First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort
Background & Aims: Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide obs...
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2025-02-01
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| author | Nicolas Adamus Julien Edeline Julie Henriques Nadim Fares Thierry Lecomte Anthony Turpin Dewi Vernerey Mathilde Vincens Brice Chanez David Tougeron Christophe Tournigand Eric Assenat Matthieu Delaye Sylvain Manfredi Olivier Bouché Nicolas Williet Angelique Vienot Lorraine Blaise Léo Mas Cindy Neuzillet Alice Boilève Gaël S. Roth |
| author_facet | Nicolas Adamus Julien Edeline Julie Henriques Nadim Fares Thierry Lecomte Anthony Turpin Dewi Vernerey Mathilde Vincens Brice Chanez David Tougeron Christophe Tournigand Eric Assenat Matthieu Delaye Sylvain Manfredi Olivier Bouché Nicolas Williet Angelique Vienot Lorraine Blaise Léo Mas Cindy Neuzillet Alice Boilève Gaël S. Roth |
| author_sort | Nicolas Adamus |
| collection | DOAJ |
| description | Background & Aims: Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL. Methods: Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups. Results: Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 vs. 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, p <0.0001), a trend for longer OS (median = 22.5 vs. 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% vs. 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, p <0.0001), and resection rate (18.7% vs. 8.8%, p = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, p <0,0001), OS (HR 0.70, 95% CI 0.58-0.85, p = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, p <0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, p <0.0001). Conclusions: Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results. Impact and implications:: Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that this study constitutes new evidence of the potential benefit of combining SIRT with chemotherapy. The safety and efficacy of this strategy whether as a bridge to intent-to-cure strategies or in a palliative setting, should encourage its adoption in a larger panel of clinical centers, or at very least, prompt clinicians to refer their patients to centers where SIRT is performed. Clinical trial number: NCT04935853. |
| format | Article |
| id | doaj-art-64e9095da6d34768847aa6c405a6ef12 |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-64e9095da6d34768847aa6c405a6ef122025-02-07T04:48:09ZengElsevierJHEP Reports2589-55592025-02-0172101279First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohortNicolas Adamus0Julien Edeline1Julie Henriques2Nadim Fares3Thierry Lecomte4Anthony Turpin5Dewi Vernerey6Mathilde Vincens7Brice Chanez8David Tougeron9Christophe Tournigand10Eric Assenat11Matthieu Delaye12Sylvain Manfredi13Olivier Bouché14Nicolas Williet15Angelique Vienot16Lorraine Blaise17Léo Mas18Cindy Neuzillet19Alice Boilève20Gaël S. Roth21Univ. Grenoble Alpes, Department of Hepato-Gastroenterology and Digestive Oncology, CHU Grenoble Alpes, Grenoble; Association pour l'étude des Cancers et Affections des voies Biliaires (ACABi); GERCOR, Paris, FranceDepartment of Medical Oncology, Centre Eugène Marquis, Rennes, France and INSERM, Univ Rennes, COSS (Chemistry Oncogenesis Stress Signaling), UMR_S 1242, Rennes, FranceDepartment of Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon; University Bourgogne Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceDepartment of Digestive Oncology, CHU of Toulouse, Rangueil Hospital, Toulouse, FranceDepartment of Hepato-Gastroenterology and Digestive Oncology, CHU Tours and UMR INSERM U 1069, Trousseau Hospital, Tours University, Tours, FranceDepartment of Medical Oncology, CHU Lille, CNRS UMR9020, INSERM UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille University; GERCOR, Paris, FranceDepartment of Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon; University Bourgogne Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceDepartment of Medical Oncology and Hepato-Gastroenterology, Hospices Civils de Lyon, Lyon, FranceDepartment of Medical Oncology, Paoli-Calmette Institute, Marseille, FranceDepartment of Hepato-Gastroenterology, Poitiers University Hospital, Poitiers, FranceDepartment of Medical Oncology, Henri Mondor Hospital, AP-HP, Paris-East Créteil University and INSERM, IMRB, Creteil, FranceDepartment of Medical Oncology, CHU St Eloi, Montpellier