed if required by law. 

 
Amendment 1: February 26, 2009 
19
 
WHAT ARE THE COSTS? 
 
Taking part in this study may lead to added costs to you or your insurance carrier.  Specifically, you or 
your insurance carrier will be responsible for the costs of the baseline blood tests, diagnostic imaging 
studies, stereotactic radiotherapy planning and delivery, and follow-up visits which would otherwise be a 
standard part of your care.  Please ask about any expected added costs or insurance problems.  St. John’s 
Mercy Medical Center has personnel that can assist you with this.   
 
Every precaution will be taken to prevent any injury to you during the study. In the event that injury 
occurs as a result of this study, treatment will be available.  You or your insurance carrier will be 
responsible for the costs of the treatment.  No funds have been set aside for compensation in the event of 
a research related injury.   
 
You or your insurance company will be charged for continuing medical care and/or hospitalization.   
You will not receive payment for participating in this study.   
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
 
Your participation is voluntary.  You may choose not to take part or may leave the study at any time.  
Your choice will not affect your doctors from providing care to you.  Choosing not to participate or 
leaving the study will not result in any penalty or loss of benefits to which you are entitled. 
 
You will be told of any important new findings developed during the course of your participation in this 
study that may affect your willingness to continue in the study.  The investigator may withdraw you from 
this study if issues occur that show that you should not continue to participate. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?    
 
If you have any questions or concerns regarding this study, or a research-related injury, you may contact 
one of the Principal Investigators, Dr. Julie Mai at 314-251-6844 or Dr. Bethany Sleckman at 314-251-
6770. 
 
For questions about your rights as a research participant, contact Dr. Donald York, Chairman of the St. 
John’s Mercy Medical Center Institutional Review Board (which is a group of people who review the 
research to protect your rights), at 314-569-6453. 
 
Your doctor understands the importance of your contribution to clinical studies that attempt to improve 
medical care.  Your doctor will make every effort to minimize, control, and treat any problems that may 
happen as a result of your participation in this study.  If you believe that you are injured solely as a result 
of the study, or if you have questions regarding the study, please contact the Principal Investigator. 
 
WHERE CAN I GET MORE INFORMATION? 
 
You may call the NCI’s Cancer Information Service at 1-800-422-6237 or TTY:1-800-322-8615 
 
Visit the NCI’s Web Sites: 
• 
Cancer Trials: comprehensive clinical trials information 
 
http://cancertrials.nci.nih.gov 
• 
CancerNet: accurate cancer information including PDQ 
 
http://cancernet.nci.nih.gov 

 
Amendment 1: February 26, 2009 
20
 
SIGNATURES 
 
I have read all the above, asked questions, and received answers concerning areas I did not understand.  I 
have had the opportunity to take this consent form home for review or discussion.  I willingly give my 
consent to participate in this study.  Upon signing this form I will receive a copy.  I may also request a 
copy of the protocol (full study plan). 
 
Participant (sign) ______________________________________________________________ 
 
Participant (written) ___________________________________________________________ 
 
Date _________________________________________________________________________ 
 
Principal Investigator ___________________________________________________________ 
 
Staff Member Performing Consent Process _________________________________________ 
 
Witness _______________________________________________________________________ 
 
IRB Stamp (This form is INVALID if the stamp is not present.) 

 
Amendment 1: February 26, 2009 
21
 
12.2 
Appendix II  
 
 
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 signs 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 pre-disease activities without restriction 
 
 
 
(KPS 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 
 
 
 
(KPS 70-80) 
 
 
 
2 
Ambulatory and capable or all self-care but unable to carry out any work  
 
 
 
activities.  Up and about more than 50% of waking hours  
 
 
 
(KPS 50-60) 
 
 
 
3 
Capable of only limited self-care, confined to bed or chair 50% of more of  
 
 
 
waking hours 
 
 
 
(KPS 30-40) 
 
 
 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or  
 
 
 
chair 
 
 
 
(KPS 10-20) 
 
 

 
Amendment 1: February 26, 2009 
22
12.3 
Appendix  III 
 
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) 
 
 
GRADE 
Toxicity 
1 
2 
3 
4 
5 
 
CONSTITUTIONAL 
 
 
 
 
 
 
Fatigue 
Mild fatigue over 
baseline 
Moderate or causing 
difficulty performing 
some ADL
Severe fatigue interfering 
with ADL 
Disabling 
- 
Fever 
100.4-102.2F
102.3-104.0F
> 104.0F for < 24 hr 
> 104.0F for > 24 hr
Death 
Weight loss 
5 - < 10% of 
baseline 
10 - < 20% of 
baseline
> 20% of baseline; tube 
feeding or TPN indicated 
- 
- 
 
