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Sonja Adebahr



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    OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      OA12.05 - Imaging-Guided Target Volume Reduction in Radiotherapy of Lung Cancer: The Prospective Randomized Multinational PET-Plan Trial (Now Available) (ID 2558)

      15:45 - 17:15  |  Author(s): Sonja Adebahr

      • Abstract
      • Presentation
      • Slides

      Background

      Advanced medical imaging offers a chance for target volume reduction in modern radiotherapy, which may lead to more effective local treatments with reduced toxicity and offer the protection of draining lymph nodes and large vessels, possibly of importance for the upcoming combination of radiotherapy and immunotherapy. Locally advanced non-small cell lung cancer (NSCLC) with improvable local control and high toxicity is an excellent model to investigate this topic.

      Method

      In the prospective randomised controlled PET-Plan trial (NCT00697333), patients with inoperable stage II/III NSCLC and an indication for radiochemotherapy were randomized at a 1:1 ratio. In conventional arm A target volumes were informed by FDG-PET and CT plus elective nodal irradiation and in experimental arm B they were solely informed by FDG-PET. In both arms, quality assured isotoxically dose-escalated IMRT or 3D-CRT (60 - 74Gy, 2Gy per fraction) was planned and applied to the respective target volumes along with simultaneous platinum-based chemotherapy. The primary objective was time to locoregional progression (LRP) in terms of non-inferiority of experimental arm B.

      Result

      311 patients were recruited, 205 patients included in the intent to treat (ITT) (A: n=99, B: n=106) and 172 patients in the per protocol (PP) analysis (A: n=84, B: n=88). Median FU time in the PP set was 16 months. Non-inferiority of experimental arm B was confirmed for the pre-specified non-inferiority margin. The risk of LRP was lower in the experimental arm B (2y-LRP 0.20 vs. 0.39; HR=0·57; 95% CI: 0·30–1·06; p=0·039) with no difference between study arms concerning survival (2y-OS 0.57 vs. 0.54), out-field recurrence and toxicity.

      Conclusion

      In radiochemotherapy for locally advanced NSCLC PET-Imaging based reduction of radiotherapy target volumes is feasible and may improve local control without increasing toxicity. However, in this trial there was no impact on survival. The procedures established in this clinical trial provide a radiotherapy standard for future NSCLC-trials including immunotherapy and may furthermore inspire trials on imaging based target volume reduction for other types of tumours.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-52 - The Role of Blood Biomarkers in Radiation Therapy for Thoracic Malignancies (ID 1635)

      09:45 - 18:00  |  Author(s): Sonja Adebahr

      • Abstract

      Background

      Radiation (RT) of malignant tumors has the potential to induce immunomodulatory and vascular effects, which can influence the anti-tumor immunity and normal tissue radiosensitivity. We prospectively evaluated the role of different chemokines and cytokines in patients treated with radiotherapy for different thoracic malignancies concerning survival (OS) and development of radiation induced lung toxicity (RILT).

      Method

      Fifty-six patients with lung cancer (n=41), esophageal cancer (n=14) or thymoma (n=1) treated either with conventionally fractionated (n=43) or hypo-fractionated (n=13) radiotherapy were enrolled prospectively in the study. The serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF-α, bFGF, Flt-1, PlGF, VEGF, VEGF-C, VEGF-D were analysed by multiplex array (MesoScale Discovery) and measured in a USA CLIA-certified core at MGH Boston.at predefined time points: before, during and at the end of treatment as well as in the first and second follow-up. Toxicities were scored according to common toxicity criteria for adverse events.

      Result

      We observed an upregulation of IL-10, IFN-γ, PlGF, VEGF-D and a downregulation of IL-8, TNF-α, VEGF, VEGF-C during and at the end of radiotherapy. IL-6 was upregulated during radiotherapy and downregulated at the end of treatment and Flt-1 was downregulated during radiotherapy and upregulated at the end of treatment. Furthermore, the baseline concentrations of several chemokines correlated with OS such as IFN-γ, IL-13, IL-6, TNF-α, but couldn’t be sustained after Bonferroni correction. On the contrary a higher IL-13 concentration during radiotherapy (p<0.000, HR 19.456, 95% CI 4.254-89.070), IL-6 (p<0.000, HR 1.055, 95% CI 1.024-1.086), IL-1β (p=0.004, HR 11.200, 95% CI 2.160-58.074), IL-8 (p=0.009, HR 1.014, 95% CI 1.003-1.024) and bFGF (p<0.000, HR 1.170, 95% CI 1.075-1.274) and of the IL-6 at the first follow up (p=0.001, HR 1.140, 95% CI 1.057-1.229) correlated with OS. Seventeen patients (30%) developed radiologic signs of RILT Grade≥1 but only two of them (3.6%) developed clinical symptoms (Grade 2). We could not find any association between the different serial blood biomarkers and a higher incidence of RILT.

      Conclusion

      In our study early changes in blood biomarkers during radiotherapy could indicate an early immune response and might play a role on the outcome of the threatmentbut they don’t seem to play a significant role in the development of early stage (grade 1) RILT.

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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-19 - Quality of Life After Pulmonary Stereotactic Fractionated Radiotherapy: Longterm Results of the Phase II STRIPE Trial (ID 2142)

      10:15 - 18:15  |  Author(s): Sonja Adebahr

      • Abstract

      Background

      Preserving health related quality of life (HRQOL) plays an important role in considering stereotactic body fractionated radiotherapy (SBRT). The prospective monocenter phase II STRIPE trial investigated long-term HRQOL after SBRT, efficacy and toxicity.

      Method

      Patients with ≤ 2 pulmonary lesions ≤ 5cm were treated with 4DPET/CT-based SBRT (3X12.5Gy or risk-adapted 5X7Gy, to the 60% isodose). Follow up (FU) was performed 2 and 7 weeks after SBRT, then 3monthly for 2 years with assessment of response (primary endpoint: 2-year cumulative incidence of local progression (LP); secondary endpoints: local progression free (LPFS), overall survival (OS) and toxicity (CTCAE)). Impact of predefined patient and treatment related factors on HRQOL (EORTC QLQ-C30 and EORTC QLQ-LC13) was evaluated.

      Result

      Between 02/2011 and11/2014, 100 patients were given SBRT for 56 NSCLC and 44 pulmonary metastases. Long-term FU overall revealed stable Quality of Life (QoL)/Global health status (GHS), functions-scores and symptoms. For QoL/GHS, patients with low initial QoL/GHS-Score below the median of 50, revealed significantly stronger improvement than those with good QoL/GHS-scores (p< 0.001). Probability for LP, LPFS and OS 2 years after SBRT was 8.1%, 53.3% and 62.2%. Lower risk for LP was revealed for 3X12.5Gy (p=0.043) and for Dmin (Biological Effective Dose10) in the Planning Target Volume>100Gy (p=0.023). ≥G3-Toxicity was < 4%, except dyspnea: ≥G3 dyspnea was 6% at baseline and 14.5% 2 years after SBRT.

      Conclusion

      These prospective data on a representative cohort of pulmonary SBRT patients confirm a stable preservation of HRQOL after SBRT and furthermore demonstrate a QoL/GHS-benefit for patients with low initial QoL/GHS-scores, the regimen of 3x12.5 Gy SBRT being efficient and well tolerated. This result may inform shared decision making when discussing SBRT for frail patients