Highs and Lows of Spatially Fractionated Radiation Therapy: Dosimetry and Clinical Outcomes.

Objectives: Spatially fractionated radiation therapy (SFRT) intentionally delivers a heterogeneous dose distribution characterized by alternating regions of high and low doses throughout a tumor. This modality may enhance response to subsequent whole tumor radiation in bulky and radioresistant lesions that are historically less responsive to conventional radiation doses alone. The current study presents a single institution experience with modern era SFRT using predominantly a volumetric modulated arc therapy (VMAT) lattice technique.

Methods: Patients treated with SFRT between 10/2019 and 6/2022 were included for analysis. Patient characteristics, tumor characteristics, and dosimetric parameters were collected retrospectively as part of an institutional review board approved registry and protocol. Descriptive statistics were used to collate patient data and Kaplan Meier analysis were generated for overall survival and local control. Univariate analyses were used to investigate factors associated with outcomes.

Results: A total of 176 patients with 186 sites treated were included. Median age was 64 and the most commonly treated histologies were non-small cell lung cancer and sarcoma. The most common SFRT dose was 20 Gy in 1 fraction with 88% of patients receiving follow-up whole tumor radiotherapy to a median EQD2 dose of 32.5 Gy (α/β=10). Median gross tumor volume (GTV) was 480.5 cc (7.8-10,897.8). Median follow-up was 322 days with 1 year overall survival 37% and 1 year local control 81%. Local control was available in 138 treated sites (131 patients. SFRT factors including dose to 10% (D10%), dose to 90% (D90%), equivalent uniform dose, and mean dose were highly predictive of local control. Grade 3 toxicity occurred in 9 patients. All of these patients received follow-up whole tumor radiation and at least two of these were attributable to unexpected rapid regression of tumor.

Conclusions: SFRT is a promising technique that appears to confer good local control across a disparate group of patients with bulky and radioresistant tumors. Dosimetric parameters of SFRT treatment plans may be independent predictors of local control. Further investigation is warranted as are prospective trials to evaluate the role of SFRT in both the palliative and definitive setting.