The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.

Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers. GDF15 modulates tumor progression through PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, thereby promoting epithelial-to-mesenchymal transition, metastasis, immune evasion, and chemoresistance via Nrf2 stabilization and oxidative stress regulation.

Censoring in trials testing immunotherapy in advanced cancers. A systematic review and a meta-research study.

Background: Informative censoring affects interpretation of trials results. We investigated censoring rates in randomized controlled trials (RCTs) of immune checkpoint inhibitors (ICIs).

Methods: We searched articles of RCTs testing ICIs in advanced cancers, published up to 12/2023.

Time tO last ChemotherApy and death in ovaRian cancEr patients: TO CARE/MITO 42 study, a retrospective analysis of italian MITO centers.

Introduction: The European Society for Medical Oncology (ESMO) 2021 Guidelines contraindicate the administration of chemotherapy in the last month of patients' life. The main objective of this multicenter observational retrospective study was to calculate the time elapsed between the date of the last chemotherapy and the date of death of patients with ovarian cancer. The secondary objectives were to identify any factors associated with a greater probability of receiving chemotherapy in the end of life.

6-year treatment follow-up with an extended-release alkaline formulation (Sibnayal) in primary distal renal tubular acidosis.

Background: Distal renal tubular acidosis (dRTA) is a rare disease characterized by hyperchloremic metabolic acidosis affecting growth, bone and kidney health.

Methods: The aim of B22CS study was to evaluate long-term safety and efficacy (anthropometric/pubertal, tubular damages/kidney function, bone biomarkers, compliance assessments) of Sibnayal, a prolonged-release alkalinizing formulation with twice daily dosing, in children and adults with dRTA. All patients were previously included in the pivotal B21CS study, so were already receiving Sibnayal when included in B22CS open-label follow-up study.

Postnatal determinants of testicular germ cell tumor by histological subtypes: The EPSAM1 and EPSAM2 studies.

The EPSAM study is an ongoing case-control study evaluating the postnatal risk factors for testicular germ-cell tumor (TGCT). We aimed at updating the risk estimates for factors identified in previous EPSAM analyses and studying heterogeneities between seminomas and non-seminomas. TGCT cases (N = 358) and controls (N = 459) were recruited in two phases (EPSAM1, population-based, and EPSAM2, hospital based).

NRG/ErbB signaling: on the trail of a molecular fingerprint in mucinous carcinoma.

Introduction: Human neuregulins (NRG) are small epidermal growth factor ligands involved in the activation of ErbBs receptors. Among genomic aberrations, NRG fusions are one of the most intriguing genetic markers reported in the latest years, due to their agnostic and potentially predictive features. Mucinous carcinoma showed a higher rate of mutations in downstream effectors of NRG/ErbB activation, thus suggesting that RAS/MAPK and PIK3K/AKT pathway are involved in mucinous phenotype development and aggressiveness.

Patient-reported outcomes (PROs) in clinical trials and in clinical practice: report from the XXI national conference of the Italian Association of Medical Oncology (AIOM).

Objective: Patient-reported outcomes (PROs) are considered the gold standard for the assessment of subjective symptoms, quality of life (QoL) and patient well-being in both clinical trials and clinical practice. Here, we report key discussions and findings from the 21st National Conference of the Italian Association of Medical Oncology, held in Bologna on 21-22 June 2024, with a focus on the integration and impact of PROs in oncology research and clinical practice.

Methods And Analysis: Leading national and international experts presented and analysed data regarding the use of PROs in clinical trials and routine oncology care.

Reading and Interpreting Quality-of-Life Results in Cancer Trials.

AbstractThere is growing attention paid to patient-reported outcomes and health-related quality of life as end points in clinical trials in oncology. Such results should contribute to the definition of treatment value, inform communication with patients in clinical practice, and impact treatment choice among various options. This review seeks to help clinicians gain familiarity with the correct reading and interpretation of quality-of-life results.

A prospective study on clinicians' attitudes and survival outcomes for patients with advanced NSCLC and poor performance status in the immunotherapy era: PICASO (GOIRC-04-2020).

Background: Therapeutic strategies for patients with advanced NSCLC and an ECOG performance status (PS) 2 at diagnosis are supported by limited evidence.

Patients And Methods: We led a prospective, observational study in 20 Italian centers on patients with advanced NSCLC and ECOG PS 2. Patients with EGFR mutations, ALK fusions or receiving first-line targeted treatments were excluded.

Comparison of baseline patient characteristics in phase 1 and phase 2/3 clinical trials for anticancer treatments.

Background: Characteristics of patients significantly differ between registrational clinical trials (CTs) and Italian real-world practice, with older median age, higher elderly (≥ 65) rate and worse performance status (PS) in the latter, without imbalance in female rate. We compared the same characteristics between registrational phase 2/3 and phase 1 CTs.

Methods: Data on age, sex and PS were extracted from European Public Assessment Reports of European Medicines Agency.

