Low-grade tumors

The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to undergo either radiation or observation in the EORTC-22845 trial.[14,15] On review of central pathology, about 25% of patients in the trial were reported to have high-grade tumors. Most of the control patients received radiation therapy at the time of progression.

The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to undergo either radiation or observation in the EORTC-22845 trial.[14,15] On review of central pathology, about 25% of patients in the trial were reported to have high-grade tumors. Most of the control patients received radiation therapy at the time of progression.

After a median follow-up of 93 months, the median progression-free survival (PFS) was 5.3 years in the radiation arm versus 3.4 years in the control arm (HR, 0.59; 95% CI, 0.45–0.77).[14,15][Level of evidence B1]

The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to undergo either radiation or observation in the EORTC-22845 trial.[14,15] On review of central pathology, about 25% of patients in the trial were reported to have high-grade tumors. Most of the control patients received radiation therapy at the time of progression.

There was no difference in the overall survival (OS). The median survival was 7.4 years in the radiation arm and 7.2 years in the control arm (HR, 0.97; 95% CI, 0.71–1.34; P = .87).[14,15][Level of evidence A1] This was caused by a longer survival after progression in the control arm (3.4 years) than in the radiation arm (1.0 year) (P < .0001).

The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to undergo either radiation or observation in the EORTC-22845 trial.[14,15] On review of central pathology, about 25% of patients in the trial were reported to have high-grade tumors. Most of the control patients received radiation therapy at the time of progression.

The investigators did not collect reliable quality-of-life measurements, so it is not clear whether the delay in initial relapse in the radiation therapy arm translated into improved function or quality of life.

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

There was no significant difference in PFS (primary end point) or health-related quality of life (secondary end point).

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

At a median follow-up of 48 months (interquartile range, 31–56), median PFS was 39 months (95% CI, 35–44) in the temozolomide group and 46 months (95% CI, 40–56) in the radiation therapy group (unadjusted HR, 1.16; 95% CI, 0.9–1.5; P = .22).[16][Level of evidence B1]

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

An exploratory analysis of 318 molecularly defined patients found that patients with IDH gene variants without codeletion of 1p/19q displayed a significantly longer PFS when treated with radiation therapy (HR, 1.86; 95% CI, 1.21–2.87; log-rank P = .0043).

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

There were no significant treatment-dependent differences in PFS for patients with IDH variants with codeletion of 1p/19q and IDH wild-type tumors.

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

Patients with wild-type IDH tumors had the worst prognosis independent of treatment type.

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

Patients with IDH variants with codeletion of 1p/19q had the best prognosis.

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17]

The O6-methylguanine-DNA methyltransferase (MGMT) promoter status was methylated in the following cases:

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17] › The O6-methylguanine-DNA methyltransferase (MGMT) promoter status was methylated in the following cases:

All IDH variants with codeletion of 1p/19q (45/45).

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17] › The O6-methylguanine-DNA methyltransferase (MGMT) promoter status was methylated in the following cases:

Sixty-two of 72 (86%) of the IDH variants without codeletion of 1p/19q.

The EORTC 22033-26033 trial (NCT00182819) included 707 patients with low-grade glioma (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) and at least one high-risk feature (age >40 years, progressive disease, tumor size >5 cm, tumor crossing the midline, or neurological symptoms). Patients were randomly assigned to receive either radiation therapy (n = 240) or temozolomide chemotherapy (n = 237). Radiation therapy consisted of conformal treatment (up to 50.4 Gy; 28 doses of 1.8 Gy daily, 5 days a week, for up to 6.5 weeks). Chemotherapy was dose-dense oral temozolomide (75 mg/m2 daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles).[16,17] › The O6-methylguanine-DNA methyltransferase (MGMT) promoter status was methylated in the following cases:

Five of nine (56%) of the IDH wild-type cases.