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Thymus Composition, Disease Control, and Toxicity in Locally Advanced Lung Cancer.

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    A new CT-based metric, percent thymic tissue (pTT), quantifies residual thymus in adults. Lower pTT correlates with increased cancer treatment toxicity and poorer survival in non-small cell lung cancer patients.

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    Area of Science:

    • Radiology
    • Immunology
    • Oncology

    Background:

    • Thymic involution is a hallmark of aging, but non-invasive methods to measure residual thymus and its clinical impact are lacking.
    • Assessing thymic function is crucial for understanding age-related immune decline and its effects on cancer outcomes.

    Purpose of the Study:

    • To develop and validate a novel CT-based metric, percent thymic tissue (pTT), for quantifying residual thymic tissue in adults.
    • To investigate the association of pTT with age, sex, clinical outcomes, and treatment-related toxicities in patients with locally advanced non-small cell lung cancer (NSCLC).

    Main Methods:

    • A Transformer-based segmentation model was used to automatically delineate the thymus on chest CT scans.
    • Percent thymic tissue (pTT) was calculated using Gaussian mixture modeling.
    • The pTT metric was applied to two cohorts (MAASTRO and MSKCC) of stage III NSCLC patients, analyzing associations with survival, metastasis, failure rates, and toxicities using Kaplan-Meier and Cox regression models.

    Main Results:

    • pTT decreased with age and was lower in males across both cohorts.
    • pTT independently predicted overall survival, distant metastasis-free survival (DMFS), and locoregional failure (LRF) in NSCLC patients.
    • Low pTT was associated with increased risk of severe pneumonitis and durvalumab discontinuation due to treatment-related adverse events.

    Conclusions:

    • Percent thymic tissue (pTT) is a reliable, non-invasive quantitative measure of thymic function.
    • pTT reflects age-related thymic involution and independently predicts survival and treatment toxicity in stage III NSCLC.
    • pTT may serve as a valuable imaging biomarker for assessing immune status and guiding cancer therapy.