Image-Guided Radiation Therapy 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.

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 < 7 mg/dL or > 12.5 mg/dL
• Glucose < 40 mg/dL or > 250 mg/dL
• Magnesium < 0.9 mg/dL or > 3 mg/dL
• Potassium < 3mmol/L or > 6 mmol/L
• Sodium < 130 mmol/L or > 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