TY - JOUR A1 - Lewitzki, Victor A1 - Klement, Rainer J. A1 - Kosmala, Rebekka A1 - Lisowski, Dominik A1 - Flentje, Michael A1 - Polat, Bülent T1 - Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma JF - Radiation Oncology N2 - Background Current standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ. Methods Data of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method. Results Median overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95% CI 1.47–3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95% CI 1.21–3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504). Conclusions Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability. KW - Brain cancer KW - Glioblastoma KW - High grade glioma KW - Radiotherapy KW - Temozolomide KW - Corticosteroids Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202614 VL - 14 ER - TY - JOUR A1 - Meyer, Till Jasper A1 - Scherzad, Agmal A1 - Moratin, Helena A1 - Gehrke, Thomas Eckert A1 - Killisperger, Julian A1 - Hagen, Rudolf A1 - Wohlleben, Gisela A1 - Polat, Bülent A1 - Dembski, Sofia A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro JF - Materials N2 - Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP\(_{20 nm}\) and ZnO-NP\(_{100 nm}\) was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP\(_{20 nm}\) or 20 µg/mL of ZnO-NP\(_{100 nm}\) in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP\(_{100 nm}\) increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP\(_{20 nm}\). ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP\(_{100 nm}\), an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect. KW - zinc oxide nanoparticles KW - irradiation KW - oxidative DNA damage KW - head and neck squamous cell carcinoma Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193897 SN - 1996-1944 VL - 12 IS - 24 ER - TY - JOUR A1 - Richter, Anne A1 - Exner, Florian A1 - Bratengeier, Klaus A1 - Polat, Bülent A1 - Flentje, Michael A1 - Weick, Stefan T1 - Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases JF - Radiation Oncology N2 - Background The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share “best practices”. Methods VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. Results The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. Conclusion The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk. KW - auto-planning KW - VMAT KW - single arc KW - double arc KW - full arc KW - partial arc KW - plan comparison Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200301 VL - 14 ER -