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Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

Impact of waiting time after surgery and overall time of postoperative radiochemotherapy on treatment outcome in glioblastoma multiforme

Authors: Annekatrin Seidlitz, Timo Siepmann, Steffen Löck, Tareq Juratli, Michael Baumann, Mechthild Krause

Published in: Radiation Oncology | Issue 1/2015

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Abstract

Background

A time factor of radiooncological treatment has been demonstrated for several tumours, most prominently for head and neck squamous cell carcinoma and lung cancer. In glioblastoma multiforme studies of the impact of postoperative waiting times before initiation of radio- or radiochemotherapy were inconclusive. Moreover analysis of the impact of overall treatment time of radiochemotherapy as well as overall duration of local treatment from surgery to the end of radiochemotherapy is lacking to date.

Methods

In this retrospective cohort study, we included 369 consecutive patients treated at our institution between 2001 and 2014. Inclusion criteria were histologically proven glioblastoma multiforme, age ≥ 18 years, ECOG performance status 0–2 before radiotherapy, radiotherapy or radiochemotherapy with 33 × 1.8 Gy to 59.4 Gy or with 30 × 2.0 Gy to 60 Gy. The impact of postoperative waiting time, radiation treatment time and overall duration of local treatment from surgery to the end of radiotherapy on overall (OS) and progression-free (PFS) survival were evaluated under consideration of known prognostic factors by univariate Log-rank tests and multivariate Cox-regression analysis.

Results

The majority of patients had received simultaneous and further adjuvant chemotherapy, mainly with temozolomide. Median survival time and 2-year OS were 18.0 months and 38.9 % after radiochemotherapy compared to 12.7 months and 12.6 % after radiotherapy alone. Median progression-free survival time was 7.5 months and PFS at 2 years was 14.3 % compared to 6.0 months and 3.3 %, respectively. Significant prognostic factors in multivariate analysis were age, resection status and application of simultaneous chemotherapy. No effect of the interval between surgery and adjuvant radiotherapy (median 27, range 11–112 days), radiation treatment time (median 45, range 40–71 days) and of overall time from surgery until the end of radiotherapy (median 54, range 71–154 days) on overall and progression-free survival was evident.

