Conformal Radiation Therapy in Treating Patients With Metastatic Cancer Outside the Brain

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well conformal radiation therapy works in treating patients with metastatic cancer outside the brain.

Detailed Description
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OBJECTIVES: Primary To evaluate local control (defined as absence of local progression) at all treated sites of metastatic disease in patients with extracranial oligometastases treated with ablative doses of highly conformal radiotherapy delivered with helical tomotherapy. To evaluate local control at each treated site of metastatic disease in these patients. Secondary To determine median time to local progression in patients treated with this regimen. To evaluate interfraction and intrafraction motion with megavoltage computed tomography (CT) imaging based on site of metastasis in these patients. To compare tumor growth during systemic therapy in tumors treated with targeted radiotherapy vs newly developed tumors that have not been treated with radiotherapy. To evaluate if treatment with hypofractionated highly conformal radiotherapy with helical tomotherapy can improve pain scores and decrease the need for analgesia in these patients. OUTLINE: Patients are stratified according to histology (renal cell carcinoma vs melanoma vs sarcoma vs other histologies). Patients undergo hypofractionated highly conformal radiotherapy with helical tomotherapy once every other day over 5 days for a total of 3 fractions. Patients undergo megavoltage imaging before and after each fraction to verify the positioning of each target lesion. Patients complete a pain assessment questionnaire at baseline and at 1 and 3 months after treatment. After completion of study therapy, patients are followed at 1 and 3 months and then every 3 months for up to 1 year.

Official Title
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A Phase II Study of Hypofractionated Highly Conformal Radiation With Helical Tomotherapy for Extra-Cranial Oligo

Conditions
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Kidney Cancer, Melanoma (Skin), Metastatic Cancer, Ovarian Cancer, Sarcoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Other: questionnaire administration
* Radiation: 3-dimensional conformal radiation therapy
* Radiation: hypofractionated radiation therapy
* Radiation: image-guided radiation therapy
* Radiation: tomotherapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed cancer No active disease at the primary site as assessed by physical examination, clinical evaluation, or site-specific imaging Measurable metastatic disease meeting the following criteria: Four or fewer sites of extracranial lesions < 5 cm in size If metastatic site(s) is within the lung, the following criteria must be met: No more than two metastases in the proximal bronchial tree area (defined as 2 cm from the trachea or mainstem bronchi) Carbon monoxide diffusing capacity (DLCO) > 30% predicted and forced expiratory volume 1 (FEV1) > 1.2 L (in patients with more than one metastatic site in the lungs) If metastatic site(s) is within 2 cm of either kidney, creatinine level must be < 1.5 times upper limit of normal (ULN) If metastatic site(s) is within 2 cm of the liver, bilirubin level must be < 1.5 times ULN Patients with metastatic disease that meets any of the following criteria are excluded: Proposed site(s) of treatment has been previously treated with radiotherapy Metastatic site(s) requires emergent treatment (e.g., spinal cord compression, cauda equina, airway compromise, or life-threatening end-organ dysfunction) Disease that is untreated or previously treated and progressive in the brain Pathologic fracture or impending pathologic fracture at the metastatic site Metastatic site(s) of a disease histology that is known to be sensitive to low doses of radiotherapy (e.g., pure seminoma, lymphoma, or small cell carcinoma) Patients in whom surgery is deemed an appropriate option as standard of care (e.g., isolated lung metastasis from sarcoma or isolated liver metastasis from colon cancer) but who refuse surgical therapy are eligible PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy > 12 weeks as assessed by the consulting radiation oncologist Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of lupus erythematosus or scleroderma No known hypersensitivity to therapeutic radiotherapy No other malignancy within the past 2 years except nonmelanoma skin cancer or in situ malignancies of the cervix, bladder, or head and neck No unrelated systemic illness that, in the judgment of the investigator, would compromise the patient's ability to tolerate study therapy or would likely interfere with study procedures or results Able or likely to adhere to study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 2 weeks since prior and no concurrent chemotherapy Prior or concurrent hormonal agents, including antiandrogens, gonadotropin-releasing hormone agonists, aromatase inhibitors, tamoxifen, or similar agents allowed No change in systemic therapy for 6 weeks before or within 4 weeks after initiating study radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy in Metastatic Cancer<br>Patients undergo hypofractionated highly conformal radiotherapy with helical tomotherapy once every other day over 5 days for a total of 3 fractions. | Other: questionnaire administration<br>* Patients complete a pain assessment questionnaire, Brief Pain Inventory at baseline and at 1 and 3 months after treatment.<br>* Other names: Brief Pain Inventory;Radiation: 3-dimensional conformal radiation therapy<br>* Conformal radiation therapy improves the ability to spare normal tissues.<br>Radiation: hypofractionated radiation therapy<br>* Hypofractionated radiation therapy is delivered to maximize pain relief while minimizing patient impact if life expectancy is short.<br>Radiation: image-guided radiation therapy<br>* Image guided radiation therapy targets the specific site of disease.<br>Radiation: tomotherapy<br>* Tomotherapy is a delivery method which provides megavoltage computed tomography (CT) localization and may provide superior conformality and localization compared to other dynamic intensity modulated radiation therapy techniques.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Local Control (i.e., Complete Response, Partial Response, or Stable Disease) at All Treated Sites of Metastatic Disease | Local control (e.g. absence of local progression) is defined as Complete response (CR), partial response (PR) or stable disease (SD) of the treated site(s). Complete response is the disappearance of the target lesion. Partial response is a >/= 50% decrease in maximal dimension compared to pretreatment imaging. Stable disease does not qualify for CR, PR, or progression.Progression is an interval increase in the maximal dimension of the target lesion. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module. | 9 months, 11 days | 
| Median Time to Local Progression | Interval from initiation of treatment on protocol to symptomatic or radiographic progression. | 6-12 months | 
| 12 Month Local Control in All Sites of Treatment, and at Each Site of Treatment | Local control (e.g. absence of local progression) is defined as Complete response (CR), partial response (PR) or stable disease (SD) of the treated site(s). Complete response is the disappearance of the target lesion. Partial response is a >/= 50% decrease in maximal dimension compared to pretreatment imaging. Stable disease does not qualify for CR, PR, or progression. Progression is an interval increase in the maximal dimension of the target lesion. | 12 months | 
| Interfraction and Intrafraction Motion With Megavoltage Computed Tomography (CT) Based on Sites of Metastasis | Megavoltage localization scans will be obtained and the physician and therapist will evaluate the cone beam image and compare this image to the expected image based on the patient's initial planning CT scan. | One to three months of followup | 
| Pain at Sites of Metastases | Improvement in pain from baseline will be assessed by the Brief Inventory for Pain criteria. | One and three months of follow up | 
| Tumor Doubling Times During Systemic Treatment Compared Between Tumors Untreated With Radiation (Newly Developed Tumors) and Tumors Which Have Received Radiation Therapy | Rate of growth of the composite (total) treated volume (up to four sites) compared to the composite volume of up to four newly identified and untreated prospectively-identified (at the time of systemic progression) metastatic sites. Volume doubling time will be calculated assuming an exponential growth pattern. | Baseline and prior to termination of systemic therapy or protocol withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, recurrent osteosarcoma, recurrent renal cell cancer, stage IV melanoma, unspecified adult solid tumor, protocol specific, recurrent adult soft tissue sarcoma, recurrent uterine sarcoma, stage IV adult soft tissue sarcoma, stage IV uterine sarcoma, ovarian sarcoma, chondrosarcoma, metastatic osteosarcoma, stage IV renal cell cancer, lung metastases, liver metastases, bone metastases