Impact of radiotherapy delay following biopsy for patients with unresected glioblastoma

Sarah Gao MD1, Lan Jin PhD, MSc2, Jennifer Moliterno MD2, Zachary A. Corbin MD3, Ranjit S. Bindra MD, PhD1, Joseph N. Contessa MD, PhD1, James B. Yu MD, MHS4,5, and Henry S. Park MD, MPH1,4
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  • 1 Department of Therapeutic Radiology, Yale School of Medicine, New Haven;
  • | 2 Department of Neurosurgery, Yale School of Medicine, New Haven;
  • | 3 Department of Neurology, Yale School of Medicine, New Haven;
  • | 4 Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut; and
  • | 5 Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
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OBJECTIVE

Because of the aggressive nature of glioblastoma, patients with unresected disease are encouraged to begin radiotherapy within approximately 1 month after craniotomy. The aim of this study was to investigate the potential association between time interval from biopsy to radiotherapy with overall survival in patients with unresected glioblastoma.

METHODS

Patients with unresected glioblastoma diagnosed between 2010 and 2014 who received adjuvant radiotherapy and concurrent chemotherapy were identified in the National Cancer Database. Demographic and clinical data were compared using chi-square and Wilcoxon rank-sum tests. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression modeling.

RESULTS

Among 3456 patients with unresected glioblastoma, initiation of radiotherapy within 3 weeks of biopsy was associated with a higher hazard of death compared with later initiation of radiotherapy. After excluding patients who received radiotherapy within 3 weeks of biopsy to minimize the effects of confounders associated with short time intervals from biopsy to radiotherapy, the median interval from biopsy to radiotherapy was 32 days (IQR 27–39 days). Overall, 1782 (66.82%) patients started radiotherapy within 5 weeks of biopsy, and 885 (33.18%) patients started radiotherapy beyond 5 weeks of biopsy. On multivariable analysis, there was no significant difference in overall survival between these two groups (HR 0.96, 95% CI 0.88–1.50; p = 0.374).

CONCLUSIONS

In patients with unresected glioblastoma, a longer time interval from biopsy to radiotherapy does not appear to be associated with worse overall survival. However, external validation of these findings is necessary given that selection bias is a significant limitation of this study.

ABBREVIATIONS

IDH = isocitrate dehydrogenase; KPS = Karnofsky Performance Status; MGMT = O6-methylguanine-DNA methyltransferase; NCDB = National Cancer Database; OS = overall survival.

Supplementary Materials

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  • 1

    Paolillo M, Boselli C, Schinelli S. Glioblastoma under siege: an overview of current therapeutic strategies. Brain Sci. 2018;8(1):15.

  • 2

    Tamimi AF, Juweid M. Epidemiology and outcome of glioblastoma. In: De Vleeschouwer S, ed. Glioblastoma [Internet]. Codon Publications;2017.Chapter 8. Accessed June 1, 2022. https://www.ncbi.nlm.nih.gov/books/NBK470003/

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987996.

  • 4

    Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459466.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Davis ME. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5 suppl):S2S8.

  • 6

    Lombardi MY, Assem M. Glioblastoma genomics: a very complicated story. In: De Vleeschouwer S, ed. Glioblastoma [Internet]. Codon Publications;2017.Chapter 1. Accessed June 1, 2022. https://www.ncbi.nlm.nih.gov/books/NBK470004/

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Tykocki T, Eltayeb M. Ten-year survival in glioblastoma. A systematic review. J Clin Neurosci. 2018;54:713.

  • 8

    Weller M, Butowski N, Tran DD, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):13731385.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Kole AJ, Park HS, Yeboa DN, et al. Concurrent chemoradiotherapy versus radiotherapy alone for "biopsy-only" glioblastoma multiforme. Cancer. 2016;122(15):23642370.

  • 10

    Balaña C, Capellades J, Teixidor P, et al. Clinical course of high-grade glioma patients with a "biopsy-only" surgical approach: a need for individualised treatment. Clin Transl Oncol. 2007;9(12):797803.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    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(5):11441150.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15(3):683690.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Nikolov V, Stojanovic M, Kostic A, et al. Factors affecting the survival of patients with glioblastoma multiforme. J BUON. 2018;23(1):173178.

  • 14

    Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys. 1993;26(2):239244.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Almenawer SA, Badhiwala JH, Alhazzani W, et al. Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis. Neuro Oncol. 2015;17(6):868881.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Wasilewski A, Serventi J, Kamalyan L, Wychowski T, Mohile N. Acute care in glioblastoma: the burden and the consequences. Neurooncol Pract. 2017;4(4):248254.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Nathan JK, Brezzell AL, Kim MM, Leung D, Wilkinson DA, Hervey-Jumper SL. Early initiation of chemoradiation following index craniotomy is associated with decreased survival in high-grade glioma. J Neurooncol. 2017;135(2):325333.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Burnet NG, Jena R, Jefferies SJ, Stenning SP, Kirkby NF. Mathematical modelling of survival of glioblastoma patients suggests a role for radiotherapy dose escalation and predicts poorer outcome after delay to start treatment. Clin Oncol (R Coll Radiol). 2006;18(2):93103.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Masui K, Cloughesy TF, Mischel PS. Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol. 2012;38(3):271291.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    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(2):357363.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    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(5):915921.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    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(1):172.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Randolph DM II, McTyre ER, Paulsson AK, et al. Impact of timing of radiotherapy in patients with newly diagnosed glioblastoma. Clin Neurol Neurosurg. 2016;151:7378.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Lai R, Hershman DL, Doan T, Neugut AI. The timing of cranial radiation in elderly patients with newly diagnosed glioblastoma multiforme. Neuro Oncol. 2010;12(2):190198.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    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(7):966974.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Press RH, Shafer SL, Jiang R, et al. Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: stratification by validated prognostic classification. Cancer. 2020;126(14):32553264.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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