ALK mutation

Findings on EGFR mutations were consistent with the national and international literature. However, PD-L1 expression rates were higher than those typically reported in Brazilian studies, highlighting regional variation in biomarker prevalence.

P1/2, N=190, Not yet recruiting, XYone Therapeutics, Inc

Preoperative identification of STAS remains a clinical challenge in stage IA lung adenocarcinoma. Our clinicoradiological model can simultaneously predict STAS and stratify recurrence risk. STAS-positive cases can be characterized by micropapillary/solid patterns and KRAS/ALK mutations. These findings may assist with surgical decision-making and facilitate tailored adjuvant therapy selection.

Recent clinical trials have led to US Food and Drug Administration approval of osimertinib and alectinib as adjuvant treatments for resected pathologic stage II/III EGFR and ALK-mutated NSCLC; their use in the neoadjuvant setting remains subject to trials. These questions are the subject of two ongoing National Clinical Trials Network trials: CTIU2317-A082304-S2402-Perioperative versus Adjuvant Systemic Therapy in Patients with Resectable NSCLC (PROSPECT-Lung; ClinicalTrials.gov Identifier: NCT04267848)-and S2414-A Randomized Phase III Trial Incorporating Pathologic Response in Participants with Early-Stage NSCLC to Optimize Immunotherapy in the Adjuvant Setting (INSIGHT; ClinicalTrials.gov Identifier: NCT06498635). We discuss why there is sufficient equipoise to justify seeking answers to these two extremely important, patient-centered questions.

P2, N=70, Recruiting, Innate Pharma | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2027

High-risk tumors were enriched for translational and ribosome biogenesis pathways, whereas low-risk tumors were enriched for adaptive immune activation programs. Cross-context transcriptomic integration identified a minimal ALK-associated three-gene signature that reproducibly predicts NB outcomes and reflects distinct underlying biological states, supporting its potential value for risk stratification and hypothesis-driven therapeutic development.

These findings were consistently validated using flow cytometry in an independent cohort. Distinct immune cell profiles highlight elevated baseline CXCR3+ CD127+ effector CD8+ T cells predicting favorable outcomes and impaired cDC-CD4+ T cell dynamics as critical contributors to anti-PD-1/PD-L1 resistance in MT-NSCLC.

This study demonstrates very high molecular concordance between primary lung adenocarcinomas and their synchronous pleural or intrapulmonary metastases. The observed 100% concordance of actionable driver alterations across paired specimens supports the clinical reliability of thoracic metastatic biopsies for baseline molecular profiling in treatment-naïve disease. Although limited by sample size, these findings support the biological stability of actionable driver alterations during early thoracic metastatic dissemination.

Baseline frequencies of peripheral CD4⁺ T TIGIT⁺ and CD8⁺ TEMRA cells were independently associated with survival outcomes in advanced NSCLC patients receiving first-line ICI-based therapy, suggesting that peripheral T cell immunophenotyping at treatment initiation may provide prognostic information beyond conventional biomarkers. Further studies incorporating external validation in independent cohorts, longitudinal immune profiling, and deeper T cell subset characterization are warranted to validate these findings and to elucidate the immune dynamics underlying treatment response and resistance.

ACT was not significantly associated with improved RFS for stage IA LUADmp patients postoperatively. This study was registered at ClinicalTrials.gov: NCT03351842.

Future strategies should prioritize multicenter validation, integration of chronobiological profiling, and exploration of combination therapies. Cost-effectiveness analyses, awareness campaigns, and clinical drives to evaluate safety and adherence will be essential to establish trust and optimize outcomes.

This study suggests that common molecular alterations in lung cancer exhibit prognostic value within specific stages, and notably, TP53, KRAS and ALK alterations hold the potential to modify the current staging system. These findings provide a valuable reference for the forthcoming 10th Edition TNM staging system.