PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation
PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation
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DOI：
10.1093/jnci/djz224
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发表时间：
2020-08-01
影响因子：
10.3
通讯作者：
Chera, Bhishamjit S.
中科院分区：
文献类型：
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作者：
Beaty, Brian T.;Moon, Dominic H.;Chera, Bhishamjit S.
PIK 3CA是人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）中最常突变的基因。这种突变的预后影响仍然未知。我们试图阐明PIK 3CA突变在接受确定性放化疗（CRT）治疗的HPV相关OPSCC患者中的临床意义。77例HPV相关OPSCC患者参加了两项II期临床试验，即去强化CRT（60戈伊调强放疗，同时每周一次顺铂）。进行靶向下一代测序。在77例患者中，9例出现疾病复发（2例局部复发，4例远处复发，3例局部和远处复发）。34例患者发现了突变; 16例患者有PIK 3CA突变。野生型PIK 3CA患者的3年无病生存率在统计学上显著高于PIK 3CA突变患者（93.4%，95%置信区间[CI] = 85.0%至99.9% vs 68.8%，95% CI = 26.7%至89.8%; P = 0.004）。在多变量分析中，PIK 3CA突变是与疾病复发统计学显著相关的唯一变量（风险比= 5.71，95%CI = 1.53至21.3; P = 0.01）。PIK 3CA突变与新诊断的HPV相关OPSCC患者接受减强CRT治疗的前瞻性队列中无病生存率较差相关。
PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P = .004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P = .01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT.