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Georg Holgersson



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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-020 - Autoantibody Profiles of Cancer-Testis Genes in Non-Small Cell Lung Cancer (ID 9330)

      09:30 - 16:00  |  Author(s): Georg Holgersson

      • Abstract
      • Slides

      Background:
      Cancer testis (CT) genes are expressed in various types of cancer but otherwise restricted to normal tissues of testis and placenta. Several CT genes have shown to encode immunogenic proteins that are able to induce an anti-tumour response in cancer patients. The presence of autoantibodies towards expressed CT proteins could indicate which CT proteins that are more suitable for immunotherapeutic interventions, as these are recognized by the patient´s immune system.

      Method:
      Suspension bead arrays (Luminex) were used to analyse the presence of autoantibodies towards expressed CT proteins in plasma samples from patients with non-small cell lung cancer (NSCLC). The technology enables to screen for autoantibodies in minute amount of patient plasma. Protein fragments with an average length of 80 amino acids, produced within the Human Protein Atlas, were coupled to unique beads, allowing multiplex analysis of 244 different autoantibodies towards antigens representing 198 unique genes in each sample. The primary sample set included 51 samples from 34 individuals taken before radiation therapy and 17 samples taken after radiation therapy. Longitudinal plasma samples taken during radiation therapy were available for most individuals resulting in a total of 89 samples.

      Result:
      Of 198 analysed CT genes, autoantibodies against antigens representing 25 genes were detected in at least one of the 51 samples from the primary study set. The autoantibody detection ranged from five different autoantibodies in two individuals to no detected autoantibodies in seven individuals. Among those individuals with samples available both before and after radiation therapy (n=13), the autoantibody profiles were not altered by the treatment. Three individuals however showed autoantibodies towards one additional protein in the sample taken after radiation therapy compared to the sample before radiation. In two individuals, autoantibodies detected towards one protein in the sample taken before radiation were not detected in the sample taken after radiation. Unsupervised hierarchical clustering with 25 detected autoantibodies and all 89 samples showed that samples from the same individual cluster based on the autoantibodies´ profile. There was no apparent association of autoantibody profiles with clinical parameters (histology, gender, age, stage). However, patients with detected autoantibodies showed a longer overall survival than patients without autoantibodies.

      Conclusion:
      This study provides a first comprehensive analysis of autoantibody detection against antigens representing 198 CT genes. Among the identified autoantibodies only AKAP4 has been reported previously in NSCLC. The individual autoantibody profiles showed only minor differences between samples taken before, during and after radiation therapy.

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    P1.14 - Radiotherapy (ID 700)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P1.14-008 - Elevated Platelet Levels Affect Prognosis in Patients with NSCLC Treated with Curatively Intended Chemoradiotherapy (ID 7528)

      09:30 - 16:00  |  Presenting Author(s): Georg Holgersson

      • Abstract
      • Slides

      Background:
      For inoperable stage III NSCLC, chemoradiotherapy is the standard of care. However, this treatment is associated with significant side effects and only offers a small chance of cure. Having adequate prognostic information at the start of treatment is essential in order to select the most appropriate treatment strategy for each individual patient. This study investigates the prognostic value of pre-treatment platelet (Plt) levels in this treatment setting.

      Method:
      Data were collected retrospectively from two phase II trials conducted from 2002 to 2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical and laboratory data at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox regression model. An optimal prognostic cut-off point for Plt was estimated by using a stepwise log-rank testing of survival comparing patients with a Plt count below and above every Plt count in the dataset. The cut-off point was defined as the Plt count that gave the lowest p-value using the log-rank test.

      Result:
      Patients with thrombocytosis (defined as Plt > 350 x 10[9]/L) had a shorter median overall survival than patients with normal Plt (≤ 350 x 10[9]/L) at baseline (14.5 and 23.7 months, respectively), which was statistically significant (p=0.0025). This significant association was retained in a multivariate model where other laboratory and clinical factors, such as performance status, were included. The optimal prognostic cut-off point for platelet levels in this patient material was estimated at Plt = 610. Figure 1



      Conclusion:
      In stage III NSCLC treated with curatively intended chemoradiotherapy, elevated platelet levels showed to be an independent prognostic marker for shorter overall survival. Further research is needed to establish the role of platelet levels and appropriate cut-off limits when making treatment decisions in this clinical setting.

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