Non-Small Cell Lung Cancer
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Oct 12 – Oct 19, 2026
Development and Validation of a Blood Test Informed Risk Prediction Model for Lung Cancer-The Copenhagen Lung Cancer Risk Model (CPH-Lung).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study developed and validated CPH-Lung, a blood test-based model, to improve 6-year lung cancer risk stratification for screening. Utilizing two prospective cohorts of ever-smokers, the model was trained and validated against the PLCOm2012 model. CPH-Lung demonstrated superior discrimination (AUC 0.783 vs. 0.720, p=.0059) and higher sensitivity (e.g., 57.6% vs. 39.2% in women, p<.0001) for detecting lung cancer. This offers a more sensitive tool for identifying high-risk individuals, particularly women and younger patients, potentially enhancing early lung cancer detection in clinical practice.
10.1200/JCO-25-02326
Sep 28 – Oct 05, 2026
Cancer and the microbiome: from association to intervention.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This review synthesizes evidence regarding the gut microbiome’s role as a modifiable determinant of efficacy and toxicity in systemic cancer therapies, particularly immune checkpoint inhibitors (ICIs). Research indicates that higher microbial diversity and specific immunostimulatory pathways correlate with improved survival and treatment response in melanoma, non-small-cell lung cancer, and renal cell carcinoma. Conversely, the use of antibiotics and proton pump inhibitors is linked to inferior clinical outcomes due to microbiome disruption, while interventions like fecal microbiota transplantation are currently under investigation. These findings suggest that modulating the intestinal microbiome could optimize anticancer treatment responses, though therapeutic strategies remain in the investigational phase.
10.1016/S1470-2045(26)00326-8
Sep 14 – Sep 21, 2026
Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
The I LUNG project (NCT05537922) evaluated AI-based decision support tools for immunotherapy selection in 2,396 NSCLC patients using real-world multimodal data. Machine learning (ML) and deep learning (DL) clinical and blood (CB)-only models achieved consistent performance (AUC up to 0.77 in the test set), significantly outperforming existing scores like PD-L1. An explainable AI tool improved physician prediction, demonstrating the clinical usefulness of AI in oncology. This pioneering framework, with ongoing prospective validation, holds significant implications for improving NSCLC treatment decisions.
10.1038/s41591-026-04488-2
Sep 07 – Sep 14, 2026
Patient-reported symptom monitoring in patients with lung cancer (SYMPRO-Lung trial): long-term, post-hoc survival results of a multicentre, stepped-wedged, cluster-randomised clinical trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This post-hoc analysis of the multicentre SYMPRO-Lung trial evaluated the impact of weekly online patient-reported outcome (PRO) symptom monitoring on long-term survival in 446 patients with stage I-IV lung cancer. At a median follow-up of 50 months, the intervention group achieved a median overall survival of 26 months compared to 21 months in the control group. Adjusted analysis indicated that PRO monitoring was associated with improved overall survival (HR 0.80, p=0.049), although no significant difference was observed in progression-free survival. These findings suggest that integrating routine digital symptom monitoring into oncology practice can provide a clinically meaningful 5-month survival advantage for lung cancer patients across all stages.
10.1016/S1470-2045(26)00305-0
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
This review examines the evolving landscape of early stage nonsmall cell lung cancer, driven by low-dose CT screening and rising never-smoker incidence. It highlights therapeutic advances including parenchyma-sparing surgery, perioperative immunotherapy, and liquid biopsy monitoring. The authors propose a risk-adaptive paradigm using artificial intelligence and multi-omics to tailor treatment intensity. This approach aims to escalate therapy for high-risk patients while safely de-escalating for low-risk individuals, addressing TNM staging limitations and global disparities.
