Cancer Health Center

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Both the proportion of patients receiving radiation and the dose of radiation administered has decreased over the last 2 decades. For example, in a trial conducted between 1990 and1995, the BFM group demonstrated that a reduced dose of prophylactic radiation (12 Gy instead of 18 Gy) provided effective CNS prophylaxis in high-risk patients.[26] In the follow-up trial conducted by that group between 1995 and 2000 (BFM-95), cranial radiation was administered to approximately 20% of patients (compared with 70% on the previous trial), including patients with T-cell phenotype, a slow early response (as measured by peripheral blood blast count after a 1-week steroid prophase), and/or adverse cytogenetic abnormalities.[42] While the rate of isolated CNS relapses was higher in the nonirradiated higher-risk patients compared with historic (irradiated) cohorts, their overall EFS rate was not significantly different.[42]

Two studies, one conducted by the SJCRH and the other by the Dutch Childhood Oncology Group (DCOG), omitted cranial radiation for all patients.[4,43] Each of these studies included four doses of high-dose methotrexate administered every 2 weeks during postinduction consolidation, as well as an increased frequency of IT triple chemotherapy (cytarabine, methotrexate, and hydrocortisone) and frequent vincristine/dexamethasone pulses during the first 1 to 2 years of therapy. The 5-year cumulative incidence of isolated CNS relapse on each trial was between 2% and 3%, although some patient subsets had a significantly higher rate of CNS relapse. On the SJCRH study, clinical features associated with a significantly higher risk of isolated CNS relapse included T-cell phenotype, the t(1;19) translocation, or the presence of blasts in the CSF at diagnosis.[43] The overall EFS for these studies was 85.6% (SJCRH) and 81% (DCOG), in line with outcomes achieved by contemporaneously conducted clinical trials on which some patients received prophylactic radiation. Of note, on the SJCRH study 33 of 498 (6.6%) patients in first remission with high-risk features (including 26 with high MRD, six with Philadelphia chromosome-positive ALL, and one with near haploidy) received an allogeneic stem cell transplant, which included total-body irradiation.[43]

Therapy for ALL patients with clinically evident CNS disease (>5 WBC/hpf with blasts on cytospin; CNS3) at diagnosis typically includes IT chemotherapy and cranial radiation (usual dose is 18 Gy).[23,42] Spinal radiation is no longer used. On the SJCRH Total XV (TOTXV) study, patients with CNS3 status (N = 9) were treated without cranial radiation (observed 5-year EFS, 43% � 23%).[43] On that study, CNS-leukemia at diagnosis (defined as CNS3 status or traumatic LP with blasts) was an independent predictor of inferior EFS. The 5-year EFS of CNS3 patients (N = 21) treated without cranial radiation on the DCOG-9 trial was 67% � 10%.[4] Larger studies will be necessary to fully elucidate the safety of omitting cranial radiation in CNS3 patients.