Conclusion

Our data do not indicate a relevant time factor in the treatment of glioblastoma multiforme in a large contemporary single-centre cohort. Although this study was limited by its retrospective nature, its results indicate that short delays of postoperative radiochemotherapy, e.g. for screening of a patient for a clinical trial, may be uncritical.
Literature
1.
go back to reference Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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):459–66. doi:10.1016/s1470-2045(09)70025-7.CrossRefPubMed Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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):459–66. doi:10.​1016/​s1470-2045(09)70025-7.CrossRefPubMed
3.
go back to reference Mirimanoff RO, Gorlia T, Mason W, Van den Bent MJ, Kortmann RD, Fisher B, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol. 2006;24(16):2563–9. doi:10.1200/jco.2005.04.5963.CrossRefPubMed Mirimanoff RO, Gorlia T, Mason W, Van den Bent MJ, Kortmann RD, Fisher B, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol. 2006;24(16):2563–9. doi:10.​1200/​jco.​2005.​04.​5963.CrossRefPubMed
4.
go back to reference Paravati AJ, Heron DE, Landsittel D, Flickinger JC, Mintz A, Chen YF, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era. J Neuro-Oncol. 2011;104(1):339–49. doi:10.1007/s11060-010-0499-8.CrossRef Paravati AJ, Heron DE, Landsittel D, Flickinger JC, Mintz A, Chen YF, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era. J Neuro-Oncol. 2011;104(1):339–49. doi:10.​1007/​s11060-010-0499-8.CrossRef
5.
go back to reference Shaw EG, Seiferheld W, Scott C, Coughlin C, Leibel S, Curran W, et al. Reexamining the radiation therapy oncology group (RTOG) recursive partitioning analysis (RPA) for glioblastoma multiforme (GBM) patients. Int J Radiat Oncol Biol Phys. 2003;57(2):S135–6. doi:10.1016/S0360-3016(03)00843-5.CrossRef Shaw EG, Seiferheld W, Scott C, Coughlin C, Leibel S, Curran W, et al. Reexamining the radiation therapy oncology group (RTOG) recursive partitioning analysis (RPA) for glioblastoma multiforme (GBM) patients. Int J Radiat Oncol Biol Phys. 2003;57(2):S135–6. doi:10.​1016/​S0360-3016(03)00843-5.CrossRef
7.
go back to reference Thames HD, Kuban D, Levy LB, Horwitz EM, Kupelian P, Martinez A, et al. The role of overall treatment time in the outcome of radiotherapy of prostate cancer: an analysis of biochemical failure in 4839 men treated between 1987 and 1995. Radiother Oncol. 2010;96(1):6–12. doi:10.1016/j.radonc.2010.03.020.CrossRefPubMed Thames HD, Kuban D, Levy LB, Horwitz EM, Kupelian P, Martinez A, et al. The role of overall treatment time in the outcome of radiotherapy of prostate cancer: an analysis of biochemical failure in 4839 men treated between 1987 and 1995. Radiother Oncol. 2010;96(1):6–12. doi:10.​1016/​j.​radonc.​2010.​03.​020.CrossRefPubMed
8.
go back to reference Withers HR, Peters LJ, Taylor JM, Owen JB, Morrison WH, Schultheiss TE, et al. Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions. Int J Radiat Oncol Biol Phys. 1995;33(3):549–62. doi:10.1016/0360-3016(95)00228-q.CrossRefPubMed Withers HR, Peters LJ, Taylor JM, Owen JB, Morrison WH, Schultheiss TE, et al. Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions. Int J Radiat Oncol Biol Phys. 1995;33(3):549–62. doi:10.​1016/​0360-3016(95)00228-q.CrossRefPubMed
11.
go back to reference Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys. 2007;68(3):654–61. doi:10.1016/j.ijrobp.2007.03.010.CrossRefPubMed Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys. 2007;68(3):654–61. doi:10.​1016/​j.​ijrobp.​2007.​03.​010.CrossRefPubMed
12.
go back to reference Bentzen SM. Repopulation in radiation oncology: perspectives of clinical research. Int J Radiat Biol. 2003;79(7):581–5.CrossRefPubMed Bentzen SM. Repopulation in radiation oncology: perspectives of clinical research. Int J Radiat Biol. 2003;79(7):581–5.CrossRefPubMed
13.
go back to reference Lawrence YR, Blumenthal DT, Matceyevsky D, Kanner AA, Bokstein F, Corn BW. Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line? J Neuro-Oncol. 2011;105(1):1–7. doi:10.1007/s11060-011-0589-2.CrossRef Lawrence YR, Blumenthal DT, Matceyevsky D, Kanner AA, Bokstein F, Corn BW. Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line? J Neuro-Oncol. 2011;105(1):1–7. doi:10.​1007/​s11060-011-0589-2.CrossRef
14.
go back to reference Chinot OL, Wick W, Cloughesy T. Bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(21):2049.CrossRefPubMed Chinot OL, Wick W, Cloughesy T. Bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(21):2049.CrossRefPubMed
