Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Surgery, Epidemiology, Clinical and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA Netw Open. 2022 Jun 1;5(6):e2218355. doi: 10.1001/jamanetworkopen.2022.18355.
Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best dictated by response to neoadjuvant therapy (as measured by CA19-9 levels and/or pathologic response), a strategy defined herein as adaptive dynamic therapy.
To evaluate the association of adaptive dynamic therapy with oncologic outcomes in patients with surgically resected pancreatic cancer.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with localized pancreatic cancer who were treated with either gemcitabine/nab-paclitaxel or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) preoperatively between 2010 and 2019 at a high-volume tertiary care academic center. Participants were identified from a prospectively maintained database and had a median follow-up of 49 months. Data were analyzed from October 17 to November 24, 2020.
The adaptive dynamic therapy group included 219 patients who remained on or switched to an alternative regimen as dictated by CA19-9 response and for whom the adjuvant regimen was selected based on CA19-9 and/or pathologic response. The nonadaptive dynamic therapy group included 103 patients who had their chemotherapeutic regimen selected independent of CA19-9 and/or tumoral response.
Prognostic implications of dynamic perioperative therapy assessed through Kaplan-Meier analysis, Cox regression, and inverse probability weighted estimators.
A total of 322 consecutive patients (mean [SD] age, 65.1 [9] years; 162 [50%] women) were identified. The adaptive dynamic therapy group, compared with the nonadaptive dynamic therapy group, had a more pronounced median (IQR) decrease in CA19-9 levels (-80% [-92% to -56%] vs -45% [-81% to -13%]; P < .001), higher incidence of complete or near-complete tumoral response (25 [12%] vs 2 [2%]; P = .007), and lower median (IQR) number of lymph node metastasis (1 [0 to 4] vs 2 [0 to 4]; P = .046). Overall survival was significantly improved in the dynamic group compared with the nondynamic group (38.7 months [95% CI, 34.0 to 46.7 months] vs 26.5 months [95% CI, 23.5 to 32.9 months]; P = .03), and on adjusted analysis, dynamic therapy was independently associated with improved survival (hazard ratio, 0.73; 95% CI, 0.53 to 0.99; P = .04). On inverse probability weighted analysis of 320 matched patients, the average treatment effect of dynamic therapy was to increase overall survival by 11.1 months (95% CI, 1.5 to 20.7 months; P = .02).
In this cohort study that sought to evaluate the role of adaptive dynamic therapy in localized pancreatic cancer, selecting a chemotherapeutic regimen based on response to preoperative therapy was associated with improved survival. These findings support an individualized and in vivo assessment of response to perioperative therapy in pancreatic cancer.
新辅助疗法在局部胰腺癌中的应用日益增多，生存与碳水化合物抗原 19-9（CA19-9）水平和新辅助治疗后的组织病理学反应相关。随着目前有多种方案可供选择，化疗的选择可以根据新辅助治疗的反应（通过 CA19-9 水平和/或病理反应来衡量）来最佳确定，本文将这种策略定义为适应性动态治疗。
评估适应性动态治疗与接受手术切除的胰腺癌患者的肿瘤学结局之间的关联。
设计、设置和参与者：本回顾性队列研究纳入了 2010 年至 2019 年期间在一家高容量的三级学术中心接受吉西他滨/ nab-紫杉醇或氟尿嘧啶、亚叶酸、伊立替康和奥沙利铂（FOLFIRINOX）术前治疗的局限性胰腺癌患者。参与者从一个前瞻性维护的数据库中确定，中位随访时间为 49 个月。数据分析于 2020 年 10 月 17 日至 11 月 24 日进行。
适应性动态治疗组包括 219 名患者，他们根据 CA19-9 反应继续使用或转换为替代方案，辅助方案的选择基于 CA19-9 和/或病理反应。非适应性动态治疗组包括 103 名患者，他们的化疗方案选择与 CA19-9 和/或肿瘤反应无关。
通过 Kaplan-Meier 分析、Cox 回归和逆概率加权估计评估动态围手术期治疗的预后意义。
共确定了 322 例连续患者（平均[标准差]年龄，65.1[9]岁；162[50%]为女性）。与非适应性动态治疗组相比，适应性动态治疗组 CA19-9 水平的中位（IQR）下降更为明显（-80%[-92%至-56%]与-45%[-81%至-13%]；P < .001），完全或接近完全肿瘤反应的发生率更高（25[12%]与 2[2%]；P = .007），以及中位（IQR）淋巴结转移数量更低（1[0 至 4]与 2[0 至 4]；P = .046）。与非动态组相比，动态组的总生存明显改善（38.7 个月[95%CI，34.0 至 46.7 个月]与 26.5 个月[95%CI，23.5 至 32.9 个月]；P = .03），在调整后的分析中，动态治疗与改善的生存独立相关（风险比，0.73；95%CI，0.53 至 0.99；P = .04）。在对 320 名匹配患者的逆概率加权分析中，动态治疗的平均治疗效果是将总生存时间延长 11.1 个月（95%CI，1.5 至 20.7 个月；P = .02）。
在这项旨在评估适应性动态治疗在局部胰腺癌中作用的队列研究中，根据术前治疗的反应选择化疗方案与生存改善相关。这些发现支持在胰腺癌中对围手术期治疗的反应进行个体化和体内评估。
