1407P - Pan-immune-inflammation value predicts the survival of patients with esophageal squamous cell carcinoma receiving immunotherapy and chemoradiotherapy: A pooled-analysis of two phase II trials

Background

The use of PD-1 inhibitors improved the clinical outcomes of patients with esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers to predict the prognostic role of immunotherapy are lacking. We aimed to evaluate the prognostic ability of a new comprehensive biomarker, pan-immune-inflammatory value (PIV), in patients with ESCC receiving chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, and to explore the underlying mechanisms and dosimetric parameters that affect PIV zenith during CRT.

Methods

In this pooled-analysis, 86 patients were included from two prospective, phase II trials (EC-CRT-001 and NEOCRTECT1901). PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The optimum cut-off value was selected by using the receiver-operating characteristics curve. Kaplan-Meier method and Cox hazard regression models were used for survival analyses. Univariate and multivariable logistic regression were used to identify predictors of high PIV zenith. Pre-treatment tumor samples from 47 patients were collected for RNA sequencing to investigate the activation of immune related biological activities.

Results

Patients experienced significant changes in immuno-inflammatory biomarkers during CRT, which gradually recovered after radiotherapy. After a median follow-up of 35.5 months, patients with high PIV zenith during CRT had a worse progression-free survival (PFS) (P=0.007) and overall survival (P=0.015). In multivariable analysis, high PIV zenith remained a significant prognostic factor for PFS. Mean lung dose (MLD) was revealed to be an independent predictor of high PIV zenith. High PIV zenith was associated with higher levels of B cell infiltration, activation, and B cell-mediated immune response.

Conclusions

PIV is a strong predictor for survival outcomes in patients with ESCC treated with anti-PD-1 immunotherapy in combination with CRT. High PIV zenith was correlated to higher MLD and higher levels of B cell-mediated immune response. Prospective trials with large samples are required to validate the value of this new parameter.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.