J Neurol Surg A Cent Eur Neurosurg 2022; 83(03): 252-258
DOI: 10.1055/s-0041-1730965
Original Article

The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass

1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
,
Clara Frydrychowicz
2   Department of Neuropathology, University Hospital Leipzig, Leipzig, Sachsen, Germany
,
Katja Jähne
1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
,
Tim Wende
1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
,
Florian Wilhelmy
1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
,
Felix Arlt
1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
,
Clemens Seidel
3   Department of Radio-Oncology, University Hospital Leipzig, Leipzig, Sachsen, Germany
,
Karl-Titus Hoffmann
4   Department of Neuro-Radiology, University Hospital Leipzig, Leipzig, Sachsen, Germany
,
Jürgen Meixensberger
1   Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany
› Author Affiliations

Abstract

Objective Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV).

Methods Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan–Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression.

Results One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival (p = 0.946) or OS (p = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached.

Conclusion Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.

Ethical Approval

Data collection and analysis were approved by the ethical committee of the Medical Faculty, University of Leipzig, and performed in accordance with data protection guidelines (144/08-ek). Informed consent for retrospective data analysis was obtained from all patients treated in the Neurosurgical Department of Leipzig University.


Availability of Supporting Data

Data and material are available from the corresponding author upon reasonable request.


Supplementary Material



Publication History

Received: 11 August 2020

Accepted: 16 December 2020

Article published online:
08 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Ostrom QT, Cioffi G, Gittleman H. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro-oncol 2019; 21 (05, Suppl 5): v1-v100
  • 2 Louis DN, Perry A, Reifenberger G. et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (06) 803-820
  • 3 Weller M, van den Bent M, Tonn JC. et al; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18 (06) e315-e329
  • 4 Blumenthal DT, Won M, Mehta MP. et al. Short delay in initiation of radiotherapy for patients with glioblastoma-effect of concurrent chemotherapy: a secondary analysis from the NRG Oncology/Radiation Therapy Oncology Group database. Neuro-oncol 2018; 20 (07) 966-974
  • 5 Katsigiannis S, Krischek B, Barleanu S. et al. Impact of time to initiation of radiotherapy on survival after resection of newly diagnosed glioblastoma. Radiat Oncol 2019; 14 (01) 73
  • 6 Santos VM, Marta GN, Mesquita MC, Lopez RVM, Cavalcante ER, Feher O. The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma. J Neurooncol 2019; 143 (01) 95-100
  • 7 Berger MS, Ojemann GA. Intraoperative brain mapping techniques in neuro-oncology. Stereotact Funct Neurosurg 1992; 58 (1–4): 153-161
  • 8 Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping for glioma resection. N Engl J Med 2008; 358 (01) 18-27
  • 9 Marongiu A, D'Andrea G, Raco A. 1.5-T field intraoperative magnetic resonance imaging improves extent of resection and survival in glioblastoma removal. World Neurosurg 2017; 98: 578-586
  • 10 Hervey-Jumper SL, Li J, Lau D. et al. Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period. J Neurosurg 2015; 123 (02) 325-339
  • 11 Stummer W, Stocker S, Wagner S. et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 1998; 42 (03) 518-525 , discussion 525–526
  • 12 Weller M, van den Bent M, Hopkins K. et al; European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 2014; 15 (09) e395-e403
  • 13 Bleehen NM, Stenning SP. The Medical Research Council Brain Tumour Working Party. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer 1991; 64 (04) 769-774
  • 14 Quillien V, Lavenu A, Ducray F. et al. Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial. Oncotarget 2016; 7 (38) 61916-61929
  • 15 Quant EC, Wen PY. Response assessment in neuro-oncology. Curr Oncol Rep 2011; 13 (01) 50-56
  • 16 Walker MD, Alexander Jr E, Hunt WE. et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978; 49 (03) 333-343
  • 17 Loureiro LVM, Victor EdaS, Callegaro-Filho D. et al. Minimizing the uncertainties regarding the effects of delaying radiotherapy for glioblastoma: a systematic review and meta-analysis. Radiother Oncol 2016; 118 (01) 1-8
  • 18 Geurts M, van den Bent MJ. Timing of radiotherapy in newly diagnosed glioblastoma: no need to rush?. Neuro-oncol 2018; 20 (07) 868-869
  • 19 Spratt DE, Folkert M, Zumsteg ZS. et al. Temporal relationship of post-operative radiotherapy with temozolomide and oncologic outcome for glioblastoma. J Neurooncol 2014; 116 (02) 357-363
  • 20 Sun MZ, Oh T, Ivan ME. et al. Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma. J Neurosurg 2015; 122 (05) 1144-1150
  • 21 Valduvieco I, Verger E, Bruna J. et al. Impact of radiotherapy delay on survival in glioblastoma. Clin Transl Oncol 2013; 15 (04) 278-282
  • 22 Blumenthal DT, Won M, Mehta MP. et al. Short delay in initiation of radiotherapy may not affect outcome of patients with glioblastoma: a secondary analysis from the radiation therapy oncology group database. J Clin Oncol 2009; 27 (05) 733-739
  • 23 Seidlitz A, Siepmann T, Löck S, Juratli T, Baumann M, Krause M. Impact of waiting time after surgery and overall time of postoperative radiochemotherapy on treatment outcome in glioblastoma multiforme. Radiat Oncol 2015; 10: 172
  • 24 Han SJ, Rutledge WC, Molinaro AM. et al. The effect of timing of concurrent chemoradiation in patients with newly diagnosed glioblastoma. Neurosurgery 2015; 77 (02) 248-253 , discussion 253
  • 25 Lopez S, Calugaru V, Lamproglou I. et al. Les effets de la liste d'attente sur la survie des patients atteints de glioblastome traité par irradiation. Cancer Radiother 2008; 12 (05) 497-499
  • 26 Alnaami I, VanderPluym J, Murtha A. et al. The potential impact of delayed radiation therapy on patients with glioblastoma. Can J Neurol Sci 2013; 40 (06) 790-794
  • 27 Peker S, Abacioglu U, Sun I, Yuksel M, Pamir MN. Irradiation after surgically induced brain injury in the rat: timing in relation to severity of radiation damage. J Neurooncol 2004; 70 (01) 17-21
  • 28 Champ CE, Siglin J, Mishra MV. et al. Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in high-grade gliomas. Radiat Oncol 2012; 7: 220
  • 29 Stupp R, Mason WP, van den Bent MJ. et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
  • 30 Hegi ME, Diserens A-C, Gorlia T. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352 (10) 997-1003
  • 31 Osborn VW, Lee A, Garay E, Safdieh J, Schreiber D. Impact of timing of adjuvant chemoradiation for glioblastoma in a large hospital database. Neurosurgery 2018; 83 (05) 915-921
  • 32 Amsbaugh MJ, Yusuf M, Gaskins J, Burton E, Woo S. The impact of timing of adjuvant therapy on survival for patients with glioblastoma: an analysis of the National Cancer Database. J Clin Neurosci 2019; 66: 92-99
  • 33 Wee CW, Kim E, Kim TM. et al. Impact of interim progression during the surgery-to-radiotherapy interval and its predictors in glioblastoma treated with temozolomide-based radiochemotherapy. J Neurooncol 2017; 134 (01) 169-175