10.3322/caac.70100
Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-label, superiority, phase 3, randomised controlled trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized controlled trial (SWOG/NRG S1914) investigated adding atezolizumab to stereotactic body radiation therapy (SBRT) for high-risk, early-stage, medically inoperable non-small-cell lung cancer (NSCLC), with overall survival as the primary objective. The trial, enrolling 402 eligible patients, closed early for futility, finding no improvement in overall survival (HR 1.04, 95% CI 0.69-1.58; 2-year OS 82% in both groups) with the combination. Importantly, grade 3 or higher adverse events were significantly higher with atezolizumab plus SBRT (12% vs 3% with SBRT alone), including two grade 5 respiratory events. These results directly inform cancer treatment, indicating that adding atezolizumab to SBRT does not improve outcomes and increases toxicity for this specific NSCLC patient population.
10.1016/S0140-6736(26)01655-7
Aug 24 – Aug 31, 2026
Perioperative Durvalumab for Resectable Non-Small Cell Lung Cancer: Updated Outcomes From the Phase III AEGEAN Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The Phase III AEGEAN trial investigated perioperative durvalumab plus neoadjuvant chemotherapy versus chemotherapy alone for resectable non-small cell lung cancer (R-NSCLC). Updated outcomes demonstrated a consistent event-free survival (EFS) benefit for the durvalumab arm (HR, 0.69 [95% CI, 0.55 to 0.88]), alongside numerical improvements in disease-free survival (DFS) (HR, 0.66) and overall survival (OS) (HR, 0.89). The safety profile was manageable, with grade 3/4 adverse events occurring in 15.4% of the durvalumab arm. These results strongly support perioperative durvalumab as a new, effective treatment option for patients with resectable lung cancer, directly impacting cancer care.
10.1200/JCO-25-02659
Thymic Radiation is Associated with Worse Outcomes in Patients with NSCLC.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This multicohort analysis of 1,107 patients with non-small cell lung cancer (NSCLC) investigated the association between incidental thymic radiation exposure and clinical outcomes using deep-learning radiographic assessments. Results showed that a 1Gy increase in Mean Thymic Dose significantly elevated distant metastasis risk by 1.57-4.21%, with adjusted hazard ratios ranging from 1.29 to 1.95 across three independent cohorts. The negative impact was most pronounced in patients with preserved pre-treatment thymic health, correlating with dose-dependent declines in circulating lymphocyte counts and immune competence. These findings suggest that implementing thymus-sparing radiotherapy strategies could preserve immune function and reduce metastasis risk in cancer patients without compromising tumor coverage.
10.1016/j.annonc.2026.07.001
Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 ALINA trial compared adjuvant alectinib to platinum-based chemotherapy in 257 patients with resected ALK-positive stage IB-IIIA non-small-cell lung cancer. Alectinib demonstrated a manageable safety profile with fewer adverse event-related discontinuations (5% vs. 13% for chemotherapy) and clinically meaningful improvements in health-related quality-of-life domains like bodily pain and mental health by week 12. Patients maintained physical and mental health scores near general population norms (mean scores ~49) throughout the two-year treatment period. These results, combined with previously reported disease-free survival benefits, establish adjuvant alectinib as a superior, well-tolerated standard-of-care option for resected ALK-positive NSCLC.
10.1016/S1470-2045(26)00283-4
Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 trial evaluated the efficacy of ivonescimab combined with chemotherapy versus chemotherapy alone in 438 patients with advanced EGFR-mutated non-small-cell lung cancer following progression on third-generation TKI therapy. Ivonescimab significantly improved median progression-free survival to 6.8 months compared to 4.4 months in the control group (HR 0.52; p<0.0001), though the overall survival benefit was not statistically significant (16.8 vs 14.0 months; HR 0.79). For clinicians treating thoracic malignancies, these results demonstrate a clear delay in disease progression for a difficult-to-treat population with limited subsequent options. While serious treatment-related adverse events were higher in the ivonescimab group (28% vs 15%), the combination represents a potential new standard of care for post-TKI EGFR-mutated lung cancer.
10.1016/S1470-2045(26)00282-2
Aug 17 – Aug 24, 2026
Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 3 randomized trial evaluated the five-year efficacy of perioperative pembrolizumab combined with neoadjuvant chemotherapy followed by surgery and adjuvant pembrolizumab in 797 patients with resectable stage II-IIIB non-small-cell lung cancer. Results demonstrated a significant improvement in five-year event-free survival (49.9% vs. 26.5%; HR 0.58) and overall survival (64.6% vs. 53.6%; HR 0.74) compared to chemotherapy and surgery alone. The treatment maintained a safety profile consistent with previous reports and showed no detriment to health-related quality of life over the extended follow-up period. These findings establish perioperative pembrolizumab as a durable standard of care for early-stage resectable lung cancer, offering nearly double the event-free survival rate at five years.
