Phase 2 Study of Vertebral Augmentation and Radiotherapy in Painful or at Risk of Collapse Spinal Metastatic Cancer/Multiple Myeloma
Phase: NA
Conditions: Metastatic Cancers, Multiple Myeloma, Vertebral Fracture
Sponsor: University of Arizona

1 
Version Date: 10-29-2015 
University of Arizona 
Medical University of South Carolina 
 
 
Protocol  
Phase 2 Study of Vertebral Augmentation and Radiotherapy in Painful or at Risk of Collapse Spinal 
Metastatic Cancer/Multiple Myeloma 
 
Principal Investigator 
Krisha Howell, MD 
Department of Radiation Oncology 
University of Arizona 
Phone: (520) 694-8961 
Email: KrishaHowell@email.arizona.edu 
 
 
Neurosurgery Co-Investigators 
Ali Baaj, MD 
PO Box 245070 
1501 N. Campbell Ave. 
Tucson, AZ 85724 
Phone: (520) 626-2164 
Email: abaaj@surgery.arizona.edu 
 
Radiation Oncology Co-Investigators 
Baldassarre Stea, MD, PhD 
1501 North Campbell Ave 
Tucson, AZ 85724 
Phone: (520) 694-7236 
Email: bstea@email.arizona.edu 
 
David T. Marshall, MS, MD 
Department of Radiation Oncology 
Medical University of South Carolina 
169 Ashley Avenue 
Charleston, SC 29425 
Phone: (843) 792-3271 
Email: marshadt@musc.edu 
 
Statistician Co-Investigator 
Elizabeth Garrett-Mayer, PhD 
Medical University of South Carolina 
86 Jonathon Lucas St, Room HO118G 
Charleston, SC 29425 
Phone: 843-792-7764 
Email: garrettm@musc.edu 
 
 
Protocol Approved:  8-20-2013 
Revised 9-9-2013 
Revised 3-6-2014 
Revised 3-19-2014 
Revised 7-16-2014 
Revised 3-11-2015 
 

2 
Version Date: 10-29-2015 
 
Table of Contents 
Schema 
Eligibility Checklist 
 
1.0 
Introduction  
 
1.1  
Bone Metastasis and Radiotherapy 
 
1.2 
Vertebral Augmentation 
 
1.3 
Improvement in Quality of Life Measurement Tools 
 
 
1.4 
Potential Benefits of the Proposed Research to the Subjects and Others 
 
1.5 
Importance of the Knowledge to be Gained 
2.0    
Objectives 
 
2.1 
Primary Objectives 
 
2.2 
Secondary Objectives 
 
3.0 
Patient Selection 
 
3.1 
Conditions for Patient Eligibility 
3.2 
Conditions for Patient Ineligibility 
 
4.0 
Patient Consenting/Screening and Eligibility  
 
4.1 
Patient Consenting and Registration Process 
 
4.2 
Screening within 8 Weeks 
 
4.3 
Screening within 4 Weeks 
 
4.4 
Screening within 2 Weeks 
5.0 
Pretreatment Evaluations/Management 
 
5.1 
Initial Assessment of Activity, Pain, and Quality of Life  
6.0 
Vertebral Augmentation 
 
6.1 
Treatment  
7.0 
Radiation Therapy 
 
7.1 
Treatment 
8.0 
Measurement of Response/Patient Follow-Up 
 
8.1 
1 Week Follow-Up Assessment 
8.2 
1 Month Follow-Up Assessment 
 
8.3 
3 Month Follow-Up Assessment 
9.0 
Quality Assurance 
10.0 
Protocol Data and Safety Monitoring Plan (Medium Risk) 
 
10.1 
Data and Safety Monitoring Plan 
 
10.2 
Adverse Events 
 
10.3 
Severe Adverse Events 
 
 
10.4 
Plan for Assuring Data Accuracy and Protocol Compliance 
11.0  
Other Therapy  
 
11.1  
Permitted Supportive Therapy 
12.0 
Tissue/Specimen Submission 
13.0 
Patient Assessments 
 
13.1 
Pain Assessment Tools 
13.2 
Assessment of Patient Activities 
 
13.3 
Assessment of Quality of Life 
 
13.4 
Assessment of Fracture Rate 
 
13.5 
Criteria for Removal from Protocol Treatment 
14.0 
Data Collection 
 
14.1 
In-House Data Collection and Analysis  
15.0 
Statistical Considerations 
 
15.1 
Study Endpoints 
 
 
15.2 
Analytic Plan 
15.3 
Sample Size 
 
References 
 
 
 
 

3 
Version Date: 10-29-2015 
Appendices 
 
Appendix I 
- Worst Pain Assessment on the Brief Pain Inventory Scale 
 
Appendix II 
- Roland-Morris Disability Questionnaire 
 
Appendix III 
- EORTC QLQ-C30 (version 3) 
 
 
Appendix IV  
- Pain Measures Index and Narcotic Score  
Appendix V 
- Baseline Data Collection Form 
 
Appendix VI 
- Follow-up Report 
 
Appendix VII 
- Karnofsky Performance Status 
 
Appendix VIII 
- Record of Current Pain Medications 
 
Appendix IX 
- Study Parameter Table 
 
 
 
 
 

4 
Version Date: 10-29-2015 
 
Phase 2 Study of Vertebral Augmentation and Radiotherapy in Painful or at Risk of Collapse Spinal Metastatic 
Cancer/Multiple Myeloma  
SCHEMA 
 
 
 
 
Patient Population: (See Section 3.1 for Eligibility) 
Adults with a suspicion of metastatic cancer to the vertebrae or multiple myeloma with a focus in a vertebral body(ies).  The lesion must be identifiable with 
radiologic evidence and the diagnosis of metastatic disease fulfilled. 
 
Required Sample Size: 20 patients (with a Pain Scale Score of equal to or greater than 5) 

5 
Version Date: 10-29-2015 
ELIGIBILITY CHECKLIST 
 
Inclusion Criteria 
_____ (Y)           1.  Does the participant have a suspicion of metastatic cancer to the vertebrae or multiple myeloma with a focus in a vertebral body(ies) per 
section 3.1?  Type of cancer:  __________ 
 
_____ (Y)           2. Has a history and physical exam been done within 8 weeks prior to registration?  Date:  ___/___/_____ 
 
_____ (Y)           3. Has a lesion(s) been identified on X-ray, bone scan, CT scan or MRI?  Type of Scan:  _______  Date:  ___./___/_____ 
 
_____ (Y)           4. Is the participant 18 or older?  Age:  ____ Date of Birth:  ___/___/_____ 
 
_____ (Y/NA)     5. Is the participant female and of childbearing potential? 
 
If yes, has a pregnancy test (urine dipstick or serum) been negative within 2 weeks prior to registration? 
 
_____ (Y)           6. Is the participant’s Karnofsky performance status > 40?  Score:  ____ 
 
_____ (Y/NA)     7. If the participant has childbearing potential, has she/he agreed to practice an adequate mean of birth control throughout treatment in this 
study and for 6 months after his/her last treatment? 
 
 
_____ (Y)           8. Are there indications for intervention per section 3.1? 
 
Either pain with a focus at the involved vertebral body that is not adequately controlled by medical management or 
Osteolysis of a vertebral body(ies), with pain, with or without fracture at a site of metastatic infiltration/multiple myeloma that 
poses a risk of impending vertebral collapse? 
Pain Level:______   (Must be 5 or greater) 
 
_____ (Y)         9. Written informed consent completed.  Date:  ___/___/_____ 
 
_____ (Y)         10. The participant is fully able to understand the English language so as to read and answer the study questionnaires. 
 
_____ (Y)         11. The participant has the absence of any serious cognitive or psychiatric problems that could potentially hamper compliance with the study 
and follow-up schedule. 
 
_____ (Y)         12.Is the participant’s pain scale score ≥ 5?  
 
_____ (Y)          13. Diagnostic imaging to be obtained at time of kyphoplasty if not previously done. 
 
 
 
 
Exclusion Criteria 
_____ (N)         14.  Does the participant have spinal cord compression? 
 
_____ (N)         15.Is the participant currently using Plavix or has a history of taking Plavix less than 7 days prior to enrollment? 
 
