Modelling hepatocellular carcinoma microenvironment phenotype to evaluate drug efficacy.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Treating HCC is challenging because of the poor drug effectiveness and the lack of tools to predict patient responses. To resolve these issues, we established a patient-centric spheroid model using HepG2, TWNT-1, and THP-1 co-culture, that mimics HCC phenotype.

SUNLAND: a randomized, double-blinded phase II GERCOR trial of sunitinib versus placebo and lanreotide in patients with advanced progressive midgut neuroendocrine tumors.

Background: Sunitinib, a multitarget tyrosine kinase inhibitor, showed encouraging antitumor activity and manageable toxicity in patients with advanced midgut neuroendocrine tumors (NETs) in earlier results from phase I and II trials.

Patients And Methods: In this phase II trial, patients with a nonresectable grade 1 or 2 midgut progressive NET and Eastern Cooperative Oncology Group performance status 0-1 were randomly assigned 1:1 to receive 37.5 mg sunitinib or a placebo, combined with 120 mg lanreotide autogel every 28 days.

Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Background & Aims: In the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was non-inferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs.

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from Lu. The objective of this work was to explore how postinfusion [Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity.

A phase Ib/II trial of capmatinib plus spartalizumab spartalizumab alone in patients with pretreated hepatocellular carcinoma.

Background & Aims: This phase Ib/II trial evaluated the safety and efficacy of capmatinib in combination with spartalizumab or spartalizumab alone in patients with advanced hepatocellular carcinoma (HCC).

Methods: Eligible patients who had progressed or were intolerant to sorafenib received escalating doses of capmatinib 200 mg, 300 mg, and 400 mg twice a day (bid) plus spartalizumab 300 mg every 3 weeks (q3w) in the phase Ib study. Once the recommended phase II dose (RP2D) was determined, the phase II study commenced with randomised 1:1 treatment with either capmatinib + spartalizumab (n = 32) or spartalizumab alone (n = 30).

Effectiveness of endoscopic ultrasound (EUS)-guided choledochoduodenostomy vs. EUS-guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study).

Objectives: The aim of this study was to compare endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) vs. EUS-gallbladder drainage (EUS-GBD) in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) for jaundice resulting from malignant distal biliary obstruction (MDBO).

Methods: This multicenter retrospective study included patients with obstructive jaundice secondary to MDBO who underwent EUS-GBD or EUS-CDS with lumen-apposing metal stents after failed ERCP.

Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations: state of the art and future perspectives.

Despite the improvements in surgical and medical therapy for hepatocellular carcinoma (HCC), recurrence still represents a major issue. Up to 70% of patients can experience HCC recurrence after liver resection (LR), as well as 20% of them even after liver transplantation (LT). The patterns of recurrence are different according to both the time and the location.

Triplet chemotherapy plus cetuximab as first-line treatment in extended RAS wild-type metastatic colorectal cancer patients.

Background: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX+cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients.

Methods: We retrospectively analyzed patients treated with FOLFIRINOX+cetuximab, using data from clinical trials and real-life practice.

FGF19 and its analog Aldafermin cooperate with MYC to induce aggressive hepatocarcinogenesis.

FGF19 hormone has pleiotropic metabolic functions, including the modulation of insulin sensitivity, glucose/lipid metabolism and energy homeostasis. On top of its physiological metabolic role, FGF19 has been identified as a potentially targetable oncogenic driver, notably in hepatocellular carcinoma (HCC). Nevertheless, FGF19 remained an attractive candidate for treatment of metabolic disease, prompting the development of analogs uncoupling its metabolic and tumor-promoting activities.

Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial.

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. In this phase II study (ClinicalTrials.

Atezolizumab and bevacizumab for non-resectable or metastatic combined hepatocellular-cholangiocarcinoma: A multicentric retrospective study.

Backgrounds: The efficacy of atezolizumab/bevacizumab has never been reported in patients with metastatic/unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA).

Patients And Methods: We retrospectively included patients with a histological diagnosis of unresectable/metastatic cHCC-CCA and treated with atezolizumab/bevacizumab (2020-2022) in 7 centers. Clinical and radiological features were collected at the beginning of atezolizumab/bevacizumab.

Circulating Tumor DNA Clinical Applications in Hepatocellular Carcinoma: Current Trends and Future Perspectives.

Background: Globally, liver cancers are the second most lethal malignancy after lung cancer (0.83 million deaths in 2020). Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer and is typically associated with liver fibrosis or cirrhosis.

A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors.

Background And Purpose: Stereotactic body radiation therapy (SBRT) has demonstrated safe and effective results for primary liver tumors. Magnetic Resonance guided Radiotherapy (MRgRT) is an innovative radiotherapy modality for abdominal tumors. The aim of this study is to report on acute and late toxicities and initial oncological results for primary liver tumors treated with MRgRT.

Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: a randomized non-comparative phase II study (TERTIO - PRODIGE 82).

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.

Large, multifocal or portal vein-invading hepatocellular carcinoma (HCC) downstaged by Y90 using personalized dosimetry: safety, pathological results and outcomes after surgery.

Background: Transarterial radioembolization (TARE) has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas (HCCs) with high rates of complete pathological necrosis (CPN) on liver explants. In patients with portal vein tumoral thrombus (PVTT), multifocal or large tumors, TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population. Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series.

Background: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.

Atezolizumab plus bevacizumab in advanced hepatocellular carcinoma after treatment failure with multikinase inhibitors.

Background And Aims: Data on the effectiveness of atezolizumab plus bevacizumab (atezo-bev) after failure of multikinase inhibitor (MKI) therapy in patients with advanced hepatocellular carcinoma are scarce.

Methods: This retrospective multicentre study included all consecutive patients treated with atezo-bev after failing one or more MKI treatments in the setting of an early access program. The primary endpoint was the objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.