10.1016/j.annonc.2026.08.005
Therapeutic targeting of RAS-mediated resistance in oncogene-driven lung cancer.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This study investigated RAS-mediated resistance mechanisms in 590 patients with oncogene-driven lung cancers using tissue and liquid biopsies alongside patient-derived models. RAS alterations were identified in 11.2% of patients progressing on first-line osimertinib and 14.7% of those resistant to lorlatinib, with KRAS G12D emerging as a frequent mutation. Preclinical testing of osimertinib combined with selective KRAS G12D or pan-RAS inhibitors demonstrated marked synergistic activity in overcoming acquired resistance in vitro and in vivo. These findings establish RAS alterations as a significant off-target resistance mechanism in approximately 10% of cases, supporting the clinical investigation of rational combination therapies to extend the paradigm of precision oncology.
10.1016/j.annonc.2026.08.004
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.3.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO Living Guideline, Version 2026.3.3, focuses on therapeutic strategies for patients with Stage IV Non-Small Cell Lung Cancer (NSCLC) who present with specific driver alterations. The guideline synthesizes current evidence to provide updated recommendations for optimal treatment approaches in this advanced cancer setting. It aims to guide clinicians in selecting targeted therapies based on molecular profiling, thereby improving patient outcomes. The primary implication is to standardize and enhance evidence-based clinical practice for advanced NSCLC.
10.1200/JCO-26-01958
Aug 10 – Aug 17, 2026
Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This phase 3 randomized trial compared first-line osimertinib plus chemotherapy against osimertinib monotherapy in 294 patients with advanced NSCLC harboring concurrent EGFR and TP53 mutations. The combination therapy significantly extended median progression-free survival to 34.0 months compared to 15.6 months for monotherapy (HR 0.44; 95% CI, 0.32-0.60; P < .001). While grade 3 or higher adverse events were more frequent in the combination group, the substantial survival benefit was consistent across subgroups, including those with brain metastases. These findings establish a strong clinical rationale for using individualized combination strategies to improve outcomes in this high-risk cancer population.
10.1001/jama.2026.10599
Aug 03 – Aug 10, 2026
SKYSCRAPER-03: A Phase III Study of Tiragolumab Plus Atezolizumab Versus Durvalumab in Locally Advanced, Unresectable, Stage III NSCLC After Platinum-Based Concurrent Chemoradiation.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The SKYSCRAPER-03 study was a phase III, open-label, randomized trial evaluating tiragolumab plus atezolizumab versus durvalumab as consolidation therapy for locally advanced, unresectable, stage III NSCLC after chemoradiation. The primary endpoint, IRF-assessed progression-free survival (PFS) in PD-L1+ patients, was not met. Median PFS was 19.4 months with the combination versus 16.6 months with durvalumab (HR 0.96; p=0.76). Median overall survival in PD-L1+ patients was not estimable versus 54.8 months, respectively (HR 0.99), indicating the combination did not offer additional benefit over durvalumab for this cancer population.
10.1016/j.annonc.2026.07.414
Jul 27 – Aug 03, 2026
SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase III trial evaluated the efficacy of adding tiragolumab to atezolizumab in 521 patients with previously untreated, PD-L1-high, locally advanced or metastatic non-small cell lung cancer. The combination reached a median progression-free survival of 7.0 months compared to 5.6 months with atezolizumab alone (HR 0.78, p=0.02), which was statistically non-significant. Median overall survival was 23.1 months for the combination versus 16.9 months for the control (HR 0.87, p=0.22), also failing to reach significance. Consequently, the addition of tiragolumab does not currently offer a statistically superior clinical benefit over PD-L1 monotherapy for this specific oncological population.
10.1200/JCO-25-02777