ESTRO 2021 Abstract Book


ESTRO 2021

Purpose or Objective A molecular mRNA signature characterizing mesenchymal / proneural character of primary stem-cell-enriched cultures of glioblastoma cells was developed based on mRNA abundances of 10 markers. Higher values for the signature and thus mesenchymal stem cell properties correlate with biological properties of the cell lines in vitro (radiosensitivity, invasiveness) as well as clinical patient-outcome (unpublished data). In this project, the mRNA signature was correlated with tumor volumes contoured on preoperative MR images of the respective patients. Materials and Methods For 24 patients primary cell lines were generated from resection material from 2015 to 2016. Clinical data are available for all patients. The molecular signature as a continuous variable with higher values corresponding to mesenchymal stem cell properties was defined for all cell lines. For 16 of the cell lines, pre-operative MR imaging and radiotherapy plans were available for analysis. Tumor volume (T1 contrast enhancing volume), necrotic volume (central hypointense volume without contrast enhancement) and edema (T2 flair hyperintense volume) were contoured manually. Ratios of necrosis / tumor volume and edema / tumor volume were calculated. Contoured volumes were correlated with the molecular signature. Results Mean contoured tumor volume was 42.0±7.1 ccm, mean necrotic volume 16.1±3.4 ccm, mean edema volume 110.2±17.7ccm. For the whole cohort, a moderate correlation was observed between edema / tumor volume and the molecular signature (r=0.43). A subgroup analysis stratified by MGMT promoter methylation status revealed no significant difference in mean tumor, necrosis and edema volume. In the cohort of MGMT promoter methylated tumors no correlations between molecular signature and imaging features was observed. However, for MGMT promoter unmethylated tumors, the molecular signature showed a strong positive correlation with edema / tumor ratio (r=0.73) and a strong negative correlation with necrosis / tumor ratio (r=-0.84). Conclusion The findings are in line with the biological properties of mesenchymal stem cells showing a more invasive growth pattern (correlating with smaller necrotic volumes) and invasiveness (correlating with edema) for MGMT unmethylated glioblastomas. Imaging parameters might help characterizing the molecular properties in this subgroup. This information might be used in the future as a prognostic factor and for treatment stratification of patients. PH-0168 Hyper-versus normofractionated radiochemotherapy with temozolomide in patients with glioblastoma. V. Lewitzki 1 , R. Sweeney 2 , R.J. Klement 3 , A. Grosu 4 , B. Polat 5 , I. Popp 6 1 Julius-Maximilians University, Radiation Oncology, Würzburg, Germany; 2 Leopoldina Hospital, Radiation Oncology, Schweinfurt, Germany; 3 Leopoldina Hospital , Radiation Oncology, Schweinfurt, Germany; 4 University of Freiburg, Radiation Oncology , Freiburg, Germany; 5 Julius-Maximilians University, Radiation Oncology , Würzburg, Germany; 6 University of Freiburg, Radiation Oncology, Freiburg, Germany Purpose or Objective Current standard of treatment for patients with glioblastoma (GB) is maximal surgical resection followed by normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) with TMZ has not been compared with standard therapy in a randomized setting, but a few available monocentric retrospective studies reported comparable efficiency. The aim of the current study was to compare HFRT and NFRT in a larger, multicenter cohort. Materials and Methods Data of 397 patients with newly diagnosed GB treated from 10/2004 to 7/2018 at three tertiary care institutions were extracted from a clinical database and retrospectively analyzed. A total of 281 patients were treated with NFRT with doses from 54 to 60 Gy in 30 fractions (249 with simultaneous and 4 with sequential TMZ). These were compared to 116 patients treated with HFRT of 54.0 Gy in 30 fraction with 1.8 Gy twice daily (101 with simultaneous and 3 with sequential TMZ). The association between fractionation scheme and clinical characteristics with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis. Results Median overall survival (OS) was 18.5 month for the entire cohort. For patients treated with NFRT median OS was 17.6 months compared to 18.7 months in patients treated with HFRT (p=0.324). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 1.973 (95% CI 1.547-2.516, p=0.0001). In multivariable analysis adjusted for MGMT promotor methylation status, salvage treatment and IDH-1 mutation status, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95% CI 1.481-2.5, p<0.001). Positive MGMT-methylation status, IDH-1 mutation and salvage treatment were highly significant positive prognostic factors. There was no significant association between fractionation scheme and OS (p=0.324), with a HR of 1.13 for hyperfractionation (95% CI 0.884-1.451). These data are in line with our previously reported monocentric experience. Conclusion Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard fractionation protocol for GB, now confirmed in a large multicenter cohort. HFRT may thus be an alternative with comparable efficacy to NFRT with the possibility of shortening treatment time. PH-0169 Proton therapy for low grade glioma, who will benefit most? H. van der Weide 1 , M. Kramer 2 , D. Scandurra 2 , M. Landeweerd 2 , R. Enting 3 , I. Bosma 3 , M. Heesters 2 , A. Bannink-Gawryszuk 2 , S. Both 2 , J. Langendijk 2 1 Univeristy Medical Centre Groningen, Radiation Oncology, Groningen, The Netherlands; 2 University Medical Centre Groningen, Radiation Oncology, Groningen, The Netherlands; 3 University Medical Centre Groningen,

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