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Neuro Oncol. 2017 Feb 1;19(2):242-251. doi: 10.1093/neuonc/now176.

Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide.

Author information

1
Department of Radiation Oncology, University of California, San Francisco, USA.
2
Department of Pathology, University of California, San Francisco, USA.
3
Department of Neurosurgery, University of California, San Francisco, USA.
4
Department of Epidemiology and Biostatistics, University of California, San Francisco , USA.
5
Department of Neurosurgery, First Affiliated Hospital of China Medical University, China.
6
Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
7
Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
8
Department of Neurology, University of California, San Francisco, USA.
9
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA.

Abstract

Background:

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.

Methods:

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).

Results:

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).

Conclusions:

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.

KEYWORDS:

clinical trials; low-grade glioma; molecular markers

PMID:
27571885
PMCID:
PMC5464133
DOI:
10.1093/neuonc/now176
[Indexed for MEDLINE]
Free PMC Article

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