Surgical Margin Reduction After Immunotargeted Neoadjuvant Therapy in Locally Advanced Hypopharyngeal Carcinoma: A Preliminary Margin Results from neoCHANCE-1 Trial.

ImportanceHypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive cancer with poor outcomes. Neoadjuvant therapy (NAT) may allow organ preservation, but determining safe surgical margins after NAT is a critical challenge.ObjectiveTo evaluate the safety of reduced surgical margins after neoadjuvant tislelizumab and afatinib in locally advanced HPSCC by comparing pathological margins to an upfront surgery control group.DesignProspective, single-center pilot cohort study.SettingTertiary referral center in Western China.ParticipantsForty-one patients with locally advanced HPSCC; 32 received NAT (treatment group), and 9 served as an upfront surgery control group.Intervention or ExposuresTreatment group: 2 cycles of neoadjuvant tislelizumab plus 6 weeks of afatinib. Control group: upfront surgery. Both groups underwent resection with a 1.5 cm naked-eye surgical margin.Main Outcome MeasuresPrimary outcomes were minimal peripheral surgical margin (MPSM) and minimal deep surgical margin (MDSM). Secondary outcomes included radiological (RECIST v1.1) and pathological tumor response.ResultsThe NAT group had a 20/32 (62.5%) radiological objective response rate and a 16/32 (50.0%) major pathological response rate [including 9/32 (28.13%) pathological complete response]. The mean MPSM was significantly greater in the treatment group versus control [3.38 mm vs 1.71 mm; 95% Confidence interval (CI): 0.10-3.24;  = .038]. The mean MDSM was also significantly greater in the treatment group versus control (2.09 mm vs 1.04 mm; 95% CI: 0.12-1.97;  = .029).ConclusionsCombined immune-targeted NAT effectively downstages HPSCC. The significantly larger pathological margins observed support that reducing clinical surgical margins after this regimen is generally safe.RelevanceThis NAT regimen may allow for less extensive resections, facilitating laryngeal preservation and improving quality of life without compromising oncologic safety. Larger validation studies are needed.