277 - Feasibility, Safety and Patient Reported Early Clinical Outcomes of Spatially Fractionated Radiotherapy of Unresectable Bulky Tumors Followed by SBRT Delivery

Purpose/Objective(s): Highly heterogenous sieve-like dose distribution via spatially fractionated radiotherapy (SFRT) to large and bulky tumors (= 6 cm) could enhance tumor cells kill via both direct/indirect cell kill mechanisms. Adding highly conformal SBRT dose post-SFRT could further enhance therapeutic ratio, reduce tumor burden, and pain relief. We present our novel treatment scheme of SBRT to large and bulky unresectable tumors immediately post-SFRT.

Materials/Methods: Utilizing a same day image-guided MLC-based SFRT, we have treated 11 select extracranial patients with large and bulky unresectable tumors of different histology using single-dose of 15 Gy (6/10MV beam, AcurosXB algorithm). These patients also received highly conformal VMAT SBRT treatment (6MV-FFF, 30-35 Gy in 5 fractions) every other day, 2-3 days post-SFRT. Average SFRT tumor size (GTV) was 354.4 cc, maximum 871.2 cc. SBRT plans were generated for 5 mm planning target volume (PTV) margin around GTV, resulting large PTV: 683.5+/-434.8 (144.5–1361.0) cc. For more accurate dose assessment, a novel voxelized spatial biological effective dose (s-BED) method was developed that combines both treatments and provided a composite s-BED; a/ß = 10 Gy (tumor) and 3 Gy (normal tissues). Dose to organs-at-risk (OAR) was evaluated via spatial EQD2 script. Treatment delivery efficiency & accuracy was assessed. To assess tumor response, pain control, and radiation induced toxicity, patients underwent follow up exams and imaging study in 3-month intervals.

Results: The SFRT plans had average peak-to-valley-dose ratio = GTVD10%÷GTVD90%, GTV(V7.5Gy) and mean GTV dose were 3.0, 50.5%, and 7.8 Gy. For highly conformal SBRT plans (conformity index = 1.04+/-0.03), mean and maximum s-BED dose to PTV were 64.1+/-10.7 (52.4–92.5) Gy and 94.2+/-10.9 (79.8–119.7) Gy, enhancing target dose via SBRT. EQD2 maximum and 1 cc of skin doses were 61.9 Gy and 39.5 Gy; other adjacent OAR were spared: EQD2 maximum dose to spinal cord (14.6 Gy), esophagus (45.1 Gy), and small bowel (71.9 Gy). Independent Monte Carlo second check for both SFRT and SBRT plans agreed within ±3.0% of AcurosXB dose. Average patient-specific QA result was 97.8 % for 2%/2mm gamma criteria. Both SFRT and SBRT IGRT treatments were delivered in <15 min via 6DOF couch corrections. Sarcoma was the common treated histology, seen in 4 (40%) patients. Median follow-up was 3 months (range 3-9 months). One patient lost to follow up. Of the 10 patients assessed 5 (50%) demonstrated local tumor control on follow-up imaging, and 7 (70%) reported clinical pain relief. No patient reported grade 2+ toxicities.

Conclusion: Our novel and clinically useful SFRT plus SBRT scheme provided short course of rapid, safe, and effective treatment option for select patients with unresectable larger tumors including deep-seated bulky masses while adequately sparing adjacent OAR. Longer clinical follow up result with larger cohort is warranted. Adapting SBRT fractions for anatomical changes post-SFRT delivery is underway.