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Published on: February 5, 2020
Risk-benefit stratification for immune checkpoint inhibitor therapy in head and neck cancer based on immune-related
Ken Kasahara1, Takeyuki Kono2, Yoichiro Sato3
1Department of Otolaryngology and Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan; Division of Otolaryngology and Head and Neck Surgery, Saiseikai Utsunomiya Hospital, 911-1 Takebayashi, Utsunomiya-shi, Tochigi, Japan.
Background:
Immune checkpoint inhibitors (ICIs) have improved outcomes in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but immune-related adverse events (irAEs) can lead to treatment interruption, underscoring the need for risk-benefit stratification. This study sought to predict ICI efficacy and toxicity using simple, combined positive score (CPS)-independent clinical indicators obtainable from routine laboratory tests.
Materials And Methods:
A total of 179 patients with R/M HNSCC treated with anti-PD-1 therapy were retrospectively analyzed. Several routine clinical parameters, including the lumbar skeletal muscle index (LSMI) derived from pretreatment CT images, were collected and subjected to multivariable analyses to identify predictors of irAEs development and permanent ICI discontinuation. Based on significant variables, we attempted to stratify patients into those likely to derive clinical benefit from ICI therapy and those at increased risk of permanent ICI discontinuation.
Results:
IrAEs occurred in 35.2% of patients and were associated with significantly better survival, with high LSMI independently predicting irAE development. In contrast, low LSMI patients showed fewer irAEs and poorer survival. Within this subgroup, advanced age (≥77 years) and elevated lactate dehydrogenase (LDH) (≥240 U/L) independently predicted permanent ICI discontinuation (AUC = 0.87). This simple two-point score using these factors effectively identified low-LSMI patients at highest risk for treatment discontinuation.
Conclusions:
Integrating routine indicators-LSMI, age, and LDH-provides a practical tool for identify patients who are likely to derive substantial benefit or experience irAE-related harm from ICIs, enabling optimized patient selection beyond PD-L1 expression in daily clinical practice.
