PURPOSE: To improve stratification of risk-adapted treatment for non-metastatic (M0), standard-risk @entity2946 @entity1 by prospective evaluation of biomarkers of reported biological or prognostic significance, alongside clinico-pathological variables, within the multi-center HIT-SIOP-PNET4 trial. METHODS: Formalin-fixed paraffin-embedded @entity5 tissues were collected from 338 M0 @entity1 (>4.0 years at diagnosis) for pathology review and assessment of the WNT subgroup (MBWNT) and genomic copy-number defects (chromosome 17, MYC/ @entity4180 , 9q22 ( @entity2750 ) and DNA ploidy). Clinical characteristics were reviewed centrally. RESULTS: The favorable prognosis of MBWNT was confirmed, however better outcomes were observed for @entity5 in this clinical risk-defined cohort compared to previous disease-wide clinical trials. Chromosome 17p/q defects were heterogeneous when assessed at the cellular copy-number level, and predicted poor prognosis when they occurred against a diploid (ch17(im)/diploid(cen)), but not polyploid, genetic background. These factors, together with post-surgical @entity5 residuum (R+) and radiotherapy delay, were supported as independent prognostic markers in multivariate testing. Notably, MYC and @entity4180 amplification were not associated with adverse outcome. In cross-validated survival models derived for the clinical standard-risk (M0/R0) disease group, (ch17(im)/diploid(cen); 14% of @entity1 ) predicted high disease-risk, while the outcomes of @entity1 without (ch17(im)/diploid(cen)) did not differ significantly from MBWNT, allowing re-classification of 86% as favorable-risk. CONCLUSIONS: Biomarkers, established previously in disease-wide studies, behave differently in clinically-defined standard-risk disease. Distinct biomarkers are required to assess disease-risk in this group, and define improved risk-stratification models. Routine testing for specific patterns of chromosome 17 imbalance at the cellular level, and MBWNT, provides a strong basis for incorporation into future trials.

Biomarker-driven stratification of disease-risk in non-metastatic XXXX : Results from the multi-center HIT-SIOP-PNET4 clinical trial.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'non-MBWNT tumors'] @entity4180 :: ('4613', 'Gene') :: ['MYCN'] @entity2946 :: ('MESH:D008527', 'Disease') :: ['medulloblastoma'] @entity2750 :: ('5727', 'Gene') :: ['PTCH1']
@entity2946 :: (MESH:D008527,Disease) :: ['medulloblastoma']
