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1.
Health Phys ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38535982

RESUMEN

ABSTRACT: Radioembolization using 90Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons' exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

2.
Dig Liver Dis ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38548580

RESUMEN

BACKGROUND: Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence. METHODS: A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves). RESULTS: Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03-3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52-3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB. CONCLUSIONS: PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients.

4.
Clin Res Hepatol Gastroenterol ; 48(2): 102282, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38191073

RESUMEN

BACKGROUND: Integrating immunotherapy with locoregional therapies marks a significant milestone in the realm of hepatocellular carcinoma (HCC) treatment . This study aimed to assess the impact of addition of Atezolizumab-Bevacizumab (AtezoBev) on the outcome patients treated with SIRT. METHODS: We conducted a study that included all Child-Pugh A HCC treated with SIRT since 2017. We examined the effects of the addition of 3 infusions of AtezoBev before the SIRT procedure and after SIRT on patients outcome (AtezoBev-SIRT group). Time-to-event data were analyzed using Kaplan-Meier with the log-rank test. RESULTS: Thirty five HCC patients treated with SIRT were included, of whom 23 % also received AtezoBev infusions. The two groups were similar in terms of liver function and HCC parameters. The median OS was not reached for patients who received AtezoBev in combination with SIRT and 14 months for patients only treated by SIRT. The median PFS was higher in the group treated by SIRT and AtezoBev vs SIRT alone (11.3 months vs 5.8 months). In the global cohort, 8 patients presented a downstaging (23 %), 4 underwent liver surgery (1 in the AtezoBev-SIRT group) and 4 liver transplantation (1 in the AtezoBev-SIRT group) CONCLUSIONS: The administration of AtezoBev, both before and after SIRT, is associated with enhanced OS and PFS outcomes compared to SIRT alone for unresectable HCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Bevacizumab/uso terapéutico , Resultado del Tratamiento
5.
Liver Int ; 44(4): 931-943, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38291735

RESUMEN

INTRODUCTION: It has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic-associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab-Bevacizumab (AtezoBev). METHODS: We collected data from 295 AtezoBev-treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model. RESULTS: Risk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow-up, 10% of patients experienced immune-related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors. CONCLUSION: Our study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hígado Graso , Neoplasias Hepáticas , Enfermedades Metabólicas , Masculino , Humanos , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico
6.
Hepatology ; 79(1): 213-223, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36631021

RESUMEN

BACKGROUND AND AIMS: Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients. RESULTS: Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT. CONCLUSIONS: Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Hipertensión Portal , Neoplasias Hepáticas , Várices , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/prevención & control , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Lagunas en las Evidencias , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Hipertensión Portal/diagnóstico , Cirrosis Hepática/complicaciones , Várices/complicaciones , Endoscopía Gastrointestinal/efectos adversos
8.
Hepatology ; 79(1): 49-60, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37870270

RESUMEN

BACKGROUND AND AIMS: We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival. APPROACH AND RESULTS: We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival ( p =0.032). CONCLUSIONS: RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Bevacizumab/uso terapéutico , Tomografía Computarizada por Rayos X
9.
Nat Commun ; 14(1): 8290, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38092727

RESUMEN

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Aprendizaje Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Estudios Retrospectivos
10.
United European Gastroenterol J ; 11(10): 985-997, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38018771

RESUMEN

BACKGROUND AND AIMS: We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). METHOD: All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. RESULTS: 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival. CONCLUSION: Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Hipertensión Portal , Hipertensión , Neoplasias Hepáticas , Humanos , Femenino , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/radioterapia , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/epidemiología , Várices Esofágicas y Gástricas/etiología , Ascitis/etiología , Ascitis/complicaciones , Resultado del Tratamiento , Hemorragia Gastrointestinal/complicaciones , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Hipertensión/complicaciones
13.
Clin Res Hepatol Gastroenterol ; 47(8): 102199, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37666414

RESUMEN

BACKGROUND: Long-term albumin infusions have been associated with improved outcomes in decompensated cirrhotic patients. This study aimed to evaluate the impact of albumin infusion on the prognosis of Child-Pugh B patients undergoing treatment with AtezoBev for advanced hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective multicentric study that included all Child-Pugh B cirrhotic patients treated with AtezoBev since 2020. We examined the effects of albumin infusion (40 g every 3 weeks) on overall survival (OS) and the occurrence of cirrhosis-related complications. Time-to-event data were analyzed using Kaplan-Meier with the log-rank test and Cox models. RESULTS: Forty-seven HCC patients with a Child-Pugh B score who received AtezoBev were included, of whom 26% also received albumin infusions every 3 weeks. The two groups were similar in terms of liver function and HCC parameters. The median OS was 4.4 and 5.8 months (p = 0.42) for patients who did or did not receive albumin, respectively. The occurrence of hepatic encephalopathy and variceal bleeding was similar between the two groups. However, albumin infusions were associated with a significantly lower rate of ascites expansion/development (13% versus 57%, p = 0.005). Cox analysis revealed that a history of ascites (HR=3.82 [95% CI: 1.73-8.48]) was independently associated with a higher risk of ascites expansion/development, whereas albumin infusions were protective (HR=0.07 [95% CI: 0.01-0.54]). CONCLUSIONS: Albumin infusion did not improve overall survival in Child-Pugh B HCC patients treated with AtezoBev, but it significantly reduced the expansion/development of ascites.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Retrospectivos , Várices Esofágicas y Gástricas/complicaciones , Ascitis/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Albúminas
14.
BMC Gastroenterol ; 23(1): 305, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37697230

RESUMEN

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.


