Exhibit Hall | Forum 2
Purpose: A phase I trial(NCT02608385) combining stereotactic body radiotherapy(SBRT), 45Gy in 3 fractions(fx), with pembrolizumab was safe with promising outcomes. A subsequent planning study suggested feasibility of ultra-high SBRT dose(90Gy in 3fx), while respecting organ-at-risk(OAR) tolerances. Online adaptation for interfractional changes may enhance safety/efficacy. This work develops a CBCT-guided adaptive radiotherapy paradigm for isotoxic treatment with ultra-high doses using retrospective data and simulated online adaptation.
Methods: Data from 15 subjects of the phase I trial were used. Disease sites: liver(n=8), pelvis(n=4), abdomen(n=2), lung(n=1). Gross tumor volumes(GTVs) averaged 177cc (67-390cc). OAR expansions, based on tolerances and achievable dose gradients, were cropped from GTV to generate a SubGTV, which was prescribed ultra-high dose(90Gy in 3fx), adapting to changing anatomy. Initial 6-arc VMAT plans used the Ethos clinical-goals-based automated plan optimization. Critical OAR Dmax goals received high priority. GTV coverage(V90Gy) and OAR volumetric constraints received medium priority. SubGTVcore was defined with further contraction away from OARs with low priority goals ensuring centralized GTV hot spots. For a subset of 9 patients(3 liver, 2 abdomen, 3 pelvis, 1 lung), online adaptation using clinical CBCTs was simulated (anatomy recontoured, plan reoptimized/evaluated) for comparison of adapted(ADP) vs. scheduled(SCH) plans.
Results: All initial plan OAR goals were satisfied. Average GTV V90Gy was 80.8cc/57.3% (53.8-144.5cc/24.4-99.1%). In online adaptive sessions, the ADP plan was preferred over SCH plan in 8/9 cases. ADP plans had superior coverage(average GTV V90Gy of 86.3cc(ADP) vs. 77.9cc(SCH)). ADP plans nearly always met OAR tolerances (one minor exception: skin D0.03cc (tolerance 11.0Gy/fx) was 11.5Gy(ADP) vs. 11.9Gy(SCH)). SCH plans often exceeded OAR tolerances: violations to bowel(n=2), stomach(n=3), duodenum(n=1), IVC(n=1), skin(n=3) and bone(n=2).
Conclusion: A true isotoxic radiotherapy paradigm maximizing ablative target dose while respecting OAR tolerances using CBCT-guided online adaptation is developed. As adaptive technologies evolve, such approaches may help maximize the therapeutic index for radiotherapy.
Funding Support, Disclosures, and Conflict of Interest: G. Redler receives grant funding from Varian Medical Systems.
Tolerance Doses, Treatment Planning, Stereotactic Radiosurgery