Week 2026-W25

This study investigates histologic transformation to lung squamous cell carcinoma (LUSC) in EGFR-mutant lung adenocarcinoma (LUAD) patients, an underrecognized resistance mechanism. Multiomic analyses revealed that patients with transforming or adenosquamous (LUAS) phenotypes experienced shorter overall survival on first-line osimertinib. Inactivation of the retinoblastoma (Rb) pathway, particularly via CDKN2A/B deletions, was identified as a key driver of this transformation. Furthermore, MET pathway upregulation was observed, and combined EGFR and MET inhibition demonstrated efficacy in preclinical models. These findings suggest novel strategies to counteract this aggressive form of resistance.

This phase 2 study investigated the efficacy of pembrolizumab in 154 patients with advanced rare cancers, conditions often lacking established treatment options. The findings demonstrated an objective response rate of 14.8% and a clinical benefit rate of 26.8%. Multi-modal analysis revealed an association between clinical benefit and biomarkers such as high microsatellite instability (MSI-H), high tumor mutation burden (TMB-H), and a PD-L1 combined positive score (CPS) ≥10. The study also highlighted features of the tumor immune microenvironment, such as increased immune infiltration and T cell activation prior to treatment, as potential predictive markers.

This prospective study evaluated the clinical value of serum-based BRAF V600E mutation detection, alone and in combination with ultrasound-guided fine-needle aspiration cytology (US-FNAC), for the preoperative diagnosis of papillary thyroid carcinoma (PTC). The study included 145 patients with small thyroid nodules. Results indicated that serum BRAF V600E detection, while comparable to US-FNAC in overall performance, showed significantly higher sensitivity for papillary thyroid microcarcinoma (micro-PTC). The integration of both methods substantially improved overall diagnostic performance, suggesting a complementary approach for earlier diagnosis and better risk stratification.

This study compared clinical characteristics and survival between molecularly defined IDH-wild-type glioblastoma (MolGBM) and histologically defined IDH-wild-type glioblastoma (HistGBM). It also characterized lower-grade IDH-wild-type astrocytic tumors lacking glioblastoma-defining genomic alterations. MolGBM exhibited a more favorable adjusted overall survival (HR 0.40) compared to HistGBM, particularly in patients aged 60 years or older. These findings highlight the clinical and biological heterogeneity among molecularly defined IDH-wild-type diffuse gliomas and the critical role of comprehensive molecular characterization. Lower-grade IDH-wild-type astrocytic tumors without glioblastoma-defining alterations warrant further in-depth molecular investigation.

This retrospective study investigated the impact of additional EWSR1 rearrangements on treatment outcomes in Ewing sarcoma. Analyzing a national cancer genomic database (C-CAT) of 90 cases, researchers found that the presence of coexisting EWSR1 rearrangements, beyond the primary EWSR1-ETS fusion, was associated with higher rates of disease progression on first-line chemotherapy. A representative case highlighted primary resistance to multiple lines of therapy in a patient with an additional ETS1-EWSR1 fusion, contrasting with a good response observed with an isolated EWSR1-FLI1 fusion. These findings suggest that these additional rearrangements may hold significant prognostic implications and warrant further investigation to optimize treatment strategies.