Association Between Health-Related Quality of Life Measures and Survival Endpoints in Oncology Clinical Trials and in Clinical Decision Making: A Narrative Review.

For decades, oncology research has primarily relied on survival-based endpoints, such as progression-free survival and overall survival, to evaluate treatment efficacy. However, recent studies and international guidelines underscore the importance of incorporating patient-reported outcomes through patient-reported outcomes measures (PROMs). PROMs provide a more comprehensive view of treatment effectiveness, integrating the concepts of 'living longer' and 'living better.

Delphi consensus on the management of adverse events in patients with metastatic triple-negative breast cancer treated with sacituzumab govitecan.

Background: Metastatic triple-negative breast cancer (BC; mTNBC) is one of the most aggressive cancers, difficult to treat due to the absence of hormone target receptors. Sacituzumab govitecan (SG) is a new therapeutic approach that exploits the combination of an antibody directed against the Trop-2 antigen expressed in solid epithelial tumors and the active metabolite SN-38, to precisely target cancer cells. The development of consensus recommendations requires synthesizing expert opinions, especially when direct evidence is limited.

Press releases of industry-sponsored clinical trials in oncology: Characteristics, timing and financial impact.

Background: Press releases (PRs) anticipate the results of a clinical trial, possibly without providing detailed data. The purpose of this analysis was to describe the characteristics of PRs in oncology, delays in the availability of results and the impact on the financial market.

Materials And Methods: PRs published between 2018 and 2022 about solid tumors, archived on the websites of the top 20 oncology pharmaceutical companies, were screened.

eNRGy: Making progress toward a future for NRG1 fusion-positive cancer.

The eNRGy trial demonstrated zenocutuzumab's efficacy in advanced cancer with NRG1 fusion, mainly non-small cell lung and pancreatic cancers. Responses were observed across multiple tumor types identified through RNA-based next-generation sequencing, with low-grade adverse events. This suggests a potentially agnostic role of NRG1 fusions in solid tumors and underscores the need for comprehensive gene fusion testing in patients with cancer.

Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status.

Background: The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) with a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) or a non-BRCA homologous recombination repair mutation (non-BRCA HRRm).

Methods: Patients were in response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then central gBRCAm testing to determine sBRCAm or gBRCAm status. An exploratory cohort evaluated non-BRCA HRRm in 13 predefined genes.

Multicenter external validation of a novel aggregated technique for percutaneous CT guided lung biopsy for multiple samplings: the ExtraPEARL study.

Objectives: To evaluate the reproducibility of the PEARL approach to decrease pneumothorax rates by different board-certified radiologists across multiple medical centers using standard CT units.

Materials And Methods: This multicenter observational study included four average volume centers in two countries. Data for the PEARL cohort were prospectively collected between January 2022 and May 2023, while the control cohort data were retrospectively collected from procedures performed between June 2021 and April 2022.

Impact of edoxaban-related adverse events in patients with cancer experiencing venous thromboembolism during antineoplastic therapy: Results of the phase IV EDOI study (GOIRC-05-2018).

Background: The oral factor Xa inhibitor, edoxaban, is effective and safe in cancer-associated Venous Thromboembolism (VTE) treatment. The EDOI study aims to evaluate compliance and quality of life (QoL) in patients with cancer-associated VTE treated with edoxaban during antineoplastic care.

Material And Methods: The EDOI was a multicentre phase IV, single-arm study.

Advancing treatment choices: CDK4/6 inhibitor switching in HR+/HER2- metastatic breast cancer.

Purpose: CDK4/6 inhibitors (CDK4/6i) use has revolutionized the treatment of hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer. The choice of a specific CDK4/6i may be influenced by adverse events (AEs). Recently, the Italian Medicines Agency (AIFA) approved the possibility of switching between CDK4/6i for unacceptable toxicity.

Health-related quality of life assessment in head and neck cancer: A systematic review of phase II and III clinical trials.

Background: Patients with head and neck cancer (HNC) bear a significant load, due to both disease-related symptoms and to toxicities associated with treatments. Evaluating quality of life (QoL) is crucial to gauge the physical and psychological impact on these patients. Our primary aim was to assess whether QoL has been incorporated as an endpoint in phase II and III clinical trials for HNC patients in the last 15 years.

Viral Hepatitis in Western Patients with Advanced Intrahepatic Cholangiocarcinoma: Retrospective Assessment of Prevalence, Prognostic and Predictive Significance.

Despite a biologically established causative role of viral hepatitis (VH), i.e. HBV and HCV infections, on intrahepatic cholangiocarcinoma (ICC), only few large Western cohorts exploring the association between VH and ICC development are available.

Breast-cancer specific comprehensive archive of Patient-Reported Outcome Measures (PROMs) for clinical research and clinical practice in oncology: Results from the PRO4All project.

Background: Inclusion of patient-reported outcomes (PROs) in oncology clinical trials is strongly recommended. However, selecting the most appropriate patient-reported outcome measures (PROMs) is not easy. This study aimed to develop a breast cancer (BC) specific comprehensive archive of PROMs.