_____ (N)         16.Is there evidence of a local infection at the puncture site or evidence of a systemic infection? 
 
_____ (N)         17.Does the participant have a known allergy to any of the components used during vertebral augmentation? 
 
_____ (N)         18.Does the participant have a co-morbidity that would cause cardiorespiratory compromise during conscious sedation or in the  
 
 
prone decubitus position? 
 
______ (N)       19.Does the participant have a life expectancy of less than 3 months? Documentation based on?    Low Clinical morbidity?   YES   NO   
Other_____ 
 
 
 
______ (N)       20. Previous radiotherapy to the current vertebral body(ies) with metastatic disease currently under consideration for treatment. 

6 
Version Date: 10-29-2015 
 
______ (N)        21.  Patient has participated in this study before.  
 
______ (N)        22. Patient was treated Samarium therapy or SM153, or lexidronam, or other hormone. 
 
______ (N)       23 . Patient has asymptomatic vertebral fracture and is at low risk for biomechanical instability and collapse.  
 
______ (N)        24. Patient has a known allergy to any of the components used during vertebroplasty (PMMA bone cement) 
 
______ (N)        25. Patient’s pain is not localized to the region of metastatic disease.  This may include diffuse non-focal back pain and/or  
 
 
 
Radiculopathy. 
 
 
 

7 
Version Date: 10-29-2015 
1.0 
INTRODUCTION 
 
The following study aims to gain a rapid improvement in the patient’s functional status and quality of life in patients with vertebral body metastases 
by decreasing the associated pain, and preventing further vertebral fracture, loss of height, and instability. Furthermore, this study aims to prevent 
further cancerous disease progression, reduce pain and bony destruction to the affected vertebral bodies. This will be accomplished by combining 
vertebral augmentation (VA) and radiotherapy. 
 
The proposed study seeks to evaluate and quantify the reduction of pain and changes in quality of life in relevance to vertebral augmentation in 
addition to radiation therapy.  This study will be conducted in those patients with metastatic cancer or multiple myeloma involving the vertebral 
body(ies).  Although there are extensive studies on vertebral augmentation in the setting of osteoporotic spinal fractures, there are few in the 
setting of metastatic disease.  Those studies that do exist either do not account for possible radiation or were not performed in a prospective 
manner with adequate follow-up.  This study aims to address the value of vertebral augmentation in combination with radiotherapy in the setting of 
cancer to the spine.  The proposed study will be the first that we are aware of with the capability to assess patient response to vertebroplasty and 
radiotherapy with a scale and time interval comparable to the historical controls treated with other approaches.  Thus, the patient’s pain, overall 
quality of life, and fracture development/avoidance will be assessed at set time intervals to determine the change from historical controls treating 
patients with radiotherapy only.   
 
 
1.1  
Bone Metastasis and Radiotherapy 
In the setting of metastatic lesions to the spine, laminectomy and surgical stabilization are common techniques for areas of symptomatic 
disease threatening instability.  Radiotherapy treats the underlying cancer, attempting local control of the disease but, during the 
immediate time period following radiation, may leave the bone in a weakened state.  In such a state there can be a risk of fracture until 
the bone can be remodeled as it heals.  As exemplified by the Radiation Therapy Oncology Group (RTOG) 7402 trial of external beam 
radiation for bone metastases, maximal pain relief develops over the course of weeks from the time of completion of radiation.  It may 
take up to 20 weeks to express the full effects of pain control.1 RTOG 7402 was a randomized control trial of patients with solitary or 
multiple metastases in the femur, humerus, pelvis, or spine.  The patients exhibited a pain or narcotic score of at least 4 and an expected 
survival of at least 3 months.  Patients were stratified based on their number of bone metastases into one of 2 or one of 4 different dose 
fractionation schedules.  Between the fractionation schedules, there was no difference in pain relief or relapse from pain relief.  Close to 
50% of patients who had complete relief, first reported it more than 4-weeks after completing treatment.  Unfortunately, relapse of the 
pain occurred in 29% of patients having experienced minimal pain relief, 41% of patients having had partial pain relief, and 54% in 
patients having had complete pain relief. 
 
Following RTOG 7402, RTOG 9714 was conducted to assess varying the fraction regimen for metastatic disease.  In this trial, 949 
patients with prostate or breast cancer and painful bone metastases were treated with 8 Gy in a single fraction or 30 Gy in 10 fractions.  
There were no significant differences in the rates for complete and partial pain relief, the use of narcotics, and/or the incidence of 
subsequent pathologic fractures. Patients treated with a single fraction were twice as likely to be retreated (18% vs 9%), which may be 
related to the convenience of a one time treatment and the comfort level of radiation oncologists with retreating after 8 Gy versus 30 Gy.2 
Radiation fractionation schedules currently in use at our institution closely parallel those assessed in both RTOG 7402 and RTOG 9714: 
30Gy in 10 fractions, 20Gy in 5 fractions, or 8Gy in 1 fraction. 
 
 
1.2 
Vertebral Augmentation 
 
Vertebroplasty was developed in 1987 in France for percutaneous treatment of a fractured vertebral body.  In this procedure the clinician 
uses a large-bore needle to access a fractured vertebral body percutaneously, under imaging guidance (fluoroscopy and/or computer 
assisted tomography (CT)), and inject bone cement, generally using conscious sedation.  Thereby, the vertebral body is stabilized and 
the bony structure reinforced.3 Kyphoplasty is the same procedure as vertebroplasty, but before injecting the cement in the vertebral 
body, a balloon is inflated in the vertebral body in order to create a chamber that should allow one to inject the cement at lower injection 
pressures.  For the vertebroplasty procedure, if cortical bone disruption is present, and the risk of cement leakage outside of the 
vertebral body, in the epidural space, or in the venous system, is increased, then coblation may be utilized.  Coblation creates a cavity in 
the vertebral body with an FDA-approved low temperature radiofrequency device that ablates tumoral tissue through plasma ionization. 
Masala and colleagues treated patients with vertebral involvement by multiple myeloma with vertebroplasty alone.  In this study of 64 
patients with refractory pain to medical management, the average pre-procedure pain level on an analogue scale was 8.04 +/-1.4.  At 1 
and 6 months post-procedure the pain was reduced to 1.82 +/-1.84 and 1.92 +/-1.68.6   
 
 
Therefore, in the setting of metastatic disease to the vertebrae, vertebroplasty can offer a means to provide earlier pain relief and 
structural stability compared to radiotherapy.  Radiation adjuvantly may enhance pain control and eradicate cancer in the localized 
region.  In a study of 57 patients with 78 sites of treated metastatic disease, the mean visual analogue scale (VAS) that measured pain 
was significantly decreased (p<0.015) one day after vertebroplasty and remained significant for 6 months following (p<0.001).4  
Assessment of vertebroplasty combined with radiotherapy in the setting of malignant tumor or hemangioma was performed in a study 
from South Korea.5  Twenty-eight patients underwent percutaneous injection of polymethylmethacrylate into the collapsed vertebral 
bodies, with either a local anesthetic or general anesthesia for pain relief and spinal stabilization.  Pain levels were assessed by using a 
VAS.  The indications for vertebroplasty were an unstable or painful osteolytic metastatic tumor without associated neurological deficits.  
Inclusion criteria were vertebral collapse with or without pain or painful vertebra in the absence of collapse.  If a radiculopathy was 

8 
Version Date: 10-29-2015 
present and not caused by encroachment of the tumor but by vertebral instability, then patients were still treated with vertebroplasty.  
Radiation therapy commenced immediately after the completion of the vertebroplasty procedure with the most common dosing schedule 
of 30Gy in fraction sizes of 3Gy.  On day #3, VAS assessments showed that complete pain relief was achieved in 48% of patients and 
moderate relief in 41%.  No major complications occurred in this study.* 
 
 
 In the setting of kyphoplasty at a median of 12 days previously, spinal radiosurgery was undertaken at the University of Pittsburgh.  In 
this study, 26 patients, with metastatic vertebral fractures, having a total of 7 lesions previously undergone external-beam radiation 
therapy with spinal cord tolerance doses, were treated.  Kyphoplasty was performed in all cases, at which time, gold fiducials were 
placed for future image guidance at the time of spinal radiosurgery.  Sixteen Gy to 20Gy was delivered to the tumor with an improvement 
in back pain of 92% and no detectable neurological signs attributable to treatment during a follow-up period of 7-20months.3 
 
