Toxicity and Survival After Intensity-Modulated Proton Therapy Versus Passive Scattering Proton Therapy for NSCLC

Abstract

Objective: Although intensity-modulated radiation therapy (IMPT) is dosimetrically superior to passive scattering proton therapy (PSPT) for locally advanced NSCLC (LA-NSCLC), direct comparisons of clinical outcomes are lacking. Here, we compare toxicity profiles and clinical outcomes after IMPT versus PSPT for LA-NSCLC.

Methods: This is a nonrandomized, comparative study of two independent cohorts with LA-NSCLC (stage II-IIIB, stage IV with solitary brain metastasis) treated with concurrent chemotherapy and proton beam therapy. Toxicity (Common Terminology Criteria for Adverse Events version 4.0) and outcomes were prospectively collected as part of a clinical trial (ClinicalTrials.gov identifier NCT00915005) or prospective registry (ClinicalTrials.gov identifier NCT00991094).

Results: Of 139 patients, 86 (62%) received PSPT and 53 (38%) IMPT; median follow-up times were 23.9 and 29.0 months, respectively. IMPT delivered lower mean radiation doses to the lungs (PSPT 16.0 Gy versus IMPT 13.0 Gy, p < 0.001), heart (10.7 Gy versus 6.6 Gy, p = 0.004), and esophagus (27.4 Gy versus 21.8 Gy, p = 0.005). Consequently, the IMPT cohort had lower rates of grade 3 or higher pulmonary (17% versus 2%, p = 0.005) and cardiac (11% versus 0%, p = 0.01) toxicities. Six patients (7%) with PSPT and zero patients (0%) with IMPT experienced grade 4 or 5 toxicity. Lower rates of pulmonary (28% versus 3%, p = 0.006) and cardiac (14% versus 0%, p = 0.05) toxicities were observed in the IMPT cohort even after propensity score matching for baseline imbalances. There was also a trend toward longer median overall survival in the IMPT group (23.9 mo versus 36.2 mo, p = 0.09). No difference was found in the 3-year rates of local (25% versus 20%, p = 0.44), local-regional (29% versus 36%, p = 0.56) and distant (52% versus 51%, p = 0.71) recurrences.

Conclusions: IMPT is associated with lower radiation doses to the lung, heart, and esophagus, and lower rates of grade 3 or higher cardiopulmonary toxicity; additional clinical studies will be needed to assess the potential differences in survival between the two techniques.

Keywords: Cardiac toxicity; Esophageal toxicity; IMPT; Lung cancer; Proton beam therapy; Pulmonary toxicity.

Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. CONSORT diagram.

This study was a comparison of 86 patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with passive scattering proton therapy (PSPT) as part of a randomized clinical trial (clinicaltrials.gov NCT00915005). The intensity-modulated proton therapy (IMPT) group included 51 patients with LA-NSCLC who received IMPT at MD Anderson while enrolled in the prospective patient registry Normal Tissue Toxicity for Proton Therapy (clinicaltrial.gov NCT00991094), plus 2 patients from the NCT00915005 who ultimately received IMPT treatment.

Figure 2.. Dosimetric analysis.

Mean radiation dose to critical organs at risk from passive scattering proton therapy (PSPT) and intensity-modulated proton therapy (IMPT) (A). Box plots of dose-volume histogram (DVH) data on radiation dose and organ volume for the lung (B), heart (C) and esophagus (D). Whiskers indicate 1.5 times the interquartile range above and below the median; dots represent outliers. P

Figure 3.. Toxicity profiles.

Rates of grade 2 (yellow) and grade ≥3 (blue) toxicity to critical organs at risk for patients treated with passive scattering proton therapy (PSPT) or intensity-modulated proton therapy (IMPT). The P values above each set of bars correspond to differences in the rates of grade ≥3 toxicity only. P < 0.05 was the threshold for statistical significance.

Figure 4.. Disease Control and Survival Analyses.

No differences were found between treatment groups in local failure-free survival (A), local-regional failure-free survival (B), distant failure-free survival (C), or overall survival (D). PSPT, passive scattering proton therapy; IMPT, intensity-modulated proton therapy.