title: Clues toward precision medicine in oral squamous cell carcinoma: utility of next-generation sequencing for the prognostic stratification of high-risk patients harboring neck lymph node extracapsular extension.
abstract: Patients with resected oral squamous cell carcinoma (OSCC) harboring extracapsular extension (ECE) of the involved lymph node, show poor and heterogeneous outcomes. We aim to improve their prognostic stratification by combining genetic information from next-generation sequencing (NGS) using traditional clinicopathological prognosticators. The hotspot mutation regions of 45 cancer-related genes were investigated using NGS with an ultra-deep (>1000×) sequencing approach in formalin-fixed paraffin-embedded samples obtained from 201 patients with resected OSCC harboring ECE. Adjuvant chemoradiotherapy (CRT) and the number of nodes with ECE were the most important traditional prognosticators for disease-specific survival (DSS). The 5-year DSS for patients with CRT versus without, was 55% versus 21% (P < 0.001), and that for 1-3 versus ≥ 4 ECEs was 60% versus 25% (P = 0.001), respectively. Multivariate analysis in patients who received adjuvant CRT for 1-3 ECEs (i.e., those with a favorable expected prognosis) identified the following adverse prognostic factors: 1) margin of < 5 mm for locoregional failure (66% versus 30%, P = 0.007) and DSS (42% versus 63%, P = 0.039); 2) HRAS mutation for distant failure (55% versus 25%, P = 0.007) and DSS (36% versus 63%, P = 0.024); and 3) TP53 DNA-binding domain missense mutations for DSS (52% versus 71%, P = 0.025) and overall survival (39% versus 61%, P = 0.007).We conclude that genetic information from NGS may improve the prognostic stratification offered by traditional prognosticators in resected OSCC patients with ECE. Our findings will contribute to implementation of precision medicine in OSCC patients.
authors: Department of Internal Medicine, Division of Medical Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Hung-Ming
authors: HM
authors: Wang
authors: Department of Otorhinolaryngology, Section of Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Chun-Ta
authors: CT
authors: Liao
authors: Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Tzu-Chen
authors: TC
authors: Yen
authors: ACT Genomics, Taipei, Taiwan, ROC.
authors: Shu-Jen
authors: SJ
authors: Chen
authors: Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Li-Yu
authors: LY
authors: Lee
authors: Department of Internal Medicine, Division of Medical Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Chia-Hsun
authors: CH
authors: Hsieh
authors: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Chien-Yu
authors: CY
authors: Lin
authors: Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors: Shu-Hang
authors: SH
authors: Ng
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D009367:Neoplasm Staging; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D000072417:Protein Domains; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TP53 DNA-binding domain; extracapsular extension; next-generation sequencing; oral squamous cell carcinoma; precision medicine