image-guided radiation therapy in treating patients with primary soft tissue sarcoma of the shoulder, arm, hip, or leg

Conditions: Lymphedema; Musculoskeletal Complications; Radiation Fibrosis; Radiation Toxicity; Sarcoma

Summary: rationale: image-guided radiation therapy uses high-energy x-rays to kill tumor cells. specialized radiation therapy that delivers a lower 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 the side effects and how well image-guided radiation therapy works in treating patients with primary soft tissue sarcoma of the shoulder, arm, hip, or leg.

objectives: primary * to determine the effect of reduced radiation volume using image-guided radiotherapy (igrt) on lymphedema ≥ grade 2, subcutaneous fibrosis, and joint stiffness at 2 years in patients with primary soft tissue sarcoma of the extremity. secondary * to estimate the rates of other grade 3-5 adverse events as measured by common toxicity criteria for adverse effects (ctcae) v3.0. * to determine the pattern of first failure, including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression. * to estimate the rates of local failure, local-regional failure, distant failure, distant disease-free survival, disease-free survival, overall survival, and second primary tumor. * to estimate the rate of wound complications. * to correlate the degree of late radiation morbidity (defined as any lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years with scores on the clinical measure, musculoskeletal tumor rating scale (msts). outline: this is a multicenter study. * neoadjuvant radiotherapy: patients are assigned to 1 of 2 treatment groups (group 1 closed to accrual as of 01/08/10). * group 1 (closed to accrual as of 01/08/10): patients undergo 3-d conformal radiotherapy (3d-crt) or intensity-modulated therapy (imrt) once daily, 5 days a week, for 4½-5 weeks. patients also receive up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy. * group 2: patients undergo 3d-crt or imrt once daily, 5 days a week, for 5 weeks. * surgery: at 4-8 weeks after completion of neoadjuvant radiotherapy, patients undergo surgical resection of the tumor. patients with positive tumor margins (residual tumor) undergo intraoperative radiotherapy boost or proceed to adjuvant radiotherapy within 2 weeks after surgery. * adjuvant radiotherapy: patients undergo either external-beam radiotherapy (ebrt) once daily for 8 fractions or brachytherapy. after completion of study treatment, patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria:
disease characteristics: * histologically confirmed primary soft tissue sarcoma of the upper extremity (including shoulder) or lower extremity (including hip) * incisional or core biopsy required within the past 8 weeks * no histopathological diagnosis of any of the following: * rhabdomyosarcoma * extraosseous primitive neuroectodermal tumor (pnet) * soft tissue ewing sarcoma * osteosarcoma * kaposi sarcoma * angiosarcoma * aggressive fibromatosis (desmoid tumor) * dermatofibrosarcoma protuberans * chondrosarcoma * extraskeletal myxoid chondrosarcoma allowed * tumor must be surgically resectable, as determined by a surgeon within the past 8 weeks * limb-preservation surgery alone would not provide adequate local control, as determined by the surgeon * no sarcoma of the hand, foot, head, neck, or intra-abdominal or retroperitoneal region or body wall * no sarcoma ≥ 32 cm in any direction * no lymph node or distant metastases, according to the following within the past 8 weeks: * history/physical examination, including a detailed description of the location, size, and stage of the sarcoma * mri with contrast of the primary tumor * the maximum dimension of the primary tumor is measured in mri images * ct scan of the chest * multiple pulmonary nodules \< 8 mm without a histological diagnosis detected incidentally on a non-screening ct scan may be allowed * ct scan with contrast of the abdomen and pelvis in patients with intermediate- or high-grade sarcoma of the upper thigh * no recurrent tumor after prior potentially curative therapy patient characteristics: * zubrod performance status 0-1 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 8.0 g/dl (transfusion or other intervention allowed) * bilirubin ≤ 1.5 mg/dl\* * aspartate aminotransferase (ast) or alanine aminotransferase (alt) ≤ 2 times upper limit of normal\* * serum creatinine ≤ 1.6 mg/dl or creatinine clearance ≥ 55 ml/min\* * left ventricular ejection fraction (lvef) ≥ 50% by multiple gated acquisition scan (muga) or echocardiogram\* * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix * no severe, active co-morbidity, including any of the following\*: * unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * transmural myocardial infarction within the past 6 months * acute bacterial infection or fungal infection requiring intravenous antibiotics * acquired immune deficiency syndrome (aids) or immunocompromised patients * hiv testing not required * no nci ctcae v 3.0 grade 3-4 electrolyte abnormalities, including any of the following\*: * calcium \ 12.5 mg/dl * glucose \ 250 mg/dl * magnesium \ 3 mg/dl * potassium \ 6 mmol/l * sodium \ 155 mmol/l note: \*applies to group 1 only, which was closed to accrual as of 01/08/10) prior concurrent therapy: * see disease characteristics * no prior excisional biopsy in which the majority of the tumor (≥ 50%) is removed * no prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields * no other concurrent investigational agents

Keywords: radiation fibrosis radiation toxicity lymphedema musculoskeletal complications stage i adult soft tissue sarcoma stage ii adult soft tissue sarcoma adult extraskeletal chondrosarcoma stage iii adult soft tissue sarcoma