• Late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis or joint stiffness) at 2 years from the start of radiotherapy as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
• Other grade 3-5 adverse events as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
• Pattern of first failure [ Designated as safety issue: No ]
• Time to local failure [ Designated as safety issue: No ]
• Time to regional failure [ Designated as safety issue: No ]
• Time to distant failure [ Designated as safety issue: No ]
• Distant disease-free survival [ Designated as safety issue: No ]
• Disease-free survival [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Time to second primary tumor [ Designated as safety issue: No ]
• Wound complications [ Designated as safety issue: No ]
• Impact of late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years on the clinical measure, Musculoskeletal Tumor Rating Scale (MTRS) [ Designated as safety issue: Yes ]

• Effect of reduced radiation volume using IGRT on late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, and joint stiffness) at 2 years from the start of radiotherapy as measured by CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
• Other grade 3-5 adverse events as measured by CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
• Pattern of first failure, including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression [ Designated as safety issue: No ]
• Time to local failure [ Designated as safety issue: No ]
• Time to regional failure [ Designated as safety issue: No ]
• Time to distant failure [ Designated as safety issue: No ]
• Distant disease-free survival [ Designated as safety issue: No ]
• Disease-free survival [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Time to second primary tumor [ Designated as safety issue: No ]
• Rate of wound complications [ Designated as safety issue: No ]
• Impact of late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years on the clinical measure, Musculoskeletal Tumor Rating Scale (MTRS) [ Designated as safety issue: Yes ]

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 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 (MTRS).

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.

• Lymphedema
• Musculoskeletal Complications
• Radiation Fibrosis
• Radiation Toxicity
• Sarcoma

• Drug: chemotherapy
  Up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy
• Radiation: 3-dimensional conformal radiation therapy
  Performed preoperatively once daily, 5 days a week, for 4½-5 weeks
• Radiation: intensity-modulated radiation therapy
  Performed preoperatively once daily, 5 days a week, for 4½-5 weeks

• Group 1 (closed to accrual as of 01/08/10): Experimental
  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.
  Interventions:

  • Drug: chemotherapy
  • Radiation: 3-dimensional conformal radiation therapy
  • Radiation: intensity-modulated radiation therapy
• Group 2: Experimental
  Patients undergo 3D-CRT or IMRT once daily, 5 days a week, for 5 weeks.
  Interventions:

  • Radiation: 3-dimensional conformal radiation therapy
  • Radiation: intensity-modulated radiation therapy

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*
• AST or ALT ≤ 2 times upper limit of normal*
• Serum creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 55 mL/min*
• LVEF ≥ 50% by 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