 
A 2008 review article from Johns Hopkins confirmed that the VAS pain scores, narcotic usage and quality of life scales have all been 
shown to improve for over one year with vertebroplasty or kyphoplasty.  Also, the procedures of vertebroplasty and kyphoplasty may be 
performed before, after or concurrently with most radiation protocols.7 
 
* Pulmonary embolisms related to vertebroplasty-kyphoplasty usually refer to bone cement (PMMA) embolisms. 
Pulmonary PMMA embolism is detected in 5-10% of patients after vertebroplasty when a post-procedure chest plain 
film is obtained, and as high as in 25% of patients when a chest CT is obtained. In nearly all cases (in most large 
series those are ALL asymptomatic) these embolisms are asymptomatic, and have no clinical consequences at 
radiological and clinical follow-up, up to 24 months. Therapy is not warranted in patients with asymptomatic PMMA 
pulmonary embolism, so that several recent articles state no need for screening imaging studies after the procedure 
in asymptomatic patients 
 
1.3 
Improvement in Quality of Life Measurement Tools 
 
In assessing pain, quality of life, and overall response to treatment, various measurement tools have been employed by the previously 
quoted studies.  The European Organisation of Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire assesses the pain 
level of the patient and the impact the pain has on daily life.   
 
 
1.4 
Potential Benefits of the Proposed Research to the Subjects and Others 
 
The benefits being assessed are the possibilities of increased and earlier pain control, decreased fracture rate, and improved quality of 
life in comparison to historical measures.  The risks are reasonable in regards to accomplishing these means given that currently both 
radiotherapy and vertebroplasty are in wide use as standard treatment options for these patients.  
 
 
1.5 
Importance of the Knowledge to be Gained 
 
The knowledge gained from this study will help guide palliative therapy to optimize comfort and quality of life in the end-stages of life.   
 
2.0    
OBJECTIVES 
 
 
2.1 
Primary Objectives 
 
Compare pain control assessed over time in patients treated with vertebral augmentation and radiation against a historical control group 
of metastatic patients treated solely with radiotherapy for pain and tumor control.  Some of the subjects will undergo the vertebral 
augmentation first, others the Radiation first.  Historical control rates will be taken from RTOG 9714 for pain control.   
 
 
2.2 
Secondary Objectives 
 
2.2.1 
 Compare activity level prior to and following treatment.  Historical control rates will be used for comparison. 
 
2.2.2 
 Compare quality of life prior to and following treatment.  Historical control rates will be used for comparison. 
2.2.3 
 Fracture rates will also be compared against historical controls treated solely with radiotherapy.  Historical control rates will be taken 
from RTOG 7402 for rates of fracture.  
 
 
3.0 
PATIENT SELECTION 
To be eligible for the study, patients must fulfill all of the following criteria: 
 
3.1 
Conditions for Patient Eligibility 
3.1.1 
The diagnosis of metastatic disease will be fulfilled by one of two criteria: Previous pathological diagnosis of cancer with suspicion of 
metastatic disease on imaging, and clinical diagnosis of metastatic disease.  If there is not pathological diagnosis, a specimen will be 
sent to pathology at the time of the surgery to confirm malignancy.   
3.1.2        Appropriate diagnosis for protocol entry, based upon the following minimal diagnostic work-up: 
3.1.2.1 
History/physical examination within 8 weeks prior to registration and:. 
3.1.2.2 
Suspicion of metastatic cancer to the vertebrae or multiple myeloma with a focus in a vertebral body(ies) and;   
 
3.1.2.3     The lesion must be identifiable with radiologic evidence (X-ray, bone scan, CT scan, MRI).  
3.1.3 
Negative pregnancy test (urine dipstick or serum) for women of childbearing potential within 2 weeks prior to registration.  
3.1.4 
The patient must be an adult (18 years of age or older). 

9 
Version Date: 10-29-2015 
3.1.5 
Life expectancy >3months AND KPS score >40 (see Appendix VIII – Legend). 
3.1.6       Pain scale score ≥ 5  
3.1.7 
Indication for intervention: 
3.1.6.1 
Pain with a focus at the involved vertebral body that is not adequately controlled by medical management; 
3.1.6.2 
Osteolysis of a vertebral body(ies) with or without fracture at a site of metastatic infiltration/multiple myeloma, that poses risk of  
impending vertebral collapse.  This is detected by the following cross-sectional imaging (MRI or CT) conditions8: 
 
In the thoracic spine:  
o 
A > 50% involvement of the vertebral body with no destruction of other structures or; 
o 
A > 25% involvement of the vertebral body associated with costovertebral joint destruction or posterior 
elements involvement. 
 
In the lumbar spine:  
o 
A > 35% involvement of the vertebral body with no destruction of other structures or; 
o 
A > 20% involvement of the vertebral body associated with involvement of posterior elements. 
3.1.8 
Women of childbearing potential and male participants must agree to practice adequate means of birth control throughout their 
participation in the study and for 6 months after their last treatment. 
3.1.9 
The patient must sign specific informed consent prior to study entry.   
3.1.10 
The patient is fully able to understand the English language so as to read and answer the study questionnaires. 
3.1.11 
Absence of any serious cognitive or psychiatric problems potentially hampering compliance with the study and follow-up schedule. 
 
3.2 
Conditions for Patient Ineligibility 
3.2.1 
    Previous treatment defined as follows: 
 
Previous participation in this study. 
 
Previous radiotherapy to the site of vertebroplasty prior to study enrollment. 
 
Samarium therapy at any previous time. 
3.2.2 
    Uncorrected coagulopathy: 
 
Plavix usage at the time of vertebroplasty or history of taking Plavix less than 7 days prior to procedure (In selected 
cases, radiation treatment can be initiated, the antiplatelet agent stopped, and vertebroplasty performed after 7days.) 
3.2.3 
    Infection: 
 
Local infection at the puncture site 
 
Systemic infection, osteomyelitis, discitis 
3.2.4 
    Anatomical considerations: 
 
If the patient has > 4 sites. Only the 3 most painful sites of disease will be treated.  Or, in the absence of pain, the 3 
levels at greatest risk of impending collapse, based on extent of involvement, presence of posterior element 
involvement, or biomechanical risk based on location (mid-thoracic area, thoraco-lumbar junction, lumbosacral 
junction). 
 
Spinal cord compression with or without peridural spread 
 
Neurologic compromise due to spinal cord compression 
3.2.5 
    Asymptomatic vertebral fracture and low risk for biomechanical instability and collapse. 
3.2.6 
    Known allergy to any of the components used during vertebroplasty (PMMA bone cement) 
3.2.7 
    Pain not localized to the region of metastatic disease.  This may include: 
 
Diffuse non-focal back pain 
 
Radiculopathy 
3.2.8 
Inappropriate risk to the patient such as cardiorespiratory compromise such that safe conscious sedation or prone decubitus cannot 
be obtained. 
3.2.9 
    Unable to obtain diagnostic imaging.  
 
 
4.0 
PATIENT CONSENTING/ SCREENING/ELIGIBILITY/REGISTRATION 
4.1  
Patient Consenting and Registration Process 
Patients may be seen on an inpatient or outpatient basis.  Patients will be approached by their treating physician regarding the study.  If 
they are interested, someone from the Radiation Oncology Research Staff will go see the patient and give them a study specific consent 
form.  If the patient is able to take the form home and discuss and/or discuss it with family members, they will be encouraged to do so.  
All Patients will be consented prior to entering this study.  The consenting will be performed in a hospital room or clinic room with the 
door closed to maintain patient confidentiality.  A member of the research team will read and review the consent with the patient (and 
family if available) and will answer questions.  If needed, the treating physician will be brought in to answer any questions that the 
research staff member is unable to answer.  The consent form will be signed (and HIPAA form) and a copy will be given to the patient.  
The patient will be assigned a sequential screening number beginning with HO-V-0001.  This number will remain consistent with the 
subject even if the subject is determined ineligible, or does not receive study treatment or complete study follow-up.  ).  The patient’s 
chart will be reviewed and the following tests will be performed or reviewed to confirm eligibility.  The patient will not need to repeat any 
of the tests if they have been performed in the time frame required by the study.  

