Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky.
Pract Radiat Oncol. 2018 Mar-Apr;8(2):95-106. doi: 10.1016/j.prro.2017.10.001. Epub 2017 Oct 7.
Stereotactic ablative radiation therapy's (SABR's) great conformity and short duration has become an attractive treatment modality. We report a phase 2 clinical trial to evaluate efficacy and safety of induction chemotherapy (ICT) followed by SABR in patient with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).
Patients with biopsy-proven BR or LA PDAC were treated with four 21-day cycles of intravenous gemcitabine and oral capecitabine. Patients were restaged within 4 weeks after ICT by computed tomography and treated by 3-fraction SABR if no metastasis or progressive disease was identified. Patients were restaged 4 weeks following SABR to determine resectability. Tumor response was assessed with carbohydrate antigen 19-9.
Thirty-five patients (19 BR/16 LA) were enrolled. The median age was 71.8 years (range, 50.6-81.1). ICT was completed in 91.4% (n = 32) of patients. All patients who completed ICT completed SABR. Of those 32 patients, 34.3% (n = 12: 10 BR, 2 LA) underwent pancreaticoduodenectomy and 11 of 12 (91.7%) received R0 resection. Median overall survival was 18.8, 28.3, and 14.3 months for the entire cohort, BR, and LA, respectively. The 2-year local progression-free survival (LPFS) was 44.9%, 40%, and 52% for the entire cohort, BR, and LA, respectively. For BR patients, multivariate analysis showed surgery was associated with better overall survival and LPFS. One-year LPFS for patients with surgery was 80% and 44% without surgery. Within the 15.4-month follow-up, no grade 3+ toxicity from SABR was observed. No significant quality of life change was observed before and after ICT, SABR, or surgery for BR or LA patients.
This is the first prospective phase 2 study to investigate the feasibility and efficacy of a 12-week gemcitabine/capecitabine ICT followed by SABR for BR or LA PDAC. The results suggest excellent tolerability, high R0 resection rates, and acceptable posttreatment complications.
立体定向消融放疗（SABR）的高度适形性和短治疗时间使其成为一种有吸引力的治疗方式。我们报告了一项 2 期临床试验，以评估诱导化疗（ICT）后序贯 SABR 治疗边界可切除（BR）和局部晚期（LA）胰腺导管腺癌（PDAC）患者的疗效和安全性。
经活检证实为 BR 或 LA PDAC 的患者接受了 4 个 21 天周期的静脉注射吉西他滨和口服卡培他滨治疗。在 ICT 后 4 周内，通过计算机断层扫描进行重新分期，如果没有转移或疾病进展，则采用 3 次分割 SABR 治疗。在 SABR 后 4 周进行重新分期，以确定可切除性。通过碳水化合物抗原 19-9 评估肿瘤反应。
共纳入 35 例患者（19 例 BR/16 例 LA）。中位年龄为 71.8 岁（范围，50.6-81.1）。91.4%（n=32）的患者完成了 ICT。所有完成 ICT 的患者均完成了 SABR。在这 32 例患者中，34.3%（n=12：10 例 BR，2 例 LA）接受了胰十二指肠切除术，其中 12 例（91.7%）获得了 R0 切除。整个队列、BR 和 LA 的中位总生存期分别为 18.8、28.3 和 14.3 个月。整个队列、BR 和 LA 的 2 年局部无进展生存期（LPFS）分别为 44.9%、40%和 52%。对于 BR 患者，多变量分析显示手术与更好的总生存期和 LPFS 相关。手术患者的 1 年 LPFS 为 80%，无手术患者为 44%。在 15.4 个月的随访中，未观察到 SABR 引起的 3+级以上毒性。BR 或 LA 患者在 ICT、SABR 或手术前后，未观察到生活质量显著变化。
这是第一项前瞻性 2 期研究，旨在研究 12 周吉西他滨/卡培他滨 ICT 后序贯 SABR 治疗 BR 或 LA PDAC 的可行性和疗效。结果表明，该方案具有良好的耐受性、高 R0 切除率和可接受的治疗后并发症。
