SynthesisBMC medicine2025
Comparative efficacy and safety of neoadjuvant immunotherapy vs chemotherapy in resectable head and neck squamous cell carcinoma: an umbrella review of randomized controlled trials and single-arm studies.
Synthesis in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Review
- Hybrid Reconstruction in Head and Neck Surgery: Integration of Virtual Planning, Navigation, and Robotic Microsurgery.Journal of clinical medicine · 2026Review
- Perioperative immunotherapy in resectable HNSCC: biological rationale to practical multidisciplinary implementation.Frontiers in oncology · 2026Review
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4 authors.
Funding
Abstract
backgroundThe evolution of neoadjuvant therapies for resectable head and neck squamous cell carcinoma (HNSCC) has accelerated with the advent of immune checkpoint inhibitors. While platinum-based induction chemotherapy (ICT) shows modest benefits, emerging neoadjuvant immunotherapy has demonstrated unprecedented pathological response rates (PRR) in early-phase trials. However, significant controversy persists regarding the survival benefits and optimal integration of these strategies into multimodality paradigms. This umbrella review synthesizes meta-analytical evidence to evaluate whether neoadjuvant immunotherapy or chemotherapy confers clinically meaningful advantages in surgical outcomes and long-term survival for resectable HNSCC.
methodsWe conducted an umbrella review of systematic reviews and meta-analyses (SRMAs) evaluating neoadjuvant immunotherapy or chemotherapy in resectable HNSCC (PubMed, Embase, Cochrane Library; January 2016-March 2025, no language restriction). Critical endpoints included pathological complete response (PCR), major pathological response (MPR), disease control rate (DCR), objective response rate (ORR), treatment-related adverse events (TRAEs), progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Methodological rigor was assessed using AMSTAR-2 (A Measurement Tool to Assess systematic Reviews 2), and GRADE (Grading of Recommendations Assessment, Development and Evaluation) with sensitivity analyses performed for corrected covered area (CCA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 for Abstracts (PRISMA 2020 for Abstracts) checklist was followed.
resultsA total of 10 systematic reviews with meta-analyses were included, with a cumulative patient population of 15,871. Neoadjuvant anti-PD-(L)1 + chemotherapy achieved PCR rates of 26.7-30.1%. Neoadjuvant anti-PD-(L)1 + radiotherapy yielded the highest downstaging rate of 93.3% (95% confidence interval [CI], 68.1-99.8%) and ORR of 57.0% (95%CI, 44.0-72.0%). Neoadjuvant immunotherapy showed 1-year OS of 84.0-89.7%, though 3-year OS converged to 78.9% (95%CI, 63.2-89.1%). ICT showed marginal benefits in locoregional control (hazard ratio [HR], 0.59; 95%CI, 0.42-0.85) but had limited impact on overall survival (HR, 1.16; 95%CI, 1.07-1.26). However, these efficacy benefits must be balanced against a significant risk of Grade 3-4 TRAEs of 9.7-35.0%.
conclusionsNeoadjuvant anti-PD-(L)1 + radiotherapy offers superior pathological and early survival outcomes in resectable HNSCC, supporting its integration into treatment algorithms. However, the lack of high-quality evidence regarding this treatment limits definitive conclusions. Further trials are needed to validate long-term benefits and guide biomarker-driven patient selection.
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