TY - JOUR
T1 - Radiofrequency Ablation and Chemotherapy vs Chemotherapy Only in Locally Advanced Pancreatic Cancer
T2 - The PELICAN Randomized Clinical Trial
AU - Seelen, Leonard W F
AU - Brada, Lilly J H
AU - Walma, Marieke S
AU - Rombouts, Steffi J E
AU - Braat, Manon N
AU - Bollen, Thomas L
AU - Borel Rinkes, Inne H
AU - Bruijnen, Rutger C G
AU - Busch, Olivier R
AU - Cirkel, Geert A
AU - Daamen, Lois A
AU - Daams, Freek
AU - van Dam, Ronald M
AU - van Delden, Otto M
AU - Derksen, Wouter J M
AU - Festen, Sebastiaan
AU - Groothuis, Karin
AU - Hagendoorn, Jeroen
AU - de Hingh, Ignace H J T
AU - D'Hondt, Mathieu
AU - Liem, Mike S L
AU - van Lienden, Krijn P
AU - Los, Maartje
AU - de Meijer, Vincent E
AU - Mekenkamp, Leonie J M
AU - Nijkamp, Maarten W
AU - Nio, C Yung
AU - Pando, Elizabeth
AU - Patijn, Gijs A
AU - Polée, Marco B
AU - Te Riele, Wouter W
AU - Roeyen, Geert
AU - Stommel, Martijn W J
AU - de Vos-Geelen, Judith
AU - de Vries, Jan J
AU - Wessels, Frank J
AU - Wilmink, Johanna W
AU - van de Ven, Peter M
AU - Besselink, Marc G
AU - van Santvoort, Hjalmar C
AU - Molenaar, I Quintus
PY - 2026/3/31
Y1 - 2026/3/31
N2 - IMPORTANCE: The poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival.OBJECTIVE: To assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC.DESIGN, SETTING, AND PARTICIPANTS: This international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025.INTERVENTION: Randomization to receive either RFA with chemotherapy or chemotherapy alone.MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module.RESULTS: Overall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14.6, -12.0, and -18.4 were observed for the Global Health Status quality-of-life scores at 1, 3, and 18 months, respectively, numerically exceeding the threshold of 10 points for clinical relevance. In the chemotherapy-only group, mean changes from baseline on the Global Health Status remained below the threshold for clinical relevance.CONCLUSIONS AND RELEVANCE: This randomized clinical trial of patients with LAPC after 2 months of multiagent chemotherapy found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and adversely affected patient's quality of life.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03690323.
AB - IMPORTANCE: The poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival.OBJECTIVE: To assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC.DESIGN, SETTING, AND PARTICIPANTS: This international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025.INTERVENTION: Randomization to receive either RFA with chemotherapy or chemotherapy alone.MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module.RESULTS: Overall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14.6, -12.0, and -18.4 were observed for the Global Health Status quality-of-life scores at 1, 3, and 18 months, respectively, numerically exceeding the threshold of 10 points for clinical relevance. In the chemotherapy-only group, mean changes from baseline on the Global Health Status remained below the threshold for clinical relevance.CONCLUSIONS AND RELEVANCE: This randomized clinical trial of patients with LAPC after 2 months of multiagent chemotherapy found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and adversely affected patient's quality of life.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03690323.
KW - Humans
KW - Pancreatic Neoplasms/therapy
KW - Male
KW - Female
KW - Middle Aged
KW - Aged
KW - Radiofrequency Ablation/methods
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Quality of Life
KW - Fluorouracil/therapeutic use
KW - Leucovorin/therapeutic use
KW - Gemcitabine
KW - Oxaliplatin/therapeutic use
KW - Combined Modality Therapy
KW - Irinotecan/therapeutic use
U2 - 10.1001/jamanetworkopen.2026.3861
DO - 10.1001/jamanetworkopen.2026.3861
M3 - Article
C2 - 41915391
SN - 2574-3805
VL - 9
JO - JAMA network open
JF - JAMA network open
IS - 3
M1 - e263861
ER -