10 
Version Date: 10-29-2015 
 
4.2 
Within 8 weeks of prior to study treatment: 
 
4.2.1 
General History and Physical Examination 
 
4.2.2 
Karnofsky Performance Status 
 
4.2.3 
Bone scan, MRI, or CT of area to be treated 
4.2.4 
Status of pain from disease site to be treated (this is to ensure that eligibility criteria #8 is met.) 
 
4.2.5 
Platelet Count Blood Test 
 
4.2.6 
Adverse Event Check 
 
 
4.3 
Within 4 weeks of study treatment: 
4.3.1 
Fluoroscopy Imaging or plain film imaging at the time of vertebroplasty or if radiation is being done first, plain film will be performed prior 
to the radiation treatment.  If vertebroplasty is done first, there will be no need for a plain film xray. 
 
 
4.3.2 
Adverse Event Check 
 
 
4.4 
Within 2 weeks prior to study treatment, patient will undergo: 
 
4.4.1 
Pregnancy test (urine dipstick or serum) 
 
4.4.2 
Adverse Event Check 
 
 
Subjects may have the vertebral augmentation or the radiation first; whichever procedure is performed first, will be considered the beginning of study 
treatment.  
 
 
5.0 
PRETREATMENT EVALUATIONS/MANAGEMENT   
After the patient’s eligibility is determined, the following assessments will be performed: 
5.1 
Initial Assessment of Activity, Pain, and Quality of Life (All assessments will be done within 8 weeks prior to study treatment) 
5.2.1 
Worst Pain Score – BPI (Appendix I) 
5.2.2 
Roland-Morris Disability Questionnaire (Appendix II)  
5.2.3 
Pain Measurement Index and Narcotic Score (Appendix IV) 
5.2.4 
EORTC QLQ-C30 (Appendix III) 
5.2.5 
Baseline Data Collection Form (Appendix V) 
5.2.6 
Record of Current Pain Medications (Appendix VIII) 
 
 
6.0 
VERTEBRAL AUGMENTATION 
 
All patients on the study must complete the vertebroplasty or kyphoplasty procedure within 0 - 4 weeks of registering for the protocol or within 0-4 
weeks of completing radiation therapy (if radiotherapy is given first).  
 
6.1 
Treatment 
 
6.1.1 
    1 – 3 sites of disease may be treated using conscious sedation (or general anesthesia) and intravenous antibiotic prophylaxis. 
 
6.1.2 
    Fluoroscopy will be utilized to guide the procedure.  In selected cases, the aid of CT may be added. 
 
6.1.3 
    If there is only clinical and imaging documented disease, a biopsy will be obtained to confirm malignancy. 
6.1.4 
A cavity within the vertebra will be created with coblation technology when needed (largeosteolytic lesions, posterior wall erosion). 
6.1.5 
    Adverse Events associated with this procedure are: 
Potential toxicities include:  bleeding at the site of puncture, in the paravertebral muscles, in the epidural space, or in the perivertebral 
soft tissues; pneumothorax; venous cement embolism to the epidural space, or to the systemic venous system; risk of nerve root or 
spinal cord compression; risk of pulmonary embolism; future vertebral fracture of the treated level or at adjacent levels; pain or 
weakness; paralysis; local or systemic infection.  Some patients may suffer from a longer than average recovery period that may 
decrease their quality of life.  
 
6.1.6 
    Post-procedure the following will occur (these are considered standard of care):  
 
Dressing at the puncture site 
 
Bed rest 2-3hrs prior to d/c (outpatients or 23hr hospitalization – if indicated) 
 
Monitor vitals & neurologic examination 
 
Gradual increase in activity over 3 days 
 
Physical therapy 
 
Medical treatment/Resume pain control as indicated 
 
7.0 
RADIATION THERAPY 
All patients on study must start radiotherapy within 0 – 4 weeks of completion of the vertebral augmentation procedure if the vertebral 
augmentation procedure is done first.. If radiotherapy is completed prior to the vertebral augmentation procedure, it must be completed within 0-4 
weeks of registration for the study. 
 
 
 
7.1 
Treatment 

11 
Version Date: 10-29-2015 
 
7.1.1 
    Palliative radiation to the focal region(s) of metastatic disease. 
 
7.1.2 
    Radiation fractionation will be dependent on the patient health status and transportation status.  
Options include: 
 
30Gy in 10 fractions 
 
20Gy in 5 fractions 
 
8Gy in 1 fraction 
 
Multiple myeloma: local control dose (30Gy in 10 fractions) 
7.1.3 
Treatment portals will be left to the discretion of the radiation oncologist.  All vertebral bodies treated with vertebroplasty/kyphoplasty 
will be encompassed in the treatment field(s). 
7.1.4 
    Adverse Events of the Radiation Therapy include: 
Potential toxicities include:  fatigue; sore throat/difficulty swallowing; radiation pneumonitis; nausea/vomiting, alopecia; and/or skin 
darkening in the treatment field.  Extremely rare but possible life-threatening side-effects include injury to the spinal cord that could 
cause pain or paralysis; and/or development of a secondary cancer due to radiation exposure. 
 
8.0 
MEASUREMENT OF RESPONSE/PATIENT FOLLOW-UP 
The time of follow-up for all patients will be initiated immediately after completion of the initial procedure (vertebroplasty/kyphoplasty or 
radiotherapy).  The patient grouping on Line 4 of the Baseline Data Collection Form will also correlate with the initial treatment. 
 
 
8.1 
1 Week Follow-Up Assessment 
Assessment of the patient’s pain, activities and quality of life will be gathered from the patient in returning for follow-up or by contacting 
the patient by phone approximately 1 week following the completion of their first procedure, whether it be the vertebral augmentation or 
the radiotherapy (5 – 10 days following).  Mandatory assessments include: 
8.1.1 
    
Worst Pain Score – Brief Pain Inventory (BPI) (Appendix I) 
8.1.2 
    
Roland-Morris Disability Questionnaire (Appendix II) 
8.1.3 
    
Pain Measurement Index and Narcotic Score (Appendix IV) 
8.1.4 
 
Adverse Event Evaluation 
 
8.2 
1 Month Follow-Up Assessment 
Assessment of the patient’s pain, activities and quality of life will be gathered from the patient in returning for the 1 month follow-up 
appointment approximately 1 month following completion of the initial procedure whether it be the vertebral augmentation or the radiation 
therapy  (3 – 5 weeks following).   Mandatory assessments include: 
8.2.1 
 
Worst Pain Score – BPI (Appendix I) 
8.2.2 
    
Roland-Morris Disability Questionnaire (Appendix II) 
8.2.3 
    
EORTC QLQ-C30 (Appendix III) 
8.2.4 
    
Follow-Up Report (Appendix VI) 
8.2.5 
   
Pain Measurement Index and Narcotic Score (Appendix IV) 
8.2.6 
   
Record of Current Pain Medications (Appendix VIII) 
8.2.7 
Plain films of the vertebrae will be obtained if the patient’s health status does not prevent him/her from travelling to the hospital. 
8.2.8 
Adverse Event Evaluation 
 
 
8.3 
3 Month Follow-Up Assessment 
Assessment of the patient’s pain, activities and quality of life will be gathered from the patient in returning for the 3 month follow-up 
appointment approximately 3 months following completion of the initial procedure whether it be the vertebral augmentation or the 
radiation therapy  (10 – 14 weeks following).  Mandatory assessments include: 
 
8.3.1 
    
Worst Pain Score – BPI (Appendix I) 
 
8.3.2 
    
Roland-Morris Disability Questionnaire (Appendix II) 
8.3.3 
    
Pain Measurement Index and Narcotic Score 
(Appendix IV) 
8.3.4 
Plain films of the vertebrae will be obtained if the patient’s health status does not prevent him/her from travelling to the hospital. 
8.3.5 
Follow-up Report (Appendix VI) 
8.3.6 
Adverse Event Evaluation 
8.3.7 
EORTC QLQ-30 (Appendix III) 
8.3.8 
Record of Current Pain Medications (Apendix VIII) 
 
9.0 
QUALITY ASSURANCE  
 
The Radiation Oncology Department holds a Dosimetry Meeting with physicians, physicists, and dosimetrists to discuss all patients undergoing 
radiation treatment. Radiation Oncology Co-chair will perform a Quality Assurance Review of all patients who receive treatment under the protocol.  
The goal of the review is to evaluate protocol compliance to determine that the radiation is given in accordance to this protocol..  All patients 
treated in the Radiation Oncology Clinic are presented at a peer review chart round meeting once per week. 
 

