Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

被引：16

作者：

Patel, Usha ^{[1
,2
]}

Pandey, Manish ^{[1
]}

Kannan, Sadhana ^{[2
,3
]}

Samant, Tanuja A. ^{[1
]}

Gera, Poonam ^{[2
,4
]}

Mittal, Neha ^{[2
,5
]}

Rane, Swapnil ^{[2
,5
]}

Patil, Asawari ^{[2
,5
]}

Noronha, Vanita ^{[2
,6
]}

Joshi, Amit ^{[2
,6
]}

Patil, Vijay M. ^{[2
,6
]}

Prabhash, Kumar ^{[2
,6
]}

Mahimkar, Manoj B. ^{[1
,2
]}

机构：

[1] Tata Mem Hosp, Adv Ctr Treatment Res & Educ Canc, Canc Res Inst, Mahimkar Lab, Navi Mumbai, Maharashtra, India

[2] Homi Bhabha Natl Inst, Training Sch Complex, Mumbai, Maharashtra, India

[3] Tata Mem Hosp, Adv Ctr Treatment Res & Educ Canc, Clin Res Secretariat, Navi Mumbai, Maharashtra, India

[4] Tata Mem Hosp, Adv Ctr Treatment Res & Educ Canc, Navi Mumbai, Maharashtra, India

[5] Tata Mem Hosp, Tata Mem Ctr, Dept Pathol, Mumbai, Maharashtra, India

[6] Tata Mem Hosp, Dept Med Oncol, Tata Mem Ctr, Mumbai, Maharashtra, India

来源：

BRITISH JOURNAL OF CANCER | 2020年 / 123卷 / 12期

关键词：

SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS STATUS; NECK-CANCER PATIENTS; COPY NUMBER; HEAD; HYPOXIA; SURVIVAL; EGFR; RESISTANCE; CETUXIMAB;

D O I：

10.1038/s41416-020-01064-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients. Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1 alpha, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1 alpha was associated with better PFS [HR (95% CI) = 0.62 (0.42-0.93)], LRC [HR (95% CI) = 0.56 (0.37-0.86)] and OS [HR (95% CI) = 0.63 (0.43-0.93)] in the CRT group. Multivariable analysis revealed HIF1 alpha as an independent negative prognostic biomarker. For patients with high HIF1 alpha, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37-0.82), LRC:HR (95% CI) = 0.55 (0.36-0.85) and OS:HR (95% CI) = 0.54 (0.36-0.81)] compared to CRT. While in patients with low HIF1 alpha, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1 alpha for OS (P = 0.008). Conclusions High HIF1 alpha expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1 alpha significantly benefited with the addition of nimotuzumab to CRT.

引用

页码：1757 / 1766

页数：10

共 49 条

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