Publications by authors named "Lorenzo Fornaro"

Article Synopsis
  • Paclitaxel plus ramucirumab is being evaluated as a second-line treatment for patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer, comparing it with continued oxaliplatin and fluoropyrimidine chemotherapy.
  • The ARMANI trial involved 280 patients, who were randomly assigned to receive either the new treatment regimen or continue with their current chemotherapy for an additional 12 weeks.
  • The primary goal of the study was to determine if the new treatment improved progression-free survival compared to the standard chemotherapy, with safety being closely monitored throughout the trial.
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Article Synopsis
  • In the TOPAZ-1 trial, patients with biliary tract cancers (BTC) who had recurrence within 6 months of surgery were excluded, which often happens in practice. This study looked into the effectiveness of cisplatin-gemcitabine-durvalumab (CGD) in patients who did experience early recurrence.
  • The study enrolled 178 BTC patients who had surgery and then underwent treatment with CGD after experiencing either early or late disease recurrence. Key goals were to measure overall survival (OS) and progression-free survival (PFS).
  • Results showed no significant differences in OS and PFS between early and late relapse groups, suggesting CGD is effective regardless of when the cancer
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Background And Aims: The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens.

Methods: A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS).

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Background: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.

Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia).

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Article Synopsis
  • The study aimed to assess the effectiveness and safety of tislelizumab combined with chemotherapy for advanced gastric cancer compared to a placebo with chemotherapy.
  • Conducted from December 2018 to February 2023 across multiple continents, it involved 1,657 adult patients with specific cancer types who had not previously undergone systemic treatment.
  • Results indicated that patients receiving tislelizumab plus chemotherapy experienced significant improvements in overall survival compared to those on placebo and chemotherapy.
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Background: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).

Objective: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting.

Patients And Methods: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone.

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Background: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6).

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Background: The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.

Objective: We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.

Methods: We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel.

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Introduction: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials.

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Prognosis in advanced gastric cancer (aGC) is predicted by clinical factors, such as stage, performance status, metastasis location, and the neutrophil-to-lymphocyte ratio. However, the role of body composition and sarcopenia in aGC survival remains debated. This study aimed to evaluate how abdominal visceral and subcutaneous fat volumes, psoas muscle volume, and the visceral-to-subcutaneous (VF/SF) volume ratio impact overall survival (OS) and progression-free survival (PFS) in aGC patients receiving first-line palliative chemotherapy.

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Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood.

Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH1, PMS2, MSH2, MSH6).

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Liver transplantation (LT) represents the primary curative option for HCC. Despite the extension of transplantation criteria and conversion with down-staging loco-regional treatments, transplantation is not always possible. The introduction of new standards of care in advanced HCC including a combination of immune checkpoint inhibitor-based therapies led to an improvement in response rates and could represent a promising strategy for down-staging the tumor burden.

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Article Synopsis
  • The study assessed the effectiveness and safety of durvalumab combined with gemcitabine and cisplatin in patients with advanced biliary tract cancer, following promising results from the TOPAZ-1 trial.
  • A total of 145 patients participated, with a median progression-free survival of 8.9 months and overall survival of 12.9 months, showing a 34.5% response rate to treatment.
  • Adverse events were common, with 94.5% experiencing some degree of side effect, but the serious immune-related side effects were relatively low at 2.1%, indicating that the treatment is generally manageable in a real-world setting.
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Background: Reliability of mismatch repair proteins and microsatellite instability assessment is essential in order to define treatment strategy and identify candidates to immune checkpoint inhibitors in locally advanced gastroesophageal carcinoma. We evaluated the concordance of deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status between endoscopic biopsies and surgical specimens.

Methods: Consecutive patients with resectable gastric or gastroesophageal junction adenocarcinoma classified as MSI-H/dMMR by polymerase chain reaction (PCR) or immunohistochemistry (IHC) and operated at three referral Institutions were included.

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Introduction: In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT.

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Cholangiocarcinoma is a rare group of tumors that involve the hepatic biliary tree. Prognosis for patients with cholangiocarcinoma remains dismal. Herein, we present survival trends over a long time period spanning almost 20 years in patients with advanced cholangiocarcinoma receiving systemic chemotherapy.

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Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms burdened by a dismal prognosis. Several studies have investigated the genomic profile of CCA and identified numerous druggable genetic alterations, including fusions/rearrangements. Approximately 5-7% of CCAs and 10-20% of intrahepatic iCCAs harbor fusions.

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Background: FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear.

Methods: This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status.

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Background: Isocitrate dehydrogenase-1 (IDH1) mutations occur in a significant proportion of intrahepatic cholangiocarcinomas (iCCAs). No data are available regarding the prognostic impact of IDH1 mutations in advanced iCCA patients after progression on first-line therapies.

Objective: We investigated the role of IDH1 mutation in advanced iCCA after progression on first-line therapies.

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Gastric cancer (GC) is recognized as one of the most common deadly malignancies worldwide and about 40-50% of patients present at diagnosis with an unresectable disease due to a locally advanced or already metastatic condition. Recently, therapeutic options for management of metastatic GC (mGC) have been approved allowing a potential improvement of patient cancer treatment response and also an establishment of a continuum of care for this aggressive disease. This report is the result of a literature review by an expert panel.

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