@article{KlementPoppKauletal.2022,
  author    = {Klement, Rainer J. and Popp, Ilinca and Kaul, David and Ehret, Felix and Grosu, Anca L. and Polat, B{\"u}lent and Sweeney, Reinhart A. and Lewitzki, Victor},
  title     = {Accelerated hyper-versus normofractionated radiochemotherapy with temozolomide in patients with glioblastoma: a multicenter retrospective analysis},
  series = {Journal of Neuro-Oncology},
  volume    = {156},
  journal   = {Journal of Neuro-Oncology},
  number    = {2},
  issn      = {1573-7373},
  doi       = {10.1007/s11060-021-03926-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269806},
  pages     = {407-417},
  year      = {2022},
  abstract  = {Background and Purpose The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis. Materials and Methods A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset. Results After a median follow-up of 15.7 months (range 0.8-88.6 months), median OS was 16.9 months (15.0-18.7 months) in the NFRT group and 14.9 months (13.2-17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis. Conclusions Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.},
  language  = {en}
}
@article{LewitzkiKlementKosmalaetal.2019,
  author    = {Lewitzki, Victor and Klement, Rainer J. and Kosmala, Rebekka and Lisowski, Dominik and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma},
  series = {Radiation Oncology},
  volume    = {14},
  journal   = {Radiation Oncology},
  doi       = {10.1186/s13014-019-1427-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202614},
  pages     = {227},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}