A Clinical Decision Support System for the Prevention of Genetic-Related Heart Disease

Drug-induced long QT syndrome (diLQTS) is a common adverse drug reaction characterized by rapid and erratic heart beats that may instigate fainting or seizures. The onset of diLQTS can lead to torsades de points (TdP), a specific form of abnormal heart rhythm that often leads to sudden cardiac arrest and death. This study aims to understand the genetic similarities between diLQTS and TdP to develop a clinical decision support system (CDSS) to aide physicians in the prevention of TdP. Highly accurate classification algorithms, including random forests, shrunken centroid, and diagonal linear discriminant analysis are considered to build a prediction model for TdP. With a feasible set of markers, we accurately predict TdP classifications with an accuracy above 90%. The methodology used in this study can be extended to dealing with other biomedical high-dimensional data

Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children\u27s Oncology Group Trial ANHL12P1

PURPOSE: Arm crizotinib (CZ) of the Children\u27s Oncology Group trial ANHL12P1 (ClinicalTrials.gov identifier: NCT01979536) examined the efficacy and toxicity of adding CZ to standard chemotherapy for children with newly diagnosed, nonlocalized ALK+ CD30+ anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: Between 2013 and 2019, 66 enrolled children received CZ with chemotherapy. Patients received a 5-day prophase followed by six chemotherapy cycles at 21-day intervals with CZ administered twice daily during each 21-day cycle. The study was temporarily closed for two periods (total 12 months) to evaluate toxicity, during which CZ was discontinued. Measurements of fusion transcripts in peripheral blood were performed at diagnosis for minimal disseminated disease (MDD). RESULTS: The 2-year event-free survival (EFS) is 76.8% (95% CI, 68.5 to 88.1) and the 2-year overall survival is 95.2% (95% CI, 85.7 to 98.4). Fifteen patients relapsed and one patient died; median time to relapse was 7.4 months from diagnosis, with relapses occurring after chemotherapy was complete. The 66 patients completed 384 cycles of chemotherapy. Thirteen of the 66 patients experienced a grade 2+ thromboembolic adverse event (19.7%; 95% CI, 11.1 to 31.3). In the 25 patients who received mandated prophylactic anticoagulation, there were two thromboembolic events (8.0%; 95% CI, 0.01 to 26). Patients with negative MDD had a superior outcome, with an EFS of 85.6% (95% CI, 68.6 to 93.8); positive MDD was associated with a lower EFS of 58.1% (95% CI, 33.4 to 76.4). CONCLUSION: Arm CZ of ANHL12P1 demonstrated that the addition of CZ to standard treatment prevented relapses during therapy for children with ALCL, MDD predicted EFS, and the addition of CZ resulted in unexpected thromboembolic events. Overall survival and EFS rates are consistent with the highest reported outcomes for children with ALCL

Intensive Multimodality Therapy for Extraocular Retinoblastoma: A Children's Oncology Group Trial (ARET0321)

PURPOSE Metastatic retinoblastoma has a poor prognosis when treated with conventional chemotherapy and radiation therapy (RT). Intensified therapy may improve the outcome. METHODS A prospective, international trial enrolled patients with extraocular retinoblastoma. Patients with stage II or III (locoregional) retinoblastoma received four cycles of chemotherapy, followed by involved field RT (45 Gy). Patients with stage IVa or IVb (metastatic or trilateral) retinoblastoma also received four cycles of chemotherapy and those with $ partial response then received one cycle of high-dose carboplatin, thiotepa, and etoposide with autologous hematopoietic stem-cell support. Patients with stage IVa or IVb with residual tumor postchemotherapy received RT. The proportion of patients who achieved event-free survival would be reported and compared with historical controls separately for each of the three groups of patients. RESULTS Fifty-seven eligible patients were included in the analyses. Event-free survival at 1 year was 88.1% (90% CI, 66.6 to 96.2) for stage II-III, 82.6% (90% CI, 61.0 to 92.9) for stage IVa, and 28.3% (90% CI, 12.7 to 46.2) for stage IVb/trilateral. Toxicity was significant as expected and included two therapy-related deaths. CONCLUSION Intensive multimodality therapy is highly effective for patients with regional extraocular retinoblastoma and stage IVa metastatic retinoblastoma. Although the study met its aim for stage IVb, more effective therapy is still required for patients with CNS involvement (ClinicalTrials.gov identifier: NCT00554788).Fil: Dunkel, Ira J.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Piao, Jin. University of Southern California; Estados UnidosFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Banerjee, Anuradha. University of California San Francisco; Estados UnidosFil: Abouelnaga, Sherif. Children's Cancer Hospital; EgiptoFil: Buchsbaum, Jeffrey C.. National Cancer Institute; Estados UnidosFil: Merchant, Thomas E.. St. Jude Children's Research Hospital; Estados UnidosFil: Granger, Meaghan M.. Cook Children's Hospital; Estados UnidosFil: Jubran, Rima F.. Children's Hospital Los Angeles; Estados UnidosFil: Weinstein, Joanna L.. Ann & Robert H. Lurie Children's Hospital of Chicago; Estados UnidosFil: Saguilig, Lauren. Children's Oncology Group; Estados UnidosFil: Abramson, David H.. Memorial Sloan-kettering Cancer Center; Estados UnidosFil: Krailo, Mark D.. University of Southern California; Estados UnidosFil: Rodriguez Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Chintagumpala, Murali M.. Texas Children's Hospital Houston; Estados Unido