1149 - Personalized Novel Isotoxic Hypofractionated Adaptive Radiotherapy for Locally Advanced Lung Cancer

Purpose/Objective(s): Standard treatment for locally advanced (LA) lung cancer is surgery or concurrent chemoradiotherapy (CRT), but many patients are ineligible due to co-morbidities. Sequential radiation (RT) and chemotherapy offers lower local control (LC) rates. Dose escalation and hypofractionated RT (HFRT) are emerging alternatives (Westover et al). Across 18 phase I/II HFRT trials, dose/fractionation varied, median PFS was poor (10-25 months), and rates of Grade 3 esophagitis (0.0-23.8%) and pneumonitis (0.0-11.8%) were high (Said et al). We hypothesize that online adaptive RT will enable isotoxic HFRT while improving target coverage with a novel approach.

Materials/Methods: Retrospective clinical data of 90 online adaptive RT (oART) sessions for LA lung cancer patients (n=6) treated at our center were analyzed. oART hybrid coverage required daily physicist and weekly physician presence (daily offline physician review). The oART process entailed image acquisition, patient modeling, plan generation/selection, verification with IGRT matching CBCT to CBCT, and treatment delivery. All treatment courses consisted of 15 fractions (Fx). IGTV45Gy (3Gy/Fx) structures are rigidly propagated and aligned. Critical OARs are recontoured on daily anatomy and the IGTV60 (4Gy/Fx) simultaneously integrated boost is adapted daily by subtracting these critical OARs (plus margin) from the IGTV45 volume to allow isotoxic dose delivery. Patient characteristics, critical OAR D_0.03cc, target V_60Gy and D_90%, as well as toxicities (CTCAE V5) were collected.

Results: Patients had Stage II-IV lung cancer with at least one mediastinal target and were started on prophylactic sucralfate and pantoprazole from Fx 1 until 2 weeks post-treatment. No acute G3 Esophagitis or G3 Pneumonitis events occurred, but all patients experienced G1-2 esophagitis. 72% of Fx were led by physicists. Average time per Fx was 29.04 (± 6.57) minutes. The adapted plan improved IGTV60 V_60Gy by 7.8% (± 10.3%) and D_90% by 2.3% (± 4.4%) while also decreasing esophagus D_0.03cc by 5.9% (± 8.1%) and proximal bronchial tree (PBT) D_0.03cc by 7.3% (± 5.8%). Additional results are summarized in Table 1. Adapted plan was selected for treatment in all 90 Fx.

Conclusion: Our data demonstrates a novel isotoxic approach to HFRT that also maximizes target dose via daily oART. oART improves target dose by 7.8% while decreasing critical OAR dose by 5.9% (esophagus) and 7.3% (PBT) on average. The treatment is well tolerated with no acute G3 toxicities. Long-term follow-up is needed to assess LC and long-term toxicities.