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IntroductionChemoradiation therapy (CRT) with concurrent high-dose cisplatin (CDDP) is one of the standard treatment options for locally advanced head and neck cancer. Since the indications specific to the older population have not been reported, we conducted a multicenter survey on the indications.MethodsIn April and May 2023, a questionnaire survey was emailed to all institutions belonging to the JCOG-HNCSG, consisting of 37 institutions.ResultsThe major factors influencing the indications for high-dose CDDP were renal function and performance status (PS). The majority agreed that the treatment is administered to patients aged 65–74 years with PS 0–1 and 65–74 years with eGFR ≥60 (ml/ min/1.73m2), and not in patients aged ≥75 years with PS 2, ≥80 years with PS 1, and ≥65 years with eGFR

BackgroundNivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.MethodsPre-treatment plasmas (N = 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature.ResultsAssays for pre-treatment blood samples (N = 104) demonstrated that a combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%; P = 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055; P = 0.0002348). Parallel biological assays demonstrated that in the paired treatment-naïve HNSCC tumor and plasma samples (N = 20), PEX HLA-E mRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor, suggesting that the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade.ConclusionThe PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs.