Skip to main content
SpringerLink
Log in

Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line?

  • Topic Review
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Glioblastoma is a malignant tumor characterized by a rapid proliferation rate. Contemporary multi-modality treatment consists of maximal surgical resection followed by radiation therapy (RT) combined with cytotoxic chemotherapy. The optimal timing of these different steps is not known. Four studies from the pre-temozolomide era, encompassing a total of 4,584 subjects, have examined the consequences of a delay between resection and starting RT. Whereas the two small single-institution studies found this delay to be detrimental, two large multi-institutional studies found delay to be either slightly beneficial or at least not harmful. Here, we critically compare the methodologies and results presented in these studies, and include a novel analysis of the combined datasets. We conclude that moderate wait periods (up to 4–6 weeks post-operatively) are safe and may be modestly beneficial. Conversely, there is no evidence to justify waiting longer than 6 weeks. Underlying radiobiological principles are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  2. Kerr D et al (2002) Redesigning cancer care. BMJ 324:164–166

    Article  PubMed  Google Scholar 

  3. Begg CB et al (1998) Impact of hospital volume on operative mortality for major cancer surgery. JAMA 280:1747–1751

    Article  PubMed  CAS  Google Scholar 

  4. Kristiansen K et al (1981) Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 47:649–652

    Article  PubMed  CAS  Google Scholar 

  5. Walker MD et al (1978) Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:333–343. doi:10.3171/jns.1978.49.3.0333

    Article  PubMed  CAS  Google Scholar 

  6. Keime-Guibert F et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535

    Article  PubMed  CAS  Google Scholar 

  7. Roa W et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1583–1588. doi:10.1200/JCO.2004.06.082

    Article  PubMed  CAS  Google Scholar 

  8. Blumenthal DT 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 27:733–739

    Article  PubMed  Google Scholar 

  9. Do V, Gebski V, Barton MB (2000) The effect of waiting for radiotherapy for grade III/IV gliomas. Radiother Oncol 57:131–136

    Article  PubMed  CAS  Google Scholar 

  10. Irwin C et al (2007) Delay in radiotherapy shortens survival in patients with high grade glioma. J Neurooncol 85:339–343

    Article  PubMed  Google Scholar 

  11. Lai R et al (2010) The timing of cranial radiation in elderly patients with newly diagnosed glioblastoma multiforme. Neurooncology 12:190–198

    Google Scholar 

  12. Coffey JC et al (2003) Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol 4:760–768

    Article  PubMed  CAS  Google Scholar 

  13. Demicheli R, Valagussa P, Bonadonna G (2001) Does surgery modify growth kinetics of breast cancer micrometastases? Br J Cancer 85:490–492. doi:10.1054/bjoc.2001.1969

    Article  PubMed  CAS  Google Scholar 

  14. Fisher B et al (1989) Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 49:1996–2001

    PubMed  CAS  Google Scholar 

  15. Oliver RT (1995) Does surgery disseminate or accelerate cancer? Lancet 346:1506–1507

    Article  PubMed  CAS  Google Scholar 

  16. Chen Z et al (2008) The relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature. Radiother Oncol 87:3–16

    Article  PubMed  Google Scholar 

  17. Ballo MT et al (2004) Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma. Int J Radiat Oncol Biol Phys 58:1461–1467. doi:10.1016/j.ijrobp.2003.09.079

    Article  PubMed  Google Scholar 

  18. Andrews SF et al (2005) Does a delay in external beam radiation therapy after tissue diagnosis affect outcome for men with prostate carcinoma? Cancer 104:299–304

    Article  PubMed  Google Scholar 

  19. Nguyen PL et al (2005) The impact of a delay in initiating radiation therapy on prostate-specific antigen outcome for patients with clinically localized prostate carcinoma. Cancer 103:2053–2059. doi:10.1002/cncr.21050

    Article  PubMed  Google Scholar 

  20. Burnet NG et al (2006) 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) 18:93–103

    CAS  Google Scholar 

  21. Mackillop WJ et al (1996) The effect of delay in treatment on local control by radiotherapy. Int J Radiat Oncol Biol Phys 34:243–250

    Article  PubMed  CAS  Google Scholar 

  22. Mackillop WJ (2007) Killing time: the consequences of delays in radiotherapy. Radiother Oncol 84:1–4

    Article  PubMed  Google Scholar 

  23. Gonzalez-SanSegundo C, Santos-Miranda JA, Cuesta-Alvaro P (2001) Comment on: the effect of waiting for radiotherapy for grade III/IV gliomas. Radiother Oncol 60:333–334

    Article  PubMed  CAS  Google Scholar 

  24. Hall E, Giaccia A (2006) Radiobiology for the radiologist. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  25. Breur K (1966) Growth rate and radiosensitivity of human tumours. II. Radiosensitivity of human tumours. Eur J Cancer 2:173–188

    PubMed  CAS  Google Scholar 

  26. Laird AK (1965) Dynamics of tumour growth: comparison of growth rates and extrapolation of growth curve to one cell. Br J Cancer 19:278–291