University 2, CNRS, UMR 5535, Institute of Molecular Genetic, Montpellier 1 University, Montpellier, FranceGI Oncology, Department of Medical Oncology, Institute Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud; Molecular Oncology, UMR144, Institute Curie, Paris, FranceBourgogne University, CHU Dijon-Bourgogne, INSERM U1231. BP 87 900, Dijon, FranceDepartment of Gastroenterology and Digestive Oncology, CHU Reims, Université Reims Champagne Ardennes (URCA), Reims, FranceDepartment of Hepato-Gastroenterology and Gastrointestinal Oncology, University Institute of Cancerology and Hematology of Saint-Etienne (ICHUSE), Saint-Etienne, FranceDepartment of Medical Oncology, University Hospital of Besançon, Besançon, FranceLiver unit, Avicenne Hospital, Universitaires Paris-Seine-Saint-Denis Hospital, Assistance-Publique Hôpitaux de Paris, Bobigny; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité; Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, FranceDepartment of Oncology, Pitié-Salpêtrière Hospital, AP-HP; University of La Sorbonne, Paris, FranceGI Oncology, Department of Medical Oncology, Institute Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud; Molecular Oncology, UMR144, Institute Curie, Paris, FranceDepartment of Medicine, Gustave Roussy Hospital, INSERM U1279, Villejuif; University of Paris Saclay, Orsay, FranceUniv. Grenoble Alpes/Department of Hepato-Gastroenterology and Digestive Oncology, CHU Grenoble Alpes/Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France; Corresponding author. Address: Department of Hepato-Gastroenterology and Digestive Oncology; Team Immunology and Cancer - Institute for Advanced Biosciences, Grenoble–INSERM U1209 - CNRS UMR 5309, University Hospital of Grenoble-Alpes, Grenoble, France; Tel.: +33 4 76 76 51 68.Background & Aims: Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL. Methods: Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups. Results: Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 vs. 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, p <0.0001), a trend for longer OS (median = 22.5 vs. 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% vs. 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, p <0.0001), and resection rate (18.7% vs. 8.8%, p = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, p <0,0001), OS (HR 0.70, 95% CI 0.58-0.85, p = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, p <0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, p <0.0001). Conclusions: Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results. Impact and implications:: Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that this study constitutes new evidence of the potential benefit of combining SIRT with chemotherapy. The safety and efficacy of this strategy whether as a bridge to intent-to-cure strategies or in a palliative setting, should encourage its adoption in a larger panel of clinical centers, or at very least, prompt clinicians to refer their patients to centers where SIRT is performed. Clinical trial number: NCT04935853.http://www.sciencedirect.com/science/article/pii/S2589555924002830cholangiocarcinomabiliary tract cancerSIRTradioembolizationCISGEMGEMOX |
| spellingShingle | Nicolas Adamus Julien Edeline Julie Henriques Nadim Fares Thierry Lecomte Anthony Turpin Dewi Vernerey Mathilde Vincens Brice Chanez David Tougeron Christophe Tournigand Eric Assenat Matthieu Delaye Sylvain Manfredi Olivier Bouché Nicolas Williet Angelique Vienot Lorraine Blaise Léo Mas Cindy Neuzillet Alice Boilève Gaël S. Roth First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort JHEP Reports cholangiocarcinoma biliary tract cancer SIRT radioembolization CISGEM GEMOX |
| title | First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort |
| title_full | First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort |
| title_fullStr | First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort |
| title_full_unstemmed | First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort |
| title_short | First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort |
| title_sort | first line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma the french acabi gercor pronobil cohort |
| topic | cholangiocarcinoma biliary tract cancer SIRT radioembolization CISGEM GEMOX |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002830 |
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