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. 2025 Jun 1;122(2):313-324.
doi: 10.1016/j.ijrobp.2024.12.036. Epub 2025 Jan 10.

Proton Radiotherapy Significantly Reduces Pneumonia in Patients With Esophageal Cancer

Mark L Frederiks  1 , Boudewijn van Etten  2 , Wendy Kelder  3 , Margriet Dieters  4 , Jannet C Beukema  4 , Charlotte IJsbrandy  4 , Jacco J de Haan  5 , Erik W Korevaar  4 , Jan Willem Haveman  2 , Ewoud Schuit  6 , Peter van Luijk  4 , Johannes A Langendijk  4 , Christina T Muijs  4
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Free article

Proton Radiotherapy Significantly Reduces Pneumonia in Patients With Esophageal Cancer

Mark L Frederiks et al. Int J Radiat Oncol Biol Phys. .
Free article

Abstract

Purpose: Neoadjuvant chemoradiation therapy (RT) (nCRT) followed by surgical resection is the current standard of care for patients with esophageal cancer (EC). This treatment is associated with a variety of complications, with pneumonia being the most common. We hypothesized that proton RT (PRT) can significantly reduce the incidence of pneumonia compared with photon RT (PhRT).

Methods and materials: We performed an analysis on a prospective cohort of patients with EC who completed nCRT with PRT or PhRT and underwent esophagectomy between October 2014 and June 2022. Multivariable logistic regression was used to analyze the effect of the RT technique on pneumonia while correcting for confounders. To access the dose-effect relationships, dose-volume histogram parameters of the lungs and the heart were analyzed using a principal component (PC) analysis.

Results: We included 313 patients, of whom 28% developed pneumonia. The incidence was lower after PRT compared with PhRT (12% vs 32%, P < .01). PRT was associated with a significant reduction of the incidence of pneumonia (odds ratio [OR], 0.33; 95% CI, 0.14-0.72; P = .01), even when correcting for surgical approach and planning target volume size. Three PCs were identified: PC1: associated with the mean dose in the heart and lungs, PC2: associated with the distribution of dose between the lungs and the heart, and PC3: associated with the volume receiving a low dose (≤20 Gy). If the dose-related variables were replaced by the PCs, PC1 (OR, 1.1; 95% CI, 1.02-1.22) and PC3 (OR, 1.27; 95% CI, 1.06-1.53) were significantly associated with pneumonia. PRT had significantly lower values for both PC1 and PC3, compared with PhRT.

Conclusions: PRT significantly reduces the incidence of pneumonia compared with PhRT in patients with EC treated with nCRT followed by surgical resection. The reduction of pneumonia was associated with the lower mean dose and a reduction of the volume irradiated to low doses in the lungs and/or heart.

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