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OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: ⢠This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. ⢠Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Antineoplásicos/uso terapéutico , Quimioembolización Terapéutica/efectos adversos , Puntaje de Propensión , Estudios RetrospectivosAsunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/cirugía , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos/cirugía , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Estudios Retrospectivos , Hepatectomía , Resultado del TratamientoRESUMEN
Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.
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BACKGROUND: Marked arterioportal shunt (APS) can be a contraindication for transarterial radioembolization (TARE) because of the risk of radiation-induced liver toxicity or pneumonitis. To date, the best method to close marked APS to reduce intrahepatic shunt (IHS) and hepatopulmonary shunt (HPS) before TARE has not been elucidated. CASE SUMMARY: This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma (HCC). The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography, and digital subtraction angiography (DSA) confirmed the shunt. Selective right portal vein embolization (PVE) was performed to close the APS outlet and DSA confirmed complete closure. Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%. Successful TARE was subsequently performed. No major procedure-related complication occurred. CONCLUSION: Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.
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There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Estudios de Cohortes , Neoplasias Hepáticas/patología , Terapia Molecular Dirigida , Estudios RetrospectivosRESUMEN
PURPOSE: Hepatocellular carcinoma (HCC) is the fifth and seventh most common cause of cancer in men and women, respectively. Transcatheter arterial chemoembolization (TACE) is the standardized therapy for the intermediate stage of HCC. However, the 3-year overall survival remains low (<30 %) in these patients. Thus, there is a critical need for the development of treatment modalities to improve the survival rate. This study aimed to evaluate whether the combination of (131)I-metuximab with chemoembolization could improve treatment efficiency. METHODS: Between January 2009 and January 2010, a prospective two-arm nonrandomized study was performed in patients with intermediate HCC. Of 138 patients, 68 (combination therapy group) received 132 courses of intraarterial (131)I-metuximab injections combined with chemoembolization (mean 1.94 per patient, median 2, range 1-2), followed by 152 sessions of TACE (mean 2.24 per patient, median 2, range 0-4). The remaining 70 patients (monotherapy group) received 296 sessions of TACE (mean 4.23 per patient, median 4, range 1-7). RESULTS: The overall median survival times for the combination therapy group and the group treated only with TACE were 26.7 months (95 % CI 20.7-31.3 months) and 20.6 months (95 % CI 15.3-24.7 months), respectively. The combination therapy group had a significantly higher survival rate than the TACE-only group (P = 0.038). Age ≥65 years, serum albumin ≤35 g/l, and treatment category (combination therapy or TACE only) were independent prognostic factors for survival according to multivariate analysis. CONCLUSION: The combination of (131)I-metuximab and chemoembolization extended survival in patients with intermediate HCC compared with TACE only, and was well tolerated by patients with Child-Pugh class A or B disease. This combination seems to be a promising treatment modality for patients with intermediate HCC.
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Anticuerpos Monoclonales/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Arteria Hepática , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones , Radioisótopos de Yodo/uso terapéutico , Marcaje Isotópico , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radiografía , Seguridad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a neoplasm that rarely develops in adults. The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy. Here, we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1 (anti-PD-1) treatment. CASE SUMMARY: A 69-year-old woman was admitted for abdominal pain that developed for 1 wk. Computed tomography showed a 16 cm mass in the right lobe of the liver. Right hemihepatectomy and lymphadenectomy were performed, and histological diagnosis was UESL. Six months later, the patient suffered from painless obstructive jaundice, and positron emission tomography-computed tomography revealed multiple metastases. Then, percutaneous transhepatic cholangial drainage was applied to reduce jaundice, and radiofrequency ablation was used to control the lesion near the hepatic hilum. However, the patient suffered from a serious fever caused by the tumor. The patient received treatment with pembrolizumab, and the prescribed dosage was 2 mg/kg every 3 wk. After the seventh dose, positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared. Radiologic exam was used to evaluate the disease state, and no new lesions were found. Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab. Tumor mutation burden, microsatellite instability, and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of these biomarkers are detected in a tumor patient, the patient may be a proper candidate for PD-1 antibodies. CONCLUSION: Anti-PD-1 treatment for tumors needs further research to identify indications and proper biomarkers.
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. MATERIALS AND METHODS: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. RESULTS: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). CONCLUSIONS: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.
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Sistema de Transporte de Aminoácidos ASC/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Quimioembolización Terapéutica/mortalidad , Neoplasias Hepáticas/genética , Hígado/metabolismo , Polimorfismo de Nucleótido Simple/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Embolia Intracraneal/etiología , Neoplasias Hepáticas/terapia , Adulto , Antineoplásicos/administración & dosificación , Medios de Contraste/efectos adversos , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Humanos , Embolia Intracraneal/inducido químicamente , Embolia Intracraneal/patología , Aceite Yodado/efectos adversos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Few options are available to treat patients with hepatocellular carcinoma (HCC). It was tested whether the combination of iodine-131(¹³¹I)-metuximab with chemoembolization could improve outcomes in patients with intermediate HCC. Between April 2008 and April 2009, 110 patients with unresectable HCC were treated with 113 intra-arterial ¹³¹I-metuximab injections combined with chemoembolization (mean, 1.03 per patient; median, 1; range, 1-2), followed by 264 sessions of transcatheter arterial chemoembolization (mean, 2.4 per patient; median, 3; range, 1-6). The survival rates at 6, 12, and 18 months were 88.2%, 79.1%, and 57.4%, respectively, by the Kaplan-Meier method. Of these patients, 12% exhibited grade 3/4 bilirubin toxicity, 5% exhibited grade 3/4 white blood count toxicity, and 7% exhibited grade 3/4 platelet toxicity. Response rates based on World Health Organization and European Association for the Study of the Liver criteria were 42.73% and 61.82%, respectively. The combination of ¹³¹I-metuximab and chemoembolization appeared to extend survival in patients with unresectable HCC compared with historical controls, as well as being well tolerated by patients with Child-Pugh A and B. This combination may represent a promising treatment modality for patients with intermediate HCC.