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ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial.

Abstract：

BACKGROUND:Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nuclease is critical to DNA repair pathways resolving cisplatin-induced lesions. METHODS:In a phase II trial, patients with untreated Stage III-IVb HNSCC were randomised to cisplatin-radiotherapy with/without erlotinib. Archived primary tumours were available from 90 of 204 patients for this planned substudy. Semi-quantitative ERCC1 protein expression (H-score) was determined using the FL297, 4F9, and 8F1 antibodies. The primary analysis evaluated the relationship between continuous ERCC1 protein expression and progression-free survival (PFS). Secondary analyses included two pre-specified ERCC1 cutpoints and performance in HPV-associated disease. RESULTS:Higher ERCC1 expression was associated with inferior PFS, as measured by the specific antibodies FL297 (HR=2.5, 95% CI=1.1-5.9, P=0.03) and 4F9 (HR=3.0, 95% CI=1.2-7.8, P=0.02). Patients with increased vs decreased/normal ERCC1 expression experienced inferior PFS (HR=4.8 for FL297, P=0.003; HR=5.5 for 4F9, P=0.007). This threshold remained prognostic in HPV-associated disease. CONCLUSION:ERCC1-XPF protein expression by the specific FL297 and 4F9 antibodies is prognostic in patients undergoing definitive cisplatin-radiotherapy for HNSCC, irrespective of HPV status.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Bauman JE,Austin MC,Schmidt R,Kurland BF,Vaezi A,Hayes DN,Mendez E,Parvathaneni U,Chai X,Sampath S,Martins RG

doi

10.1038/bjc.2013.576

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

2096-105

issue

8

eissn

0007-0920

issn

1532-1827

pii

bjc2013576

journal_volume

109

pub_type

杂志文章,随机对照试验

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