title: Identification of therapy-sensitive and therapy-resistant neuroblastoma subtypes in stages III, IVs and IV.
abstract: The aim was to present a new model of risk stratification with high predictive sensitivity for non-localized neuroblastomas (NBs). "MYCN amplification", "unfavorable histology of the International Neuroblastoma Pathology Classification (INPC) system" and "low Ha-ras/trk A expression" could be defined as an independent predictor for high-risk NBs. A risk stratification flow chart was applied to 103 advanced NBs in which all three factors were examined and 69 were grouped as high-risk NBs of which 38 patients died. The predictive sensitivity for poor patient outcome was 86%, which included 38 of the 44 total deaths in this analysis. Using the number of the three independent risk factors in each tumor, the 69 high-risk NBs were classified into three subgroups. NBs with the three risk factors (triple risk) represented the most aggressive character and survival of the affected patients was only 10% ("therapy-resistant NBs"). Survivals of the patients with NBs possessed the two (double) risk factors or the one (single) risk factor were 29% and 66%, respectively. This stratification also elucidated a subgroup in which patient survival was 90% ("therapy-sensitive"). There were 21 NBs with "high Ha-ras/trk A expression", "favorable INPC histology" and "unamplified MYCN" (no risk NBs). Among the four subgroups without a risk factor, with a single risk factor, with double risk and with triple risk, Kaplan-Meier analysis showed a significant difference in NB patient outcome (p<0.0001). Risk stratification might improve the therapeutic efficacy for the high-risk NBs and might decrease therapy-related sequelae in the lower risk NBs.
authors.affiliation: National Hospital Organization Hiroshimanishi Medical Center, Hiroshima, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Kyo
authors.forename: Takeo
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iehara
authors.forename: Michio
authors.initials: M
authors.lastname: Kaneko
authors.forename: Hajime
authors.initials: H
authors.lastname: Hosoi
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Hamasaki
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sawada
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging / Q000379:methods*; D009447:Neuroblastoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents