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St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem.

ABSTRACT: Effective data sharing is key to accelerating research to improve diagnostic precision, treatment efficacy, and long-term survival in pediatric cancer and other childhood catastrophic diseases. We present St. Jude Cloud (https://www.stjude.cloud), a cloud-based data-sharing ecosystem for accessing, analyzing, and visualizing genomic data from >10,000 pediatric patients with cancer and long-term survivors, and >800 pediatric sickle cell patients. Harmonized genomic data totaling 1.25 petabytes are freely available, including 12,104 whole genomes, 7,697 whole exomes, and 2,202 transcriptomes. The resource is expanding rapidly, with regular data uploads from St. Jude's prospective clinical genomics programs. Three interconnected apps within the ecosystem-Genomics Platform, Pediatric Cancer Knowledgebase, and Visualization Community-enable simultaneously performing advanced data analysis in the cloud and enhancing the Pediatric Cancer knowledgebase. We demonstrate the value of the ecosystem through use cases that classify 135 pediatric cancer subtypes by gene expression profiling and map mutational signatures across 35 pediatric cancer subtypes. SIGNIFICANCE: To advance research and treatment of pediatric cancer, we developed St. Jude Cloud, a data-sharing ecosystem for accessing >1.2 petabytes of raw genomic data from >10,000 pediatric patients and survivors, innovative analysis workflows, integrative multiomics visualizations, and a knowledgebase of published data contributed by the global pediatric cancer community.This article is highlighted in the In This Issue feature, p. 995.

SUBMITTER: McLeod C

PROVIDER: S-EPMC8102307 | biostudies-literature |

REPOSITORIES: biostudies-literature

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St. Jude Survivorship Portal: sharing and analyzing large clinical and genomic datasets from pediatric cancer survivors.

Project description:Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. Over 1,600 phenotypic variables and 400 million genetic variants from over 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry.

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Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Project description:BackgroundRadiation therapy (RT) confers local tumor control and survival advantages in some patients with osteosarcoma, yet pediatric and adolescent and young adult (AYA) population studies are limited.MethodsTwenty-eight patients treated with curative-intent RT (median dose, 59.4 Gy; range, 40-76 Gy) at our institution from 1990 to 2017 were retrospectively identified. Cumulative incidence (CIN) of local failure (LF) was estimated by Gray's method and overall survival (OS) by the Kaplan-Meier method. Competing-risk regression and Cox proportional hazards models determined predictors of outcome. Toxicity was reported according to CTCAE v4.0.ResultsWith a median follow-up of 99.1 months in living patients, nine patients (32.1%) developed LF. Estimated CINs of LF with competing risk of death at 5 years for the entire cohort, patients at initial diagnosis (n = 16), and recurrent/refractory patients (n = 12) were 32.7% (95% CI, 16.0-50.5%), 25.0% (95% CI, 7.3-48.0%), and 43.8% (95% CI, 13.6-71.0%), respectively (P = 0.31). Estimated 5-year OS was 42.6% (95% CI, 23.2-62.0%), 54.6% (95% CI, 29.5-79.6%), and 24.3% (95% CI, 0-52.2%), respectively (P = 0.15). No clinicopathologic features were significantly associated with LF, yet lack of chemotherapy or metastasis at the time of RT was independent significant prognostic factors of decreased OS. Eleven patients experienced RT-related morbidity, with two grade 3 toxicities and no grade 4/5 events.ConclusionsCurative-intent RT in pediatric and AYA patients was well tolerated and achieved a local tumor control rate of 75% in patients with primary disease. Local control rates were similar to those in primarily adult studies, with similar or lower doses.

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Patient-derived orthotopic xenografts of pediatric brain tumors: a St. Jude resource.

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Genomic Data-Sharing Practices.

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Cohort Profile: The St. Jude Lifetime Cohort Study (SJLIFE) for paediatric cancer survivors.

Project description: Not available

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Trial design: The St. Jude Children's Research Hospital Cancer Survivors Tobacco Quit Line study.

Project description:Nearly, one-fifth of childhood cancer survivors (CCSs) smoke cigarettes. Because CCSs are already at greater medical smoking-related risks, targeting them for smoking cessation efforts is a high priority. One of the major challenges with smoking cessation in CCSs is how to reach such a geographically dispersed population. This study aims to demonstrate that these challenges can be overcome through the use of telephone-based tobacco quit lines (QLs). This report describes the design of the St. Jude Cancer Survivor Tobacco QL study, which is a randomized controlled clinical trial that will examine the long-term (1-year) efficacy of a counselor initiated vs. participant initiated tobacco QL with adjunctive nicotine replacement therapy (NRT) in both groups. Participants (N=950) will be recruited nationally and randomly assigned to one of the two interventions. The counselor initiated intervention includes six scheduled telephone sessions of a behavioral intervention and provision of 8 weeks of NRT. The participant initiated intervention allows the participant to call the QL at their convenience, but includes the same six telephone sessions and provision of 2 weeks of NRT. Both groups will receive two follow-up phone calls at 8 weeks and 1 year after enrollment to assess their smoking status. The primary outcome measure is cotinine-validated self-reported smoking abstinence at 1-year follow-up. Results from this study will provide the first evidence about the efficacy of intensive QL cessation intervention in this high-risk population. Such evidence can lead as well to the dissemination of this intervention to other medically compromised populations.

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Progression of Frailty in Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Report.

Project description:BackgroundSome adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail.MethodsFrailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates.ResultsCancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32).ConclusionsPrevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors.

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