MRI-guided stereotactic ablative body radiotherapy versus CT-guided percutaneous irreversible electroporation for locally advanced pancreatic cancer (CROSSFIRE): a single-centre, open-label, randomised phase 2 trial.

Autor:	Timmer FEF; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands. Electronic address: interventieradiologie@amsterdamumc.nl., Geboers B; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Ruarus AH; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Vroomen LGPH; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Schouten EAC; Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands., van der Lei S; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Vos DJW; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Dijkstra M; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Schulz HH; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Bakker J; Department of Medical Oncology, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., van den Bemd BAT; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., van den Tol PM; Department of Surgery, Medical Center Leeuwarden, Leeuwarden, Netherlands., Puijk RS; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands., Lissenberg-Witte BI; Department of Epidemiology and Data Science, Amsterdam University Medical Center, Amsterdam, Netherlands., de Gruijl TD; Department of Medical Oncology, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., de Vries JJJ; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands., Lagerwaard FJ; Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Scheffer HJ; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, Northwest Clinics, Alkmaar, Netherlands., Bruynzeel AME; Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands., Meijerink MR; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	The lancet. Gastroenterology & hepatology [Lancet Gastroenterol Hepatol] 2024 May; Vol. 9 (5), pp. 448-459. Date of Electronic Publication: 2024 Mar 19.
DOI:	10.1016/S2468-1253(24)00017-7
Abstrakt:	Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Adessium Foundation, AngioDynamics. Competing Interests: Declaration of interests MM, HS, BG, AR, LV, TdG, and FT received research funding from the Adessium Foundation for the conduct of the CROSSFIRE trial and PANFIRE 3 trial. MM, HS, BG, AR, LV, TdG, and FT received research funding from AngioDynamics for the conduct of the PANFIRE trials, and the CROSSFIRE trial. MM, HS, FT, TdG, and BG received research funding from Idera Pharmaceuticals and BMS for the conduct of the PANFIRE 3 trial. TdG received research funding from Glycostem. MM, HS, TdG, and DV received research funding from AngioDynamics and Immunophotonics for the conduct of the INJECTABLE-II trial. AB received research funding from ViewRay. MM received research funding from Johnson & Johnson and Medtronic. MM, HS, BG, FT, HHS, SvdL, MD, BvdB and RP received travel support from AngioDynamics. AB received speaker fees and travel support from ViewRay. MM and HS received consulting fees from AngioDynamics, and MM received consulting fees from Medtronic. TdG received consulting fees from LAVA Therapeutics, GE Health, and Mendus. ES, JB, PvdT, BLW, FL, and JdV declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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