ESTRO 36 Abstract Book

S527 ESTRO 36 _______________________________________________________________________________________________

5 University of Luebeck, Department of Visceral Surgery, Luebeck, Germany 6 German Cancer Consortium DKTK and German Cancer Research Center DKFZ, Institute of Molecular Medicine and Cell Research- Freiburg, Heidelberg, Germany Purpose or Objective Complete surgical resection remains the only curative option in patients with pancreatic ductal adenocarcinoma (PDAC). Microscopically incomplete resection (R1) is often associated with early local recurrence (LR) and, therefore, represents a negative prognostic factor. The aim of this study was to analyze the total PDAC proteome of patients who received radiochemotherapy (RCT) following incomplete resection in order to identify proteins associated with post-RCT LR. Material and Methods Thee patients with early LR (median 6 months after resection, range 5 to 10 months) and three patients with late LR (median 18 months after resection, range 13 to 27 months) were identified from our clinical database. Formalin fixed paraffin-embedded tissue obtained from surgical PDAC specimens was used for proteome analysis. After micro-dissection, tissue was de-paraffinized and rehydrated, followed by protein extraction and trypsin digestion. The samples were analyzed by tandem mass spectrometry. To identify significantly up- or down- regulated proteins, linear models for microarray data (LIMMA) were applied; the p-value was set to 0.01. Results Patients received a median RT total dose of 50.4Gy and concurrent chemotherapy with two courses of 5-FU. Overall survival was reduced in patients with early LR as compared to patients with late LR (7 vs. 30 months, p=0.0001). A total of 1,878 proteins were quantified in both cohorts with 1,656 proteins quantified in the early LR group and 1,769 quantified in the late LR group. LIMMA method identified 18 proteins significantly up- or down- regulated. 7 proteins were up-regulated in the early LR group such as MAOA, ALDH1A1, creatine kinase B and mucin-5AC being involved in tumorigenesis. 11 proteins were up-regulated in the late LR group including fascin, integrin beta-4, histidine rich glycoprotein and CDC42. Further analysis demonstrated the early LR group to exhibit an exocrine-like phenotype including expression of pancreatic proteins absent in the late LR group. 13 exocrine-related proteins were identified such as carboxypeptidase B and chymotrypsin-C. Conclusion Analyzing proteomic data of PDAC patients undergoing post-operative RCT after R1-resection, proteomic expression profiles associated with early vs. late post-RCT LR were identified. These proteomic biomarkers may serve to stratify patients according to prognosis in future trials and to assess a potential benefit of post-operative RCT. PO-0954 A model to study long-term impact of radiation towards the colorectal area F. Sjöberg 1 , D. Malipatlolla 1 , G. Steineck 1 , C. Bull 1 1 The Division of Clinical Cancer Epidemiology, Department of Oncology- University of Gothenburg, Gothenburg, Sweden Purpose or Objective A deeper understanding of the radiophysiology following radiotherapy is imperative. With a few exceptions, rodent models of high-dose gastrointestinal radiation injury typically cause lethality within 5-8 days, limiting the possibility to study the progression of injury over time. We have developed a model that allows for delivering radiation in fractions at high doses, while maintaining excellent survival.

Poster: Radiobiology track: Normal tissue biology of the heart

PO-0952 Integral heart dose and lymphocytopaenia in lung cancer patients treated with radical radiotherapy N. Joseph 1 , A. McWilliam 2 , K. Haslett 2 , J. Kennedy 2 , C. Faivre-Finn 2 , A. Choudhury 2 1 General Hospital Polonnaruwa, Clinical Oncology, Polonnaruwa, Sri Lanka 2 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom Purpose or Objective Optimal radiation dose delivery in lung cancer patients is limited by the risk of toxicity to adjacent organs especially the heart, lung and spinal cord. Post-treatment lymphocytopaenia is a recognised complication in patients undergoing thoracic radiotherapy and if severe, can lead to opportunistic infections. We hypothesised that a higher integral heart dose is associated with post-treatment lymphocytopaenia in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) treated with radical radiotherapy. Material and Methods 138 patients (103 NSCLC and 32 SCLC) treated with radical radiotherapy were included in this study. Concurrent chemotherapy was administered in 85/135 patients. Prescribed dose to planning target volume ranged from 41.4 to 72 Gy with a median of 66 Gy. Lymphocyte counts prior to treatment and up to 100 days post-treatment were obtained. The integral heart dose was derived by using the product of mean dose and volume. A linear mixed effects model, incorporating the following variables: integral heart dose, integral heart dose per fraction, baseline lymphocyte count, time from start of treatment and use of concurrent chemotherapy was used to analyse the effect on post-treatment lymphocyte counts Results The median integral heart dose in the cohort was 14.5 Litres-Gy (range 4-35.6). Integral heart dose (p=0.03) and time from start of therapy (p < 0.001) were negatively correlated with post-treatment lymphocyte counts while integral heart dose per fraction (p=0.05) and baseline lymphocyte count (p<0.001) were positively correlated. Use of concurrent chemotherapy was not statistically significant in the model. Conclusion Total integral heart dose predicts a lower post-treatment lymphocyte count in lung cancer patients treated with radical radiotherapy. The positive correlation with higher integral heart dose per fraction suggests that fractionation has an adverse effect on post-radiotherapy lymphocyte counts. PO-0953 Proteome profiles in PDAC patients with local recurrence after postoperative radiochemotherapy L. Bolm 1 , V. Oria 2 , L. Kaesmann 3 , P. Bronsert 4 , U.F. Wellner 5 , O. Schilling 6 , D. Rades 3 1 University of Luebeck, Department of Radiation Oncology- Department of Visceral Surgery, Lübeck, Germany 2 University of Freiburg, Department of Molecular Medicine and Cell Research, Freiburg, Germany 3 University of Luebeck, Department of Radiation Oncology, Luebeck, Germany 4 German Cancer Consortium DKTK and German Cancer Research Center DKFZ, Department of Pathology, Heidelberg, Germany Poster: Radiobiology track: Radiobiology of the intestinal track