15.
go back to reference Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1100–8. doi:10.1016/s1470-2045(14)70379-1.CrossRefPubMed Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1100–8. doi:10.​1016/​s1470-2045(14)70379-1.CrossRefPubMed
16.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:10.1056/NEJMoa043330.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:10.​1056/​NEJMoa043330.CrossRefPubMed
17.
go back to reference Curran Jr WJ, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993;85(9):704–10.CrossRefPubMed Curran Jr WJ, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993;85(9):704–10.CrossRefPubMed
18.
go back to reference Glinski B, Urbanski J, Hetnal M, Malecki K, Jarosz M, Mucha-Malecka A, et al. Prognostic value of the interval from surgery to initiation of radiation therapy in correlation with some histo-clinical parameters in patients with malignant supratentorial gliomas. Contemp Oncol (Poznan, Poland). 2012;16(1):34–7. doi:10.5114/wo.2012.27334. Glinski B, Urbanski J, Hetnal M, Malecki K, Jarosz M, Mucha-Malecka A, et al. Prognostic value of the interval from surgery to initiation of radiation therapy in correlation with some histo-clinical parameters in patients with malignant supratentorial gliomas. Contemp Oncol (Poznan, Poland). 2012;16(1):34–7. doi:10.​5114/​wo.​2012.​27334.
20.
go back to reference 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):93–103.CrossRef 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):93–103.CrossRef
21.
go back to reference Do V, Gebski V, Barton MB. The effect of waiting for radiotherapy for grade III/IV gliomas. Radiother Oncol. 2000;57(2):131–6.CrossRefPubMed Do V, Gebski V, Barton MB. The effect of waiting for radiotherapy for grade III/IV gliomas. Radiother Oncol. 2000;57(2):131–6.CrossRefPubMed
24.
go back to reference Noel G, Huchet A, Feuvret L, Maire JP, Verrelle P, Le Rhun E, et al. 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 Neuro-Oncol. 2012;109(1):167–75. doi:10.1007/s11060-012-0883-7.CrossRef Noel G, Huchet A, Feuvret L, Maire JP, Verrelle P, Le Rhun E, et al. 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 Neuro-Oncol. 2012;109(1):167–75. doi:10.​1007/​s11060-012-0883-7.CrossRef
25.
26.
go back to reference Blumenthal DT, Won M, Mehta MP, Curran WJ, Souhami L, Michalski JM, 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(5):733–9. doi:10.1200/jco.2008.18.9035.PubMedCentralCrossRefPubMed Blumenthal DT, Won M, Mehta MP, Curran WJ, Souhami L, Michalski JM, 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(5):733–9. doi:10.​1200/​jco.​2008.​18.​9035.PubMedCentralCrossRefPubMed
28.
go back to reference Pedicini P, Fiorentino A, Simeon V, Tini P, Chiumento C, Pirtoli L, et al. Clinical radiobiology of glioblastoma multiforme: estimation of tumor control probability from various radiotherapy fractionation schemes. Strahlenther Onkol. 2014;190(10):925–32. doi:10.1007/s00066-014-0638-9.CrossRefPubMed Pedicini P, Fiorentino A, Simeon V, Tini P, Chiumento C, Pirtoli L, et al. Clinical radiobiology of glioblastoma multiforme: estimation of tumor control probability from various radiotherapy fractionation schemes. Strahlenther Onkol. 2014;190(10):925–32. doi:10.​1007/​s00066-014-0638-9.CrossRefPubMed
30.
go back to reference Budach W, Gioioso D, Taghian A, Stuschke M, Suit HD. Repopulation capacity during fractionated irradiation of squamous cell carcinomas and glioblastomas in vitro. Int J Radiat Oncol Biol Phys. 1997;39(3):743–50.CrossRefPubMed Budach W, Gioioso D, Taghian A, Stuschke M, Suit HD. Repopulation capacity during fractionated irradiation of squamous cell carcinomas and glioblastomas in vitro. Int J Radiat Oncol Biol Phys. 1997;39(3):743–50.CrossRefPubMed
33.
go back to reference Gupta T, Nair V, Paul SN, Kannan S, Moiyadi A, Epari S, et al. Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma? J Neuro-Oncol. 2012;109(1):195–203. doi:10.1007/s11060-012-0887-3.CrossRef Gupta T, Nair V, Paul SN, Kannan S, Moiyadi A, Epari S, et al. Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma? J Neuro-Oncol. 2012;109(1):195–203. doi:10.​1007/​s11060-012-0887-3.CrossRef
Metadata
Title
Impact of waiting time after surgery and overall time of postoperative radiochemotherapy on treatment outcome in glioblastoma multiforme
Authors
Annekatrin Seidlitz
Timo Siepmann
Steffen Löck
Tareq Juratli
Michael Baumann
Mechthild Krause
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0478-5

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