Safety of Pre‐Operative Radiotherapy Combined With Intraoperative Radiotherapy for Retroperitoneal Sarcoma

BACKGROUND: Local recurrence in retroperitoneal sarcomas (RPS) with high-risk surgical margins remains a significant clinical challenge. Previous randomized trials have evaluated neoadjuvant external beam radiation therapy (EBRT) without intraoperative radiotherapy (IORT). Following multidisciplinary consensus, our institution employs neoadjuvant EBRT combined with IORT for the management of RPS. This study evaluates the safety and feasibility of this combined strategy. METHODS: A single-institution retrospective review was conducted of patients with RPS treated with neoadjuvant EBRT, surgical resection, and IORT between June 1, 2004, and June 30th, 2024. Postoperative complications and 90-day readmission rates were identified through electronic medical records, pathology reports, and death registries. Postoperative complications were graded by the Clavien-Dindo (CD) classification system. RESULTS: Twenty-eight patients underwent neoadjuvant EBRT followed by resection with IORT. The median age was 66 years (IQR 59.6-69.6 years) and 57% were female. Twenty-three patients (83%) were treated for primary disease, and five patients (17%) were being treated for recurrent disease, with one patient undergoing treatment for recurrence twice. Median number of neoadjuvant EBRT cycles was 25 (IQR 25). Patients received a median neoadjuvant EBRT dose of 4,500 cGy (IQR 45-4,500 cGy) and median IORT dose of 1375 cGy (IQR 1250-1500 cGy). The median tumor size was 11.9 cm (IQR 7-22.6 cm) and most commonly leiomyosarcoma (42%) and well-differentiated liposarcoma (29%). Multi-visceral resection was required in 71% of cases, most often involving the kidney (64%), adrenal gland (39%), and gallbladder (32%). Complete (R0) resection was achieved in 14 (54%) patients, while incomplete (R1) resection was achieved in 12 (46%) patients. Median hospital stay was 7 days (IQR 6-9 days). Postoperative morbidity occurred in 78% of patients, with 25% experiencing major (Clavien-Dindo III-V) complications. There was one mortality within 90 days of index operation. CONCLUSION: Neoadjuvant EBRT followed by resection with IORT is associated with frequent low-grade complications and a 25% rate of major complications, similar to neoadjuvant EBRT alone.