Neoadjuvant Short-course Hypofractionated PBT for Non-metastatic RPS

PROTONS-RPS: a Phase II Non-Randomized Open-label Single-arm Trial Of Neoadjuvant Short-course Hypofractionated Proton Beam Therapy for Non-metastatic RetroPeritoneal Sarcoma

The investigators' study titled "PROTONS-RPS: a Phase II non-Randomized Open-label single-arm Trial Of Neoadjuvant Short-course hypofractionated proton beam therapy for non-metastatic RetroPeritoneal Sarcoma" is a phase II trial evaluating the safety and efficacy of hypofractionated proton beam therapy (H-PBT) in the neoadjuvant (NA) setting for patients with non-metastatic retroperitoneal sarcoma (RPS) planned for surgical resection. This trial will include adult patients with resectable RPS.

The investigators' primary outcome is overall complication rate after treatment with NA H-PBT and surgical resection based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.2 Secondary objectives include evaluating the acute toxicity of H-PBT prior to surgical resection, rate of progression between diagnosis and definitive resection, early post-operative complication rate after resection of RPS in patients who received NA H-PBT, and local recurrence-free survival at 1 and 2 years. A priori subset analyses will be conducted for patients with well-differentiated and dedifferentiated liposarcoma.

The investigators plan to accrue a minimum of 44 patients to evaluate the investigators' primary outcome. Treatment will be 5 doses of H-PBT including a simultaneous integrated boost to at-risk margins followed by surgical resection after 4-6 weeks. Patients will be followed in the post-operative setting according to standard of care surveillance for RPS.

Inclusion Criteria:

• Adult patients (≥18 years of age)
• Patients with primary non-recurrent retroperitoneal sarcoma
• Calculated creatinine clearance ≥50 mL/min and functional contralateral kidney based on nuclear medicine renal scan
• Normal bone marrow function (WBC ≥ 4 x109 /L)
• Eastern Cooperative Oncology Group status ≤ 2
• Cardiac function ≤ New York Heart Association class II
• Proton beam therapy approved by insurance (including Medicare/Medicaid)

Exclusion Criteria:

• Evidence of metastatic disease on staging CT of chest/abdomen/pelvis
• History of abdominal or pelvic radiation therapy
• Inability to tolerate supine position for duration of PBT simulation or treatment
• Tumor originating from gastrointestinal or gynecologic organs
• Specific sarcoma histologies including osteosarcoma, desmoid tumors, chondrosarcoma arising from vertebrae or pelvic bones, embryonal rhabdomyosarcoma
• Tumor extending into femoral or obturator canal
• History of systemic lupus erythematosus or ulcerative colitis
• Genetic syndrome with radiation-associated tumorigenicity (i.e.: Li-Fraumeni)
• Presence of clinically significant ascites
• Co-existing malignancy or treated malignancy in the last 2 years expected to limit life expectancy; does not include completely resected cutaneous basal cell carcinoma, squamous cell carcinoma, in situ breast or cervical malignancies, or other pathologies at the discretion of the investigators.