Citations 2
Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort
Yanagihara, Ted K. , Dawson, Laura A., Yu, Jeong Il, Lawrence, Theodore S. , Kim, T S, Yan, Michael, Iwata, Hiromitsu , Nabavizadeh, Nima , Apisarnthanarax, Smith , Dunne, Emma M., Lock, Michael , Chuong, Michael D., Chiang, Chi Leung, Katoh, Norio , Sioshansi, Shirin, Numata, Kazushi, Liu, Howard , Wakatsuki, Masaru , Chen, YiXing, Pollom, Erqi L., Gkika, Eleni , Dutta, Debnarayan , Hajj, Carla , Hallemeier, Christopher L. , Feldman, Aharon, Romero, Alejandra Méndèz , Tan, Xianming , Tepper, Joel E. , Torres, Ferràn , Bergman, Alanah M., Crane, Christopher, Cuneo, Kyle C., Grindrod, Natalie, Grosu, Anca-Ligia, Far, R. El, Funaoka, Akihiro, Gilbert, Marissa, Itasaka, Satoshi , Lee, Sung Uk , Mases, Joel , Ogino, Hiroyuki , Qu, Vera , Park, Hee Chul, Rahmani, Ramtin, Shing, Lee Ann, Stanescu, Teodor, Thonglert, Kanokphorn , Toom, Wilhelm den , Uchinami, Yusuke , Zeng, Zhaochong, Moon, Andrew M , Yanagihara, Ted K , Lawrence, Theodore S , Kim, Tae Hyun , Iwata, Hiromitsu , Nabavizadeh, Nima , Apisarnthanarax, Smith , Lock, Michael I , Chuong, Michael , Chiang, Chi Leung , Scorsetti, Marta , Katoh, Norio , Liu, Howard Yu-Hao , Iwamoto, Hideki , Pollom, Erqi Liu , Gkika, Eleni , Jabbour, Salma K , Munoz-Schuffenegger, Pablo , Dutta, Debnarayan , Hajj, Carla , Ueno, Masayuki , Hallemeier, Christopher Leigh , Feldman, Aharon M , Méndèz Romero, Alejandra , Tan, Xianming , Tepper, Joel E , Torres, Ferran , Reig, Maria , Dawson, Laura A. , Yu, Jeong Il , Dunne, Emma Maria , Chuong, Michael D. , Numata, Kazushi , Mollà, Meritxell , Crane, Christopher H. , Cuneo, Kyle Clifford , Grindrod, Natalie , Franzese, Ciro , Gilbert, Marissa, Lee, Yoo Young , Lee, Ann‐Shing, Shirono, Tomotake , Stanescu, Teo
Journal of Clinical Oncology | May 15, 2026 | Volume: 44 | Issue: 19 | Pages: 1784-1797
PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.
Simvastatin and Rifaximin in Decompensated Cirrhosis
Pose, Elisa , Jiménez, César , Zaccherini, Giacomo , Campion, Daniela , Wit, Koos de , Gananandan, Kohilan , Laleman, Wim , López, Sonia Alonso , Cuyàs, Berta , Ariza, Xavier , T., Ann , Napoleone, Laura , Gratacós‐Ginès, Jordi , Tonon, Marta , Pompili, Enrico , Sánchez‐Delgado, Jordi , Allegretti, Andrew S. , Carol, Marta, Pich, Judit, Martell, Claudia, Joyera, María, Domènech, Gemma, Ríos, José , Torres, Ferràn , Serra‐Burriel, Miquel , Graupera, Isabel , Bañares, Rafael, Beuers, Ulrich , Angeli, Paolo, Alessandria, Carlo , Kamath, Patrick S. , Vargas, Vı́ctor , Ma, Ann T , de Wit, Koos , Vargas, Victor , Jiménez, César , Cuyas, Berta , Torres, Ferran , Piano, Salvatore , Uschner, Frank Erhard , Roux, Olivier , Solé, Cristina , Juanola, Adrià , Morales‐Ruiz, Manuel , Pérez, Martina , Fabrellas, Núria , Joyera, Maria, Hernaez, Ruben , Solà, Elsa , Watson, Hugh R , Soriano, German , Bañares, Rafael , Mookerjee, Rajeshwar P. , Francoz, Claire , Trebicka, Jonel , Angeli, Paolo , Caraceni, Paolo , Vargas, Víctor M., Abraldeṣ, Juan G. , Ginès, Pere
JAMA | February 5, 2025 | Volume: 333 | Issue: 10 | Pages: 864
ImportanceThere are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.ObjectiveTo assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.Design, Setting, and ParticipantsDouble-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.InterventionsPatients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months in addition to standard therapy, stratified according to Child-Pugh class B or C.Main Outcomes and MeasuresThe primary end point was incidence of severe complications of liver cirrhosis associated with organ failure meeting criteria for acute-on-chronic liver failure. Secondary outcomes included transplant or death and a composite end point of complications of cirrhosis (ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection).ResultsAmong the 237 participants randomized (Child-Pugh class B: n = 194; Child-Pugh class C: n = 43), 72% were male and the mean age was 57 years. There were no differences between the 2 groups in terms of development of acute-on-chronic liver failure (21 [17.9%] vs 17 [14.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 1.23; 95% CI, 0.65-2.34; P = .52); transplant or death (22 [18.8%] vs 29 [24.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.75; 95% CI, 0.43-1.32; P = .32); or development of complications of cirrhosis (50 [42.7%] vs 55 [45.8%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.93; 95% CI, 0.63-1.36; P = .70). Incidence of adverse events was similar in both groups (426 vs 419; P = .59), but 3 patients in the treatment group (2.6%) developed rhabdomyolysis.Conclusions and RelevanceThe addition of simvastatin plus rifaximin to standard therapy does not improve outcomes in patients with decompensated liver cirrhosis.Trial RegistrationClinicalTrials.gov Identifier: NCT03780673