Clinical outcomes and toxicity after proton- versus photon-based spatially fractionated radiotherapy for soft-tissue sarcoma: a retrospective cohort
4 affiliations
- 1Department of Radiation Oncology, University of Maryland Medical Center
- 2LifeBridge Health
- 3University of Maryland School of Medicine
- 4Partners in Healthcare Technology, LLC
Abstract
Introduction: Spatially fractionated radiotherapy (SFRT) enables focal dose escalation in bulky/high-grade STS. Proton SFRT, leveraging its Bragg peak, reduces low-dose exposure but may increase proximal skin dose, potentially influencing perioperative wound complications. Comparative data remain limited.
Methods: We retrospectively reviewed 37 high-grade or bulky STS patients (2009–2023) treated with preoperative SFRT (photon or proton GRID/Lattice) followed by conventional fractionated radiotherapy (CFRT) and surgery. Toxicities (including major wound complications per NCIC criteria) and oncologic outcomes were analyzed using Fisher’s exact tests and Kaplan–Meier.
Results: Median follow-up was 40 months. Sixteen patients (43.2%) received proton SFRT; all received CFRT (median: 50.4 Gy). Major wound complications 6/16 (37.5%) proton SFRT vs 8/21 (38.1%) photon SFRT patients, with no significant difference (P = 1.000). Acute grade 2-3 (6/16 vs 11/21) and late (3/16 vs 9/21) toxicities did not differ significantly between modalities; no grade 4 or 5 toxicities occurred. Major pathological response (MPR, ≥80% necrosis) was achieved in 12/35 evaluable patients (34.3%) and was not associated with SFRT type (P = 0.489). In exploratory analysis, MPR was associated with longer disease-free survival (median 80 vs. 27 months, P = 0.014). Proton SFRT plans had significantly higher dose heterogeneity (D90/D10 = 0.038 vs 0.093, P = 0.04).
Discussion: In this largest-to-date retrospective cohort of neoadjuvant proton- versus photon-based SFRT + CFRT for STS, no statistically significant differences in perioperative or skin toxicity were observed, and MPR (≥80% necrosis) occurred in 34.3% of evaluable patients; given the small, non-randomized sample these results should be considered hypothesis-generating.
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BibTeX
@article{olabumuyi2026clinical,
title = {{Clinical outcomes and toxicity after proton- versus photon-based spatially fractionated radiotherapy for soft-tissue sarcoma: a retrospective cohort}},
author = {Adeniyi A. Olabumuyi and Matthew H. Brown and Soha Bazyar and Sina Mossahebi and James W. Snider and Dan Kunaprayoon and Vincent Y. Ng and William F. Regine and Jason K. Molitoris},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1741156},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1741156/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical outcomes and toxicity after proton- versus photon-based spatially fractionated radiotherapy for soft-tissue sarcoma: a retrospective cohort
AU - Adeniyi A. Olabumuyi
AU - Matthew H. Brown
AU - Soha Bazyar
AU - Sina Mossahebi
AU - James W. Snider
AU - Dan Kunaprayoon
AU - Vincent Y. Ng
AU - William F. Regine
AU - Jason K. Molitoris
PY - 2026
DA - 2026/10/28
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1741156
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1741156/full
AB - Introduction: Spatially fractionated radiotherapy (SFRT) enables focal dose escalation in bulky/high-grade STS. Proton SFRT, leveraging its Bragg peak, reduces low-dose exposure but may increase proximal skin dose, potentially influencing perioperative wound complications. Comparative data remain limited. Methods: We retrospectively reviewed 37 high-grade or bulky STS patients (2009–2023) treated with preoperative SFRT (photon or proton GRID/Lattice) followed by conventional fractionated radiotherapy (CFRT) and surgery. Toxicities (including major wound complications per NCIC criteria) and oncologic outcomes were analyzed using Fisher’s exact tests and Kaplan–Meier. Results: Median follow-up was 40 months. Sixteen patients (43.2%) received proton SFRT; all received CFRT (median: 50.4 Gy). Major wound complications 6/16 (37.5%) proton SFRT vs 8/21 (38.1%) photon SFRT patients, with no significant difference (P = 1.000). Acute grade 2-3 (6/16 vs 11/21) and late (3/16 vs 9/21) toxicities did not differ significantly between modalities; no grade 4 or 5 toxicities occurred. Major pathological response (MPR, ≥80% necrosis) was achieved in 12/35 evaluable patients (34.3%) and was not associated with SFRT type (P = 0.489). In exploratory analysis, MPR was associated with longer disease-free survival (median 80 vs. 27 months, P = 0.014). Proton SFRT plans had significantly higher dose heterogeneity (D90/D10 = 0.038 vs 0.093, P = 0.04). Discussion: In this largest-to-date retrospective cohort of neoadjuvant proton- versus photon-based SFRT + CFRT for STS, no statistically significant differences in perioperative or skin toxicity were observed, and MPR (≥80% necrosis) occurred in 34.3% of evaluable patients; given the small, non-randomized sample these results should be considered hypothesis-generating.
SN - 2234-943X
ER -