Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-27T13:33:34.988Z Has data issue: false hasContentIssue false
  • English
  • Français

Glioblastoma: Patterns of Recurrence and Efficacy of Salvage Treatments

Published online by Cambridge University Press:  02 December 2014

Jiwon Oh ,
Arjun Sahgal ,
Paul Sanghera ,
May N. Tsao ,
Phil Davey ,
Kelvin Lam ,
Sean Symons ,
Richard Aviv  and
James R. Perry
Jiwon Oh*
Affiliation:
Divison of Neurology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Arjun Sahgal
Affiliation:
Departments of Medicine, and Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Paul Sanghera
Affiliation:
Departments of Medicine, and Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
May N. Tsao
Affiliation:
Departments of Medicine, and Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Phil Davey
Affiliation:
Departments of Medicine, and Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Kelvin Lam
Affiliation:
Divison of Neurology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Sean Symons
Affiliation:
Division of Neuroradiology, Department of Medical Imaging, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Richard Aviv
Affiliation:
Division of Neuroradiology, Department of Medical Imaging, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
James R. Perry
Affiliation:
Divison of Neurology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
*
Sunnybrook Health Sciences Centre, University of Toronto, A402, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.

Methods:

We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.

Results:

58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).

Conclusion:

The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 38 , Issue 4 , July 2011 , pp. 621 - 625
Copyright
Copyright © The Canadian Journal of Neurological 2011

References

1.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):987–96.CrossRefGoogle ScholarPubMed
2.Hochberg, FH, Pruitt, A.Assumptions in the radiotherapy of glioblastoma. Neurology. 1980;30(9):907–11.CrossRefGoogle ScholarPubMed
3.Lee, SW, Fraass, BA, Marsh, LH, et al.Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999;43(1):79–88.CrossRefGoogle ScholarPubMed
4.Perry, JR, Rizek, P, Morrison, T, Morrison, M, Cashman, R.Temozolomide rechallenge in recurrent malignant glioma using a continuous temozolomide schedule: the “rescue” approach. Cancer. 2008;113(8):2152–7.CrossRefGoogle ScholarPubMed
5.Therasse, P, Arbuck, SG, Eisenhauer, EA, et al.New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefGoogle ScholarPubMed
6.Burnet, NG, Lynch, AG, Jefferies, SJ, et al.High grade glioma: imaging combined with pathological grade defines management and predicts prognosis. Radiother Oncol. 2007;85:371–8.CrossRefGoogle ScholarPubMed
7.Sanghera, P, Perry, J, Sahgal, A, et al.Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci. 2010;37(1):36–42.CrossRefGoogle ScholarPubMed
8.van Nifterik, KA, van den Berg, J, Stalpers, LJ, et al.Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. Int J Rad Onc Biol Phys. 2007;69(4):1246–53.CrossRefGoogle ScholarPubMed
9.Chakravarti, A, Erkkinen, MG, Nestler, U, et al.Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clin Cancer Res. 2006;12(15):4738–46.CrossRefGoogle ScholarPubMed
10.Wick, W, Wick, A, Schulz, JB, Dichgans, J, Rodemann, HP, Weller, M.Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase-3-activity and cleavage of focal adhesion kinase. Cancer Res. 2002;62(6):1915–19.Google ScholarPubMed
11.Wick, W, Stupp, R, Beule, A, et al.A novel tool to analyze MRI recurrence patterns. Neuro Oncol. 2008;10(6):1019–24.CrossRefGoogle ScholarPubMed
12.Brandes, AA, Tosoni, A, Franceschi, E, et al.Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation with MGMT promoter methylation status. J Clin Oncol. 2009;27(8): 1275–9.CrossRefGoogle ScholarPubMed
13.Milano, MT, Okunieff, P, Donatello, RS, et al.Patterns and timing of recurrence after temozolomide-based chemoradiation for glioblastoma. Int J Radiat Oncol Biol Phys. 2010;78(4):1147–55.CrossRefGoogle ScholarPubMed
14.Tolcher, AW, Gerson, SL, Denis, L, et al.Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer. 2003;88(7):1004–11.CrossRefGoogle ScholarPubMed
15.Kerbel, RS, Kamen, BA.The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4(6):423–6.CrossRefGoogle ScholarPubMed
16.Perry, JR, Bélanger, K, Mason, WP, et al.Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Onc. 2010;28(12):2051–7.CrossRefGoogle ScholarPubMed