Relationship Between Spatial Distribution Tumor Location and Dosimetric Outcomes in Patients Receiving Definitive Proton Therapy for Locally Advanced Lung Cancer

Abstract

Intensity Modulated Proton Therapy with Pencil Beam Scanning (IMPT/PBS) has been postulated to have dosimetric benefits, especially for sparing of normal tissues in the treatment of thoracic malignancies. Distinguishing which patients may benefit most from IMPT/PBS treatment has important implications when counseling patients on optimal treatment modality, treatment approval turnaround time, and potential toxicities. We herein present a single institution experience assessing the relationship between spatial distribution of tumor location and dosimetric outcomes in patients receiving definitive IMPT/PBS for locally advanced lung cancer. Consecutive patients treated with IMPT/PBS for locally advanced lung cancer from 2016-2022 at an academic proton center were retrospectively analyzed. Treatment, tumor volume, and patient characteristics were collected. Distance from the posterior pleura to the anterior-most portion of the clinical tumor volume (CTV) of the tumor was measured. A ratio of this distance to the pleura-to-pleura distance at that corresponding lung level was used to classify anterior (>0.7) versus posterior tumors. Dosimetric details including beam angles, dose-volume parameters for the ipsilateral, contralateral, total lung and heart for each patient were recorded. Statistical differences between groups were determined using Wilcoxon Signed Rank test. Pearson's correlation coefficient was used to determine impact of CTV volume and the anterior-most distance of CTV on dosimetric parameters. Fifty-eight patients treated for Stage IIB-IIIC locally advanced lung cancer with a median CTV volume of 258 cc's were identified and included in this retrospective study. Median age was 68 years and there was an equal distribution of male (29, 50%) and female patients (29, 50%) as well as anterior (>0.7) and posterior lying tumors in this cohort. The majority of patients were white (42, 72%) Forty patients (69%) had right sided lung tumors. Median cumulative dose was 61.2 Gy (range 59.4-70 Gy) while median dose per fraction was 2 Gy (range 1.8-2 Gy). When compared to anterior tumors, posterior tumors had a lower Lung V20 (19.1% vs 21.6%, p = 0.1,), V5 (27.6% vs 32.4%, p = 0.03), Mean Lung (9.9 Gy vs 11.7 Gy, p = 0.04), Mean Heart (4.8 Gy vs 6.3 Gy, p = 0.1), and Heart V50 (3.1% vs. 4.6%, p = 0.15). Anterior-most distance of CTV from the posterior pleura was positively correlated with Lung V20 (r = .435, p = 0.001), Lung V5 (r = .390, p = 0.002), Mean Lung (r = .479, p = 0.001), Mean Heart (r = .304, p = 0.020), and Heart V50 (r = .322, p = 0.014). CTV volume was also significantly positively correlated (p <.01) with these parameters. Spatial distribution and treatment volume size are predictive of dosimetric outcomes for locally advanced lung cancer. Posterior lying tumors may derive greater dosimetric advantage when compared to anterior lesions when utilizing IMPT/PBS.