ESTRO 2020 Abstract Book

S527 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

PO-0990 Prevention of oncologic pulmonary death by control for pulmonary oligometastases treated with SBRT T. Yamamoto 1 , N. Yuzuru 2 , K. Yamada 3 , M. Aoki 4 , H. Onishi 5 , K. Katsui 6 , Y. Dekura 7 , A. Nishikawa 8 , Y. Manabe 9 , S. Kubota 10 , H. Yamashita 11 , K. Jingu 1 1 Tohoku University Hospital, Radiation Oncology, Sendai, Japan ; 2 Toho University Omori Medical Center, Radiology, Tokyo, Japan ; 3 Seirei Mikatahara General Hospital, Radiation Oncology, Hamamatsu, Japan ; 4 Hirosaki University, Radiology, Hirosaki, Japan ; 5 Yamanashi University, Radiology, Yamanashi, Japan ; 6 Okayama University, Proton Beam Therapy, Okayama, Japan ; 7 Keiyu-kai Sapporo Hospital, Radiation Oncology, Sapporo, Japan ; 8 Shikoku Cancer Center, Radiation Oncology, Ehime, Japan ; 9 Nagoya City University, Radiology, Nagoya, Japan ; 10 Nagoya University Hospital, Radiology, Nagoya, Japan ; 11 University of Tokyo, Radiology, Tokyo, Japan Purpose or Objective The purpose of current study is to investigate freedom from oncologic pulmonary death (FOPD) rate and to analyze affecting factors for FOPD. Material and Methods Eligibility of this retrospective survey needed that SBRT was performed between 2004 and 2015, number of metastases was 5 or fewer and all metastases located in lung (i.e., pulmonary oligometastases), primary lesion and extrathoracic metastases needed to be controlled before SBRT and biological effective dose needed 75 Gy or more. FOPD was defined as freedom from oncologic pulmonary death which was caused by respiratory failure or hemoptysis following lung metastases, pleural effusion or intrathoracic dissemination, but fatal lung toxicity of SBRT was not included. Primary disease death from non- oncologic pulmonary cause was censored in model 1 and excluded in model 2, and non-primary disease death was censored in both models. Kaplan-Meier estimator and a log-rank test was used to calculate and compare the stratified FOPD. Cox proportional hazards model was applied to multivariate analyses (MVA). Results A total of 1172 patients with 1315 tumors were enrolled. During a median follow-up of 24.5 months, oncologic pulmonary deaths occurred in 101 out of 221 primary disease deaths. The 3-year local control rate, cause- specific survival (CSS) rate, OS rate were 82.9%, 78.5% and 69.6%, respectively. The 1-, 3-, 5-year FOPD rate was 98.2%, 89.4% and 84.0%, respectively. Median interval to pulmonary death was 23.0 months. MVA for FOPD revealed that local failure of irradiated tumor, squamous cell pathology and chemotherapy after SBRT had significant relationship with worse FOPD rates in both models 1 and 2.