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M. Schram

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    MINI 18 - Radiation Topics in Localized NSCLC (ID 139)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI18.03 - Immune Activation in Early Stage Non-Small Cell Lung Cancer (NSCLC) following Stereotactic Ablative Radiotherapy (SABR) and Surgery (ID 2123)

      16:45 - 18:15  |  Author(s): M. Schram

      • Abstract
      • Presentation
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      An anatomical surgical resection is considered to be the standard of care in fit patients, but non-randomized comparative effectives studies suggest that survival outcomes may be similar following SABR. An antitumor immune microenvironment was found to be a prognostic factor in surgically resected early stage NSCLC. SABR has been reported to activate the immunesystem in malignant diseases via a number of mechanisms. We investigated the impact of both surgery and SABR in early stage NSCLC on the immunesystem, studied in peripheral blood over time.

      This is a non-randomised trial. Treatment by either surgery or SABR treatment for early stage (cT1-T2aN0M0) were determined by an institutional multi-disciplinary tumorboard, and in accordance with the patient’s preference . SABR was typically delivered in 3-8 fractions in 1-2 weeks, based on risk-adapted radiotherapy schemes that delivered a biologically effective dose of >100 Gy. Surgery generally involved a VATS lobectomy. Blood was collected prior to treatment, and at weeks 1, 2, 3 and 6 after start of treatment. The peripheral blood mononuclear cell (PBMC) fraction was isolated and was stimulated for 4 hours with phorbol 12-myristate 13-acetate (PMA) and ionomycin, to activate the T cells. Subsequently, the T-cells cells were harvested and analyzed by flow cytometry on the expression of CD4 and/or CD8, granzyme B and interferon (IFN) γ. As PD-1 expression is induced in T-cells after antigen exposure the expression of PD-1 was determined. Changes of population proportions between the different time points were analyzed with the related-samples Wilcoxon signed rank test.

      23 early stage non-small cell lung cancer (NSCLC) patients were included in the study. Of these, 13 patients underwent surgical resection at a mean age (±standard deviation) of 62,9± 8,4 years, and 10 patients who underwent SABR at a median age of 70,0 ±10,4 years. SABR patients had more comorbidities, and a poorer WHO performance score, but clinical tumor stage was comparable. A significant increase in the proportion of IFNγ[+]Granzyme B[+] CD8 T cells (p<.05) was observed at week 2 in the SABR treated group, whereas no difference was found after surgical resection. The PD1[+] fraction of CD4[+] T cells was significantly increased at week 2 in the SABR treated group (p<.05), whereas no differences were seen at two weeks after surgical resection. Proportions of PD1[+ ]CD4 T cells remained elevated in the SABR group at week 3 and 6. A similar trend was observed in the CD8[+] T cell population, although this did not reach statistical significance (p<.1).

      SABR but not surgery, enhances T-cell activation and PD-1 upregulation. The results of our study warrant further investigation as to whether SABR induces an anti-tumor response in patients with early stage NSCLC . The upregulation of PD-1 inherently accompanied with this activation of the immune system potentially warrants combination treatment with PD-(L)1 blockade.

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