    Article  PubMed  CAS  Google Scholar 

  27. Demicheli R et al (2008) The effects of surgery on tumor growth: a century of investigations. Ann Oncol 19:1821–1828

    Article  PubMed  CAS  Google Scholar 

  28. Norton L (1988) A Gompertzian model of human breast cancer growth. Cancer Res 48:7067–7071

    PubMed  CAS  Google Scholar 

  29. Hoshino T et al (1992) Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine. Int J Cancer 50:1–5

    Article  PubMed  CAS  Google Scholar 

  30. Wang CH et al (2009) Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model. Cancer Res 69:9133–9140. doi:10.1158/0008-5472.CAN-08-3863

    Article  PubMed  CAS  Google Scholar 

  31. Mukherji SK et al (1999) Tumor volume: an independent predictor of outcome for laryngeal cancer. J Comput Assist Tomogr 23:50–54

    Article  PubMed  CAS  Google Scholar 

  32. Shipley WU, Stanley JA, Steel GG (1975) Tumor size dependency in the radiation response of the Lewis lung carcinoma. Cancer Res 35:2488–2493

    PubMed  CAS  Google Scholar 

  33. Jochen W et al (2002) Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 52:382–389

    Article  Google Scholar 

  34. Willner J et al (1999) Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma. Acta Oncol 38:1025–1030

    Article  PubMed  CAS  Google Scholar 

  35. Gorlia T 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 9:29–38. doi:10.1016/S1470-2045(07)70384-4

    Article  PubMed  Google Scholar 

  36. Stummer W et al (2008) Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 62:564–576. doi:10.1227/01.neu.0000317304.31579.17

    Article  PubMed  Google Scholar 

  37. Wood JR, Green SB, Shapiro WR (1988) The prognostic importance of tumor size in malignant gliomas: a computed tomographic scan study by the Brain Tumor Cooperative Group. J Clin Oncol 6:338–343

    PubMed  CAS  Google Scholar 

  38. Johnson CR et al (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 33:281–287

    Article  PubMed  CAS  Google Scholar 

  39. Koch U, Krause M, Baumann M (2010) Cancer stem cells at the crossroads of current cancer therapy failures—radiation oncology perspective. Semin Cancer Biol 20:116–124

    Article  PubMed  Google Scholar 

  40. Burger PC et al (1983) Computerized tomographic and pathologic studies of the untreated, quiescent, and recurrent glioblastoma multiforme. J Neurosurg 58:159–169. doi:10.3171/jns.1983.58.2.0159

    Article  PubMed  CAS  Google Scholar 

  41. Manon R et al (2004) The impact of mid-treatment MRI on defining boost volumes in the radiation treatment of glioblastoma multiforme. Technol Cancer Res Treat 3:303–307

    PubMed  Google Scholar 

  42. Rampling R et al (1994) Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors. Int J Radiat Oncol Biol Phys 29:427–431

    Article  PubMed  CAS  Google Scholar 

  43. Evans SM et al (2004) Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 10:8177–8184

    Article  PubMed  CAS  Google Scholar 

  44. Rankin EB, Giaccia AJ (2008) The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 15:678–685

    Article  PubMed  CAS  Google Scholar 

  45. Soeda A et al (2009) Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1[alpha]. Oncogene 28:3949–3959

    Article  PubMed  CAS  Google Scholar 

  46. Murray D et al (2003) Influence of oxygen on the radiosensitivity of human glioma cell lines. Am J Clin Oncol 26(5):e169–e177

    Google Scholar 

  47. Gordillo GM, Sen CK (2003) Revisiting the essential role of oxygen in wound healing. Am J Surg 186:259–263

    Article  PubMed  CAS  Google Scholar 

  48. Fortin B et al (2006) Waiting time for radiation therapy in breast cancer patients in Quebec from 1992 to 1998: a study of surgically treated breast cancer patients in Quebec documents and helps to explain increased waiting times for radiation therapy. Health Policy 1:152–167

    Google Scholar 

  49. Veronique B et al (1998) Predictors of delay in starting radiation treatment for patients with early stage breast cancer. Int J Radiat Oncol Biol Phys 41:109–115

    Article  Google Scholar 

  50. Kies MS et al (2001) Concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and hyperfractionated radiation for locally advanced squamous head and neck cancer. J Clin Oncol 19:1961–1969

    PubMed  CAS  Google Scholar 

  51. Peker S et al (2004) Irradiation after surgically induced brain injury in the rat: timing in relation to severity of radiation damage. J Neurooncol 70:17–21

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Translational Research in Radiation Oncology, Sheba Medical Center, 52621, Tel Hashomer, Israel

    Yaacov Richard Lawrence

  2. Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Deborah T. Blumenthal & Felix Bokstein

  3. Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Diana Matceyevsky

  4. Stereotactic Radiosurgery Unit, Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Andrew A. Kanner

  5. Department of Radiation Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Benjamin W. Corn

Authors
  1. Yaacov Richard Lawrence
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deborah T. Blumenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diana Matceyevsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew A. Kanner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Felix Bokstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Benjamin W. Corn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin W. Corn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lawrence, Y.R., Blumenthal, D.T., Matceyevsky, D. et al. Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line?. J Neurooncol 105, 1–7 (2011). https://doi.org/10.1007/s11060-011-0589-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0589-2

Keywords

Search

Navigation