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    Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617

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    Author
    Jin, Jian-Yue
    Hu, Chen
    Xiao, Ying
    Zhang, Hong
    Paulus, Rebecca
    Ellsworth, Susannah G
    Schild, Steven E
    Bogart, Jeffrey A
    Dobelbower, Michael Chris
    Kavadi, Vivek S
    Narayan, Samir
    Iyengar, Puneeth
    Robinson, Cliff
    Greenberger, Joel S
    Koprowski, Christopher
    Machtay, Mitchell
    Curran, Walter
    Choy, Hak
    Bradley, Jeffrey D
    Kong, Feng-Ming Spring
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    Date
    2021-12-08
    Journal
    Cancers
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.3390/cancers13246193
    Abstract
    Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC-survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1-12.2 Gy) and 6.3 Gy (2.1-11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6-8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.
    Keyword
    non-small-cell lung cancer
    radiation-induced immune toxicity
    radiotherapy
    survival
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17463
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers13246193
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