Impact of accumulated target dose on tumor response in distal esophageal cancer treated with intensity-modulated proton therapy.

Abstract

In esophageal cancer, respiratory motion and anatomical changes can compromise dose delivery during proton radiotherapy. Adequate internal target volume (ITV) coverage does not necessarily ensure sufficient gross tumor volume (GTV) dose, particularly for distal tumors near the diaphragm. This study evaluated whether deviations in accumulated target dose affect tumor response. We retrospectively evaluated 135 patients with distal esophageal cancer treated with neoadjuvant chemoradiotherapy and intensity-modulated proton therapy (IMPT) between 2020 and 2024. Accumulated ITV dose was assessed weekly on repeat CTs using a robust voxel-wise minimum dose criterion (ITV D98 % < 94 %). Cumulative dose deposition was estimated using robust dose accumulation. Primary endpoints were persistent clinical complete response (cCR) at 12 months and pathologic complete response (pCR). Secondary endpoints included post-treatment cCR and two-year overall survival (OS). Median baseline diaphragm amplitude was 1.6 cm (range 0.5-8.7 cm). ITV underdosage occurred in 21 % of patients. No cases of GTV underdosage were observed. Post-treatment cCR rates did not differ between patients with and without ITV underdosage (p = 0.90). Complete tumor response, defined as persistent cCR at 12 months or pCR, was observed in 28 % and 30 % of patients with and without ITV underdosage, respectively. Baseline diaphragm amplitude > 2 cm was not associated with target underdosage, and two-year OS was similar between groups (64 % vs. 64 %, p = 0.7). Despite frequent ITV underdosage, GTV coverage remained preserved and no association with tumor response or OS was observed. Baseline diaphragm amplitude alone does not appear to warrant exclusion from treatment with IMPT.