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).

Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: A multicentre case-control study.

Background & Aims: Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients.

Methods: Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment.

Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: Longer Term Follow-Up from the Phase 3 KEYNOTE-240 Trial.

Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.

Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo.

A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors.

Background: Deregulation of FGF19-FGFR4 signaling is found in several cancers, including hepatocellular carcinoma (HCC), nominating it for therapeutic targeting. FGF401 is a potent, selective FGFR4 inhibitor with antitumor activity in preclinical models. This study was designed to determine the recommended phase 2 dose (RP2D), characterize PK/PD, and evaluate the safety and efficacy of FGF401 alone and combined with the anti-PD-1 antibody, spartalizumab.

Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial.

Purpose: KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with advanced HCC and no prior systemic therapy.

Patients And Methods: KEYNOTE-224 was an open-label, multicountry phase II trial.

Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib.

Objective: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported.

Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial.

Objective: In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy.

Methods: CELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo.

Curative Irradiation Treatment of Hepatocellular Carcinoma: A Multicenter Phase 2 Trial.

Purpose: Liver transplantation is the standard definitive treatment for nonmetastatic hepatocellular carcinoma (HCC). However, less than 5% of patients are ultimately candidates as a result of frequent comorbidities and graft shortage. The aim of this study was to evaluate stereotactic body radiation therapy (SBRT) as an ablative treatment for inoperable HCC.

MSH2 c.1022T>C, p.Leu341Pro is a founder pathogenic variation and a major cause of Lynch syndrome in the North of France.

Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well-known genes such as the DNA-mismatch repair (MMR) genes involved in Lynch syndrome. We report the characterization of a variant in MSH2: c.1022T>C, which was identified in 20 apparently unrelated families living in the North of France.

Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial.

Background: Immune checkpoint blockade therapy has shown promising results in patients with advanced hepatocellular carcinoma. We aimed to assess the efficacy and safety of pembrolizumab in this patient population.

Methods: KEYNOTE-224 is a non-randomised, multicentre, open-label, phase 2 trial that is set in 47 medical centres and hospitals across ten countries.

In which context is physician empathy associated with cancer patient quality of life?

Objective: In cancer settings, physician empathy is not always linked to a better patient emotional quality of life quality of life (eQoL). We tested two possible moderators of the inconsistent link: type of consultation (bad news versus follow-up) and patient emotional skills (emoSkills, i.e.

Patients with Crohn's Disease with High Body Mass Index Present More Frequent and Rapid Loss of Response to Infliximab.

Background: Infliximab (IFX) is effective in inducing and maintaining remission in patients with luminal and anoperineal Crohn's disease (CD). However, treatment failure within 12 months after initiating IFX is observed in a significant proportion of patients. The aim of the present study was to determine whether the body mass index (BMI) affects response to IFX during the first year of treatment in patients with CD.

Locally Advanced or Metastatic Pancreatic Adenocarcinoma: Easily Available Factors of Predictive Prolonged Survival Under Gemcitabine.

Background: Prognosis of patients with locally advanced or metastatic pancreatic adenocarcinoma is poor. In this study, we assessed the predictive value of easily available baseline factors for prolonged survival.

Patients And Methods: We conducted a retrospective study on patients who received gemcitabine between 1999 and 2010 for locally advanced or metastatic pancreatic adenocarcinoma.

CA-125, but not galectin-3, complements CA 19-9 for discriminating ductal adenocarcinoma versus non-malignant pancreatic diseases.

Background/objectives: CA 19-9 is the gold standard biomarker of pancreatic adenocarcinoma despite several weaknesses in particular a high rate of false positives or negatives. CA-125 corresponding to MUC16 and galectin-3, a lectin able to interact with mucin-associated carbohydrates, are tumor-associated proteins. We investigated whether combined measurement of CA 19-9, galectin-3 and CA-125 may help to better discriminate pancreatic adenocarcinoma versus non-malignant pancreatic diseases.

Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial.

Importance: Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma.

Objective: To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed.

Design, Setting, And Participants: EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib.

[Hereditary predisposition to cancers of the digestive tract, breast, gynecological and gonadal: focus on the Peutz-Jeghers].

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%).

Hepatocellular carcinoma screening in patients with compensated hepatitis C virus (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling approach.

Unlabelled: Because of the ongoing debate on the benefit of ultrasound (US) screening for hepatocellular carcinoma (HCC), we assessed the impact of screening on hepatitis C virus (HCV)-related compensated cirrhosis patients aware of their HCV status. A Markov model simulated progression from HCC diagnosis to death in 700 patients with HCV-related compensated cirrhosis aware of their HCV status to estimate life expectancy (LE) and cumulative death at 5 years. Five scenarios were compared: S1, no screening; S2, screening by currently existing practices (57% access and effectiveness leading to the diagnosis of 42% at Barcelona Clinic Liver Cancer stage [BCLC-0/A]); S3, S2 with increased access (97%); S4, S2 with an efficacy of screening close to that achieved in a randomized controlled trial leading to the diagnosis of 87% of patients at stage BCLC-0/A; S5, S3+S4.

High-dose FOLFIRI, surgery, and radiofrequency ablation for patients with unresectable liver metastases from colorectal cancer.

Background: To evaluate a strategy combining high-dose 5FU-irinotecan-leucovorin (HD-FOLFIRI) chemotherapy, radiofrequency ablation and surgery in patients with unresectable liver metastases from colorectal cancer.

Patients And Methods: Patients, all presenting UDP glucuronosyl transferase-1A1 (UGT1A1) 6/6 or 6/7 genotype, received HD-FOLFIRI (with high-dose irinotecan: 260 mg/m(2)), one cycle every two weeks. The feasibility of local therapy (surgery and/or radiofrequency) was assessed every four cycles.

Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large multicenter AGEO study.

Background & Aims: The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed.

Methods: This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010.

Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301).

Purpose: Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted.

Experience of gemcitabine plus oxaliplatin chemotherapy in patients with advanced biliary tract carcinoma.

Backgrounds: The combination gemcitabine-oxaliplatin (GEMOX) is frequently used in patients with advanced biliary tract carcinoma (BTC). However, this is only based on phase II studies performed in selected patients.We assessed the efficacy and safety of the GEMOX regimen in non-selected patients with advanced BTC.

Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a phase III multicentre, randomised, double blind placebo-controlled study.

Background: A previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma (HCC). This was investigated further in this multicentre study.

Patients And Methods: Two hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were randomised to receive long-acting octreotide, 30 mg as an intramuscular injection once every 4 weeks for up to 2 years, or placebo.

Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis.

Familial adenomatous polyposis has been linked to germline mutations in the APC tumor suppressor gene. However, a number of patients with familial adenomatous polyposis (with either classical or attenuated phenotype) have no APC mutation. Recently, germline mutations in the Wnt pathway component gene AXIN2 have been associated with tooth agenesis-colorectal cancer syndrome.

Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer.

In patients with metastatic colorectal cancer, the use of cetuximab currently requires a documented tumoral epidermal growth factor receptor positivity. Responses to cetuximab, however, have been described in patients with epidermal growth factor receptor-negative tumors. We have used cetuximab in all eligible patients with metastatic colorectal cancer, whether their tumor expressed epidermal growth factor receptor or not.