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Journal of Neuro-Oncology

, Volume 125, Issue 3, pp 609–630 | Cite as

Management of patients with recurrence of diffuse low grade glioma

A systematic review and evidence-based clinical practice guideline
  • Brian V. Nahed
  • Navid Redjal
  • Daniel J. Brat
  • Andrew S. Chi
  • Kevin Oh
  • Tracy T. Batchelor
  • Timothy C. Ryken
  • Steven N. Kalkanis
  • Jeffrey J. Olson
Topic Review & Clinical Guidelines

Abstract

Target population

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

Question

Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence?

Recommendations

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

Question

What role does chemotherapy have in LGG recurrence?

Recommendations

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

Question

What role does radiation have in LGG recurrence?

Recommendations

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.

Keywords

Low-grade gliomas Recurrence Surgery Pathology Chemotherapy Radiation Observation 

Notes

Acknowledgments

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.

Disclosures

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.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Brian V. Nahed
    • 1
  • Navid Redjal
    • 2
  • Daniel J. Brat
    • 3
  • Andrew S. Chi
    • 4
  • Kevin Oh
    • 5
  • Tracy T. Batchelor
    • 4
  • Timothy C. Ryken
    • 6
  • Steven N. Kalkanis
    • 7
  • Jeffrey J. Olson
    • 8
  1. 1.Department of NeurosurgeryMassachusetts General HospitalBostonUSA
  2. 2.Department of NeurosurgeryMassachusetts General HospitalBostonUSA
  3. 3.Department of PathologyEmory University School of MedicineAtlantaUSA
  4. 4.Laura and Isaac Perlmutter Cancer CenterNYU Langone Medical CenterNew YorkUSA
  5. 5.Department of Radiation OncologyMassachusetts General HospitalBostonUSA
  6. 6.Department of NeurosurgeryKansas University Medical CenterKansas CityUSA
  7. 7.Department of NeurosurgeryHenry Ford Health SystemDetroitUSA
  8. 8.Department of NeurosurgeryEmory University School of MedicineAtlantaUSA

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