TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial

Cyrille Féray (1) , Loic Campion (2) , Philippe Mathurin (3, 4) , Isabelle Archambreaud (5, 6) , Xavier Mirabel (7) , Jean Pierre Bronowicki (8, 9) , Emmanuel Rio (2) , Christophe Perret (10) , Laurent Mineur (11) , Frédéric Oberti (12) , Yann Touchefeu (5) , Jérôme Gournay (5, 6) , Hélène Regnault (13) , Julien Edeline (14) , Agnès Rode (15) , Patrick Hillion (16) , Jean Frédéric Blanc (17, 18) , Eric Nguyen Khac (19, 20) , Daniel Azoulay (1) , Alain Luciani (21) , Athena Galetto Preglisasco (21) , Elodie Faurel-Paul (10) , Hélène Auble (10) , Françoise Mornex (22, 23) , Philippe Merle (24, 25)

1 Physiopathologie et traitement des maladies du foie
2 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
3 Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
4 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
5 CHU Nantes - Centre Hospitalier Universitaire de Nantes
6 Institut des Maladies de l'Appareil Digestif
7 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
8 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
9 Service d'Hépato-gastro-entérologie [CHRU Nancy]
10 Hôtel-Dieu de Nantes
11 Institut Sainte Catherine [Avignon]
12 CHU Angers - Centre Hospitalier Universitaire d'Angers
13 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
14 OSS - Oncogenesis, Stress, Signaling
15 Service de Radiologie [Hôpital de la Croix-Rousse - HCL]
16 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
17 Hôpital Haut-Lévêque [CHU Bordeaux]
18 BaRITOn - Bordeaux Research In Translational Oncology [Bordeaux]
19 CHU Amiens-Picardie
20 GRAP - Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247
21 Service de Radiologie [Mondor]
22 CICLY - Centre pour l'innovation en cancérologie de Lyon
23 Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL]
24 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
25 Service d'Hépatologie et de Gastroentérologie [Lyon]

Background & aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical TACE.Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy.Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the 'per-protocol' group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40-1.18; p = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34-1.06; p = 0.081) than in arm A. Liver-related grade III-IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23-35) in arm A and 22 months (95% CI 15.7-26.2) in arm B.Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects.Impact and implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment.

Mots clés: 3-DCRT; three-dimensional conformal radiotherapy; AE; adverse event; ALBI; albumin–bilirubin; BCLC; Barcelona Clinic Liver Cancer; CRT; conformal radiotherapy; CT; computed tomography; CTV; clinical tumour volume; Conformal external radiotherapy; ECOG; Eastern Cooperative Oncology Group; HCC; hepatocellular carcinoma; HR; hazard ratio; Hepatocellular carcinoma; ITT; intention-to-treat; OS; overall survival; PFS; progression-free survival; PS; propensity score; RILD; radio-induced liver disease; SBRT; stereotaxic body radiation therapy; TACE; transcatheter arterial chemoembolisation; TTP; time to tumour progression; mRECIST; modified Response Evaluation Criteria in Solid Tumour

Domaines: Médecine humaine et pathologie

Cyrille Féray, Loic Campion, Philippe Mathurin, Isabelle Archambreaud, Xavier Mirabel, et al.. TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial. JHEP Reports Innovation in Hepatology, 2023, 5 (4), pp.100689. ⟨10.1016/j.jhepr.2023.100689⟩. ⟨hal-04044132⟩