Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2

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

Treatments: Drug: Chemotherapy; Procedure: Surgery; Radiation: Radiation therapy

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00589121

CDR0000582196

RTOG-0630

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 98 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 < 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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98 participants in 2 patient groups

Cohort A - Chemotherapy

Experimental group

Description:

Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Treatment:

Radiation: Radiation therapy

Drug: Chemotherapy

Procedure: Surgery

Cohort B - No Chemotherapy

Experimental group

Description:

Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Treatment:

Radiation: Radiation therapy

Procedure: Surgery