Background: Inflammation is suggested to play a central role in cancer-related appetite loss, yet the available evidence remains limited. Methods: This study analyzed data from a prospective, longitudinal, multicenter study of patients with metastatic cancer followed for one year. The longitudinal associations between appetite loss and both clinical characteristics and inflammatory markers were examined. Logistic generalized equation model (GEE) was used. Results: Among 526 patients, 299 (57%) experienced appetite loss at baseline. During longitudinal observation appetite loss was associated with older age (OR 1.19, CI 1.01–1.39 as per 10-year years increase), poorer performance status (OR 0.85, CI 0.77–0.94), recent weight loss (OR 2.74, CI 2.11–3.56), and symptoms including constipation, nausea, fatigue, and lower emotional functioning. Corticosteroid use was associated with lower risk of appetite loss (OR 0.69, CI 0.53–0.90). Several inflammatory markers were also associated with appetite loss, including IL-8, IP-10, IL-6, CRP, eotaxin, albumin. Conclusions: Appetite loss in metastatic cancer is linked to clinical factors, symptom burden, and inflammatory markers. Optimizing symptom management and targeting inflammation might have a positive impact.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Immune checkpoint inhibitor (ICI)-based combinations have become the standard first-line systemic therapy, yet objective response rates remain modest (20–36%), and no HCC-specific immune biomarker has been validated to guide selection among standard ICI-based regimens. This review examines the prognostic and exploratory treatment-response associations of potential immune biomarkers in HCC, including markers within the tumor microenvironment (TME) and peripheral blood. A narrative review was conducted evaluating PD-L1 and soluble PD-L1, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), including machine learning-based assessment, gene expression profiles and tumor-intrinsic pathway alterations, long non-coding RNAs, inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alpha-fetoprotein), gut microbiota, and liquid biopsy analytes (circulating tumor DNA, circulating tumor cells, cell-free DNA). PD-L1 expression shows prognostic associations and inconsistent associations with ICI outcomes; inter-assay heterogeneity further limits its use, and routine PD-L1 testing is not recommended by current guidelines. TMB is generally low in HCC, with inconsistent associations with ICI response. High CD8+ TIL density is associated with improved survival after resection and favorable outcomes in exploratory ICI-treated cohorts, without validated treatment-selective utility. Inflammatory gene signatures and WNT/β-catenin pathway activation are associated with ICI outcomes. Gut microbiome features have shown exploratory associations with anti-PD-1 outcomes, with limited consistency across small datasets. Liquid biopsy markers, particularly ctDNA, show promise for recurrence prediction and treatment monitoring but lack assay standardization. Multiple immune biomarkers demonstrate prognostic value in HCC, and pre-existing immunity characterized by high CD8+ T-cell infiltration and inflammatory gene signatures is associated with improved ICI-based therapy outcomes in exploratory studies. However, these exploratory markers have not been validated for routine selection among HCC regimens. Future directions include prospective validation of composite biomarker panels, standardization of assessment methodologies, and integration of artificial intelligence for TME characterization.
Background/Objectives: Medullary thyroid cancer (MTC) is a rare but aggressive neuroendocrine malignancy arising from parafollicular C cells. Despite its low incidence, MTC has historically been estimated to account for 13.4% of thyroid cancer-related deaths. Survival outcomes remain limited in advanced disease, with a historical cohort reporting a 10-year survival of 21% for stage IV MTC, supporting the need for novel therapeutic approaches. Carcinoembryonic antigen (CEA), a fetal glycoprotein minimally expressed in normal adult tissues, is elevated in various malignancies and plays an established role in carcinogenesis, metastasis, and therapy resistance. In MTC, CEA is produced by neoplastic C cells alongside calcitonin, and both serum and tumor-associated CEA levels are markedly elevated relative to healthy tissue. More than half of MTC patients demonstrate elevated CEA, and intense CEA immunohistochemical staining correlates with aggressive, disseminated disease, highlighting its potential utility as both a biomarker and investigational therapeutic target in the disease. For MTC, surgery is the mainstay for locoregional disease with the intent for complete surgical resection when possible. Systemic therapy is generally reserved for structurally progressive, unresectable, symptomatic, or threatening advanced disease, with selective RET inhibitors used in RET-mutant disease and multi-kinase TKIs as additional treatment options. Although TKIs have improved progression-free survival, treatment can be limited by toxicities and the development of resistance over time. These limitations underscore the need for novel therapeutic strategies that can achieve more durable disease control and improve overall survival. Given its strong association with tumor burden, disease progression, and aggressive pathology, CEA represents a promising investigational target for therapeutic exploration in MTC. Methods: A narrative literature review was performed to evaluate carcinoembryonic antigen (CEA) as a therapeutic target and biomarker in medullary thyroid cancer (MTC). Searches were conducted in 2025 and 2026 using PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. Conclusions: The current literature supports further investigation of CEA targeting as a therapeutic strategy in MTC. However, CEA is not yet a clinically validated therapeutic target and clinical trial data remain limited.
Background: Outcomes for advanced or recurrent endometrial cancer (EC) remain poor, with historically limited systemic options beyond platinum-based chemotherapy. EC is uniquely immunotherapy-amenable among solid tumors: it harbors the highest prevalence of mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) status of any cancer, and its molecular classification into four major molecular subtypes defines a spectrum of tumor mutational burden, neoantigen load, and immune infiltration that predicts the response to checkpoint blockade. Current Landscape: Over the past several years, multiple programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have received regulatory approval in EC, spanning monotherapy in dMMR/MSI-H disease, combination with carboplatin–paclitaxel in the first-line advanced setting, and combination with anti-angiogenic therapy in biomarker-unselected recurrent disease, fundamentally altering the standard of care. Scope and Objectives: This narrative review synthesizes the molecular rationale for checkpoint inhibition in EC, including the biological basis of its molecular subtypes and their immune microenvironments, and provides a focused overview of the trial evidence supporting each major checkpoint inhibitor class, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T-lymphocyte-associated protein 4 inhibitors, and emerging targets. We further review the landscape of ongoing trials addressing unresolved questions, including chemotherapy-free regimens in dMMR disease, maintenance intensification for mismatch repair-proficient (pMMR) disease, neoadjuvant and fertility-sparing approaches, and novel combinations. This review aims to provide a comprehensive, up-to-date synthesis of this rapidly evolving field and to identify challenges and opportunities that will shape the next phase of immunotherapy in EC.
Venous tumor thrombus (VTT) is a clinically important manifestation of malignancy that creates diagnostic, therapeutic, and prognostic challenges. Evidence is highly uneven across tumor types: renal cell carcinoma and hepatocellular carcinoma account for much of the available clinical experience, whereas data for rarer tumors, including sarcomas, remain limited. This narrative review was based on a structured PubMed search supplemented by relevant publications identified through reference checking and subsequent topic-specific reading. We review the incidence, imaging evaluation, surgical and non-surgical management, and prognosis of VTT across major malignancies. Although several considerations are shared across tumor types, including assessment of thrombus extent, venous wall involvement, venous patency, collateral circulation, resectability, and systemic disease status, their clinical implications differ according to the underlying malignancy. In particular, treatment strategies established in well-studied tumors should not be directly extrapolated to rarer malignancies with different tumor biology, treatment sensitivity, and patterns of disease progression. A cross-tumor approach may therefore be most useful for defining common questions in VTT assessment and multidisciplinary planning, while treatment decisions remain tumor-specific. Future progress will require standardized reporting, multicenter collaboration, and better integration of emerging systemic therapies into multidisciplinary care.
