Cribriform neuroepithelial tumor: molecular characterization of a SMARCB1-deficient non-rhabdoid tumor with favorable long-term outcome.

Rhabdoid phenotype and loss of SMARCB1 expression in a brain tumor are characteristic features of atypical teratoid/rhabdoid tumors (ATRT). Rare non-rhabdoid brain tumors showing cribriform growth pattern and SMARCB1 loss have been designated cribriform neuroepithelial tumor (CRINET). Small case series suggest that CRINETs may have a relatively favorable prognosis. However, the long-term outcome is unclear and it remains uncertain whether CRINET represents a distinct entity or a variant of ATRT. Therefore, 10 CRINETs were clinically and molecularly characterized and compared with 10 ATRTs of each of three recently described molecular subgroups (i.e. ATRT-TYR, ATRT-SHH and ATRT-MYC) using Illumina Infinium HumanMethylation450 arrays, FISH, MLPA, and sequencing. Furthermore, outcome was compared to a larger cohort of 27 children with ATRT-TYR. Median age of the 6 boys and 4 girls harboring a CRINET was 20 months. On histopathological examination, all CRINETs demonstrated a cribriform growth pattern and distinct tyrosinase staining. On unsupervised cluster analysis of methylation data, all CRINETs examined exclusively clustered within the ATRT-TYR molecular subgroup. As ATRT-TYR, CRINETs mainly showed large heterozygous 22q deletions (9/10) and SMARCB1 mutations of the other allele. In two patients, SMARCB1 mutations were also present in the germline. Estimated mean overall survival in patients with CRINETs was 125 months (95% confidence interval 100-151 months) as compared to only 53 (33-74) months in patients with ATRTs of the ATRT-TYR subgroup (Log-Rank P < 0.05). In conclusion, CRINET represents a SMARCB1-deficient non-rhabdoid tumor, which shares molecular similarities with the ATRT-TYR subgroup but has distinct histopathological features and favorable long-term outcome.

Patient knowledge of late effects of acute lymphoblastic leukaemia.

BACKGROUND: Over 80% of children with acute lymphatic leukaemia (ALL) survive, but many develop long-term effects after the therapy. The aim of the study was to reveal how much Norwegian adults treated for acute lymphatic leukaemia before the age of 16 know about the risk of long-term effects. MATERIAL AND METHOD: The participants (n = 139) were recruited from a cross-sectional study (ALLBARN) of adults treated for acute lymphatic leukaemia before the age of 16 in the period 1970-2002. Their knowledge of diagnosis, treatment and long-term effects was investigated in a semi-structured interview. RESULTS: A median number of 23 years after treatment for acute lymphatic leukaemia, 85 (61%) of the participants were unable to give examples of possible long-term effects of cancer treatment. Reduced fertility was known to 35 participants (25%), while few were aware of the risk of heart failure (n = 3) or secondary malignancy (n = 5). Those who were aware of long-term effects usually had personal experience of the problem. However, the participants had a sound knowledge of their own diagnosis and the therapy they had been submitted to. INTERPRETATION: Long-term survivors of acute lymphatic leukaemia in childhood and adolescence know little of the risk of long-term effects. The dissemination of information about the potential consequences of the therapy should be improved.

Genomic aberrations in pediatric gliomas and embryonal tumors.

The pathogenesis of pediatric central nervous system tumors is poorly understood. To increase knowledge about the genetic mechanisms underlying these tumors, we performed genome-wide screening of 17 pediatric gliomas and embryonal tumors combining G-band karyotyping and array comparative genomic hybridization (aCGH). G-banding revealed abnormal karyotypes in 56% of tumor samples (9 of 16; one failed in culture), whereas aCGH found copy number aberrations in all 13 tumors examined. Pilocytic astrocytomas (n = 3) showed normal karyotypes or nonrecurrent translocations by karyotyping but the well-established recurrent gain of 7q34 and 19p13.3 by aCGH. Our series included one anaplastic oligoastrocytoma, a tumor type not previously characterized genomically in children, and one anaplastic neuroepithelial tumor (probably an oligoastrocytoma); both showed loss of chromosome 14 by G-banding and structural aberrations of 6q and loss of 14q, 17p, and 22q by aCGH. Three of five supratentorial primitive neuroectodermal tumors showed aberrant karyotypes: two were near-diploid with mainly structural changes and one was near-triploid with several trisomies. aCGH confirmed these findings and revealed additional recurrent gains of 1q21-44 and losses of 3p21, 3q26, and 8p23. We describe cytogenetically for the first time a cribriform neuroepithelial tumor, a recently identified variant of atypical teratoid/rhabdoid tumor with a favorable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and 22q by aCGH. This study indicates the existence of distinct cytogenetic patterns in pediatric gliomas and embryonal tumors; however, further studies of these rare tumors using a multimodal approach are required before their true genomic aberration pattern can be finally established.

Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma.

BACKGROUND: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). METHODS: Children with standard-risk hepatoblastoma who were younger than 16 years of age were eligible for inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered in three preoperative cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection). RESULTS: Between June 1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin-doxorubicin group in the intention-to-treat analysis (difference, 1.4%; 95% confidence interval [CI], -4.1 to 7.0); these rates were 99% and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to 98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent with combination therapy (74.4% vs. 20.6%). CONCLUSIONS: As compared with cisplatin plus doxorubicin, cisplatin monotherapy achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number, NCT00003912.)

[Children with cancer and their use of natural products]. / Bruk av naturpreparater og kosttilskudd hos kreftsyke barn i Norge.

BACKGROUND: Little is published about use of dietary supplements and natural products in children with cancer. The aim of the study was to document the experience and attitudes parents to Norwegian children with cancer have on use of such products. MATERIAL AND METHODS: The parents of 56 children at the three University hospitals in and around Oslo were asked to participate in the study. The mother or father of 21 children accepted the invitation to participate in interviews in focus groups. RESULTS: The parents were very restrictive about giving their children natural products. They said they did not have the capacity to search for information, but they were more open when it came to own use of these products. The parents in this study felt a strong pressure to try natural products from advertisements, media and health stores. The families had been given advice from friends and relatives about giving natural products, and not following the advice ended up being an extra burden. The participants had not received information from physicians or other health workers about such products, but would prefer to receive information from them. INTERPRETATION: The parents in this study were very restrictive about giving their children natural products. They all had confidence in the doctor and would like the doctor to advise them. It is challenging to convey correct and evidence-based information appropriately.