Cancers

Background: Glypican-3 (GPC3) is overexpressed in most hepatocellular carcinoma (HCC) tissues but is absent in normal adult liver. We evaluated whether tumor GPC3 expression is associated with clinical outcomes in patients with advanced HCC treated with atezolizumab–bevacizumab (AB). Methods: We conducted a single-center retrospective cohort study of 139 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received AB between January 2022 and August 2025. Tumor GPC3 expression was assessed by immunohistochemistry. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Baseline characteristics were largely balanced between GPC3-positive (n = 87) and GPC3-negative (n = 52) groups. Median OS was significantly shorter in patients with GPC3-positive tumors than in those with GPC3-negative tumors (p = 0.006). In multivariable analysis, GPC3 positivity remained independently associated with higher mortality (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.05–3.00; p = 0.033), along with Child–Pugh class B. PFS did not differ significantly between the groups (p = 0.712). ORR was lower in GPC3-positive tumors than in GPC3-negative tumors (approximately 17–18% vs. ~32%; p = 0.023). Membranous GPC3 localization was associated with inferior OS compared with cytoplasmic or absent expression (p = 0.025). Conclusions: Tumor GPC3 expression was associated with decreased OS and lower ORR among AB-treated patients with advanced HCC, suggesting potential clinical relevance and may help in risk stratification.

Objectives: To evaluate the prognosis and costs of gemcitabine + cisplatin + S-1 (GCS) versus gemcitabine + cisplatin + durvalumab (GCD), the standard of care for advanced cholangiocarcinoma, in a prospective observational study. Methods: We enrolled 52 patients who received GCS as first-line treatment from April 2020 to April 2024 and 44 patients who received GCD from March 2023 to April 2024. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were examined. Propensity score matching (PSM) was performed to balance baseline characteristics between the two groups, and OS, PFS and ORR were then analysed in the matched cohorts. Drug costs were compared until the end of treatment. Results: OS was not significantly different between GCS and GCD at 18.6 months (95% confidence interval [CI]: 13.3–21.9) (p = 0.0935) versus 12.2 months (95% CI: 7.5–16). PFS was 10.2 months (95% CI: 6.5–13.8) versus 6.2 months (95% CI: 3.2–8.8) for GCS versus GCD, respectively (p = 0.0151). The ORR was also higher for GCS (36.5%) than for GCD (15.9%) (p = 0.0234). Twenty-seven patients were included in the PSM analysis, which showed no significant differences in OS or ORR, and better PFS for GCS (9.3 months, 95% CI: 7.4–21.1 versus 4.8 months, 95% CI: 2.7–8.8; p = 0.007). The cost of GCS versus GCD was $6350 (95% CI: 2300–9800) versus $97,200 (95% CI: 69,400–138,800) by treatment end (p = 0.0001). Conclusions: GCS was significantly less expensive than GCD and showed comparable OS and better PFS.

Background/Objectives: Myeloid sarcoma (MS) is a rare extramedullary manifestation of myeloid blasts, with limited systematic data, particularly regarding molecular (NGS) concordance between MS tissue and bone marrow. We hypothesized that clonal heterogeneity may exist between these sites due to their distinct biological environments. Methods: We conducted a systematic review and meta-analysis of 85 studies encompassing 7241 MS patients, to evaluate clinical characteristics, mutational profiles, treatment patterns, and outcomes. Mutational concordance or discordance between MS and bone marrow was assessed in a subset of 112 patients. Results: Male predominance (59%) and skin/soft tissue localization (31%) were most common. NPM1 (25%) and FLT3 (20%) were the most frequently reported mutations. Among 112 patients with paired sequencing, 56% showed discordance in mutational profiles. NPM1 was significantly enriched in MS sites compared to bone marrow (35% vs. 21%, p = 0.02) and was associated with skin involvement. Discordance was more frequent in isolated and secondary MS. Venetoclax with hypomethylating agents achieved a 44% response rate, mainly in secondary MS. Post-transplant isolated extramedullary relapse occurred in 46% of relapsed patients and was linked to high rates of graft-versus-host disease. The pooled median overall survival was 12.8 months. Conclusions: MS demonstrates significant molecular heterogeneity. Routine site-specific NGS profiling may guide targeted therapy in this rare disease.