Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival.

Importance: Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined. Objective: To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival. Design, Setting, and Participants: This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017. Exposure: Uveal melanoma with or without partial loss of chromosome 3. Main Outcomes and Measures: Metastasis-free survival and overall survival at 60 months. Results: Of the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001). Conclusions and Relevance: These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.

Radiogenomics of neuroblastomas: Relationships between imaging phenotypes, tumor genomic profile and survival.

PURPOSE: This study investigated relationships between neuroblastomas (NBs) imaging phenotypes, tumor genomic profile and patient outcome. PATIENTS AND METHODS: This IRB-approved retrospective observational study included 133 NB patients (73 M, 60 F; median age 15 months, range 0-151) treated in a single institution between 1998 and 2012. A consensus review of imaging (CT-scan, MRI) categorized tumors according to both the primarily involved compartment (i.e., neck, chest, abdomen or pelvis) and the sympathetic anatomical structure the tumors rose from (i.e., cervical, paravertebral or periarterial chains, or adrenal gland). Tumor shape, volume and image-defined surgical risk factors (IDRFs) at diagnosis were recorded. Genomic profiles were assessed using array-based comparative genomic hybridization and divided into three groups: "numerical-only chromosome alterations" (NCA), "segmental chromosome alterations" (SCA) and "MYCN amplification" (MNA). Statistical analyses included Kruskal-Wallis, Chi2 and Fisher's exact tests and the Kaplan-Meier method with log-rank tests and Cox model for univariate and multivariate survival analyses. RESULTS: A significant association between the sympathetic structure origin of tumors and genomic profiles was demonstrated. NBs arising from cervical sympathetic chains were all NCA. Paravertebral NBs were NCA or SCA in 75% and 25%, respectively and none were MNA. Periarterial NBs were NCA, SCA or MNA in 33%, 56% and 11%, respectively. Adrenal NBs were NCA, SCA or MNA in 16%, 36% and 48%, respectively. Among MNA NBs, 92% originated from the adrenal gland. The sympathetic anatomical classification was significantly better correlated to overall survival than the compartmental classification (P < .0003). The tumor volume of MNA NBs was significantly higher than NCA or SCA NBs (P < .0001). Patients with initial volume less than 160 mL had significantly better overall survival (P < .009). A "single mass" pattern was significantly more frequent in NCA NBs (P = .0003). The number of IDRFs was significantly higher in MNA NBs (P < .0001). CONCLUSION: Imaging phenotypes of neuroblastomas, including tumor origin along the sympathetic system, correlate with tumor genomic profile and patient outcome.

[Care pathways before diagnosis in children and adolescents with malignancies]. / Parcours prédiagnostique des enfants et adolescents atteints de tumeurs solides.

OBJECTIVE: to describe medical care pathways between first symptoms and first oncologic consultation in children and adolescents with solid cancers in order to analyze a possible relationship between delayed diagnosis and its potential consequences. METHODS: Retrospective study on patients aged less than 25 years at first consultation in the oncology department of pediatric, adolescent and young adult in Institut Curie during one year. Were collected data on cancer characteristics, components of care pathways, and sociodemographic parents' characteristics. RESULTS: Hundred and six patients were selected, with median age of 6 years. Most represented tumor was low-grade cerebral tumor (17.0%). Pain was the most frequent type of disorder observed as first sign (34.3% of patients). First signs were unspecific in only 27.6% of cases. Most patients were first seen by a general practitioner (29.3%). Median total time to diagnosis was one month [ranges: 0-64]. Median number of consultations before referral to oncology expert was 2 [0-7]. Retrospective analysis found a possible delayed diagnosis in 44.3% of patients, with potential vital and functional risks estimated respectively at 14.1 and 20.7% of overall population. Time to diagnosis was shorter if father was of foreign nationality vs. French (34 days vs. 72 days, P<0.05), and longer if parents were separated (74.5 days vs. 42.5 days, P<0.03). CONCLUSIONS: Overall time to diagnosis is quite fast, even if first signs of pediatric cancers are very polymorphic. Some medical and sociodemographic factors could influence characteristics of care pathways.