12 
Version Date: 10-29-2015 
 
Dr. Howell/Dr. Baaj will perform a Quality Assurance Review after complete data for the first 5 cases enrolled has been received.  Dr. Howell/Dr. 
Baaj will perform the next reviews for subsequent blocks of 5 cases after the complete data for these cases becomes available at the University.  
The final cases will be reviewed within 3 months after this study has reached the target accrual. 
 
10.0 
PROTOCOL DATA AND SAFETY MONITORING PLAN (MEDIUM RISK) 
Medium risk studies are intended to include all trials involving therapeutic intervention(s), which are not designated as high risk per NCI, do not 
meet the above criteria of medium plus IND risk, and do not require an the IND (i.e. IND exempt).  
 
10.1 
Data and Safety Monitoring Plan: 
10.1.1 
Identification of the DSMB obligated for oversight responsibilities: 
The Arizona Cancer Center Data and Safety Monitoring Board (DSMB) will provide ongoing oversight for this trial. 
 
10.1.2 
Identification of the entity obligated for routine monitoring duties: 
Routine monitoring will be provided by the Quality Assurance/Quality Control (QA/QC) Program to ensure that the investigation is 
conducted according to protocol design and regulatory requirements.  
 
10.1.3 
Monitoring progress and data review process: 
Routine monitoring of subject data will be conducted at least every six months.  
The first routine monitoring visit will include at a minimum: 
• 
 
Informed consent – 100% of cases enrolled;  
• 
Subject eligibility - 50% of cases, up to two subjects; 
• 
Data review - 50% of cases, up to two subjects. 
 
All subsequent monitoring visits will consist of randomly selected subject cases based on current enrollment and include continuing review of 
previously selected cases, as applicable. 
 
A monitoring visit report and follow-up letter will be completed approximately two weeks after the routine monitoring visit; a copy will be maintained 
in the study file. A query/finding form or an electronic record will also be completed by the monitor to request additional source documentation, 
clarification, information or corrections to the CRF and/or regulatory records. The Clinical Research Coordinator or other applicable staff 
responsible for the study will be given a copy of this form, or will be notified of the electronic record  for resolution of queries/findings. The 
query/finding form will be maintained with a copy of the visit report for follow-up at the next monitoring visit. Electronic records will be available in 
the institution database or provided by the QA/QC Program staff.  
 
The Principal Investigator will ensure the accuracy, completeness, legibility and timeliness of the data reported in the Case Report Form (CRF), or 
other acceptable data formats. Source documentation supporting the study data should indicate the subject’s participation in the trial and should 
document the dates and details of study procedures, adverse events, and patient status.  
 
Case report forms, which include the inclusion/exclusion criteria form, adverse event forms and serious adverse event forms [other forms, 
depending on study] should be completed via the institution database or other acceptable data formats. Trials using paper CRFs will have the data 
entered with a black ball-point pen or typed. Corrections to the forms should not obscure the original entry and should be made by striking the 
incorrect information with a single line. Each strike should be accompanied by the initials of the corrector and the correction date. All subject forms 
and study files will be stored in a secure area limited to authorized staff 
 
Note: Routine monitoring of regulatory documents and test article will be conducted at least annually.  
10.1.4 
Process to implement study closure when significant risks or benefits are identified:  If there is a grade 5 toxicity of any kind 
related to the study procedures reported in two of the patients, the study will be discontinued. 
 
 
 
 
10.2 
Adverse Events  
10.2.1 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical 
product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related 
to the medicinal (investigational) product.  
 
10.2.2 
Any and all adverse events will be recorded on the UMC adverse events record form and reviewed by the Principal Investigator. 
 
10.2.3 
All adverse events will be classified using either the MedDRA term or NCI Common Terminology Criteria for Adverse Events (CTCAE) 
version 4.0 (A copy of the CTCAE version 4.0 can be downloaded from the National Cancer Institute, Adverse Event Reporting 
Guidelines http://ctep.cancer.gov) and will address:  
10.2.3.1 Grade 

13 
Version Date: 10-29-2015 
10.2.3.2 Relationship to study drug(not related, unlikely, possible, probable, definitely)  
10.2.3.3 Causality other than study drug (disease related, concomitant medication related, intercurrent illness, other)   
10.2.3.4 Date of onset, date of resolution 
10.2.3.5 Frequency of event (single, intermittent, continuous) 
10.2.3.6 Event outcome (resolved, ongoing, death) 
10.2.3.7 Action taken (none, held, dose reduced, discontinued, medication given) 
 
10.2.4 
If an adverse event should arise during radiotherapy that is felt to increase the likelihood of patient mortality or morbidity greater than the 
benefit provided, than radiotherapy may be stopped.  If the patient should experience a consequence of vertebral augmentation then 
he/she may still proceed with radiotherapy for pain relief.  All other side-effects may be treated medically as clinically indicated. 
 
 
10.3 
Serious Adverse Events 
 
10.3.1 
A serious adverse event (SAE) is any untoward medical occurrence that at any dose:  
 
 
 
1) Results in death;  
 
 
 
2) Is life-threatening; 
3) Requires in-patient hospitalization or prolongation of an existing hospital stay;  
 
 
 
4) Results in disability persistent or significant disability/incapacity, or: 
 
 
 
5) Is a congenital anomaly/birth defect.  
 
Note: A SAE may also be an important medical event, in the view of the investigator that requires medical or surgical intervention to 
prevent one of the outcomes listed above.  
10.3.2 
All serious adverse events, regardless of attribution, and any deaths will be reported within 24 hours of notification of the event to the 
sponsor and DSMB Coordinator and the study PI. For both serious and non-serious adverse events, the investigator must determine 
both the intensity of the event and the relationship of the event to the study.  All serious adverse events will be reported to the University 
of Arizona Human Subjects Protection Program according to their policies and procedures.  
10.3.3 
All serious adverse events will be processed by the DSMB Coordinator monthly for initial trend analysis and fully reviewed by the DSMB, 
every six months. The DSMB coordinator will review the SAE reporting process to confirm reporting requirements are met. 
 
10.4 
Plan for Assuring Data Accuracy and Protocol Compliance: 
10.4.1 
Routine study activity and safety information will be reported to the DSMB every six months, or more frequently if requested. These 
reports will include: 
10.4.1.1 Study activity, cumulative and for the period under review; 
10.4.1.2 Safety (narrative description on non-serious and serious adverse events, protocol pre-determined early stopping rules for 
safety or treatment-emergent adverse events); 
10.4.1.3 Predetermined protocol early stopping rules for efficacy/futility;  
10.4.1.4 Status of study in relationship to stopping rules;   
10.4.1.5 Current dose level of study agent;  
10.4.1.6 Routine monitoring and protocol compliance (describe the monitoring process and identify the status of the monitoring); 
10.4.1.7 Comments;  
10.4.1.8 Attachments (AE data reviewed by the PI to compile the report, SAE letters and reports, results of any review(s), applicable 
correspondence with the IRB or other regulatory agencies 
 
10.4.2 
Data, safety and study progress will be reported to: 
10.4.2.1 Human Subjects Protection Program (IRB) at least annually; 
10.4.2.2 Sponsor (if applicable) at least every six months. 
10.4.3 
Identification of the sponsor or funding agency, as applicable: 
The PI will immediately notify; in writing, the funding agency, if applicable, any action resulting in a temporary or permanent suspension 
of the study. A copy of this correspondence will also be forwarded to the DSMB and the SRC.  
 
 
11.0  
OTHER THERAPY 
 
11.1  
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.  This may include but is not limited to: 
 
Narcotics for pain control 
 
Bisphosphonates 
 
Hormone Therapy 
 
Chemotherapy 
 
12.0 
TISSUE/SPECIMEN SUBMISSION 
 
A tissue biopsy will be collected at the time of vertebroplasty for confirmation of malignancy for those patients without a previous diagnosis of 
metastatic cancer or multiple myeloma. 

