2105 - Dosimetric Impact of Online Adaptive Radiotherapy on a Phase II Study of Hypofractionated Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer

R. Mueller¹, C. G. Robinson², S. Waqar³, L. Marut⁴, T. Zhu⁵, E. Laugeman⁶, D. Morgensztern³, R. Govindan³, H. Kim⁷, T. Kim⁸, Y. Huang⁸, P. Samson², and G. R. Vlacich⁹; ¹Washington University School of Medicine in St. Louis, St. Louis, MO, ²Washington University in St Louis, St Louis, MO, ³Washington University School of Medicine, Department of Medicine, Division of Oncology, St. Louis, MO, ⁴Washington University in St. Louis, St. Louis, MO, ⁵Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ⁶Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, ⁷Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, ⁸Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, ⁹Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO

Purpose/Objective(s): Hypofractionation with concurrent chemotherapy for locally advanced non-small cell lung cancer (LA-NSCLC) has historically been limited by toxicity. A Phase II MR-guided radiation therapy (MRgRT) study was designed to improve tolerability and feasibility through periodic adaptation. We assessed if predetermined intermittent online adaptation allows for significant change in target coverage or organ-at-risk (OAR) sparing. Materials/

Methods: Patients with inoperable Stage IIB, IIIA and select IIIB/IIIC LA-NSCLC received MRgRT to 60 Gy in 15 fractions with concurrent carboplatin/paclitaxel and consolidation durvalumab on a phase II institutional trial. Online adaptation was performed on fractions 6, 9 and 12 with contours and plans generated by a rotating doctor-of-the-day. Spinal cord and esophageal constraints were Priority 1, PTV coverage was priority 2, and remaining OAR constraints were priority 3. Acceptable variation on priority 3 OARs was a max dose <105% prescription. Prospective changes in tumor volume and OAR dose were compared between initial and adaptive fractions. Tumor volume was compared on adaptive fractions to retrospective, offline contours performed by a single, experienced physician based on initial contours and plan.
Results: Twenty-six patients were enrolled and completed the course of chemoradiation. Most were male (54%) and stage IIIA (54%). Median combined GTV (primary and nodal volumes) and PTV were 82.7 cc (8.05 to 412.4) and 287.21 cc (47.28 to 808.87), respectively. Median change in combined GTV and PTV between initial and fraction 12 was -7.47 cc (-28.48 to +126.04) and -17.25 cc (-114.23 to +236.37), respectively. Minimum PTV coverage was met in 25 patients (96%) on initial plan and maintained in all but 2 adaptive plans. Per-protocol priority 3 constraints were met and maintained in 3 patients (12%). Priority 3 OAR variance of 63 Gy < 0.5 cc was needed in =1 OAR in 22 patient (85%) initial plans and these were resolved in =1 adaptive plan in 6 patients. Two (8%) patients who met ideal priority 3 constraints on initial plans required max dose variance in =1 adaptive plan. There was a 13% decrease in GTVp volume from initial to fraction 12 plans (p<0.001), mainly driven by tumors > 50 cc (median D -28.3 cc, range: -97.4 to +113.9 vs tumors <50 cc median D -0.13 cc, range: -7.9 to +10.8). There was a 7% and 5% increase in prospective GTVn and PTV volumes, respectively (p<0.001). Retrospective offline contouring resulted in a consistent decrease in GTV/PTV volumes on all adaptive fractions (p<.001).
Conclusion: Prospective online adaptation has limited benefit in accounting for tumor shrinkage or OAR constraint violations in this setting with benefit more likely derived with larger primary tumors. Offline adaptation may better account for tumor response with appropriate frequency to be determined.