ATM，RB1，ERCC2和FANCC突变的相关性分析以及新辅助化疗后的病理完全反应在肌肉侵入性膀胱癌患者中：SWOG S1314试验的结果
Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial
影响因子:25.20000
分区:医学1区 Top / 泌尿学与肾脏学1区
发表日期:2024 Oct
作者:
Elizabeth R Plimack, Catherine Tangen, Melissa Plets, Rutika Kokate, Joanne Xiu, Chadi Nabhan, Eric A Ross, Erin Grundy, Woonyoung Choi, Colin P N Dinney, I-Ling C Lee, Megan Fong, M Scott Lucia, Siamak Daneshmand, Dan Theodorescu, Amir Goldkorn, Seth P Lerner, Thomas W Flaig, David J McConkey
摘要
我们先前报道说，具有四个基因突变（ATM，RB1，FANCC或ERCC2）中的任何一种的肿瘤可能会对基于新辅助的基于顺铂化疗（NAC）反应，从而在囊肿术时（PT0）进行无癌症的手术标本。在这里，我们报告了我们对这一发现的验证。使用CARIS 592基因面板（Caris Life Sciences，AZ，AZ，美国），我们通过大型多中心试验（S1314）分析了105个NAAC肿瘤样本（Neoadjuvant gemcitabine and Cisplatin和顺铂（GC）（GC），或剂量浓度浓度甲基甲基甲基酸酯，ciScinblastine，cisplatin，cissplatin（gc） （DDMVAC）。我们发现，在手术时预测PT0的这四个基因中的任何一个突变（优势比= 5.36; 95％置信区间[CI] 2.05，14.02;双向P = 0.0006）。生物标志物比不存在疾病（PT0 48％的正预测值； 95％CI 35％，62％的阳性预测价值，比不存在疾病的疾病（PT0 86％，94％，94％）更好地预测存在的生物标志物（95％CI 73％，94％）。没有证据表明治疗组（DDMVAC与GC）与PT0的遗传变异之间存在相互作用。当与临床评估结合使用时，这些发现有助于为患者的选择提供基于顺铂的化学疗法后的膀胱保存。
Abstract
We previously reported that tumors harboring any one of four gene mutations (ATM, RB1, FANCC, or ERCC2) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC). We found that a mutation in any one of these four genes predicted for pT0 at surgery (odds ratio = 5.36; 95% confidence interval [CI] 2.05, 14.02; two-sided p = 0.0006). The biomarker was better at predicting the presence of disease (negative predictive value for pT0 86%; 95% CI 73%, 94%) than the absence of disease (positive predictive value for pT0 48%; 95% CI 35%, 62%). There was no evidence of an interaction between the treatment arm (DDMVAC vs GC) and the genetic variant in terms of pT0. When combined with clinical assessment, these findings help inform patient selection for bladder preservation after cisplatin-based chemotherapy.