14 
Version Date: 10-29-2015 
 
13.0 
PATIENT ASSESSMENTS 
 
A series of patient questionnaires will be mandatory at the patient evaluation and intervals after completing treatment to assess for pain control, 
quality of life and films performed to determine fracture rates post-treatment. 
 
13.1 
Pain Assessment Tools 
13.1.1 
Worst Pain Score – BPI 
The Worst Pain Score – BPI will provide pain measures.  Pain rating scale from 0 – 10 with 0 representing no pain and 10 representing 
the worst pain possible.  Prior to treatment patients will be asked to rank their current pain intensity and also pain within the last 24hours 
at its worst, while not being controlled with narcotics.  Patients considered to have painful metastasis, at least 5 on a scale of 10, will be 
evaluated for control of pain.  Patients will be judged as having a complete response if the pain is scored as 0 after the procedure(s).  A 
partial response is determined as when the pain rating is >2 points lower than before the procedure(s).  A stable response is 1 point 
change in either direction on the pain scale.  Progressive pain will be considered an increase of >2 points on the pain scale. Those 
patients not initially having pain (<5 on the pain scale) will be monitored for an increase in pain score (>5 AND an increase of >2 points) 
versus stable response (1 point change in either direction OR overall score 0-4). See Appendix I. 
 
13.1.2     Pain Measure Index 
Enable measurement of pain by assessing narcotic usage.  See appendix IV for further details.   
13.2 
Assessment of Patient Activities 
 
13.2.1 
Roland-Morris Disability Questionnaire  
Brief survey detailing the amount of time the patient can tolerate activities of daily living.  See appendix II for further details.   
 
13.3 
Assessment of Quality of Life 
 
13.3.1 
EORTC QLQ-C30 (version 3) 
The EORTC QLQ-C30 is the most frequently used measure in cancer clinical trial research and is well established as a quality of life 
instrument for cancer patients in general.  See appendix III for further details. 
 
13.3.2 
Baseline Data Collection Form 
 
 
See appendix V for further details.  
 
13.3.3 
Follow-Up Report 
 
 
 See appendix VI for further details.  
 
13.4 
Assessment of Fracture Rate 
Plain films will be acquired at 1 month and 3 months status post treatment.  The height of the vertebral body will be compared with the 
height as determined on fluoroscopy at the time of VA.  A loss of height of >10% will be considered an increase in the compression 
fracture of the vertebrae.  Fractures in adjacent vertebra will also be noted.  The fracture rate will be documented as fracture (yes/no) per 
vertebral body. 
 
13.5 
Criteria for Removal from Protocol Treatment 
13.5.1 
Unacceptable adverse event(s) to the patient (at the discretion of the treating physician) – Reasons for removal must be clearly 
documented in the patient’s records. 
13.5.2 
The investigators or treating physician may withdraw the patient from protocol treatment if it is felt to be in the patient’s best interest.  The 
reasons for removal must be clearly documented in the patient’s records. 
 
13.5.3 
Patients discontinuing the treatment portion of the protocol should continue to be followed for study endpoints. 
 
14.0 
DATA COLLECTION 
 
14.1 
In-House Data Collection and Analysis  
The data collected for this study will be kept in the patient’s research charts and will be identified by both patient name and medical 
record number. A secure computer database will be constructed to house the data for statistical analyses and interpretation.  
 
14.1.1 
Summary of Data Available for Study Analysis 
 
Patient consultations 
 
Radiographic images relevant to diagnosis and treatment (MRI, CT, Bone Scan, Plain Films, Fluoroscopy) 
 
Procedure Notes 
 
On Treatment Visits 
 
Treatment Summary Notes 
 
In-Patient Notes as related to possible complications 
 
Follow-Up Notes 
 
Follow-Up radiographic images of the area of treatment 
 
Worst Pain Score as rated on the Brief Pain Inventory Scale (BPI) 
 
Roland-Morris Disability Questionnaire 
 
EORTC QLQ-C30Baseline Data Collection Form 
 
Pain Measurement Index and Narcotic Score 
 
Follow-Up Report (supplement to the EORTC questionnaires) 
 
Record of Current Pain Medications 
 

15 
Version Date: 10-29-2015 
15.0         STATISTICAL CONSIDERATIONS 
                15.1         Study Endpoints                                        
 
 
15.1.1      Primary Endpoint:  
Total change in pain status will be calculated as the difference between the pain score at 3 months and the pain score at baseline.   A 
decrease from baseline to 3 months of 2 or more points or no pain at 3 months is considered a positive outcome and the rate of pain 
control is defined as the proportion of patients with a positive outcome.   From the RTOG 9714 experience, this is the complete plus 
partial response rate at a 3 month follow-up time period. 
                15.1.2      Secondary Endpoints: 
Change from baseline to other points in time for pain will be calculated.  Activity level prior to and following treatment will be assessed 
using the difference between the activity level at 3 months and the activity level at baseline.  Quality of life prior to and following 
treatment will be calculated by subtracting baseline quality of life measure(s) from the measures taken at follow-up time 
points.  Fractures per patient will be assessed at 1 and 3 months and recorded as a binary variable (yes/no).  Fractures will be counted 
as the involvement per each vertebral body.  In analysis this will be compared to RTOG 7402 fracture rates.  Any increase in 
compression of a vertebra by >10% by imaging will be considered positive for development of a fracture.  Toxicity will be graded 
according to CTCAE 3.0 for each patient.   
                 
15.2         Analytic Plan 
15.2.1 
Analysis of Primary Endpoint:  The proportion of patients that experience a change in pain from baseline to 3 months of at least 2 or 
more points (or improve to no pain) will be estimated with its 95% confidence interval.  The historical control rate of pain control, defined 
in the same way, in RTOG 9714 was 66%. We will use an exact binomial test with a one-sided alpha of 0.05 to test the null hypothesis 
that the pain control rate in our study is 65%.   
15.2.2 
Analysis of Secondary Endpoints:  Graphical displays will be used to show scores over time.  Changes from baseline to follow-up will be 
calculated and tested for significance using paired t-tests of non-parametric tests.  The rate of fractures will be estimated as a proportion 
with its 95% confidence interval.  It will be compared to the fracture rate from RTOG 7402 (6% spinal sites) using an exact binomial 
test.  The study is not powered to detect a difference in fracture rates and only very large differences will be detectable.   
                
15.3        Sample Size 
Given the average number of patients treated in 1 month at a comparable cancer center, 25 patients with painful metastasis may be accrued within 
our department in a time frame of 1-2 years.  This will allow for approximately 5 patients being deemed ineligible or not completing study treatment 
or follow-up.  With 20 patients and a null pain control rate at 3 months of 65%, we can detect a pain control rate of 89% with 83% power using a 
one-sided alpha of 0.05.   
 
Projected Distribution of Gender 
 
Gender Category 
Percentage 
Absolute 
Females 
55% 
11 
Males 
45% 
9 
Total 
100% 
20 patients 
 
 
 
 
 
 

16 
Version Date: 10-29-2015 
REFERENCES 
 
1.  Daphne Tong, Laurence Gillick, et al. The Palliation of Symptomatic Osseous Metastases: Final Results of the Study by the Radiation Therapy Oncology 
Group. Cancer 50:893-899, 1982. 
 
2.  William F. Hartsell, Charles B. Scott, et al. Randomized Trial of Short- Versus Long-Course Radiotherapy for Palliation of Painful Bone Metastases. 
Journal of the National Cancer Institute 97(11):798-904, 2005. 
 
3.  Peter C. Gerszten, Anand Germanwala, et al. Combination Kyphoplasty and Spinal Radiosurgery: a New Treatment Paradigm for Pathological Fractures. 
Neurosurg Focus 18(3):E8, 2005. 
 
4.  Y.-Y. Tseng, S.-T. Tang et al.  Minimally Invasive Vertebroplasty in the Treatment of Pain Induced by Spinal Metastatic Tumor. Minim Invas Neurosurg 
51:280-284, 2008. 
 
