title: The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma : A systematic review and evidence-based clinical practice guideline.
abstract: METHODS
  Adult patients (older than 18 years of age) with newly diagnosed World Health Organization (WHO) Grade II gliomas (Oligodendroglioma, astrocytoma, mixed oligoastrocytoma).
  
  
  OBJECTIVE
  Is there a role for chemotherapy as adjuvant therapy of choice in treatment of patients with newly diagnosed low-grade gliomas?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  Chemotherapy is recommended as a treatment option to postpone the use of radiotherapy, to slow tumor growth and to improve progression free survival (PFS), overall survival (OS) and clinical symptoms in adult patients with newly diagnosed LGG.
  
  
  OBJECTIVE
  Who are the patients with newly diagnosed LGG that would benefit the most from chemotherapy?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  Chemotherapy is recommended as an optional component alone or in combination with radiation as the initial adjuvant therapy for all patients who cannot undergo gross total resection (GTR) of a newly diagnosed LGG. Patient with residual tumor >1 cm on post-operative MRI, presenting diameter of >4 cm or older than 40 years of age should be considered for adjuvant therapy as well.
  
  
  OBJECTIVE
  Are there tumor markers that can predict which patients can benefit the most from initial treatment with chemotherapy?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  The addition of chemotherapy to standard RT is recommended in LGG patients that carry IDH mutation. In addition, temozolomide (TMZ) is recommended as a treatment option to slow tumor growth in patients who harbor the 1p/19q co-deletion.
  
  
  OBJECTIVE
  How soon should the chemotherapy be started once the diagnosis of LGG is confirmed?
  
  
  CONCLUSIONS
  There is insufficient evidence to make a definitive recommendation on the timing of starting chemotherapy after surgical/pathological diagnosis of LGG has been made. However, using the 12 weeks mark as the latest timeframe to start adjuvant chemotherapy is suggested. It is recommended that patients be enrolled in properly designed clinical trials to assess the timing of chemotherapy initiation once diagnosis is confirmed for this target population.
  
  
  OBJECTIVE
  What chemotherapeutic agents should be used for treatment of newly diagnosed LGG?
  
  
  CONCLUSIONS
  There is insufficient evidence to make a recommendation of one particular regimen. Enrollment of subjects in properly designed trials comparing the efficacy of these or other agents is recommended so as to determine which of these regimens is superior.
  
  
  OBJECTIVE
  What is the optimal duration and dosing of chemotherapy as initial treatment for LGG?
  
  
  CONCLUSIONS
  Insufficient evidence exists regarding the duration of any specific cytotoxic drug regimen for treatment of newly diagnosed LGG. Enrollment of subjects in properly designed clinical investigations assessing the optimal duration of this therapy is recommended.
  
  
  OBJECTIVE
  Should chemotherapy be given alone or in conjunction with RT as initial therapy for LGG?
  
  
  CONCLUSIONS
  Insufficient evidence exists to make recommendations in this regard. Hence, enrollment of patients in properly designed clinical trials assessing the difference between chemotherapy alone, RT alone or a combination of them is recommended.
  
  
  OBJECTIVE
  Should chemotherapy be given in addition to other type of adjuvant therapy to patients with newly diagnosed LGG?
  
  
  CONCLUSIONS
  Level II: It is recommended that chemotherapy be added to the RT in patients with unfavorable LGG to improve their progression free survival.
authors.affiliation: Department of Neurosurgery, Seton Brain and Spine Institute, 1400 N IH-35, Suite 300, Austin, TX, 78701, USA. mziu@seton.org.
authors.forename: Mateo
authors.initials: M
authors.lastname: Ziu
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Kalkanis
authors.affiliation: Center for Cancer Research, Neuro-Oncology Branch at National Cancer Institute, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gilbert
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, 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 / Q000188:drug therapy / Q000473:pathology; D019317:Evidence-Based Medicine; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D060787:Neoplasm Grading
keywords: Chemotherapy; Guidelines; Low grade glioma; PCV; Temozolomide; Treatment