title: Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide.
abstract: Optimal adjuvant management of adult low-grade gliomas is controversial. Recently described tumor classification based on molecular subtype has the potential to individualize adjuvant therapy but has not yet been evaluated as part of a prospective trial.
  
  
  
  Patients aged 18 or older with newly diagnosed World Health Organization grade II low-grade gliomas and gross residual disease after surgical resection were enrolled in the study. Patients received monthly cycles of temozolomide for up to 1 year or until disease progression. For patients with available tissue, molecular subtype was assessed based upon 1p/19q codeletion and isocitrate dehydrogenase-1 R132H mutation status. The primary outcome was radiographic response rate; secondary outcomes included progression-free survival (PFS) and overall survival (OS).
  
  
  
  One hundred twenty patients were enrolled with median follow-up of 7.5 years. Overall response rate was 6%, with median PFS and OS of 4.2 and 9.7 years, respectively. Molecular subtype was associated with rate of disease progression during treatment (P<.001), PFS (P=.007), and OS (P<.001). Patients with 1p/19q codeletion demonstrated a 0% risk of progression during treatment. In an exploratory analysis, pretreatment lesion volume was associated with both PFS (P<.001) and OS (P<.001).
  
  
  
  While our study failed to meet the primary endpoint for objective radiographic response, patients with high-risk low-grade glioma receiving adjuvant temozolomide demonstrated a high rate of radiographic stability and favorable survival outcomes while meaningfully delaying radiotherapy. Patients with 1p/19q codeletion are potential candidates for omission of adjuvant radiotherapy, but further work is needed to directly compare chemotherapy with combined modality therapy.
authors: Department of Radiation Oncology, University of California, San Francisco, USA.
authors: Michael
authors: M
authors: Wahl
authors: Department of Pathology, University of California, San Francisco, USA.|Department of Neurosurgery, University of California, San Francisco, USA.
authors: Joanna J
authors: JJ
authors: Phillips
authors: Department of Neurosurgery, University of California, San Francisco, USA.|Department of Epidemiology and Biostatistics, University of California, San Francisco , USA.
authors: Annette M
authors: AM
authors: Molinaro
authors: Department of Neurosurgery, University of California, San Francisco, USA.|Department of Neurosurgery, First Affiliated Hospital of China Medical University, China.
authors: Yi
authors: Y
authors: Lin
authors: Department of Pathology, University of California, San Francisco, USA.|Department of Neurosurgery, University of California, San Francisco, USA.
authors: Arie
authors: A
authors: Perry
authors: Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Daphne A
authors: DA
authors: Haas-Kogan
authors: Department of Neurosurgery, University of California, San Francisco, USA.
authors: Joseph F
authors: JF
authors: Costello
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
authors: Manisha
authors: M
authors: Dayal
authors: Department of Neurosurgery, University of California, San Francisco, USA.
authors: Nicholas
authors: N
authors: Butowski
authors: Department of Neurosurgery, University of California, San Francisco, USA.|Department of Neurology, University of California, San Francisco, USA.
authors: Jennifer L
authors: JL
authors: Clarke
authors: Department of Neurosurgery, University of California, San Francisco, USA.
authors: Michael
authors: M
authors: Prados
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.|Department of Neurology, University of California, San Francisco, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA.
authors: Sarah
authors: S
authors: Nelson
authors: Department of Neurosurgery, University of California, San Francisco, USA.
authors: Mitchel S
authors: MS
authors: Berger
authors: Department of Neurosurgery, University of California, San Francisco, USA.
authors: Susan M
authors: SM
authors: Chang
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; D000077204:Temozolomide
keywords: clinical trials; low-grade glioma; molecular markers