ESTRO 38 Abstract book

S189 ESTRO 38

induced cell cycle distribution was quantified by flow cytometry. Apoptosis and senescence levels were determined using caspase-3, annexin-V and β- galactosidase stainings. Immunofluorescence analyses of γH2AX foci were performed to assess DNA double strand break (DSB) repair, and the expression and activation of various proteins involved in human damage signaling and DSB repair were elucidated by Western blot in MSCs from different tissues of origin. Results All MSCs exhibited a relative radioresistance independent of their tissue source and comparable to adult fibroblasts. The defining stem cell characteristics and multi-lineage differentiation potential remained largely unaffected by IR Independent of the MSCs' tissue source. While adMSCs and bmMSCS showed a strong IR-induced accumulation in the G2/M phase, wjMSCs exhibited virtually no G2/M phase arrest. Very low apoptosis levels were found in adMSCs and bmMSCs after IR, whereas IR induced apoptosis in up to 20% of wjMSCs as measured by caspase- 3 activation. In adMSCs and bmMSCs, γH2AX foci numbers induced by up to 8 Gy returned to baseline levels within 24 hours after treatment. In contrast, 8 Gy led to significant residual γH2AX foci and hence unrepaired DSBs in wjMSC1. Expression of β-galactosidase cells was found to be unaffected in wjMSCs, while irradiated adMSCs and bmMSCs demonstrated an increase of β-galactosidase- positive cells. Levels of phospho-ATM and phospho-Chk2 observed after IR were found strongly decreased in all MSCs at 24 hours after IR. Contrary to adMSCs and bmMSCs, wjMSCs exhibited increased phospho-BRCA1 expression still at 24 hours after IR. Conclusion Despite a comparable radiation resistance of MSCs derived from different human tissues, MSCs exhibited differential responses to IR regarding apoptosis, senescence and and cell cycle distribution that depended on their tissue source. As the radiation resistance of human MSCs was found independent of their tissue of origin, MSCs from various tissues may aid the regeneration of radiation- induced tissue damages. However, the observed tissue- specific differences of MSCs may need to be taken into account in order to find the optimal tissue source when devising MSC-based clinical therapies for IR-induced tissue damage. OC-0380 Dose response relation in esophageal cancer after neoadjuvant therapy: multi-institutional analysis M. Thomas 1,2 , A.S. Borggreve 3,4 , P.S. Van Rossum 4 , C. Perneel 5 , J. Moons 6 , E. Van Daele 7 , R. Van Hillegersberg 3 , W. Deng 8 , P. Pattyn 7 , S. Mook 4 , T. Boterberg 9 , J.P. Ruurda 3 , P. Nafteux 6 , S.H. Lin 8 , K. Haustermans 1,2 1 KU Leuven – University of Leuven, Department of Oncology – Laboratory Experimental Radiotherapy, B- 3000 Leuven, Belgium; 2 UZ Leuven – University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium; 3 University Medical Center Utrecht, Department of Surgery, 3584CX Utrecht, The Netherlands; 4 University Medical Center Utrecht, Department of Radiation Oncology, 3584CX Utrecht, The Netherlands; 5 Royal Military Academy, Department of Applied Mathematics, B-1000 Brussels, Belgium; 6 UZ Leuven – University Hospitals Leuven, Department of Thoracic Surgery, B-3000 Leuven, Belgium ; 7 UZ Gent – Ghent University Hospital, Department of Pediatric and Gastrointestinal Surgery, B-9000 Ghent, Belgium ; 8 The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston – Texas, USA; 9 UZ Gent – Ghent University Hospital, Department of Radiation Oncology, B-9000 Ghent, Belgium Proffered Papers: CL 7 :Proffered papers: GI

Purpose or Objective Curative treatment for locally advanced esophageal cancer (EC) consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Various chemotherapy and radiotherapy regimens are currently used worldwide. The aim of this study was to explore whether a higher total radiation dose leads to a higher probability to obtain a pathological major response (pMR). Material and Methods All consecutive patients who underwent nCRT followed by surgery for locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus between 2000 and 2017 at four major university medical centres were included and stratified according to a prescribed dose of 36Gy, 40Gy, 41.4Gy, 45Gy or 50.4Gy in fractions of 1.8Gy or 2Gy. Clinical and treatment-related characteristics were collected from the prospectively obtained databases: age at diagnosis, sex, clinical tumor and nodal stage, histology, chemotherapy regimen, use of induction chemotherapy and the time interval from nCRT to surgery. The primary endpoint for the analysis was a pMR, defined as Mandard 1 (no residual tumor cells) or Mandard 2 (fibrosis with scattered tumor cells). A multivariable logistic regression analysis was used to analyse the relation between neoadjuvant radiation dose and pMR. Subgroup analysis was performed according to histology. Results A total of 1102 patients were eligible for analysis, who received either 36Gy (162; 14.7%), 40Gy (79; 7.2%), 41.4Gy (211; 19.1%), 45Gy (271; 24.6%) or 50.4Gy (379; 34.4%). A pMR was achieved in 604 patients (54.8%). In multivariable analysis, the total radiation dose was the only factor increasing the probability of reaching a pMR (odds ratio (OR) 1.031), Table 1. Factors reducing this probability were a higher cT stage (cT1: reference; cT2: OR 1.030; cT3: OR 0.556; cT4: OR 0.448), the presence of an AC (OR 0.362) and the use of non-platinum versus platinum based chemotherapy (OR 0.294). The interaction between tumor type and chemotherapy regimen indicated that using non-platinum based chemotherapy for AC patients increases the likelihood of achieving a pMR (OR 4.336). The interaction between tumor type and the use of induction chemotherapy showed that the use of induction chemotherapy is beneficial to reach a pMR in AC patients (OR 1.731). For AC, 417 of 819 patients (50.9%) achieved a pMR. Factors increasing the probability to achieve a pMR were total radiation dose (OR 1.027) and the use of induction chemotherapy (OR 1.702), Table 1. Tumor stage was the only factor reducing this probability (cT1: reference; cT2: OR 0.423, cT3: OR 0.260; cT4: OR 0.241). For SCC, 187 of 283 patients (66.1%) achieved a pMR. No subgroup analysis with reliable adjustment of covariables was possible for the cohort of SCC patients.

Conclusion