Management of patients with recurrence of diffuse low grade glioma
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These recommendations apply to adult patients with recurrent low-grade glioma (LGG) with initial pathologic diagnosis of a WHO grade II infiltrative glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
Pathology at recurrence
Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence?
IDH status and recurrence
(Level III) IDH mutation status should be determined as LGGs with IDH mutations have a shortened time to recurrence. It is unclear whether knowledge of IDH mutation status provides benefit in predicting time to progression or overall survival.
TP53 status and recurrence
(Level III) TP53 mutations occur early in LGG pathogenesis, remain stable, and are not recommended as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis.
MGMT status and recurrence
(Level III) Assessment of MGMT status is recommended as an adjunct to assessing prognosis as LGGs with MGMT promoter methylation are associated with shorter PFS (in the absence of TMZ) and longer post-recurrence survival (in the presence of TMZ), ultimately producing similar overall survival to LGGs without MGMT methylationThe available retrospective reports are conflicting and comparisons between reports are limited
CDK2NA status and recurrence
(Level III) Assessment of CDK2NA status is recommended when possible as the loss of expression of the CDK2NA via either methylation or loss of chromosome 9p is associated with malignant progression of LGGs.
Proliferative index and recurrence
(Level III) It is recommended that proliferative indices (MIB-1 or BUdR) be measured in LGGs as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival.
1p/19q status and recurrence
There is insufficient evidence to make any recommendations.
Chemotherapy at recurrence
What role does chemotherapy have in LGG recurrence?
Temozolomide and recurrence
(Level III) Temozolomide is recommended in the therapy of recurrent LGG as it may improve clinical symptoms. Oligodendrogliomas and tumors with 1p/19q co-deletion may derive the most benefit.
PCV and recurrence
(Level III) PCV is recommended in the therapy of LGG at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas.
Carboplatin and recurrence
(Level III) Carboplatin is not recommended as there is no significant benefit from carboplatin as single agent therapy for recurrent LGGs.
Other treatments (Nitrosureas, Hydroxyurea/Imanitib, irinotecan, paclitaxel) and recurrence
There is insufficient evidence to make any recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess these chemotherapeutic agents.
Radiation at recurrence
What role does radiation have in LGG recurrence?
Radiation at recurrence with no previous irradiation
(Level III) Radiation is recommended at recurrence if there was no previous radiation treatment.
Re-irradiation at recurrence
(Level III) It is recommended that re-irradiation be considered in the setting of LGG recurrence as it may provide benefit in disease control.
Surgery at recurrence
There is insufficient evidence to make any specific recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess the role of surgery at recurrence.
KeywordsLow-grade gliomas Recurrence Surgery Pathology Chemotherapy Radiation Observation
We acknowledge the significant contributions of Laura Mitchell, Senior Manager of Clinical Practice Guidelines for the CNS, and also the AANS/CNS Joint Guidelines Committee (JGC) for their review, comments and suggestions, as well as Anne Woznica, Medical Research Librarian.
Dr. Batchelor is a consultant for EMD-Serono. Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck.
- 26.van den Bent MJ, Taphoorn MJ, Brandes AA et al (2003) Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European organization for research and treatment of cancer brain tumor group study 26971. J Clin Oncol 21(13):2525–2528CrossRefPubMedGoogle Scholar
- 43.Karim AB, Afra D, Cornu P et al (2002) Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European organization for research and treatment of cancer study 22845 with the medical research council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 52(2):316–324CrossRefPubMedGoogle Scholar
- 55.Streffer J, Schabet M, Bamberg M, Grote EH, Meyerman R, Voigt K, Dicgans J, Weller M (2000) A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors. J Neurooncol 247(4):297–302Google Scholar
- 56.Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand BC, Helie M, Kleinman G, Yahanda A, Fearon ER, Kleihues P, Reale MA (1997) Loss of DCC expression and glioma progression. Cancer Res 57(3):382–386Google Scholar