Medulloblastoma is the most common brain tumors of childhood. The extent of the surgical resection and regional spread of the tumor are key variables in determining whether chemo-therapy [C] is added to the treatment regimen of surgery and irradiation [RT] in most centers. We studied 20 patients, 10 high risk [HR] children treated with RT and C and 10 low risk [LR] patients treated with RT alone, to evaluate the possibility that apoptosis detectable in tumor sections prior to the administration of antineoplastic therapy might predict outcome. To characterize apoptosis we determined an apoptosis index [AI] by averaging the number of apoptotic cells in 20 randomly-selected high power fields [hpf] in a histologic tumor specimen from each patient. Apoptosis was detected by an in situ end-labeling technique which recognizes DNA breaks resulting from endonuclease activity [FragEL™-Klenow DNA fragmentation kit, Oncogene Research Products, Cambridge, MA.].
Five HR patients, with a median AI of 8.9/hpf [range 2.85-13.40] at diagnosis have died [mean time to progression 17 months and 20.8 months to death]. Four HR children who are alive and well [mean disease-free survival of 60 months] have a median AI of 19.0/hpf [range-2.25-37.87]. A 6th patient has developed spinal metastases 48 months following treatment [AI of 1.10/hpf].