Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma

Purpose: To determine if the degree of tumor cell apoptosis at diagnosis pr edicts outcome, tissue sections of medulloblastoma were examined and the am ount of apoptosis and progression-free survival were correlated. Patients and Methods: The study cohort consisted of 43 children in whom med ulloblastoma was diagnosed between 1984 and 1995: 29 patients at high risk (HR) treated with radiation and chemotherapy, and 14 children at low risk ( LR) treated with radiation alone. A terminal deoxynucleotidyl transferase ( TdT) end-labeling assay was used to detect apoptosis in paraffin-embedded t issue sections prepared at diagnosis. Results: Progression-free survival was examined in cohorts of children whos e tumors were divided into quartiles based on the apoptotic index (AI) of t heir pretreatment tumor specimens. A comparison of these four groups of chi ldren revealed an association between AI and outcome (p = 0.03); patients w ith tumors in the highest AI quartile had substantially improved outcome co mpared to all other patients combined (p = 0.02). In this cohort of patient s treated with different therapies, assignment at the time of diagnosis to LR and HR groups based on widely-accepted clinical criteria was not closely associated with outcome (p = 0.47). Conclusion: AI is a strong indicator of treatment outcome for children with medulloblastoma after treatment with cytotoxic therapy, independent of ris k group. Because HR and LR patients included in this study received differe nt modalities of cytotoxic therapy, it is possible that Al predicts outcome independent of the precise antineoplastic therapy a patient receives.