Rapid Radiation Therapy for Painful Osseous Metastatic Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to evaluate the safety and effectiveness of an experimental workflow that may result in a faster way to plan and deliver radiation for the treatment of pain caused by metastatic bone tumors (tumors that originally came from another organ and have spread to bones causing pain) or multiple myeloma (a type of cancer that begins in white blood cells that produce antibodies). The current standard of care radiation treatment planning and delivery takes 2 to 3 weeks from start to finish. The investigators have developed an experimental workflow: a radiation treatment planning and delivery workflow called STAT RT (STAT means right away, and RT means radiation therapy). This experimental workflow may shorten the time it takes to plan and treat painful bone metastases to 1 week or less. All steps in this process will be performed within the current standard of care but in a shorter time frame to allow treatment to start sooner. The investigators will evaluate effectiveness by requesting patients to complete pain and quality of life questionnaires before and after treatment. The investigators will also be collecting additional information from their treatments that will help us make future workflows even more efficient.

Detailed Description
-----------------
Background: Osseous metastatic disease causes significant pain, decreased functioning, and decreased quality of life. Progressive bone destruction can lead to pathologic fractures or spinal cord compression leading to orthopedic surgery, paralysis, and/or patients becoming bedridden. Opioids can alleviate pain but have neurologic and gastrointestinal side effects that further decrease quality of life. Radiation therapy can effectively reduce pain and opioid use and prevent further bone destruction, however, its use is limited because the current workflow frequently requires one week for planning and two weeks for delivery. Additionally, typical palliative radiation plans for osseous metastases lack conformality of dose to the tumor volume, and therefore, result in radiation-induced toxicity to large volumes of adjacent normal tissue. Recent software and hardware advancements provide the opportunity to revolutionize the palliative treatment of osseous metastases. The investigators propose to investigate a novel TomoTherapy-based workflow, called STAT RT, which includes same day CT simulation, treatment planning, and quality assurance measurements coupled with highly conformal treatment delivery for patients with osseous metastases in a pilot clinical trial. Objective: The overall goal of this STAT RT proposal is to develop a more rapid, convenient, and effective palliative radiation approach for patients with osseous metastases that is less toxic and less expensive than current treatment regimens. The investigators have already optimized the conformality of TomoTherapy-based radiation doses for osseous metastases, and the investigators have developed a STAT RT workflow that condenses standard of care simulation, planning, quality assurance, and treatment delivery into 5-6 hours. Additional optimization and integration of new radiation therapy computing processes will allow for real time simulation, planning, and delivery via a novel Scan-Plan-Treat STAT RT workflow that will ultimately require only 30 minutes. In this study the investigators will evaluate the effectiveness of the current STAT RT workflow, and the investigators will investigate techniques for further optimization that will be needed to create a 30 minute Scan-Plan-Treat STAT RT workflow. Primary Specific Aim/ Hypothesis: The investigators will quantify the time for pain relief, amount of pain relief, opioid use reduction, functional scores, quality of life, and satisfaction of patients treated with STAT RT for osseous metastases. The investigators hypothesize that these patients will have rapid and significant pain relief, improved quality of life, and high patient satisfaction. Secondary Specific Aim/ Hypothesis: The investigators will optimize the integration of commercially available and in-development software to develop the Scan-Plan-Treat STAT RT workflow. Specifically, the investigators will A) optimize rigid and deformable co-registration of pre-contoured diagnostic image sets to MVCT simulation scans and compare the accuracy to the same pre-contoured diagnostic image sets co-registered to kilovoltage CT (kVCT) simulation images and then kVCT simulation to MVCT scan co-registration, B) optimize CT-detector-based exit dose measurement algorithms for quality assurance and compare to standard of care phantom-based quality assurance, C) optimize the accuracy of an in-house real time infrared tracking system for intrafractional patient position monitoring to ensure accurate patient treatment. The investigators hypothesize that these new components will provide effective and efficient methods for treatment planning, quality assurance, and patient position monitoring that can be used in a future 30 minute Scan-Plan-Treat STAT RT workflow. Study design: The investigators will recruit 30 cancer patients with 1-3 painful osseous metastatic lesions (target sites) who are candidates for palliative radiation therapy. Patients will receive 1-5 fractions of 5-8 Gray (Gy) (minimum biologic effective dose of 25 Gy) of conformal radiation therapy delivered to the target sites via the Helical TomoTherapy system using the STAT RT workflow. Data will be collected to evaluate the effectiveness of our novel image co-registration techniques, CT-detector-based exit dose calculations, and infrared patient position monitoring. These novel techniques for image co-registration, radiation dose calculations, and patient position monitoring will not alter or replace standard of care techniques. Using validated surveys the investigators will record patient pain, analgesic use, function, quality of life, and patient satisfaction prior to treatment and at 1 week, 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months after therapy. Radiation-induced treatment related toxicities will be captured during treatment and at the above time points.

