A Prospective Randomized Trial of Pre-Operative IMRT+Surgery Versus Surgery Alone For Primary Retroperitoneal Sarcoma

Primary Objective: To ascertain whether patients with completely resected (R0 + R1), primary retroperitoneal sarcoma who are randomized to pre-operative IMRT and surgery have a longer recurrence-free survival compared to patients randomized to treatment with surgery alone.

Secondary Objectives: To ascertain whether patients with completely resected (R0 + R1), primary retroperitoneal sarcoma randomized to pre-operative IMRT and surgery have longer overall survival compared to patients randomized to treatment with surgery alone.

• To compare the resectability rate between the two arms
• Determine the variability of NMR biochemical profiles and the variability of expression for genes/proteins involved in adipocyte differentiation, cell cycle control and apoptosis within different regions of the primary retroperitoneal sarcoma in patients treated with surgery alone and pre-operative radiotherapy.
• Analyze NMR biochemical patterns and expression patterns for genes/proteins involved in adipocyte differentiation, cell cycle control and apoptosis to identify markers that can provide an objective measure of sarcoma differentiation, proliferation, and apoptosis.
• Predict the response of sarcoma to radiation therapy and the risk of local recurrence, based on data derived from NMR biochemical and gene/protein expression patterns in patient tumors that recurred compared to those without recurrence.
• Determine if diffusion-weighted MRI early in course of radiation therapy can predict the ultimate pathologic response of sarcoma following resection and the risk of local recurrence.
• Analyze plasma levels of VEGF, FGF, Ang-1, Ang-2 and endostatin prior to and following therapy and correlate with treatment response, local and distant recurrence.

Inclusion criteria

• Patients with primary retroperitoneal/pelvic soft tissue sarcoma.
• Gross total resection (RO or R1) must be feasible.
• No prior chemotherapy, immunotherapy or radiotherapy is allowable.
• Patients should be over 18 years of age and capable of providing informed consent indicating awareness of the investigational nature of this trial, in keeping with hospital policy.
• Karnofsky performance status of >= 70 %
• No other concurrent chemotherapy, immunotherapy or radiotherapy is allowable.
• Adequate organ function defined as follows: absolute granulocytes >= 1,500/mm 3, platelets >= 150,000/mm 3, serum bilirubin <= 1.5 mg/dl, serum creatinine <= 1.5 mg/dl.
• Written informed consent (study specific) must be obtained from each patient prior to entering the study.
• Patients should be willing to be followed at Memorial Sloan-Kettering Cancer Center during the course of treatment and follow-up.
• Patients must be able to get IMRT radiotherapy at Memorial Sloan-Kettering Cancer Center

Exclusion criteria

• Patients presenting with primary non-retroperitoneal soft tissue sarcoma or recurrent retroperitoneal sarcoma.
• Patients who are deemed unresectable by clinical/imaging criteria.
• Patients with histologic diagnosis of gastrointestinal stromal sarcoma, desmoplastic small round cell tumor, desmoid, Ewing's sarcoma, PNET, adenosarcoma, granular cell tumor, mesothelioma or rhabdomyosarcoma are excluded from the study.
• Patients with known metastatic disease, or those with radiologically evident metastases.
• Patients with clinically significant heart disease (NYHA Class III/IV), history of active angina or myocardial infarction within 6 months, history of significant ventricular arrhythmia requiring medication with antiarrhythmics or a history of clinically significant conduction system abnormality. Patients with any of the above conditions who are seen by a cardiologist at MSKCC and are found to be an acceptable risk for surgery will be allowed to participate in this study.
• Patients with any active concurrent malignancy other than non-melanoma skin cancers or carcinoma-in situ of the cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be eligible.
• Women who are pregnant.
• Patients currently participating in other clinical trials the requirements of which may preclude their complete involvement in this study
• Patients with serious intercurrent infections or non-malignant uncontrolled illnesses