KEY POINTS
- This single-centre real-world study included 135 consecutive patients with distal esophageal cancer treated from 2020–2024 with neoadjuvant 41.4 Gy in 23 fractions IMPT plus weekly carboplatin/paclitaxel according to CROSS.
- Plans used robust optimization with ±5-mm setup and ±3% range uncertainty. Weekly repeat 4D-CTs monitored anatomy, with adaptive replanning triggered by ITV D98 <94% or an increase in mean heart dose of ≥1.5 Gy.
- Despite this workflow, accumulated ITV underdosage occurred in 29/135 patients (21%). Median accumulated ITV D98 was 96% of prescription—but importantly, no patient experienced accumulated GTV underdosage, with median GTV D98 of 99%.
- Plan adaptation was performed in 56 patients (42%). ITV coverage triggered replanning in 36 and cardiac dose in 27; among patients ultimately showing accumulated ITV underdosage, only 45% had been adapted specifically for coverage.
- Early clinical complete response was essentially identical with versus without ITV underdosage (41% vs 37%; p=0.90). Overall complete tumor response—persistent 12-month cCR or pathological complete response—was 28% versus 30%.
- A baseline diaphragm amplitude >2 cm also failed as a useful screening marker: ITV underdosage occurred in 28% versus 19% with >2 versus ≤2 cm motion (p=0.32), with no association with clinical or pathological response.
- At a median follow-up of 37 months, estimated 2-year overall survival was 64% in both groups (p=0.73). Dose accumulation relied on weekly rather than daily anatomy and did not explicitly model interplay, so reconstructed dose remains an estimate rather than exact delivered fraction-level dosimetry.
CLINICAL TAKEAWAY
In a robustly optimized and adaptively monitored IMPT workflow, partial undercoverage of the broad ITV did not translate into loss of gross-tumor dose or worse tumor response. Most clinically relevant, large baseline diaphragm motion alone does not appear to justify excluding otherwise suitable distal esophageal cancer patients from IMPT.