The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma

  • Vanessa Montes Santos
  • Gustavo Nader MartaEmail author
  • Marcella Coelho Mesquita
  • Rossana Veronica Mendoza Lopez
  • Edla Renata Cavalcante
  • Olavo Feher
Clinical Study



The standard treatment for newly diagnosed glioblastoma includes maximal safe surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) and maintenance TMZ. The impact of time to start radiation therapy (TRT) on overall survival (OS) in glioblastoma patients is controversial. The study aimed to evaluate the impact of TRT on OS in patients diagnosed with glioblastoma who received standard treatment.


In this retrospective study, we included patients with confirmed diagnosis of glioblastoma treated from 2011 to 2016. TRT was defined as the time between surgery (biopsy or resection) and the first day of radiation therapy. The endpoint was OS. The patients were divided according to the TRT in three categories: < 30 days, 30–60 days and ≥ 60 days.


A total of 134 patients were included with a mean age of 51.82 years (range 19–78 years). Median TRT was 80 days. On univariate and multivariable analysis, we identified age as the only significant independent predictor for OS. There was no statistically significant negative impact of TRT on OS (p = 0.47).


There was no clear evidence that delaying post-operative combined chemoradiotherapy negatively impacts OS, not even for TRT longer than 60 days.


Glioblastoma Treatment Radiation therapy Survival 


Compliance with ethical standards

Conflict of interest

The authors have declared no conflicts of interest.


