CNS Therapy for Patients With CNS3 Disease at Diagnosis

The SJCRH, DCOG, and the EORTC have published results of trials that omitted cranial radiation therapy for all patients, including high-risk subsets.[12,27] These trials have included at least four doses of high-dose methotrexate during postinduction consolidation and an increased frequency of intrathecal chemotherapy. The SJCRH study also included higher cumulative doses of anthracycline than on Children’s Oncology Group (COG) trials, and frequent vincristine/dexamethasone pulses and intensified dosing of pegaspargase,[12] while the EORTC trials included additional high-dose methotrexate and multiple doses of high-dose cytarabine, during postinduction treatment phases for CNS3 (CSF with ≥5 WBC/µL and cytospin positive for blasts) patients.[27]

The SJCRH, DCOG, and the EORTC have published results of trials that omitted cranial radiation therapy for all patients, including high-risk subsets.[12,27] These trials have included at least four doses of high-dose methotrexate during postinduction consolidation and an increased frequency of intrathecal chemotherapy. The SJCRH study also included higher cumulative doses of anthracycline than on Children’s Oncology Group (COG) trials, and frequent vincristine/dexamethasone pulses and intensified dosing of pegaspargase,[12] while the EORTC trials included additional high-dose methotrexate and multiple doses of high-dose cytarabine, during postinduction treatment phases for CNS3 (CSF with ≥5 WBC/µL and cytospin positive for blasts) patients.[27]

On the SJCRH Total XV (TOTXV) study, patients with CNS3 status (N = 9) were treated without cranial radiation therapy (observed 5-year EFS rate, 43% ± 23%; OS rate, 71% ± 22%).[12] On this study, CNS leukemia at diagnosis (defined as CNS3 status or traumatic lumbar puncture with blasts) was an independent predictor of inferior EFS.

The SJCRH, DCOG, and the EORTC have published results of trials that omitted cranial radiation therapy for all patients, including high-risk subsets.[12,27] These trials have included at least four doses of high-dose methotrexate during postinduction consolidation and an increased frequency of intrathecal chemotherapy. The SJCRH study also included higher cumulative doses of anthracycline than on Children’s Oncology Group (COG) trials, and frequent vincristine/dexamethasone pulses and intensified dosing of pegaspargase,[12] while the EORTC trials included additional high-dose methotrexate and multiple doses of high-dose cytarabine, during postinduction treatment phases for CNS3 (CSF with ≥5 WBC/µL and cytospin positive for blasts) patients.[27]

On the DCOG-9 trial, the 5-year EFS rate of CNS3 patients (n = 21) treated without cranial radiation therapy was 67% (± 10%).[13]

The SJCRH, DCOG, and the EORTC have published results of trials that omitted cranial radiation therapy for all patients, including high-risk subsets.[12,27] These trials have included at least four doses of high-dose methotrexate during postinduction consolidation and an increased frequency of intrathecal chemotherapy. The SJCRH study also included higher cumulative doses of anthracycline than on Children’s Oncology Group (COG) trials, and frequent vincristine/dexamethasone pulses and intensified dosing of pegaspargase,[12] while the EORTC trials included additional high-dose methotrexate and multiple doses of high-dose cytarabine, during postinduction treatment phases for CNS3 (CSF with ≥5 WBC/µL and cytospin positive for blasts) patients.[27]

On the EORTC trial, the 8-year EFS rate of CNS3 patients (n = 49) treated without cranial radiation therapy was 68%. The cumulative incidence of isolated CNS relapse for those patients was 9.4%.[27][Level of evidence B4]

A meta-analysis of aggregated data from more than 16,000 patients treated between 1996 and 2007 by ten cooperative groups evaluated whether the use of cranial radiation therapy affected outcome in high-risk patient subsets.[14]

A meta-analysis of aggregated data from more than 16,000 patients treated between 1996 and 2007 by ten cooperative groups evaluated whether the use of cranial radiation therapy affected outcome in high-risk patient subsets.[14]

In subgroup analyses of high-risk subsets, only those with CNS3 status at diagnosis appeared to benefit from cranial radiation therapy, with a significantly lower rate of CNS relapses (isolated/any) in irradiated patients. However, even within this subgroup, OS rates were similar with or without the use of radiation therapy.