Efficacy
Radiation therapy vs. observation (after biopsy or surgical resection)
There is randomised evidence that the addition of adjuvant radiation therapy to the tumour/tumour bed following biopsy or surgical resection improves survival over surgery ± chemotherapy in high grade gliomas.r
Chemotherapy plus radiation therapy vs radiation therapy alone
The evidence supporting the addition of chemotherapy to adjuvant radiation therapy for 1p19q co-deleted tumours comes from the phase III randomised controlled trials: EORTC 26951 (2006r and 2013r), RTOG 9402 (2006r and 2013r) and for 1p/19q non-co-deleted anaplastic tumours, the EORTC study 26053-22054/RTOG 8034 (CATNON) (2017r).
EORTC 26951 and RTOG 9402 involved a total of 659 patients comparing post-operative procarbazine, lomustine and vincristine (PCV) chemotherapy and radiation therapy with radiation therapy alone in patients with grade III glioma.r In patients with 1p/19q co-deleted and IDH-1 mutant tumours there is evidence to support the use of post-operative PCV chemotherapy either pre- or following radiation therapy.rrr Patients with 1p/19q non-codeleted tumours had worse outcomes than patients with 1p/19q co-deletion tumours and did not derive a survival benefit from PCV.rr Although, Cairncross et al. reported patients with 1p/19q co-deletion tumours may derive some benefit from PCV (HR 0.56, 95% CI: 0.32-0.99, P=0.05).r
The CATNON trial provides evidence to support the use of temozolomide following radiation in patients with 1p/19q non-co-deleted anaplastic glioma.r The CATNON trial randomly assigned 748 to one of four treatment groups: radiation therapy alone (59.4 Gy in 33 fractions of 1.8 Gy), radiation therapy with adjuvant temozolomide (TMZ), or radiation therapy with concurrent TMZ (with or without adjuvant TMZ). Interim analyses (2017 publication and 2019 ASCO update) demonstrated an overall survival (OS) benefit with adjuvant TMZ in IDH mutant tumours (HR 0.41, 95% CI: 0.27-0.64) but not in IDH wild type (HR 1.05, 95% CI: 0.73-1.52).rr There was no benefit seen with concurrent TMZ administered prior to adjuvant TMZ in IDH mutant tumours (p=0.32) but assessment is ongoing. Median OS was 116 months in IDH mutant and 19 months in IDH wild type.
For further information on the evidence supporting these chemotherapy regimens see link to Anaplastic glioma PCV (procarbazine lomustine vinCRISTine) and Anaplastic glioma temozolomide following radiation protocols.
Sequencing of post-operative chemotherapy and radiation therapy
NOA-04 assessed the impact of sequencing of post-operative chemotherapy and radiation therapy in both 1p/19q co-deleted and non- co-deleted anaplastic tumours.rr In this crossover study, patients were treated with either post-operative radiation therapy (60 Gy) or PCV/TMZ with crossover to the alternative arm in the event of progression or toxicity. Median time to treatment failure, progression free survival, and OS were similar for both sequencing strategies. Median time to treatment failure ~4.5 years, progression free survival ~2.6 years, OS 8 years vs. 6.5 years (not significant). IDH1 mutation was the strongest prognostic factor. The sequencing order did not change outcomes in this trial.
Anaplastic astrocytoma, IDH wild type
IDH wild type anaplastic astrocytomas are less common, and most have genetic features characteristic of IDH wild type glioblastoma. Management of these tumours is often extrapolated from glioblastoma.
Summary of treatment regimens
Type |
IDH mutation |
1p/19q co-deletion |
Treatment regimen |
Anaplastic oligodendroglioma |
IDH mutant or wild type |
1p/19q co-deleted |
RT (radiation therapy) and PCV (sequential) |
Anaplastic astrocytoma |
IDH mutant |
1p/19q non-co-deleted |
RT and PCV or RT and at least adjuvant TMZ |
Anaplastic astrocytoma |
IDH wild type |
1p/19q non-co-deleted |
Can be managed along the lines of glioblastoma
|