PAIN 
 
 
 
 
 
 
Pain due to radiation 
Mild pain not 
interfering with 
function 
Moderate pain: pain 
or analgesics 
interfering with 
function, but not 
interfering with ADL
Severe pain: pain or 
analgesics severely 
interfering with ADL 
Disabling 
- 
Myositis (inflammation or 
damage of muscle) 
Mild pain not 
interfering with 
function 
Pain interfering with 
function, but not 
interfering with ADL
Pain interfering with ADL 
Disabling 
Death 
 
SKIN 
 
 
 
 
 
 
Radiation dermatitis 
Faint erythema or 
dry desquamation 
Moderate to brisk 
erythema; patchy 
moist desquamation, 
mostly confined to 
skin folds and 
creases; moderate 
edema
Moist desquamation other 
that skin folds and creases; 
bleeding induced by minor 
trauma or abrasion 
Skin necrosis or ulceration 
of full thickness dermis; 
spontaneous bleeding from 
involved site 
 
Telangiectasia 
Few 
Moderate number
Many and confluent 
-
-
Ulceration 
- 
Superficial ulceration  
< 2 cm size; local 
wound care; medical 
intervention indicated 
Ulceration > 2 cm size; 
operative debridement, 
primary closure or other 
invasive intervention 
indicated (ex. Hyperbaric 
oxygen)
Life-threatening 
consequences; major 
invasive intervention (ex. 
Complete resection, tissue 
reconstruction, flap, 
grafting)
Death 
Fibrosis 
Increased density, 
“spongy” feel 
Increased density with 
firmness or tethering 
Increased density with 
fixation of tissue; operative 
intervention indicated; 
interfering with ADL 
Life-threatening; disability; 
loss of limb; interfering 
with vital organ function 
Death 
Soft Tissue Necrosis 
- 
Local wound care; 
medical intervention 
indicated 
Operative debridement or 
other invasive intervention 
indicated (ex. Hyperbaric 
oxygen) 
Life-threatening 
consequences; major 
invasive intervention 
indicated (ex. Tissue 
reconstruction, flap, or 
grafting)
Death 
 
NEUROLOGY 
 
 
 
 
 
 
Neuropathy:  Motor 
Asymptomatic, 
weakness on 
exam/testing only 
Symptomatic 
weakness interfering 
with function, but not 
interfering with ADL
Weakness interfering with 
ADL; bracing or assistance 
to walk (e.g. cane or 
walker) indicated
Life-threatening; disabling 
(e.g. paralysis) 
Death 
Neuropathy:  Sensory 
Asymptomatic, lost 
deep tendon reflexes 
or paresthesia 
(including tingling), 
not interfering with 
function 
Symptomatic 
alteration or 
paresthesia (including 
tingling), interfering 
with function, not 
interfering with ADL 
Sensory alteration or 
paresthesia interfering with 
ADL 
Disabling 
Death 

 
Amendment 1: February 26, 2009 
23
 
ENDOCRINE 
 
 
 
 
 
 
Thyroid function, low 
(hypothyroidism) 
Asymptomatic, 
intervention not 
indicated 
Symptomatic, not 
interfering with ADL; 
thyroid replacement 
indicated
Symptoms interfering with 
ADL; hospitalization 
indicated 
Life-threatening myxedema 
coma 
Death 
 
PULMONARY/UPPER 
RESPIRATORY 
 
 
 
 
 
