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Research Article: Efficacy and safety of radiotherapy combined with chemoimmunotherapy versus chemoimmunotherapy alone as first-line treatment for metachronous oligorecurrent esophageal squamous cell carcinoma

Date Published: 2026-06-17

Abstract:
Metachronous oligorecurrence is usually defined as oligometastatic disease diagnosed more than 6 months after primary tumor diagnosis in the absence of active systemic therapy. This study aimed to assess the safety and efficacy of radiotherapy combined with chemoimmunotherapy (RCIT) versus chemoimmunotherapy (CIT) alone as the first-line treatment for metachronous oligorecurrent esophageal squamous cell carcinoma (MOR-ESCC). We retrospectively evaluated 195 patients with MOR-ESCC treated with first-line RCIT (n=102) or CIT (n=93) between June 2018 and June 2023. Propensity score matching (PSM) was performed to reduce baseline imbalance and potential confounding. Following 1:1 PSM, 72 well-paired patients were identified. The median follow-up was 17.9 months. RCIT was associated with significantly longer progression-free survival (PFS) than CIT, while overall survival (OS) showed a borderline non-significant trend favoring RCIT. The median PFS was 13.1 months (95% CI: 8.9-17.3) in the RCIT group and 9.0 months (95% CI: 6.9-11.1) in the CIT group ( P = 0.002). The median OS was 21.5 months (95% CI: 13.4-29.7) in the RCIT group and 16.0 months (95% CI: 13.2-18.8) in the CIT group ( P = 0.051). Subgroup analyses of OS suggested greater benefit from RCIT for patients with recurrence interval ?18 months ( P = 0.023), lymph node-only recurrence ( P = 0.020), 1–2 recurrent lesions ( P = 0.016), or single-organ recurrence ( P = 0.022). Safety analysis demonstrated comparable rates of grade ?3 treatment-related adverse events (TRAEs) (48.6% vs. 34.7%; P = 0.091) and treatment-related fatal events (8.3% vs. 4.2%; P = 0.491) between groups. Notably, RCIT showed a numerically higher incidence of grade ?3 pneumonitis (16.7% vs. 5.6%; P = 0.063). RCIT was associated with significantly prolonged PFS and numerically longer OS compared with CIT alone in patients with MOR-ESCC. Although no statistically significant increase in grade ?3 TRAEs was observed, RCIT showed numerically higher toxicity, particularly pneumonitis. This study provides real-world evidence supporting the role of radiotherapy in MOR-ESCC, identifying long recurrence intervals (?18 months), nodal-only recurrence, and low tumor burden (1–2 lesions/single organ) as key predictors of RCIT efficacy. These findings support RCIT as a potential strategy for carefully selected patients with MOR-ESCC, although the pneumonitis signal warrants cautious patient selection and prospective validation.

Introduction:
Oligometastatic disease (OMD) is an intermediate stage between locoregional and extensive systemic metastasis and is typically defined by fewer than 3–5 metastatic foci ( 1 ). This state may represent a clinically meaningful window in which local consolidative treatment can improve disease control and survival outcomes. To better define this entity, the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a nine-category…

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