Biomedical subjects

Lin Shen

Publications and source records attributed to Lin Shen.

4 recordsLinked to original sources

PubMed2026

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p < 0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq + PTX (HR: 0.40, 95% CI: 0.32-0.50; p < 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p < 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p < 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p < 0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq + PTX may be more effective than RAM + PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq + PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult↗

PubMed2026

Enhancing pan-cancer spatial transcriptomics at single-cell resolution with stPainter.

Subcellular spatial transcriptomics can resolve tissue architecture at cellular scale, but sparse gene panels and limited detection sensitivity constrain downstream analysis. Existing enhancement methods often require tissue-matched single-cell RNA sequencing (scRNA-seq) references and dataset-specific retraining. Here we show that stPainter, a conditional generative model pretrained on a pan-cancer scRNA-seq atlas, can enhance spatial transcriptomics data without matched references or retraining. Using a latent diffusion architecture guided by Stochastic Differential Equations (SDE), stPainter reconstructs expanded expression profiles from sparse measurements and produces latent representations for clustering and cell-state analysis. When we apply stPainter upon 6 spatial transcriptomics datasets of different cancer types, we demonstrate that our model empowers downstream biological analyses, including fine-grained subpopulation clustering and pathway enrichment. Comparison with spatially resolved proteomics (CODEX) provided independent support for regional agreement between imputed cellular compositions and protein-level tissue organization. These results establish stPainter as a scalable approach for analyzing tumor microenvironments without auxiliary sequencing data.

Spatial Transcriptomics↗

PubMed2026

Efficacy and safety of infigratinib in patients with refractory advanced gastric or gastroesophageal junction adenocarcinoma harboring FGFR2 gene amplification: a single-arm, multicenter phase 2 trial.

BACKGROUND: FGFR2 has garnered attention as a promising therapeutic target for gastric cancer (GC) because of its role in GC progression. Infigratinib, an FGFR1-3 selective tyrosine kinase inhibitor, has shown potential in preclinical GC models. METHODS: Infigratinib was evaluated in a phase 2 trial for patients with FGFR2-amplified GC or gastroesophageal junction (GEJ) adenocarcinoma who had failed two or more lines of systemic treatment for locally advanced or metastatic disease. A total of 21 patients received 125 mg of infigratinib orally once daily on a "3 weeks on, 1 week off" schedule. RESULTS: Infigratinib showed preliminary antitumor activity in this molecularly selected population, as reflected by a confirmed objective response rate of 23.8% (95% CI, 8.2-47.2) with median progression-free survival of 3.4 months and median overall survival of 6.7 months. The most common grade 3-4 adverse events were elevated aspartate aminotransferase, decreased white blood cell count, and neutropenia. No treatment-related deaths occurred. Exploratory genomic analyses identified alterations in individual patients with disease progression that may be associated with resistance; however, these findings were based on a limited number of cases and should be interpreted as hypothesis-generating. CONCLUSIONS: The findings support continued investigation of FGFR-targeted strategies in FGFR2-amplified GC/GEJ adenocarcinoma, while underscoring the need for larger studies, refined biomarker selection, and deeper characterization of resistance mechanisms. TRIAL REGISTRATION: NCT05019794, Registered 28 July 2021, https://clinicaltrials.gov/study/NCT05019794 .

Humans↗

PubMed2026

The clinical landscape of POLE-mutant colorectal cancer: a retrospective analysis of real-world outcome.

BACKGROUND: Pathogenic mutations in the POLE gene disrupt its proofreading function during DNA replication, causing an accumulation of erroneous nucleotide incorporations. This defect leads to a significantly elevated tumor mutation burden (TMB) and increased generation of tumor neoantigens. These molecular characteristics suggest a potential association between POLE-mutant tumors and distinct prognostic outcomes in colorectal cancer (CRC); however, clinical evidence supporting this correlation remains limited. METHODS: We retrospectively collected a cohort of CRC patients harboring pathogenic POLE mutations. Comparative analyses were performed between POLE-mutant and POLE wild-type CRCs regarding their clinical characteristics, prognostic outcomes, and genomic profiles. Additionally, we evaluated the response to immunotherapy in metastatic POLE-mutant CRC cases. RESULTS: Among 35,108 CRC patients, pathogenic POLE mutations were identified in 261 individuals, accounting for 0.74% of the cohort. The median age at diagnosis for POLE-mutant patients was 48 years, with a male predominance (74.4%) and a substantial proportion (50.4%) of tumors localized in the right-sided colon. All patients with pathogenic POLE mutations exhibited hypermutated phenotypes, characterized by a median TMB of 235.26 mutations per megabase (range: 71.20-719.00 mutations/Mb). In stage II CRC, POLE mutations were significantly associated with a reduced risk of recurrence (hazard ratio [HR] 0.344, 95% confidence interval [CI] 0.157-0.754, p = 0.008) when compared to POLE wild-type, microsatellite stable CRC patients. However, this association was not evident in stage III patients (HR 1.004, 95% CI 0.490-2.057, p = 0.992). Importantly, the incorporation of immune checkpoint inhibitors in first-line treatment regimens significantly improved progression-free survival (HR = 0.247, 95% CI 0.117-0.552, p = 0.0002) and overall survival (HR = 0.317, 95% CI 0.103-1.143, p = 0.0832) in metastatic CRC patients with pathogenic POLE mutations. CONCLUSIONS: Pathogenic POLE-mutant CRC constitutes a relatively rare, yet clinically important, subtype. These cancers exhibit distinct clinicopathological and genomic features. Our results indicate that mutations in the POLE gene may serve as a valuable prognostic marker and a potential indicator of benefit to immunotherapy in CRC, offering promising avenues for personalized treatment strategies.

Humans↗