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Targeted therapies in lung cancer: personalizing treatment across the age spectrum

Front Oncol. 2026 Feb 25;16:1743620. doi: 10.3389/fonc.2026.1743620. eCollection 2026.

ABSTRACT

Lung cancer remains the leading cause of cancer-related mortality, yet current precision oncology approaches remain overwhelmingly tumor-centric, guided by genomic alterations and immune biomarkers, while largely neglecting the profound impact of aging biology on treatment response. While emerging evidence suggests that aging biology can modify therapeutic benefit and toxicity, its clinical integration remains uneven and largely investigational. In this review, we explicitly distinguish the chronological aging from biological aging to clarify how host biology modifies therapeutic benefit and toxicity. We synthesize mechanistic, translational, and early clinical evidence, while explicitly noting areas where prospective validation is lacking, to reframe personalization of lung cancer therapy through an age-conscious lens. We summarize data indicating that immunosenescence is associated with T-cell exhaustion, myeloid dominance, and extracellular matrix stiffening, features that may contribute to immune-evasive tumor phenotypes and attenuated responses to immune checkpoint blockade in subsets of patients, while pediatric cases, though rare, illustrate how global precision initiatives like iTHER and ZERO enable cautious adaptation of adult therapies. Moving beyond chronological age, we discuss biological age biomarkers, including PhenoAgeAccel, epigenetic clocks, telomere length, and frailty indices, which outperform traditional metrics in predicting risk, resistance, and toxicity, and propose integrating these tools into trial design, screening, and care planning which show promise for risk stratification and toxicity prediction but are not yet validated for routine treatment selection. Looking forward, we outline investigational strategies at the intersection of geroscience and oncology, including immune engineering, senolytics, microenvironmental modulation, and AI-driven multi-omic modeling. Overall, this review argues that biological age represents a critical but still underdeveloped dimension of precision oncology, and highlights key evidence gaps that must be addressed before age-aware personalization can be implemented in routine lung cancer care.

PMID:41821888 | PMC:PMC12975599 | DOI:10.3389/fonc.2026.1743620

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A Joint Neural Baseline for Concept, Assertion, and Relation Extraction from Clinical Text

arXiv:2603.07487v1 Announce Type: cross Abstract: Clinical information extraction (e.g., 2010 i2b2/VA challenge) usually presents tasks of concept recognition, assertion classification, and relation extraction. Jointly modeling the multi-stage tasks in the clinical domain is an underexplored topic. The existing independent task setting (reference inputs given in each stage) makes the joint models not directly comparable to the existing pipeline work. To address these issues, we define a joint task setting and propose a novel end-to-end system to jointly optimize three-stage tasks. We empirically investigate the joint evaluation of our proposal and the pipeline baseline with various embedding techniques: word, contextual, and in-domain contextual embeddings. The proposed joint system substantially outperforms the pipeline baseline by +0.3, +1.4, +3.1 for the concept, assertion, and relation F1. This work bridges joint approaches and clinical information extraction. The proposed approach could serve as a strong joint baseline for future research. The code is publicly available.
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VANGUARD: Vehicle-Anchored Ground Sample Distance Estimation for UAVs in GPS-Denied Environments

arXiv:2603.04277v1 Announce Type: cross Abstract: Autonomous aerial robots operating in GPS-denied or communication-degraded environments frequently lose access to camera metadata and telemetry, leaving onboard perception systems unable to recover the absolute metric scale of the scene. As LLM/VLM-based planners are increasingly adopted as high-level agents for embodied systems, their ability to reason about physical dimensions becomes safety-critical -- yet our experiments show that five state-of-the-art VLMs suffer from spatial scale hallucinations, with median area estimation errors exceeding 50%. We propose VANGUARD, a lightweight, deterministic Geometric Perception Skill designed as a callable tool that any LLM-based agent can invoke to recover Ground Sample Distance (GSD) from ubiquitous environmental anchors: small vehicles detected via oriented bounding boxes, whose modal pixel length is robustly estimated through kernel density estimation and converted to GSD using a pre-calibrated reference length. The tool returns both a GSD estimate and a composite confidence score, enabling the calling agent to autonomously decide whether to trust the measurement or fall back to alternative strategies. On the DOTA~v1.5 benchmark, VANGUARD achieves 6.87% median GSD error on 306~images. Integrated with SAM-based segmentation for downstream area measurement, the pipeline yields 19.7% median error on a 100-entry benchmark -- with 2.6x lower category dependence and 4x fewer catastrophic failures than the best VLM baseline -- demonstrating that equipping agents with deterministic geometric tools is essential for safe autonomous spatial reasoning.
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