243 - Long-Term Outcomes of a Prospective Randomized Trial of Passive Scattering Proton Therapy vs. Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

T. Su¹, J. J. Lee², Q. N. Nguyen³, S. H. Lin³, J. Heymach⁴, X. Zhang⁵, J. Y. Chang³, C. Lu¹, G. R. Blumenschein⁴, F. V. Fossella⁴, A. A. Vaporciyan⁶, S. G. Swisher⁶, M. S. OReilly³, R. Mohan⁵, and Z. Liao¹; ¹The University of Texas MD Anderson Cancer Center, Houston, TX, ²MD Anderson Cancer Center, Houston, TX, ³Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): We report long-term outcomes from the first prospective randomized trial of passive scattering proton therapy (PSPT) vs intensity-modulated photon radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). Materials/

Methods: Eligible patients had stage IIB–IIIB NSCLC (or stage IV with single brain metastasis or recurrent lung or mediastinal disease after surgery) suitable for concurrent chemoradiation therapy (dose 60–74 Gy). Primary endpoints were (1) survival without grade 3 treatment-related pneumonitis, and (2) local recurrence-free survival (LRFS). Enrollment was completed in 2014.
Results: Bayesian adaptive randomization was used to allocate patients to IMRT (n=105) or PSPT (n=76). However, only 92 patients in the IMRT and 57 in the PSPT group received treatment according to randomization, and 35 patients (16 in IMRT and 19 in PSPT) crossed over. Median follow-up time for the entire group was 27.2 months (range 0.33–149) [IMRT 28.9 months (range 0.33–142) and PSPT 24.4 months [range 0.6–149)]. For surviving patients, the median follow-up time was 69.7 months (range 12.6–115.7 months). At the last update [March 2024], no differences were present in local failure (21 of 92 IMRT [22.8%] vs. 14 of 57 PSPT [24.6%]; P=0.965). Grade 3 RP may have been more prevalent in the PSPT group (9 of 92 [9.8%] vs. 13 of 57 [22.8%]; P=0.052), but the IMRT group had 2 cases of grade 5 RP. Grade =2 esophageal adverse events were noted in 44 of 92 (47.8%) in the IMRT group compared with 37 of 57 (64.9%) in the PSPT group (P=0.062). Treatment-related cardiac adverse events were noted in 28 of 92 IMRT patients (30.4%) vs 18 of 57 (31.6%) PSPT (P=0.99). Overall survival (OS) rates for the entire group were 40.0% at 3 years, 28.9% at 5 years, and 10.0% at 10 years; corresponding LRFS rates were 33.9%, 25.1%, and 8.82%; distant metastasis-free survival rates 27.9%, 19.8%, and 5.83%; and progression-free survival rates 22.4%, 17.6%, 6.67%. For the PSPT group, OS rates were 36.8% at 3 years, 22.7% at 5 years, and 3.4% at 10%; median OS time was 24.5 months (95% CI 16.6–36.8). By comparison, for the IMRT group, OS rates were 43.01% at 3 years, 33.10% at 5 years, and 14.55% at 10 years; median OS time was 29.5 months (95% CI 25.3–53.6) (P=0.074). Median PFS time was 9.85 months (95% CI 7.53–17.5) in the IMRT group and 9.43 months (95% CI 5.37–19.2) in the PSPT group (P=0.35). Median LRFS time was 21.7 months (95% CI 14.7–35.0) in the IMRT group and 17.2 months (95% CI 11.0–26.6) in the PSPT group (P=0.12). Median DMFS time was 16.8 months (95% CI 9.03–25.9) in the IMRT group and 10.4 months (95% CI 6.40–24.4) in the PSPT group (P=0.23).
Conclusion: Long-term outcomes of this study are consistent with those in the original trial report, in that neither primary endpoint was different between treatment groups. [Trial registration number: NCT00915005]