  1. 1.
    Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y et al (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–ii56CrossRefGoogle Scholar
  2. 2.
    Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507CrossRefGoogle Scholar
  3. 3.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefGoogle Scholar
  4. 4.
    Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC et al (2009) 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 10:459–466CrossRefGoogle Scholar
  5. 5.
    Stensjoen AL, Solheim O, Kvistad KA, Haberg AK, Salvesen O, Berntsen EM (2015) Growth dynamics of untreated glioblastomas in vivo. Neuro Oncol 17:1402–1411CrossRefGoogle Scholar
  6. 6.
    Silva SB, Pereira AAL, Marta GN, de Barros Lima KML, de Freitas TB, Matutino ARB et al (2018) Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer. Breast 38:39–44CrossRefGoogle Scholar
  7. 7.
    Lee AW, Chan DK, Fowler JF, Poon YF, Law SC, Foo W et al (1994) T1 nasopharyngeal carcinoma: the effect of waiting time on tumor control. Int J Radiat Oncol Biol Phys 30:1111–1117CrossRefGoogle Scholar
  8. 8.
    Irwin C, Hunn M, Purdie G, Hamilton D (2007) Delay in radiotherapy shortens survival in patients with high grade glioma. J Neuro Oncol 85:339–343CrossRefGoogle Scholar
  9. 9.
    Lai R, Hershman DL, Doan T, Neugut AI (2010) The timing of cranial radiation in elderly patients with newly diagnosed glioblastoma multiforme. Neuro Oncol 12:190–198CrossRefGoogle Scholar
  10. 10.
    Blumenthal DT, Won M, Mehta MP, Curran WJ, Souhami L, Michalski JM et al (2009) 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 27:733–739CrossRefGoogle Scholar
  11. 11.
    Spratt DE, Folkert M, Zumsteg ZS, Chan TA, Beal K, Gutin PH et al (2014) Temporal relationship of post-operative radiotherapy with temozolomide and oncologic outcome for glioblastoma. J Neuro-Oncol 116:357–363CrossRefGoogle Scholar
  12. 12.
    Sun MZ, Oh T, Ivan ME, Clark AJ, Safaee M, Sayegh ET et al (2015) Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma. J Neurosurg 122:1144–1150CrossRefGoogle Scholar
  13. 13.
    Han SJ, Rutledge WC, Molinaro AM, Chang SM, Clarke JL, Prados MD et al (2015) The effect of timing of concurrent chemoradiation in patients with newly diagnosed glioblastoma. Neurosurgery 77:248–253 (discussion 53)CrossRefGoogle Scholar
  14. 14.
    Wang TJ, Jani A, Estrada JP, Ung TH, Chow DS, Soun JE et al (2016) Timing of adjuvant radiotherapy in glioblastoma patients: a single-institution experience with more than 400 patients. Neurosurgery 78:676–682CrossRefGoogle Scholar
  15. 15.
    Osborn VW, Lee A, Garay E, Safdieh J, Schreiber D (2018) Impact of timing of adjuvant chemoradiation for glioblastoma in a large hospital database. Neurosurgery 83:915–921CrossRefGoogle Scholar
  16. 16.
    Noel G, Huchet A, Feuvret L, Maire JP, Verrelle P, Le Rhun E et al (2012) Waiting times before initiation of radiotherapy might not affect outcomes for patients with glioblastoma: a French retrospective analysis of patients treated in the era of concomitant temozolomide and radiotherapy. J Neurooncol 109:167–175CrossRefGoogle Scholar
  17. 17.
    Hoshino T, Ito S, Asai A, Shibuya M, Prados MD, Dodson BA et al (1992) Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine. Int J Cancer 50:1–5CrossRefGoogle Scholar
  18. 18.
    Wang CH, Rockhill JK, Mrugala M, Peacock DL, Lai A, Jusenius K et al (2009) Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model. Cancer Res 69:9133–9140CrossRefGoogle Scholar
  19. 19.
    Willner J, Baier K, Caragiani E, Tschammler A, Flentje M (2002) Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 52:382–389CrossRefGoogle Scholar
  20. 20.
    Willner J, Baier K, Pfreundner L, Flentje M (1999) Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma. Acta Oncol 38:1025–1030CrossRefGoogle Scholar
  21. 21.
    Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG et al (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE.3. Lancet Oncol 9:29–38CrossRefGoogle Scholar
  22. 22.
    Johnson CR, Thames HD, Huang DT, Schmidt-Ullrich RK (1995) The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography. Int J Radiat Oncol Biol Phys 33:281–287CrossRefGoogle Scholar
  23. 23.
    Koch U, Krause M, Baumann M (2010) Cancer stem cells at the crossroads of current cancer therapy failures–radiation oncology perspective. Semin Cancer Biol 20:116–124CrossRefGoogle Scholar
  24. 24.
    Blumenthal DT, Won M, Mehta MP, Gilbert MR, Brown PD, Bokstein F et al (2018) 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 20:966–974CrossRefGoogle Scholar
  25. 25.
    Louvel G, Metellus P, Noel G, Peeters S, Guyotat J, Duntze J et al (2016) Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients. Radiother Oncol 118:9–15CrossRefGoogle Scholar
  26. 26.
    Loureiro LV, Victor Eda S, Callegaro-Filho D, Koch Lde O, Pontes Lde B, Weltman E et al (2016) Minimizing the uncertainties regarding the effects of delaying radiotherapy for Glioblastoma: a systematic review and meta-analysis. Radiother Oncol 118:1–8CrossRefGoogle Scholar
  27. 27.
    Adeberg S, Bostel T, Harrabi S, Bernhardt D, Welzel T, Wick W et al (2015) Impact of delays in initiating postoperative chemoradiation while determining the MGMT promoter-methylation statuses of patients with primary glioblastoma. BMC Cancer 15:558CrossRefGoogle Scholar
  28. 28.
    Peker S, Abacioglu U, Sun I, Yuksel M, Pamir MN (2004) Irradiation after surgically induced brain injury in the rat: timing in relation to severity of radiation damage. J Neuro-Oncol 70:17–21CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hospital Israelita Albert Einstein - Clinical Oncology UnitSão PauloBrazil
  2. 2.Department of Radiology and Oncology, Radiation Oncology Unit, Instituto do Câncer do Estado de São Paulo (ICESP)Universidade de São PauloSão PauloBrazil
  3. 3.Department of Radiation OncologyHospital Sírio-LibânesSão PauloBrazil
  4. 4.Department of Radiology and Oncology, Clinical Oncology Unit, Instituto do Câncer do Estado de São Paulo (ICESP)Universidade de São PauloSão PauloBrazil
  5. 5.Instituto do Câncer do Estado de São Paulo (ICESP) - Center for Translational Research in OncologyUniversidade de São PauloSão PauloBrazil
  6. 6.Department of Clinical OncologyHospital Sírio-LibânesSão PauloBrazil

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