Background: The increasing methodological and regulatory demands of clinical trials have increased the need for clearly defined roles, particularly for Clinical Study Coordinators (CSCs) and Data Managers (DMs). While these professionals play crucial roles in the successful conduction of trials, the lack of established consensus on their profile, role, and responsibilities can lead to overlap and inefficiencies. This review aimed to identify the distinct roles of CSCs and DMs, examine their responsibilities, and explore the roles and responsibilities of CSCs and DMs and, when available, aspects of their collaboration. Methods: We conducted a systematic review to analyze the distinct roles and responsibilities of CSCs and DMs. A literature search was performed in PubMed, CINAHL, Scopus, and Web of Science for primary studies published between 1 January 2000 and 30 September 2024. Eligible studies focused on defining CSC and DM roles, competencies, and professional responsibilities in clinical trials. Two independent reviewers screened articles, assessed methodological quality, and evaluated the risk of bias. The registration number is PROSPERO CRD42024599819. Results: Of the 599 records identified, we included 10 studies. CSCs are responsible for the operational side of trials, including patient recruitment, regulatory compliance, and oversight of trial procedures. At the same time, DMs focus on ensuring data accuracy, integrity, and adherence to regulatory standards. The review highlighted the complementary nature of these roles, suggesting that future research could explore how collaboration between the roles may help maintain data quality and meet the demands of modern clinical research. However, the need for standardized role definitions and formal training programs was a significant challenge. Discussion: This systematic review analyzes the roles of CSCs and DMs, emphasizing their complementary responsibilities in clinical trials. It highlights the need for structured training, standardized workflows, and certification programs to enhance efficiency, ensure regulatory compliance, and improve data quality. Conclusion: Clarifying the roles of CSCs and DMs and implementing structured training and certification programs are essential to improving trial efficiency. While direct evidence of CSC–DM collaboration was limited, included studies indicate that clear role delineation enhances data quality and regulatory compliance.

Patient-derived organoids (PDOs) have emerged as promising preclinical models for studying tumor biology and testing therapeutic strategies in oncology. These three-dimensional culture systems retain key histological, genetic, and functional characteristics of the original tumors, offering a unique opportunity to advance personalized medicine approaches in liver cancer. In this study, we present the methodological framework and preliminary findings of a prospective study aimed at generating and characterizing PDOs from patients with hepatocellular carcinoma (HCC) undergoing surgical resection. Tumor specimens were processed using an optimized protocol for organoid derivation, expansion, and cryopreservation. We evaluated the success rate of organoid establishment and the histo-molecular fidelity to the parental tumor. These early results demonstrate promising engraftment efficiency and maintenance of tumor-specific markers across passages. Our work highlights the potential of PDOs as a reliable and scalable platform for translational research in HCC, setting the stage for future applications in drug screening and biomarker discovery.

Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide and represents the second cause of cancer-related death worldwide, according to the estimates by Global Cancer Observatory in 2020. Its prognosis is strictly associated with neoplastic stage and liver function. Several treatments are involved in the management of HCC, according to its stage and the patients’ performance status. The abscopal effect is a particular phenomenon taking place in locally advanced or in metastatic cancer, as a positive off-target result of ionizing radiation at a certain distance from the irradiated zone determining a systemic effect due to the increase in tumor immune response, and resulting in the shrinkage of neoplastic lesions with a subsequent increase in tumor prognosis. If future studies will allow one to master its etiological mechanisms and deliberately trigger them, it could represent a notable weapon in the treatment of hepatocellular carcinoma, particularly at advanced stages, in which sometimes it is able to positively modify the patients’ prognosis. The aim of this review is to evaluate the literature available on this intriguing topic and the characteristics of the mechanisms that originate the abscopal effect, the treatments that can elicit this phenomenon, and the possible relevant therapeutic implications.

Background/Objectives: Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide and a leading cause of cancer-related mortality. The majority of cases arise in the setting of chronic liver disease, where immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of systemic therapy for advanced disease. However, durable clinical benefit remains limited to a minority of patients, and reproducible biomarkers of ICI response are lacking. The gut–liver axis—encompassing bidirectional exchange of microbial products, metabolites, bile acids, and immune signals—has emerged as a biologically plausible determinant of both hepatocarcinogenesis and immunotherapy response. This narrative review synthesises current evidence on the role of the gut–liver axis in HCC and ICI response and proposes a unifying conceptual framework to resolve discrepancies in the existing literature. Methods: A narrative review was conducted through systematic searches of PubMed/MEDLINE, Embase, and Web of Science. Studies were selected based on relevance to the biological mechanisms, clinical associations, and experimental models underpinning gut–liver–immune interactions in HCC, with particular emphasis on studies providing mechanistic insight, addressing immunotherapy outcomes, or highlighting temporal and context-dependent effects. Results: Observational studies consistently associate higher microbial diversity and enrichment of homeostasis-promoting taxa—including Akkermansia, Bifidobacterium, and short-chain fatty acid-producing Ruminococcaceae—with ICI responsiveness in HCC. Functional microbial outputs, particularly short-chain fatty acids and secondary bile acids, exert mechanistically grounded effects on hepatic immune tone and T cell activity that are biologically proximate to ICI effector pathways. Therapeutic modulation of the gut–liver axis through probiotics, dietary interventions, faecal microbiota transplantation, and antibiotic exposure demonstrates context-dependent effects on immune activation and ICI outcomes, with timing and disease severity emerging as critical determinants. The limited reproducibility of microbiome-immunotherapy associations across cohorts is attributable primarily to the dynamic and treatment-sensitive nature of the gut–liver axis rather than a fundamental lack of mechanistic coupling. Conclusions: The gut–liver axis in HCC is best understood as a dynamic, treatment-sensitive system rather than a static baseline trait. This reframing shifts emphasis from single-timepoint taxonomic signatures toward functional and longitudinal readouts and provides a coherent rationale for the heterogeneity observed across existing studies. Longitudinal clinical studies incorporating mechanistic endpoints and functional biomarker assessment are needed to translate this framework into clinically actionable strategies for patient stratification and microbiota-targeted intervention in HCC immunotherapy.