Expanded clinical target volume and survival in non-operative ESCC: Prognostic benefits and inflammatory risks

Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, out-of-field locoregional relapse remains common. The optimal longitudinal expansion from gross tumor volume (GTV) to clinical target volume (CTV) varies across practice, and its impact on local control is not fully defined.

To explore the relationship between GTV-CTV margin expansion and inflammatory biomarkers and their combined impact on prognosis to determine a more optimal target volume range for esophageal cancer (EC).

A retrospective analysis of 209 ESCC patients undergoing radical CRT was conducted. Patients were categorized into small (SM), medium (MM) and large (LM) margin groups based on GTV-CTV expansion. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and their respective fold changes were calculated and analyzed for correlations with CTV margin expansion and patient prognosis.

Larger radiation fields led to higher post-treatment inflammatory markers with significant fold changes. Kaplan-Meier (KM) curves and receiver operating characteristic (ROC) curves indicated that the LM group, low pre-treatment NLR, low post-treatment NLR, PLR and SII, and fold changes in NLR, PLR and SII before and after treatment could predict local recurrence-free survival (LRFS). However, Cox analysis identified pre-treatment NLR, the change in SII from preto post-treatment, and GTV-CTV margin expansion as independent predictors.

Although inflammatory biomarkers offer prognostic value, primary GTV-CTV margin expansion has a stronger influence on LRFS in ESCC patients undergoing CRT. Further multi-institutional studies are needed to validate these findings and address current study limitations, including single-center design, small sample size and exclusion of in-field recurrences.