A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma

Abstract

BACKGROUND: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population. METHODS: To study the association of PSI with disease stage at diagnosis, tumour control and survival in children with medulloblastoma, prospectively collected data on PSI, clinical, and biological features were analysed in 224 patients diagnosed at the age of 3-18years and treated within the prospective randomised multicentre trial HIT'91. RESULTS: Patients with lower-stage disease tended towards a longer median PSI than those with higher-stage disease (M0 stage, 2.0months; M1 stage, 2.0months; M2/M3 stage, 1month; p=0.094. M0/1 stage versus M2/3 stage; p=0.025). The patient group with the longest PSI had the best survival outcome (PSI 4.0months: 10-year overall survival rate (OS), 71%; PSI <4.0months, 10-year OS, 61%; p=0.056). Age at diagnosis was positively correlated with PSI (p=0.027). No associations were found between PSI and sex histological subtype, presence of postoperative residual tumour, or c-myc and TrkC mRNA expression. CONCLUSION: Contrary to a common belief that a longer PSI may adversely affect prognosis, a longer PSI was associated with a trend towards lower metastatic stage and better survival probabilities. Nevertheless these findings do not obviate the importance of a timely diagnosis in paediatric patients with medulloblastoma. CONCLUSION: Contrary to a common belief that a longer PSI may adversely affect prognosis, a longer PSI was associated with a trend towards lower metastatic stage and better survival probabilities. Nevertheless these findings do not obviate the importance of a timely diagnosis in pediatric patients with medulloblastoma.3

Duration of the pre‐diagnostic interval in medulloblastoma is subgroup dependent

“…Our finding that shorter pre‐diagnostic intervals correlate with poor survival is consistent with several previously published studies . However, this interaction is no longer significant when controlling for subgroup, and is no longer significant within each subgroup.…”

“…Indeed, in the WNT, SHH and Group 3 subgroups, we observe no trend towards longer pre‐diagnostic intervals with increasing age. Several previous reports have suggested metastatic disease being associated with shorter pre‐diagnostic intervals . We did not find an association between the presence of metastasis and shorter pre‐diagnostic intervals.…”

“…Previous studies have shown an inverse relationship between increasing pre‐diagnostic interval and poor survival . Median pre‐diagnostic interval in our cohort was 4 weeks.…”

Natural history of a medulloblastoma: 30 months of wait and see in a child with a cerebellar incidentaloma

“…MBs) having shorter PSIs than low-grade tumours [4,10,12,17,19], but considerable variability is seen within the patient group with MB [2,8]: In a large prospective series, we found PSIs ranging from 0 to 24 months, with a median of 2 months. Interestingly, the group of patients with the longest PSIs had lower stage disease at diagnosis and a better overall survival probability than that with shorter PSIs [6]. The likely explanation for these results probably lies in the broad spectrum of biologic behaviour within the whole group of MB [3,15].…”

Isolation and characterization of cancer stem cells from medulloblastoma

“…Medulloblastoma (MB) is the most common malignant brain tumor in children (in contrast to adults) and the incidence mostly occurs between 4 and 7 years (Kaatsch et al, 2001;Louis et al, 2007;von Hoff and Rutkowski, 2012). The median life span of MB patients after diagnosis of the first symptoms ranges from 2 months to possibly years (Gerber et al, 2012). Despite advances in radio-or chemotherapy and surgery, the complete eradication of tumors is still complicated.…”