5.  Jee-Soo Jang, MD, and Sang-Ho Lee, MD. Efficacy of Percutaneous Vertebroplasty Combined with Radiotherapy in Osteolytic Metastatic Spinal Tumors. 
J. Neurosurg Spine 2:243-248, 2005. 
 
6.  Salvatore Masala, Giovanni Anselmetti, et al. Percutaneous Vertebroplasty in Multiple Myeloma Vertebral Involvement.  J Spinal Disord Tech 21(5), July 
2008. 
 
7.  John Chi and Ziya Gokaslan. Vertebroplasty and kyphoplasty for spinal metastases.  Current Opinion in Supportive & Palliative Care. 2(1):9-13, March 
2008. 
 
8.  B.A. Georgy. Metastatic Spinal Lesions: State-of-the-Art Treatment Options and Future Trends. American Journal of Neuroradiology. 29:1605-11, 
October 2008. 
 
 

17 
Version Date: 10-29-2015 
APPENDIX I 
 
Worst Pain Assessment on the Brief Pain Inventory Scale1 
 
The Worst Pain Assessment on the Brief Inventory Scale is an assessment tool of current pain intensity and pain intensity 
within the last 24 hours when not on pain control medications. 
 
 
Please scale the intensity of your pain within the last 24hours on the scale below.  0 being no pain and 10 is the worst pain possible.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  Serlin RC, Mendoza TR, Nakamura Y, Edward KR, Cleeland CS.  When is cancer pain mild, moderate or severe? Grading pain severity by its 
interference with function. Pain 1995;61 277‐84. 

18 
Version Date: 10-29-2015 
APPENDIX II 
 
Roland‐Morris Disability Questionnaire1 
 
As you read the list, think of yourself today.  When you read a sentence that describes you today, put a tick against it.  If the sentence does 
not describe you, then leave the space blank and go on to the next one.   
 
Remember, only tick the sentence if you are sure it describes you today. 
1. 
I stay at home most of the time because of my back.  
 
 
 
 
2. 
I change position frequently to try and get my back comfortable. 
 
 
 
3. 
I walk more slowly than usual because of my back. 
4. 
Because of my back I am not doing any of the jobs that I usually do around the house. 
5. 
Because of my back, I use a handrail to get upstairs. 
6. 
Because of my back, I lie down to rest more often. 
7. 
Because of my back, I have to hold on to something to get out of an easy chair. 
8. 
Because of my back, I try to get other people to do things for me. 
9. 
I get dressed more slowly then usual because of my back. 
10. 
I only stand for short periods of time because of my back. 
11. 
Because of my back, I try not to bend or kneel down. 
12. 
I find it difficult to get out of a chair because of my back. 
13. 
My back is painful almost all the time. 
14. 
I find it difficult to turn over in bed because of my back. 
15. 
My appetite is not very good because of my back pain. 
16. 
I have trouble putting on my socks (or stockings) because of the pain in my back. 
17. 
I only walk short distances because of my back. 
18. 
I sleep less well because of my back. 
19. 
Because of my back pain, I get dressed with help from someone else. 
20. 
I sit down for most of the day because of my back. 
21. 
I avoid heavy jobs around the house because of my back. 
22. 
Because of my back pain, I am more irritable and bad tempered with people than usual. 
23. 
Because of my back, I go upstairs more slowly than usual. 
24. 
I stay in bed most of the time because of my back. 
 
Scoring: 
The score of the RDQ is the total number of items checked – i.e. from a minimum of 0 to a maximum of 24. 
 
1.  Roland MO, Morris RW. A study of the natural history of back pain. Part 1: Development of a reliable and sensitive measure of disability 
in low back pain. Spine 1983; 8: 141‐144 

19 
Version Date: 10-29-2015 
APPENDIX III 
 
 
 
 
EORTC QLQ‐C30 (version 3)  
We are interested in some things about you and your health. Please answer all of the questions yourself by circling the number 
that best applies to you. There are no “right” or “wrong” answers. The information that you provide will remain strictly 
confidential. 
 
 
   Not at     A  
     Quite    Very 
   
 
 
 
 
 
 
 
 
   All     Little      a Bit      Much 
 
1. 
Do you have any trouble doing strenuous activities,  
1 
2 
3 
4 
 
like carrying a heavy shopping bag or a suitcase? 
1 
2 
3 
4 
2. 
Do you have any trouble taking a long walk? 
1 
2 
3 
4 
3. 
Do you have any trouble taking a short walk outside of the house? 
1 
2 
3 
4 
4. 
Do you need to stay in bed or a chair during the day? 
1 
2 
3 
4  
5. 
Do you need help with eating, dressing, washing  
1 
2 
3 
4 
 
yourself or using the toilet? 
 
 
During the past week:    
 
 
  
 
 
  Not at       A  
     Quite     Very 
   
 
 
 
 
 
 
 
   
   All         Little      a Bit     Much 
 
6. 
Were you limited in doing either your work or other daily activities? 
1 
2 
3 
4 
7. 
Were you limited in pursuing your hobbies or other 
1 
2 
3 
4 
 
leisure time activities? 
 
8. 
Were you short of breath? 
1 
2 
3 
4 
9. 
Have you had pain? 
1 
2 
3 
4 
10.  Did you need to rest? 
1 
2 
3 
4 
11.  Have you had trouble sleeping? 
1 
2 
3 
4 
12.  Have you felt weak? 
1 
2 
3 
4 
13.  Have you lacked appetite? 
1 
2 
3 
4 
14.  Have you felt nauseated? 
1 
2 
3 
4 
15.  Have you vomited? 
1 
2 
3 
4 
16.  Have you been constipated? 
1 
2 
3 
4 
17.  Have you had diarrhea? 
1 
2 
3 
4 
18.  Were you tired? 
1 
2 
3 
4 
19.  Did pain interfere with your daily activities? 
1 
2 
3 
4 
Study ID: __________ 
Date: _____________ 
Country: __________ 
 
Please Circle: 
Group: A  B  C  D  E  F  G 

20 
Version Date: 10-29-2015 
 
Please go on to the next page 
 
During the past week:    
 
 
 
 
 
 Not at         A         Quite    Very 
   
 
 
 
 
 
 
 
   
    All        Little      a Bit     Much 
20.  Have you had difficulty in concentrating on things, 
 
like reading a newspaper or watching television? 
1 
2 
3 
4 
21.  Did you feel tense? 
1 
2 
3 
4 
22.  Did you worry? 
1 
2 
3 
4 
23.  Did you feel irritable? 
1 
2 
3 
4 
24.  Did you feel depressed? 
1 
2 
3 
4 
25.  Have you had difficulty remembering things? 
1 
2 
3 
4 
26.  Has your physical condition or medical treatment 
 
interfered with your family life? 
1 
2 
3 
4 
27.  Has your physical condition or medical treatment 
 
interfered with your social activities? 
1 
2 
3 
4 
28.  Has your physical condition or medical treatment 
 
caused you financial difficulties? 
1 
2 
3 
4 
 
For the following questions please circle the number between 1 and 7 that best applies to you 
 
29. 
How would you rate your overall health during the past week? 
 
 
   
1 
2 
3 
4 
5 
6 
7 
 
 
   Very poor   
 
 
 
 
 
Excellent 
 
 
30. 
How would you rate your overall quality of life during the past week? 
 
 
   
1 
2 
3 
4 
5 
6 
7 
 
 
   Very poor   
 
 
 
 
 
Excellent 
 
 
 
 
 
 
 

21 
Version Date: 10-29-2015 
APPENDIX IV 
 
PAIN MEASURES INDEX AND NARCOTIC SCORE1 
 
 
I. Severity of pain at treatment site 
 
0: None 
 
1: Mild 
 
2: Moderate 
 
3: Severe 
 
II. Frequency of pain at treatment site 
 
0: No pain 
 
1: Occasional (less than daily) 
 
2: Intermittent (at least once a day) 
 
3: Constant (most of the time) 
 
III. Type of pain medication administered 
 
0: None 
 
1: Analgesic (aspirin, bufferin, anacin, darvon) 
 
2: Mild narcotic (one-half gram codeine, percodan, etc.) 
 
