3055 - Promising Pathologic Response of Spatially Fractionated Radiotherapy Preceding Standard Neoadjuvant Conventionally Fractionated Radiotherapy in Aggressive Soft Tissue Sarcoma

A. A. Olabumuyi¹, M. H. Brown¹, S. Bazyar¹, D. Kunaprayoon¹, V. Ng², W. F. Regine Jr¹, and J. K. Molitoris¹; ¹Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, ²University of Maryland School of Medicine, Baltimore, MD

Purpose/Objective(s): Spatially fractionated radiotherapy (SFRT) offers a safe dose-escalation method. Given the radioresistant nature and substantial tumor burden in STS, this method complements standard fractionated radiotherapy, potentially improving local control rates. Our institution adopts a standard practice involving a single SFRT fraction before neoadjuvant conventional fractionated radiotherapy (CFRT) in aggressive STS. The study aims to assess clinical outcomes in 37 patients following this regimen. Materials/

Methods: A single-institution retrospective (2009-2023) IRB-approved analysis was conducted of all patients with aggressive STS who received SFRT protocol (GRID or Lattice). Descriptive statistics covered patient and treatment characteristics, dosimetric parameters, surgical margins, pCR (defined as necrosis = 80%), local recurrence, disease progression, and major wound complications. Crosstabulations analyzed the association between pCR and photon vs. proton SFRT using Fisher’s exact test. Disease-free survival (DFS) and overall survival (OS) curves were generated and analyzed with Kaplan-Meier and log-rank test, respectively. Cox-proportional hazards models were used for multivariable analysis of DFS. Major wound complications per NCIC trial were assessed.
Results: Mean age of 57.03 ± 17.4 years; 22 (59.5%) male; 15 (40.5%) female; 21 (56.8%) white; ECOG status 0 in 27 (73%). One patient received a 12Gy lattice dose, while 36 received 15Gy GRID dose. Twenty (54.1%) received photon SFRT, and 17 (45.9%) received proton SFRT. Median CFRT dose 50.4 Gy (range 45 Gy – 61.33 Gy). All 37 patients underwent surgery following SFRT and CFRT. Median largest pathological dimension 13 cm (range 5.9-32 cm). Negative surgical margin was achieved in 86.4%. pCR was 32.4%, with no difference between proton or photon SFRT (p = 0.476). Median follow-up was 40 months. Local recurrence in 18.9%, any disease progression in 45.9%. Median DFS was 47 months (5-year DFS 46.7%), median OS was 96 months (5-year OS 67.6%). Patients with pCR had better DFS (mean 85 vs. 36 months, p = 0.012). Cox regression showed gender, age, tumor grade, ypT stage, and residual tumor size or location were not confounding factors for DFS. Mean OS of patients with pCR was longer (110 vs. 59 months), but not statistically significant (p = 0.161). Post-surgical major wound complications reported in 14 (37.8%) patients.
Conclusion: SFRT preceding neoadjuvant CFRT in aggressive STS achieved favorable surgical margins and higher pCR rate (32.4%) than RTOG 0630 (19.4%) and 9514 (27.5%). This regimen exhibited favorable DFS with wound complication rates (37.8%) comparable to preoperative arm of NCIC (35%) and RTOG 0630 (36.6%). Longer follow-up with a larger patient cohort is essential for a comprehensive evaluation.