 
Edema, larynx 
Asymptomatic 
edema by exam only 
Symptomatic edema, 
no respiratory distress 
Stridor; respiratory distress; 
interfering with ADL 
Life-threatening airway 
compromise; tracheotomy, 
intubation, or laryngectomy 
indicated 
Death 
Voice changes/ 
Dysarthria (e.g. hoarseness, loss 
or alteration in voice, 
laryngitis) 
Mild or intermittent 
hoarseness or voice 
change, but fully 
understandable 
Moderate or persistent 
voice changes, may 
require occasional 
repetition but 
understandable on 
telephone 
Severe voice changes, 
including predominantly 
whispered speech; may 
require frequent repetition 
or face-to-face contact for 
understandability; requires 
voice aid (e.g. 
electrolarynx) for < 50% 
communication
Disabling; non-
understandable voice or 
aphonic; requires voice aid 
(e.g. electrolarynx) for > 
50%  communication or 
requires > 50% written 
communication 
Death 
Pneumonitis/ 
Pulmonary infiltrates 
Asymptomatic, 
radiographic 
findings only
Symptomatic, not 
interfering with ADL 
Symptomatic, interfering 
with ADL; O2 indicated 
Life-threatening; 
ventilatory support 
indicated 
Death 
Pulmonary fibrosis 
Minimal 
radiographic 
findings (or patchy 
or bibasilar changes) 
with estimated 
radiographic 
proportion of total 
lung volume that is 
fibrotic of < 25%
Patchy or bi-basilar 
changes with 
estimated 
radiographic 
proportion of total 
lung volume that is 
fibrotic of 25 - <50% 
Dense or widespread 
infiltrates/consolidation 
with estimated radiographic 
proportion of total lung 
volume that is fibrotic of  
50% - <75% 
Estimated radiographic 
proportion of total lung 
volume that is fibrotic of > 
75% 
Death 
 
GI TRACT 
 
 
 
 
 
 
Nausea 
Loss of appetite 
without alteration in 
eating habits 
Oral intake decreased 
without significant 
weight loss, 
dehydration, or 
malnutrition; IV 
fluids indicated < 24 
hr
Inadequate oral caloric or 
fluid intake; IV fluids, tube 
feedings, or TPN indicated 
> 24 hr 
Life-threatening 
consequences 
Death 
Vomiting 
1 episode in 24 hr 
2-5 episodes in 24 hr; 
IV fluids indicated < 
24 hr
> 6 episodes in 24 hr; IV 
fluids or TPN indicated > 
24 hr
Life-threatening 
consequences 
Death 
Diarrhea 
Increase of < 4 stools 
per day over 
baseline; mild 
increase in ostomy 
output compared to 
baseline 
Increase of 4-6 stools 
per day over baseline; 
IV fluids indicated < 
24 hrs; moderate 
increase in ostomy 
output compared to 
baseline; not 
interfering with ADL
Increase of > 7 stools per 
day over baseline; IV fluids 
indicated > 24 hrs; 
hospitalization; severe 
increase in ostomy output 
compared to baseline; 
interfering with ADL 
Life-threatening 
consequences (e.g., 
hemodynamic collapse) 
Death 
Enteritis 
Asymptomatic, 
pathologic or 
radiographic 
findings only
Abdominal pain; 
mucous or blood in 
stool 
Abdominal pain, fever, 
change in bowel habits with 
ileus; peritoneal signs 
Life-threatening 
consequences (ex. 
Perforation, bleeding, 
ischemia, necrosis)
Death 
Esophagitis 
Asymptomatic, 
pathologic, 
radiographic or 
endoscopic findings 
only 
Symptomatic; altered 
eating/swallowing 
(e.g. altered dietary 
habits, oral 
supplements); IV 
fluids indicated  
< 24 hrs 
Symptomatic and severely 
altered eating/swallowing 
(e.g. inadequate oral caloric 
or fluid intake); IV fluids, 
tube feedings, or TPN 
indicated > 24 hrs 
Life-threatening 
consequences 
Death 

 
Amendment 1: February 26, 2009 
24
Ulceration 
Asymptomatic, 
radiographic or 
endoscopic findings 
only 
Symptomatic; altered 
GI function (altered 
dietary habits, oral 
supplements); IV 
fluids indicated < 24 
hr
Symptomatic and severely 
altered GI function 
(inadequate oral caloric or 
fluid intake); IV fluids, tube 
feedings, or TPN indicated 
> 24 hr
Life-threatening 
consequences 
Death 
Bleeding 
Mild, intervention 
(other than iron 
supplements) not 
indicated 
Symptomatic and 
medical intervention 
or minor cauterization 
indicated 
Transfusion, interventional 
radiology, endoscopic, or 
operative intervention 
indicated
Life-threatening 
consequences; major urgent 
intervention indicated 
Death 
Perforation 
Asymptomatic 
radiographic 
findings only 
Medical intervention 
indicated; IV fluids 
indicated < 24 hr 
IV fluids, tube feedings, or 
TPN indicated > 24 hr; 
operative intervention 
indicated
Life-threatening 
consequences 
Death 
Stricture 
Asymptomatic 
radiographic 
findings only 
Symptomatic; altered 
GI function (altered 
dietary habits, 
vomiting, bleeding, 
diarrhea); IV fluids 
indicated < 24 hr 
Symptomatic and severely 
altered GI function (altered 
dietary habits, diarrhea, or 
GI fluid loss); IV fluids, 
tube feedings, or TPN 
indicated > 24 hr; operative 
intervention indicated 
Life-threatening 
consequences; operative 
intervention requiring 
complete organ resection 
Death 
Fistula 
Asymptomatic; 
radiographic 
findings only 
Symptomatic; altered 
GI function (ex. 
Altered dietary habits, 
diarrhea, or GI fluid 
loss); IV fluids 
indicated < 24 hr
Symptomatic and severely 
altered GI function (ex. 
Altered dietary habits, 
diarrhea, or GI fluid loss); 
IV fluids, tube feedings, or 
TPN indicated > 24 hr 
Life-threatening 
consequences 
Death 
 