3: Strong narcotic (one gram or more of codeine, morphine, demerol, etc) 
 
IV. Frequency of pain medication administration 
 
0: None 
 
1: Less than daily 
 
2: Once per daily 
 
3: More frequently than once per day 
 
V. Pain Score = (pain severity) x (pain frequency) 
 
VI. Narcotic score = (medication type) x (medication frequency) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1Daphne Tong, Laurence Gillick, et al. The palliation of symptomatic osseous metastases: final results of the study by the radiation therapy oncology group. 
Cancer 50:893-899, 1982. 
 

22 
Version Date: 10-29-2015 
APPENDIX V 
 
BASELINE DATA COLLECTION FORM  
 
 
1. Patient Name:  
2. Patient Date of Birth: 
3. Date of Visit: 
4. Patient Status (please circle): 
Inpatient 
Outpatient 
5. Karnofsky Performance Status (please refer to table below):  
6. Date of Interview: 
7.  Patient allergies:  ___________________________ 
 
8. Current Age: 
9. Gender (please circle):   
Male 
Female 
10. Marital Status (please circle): 
Single 
Partner (unmarried) 
Married 
Widowed 
Other 
Specify: __________ 
11. Cohabitants (please circle): 
Alone 
Spouse 
Spouse & child(ren) 
Child(ren) 
Other 
Specify: __________ 
12. Primary Cancer Site (please circle): 
Breast 
Prostate 
Lung 
Multiple Myeloma 
Colorectal 
Renal Cell/Kidney 
Stomach 
Oesophagus 
Pancreas 
Liver 
Ovarian 
Other 
Specify: ____________________________________ 
13. Year of Diagnosis of Primary Cancer: 
14. Year of Diagnosis of Bone Metastases: 
15. Number of Bone Metastases (please circle):  
                  1 
                   2 
                  3 
 
16. Level of vertebral bodies involved: 
1 
2 
3 
 
 
 

23 
Version Date: 10-29-2015 
179. Other Sites of Metastasis (if known) (please circle): 
Lymph 
Lung 
Brain 
Liver 
Other 
Specify: __________ 
18. Skeletal Related Event? (please circle):                  Yes                                  No 
If “Yes”, please answer items 18 a) to e) 
a) Radiotherapy for Bone Metastases (please circle):          Yes         No          Date of Last Treatment:  
b) Pathological Fracture (please circle):                                  Yes         No          Date of Diagnosis:  
c) Spinal Cord/Cauda Equina Compression (please circle):  Yes        No          Date of Diagnosis: 
d) Orthopaedic Surgery (please circle):                                   Yes        No          Date of Surgery: 
e) Hypercalcaemia (please circle):                                           Yes        No          Date of Diagnosis:  
19. Previous Systemic Treatment? (please circle):               Yes        No 
If “Yes”, please answer items 19 a) to c) 
a) Chemotherapy (please circle):                                            Yes        No         Date of Last Treatment: 
b) Bisphosphonate (please circle):                                          Yes        No         Date of Last Treatment:  
c) Hormone Therapy (please circle):                                      Yes        No         Date of Last Treatment:  
NOTES 
 
 
 
 

24 
Version Date: 10-29-2015 
APPENDIX VI 
 
FOLLOW‐UP REPORT 
 
 
 
1. Study I.D.: 
Patient Initials: 
2. Date of Interview: 
3. Patient Status (please circle): 
Inpatient 
Outpatient 
4. Karnofsky Performance Status (please refer to table below):  
5. Skeletal Related Event since completion of treatment or last follow‐up? (please circle):                               
Yes 
No 
If “Yes”, please answer items 6 a) to e) 
a) Radiotherapy for Bone Metastases (please circle):           Yes         No          Date of Last Treatment:  
b) Pathological Fracture (please circle):                                Yes        No          Date of Diagnosis:  
c) Spinal Cord/Cauda Equina Compression (please circle):  Yes        No          Date of Diagnosis: 
d) Orthopaedic Surgery (please circle):                                 Yes        No          Date of Surgery: 
e)  Hypercalcaemia (please circle):                                        Yes        No          Date of Diagnosis:  
6. Change in Systemic Treatment since completion of treatment or last follow‐up? (please circle): 
Yes 
No 
If “Yes”, please answer items 7 a) to c) 
a) Chemotherapy (please circle):                                          Yes        No         Date of Last Treatment: 
b) Bisphosphonate (please circle):                                        Yes        No         Date of Last Treatment:  
c) Hormone Therapy (please circle):                                    Yes        No         Date of Last Treatment:  
7. Hospitalization since completion of treatment of last follow‐up?(please circle): 
Yes 
No 
If “Yes”, please answer item 8 a) 
a) Hospitalization Related to Bone Metastases? (please circle):       Yes          No          Details:    
NOTES 
 
 
 

25 
Version Date: 10-29-2015 
 
 
Appendix VII 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Karnofsky Performance Status (KPS) 
Description 
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 of his/her needs. 
50 ‐ Requires considerable assistance and frequent medical care. 
40 ‐ Disabled, requires special care and assistance. 
30 ‐ Severely disabled, hospitalization indicated. Death not imminent. 
20 ‐ Very sick, hospitalization indicated. Death not imminent. 
10 ‐ Moribund, fatal processes progressing rapidly. 

26 
Version Date: 10-29-2015 
Appendix VIII 
 
RECORD OF CURRENT PAIN MEDICATIONS 
 
Please write ALL the regular pain medications you have been taking during the past 24 hours. 
(If using a fentanyl patch, or “Duragesic”, please indicate strength of each patch.) 
Please write ALL the breakthrough pain medications you have been taking during the past 24 hours.  
 
 
Name of Medication 
Route of 
Administration 
Strength 
(mg) 
Number of Pills/ 
Administrations 
per day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Possible routes: oral / intravenous / subcutaneous / rectal / patch / sublingual (under tongue) / intramuscular 
In the last 24 hours, how much relief have pain treatments or medications provided? 
Please circle the one percentage that most shows how much relief you have received: 
No Relief = 0% 10% 
20% 
30% 
40% 
50%  60%  70%  80% 90% 100% = Complete Relief 
 
Please rate your pain by circling the one number that best describes your pain at its worst during the past day. 
 
No Pain 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Pain as bad as you can 
imagine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

27 
Version Date: 10-29-2015 
APPENDIX IX 
STUDY PARAMETER TABLE 
 
 
 
 
 
 
Pre-treatment 
(within 8 wks prior 
to treatment) 
 
 
Pre-treatment 
(within 4 weeks 
of treatment) 
 
Pre-treatment 
(within 2 weeks 
of treatment 
 
 
At time of VA or 
Radiotherapy  
 
 
1 week follow-
up (5 – 9 days 
following initial 
procedure) 
 
1 month follow-
up  (3 – 5 
weeks 
following initial 
procedure) 
 
3 month follow-
up (10 – 14 
weeks 
following initial 
procedure) 
 
 
History/physical 
(including KPS) 
 
x 
 
 
 
 
 
 
 
 
Imaging (X-ray, 
bone scan, CT 
scan or MRI) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
B-HCG (if 
applicable) 
 
 
x 
 
 
 
 
 
 
Fluoroscopy   
 
Plain film 
Imaging 
 
 
 
 
X2 
 
 
 
 
 
 
X2 
 
 
 
 
 
Worst Pain 
Score - BPI 
x 
 
 
 
x 
x 
x 
 
 
 
Roland-Morris 
Disability 
Questionnaire 
x 
 
 
 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 EORTC QLQ-
C30 
x 
 
 
 
 
x 
 
 
 
Baseline Data 
Collection Form 
x 
 
 
 
 
 
 
 
 
Pain 
Measurement 
Index and 
Narcotic Score 
x 
 
 
 
x 
x 
x 
 
 
 
 
Follow-Up 
Report 
 
 
 
 
 
x 
x 
 
 
Record of 
Current Pain 
Medications 
x 
 
 
 
x 
x 
 
 
 
Plain films 
 
 
 
 
 
x 
x 
 
 
Biopsy  
 
 
 
 
x1  
 
 
 
 
 
Adverse event 
evaluation 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
 

28 
Version Date: 10-29-2015 
1 
If no previous pathology confirmation, a biopsy will be collected at the time of the Vertebral Augmentation 
2 
2  Fluoroscopy will be done at time of vertebral augmentation,  If radiation is done firs, a plain film Xray will be done prior to radiation treatment