Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
Comparison of induction chemotherapy followed by concurrent chemoradiotherapy versus neoadjuvant chemotherapy followed by surgery and (chemo)radiotherapy in locoregionally advanced hypopharyngeal carcinoma: a prospective cohort study.
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Zhao Da-Wei, Li Shi-Rui, Yang Fei, Guo Xiong-Fang, Sun Xiao-Zhe, Li Ling, Tan Su-Cheng, Qin Jin-Yang, Qu Ya-Jing, Wang Zhong-Qiu, Ma Lin, Wang Pei-Guo
Аннотация
BACKGROUND: The optimal strategy for laryngeal preservation in locally advanced hypopharyngeal carcinoma (LAHPC) remains undefined. This prospective observational study compared long-term outcomes between two primary treatment approaches: induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) and neoadjuvant chemotherapy followed by surgery and adjuvant (chemo)radiotherapy (NAC-Sur-RT).
METHODS: From December 2018 to December 2023, 199 patients with LAHPC were prospectively enrolled and treated with either IC-CCRT (n = 124) or NAC-Sur-RT (n = 75). The primary endpoints were survival with functional larynx (SFL), overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS). Prognostic factors were identified using multivariable Cox regression.
RESULTS: In the matched cohort (median follow-up 49 months), NAC-Sur-RT was associated with significantly superior 5-year OS (58.3% vs 46.2%; adjusted HR = 0.60; 95% CI 0.38-0.95; P = 0.031) and DMFS (56.2% vs 41.6%; adjusted HR = 0.59; 95% CI 0.38-0.92; P = 0.023), and PFS (52.2% vs 37.2%; adjusted HR = 0.64; 95% CI 0.42-0.98; P = 0.040). Conversely, NAC-Sur-RT was associated with a significantly higher risk of SFL failure (27.0% vs 43.1%; adjusted HR = 2.18; 95% CI 1.45-3.27; P < 0.001). No significant differences were found in LFFS or LRFFS. Failure pattern analysis indicated more isolated local recurrences with IC-CCRT (15.3% vs 5.3%) but higher regional recurrence with NAC-Sur-RT (1.6% vs 6.7%). Multivariable analysis confirmed NAC-Sur-RT as an independent predictor of improved OS (HR = 0.60; P = 0.031), PFS (HR = 0.64; P = 0.040), and DMFS (HR = 0.59; P = 0.023), but also of worse SFL (HR = 2.18; P < 0.001). AJCC stage IVB disease independently predicted inferior OS (HR = 9.05; 95% CI 1.52-53.81; P = 0.015) and DMFS (HR = 8.49; 95% CI 1.53-47.23; P = 0.015). Additionally, NAC-Sur-RT was associated with significantly higher rates of severe (grade 3-4) toxicities, including laryngeal/esophageal, mucosal, hematologic, and functional adverse events.
CONCLUSION: In this non-randomized prospective comparison, the NAC-Sur-RT strategy was associated with superior survival outcomes (OS, PFS, DMFS) but at the cost of increased severe toxicity and a significantly lower rate of functional larynx preservation. IC-CCRT offers a higher probability of survival with a functional larynx despite a higher risk of local recurrence. Treatment selection should be individualized, balancing survival benefits, functional outcomes, and toxicity profiles.
TRIAL REGISTRATION: The study was approved by the ethics board of the Chinese PLA General Hospital and registered in the Chinese Clinical Trial Registry (registered number: ChiCTR2000039813).
METHODS: From December 2018 to December 2023, 199 patients with LAHPC were prospectively enrolled and treated with either IC-CCRT (n = 124) or NAC-Sur-RT (n = 75). The primary endpoints were survival with functional larynx (SFL), overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS). Prognostic factors were identified using multivariable Cox regression.
RESULTS: In the matched cohort (median follow-up 49 months), NAC-Sur-RT was associated with significantly superior 5-year OS (58.3% vs 46.2%; adjusted HR = 0.60; 95% CI 0.38-0.95; P = 0.031) and DMFS (56.2% vs 41.6%; adjusted HR = 0.59; 95% CI 0.38-0.92; P = 0.023), and PFS (52.2% vs 37.2%; adjusted HR = 0.64; 95% CI 0.42-0.98; P = 0.040). Conversely, NAC-Sur-RT was associated with a significantly higher risk of SFL failure (27.0% vs 43.1%; adjusted HR = 2.18; 95% CI 1.45-3.27; P < 0.001). No significant differences were found in LFFS or LRFFS. Failure pattern analysis indicated more isolated local recurrences with IC-CCRT (15.3% vs 5.3%) but higher regional recurrence with NAC-Sur-RT (1.6% vs 6.7%). Multivariable analysis confirmed NAC-Sur-RT as an independent predictor of improved OS (HR = 0.60; P = 0.031), PFS (HR = 0.64; P = 0.040), and DMFS (HR = 0.59; P = 0.023), but also of worse SFL (HR = 2.18; P < 0.001). AJCC stage IVB disease independently predicted inferior OS (HR = 9.05; 95% CI 1.52-53.81; P = 0.015) and DMFS (HR = 8.49; 95% CI 1.53-47.23; P = 0.015). Additionally, NAC-Sur-RT was associated with significantly higher rates of severe (grade 3-4) toxicities, including laryngeal/esophageal, mucosal, hematologic, and functional adverse events.
CONCLUSION: In this non-randomized prospective comparison, the NAC-Sur-RT strategy was associated with superior survival outcomes (OS, PFS, DMFS) but at the cost of increased severe toxicity and a significantly lower rate of functional larynx preservation. IC-CCRT offers a higher probability of survival with a functional larynx despite a higher risk of local recurrence. Treatment selection should be individualized, balancing survival benefits, functional outcomes, and toxicity profiles.
TRIAL REGISTRATION: The study was approved by the ethics board of the Chinese PLA General Hospital and registered in the Chinese Clinical Trial Registry (registered number: ChiCTR2000039813).