title: Management of patients with recurrence of diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.
abstract: METHODS
  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).
  
  
  
  OBJECTIVE
  Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence?
  
  
  CONCLUSIONS
  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 methylation. The 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.
  
  
  
  OBJECTIVE
  What role does chemotherapy have in LGG recurrence?
  
  
  CONCLUSIONS
  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.
  
  
  
  OBJECTIVE
  What role does radiation have in LGG recurrence?
  
  
  CONCLUSIONS
  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.
  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.
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, 15 Parkman Street, Wang 745, Boston, MA, 02114, USA. bnahed@partners.org.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Nahed
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Navid
authors.initials: N
authors.lastname: Redjal
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.affiliation: Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Chi
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Oh
authors.affiliation: Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: Department of Neurosurgery, Kansas University Medical Center, Kansas City, KS, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Ryken
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Kalkanis
authors.affiliation: Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
mesh_terms: D006801:Humans; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy; D019317:Evidence-Based Medicine; D005910:Glioma / Q000473:pathology / Q000628:therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000628:therapy
keywords: Chemotherapy; Low-grade gliomas; Observation; Pathology; Radiation; Recurrence; Surgery