MUSCULOSKELETAL 
 
 
 
 
 
 
Fracture 
Asymptomatic, 
radiographic 
findings only  
Symptomatic but non-
displaced; 
immobilization 
indicated
Symptomatic and 
displaced; operative 
intervention indicated 
Disabling 
Death 
 
HEPATOBILIARY 
 
 
 
 
 
 
 
Liver Dysfunction 
 
 
- 
 
Jaundice 
 
Asterixis 
 
Encephalopathy or come 
 
Death 
 
RENAL 
 
 
 
 
 
 
Renal failure 
- 
- 
Chronic dialysis not 
indicated
Chronic dialysis or renal 
transplant indicated
Death 
 
METABOLIC 
 
 
 
 
 
 
Albumin 
3-4 g/dL 
2-2.99 g/dL
< 2 g/dL
Death
Alkaline phosphatase 
> nl – 2.5 x nl
> 2.5 – 5 x nl
> 5 – 20 x nl
> 20 x nl
-
ALT 
> nl – 2.5 x nl
> 2.5 – 5 x nl
> 5 – 20 x nl
> 20 x nl
-
AST 
> nl – 2.5 x nl
> 2.5 – 5 x nl
> 5 – 20 x nl
> 20 x nl
-
Bilirubin 
> nl – 1.5 x nl
> 1.5 – 3 x nl
> 3 – 10 x nl
> 10 x nl
-
Creatinine 
> nl – 1.5 x nl
> 1.5 – 3 x nl
> 3 – 6 x nl
> 6 x nl
Death
 
SECONDARY 
MALIGNANCY 
 
- 
- 
Non-life-threatening basal 
or squamous cell carcinoma 
of the skin 
Solid tumor, leukemia, or 
lymphoma 
Death 
 

 
Amendment 1: February 26, 2009 
25
12.4 
Appendix IV  
 
ASIA Impairment Scale 
 
 
A          Complete        
No motor or sensory function is preserved in the sacral segments S4-S5 
 
B          Incomplete 
Sensory but not motor function is preserved below the neurological level and  
 
includes the sacral segments S4-S5 
 
C          Incomplete 
Motor function is preserved below the neurological level, and more than half  
 
of key muscles below the neurological level have a muscle grade of less  
 
than 3 
 
D          Incomplete 
Motor function is preserved below the neurological level, and at least half of  
 
key muscles below the neurological level have a muscle grade of 3 or more 
 
E          Normal 
Motor and sensory function are normal 
 
 
 
 
Muscle Grading 
 
 
0          Total paralysis 
 
1          Palpable or visible contraction 
 
2          Active movement, full range of motion, gravity eliminated 
 
3          Active movement, full range of motion, against gravity 
 
4          Active movement, full range of motion, against gravity and provides some resistance 
 
5          Active movement, full range of motion, against gravity and provides normal resistance 
 
5*        Muscle able to exert, in examiner’s judgement, sufficient resistance to be considered normal if  
            identifiable inhibiting factors were not present 
 
NT      Not testable.  Patient unable to reliably exert effort or muscle unavailable for testing due to factors  
            such as immobilization, pain on effort or contracture 
 
 

 
Amendment 1: February 26, 2009 
26
12.5 
Appendix V  
 
10-point Visual Analog Pain Scale 

 
Amendment 1: February 26, 2009 
27
12.6 
Appendix VI 
 
DEMOGRAPHIC FORM – Page 1 of 1 
 
 
1.  Name ____________________(last)   ____________________(first)    
 
2.  Date of Birth  ____/____/__________ 
 
3. RT Number ____________________ 
 
4.  Race: 
 Asian 
 Caucasian 
 Black 
 Other, specify _______________________ 
 
 
5.  Zubrod PS:  
 0 
 1 
 2 
 
6. Radiation oncologist:  __________________________________ 
 
7. Medical oncologist:  ___________________________________ 
 
8.  Surgeon:  ___________________________________________ 
 
9. Tumor category:  
 Metastases, specify location (cervical, thoracic, lumbosacral) ________________  
 
 
 
