Long-term nucleos(t)ide analog (NUC) treatment improves the outcomes of patients with chronic hepatitis B virus (HBV) infection. However, only a limited number of patients treated with NUC can achieve hepatitis B surface antigen (HBsAg) seroclearance, the so-called “functional cure.” However, it remains unclear how on-treatment viral factors affect HBsAg seroclearance during long-term NUC treatment. We aimed to investigate whether the baseline and on-treatment HBV markers can predict HBsAg seroclearance and reduction in patients treated with long-term NUC treatment. This study included two independent cohorts consisting of 843 patients in the derivation cohort and 1781 patients in the validation cohort. HBsAg seroclearance was infrequent (3.7–6.2
BACKGROUND:First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab (Bev) as maintenance therapy for mCRC, omitting both oxaliplatin and fluoropyrimidines. MATERIALS AND METHODS:Patients with untreated mCRC initially received induction chemotherapy with fluoropyrimidine, oxaliplatin plus bevacizumab for 3-4 months. After achieving stable disease or better on imaging, 52 patients transitioned to maintenance therapy with TAS+Bev: TAS-102 (35 mg/m2, twice daily on days 1-5 and 8-12) plus Bev (5.0 mg/kg on Days 1 and 15, intravenously). Progression-free survival 1 (PFS1), defined as the time from the start of maintenance therapy to disease progression or death, was evaluated as the primary endpoint. RESULTS:The median cumulative dose of oxaliplatin during induction was 529 mg/m2. Median PFS1 during TAS+Bev maintenance was 8.7 months (95% CI: 5.5-12.3). The response rate and disease control rate during maintenance were 59.6% and 94.2%, respectively. Oxaliplatin reintroduction was feasible in 53.8% (28/52) of patient with a median total first-line chemotherapy duration was 16.2 months (95% CI: 14.5-20.6). Safety outcomes, including dose intensity and adverse events, were acceptable. CONCLUSION:This strategy of switching to first-line maintenance therapy with TAS+Bev demonstrated promising efficacy and safety. This strategy effectively avoided cumulative neurotoxicity, preserved quality of life and enabled reintroduction of oxaliplatin, suggesting it may represent a promising alternative strategy for patients ineligible for prolonged oxaliplatin-based treatment. Overall survival analysis is currently ongoing. [UMIN Trial ID: UMIN000031317].
Myelodysplastic syndrome (MDS) often coexists with systemic autoimmune diseases. Chronic myelogenous leukemia (CML) is an independent risk factor for intrarenal arterial hyalinosis. We describe a case of glomerulopathy that developed at the transition from CML with 5q deletion (relatively rare) to MDS with 5q and 13q deletion. Kidney histology showed glomerular hyalinosis due to intrarenal arterial changes from CML, in addition to podocytic infolding glomerulopathy (PIG) due to systemic immune responses from MDS or tyrosine kinase inhibitors, or which was coincidental. To our knowledge, this is the first case of PIG developing during the transition from CML to MDS.
Abstract Introduction: Plasminogen activator inhibitor-1 (PAI-1), is an inhibitor for urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). PAI-1 has proangiogenic effects and plays a role in epithelial-mesenchymal transition and metastasis. PAI-1 is a modulator of endothelial cell proliferation and migration in vitro and of angiogenesis and tumor growth in vivo. PAI-1 promotes tumor progression by modulating extracellular matrix proteolysis, cellular adhesion, and detachment; it also facilitates invasion/migration of cancer cells. PAI-1 overexpression has been reported in breast and colorectal cancer(CRC). Plasma levels of PAI-1 in CRC patients (pts) have not been well studied. This study’s purpose was to compare preoperative (PreOp) plasmaPAI-1 levels in CRC and benign colonic pathology (BCP) patients. Methods: Patients (pts) who underwent colorectal resection for BCP or CRC were prospectively enrolled in an IRB-approved tissue and data bank. Preop blood samples, demographic and clinical data, and pathology results were collected prospectively. Plasma PAI-1 levels were measured in duplicate (ng/ml) using ELISA, with results presented as median ± 95% CI. PAI-1 expression levels were also assessed in paired tumor/normal tissues for a subset of pts using QRT-PCR; immunohistochemistry (IHC) was also carried out on CRC and normal tissue samples. The ROC curve and AUC were used to assess plasma PAI-1 as a CRC diagnostic marker. The Mann-Whitney test was used for statistical analysis (significance p<0.05.) Results: A total of 156 CRC (71%colon, 29%rectal) and 101 BCP pts (adenoma 57%, diverticulitis 32%, other11%) were studied. The Stage (S) breakdown for the CRC group was: S 1, 29%; S 2, 29%; S 3, 36%; and S 4, 6%. The median CRC plasma PAI-1 levels were significantly higher (11.75, CI: 9.06, 15.32) vs. BCP pts (2.95, CI: 2.33, 3.49; P< 0.0001). A non-significant rise in mean PAI-1 levels was observed in Stage II, III, and IV pts compared to S.I (12% - 33%, p=ns). mRNA PAI-1 expression levels were higher (p<0.05) in 50% (9/18) of the CRC tissue samples tested vs. paired normal tissues. IHC confirmed the presence of PAI-1 protein in CRC vs. normal colon tissue. The AUC value for the ROC curve was 0.759 (sensitivity 68%, specificity 77%). Conclusion: The median Preop plasma PAI-1 was 3.9 X higher in the CRC vs. the BCP group. Although not proven, the added PAI-1 found in the plasma of CRC pts is likely produced by tumor cells and the surrounding inflammatory cells. Elevated PAI-1 levels may be related to neovascularization and inflammation-induced tissue remodeling at tumor sites. The AUC results suggest PAI-1 may have value as a CRC prognostic marker in a panel of proteins. Further studies with a larger population of controls and CRC pts are needed to better determine if there is a correlation between plasma PAI-1 levels and cancer stage or progression. Citation Format: Chandana S. K. Herath Mudiyanselage, Yi-Ru Chen, Hiromichi Miyagaki, Neil Mitra, Monica S. Naparst, Vesna Cekic, Richard L. Whelan. Plasma levels of Serphin-E1 (PAI-1) are significantly increased in patients with colorectal cancer compared to patients with benign colonic disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2531.
