Bolm Louisa, Fraunhoffer Nicolas, Dusetti Nelson, Straesser Julia, Petruch Natalie, Fernandez Del Castillo Carlos, Iovanna Juan
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, United States.
Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck 23562, Germany.
Oncologist. 2025 May 8;30(5). doi: 10.1093/oncolo/oyaf083.
In the current study, we aimed to assess the efficacy of a gemcitabine response predictive signature that is part of the PancreasView transcriptomic predictive tool (Gem + or Gem-).
We used a cohort of pancreatic ductal adenocarcinoma patients treated from the Massachusetts General Hospital who underwent upfront resection.
In this cohort of 43 patients, 20 (46.5%) received adjuvant gemcitabine (GEM arm) and 23 (53.5%) did not receive any adjuvant chemotherapy. Among the 43 patients, the Gem signature defined a subgroup of 16 patients (37.2%) who were sensitive (Gem+) and 27 (62.8%), who were resistant to gemcitabine (Gem-). The Gem+ patients who received adjuvant gemcitabine had significantly better median disease-free survival (DFS) compared to the Gem- patients (NR until 72 months of follow-up vs 19.0 months; stratified hazard ratio [HR]: 0.19; 95% CI, 0.04-0.86; P = .032) and longer median cancer-specific survival (CSS) (NR until 96 months of follow-up vs 37.0 months; stratified HR: 0.18; 95% CI, 0.04-0.85; P = .030) when treated with gemcitabine. The gemcitabine signature remained an independent predictive factor for DFS (HR: 0.41; 95% CI, 0.19-0.89; P = .024) and CSS (HR: 0.47; 95% CI, 0.22-1.23; P = .059) after adjusting for clinicopathological characteristics in an unstratified univariate Cox hazard model.
This validation of the gemcitabine predictive transcriptomic signature in an independent cohort from Massachusetts General Hospital reinforces the robustness and reliability of this tool. This study highlights the potential of the signature to aid in the personalization of chemotherapy and enhance patient outcomes in pancreatic ductal adenocarcinoma.
在本研究中,我们旨在评估作为PancreasView转录组预测工具(Gem+或Gem-)一部分的吉西他滨反应预测特征的疗效。
我们使用了一组来自麻省总医院接受 upfront 切除的胰腺导管腺癌患者。
在这43例患者队列中,20例(46.5%)接受了辅助吉西他滨治疗(GEM组),23例(53.5%)未接受任何辅助化疗。在这43例患者中,Gem特征定义了一个亚组,其中16例(37.2%)对吉西他滨敏感(Gem+),27例(62.8%)对吉西他滨耐药(Gem-)。接受辅助吉西他滨治疗的Gem+患者与Gem-患者相比,无病生存期(DFS)的中位值显著更长(随访72个月时未达到 vs 19.0个月;分层风险比[HR]:0.19;95%可信区间,0.04 - 0.86;P = 0.032),癌症特异性生存期(CSS)的中位值也更长(随访96个月时未达到 vs 37.0个月;分层HR:0.18;95%可信区间,0.04 - 0.85;P = 0.030)。在未分层的单变量Cox风险模型中,调整临床病理特征后,吉西他滨特征仍然是DFS(HR:0.41;95%可信区间,0.19 - 0.89;P = 0.024)和CSS(HR:0.47;95%可信区间,0.22 - 1.23;P = 0.059)的独立预测因素。
在麻省总医院的一个独立队列中对吉西他滨预测转录组特征的验证加强了该工具的稳健性和可靠性。本研究突出了该特征在辅助胰腺导管腺癌化疗个体化及改善患者预后方面的潜力。