Asunto(s)
Gastroenterólogos , Hidrotórax , Hipertensión Portal , Derrame Pleural , Humanos , Hidrotórax/diagnóstico , Hidrotórax/etiología , Hidrotórax/terapia , Neumólogos , Derrame Pleural/diagnóstico , Derrame Pleural/etiología , Derrame Pleural/terapia
15.
JHEP Rep ; 5(8): 100794, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37520673

RESUMEN

Background & Aims: Liver regeneration is a repair process in which metabolic reprogramming of parenchymal and inflammatory cells plays a major role. Monoacylglycerol lipase (MAGL) is an ubiquitous enzyme at the crossroad between lipid metabolism and inflammation. It converts monoacylglycerols into free fatty acids and metabolises 2-arachidonoylglycerol into arachidonic acid, being thus the major source of pro-inflammatory prostaglandins in the liver. In this study, we investigated the role of MAGL in liver regeneration. Methods: Hepatocyte proliferation was studied in vitro in hepatoma cell lines and ex vivo in precision-cut human liver slices. Liver regeneration was investigated in mice treated with a pharmacological MAGL inhibitor, MJN110, as well as in animals globally invalidated for MAGL (MAGL-/-) and specifically invalidated in hepatocytes (MAGLHep-/-) or myeloid cells (MAGLMye-/-). Two models of liver regeneration were used: acute toxic carbon tetrachloride injection and two-thirds partial hepatectomy. MAGLMye-/- liver macrophages profiling was analysed by RNA sequencing. A rescue experiment was performed by in vivo administration of interferon receptor antibody in MAGLMye-/- mice. Results: Precision-cut human liver slices from patients with chronic liver disease and human hepatocyte cell lines exposed to MJN110 showed reduced hepatocyte proliferation. Mice with global invalidation or mice treated with MJN110 showed blunted liver regeneration. Moreover, mice with specific deletion of MAGL in either hepatocytes or myeloid cells displayed delayed liver regeneration. Mechanistically, MAGLHep-/- mice showed reduced liver eicosanoid production, in particular prostaglandin E2 that negatively impacts on hepatocyte proliferation. MAGL inhibition in macrophages resulted in the induction of the type I interferon pathway. Importantly, neutralising the type I interferon pathway restored liver regeneration of MAGLMye-/- mice. Conclusions: Our data demonstrate that MAGL promotes liver regeneration by hepatocyte and macrophage reprogramming. Impact and Implications: By using human liver samples and mouse models of global or specific cell type invalidation, we show that the monoacylglycerol pathway plays an essential role in liver regeneration. We unveil the mechanisms by which MAGL expressed in both hepatocytes and macrophages impacts the liver regeneration process, via eicosanoid production by hepatocytes and the modulation of the macrophage interferon pathway profile that restrains hepatocyte proliferation.

16.
BMC Cancer ; 23(1): 710, 2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37516867

RESUMEN

BACKGROUND: Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non-small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. METHODS: Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. DISCUSSION: Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. TRIAL REGISTRATION: NCT05528952.


Asunto(s)
Vacunas contra el Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Telomerasa , Humanos , Bevacizumab , Vacunas contra el Cáncer/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Microambiente Tumoral
18.
Ann Hepatol ; 28(6): 101141, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37468096

RESUMEN

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

19.
Aliment Pharmacol Ther ; 58(3): 346-356, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37300315

RESUMEN

BACKGROUND: Baveno VI and VII criteria are used in patients with cirrhosis to rule out large size oesophageal varices (EV) and rule in/out clinically significant portal hypertension (CSPH). AIM: To evaluate their diagnostic performance in these patients. METHODS: We retrospectively included all patients with Child-Pugh A cirrhosis and HCC who had endoscopy, liver stiffness measurement (LSM) and platelet count within 6 months. They were classified according to the BCLC stage. Favourable Baveno VI criteria were defined by LSM < 20 kPa and platelets > 150 G/L (to rule out large EV), favourable Baveno VII criteria if LSM ≤ 15 kPa and platelets ≥ 150 G/L (to rule out CSPH, which was defined by a HVPG ≥ 10 mm Hg. RESULTS: We included 185 patients; 46% were BCLC-0/A, 28% BCLC-B and 26% BCLC-C. EV were present in 44% (23% large), and HVPG ≥ 10 mm Hg in 42% (mean 8 mm Hg). In patients with favourable Baveno VI criteria, 8% of the whole cohort (Se 93%, NPV 92%), 11% of BCLC-0-A (Se 89%, NPV 89%) and 10.0% of BCLC-C patients (Se 91%, NPV 90%) had large EV. Among patients with HVPG < 10 mm Hg, 6% had large EV and 17% small. CSPH was present in 23% of patients with favourable Baveno VII criteria among the whole cohort, and in 25% of those with BCLC-0/A. The specificity of LSM ≥ 25 kPa to rule in CSPH was 48%. CONCLUSIONS: Favourable Baveno VI criteria are not appropriate to rule out the presence of high-risk EV, or Baveno VII criteria to rule CSPH in/out in patients with HCC.


Asunto(s)
Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas , Hipertensión Portal , Neoplasias Hepáticas , Várices , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Estudios Retrospectivos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Hipertensión Portal/diagnóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Endoscopía Gastrointestinal
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