Proton radiotherapy significantly reduces pneumonia in oesophageal cancer patients

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is the current standard of care for oesophageal cancer (EC) patients. This treatment is associated with a variety of complications, with pneumonia being the most common. We hypothesize that proton radiotherapy (PRT) can significantly reduce the incidence of pneumonia compared to photon radiotherapy (PhRT).

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

Results: We included 313 patients, of whom 28% developed pneumonia. The incidence was lower after PRT compared to PhRT (12% vs 32%, p < 0.01). PRT was associated with a significant reduction of the incidence of pneumonia (OR = 0.33[0.14 - 0.72], p = 0.01), even when correcting for surgical approach and PTV-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 (≤20Gy). If the dose related variables were replaced by the PCs; PC1 (OR = 1.11[1.02 - 1.22]) and PC3 (OR = 1.27[1.06 - 1.53]) were significantly associated with pneumonia. PRT had significantly lower values for both PC1 and PC3, compared to PhRT.

Conclusions: PRT significantly reduces the incidence of pneumonia compared to PhRT in EC patients 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.