Official Title
-----------------
Phase II Pilot Single Arm Prospective Clinical Trial of Rapid Institution of Helical TomoTherapy-based Radiation Therapy for Patients With Painful Osseous Metastatic Disease

Conditions
-----------------
Bone Metastases

Intervention / Treatment
-----------------
* Radiation: STAT RT planning and delivery workflow


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has a biopsy proven diagnosis of cancer. The osseous metastatic lesions do not need to be biopsied. Patients with multiple myeloma are eligible for the study. Patient has 1-3 major painful osseous metastases (target lesions) from any primary cancer or unknown primary cancer. Long bone target lesions must have a Mirels fracture score of ≤ 7. Patients with spinal cord compression from vertebral body metastases are not eligible. Target lesions have not previously been treated with radiation. Radiation oncologist determines that the patient is medically able to undergo palliative radiation therapy. Patient has target lesions that are radiographically consistent with metastatic disease on CT, MR, or PET CT obtained within 8 weeks of treatment. Persistent distinguishable pain associated with target sites to be treated. Patient average BPI pain score for last 72 hours at specified location is > 3 (0-10 scale) Patients may have additional non-painful or minimally painful osseous metastases (if patient has pain from additional sites, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the BPI compared to the site(s) treated) The patient may have previously been treated with radiation therapy to other body sites, but not to the target lesions. The patient may have previously or currently be undergoing chemotherapy or bisphosphonate therapy. The patient will be able understand English (or a medical interpreter for their native language must be available for all study visits). 18 years of age or older. Life expectancy > 12 weeks. Able and willing to answer simple survey questionnaires. Able and willing to keep a logbook of analgesic use (with or without assistance). Willing to return to clinic for follow-up visits after first treatment. Signed study-specific informed consent form Exclusion Criteria: Inability to lie flat on table for treatment Patient with < 12 weeks life expectancy Systemic radionuclide delivery within 30 days prior to treatment Epidural compression of spinal cord or cauda equine Spinal canal compromise > 25% Unstable spine requiring surgical stabilization Target lesions have previously been treated with radiation. Tumor located within 5mm of spinal cord or cauda equina. A serious uncontrolled medical disorder that, in the opinion of the Investigator, would impair the ability of the patient to receive protocol therapy. Pregnant and breastfeeding women are excluded from this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STAT RT planning and delivery workflow<br>single arm | Radiation: STAT RT planning and delivery workflow<br>* Patients will receive simulation, planning, quality assurance, and their first treatment in a single day using the STAT RT workflow. Patients will receive a total of 1-5 fractions of high dose palliative radiation therapy via TomoTherapy consisting of 5-10 Gray per fraction. Data will be collected to evaluate the effectiveness of our novel image co-registration techniques, CT-detector-based exit dose calculations, and infrared patient position monitoring. These novel techniques for image co-registration, radiation dose calculations, and patient position monitoring will not alter or replace standard of care techniques.<br>* Other names: TomoTherapy-based Radiation Therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Complete Response, Partial Response, or Stable Pain After Receiving Treatment Via the STAT RT Workflow at 12-months | The Brief Pain Inventory (BPI) and Oral Morphine Equivalent Doses (OMED) were used to categorize the number of participants who had a Complete Response (no pain), Partial Response (pain reduction), Stable Pain (no change in pain), and Pain Progression at 12 months after receiving treatment via the STAT RT workflow. | 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Toxicity | Toxicity will be assessed by CTCAE Version 4.0 Toxicity will be assessed up to 12 months after treatment. | 12 months after treatment | 
| Number of Participants With an Improved Quality of Life Function Score at 1 Week Post Treatment | The patient's quality of life function will be assessed using the Brief Pain Inventory (BPI) 1 week post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 1 Week Post Treatment | 
| Number of Participants With an Improved Quality of Life Function Score at 4 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 4 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 4 weeks post treatment | 
| Number of Participants With an Improved Quality of Life Function Score at 8 Weeks After Initial Treatment | The patient's quality of life function will be assessed using the Brief Pain Inventory (BPI) 8 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 8 weeks post initial treatment | 
| Number of Participants With an Improved Quality of Life Function Score at 12 Weeks Post Initial Treatment | The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 12 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 12 weeks post treatment. | 
| Number of Participants With an Improved Quality of Life Function Score at 6 Months After Initial Treatment | the patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 6 months post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 6 months post treatment | 
| Number of Participants With an Improved Quality of Life Function Score at 12 Months After Initial Treatment | The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 12 months post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain. | 12 months post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 1 Week Post Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 1 week post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 1 week post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 4 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 4 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 4 weeks post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 8 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 8 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 8 weeks post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 12 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 12 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 12 weeks post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 6 Months After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 6 months post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 6 months post treatment | 
| Patient Quality of Life and Function (FACT-BP) Assessed 12 Months After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 12 months post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function. | 12 months post treatment | 
| Patient Quality of Life and Function (FACT-G) Assessed 1 Week After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 1 week post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 1 week post treatment | 
| Patient Quality of Life and Function (FACT-G) Assessed 4 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 4 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 4 weeks post treatment | 
| Patient Quality of Life and Function (FACT-G) Assessed 8 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 8 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 8 weeks post treatment | 
| Patient Quality of Life and Function (FACT-G) Assessed 12 Weeks After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 12 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 12 weeks post treatment. | 
| Patient Quality of Life and Function (FACT-G) Assessed 6 Months After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 6 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 6 months post treatment | 
| Patient Quality of Life and Function (FACT-G) Assessed 12 Months After Initial Treatment | The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 12 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL). | 12 months post treatment | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 1 Week After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 1 week post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 1 week post treatment | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 4 Weeks After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 4 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 4 weeks post treatment | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 8 Weeks After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 8 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 8 weeks post treatment | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 12 Weeks After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 12 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 12 weeks post treatment | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 6 Months After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 6 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 6 months post treatment. | 
| Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 12 Months After Initial Treatment | Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 12 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL). | 12 months post treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastatic bone disease, Bone metastases, Radiation therapy, TomoTherapy