Takeshi Kodaira

To develop and validate a machine-learning–based prediction model for overall survival (OS) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) that integrates both surgery-based and chemoradiotherapy (CRT) cohorts within a single framework. A total of 1,005 LA-HNSCC patients receiving curative-intent surgery-based treatment or CRT were retrospectively assembled from a domestic multicenter cohort ( n = 678) and publicly available datasets from The Cancer Imaging Archive ( n = 327). Candidate predictors were pre-specified from routinely available clinical variables. Elastic net regularization with 10-fold cross-validation was applied for variable selection and weighting, followed by a multivariable Cox proportional hazards model. Elastic net selected 12 variables, of which p16 status, performance status, nodal stage, serum albumin, T stage, and age were most influential. The model showed good discrimination (C-index 0.73), with time-dependent AUCs of 0.78–0.73 across 1–5 years and good calibration at 1 and 3 years. Decision curve analysis confirmed clinical utility across relevant threshold probabilities in both cohorts. By relying on prognostic factors common to both surgery-based treatment and CRT, this interpretable model demonstrated stable performance and may support prognostic risk stratification applicable across treatment modalities in LA-HNSCC.

The interim analysis of JCOG1008 demonstrated that chemoradiotherapy with cisplatin 40 mg/m ² once a week for seven cycles (weekly cisplatin) was noninferior in terms of overall survival (OS) compared with chemoradiotherapy with cisplatin 100 mg/m ² once every 3 weeks for three cycles (3-weekly cisplatin) for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This report presents the long-term follow-up results of JCOG1008. In this phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin or with weekly cisplatin. A total of 261 patients were enrolled. At the final analysis, with a median follow-up of 5.6 years, 5-year OS was 58.7% in the 3-weekly arm and 71.2% in the weekly arm (hazard ratio, 0.76 [95% CI, 0.52 to 1.12 [<1.32]]), confirming the noninferiority of the weekly regimen. Both 5-year relapse-free survival (RFS) and 5-year local RFS were numerically better in the weekly arm. No late adverse event showed more than a 10% difference between the two arms. In conclusion, 5-year follow-up confirmed that chemoradiotherapy with weekly cisplatin is noninferior in OS to chemoradiotherapy with 3-weekly cisplatin in patients with postoperative high-risk LA-SCCHN. These results further support the use of weekly cisplatin plus radiotherapy as a reasonable alternative for this patient population.

Head and neck squamous cell carcinoma (HNSCC) often requires invasive multimodal therapy, including surgery, radiotherapy, and chemotherapy. Although these interventions have improved treatment outcomes, patients frequently experience long-term functional impairment and treatment-related morbidity. Consequently, clinical research has shifted toward treatment de-escalation, a paradigm aimed at preserving quality of life while maintaining oncologic control. This review summarizes the current evidence from prospective clinical trials on de-escalation strategies for HNSCC of the oropharynx, hypopharynx, larynx, and oral cavity, with a focus on radiotherapy-based approaches. Investigators have evaluated several de-escalation strategies, including total radiation dose reduction in definitive chemoradiotherapy, modification or omission of concurrent systemic therapy, de-intensification of prophylactic nodal irradiation, response-adapted treatment de-intensification, and minimally invasive approaches such as transoral surgery with risk-adapted postoperative therapy. These strategies target favorable-risk populations, particularly patients with human papillomavirus-associated oropharyngeal cancer. Although numerous phase II studies have reported encouraging clinical outcomes and acceptable toxicity profiles, definitive evidence supporting the safety and efficacy of de-escalation strategies remains unestablished in large-scale phase III trials. Unwarranted de-escalation for HNSCC should be avoided, particularly for medically fit patients, and promising strategies require validation in phase III trials before routine clinical adoption. Future challenges include prospective validation through clinical trials and the integration of predictive biomarkers to balance the delicate trade-off between toxicity reduction and oncologic safety.

Population aging is rapidly progressing worldwide, and Japan has the most advanced aging population. Consistent with this trend, the proportion of older patients with head and neck cancer has markedly increased. Non-surgical definitive treatment for locally advanced head and neck cancer consists of radiotherapy (RT) alone or RT combined with systemic therapy; however, optimal treatment selection in older patients remains challenging due to their increased vulnerability to treatment-related toxicities and the limited availability of age-specific evidence. This review summarizes current evidence on non-surgical treatment strategies and the role of geriatric assessment (GA) in older patients with locally advanced oropharyngeal, hypopharyngeal, and laryngeal cancers. Although concurrent chemoradiotherapy (CRT) with high-dose cisplatin remains the standard of care for fit patients, its survival benefit appears attenuated in patients aged 70 years or older. Alternative approaches, including weekly cisplatin-based CRT, RT with other systemic agents, or RT alone, are frequently considered; however, the strength of supporting evidence varies. International guidelines recommend that treatment decisions for older adults be based on overall health status rather than chronological age alone. GA provides a structured framework to evaluate vulnerability across multiple domains, but remains underutilized in routine practice. Individualized, GA-guided treatment strategies with multidisciplinary discussion are essential for optimizing outcomes in this growing patient population.