Primary Site: 
 Prostate cancer 
 
 
 
 Breast cancer 
 
 
 
 Lung cancer 
 
 
 
 Colorectal cancer 
 
 
 
 Renal cancer 
 
 
 
 Melanoma 
 
 
 
 Other, specify ____________________ 
 
 
 Primary spine tumor, specify histology ____________ 
 
10. Maximum tumor diameter:  _______ cm 
 
 
11.  Location of extraspinal disease:  
 No gross extraspinal disease 
                                                            
 Stable extraspinal diasease 
                                                            
 Progressive extraspinal diasease 
 
12.  Baseline Labs (if clinically indicated): 
                                  Total bilirubin __________  
ALT __________ 
 
AST __________ 
                                  Alkaline phosphatase __________ 
PT __________ 
 
PTT __________ 
                                  Creatinine __________ 
                                  WBC __________ 
 
Hb __________ 
 
Platelets __________ 
 
13.  Baseline neurologic function using the ASIA Impairment Score:  _______ 
 
14.  Baseline assessment of pain using a 10-point visual analog scale:  _______ 
 
15.  Amount and type of narcotic analgesic usage:  ___________________________________________________ 
 
16.  Prior in-field spine radiation:  
 No 
 Yes, explain ___________________________________________ 
 
17.  Pre-SBRT chemotherapy: 
 No 
 
 
 Yes, regimen & last cycle date _______________________________________ 
 
 
Person completing form :  Signature _________________________     Print Name __________________________ 

 
Amendment 1: February 26, 2009 
28
 
12.7 
Appendix VII 
 
TREATMENT FORM – Page 1 of 1 
 
 
1.  Name ____________________(last)   ____________________(first)    
 
2. RT Number ____________________ 
 
3.  Tumor Details:   
 
 
 Metastases, specify location (cervical, thoracic, lumbosacral) ________________  
 
 
 
Primary Site: 
 Prostate cancer 
 
 
 
 Breast cancer 
 
 
 
 Lung cancer 
 
 
 
 Colorectal cancer 
 
 
 
 Renal cancer 
 
 
 
 Melanoma 
 
 
 
 Other, specify ____________________ 
 
 
             Number of Vertebral Levels Involved:  
 One 
 
 
 
 
 
          
 Two 
 
 
 Primary spine tumor, specify histology ____________ 
 
Maximum Diameter  
(cm) 
GTV Volume 
(cc) 
PTV Margin 
(mm) 
AP      R-L      C-C
PTV Volume  
(cc) 
 
 
 
 
 
 
 
5. Treatment Portal Design: 
 
 
 Static gantry angle (coplanar), specify number of fields __________ 
 
 
 Static gantry angle (non-coplanar), specify number of fields __________ 
 
 
 Dynamic arc (coplanar), specify number of arcs __________ 
 
 
 Dynamic arc (non-coplanar), specify number of arcs __________ 
 
6. Dose-Fractionation Scheme:  
Total Dose  
(Gy) 
Dose per 
Fraction (Gy) 
# of 
Fractions 
Prescription 
IDL (%) 
Dmax 
(Gy) 
BED/=10 
(Gy) 
BED/=3 
(Gy) 
C.I. 
 
 
 
 
 
 
 
 
 
 
7.  Dose to Normal Tissues: 
 
   Spinal Cord:  maximum dose __________ in _________ fractions 
 
   
 
 __________ cc to > 8 Gy in 1 fraction 
 
 
 
 __________ cc to > 10 Gy in 1 fraction 
 
 
 
 __________ cc to > 12 Gy in 1 fraction  
  
  
   Cauda Equina:  maximum dose __________ in _________ fractions 
 
 
   Liver:  __________ cc of normal liver volume received < BED 2Gy (/=3) of 40 Gy 
 
 
  __________ % of normal liver volume received < BED 2Gy (/=3) of 40 Gy 
 
 
 
 
    (9.5 Gy in 1 fraction; 15 Gy in 3 fractions; 18 Gy in 5 fractions) 
 

 
Amendment 1: February 26, 2009 
29
 
   Kidneys:  mean right kidney dose of __________ 
 
 
       mean left kidney dose of __________ 
 
 
       V10 right kidney __________ 
 
 
 
V10 left kidney __________ 
 
 
   Lung, Right:  mean dose __________ 
 
 
 
      V5 __________ 
 
 
 
      V10 __________ 
 
 
 
      V20 __________ 
 
 
   Lung, Left:    mean dose __________ 
 
 
 
      V5 __________ 
 
 
 
      V10 __________ 
 
 
 
      V20 __________ 
 
Normal Tissue 
Dmax (Gy) 
Esophagus 
 
Stomach 
Bowel 
Larynx 
Skin 
 
7. Premedication: 
 
 
 None 
 
 
 Anti-nausea, specify drug __________, dose _____ mg,  
 
 
 Decadron, specify dose _____ mg  
 
 
 Analgesics, specify drug __________, dose _____ mg 
 
 
Person completing form :  Signature _________________________     Print Name __________________________ 
 
 
 

 
Amendment 1: February 26, 2009 
30
 
12.8 
Appendix VIII 
 
FOLLOW-UP VISIT FORM – Page 1 of 2 
 
1.  Name ____________________(last)   ____________________(first)    
 
2. RT Number ____________________ 
 
3. Date of Visit:  ____/____/__________ 
 
4.  Blood work:  
Lab 
Date: 
Date:
Date: 
Total Bilirubin 
 
 
Alkaline Phosphatase 
 
 
ALT 
AST 
 
 
PT 
PTT 
 
 
Creatinine 
 
 
WBC 
 
 
Hb 
 
 
Platelets 
 
 
 
 
4. Radiation Therapy related adverse events 
Adverse Event 
CTC V3.0 Grade
Timing 
Treatment 
Comments
ACUTE 
                
 Fatigue  
 Nausea 
 Vomiting  
 Loss of appetite 
 Weight loss 
 Enteritis  
 Diarrhea 
 Alopecia 
 Radiation dermatitis 
 
 Esophagitis 
 
 Hoarseness 
 
 Pneumonitis 
 
 Musculoskeletal Pain 
 
 Neuropathy, Motor 
 
 Neuropathy, Sensory 
 
 
 
LATE 
 
 GI Bleeding 
 
 GI Ulceration 
 
 GI Perforation 
 
 GI Stricture 
 
 Fistula 
 
 Liver Dysfunction 
 
 Kidney Dysfunction 
 
 Hoarseness 
 
 Pulmonary Fibrosis 
 
 Neuropathy, Motor 
 
 Neuropathy, Sensory 
 
 Thyroid Dysfunction 
 

 
Amendment 1: February 26, 2009 
31
 Vertebral Fracture 
 
 Telangiectasia 
 
 Skin Ulceration 
 
 Skin/SubQ Tissue Fibrosis 
 
 Soft Tissue Necrosis 
 
 Radiation-induced Malignancy
 
 
5. Serious adverse event?  
 No   
 Yes, submit report to HIC 
 
6. Has systemic therapy been given?  
 No   
 Yes 
 
If yes, list therapy 
 
Agent(s) 
Start Date 
Stop Date 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
__________________________ 
____/____/__________ 
____/____/__________ 
 
7.  Neurologic function assessment using the ASIA Impairment Score:  _______ 
 
8.  Pain assessment using a 10-point visual analog scale:  _______ 
 
9.  Amount and type of narcotic analgesic usage:  ___________________________________________________ 
 
10. MRI scan of the involved spine since last follow-up visit?  
 No   
 Yes, date ____ / ____ / __________ 
 
Tumor Response: 
 Complete response 
 
 
 Partial response 
 
 
 Stable disease 
 
 
 Progressive disease 
 
11. PET/CT scan since last follow-up visit?  
 No   
 Yes, date ____ / ____ / __________ 
 
Tumor Response: 
 Complete response 
 
 
 Partial response 
 
 
 Stable disease 
 
 
 Progressive disease 
 
12. Disease Status  
 
 No evidence of tumor 
Date of Diagnosis 
 
 Local recurrence within the treatment volume 
____/____/_________ 
 
 Distant recurrence, specify site _______________________ 
____/____/_________ 
 
12. Additional treatment for recurrent disease  
 
Surgery 
 Yes  
 No   
Date of surgery ____/____/_________ 
 
Chemotherapy, agents ___________________ 
 Yes  
 No   
Start date ____/____/_________ 
 
Other, specify _________________________ 
 Yes  
 No   
Start date ____/____/_________ 
  
13. Death?   
  No   
 Yes, date ____/____/__________  Cause? ____________________________ 
 
 
Person completing form :  Signature _________________________     Print Name __________________________