Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands.
Lancet Gastroenterol Hepatol. 2024 May;9(5):448-459. doi: 10.1016/S2468-1253(24)00017-7. Epub 2024 Mar 19.
Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal prognosis. Stage III locally advanced pancreatic cancer is considered unresectable and current palliative chemotherapy regimens only modestly improve survival. Guidelines suggest chemoradiation or stereotactic ablative body radiotherapy (SABR) could be beneficial in certain circumstances. Other local treatments such as irreversible electroporation could enhance patient outcomes by extending survival while preserving quality of life. We aimed to compare the efficacy and safety of MRI-guided SABR versus CT-guided percutaneous irreversible electroporation following standard FOLFIRINOX chemotherapy.
CROSSFIRE was an open-label, randomised phase 2 superiority trial conducted at the Amsterdam University Medical Centre (Amsterdam, Netherlands). Eligible patients were aged 18 years or older with confirmed histological and radiological stage III locally advanced pancreatic cancer. The maximum tumour diameter was 5 cm and patients had to be pretreated with three to eight cycles of FOLFIRINOX. Patients were randomly assigned (1:1) to MRI-guided SABR (five fractions of 8 Gy delivered on non-consecutive days) or CT-guided percutaneous irreversible electroporation using a computer-generated variable block randomisation model. The primary endpoint was overall survival from randomisation, assessed in the intention-to-treat population. Safety was assessed in the per-protocol population. A prespecified interim futility analysis was done after inclusion of half the original sample size, with a conditional probability of less than 0·2 resulting in halting of the study. The trial was registered at ClinicalTrials.gov, NCT02791503.
Between May 1, 2016, and March 31, 2022, 68 patients were enrolled and randomly assigned to SABR (n=34) or irreversible electroporation (n=34), of whom 64 were treated according to protocol. Of the 68 participants, 36 (53%) were male and 32 (47%) were female, with a median age of 65 years (IQR 57-70). Median overall survival from randomisation was 16·1 months (95% CI 12·1-19·4) in the SABR group versus 12·5 months (10·9-17·0) in the irreversible electroporation group (hazard ratio [HR] 1·39 [95% CI 0·84-2·30]; p=0·21). The conditional probability to demonstrate superiority of either technique was 0·13; patient accrual was therefore stopped early for futility. 20 (63%) of 32 patients in the SABR group versus 19 (59%) of 32 patients in the irreversible electroporation group had adverse events (p=0·8) and five (16%) patients in the SABR group versus eight (25%) in the irreversible electroporation group had grade 3-5 adverse events (p=0·35). The most common grade 3-4 adverse events were cholangitis (two [6%] in the SABR group vs one [3%] in the irreversible electroporation group), abdominal pain (one [3%] vs two [6%]), and pancreatitis (none vs two [6%]). One (3%) patient in the SABR group and one (3%) in the irreversible electroporation group died from a treatment-related adverse event.
CROSSFIRE did not identify a difference in overall survival or incidence of adverse events between MRI-guided SABR and CT-guided percutaneous irreversible electroporation after FOLFIRINOX. Future studies should further assess the added value of local ablative treatment over chemotherapy alone.
Adessium Foundation, AngioDynamics.
胰腺导管腺癌是一种侵袭性疾病，预后不良。局部晚期胰腺癌 III 期被认为不可切除，目前的姑息性化疗方案仅能适度改善生存。指南建议，在某些情况下，放化疗或立体定向消融体放射治疗（SABR）可能有益。其他局部治疗方法，如不可逆电穿孔，可以通过延长生存时间同时保持生活质量来提高患者的治疗效果。我们旨在比较 MRI 引导的 SABR 与 CT 引导的经皮不可逆电穿孔在标准 FOLFIRINOX 化疗后的疗效和安全性。
CROSSFIRE 是一项在阿姆斯特丹大学医学中心（荷兰阿姆斯特丹）进行的开放性、随机 2 期优效性试验。入组患者年龄在 18 岁或以上，组织学和影像学均确诊为局部晚期胰腺癌 III 期。最大肿瘤直径为 5cm，患者须接受 FOLFIRINOX 化疗 3-8 个周期。患者按 1:1 随机分配至 MRI 引导的 SABR（5 个 8Gy 剂量分次在非连续日给予）或 CT 引导的经皮不可逆电穿孔治疗，采用计算机生成的可变块随机化模型。主要终点是从随机分组开始的总生存期，在意向治疗人群中进行评估。安全性在方案人群中进行评估。在纳入原始样本量的一半后进行了预设的中期无效性分析，条件概率小于 0.2 导致研究停止。该试验在 ClinicalTrials.gov 上注册，NCT02791503。
2016 年 5 月 1 日至 2022 年 3 月 31 日，共纳入 68 例患者并随机分配至 SABR（n=34）或不可逆电穿孔（n=34）组，其中 64 例按方案接受治疗。68 名参与者中，36 名（53%）为男性，32 名（47%）为女性，中位年龄为 65 岁（IQR 57-70）。从随机分组开始的中位总生存期在 SABR 组为 16.1 个月（95%CI 12.1-19.4），在不可逆电穿孔组为 12.5 个月（10.9-17.0）（HR 1.39 [95%CI 0.84-2.30]；p=0.21）。证明两种技术均具有优势的条件概率为 0.13；因此，出于无效性的原因，患者的入组提前停止。32 例 SABR 组患者中有 20 例（63%）和 32 例不可逆电穿孔组患者中有 19 例（59%）发生不良事件（p=0.8），32 例 SABR 组中有 5 例（16%）和 32 例不可逆电穿孔组中有 8 例（25%）发生 3-5 级不良事件（p=0.35）。最常见的 3-4 级不良事件是胆管炎（SABR 组 2 例[6%]，不可逆电穿孔组 1 例[3%]）、腹痛（SABR 组 1 例[3%]，不可逆电穿孔组 2 例[6%]）和胰腺炎（SABR 组无，不可逆电穿孔组 2 例[6%]）。SABR 组 1 例（3%）和不可逆电穿孔组 1 例（3%）患者因治疗相关不良事件死亡。
CROSSFIRE 并未发现 FOLFIRINOX 化疗后 MRI 引导的 SABR 与 CT 引导的经皮不可逆电穿孔在总生存期或不良事件发生率方面存在差异。未来的研究应进一步评估局部消融治疗与单纯化疗相比的附加价值。
Adessium 基金会，AngioDynamics。
