A Clinicobiological Model Predicting Survival in Medulloblastoma

Abstract

Purpose: The purpose of this study was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).Experimental Design: Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-␣, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram.Results: The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P ‫؍‬ 0.01) and p53 (HR, 2.29; P ‫؍‬ 0.02), TrkC (HR, 0.65; P ‫؍‬ 0.14), and ErbB2 (HR, 1.51; P ‫؍‬ 0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10 th , 50 th , and 90 th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.Conclusions: In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies.

Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma

“…Tissue arrays were prepared as described earlier by our group (Ray et al, 2004;Tabori et al, 2006a). Briefly, for each patient, all pathologic blocks and corresponding slides were obtained and reviewed by a neuropathologist (CH) for diagnostic accuracy and tissue adequacy.…”

Medulloblastoma Comprises Four Distinct Molecular Variants

“…[1][2][3] Cytogenetic and genetic events, including chromosome 17 aberrations, CTNNB1 mutation/monosomy 6, and MYC family amplification, are informative predictors of patient outcome. [4][5][6][7][8][9][10] Recently, a molecular risk stratification approach based on multicolor fluorescence in situ hybridization (FISH) of MYC and MYCN loci, as well as chromosomal alterations on 17q and 6q, proved…”

Accumulation of genomic aberrations during clinical progression of medulloblastoma

“…Considerable advances have been made in the treatment of MB in the last three decades by using multimodal therapeutic regimens involving surgery, radiotherapy, and chemotherapy. About 10-15% of patients die from disease within 2 years after diagnosis, whereas approximately 60% of patients can nowadays be cured [9,11,22,23]. However, the predictive performance of current risk stratiWcation, which is entirely based on clinical variables, needs to be improved because of the dismal prognosis of children with tumor relapse, and because of relevant treatment-induced long-term eVects of survivors [21].…”