Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.
Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.
复制标题
可手术头颈癌对新辅助靶向治疗的反应可带来生存获益。
DOI：
10.1158/1078-0432.ccr-22-1768
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Herman,James
中科院分区：
文献类型：
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作者：
Mascarella,MarcoA;Olonisakin,TolaniF;Rumde,Purva;Vendra,Varun;Nance,MelonieA;Kim,Seungwon;Kubik,MarkW;Sridharan,ShaumS;Ferris,RobertL;Fenton,MoonJ;Clayburgh,DanielR;Ohr,JamesP;Joyce,SonaliC;Sen,Malabika;Herman,James
目的新辅助靶向治疗提供了一个短暂的术前机会窗口，可以根据治疗反应进行个体化癌症治疗。我们调查了在术前窗口期对新辅助治疗的反应是否能使可手术的头颈部鳞状细胞癌（HNSCC）患者的生存获益。患者和方法对2009年至2020年参加三项临床试验（NCT 00779389，NCT 01218048，NCT 02473731）之一的可手术的HNSCC初治患者进行了汇总分析。新辅助治疗方案包括手术后28天内的EGFR抑制剂（n = 83）或抗ErbB3抗体治疗（n = 9）。采用多变量考克斯回归分析对混杂因素进行校正后，将临床分期迁移至病理分期与无病生存期（DFS）和总生存期（OS）进行比较。结果118例患者中有92例接受了新辅助治疗，所有患者均接受了手术。与对照组相比，接受新辅助靶向治疗的患者中临床至病理分期下调的频率更高（P = 0.048）。与无分期变化（58%; 95% CI，46.2 - 69.8）或分期升高（40%; 95% CI，9.6 - 70.4; P = 0.003）的患者相比，病理性分期提前迁移的患者的OS最高[89.5%; 95% CI，75.7 - 100]。在调整测量的混杂因素时，分期迁移仍然是OS的积极预后因素（HR，0.22; 95% CI，0.05 - 0.90）。低分期迁移与循环肿瘤标志物SOX 17和TAC 1降低相关（P = 0.0078）。结论短期新辅助治疗在一部分患者中实现了病理低分期，并与显著更好的DFS和OS以及循环甲基化SOX 17和TAC 1降低相关。
PurposeNeoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC).Patients and MethodsA pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n= 83) or anti-ErbB3 antibody therapy (n= 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed.Results92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P= 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7–100] compared with those with no stage change (58%; 95% CI, 46.2–69.8) or upstage (40%; 95% CI, 9.6–70.4;P= 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05–0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers,SOX17andTAC1(P= 0.0078).ConclusionsBrief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylatedSOX17andTAC1.