Herman Joseph M, Jabbour Salma K, Lin Steven H, Deek Matthew P, Hsu Charles C, Fishman Elliot K, Kim Sinae, Cameron John L, Chekmareva Marina, Laheru Daniel A, Narang Amol K, Pawlik Timothy M, Hruban Ralph H, Wolfgang Christopher L, Iacobuzio-Donahue Christine A
Pancreas. 2018 Feb;47(2):208-212. doi: 10.1097/MPA.0000000000000985.
The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined whether Smad4 tumor status was associated with outcomes after adjuvant chemoradiation (CRT) for resected PDAs.
Patients treated with adjuvant CRT were identified (N = 145). Smad4 status was determined by immunolabeling and graded as intact or lost. Kaplan-Meier method and multivariable competing risk analyses were performed.
On multivariate competing risk analysis, Smad4 loss was associated with increased risk of local recurrence (LR) (hazard ratio, 2.37; 95% confidence interval, 1.10-5.11; P = 0.027), distant failure (DF) (hazard ratio, 1.71; 95% confidence interval, 1.03-2.83; P = 0.037), and synchronous LR and DF at first recurrence (14.9 % vs 5.3%, P = 0.07) compared with Smad4 intact cancers. Smad4 loss was not associated with median overall survival (22 vs 22 months; P = 0.63) or disease-free survival (lost [13.6 months] vs intact [13.5 months], P = 0.79).
After PDA resection and adjuvant CRT, Smad4 loss correlated with higher risk of LR and DF, but not with survival. Smad4 loss may help predict which surgical patients are at higher risk for failure after definitive management and may benefit from intensified adjuvant therapy.
肿瘤抑制基因SMAD4（DPC4）在大约一半的胰腺导管腺癌（PDA）中发生基因失活。我们研究了Smad4肿瘤状态与切除的PDA辅助放化疗（CRT）后的预后是否相关。
确定接受辅助CRT治疗的患者（N = 145）。通过免疫标记确定Smad4状态，并分为完整或缺失。进行了Kaplan-Meier法和多变量竞争风险分析。
在多变量竞争风险分析中，与Smad4完整的癌症相比，Smad4缺失与局部复发（LR）风险增加相关（风险比，2.37；9�%置信区间，1.10 - 5.11；P = 0.027）、远处转移（DF）风险增加相关（风险比，1.71；95%置信区间，1.03 - 2.83；P = 0.037），以及首次复发时同步出现LR和DF的风险增加相关（14.9%对5.3%，P = 0.07）。Smad4缺失与中位总生存期（22个月对22个月；P = 0.63）或无病生存期无关（缺失[13.6个月]对完整[13.5个月]，P = 0.79）。
PDA切除并辅助CRT后，Smad4缺失与LR和DF风险较高相关，但与生存率无关。Smad4缺失可能有助于预测哪些手术患者在确定性治疗后失败风险较高，并可能从强化辅助治疗中获益。
