麻豆传媒

The use of either MRI-guided stereotactic ablative body radiotherapy (SABR) or CT-guided percutaneous irreversible electroporation after standard FOLFIRINOX chemotherapy did not result in any significant difference in overall survival (OS) for adults with locally advanced pancreatic ductal adenocarcinoma, the phase II CROSSFIRE trial showed.

Among 68 patients, median OS from randomization was 16.1 months in the SABR group versus 12.5 months in the irreversible electroporation group (HR 1.39, 95% CI 0.84-2.30, P=0.21), with the trial stopped early due to meeting prespecified stopping rules for futility, reported Florentine Timmer, MSc, of Amsterdam University Medical Center, and colleagues.

There was also no significant difference in progression-free survival (PFS): 8.5 months in the SABR group versus 9.5 months in the irreversible electroporation group (HR 0.82, 95% CI 0.48-1.42, P=0.48), or in the rate of adverse events.

Thus, "SABR and irreversible electroporation might both be considered for temporary disease control in certain circumstances after FOLFIRINOX," Timmer and colleagues wrote in the .

In an , Zachary T. Berman, MD, and Rebekah R. White, MD, both of Moores Cancer Center at the University of California San Diego, noted that "this trial is important as it establishes that irreversible electroporation is at least comparable with SABR and that -- at an experienced center -- both techniques have considerable but acceptable rates of complications."

However, they suggested that a problem with generalizing results of local therapy studies "is the difficulty of assuring quality across multiple centers." This has been a criticism of previous radiation studies, and could be even more of an issue with irreversible electroporation, which has a considerable learning curve, they said, adding that these technologies are still evolving.

"For now, it is clear that some patients do benefit from local ablation, but more studies are needed to identify which patients, what modality of ablation, with what concomitant systemic therapies, and when," Berman and White wrote.

The was an open-label, randomized superiority study conducted at a center in Amsterdam. Eligible patients had confirmed histological and radiological stage III locally advanced pancreatic cancer, with a maximum tumor diameter of 5 cm. Patients had to be pretreated with three to eight cycles of FOLFIRINOX.

The 68 participants (median age 65, 53% men) were randomized to MRI-guided SABR consisting of five fractions of 8 Gy delivered on non-consecutive days, or CT-guided percutaneous irreversible electroporation using a computer-generated variable block randomization model.

Timmer and colleagues conducted several post-hoc survival analyses and found that median OS from diagnosis was 21.4 months in the SABR group compared with 18.2 months in the irreversible electroporation group (HR 1.29, 95% CI 0.78-2.1, P=0.33). Median local tumor PFS was 17.9 months versus 10.2 months, respectively (HR 1.83, 95% CI 0.87-3.9, P=0.11), and median distant PFS was 8.5 months versus 13.2 months (HR 0.43, 95% CI 0.23-0.81, P=0.007).

Regarding safety, 63% of patients in the SABR group experienced adverse events of any grade compared with 59% of those in the irreversible electroporation group, while 16% and 25%, respectively, experienced grade 3-5 adverse events.

The most common grade 3-4 adverse events were cholangitis (6% in the SABR group vs 3% in the irreversible electroporation group), abdominal pain (3% vs 6%), and pancreatitis (0% vs 6%).

One patient in each group died from a treatment-related adverse event. In the SABR group, the patient had bleeding of the ampulla of Vater, resulting in hemodynamic instability followed by death, while in the irreversible electroporation group, the patient had a fatal duodenal perforation.

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