ESTRO 2020 Abstract book

S572 ESTRO 2020

PO-0989 Radiation therapy for thoracic malignancies: the impact on immune and vascular blood biomarkers S. Adebahr 1 , E. Gkika 2 , A. Brenner 3 , T. Schimek-Jasch 2 , G. Niedermann 1 , U. Nestle 4 , A. Grosu 1 , D.G. Duda 5 1 Medical Center- Faculty of Medicine- University of Freiburg, Department of Radiation Oncology- Freiburg- Germany and German Cancer Consortium DKTK Partner Site Freiburg and German Cancer Research Center DKFZ- Heidelberg- Germany, Freiburg im Breisgau, ; 2 Medical Center- Faculty of Medicine- University of Freiburg, Department of Radiation Oncology- Freiburg- Germany, Freiburg im Breisgau, Germany ; 3 Ortenau Klinikum Offenburg - Kehl- Offenburg- Germany, Anästhesie -, Offenburg, Germany ; 4 Medical Center- Faculty of Medicine- University of Freiburg, Department of Radiation Oncology- Freiburg- Germany and Kliniken Maria Hilf GmbH Mönchengladbach- Department of Radiation Oncology- Mönchengladbach-Germany, Freiburg im Breisgau, Germany ; 5 Massachusetts General Hospital and Harvard Medical School- Boston- United States, E. L. Steele Laboratories for Tumor Biology- Department of Radiation Oncology, Boston, USA Purpose or Objective Radiation (RT) of malignant tumors potentially induces immunomodulatory and vascular effects, which might influence normal tissue radiosensitivity and anti-tumor immunity. We prospectively evaluated the role of different blood circulating cytokines and chemokines in patients treated with radiotherapy for different thoracic malignancies concerning development of radiation induced lung toxicity (RILT) and survival (OS). Material and Methods We prospectively enrolled 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. The plasma levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF- α, bFGF, sFlt-1, PlGF, VEGF, VEGF-C, VEGF-D were analyzed by multiplex arrays (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. Results During and at the end of radiotherapy we observed an upregulation of circulating IL-10, IFN-γ, PlGF, VEGF-D and a downregulation of IL-8, TNF-α, VEGF, VEGF-C. IL-6 was upregulated during radiotherapy and downregulated at the end of treatment and sFlt-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. Conversely, a higher concentration during radiotherapy of biomarkers IL-13 (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 post-radiotherapy (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), which precluded any analysis of the association between the different serial blood biomarkers and a higher incidence of severe RILT. Conclusion In our study, early changes in blood biomarkers during radiotherapy could potentially indicate an early immune and vascular response and might play a role on the outcome of the treatment in lung cancer

418 patients were treated as follows: 54Gy/3# (86pts); 55Gy#5 (237pts); 60Gy/8# (61pts); 50Gy/10# (33pts). Median age 76yrs (range 48-93yrs). Histological diagnosis obtained in 57%. 5 year OS of entire cohort was 37.3% (Fig.1). Median OS was 3.47 years. No difference in 5yr OS between the different fractionation schedules, except the 10 fraction schedule, which had poorer OS (p=0.016). No difference in survival between the different treating consultants who varied significantly in experience (Range: 26-195 patients treated, Fig.2). Also no difference in survival for the first 25 patients treated, versus subsequent patients (consultants A,C,E Fig.3) . Toxicity rates were very low with only 4 patients with recorded G3 toxicity (all pneumonitis). Conclusion We have demonstrated that lung SABR can be safely implemented and delivered in the real world, non- academic cancer centre setting, with 5yr Overall Survival rates comparable to the published literature. Toxicity was minimal. There were no differences in OS outcomes between consultants with differing experience, and no differences in OS between the first 25 patients treated and subsequent patients in 3 separate consultant cohorts. This suggests that there may not be a significant learning curve to lung SABR that affects overall survival outcomes, as long as centres follow national guidelines and radiotherapy QA processes (eg UK SABR Consortium and RTTQA guidelines).