Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy.
Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy.
JAMA Surg. 2019 Oct 1;154(10):932-942. doi: 10.1001/jamasurg.2019.2277.
Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood.
To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS: This prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018.
The chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center.
Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival.
Of 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy.
This pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.
在交界可切除和局部进展期胰腺导管腺癌中，化疗是推荐的诱导策略。然而，基于意向治疗的相关结果了解甚少。
研究接受新辅助化疗的交界可切除和局部进展期胰腺导管腺癌患者的治疗依从性、转化为手术以及生存结局。
设计、地点和参与者：这项前瞻性研究在意大利的一个胰腺疾病国家转诊中心进行。连续招募了交界可切除和局部进展期胰腺导管腺癌患者，在诊断时（2013 年 1 月至 2015 年 12 月）入组，并随访至 2018 年 6 月。
根据多学科评估分配的化疗方案在中心医院或卫星医院进行。根据常规，新辅助化疗在 6 个月后被认为完成。在重新分期后，根据放射学和生化反应选择手术候选者。所有手术均在中心医院进行。
接受和完成化疗的比率、转化为手术的比率以及疾病特异性生存率。
在 680 名患者中，267 名（39.3%）患有交界可切除性，413 名（60.7%）患有局部进展性胰腺导管腺癌。总体而言，66 名患者（9.7%）失访。接受化疗的比例为 92.9%（n=570）。最常用的化疗方案包括 FOLFIRINOX（氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康）（260 例[45.6%]）和吉西他滨加纳米白蛋白结合型紫杉醇（123 例[21.6%]）。19 名（3.3%）接受化疗的患者在 6 个月内死亡，主要是由于疾病进展。治疗完成率为 71.6%（408/570）。总体切除率为 15.1%（93/614）（交界可切除性 60/249 [24.1%]；局部进展性 33/365 [9%]；切除：探查比，63.3%）。切除的独立预测因素包括年龄、交界可切除疾病、化疗完成、放射学反应和生化反应。整个队列的中位总生存期为 12.8 个月（95%CI，11.7-13.9）。与生存相关的独立因素包括化疗完成、接受补充放疗和切除。在接受切除术的患者中，最初交界可切除的中位总生存期为 35.4 个月（95%CI，27.0-43.7），最初局部进展性疾病的中位总生存期为 41.8 个月（95%CI，27.5-56.1）。在手术后，没有治疗前和治疗后的因素与胰腺切除术的生存相关。
这项采用意向治疗设计的实用观察性队列研究提供了关于交界可切除和局部进展期胰腺导管腺癌患者最常用新辅助化疗方案相关结局的真实世界证据。
