24 results on '"Aplenc R"'
Search Results
2. Data standards in pediatric oncology: Past, present, and future.
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Wyatt KD, Noyd DH, Wood NM, Phillips CA, Miller TP, Rubin EM, Winestone LE, Waanders AJ, Perentesis JP, and Aplenc R
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- Child, Humans, Medical Oncology, Forecasting, Patients, Oncology Nursing, Neoplasms therapy
- Abstract
In this commentary, we highlight the central role that data standards play in facilitating data-driven efforts to advance research in pediatric oncology. We discuss the current state of data standards for pediatric oncology and propose five steps to achieve an improved future state with benefits for clinicians, researchers, and patients., (© 2022 Wiley Periodicals LLC.)
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- 2023
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3. Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.
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Devine KJ, Diorio C, Richman SA, Henderson AA, Oranges K, Armideo E, Kolb MS, Freedman JL, Aplenc R, Fisher MJ, Minturn JE, Olson T, Bagatell R, Barakat L, Croy C, Mauro J, Vitlip L, Acord MR, Mattei P, Johnson VK, Devine CM, Pasquariello C, and Reilly AF
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- Anesthesia, General adverse effects, Child, Consensus, Diagnostic Imaging, Humans, Hematopoietic Stem Cell Transplantation, Neoplasms therapy
- Abstract
Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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4. Electronic symptom monitoring in pediatric patients hospitalized for chemotherapy.
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Leahy AB, Schwartz LA, Li Y, Reeve BB, Bekelman JE, Aplenc R, and Basch EM
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- Adolescent, Adult, Child, Electronics, Hospitalization, Humans, Medical Oncology, Neoplasms diagnosis, Neoplasms drug therapy, Patient Reported Outcome Measures
- Abstract
Background: Using patient-reported outcomes for symptom monitoring in oncology has resulted in significant benefits for adult patients with cancer. The feasibility of this approach has not been established in the routine care of children with cancer., Methods: The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) is an item library that enables children and caregivers to self-report symptoms. Ten symptom items from the Ped-PRO-CTCAE were uploaded to an online platform. Patients at least 7 years old and their caregivers were prompted by text/email message to electronically self-report daily during a planned hospitalization for chemotherapy administration. Symptom reports were emailed to the clinical team caring for the patient, but no instructions were given regarding the use of this information. Rates of patient participation and clinician responses to reports were systematically tracked., Results: The median age of the participating patients (n = 52) was 11 years (range, 7-18 years). All patients and caregivers completed an initial login, with 92% of dyads completing at least 1 additional symptom assessment during hospitalization (median, 3 assessments; range, 0-40). Eighty-one percent of participating dyads submitted symptom reports on at least half of hospital days, and 54% submitted reports on all hospital days. Clinical actions were taken in response to symptom reports 21% of the time. Most patients felt that the system was easy (73%) and important (79%). Most clinicians found symptom reports easy to understand and useful (97%)., Conclusions: Symptom monitoring using patient-reported outcome measures for hospitalized pediatric oncology patients is feasible and generates data valued by clinicians and patients., (© 2021 American Cancer Society.)
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- 2021
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5. Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer.
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Kerlavage AR, Kirchhoff AC, Guidry Auvil JM, Sharpless NE, Davis KL, Reilly K, Reaman G, Penberthy L, Deapen D, Hwang A, Durbin EB, Gallotto SL, Aplenc R, Volchenboum SL, Heath AP, Aronow BJ, Zhang J, Vaske O, Alonzo TA, Nathan PC, Poynter JN, Armstrong G, Hahn EE, Wernli KJ, Greene C, DiGiovanna J, Resnick AC, Shalley ER, Nadaf S, and Kibbe WA
- Subjects
- Adolescent, Child, Data Science, Humans, Pandemics, SARS-CoV-2, Young Adult, COVID-19, Medical Informatics, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative., Competing Interests: Anne C. KirchhoffStock and Other Ownership Interests: Medtronic Kara L. DavisHonoraria: NovartisResearch Funding: Jazz Pharmaceuticals Karlyne ReillyConsulting or Advisory Role: Saul Ewing LLCPatents, Royalties, Other Intellectual Property: I hold a patent to a potential therapeutic: Reilly KM, Beutler JA, Turbyville T, Wiemer DF: The Natural Product Schweinfurthin A and Synthetic Schweinfurthin Analogs Specifically Inhibit Nf1-Null Cells and may be Useful as a Therapy for Neurofibromatosis Type 1. US patent 61/174,338, April 19, 2014; International patent PCT/US10/33153. There are no royalties or licensing fees from this patent at the time Richard AplencExpert Testimony: Vorys Samuel L. VolchenboumStock and Other Ownership Interests: Litmus HealthConsulting or Advisory Role: AccordantTravel, Accommodations, Expenses: Sanford Health Bruce J. AronowPatents, Royalties, Other Intellectual Property: Patents issued for some data analysis algorithms related to data mining and discovery approaches to drug repositioning for new clinical indications Olena VaskeEmployment: NantWorksStock and Other Ownership Interests: NantHealth Casey GreeneOther Relationship: Alex's Lemonade Stand Foundation Jack DiGiovannaEmployment: Biogen (I)Stock and Other Ownership Interests: Biogen Sorena NadafThis author is a member of the JCO Clinical Cancer Informatics Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Warren A. KibbeThis author is a member of the JCO Clinical Cancer Informatics Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.No other potential conflicts of interest were reported.
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- 2021
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6. Clinical impact of genomic characterization of 15 patients with acute megakaryoblastic leukemia-related malignancies.
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Lalonde E, Rentas S, Wertheim G, Cao K, Surrey LF, Lin F, Zhao X, Obstfeld A, Aplenc R, Luo M, and Li MM
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- Child, Child, Preschool, Chromosomes, DNA-Binding Proteins genetics, Down Syndrome complications, Down Syndrome genetics, Female, GATA1 Transcription Factor, Genetic Predisposition to Disease genetics, High-Throughput Nucleotide Sequencing, Histone-Lysine N-Methyltransferase genetics, Humans, Infant, Infant, Newborn, Karyotype, Kruppel-Like Transcription Factors genetics, Leukemoid Reaction genetics, Male, Myeloid-Lymphoid Leukemia Protein genetics, Neoplasm Proteins genetics, Repressor Proteins genetics, Retinoblastoma-Binding Protein 2 genetics, Genomics, Leukemia genetics, Leukemia, Megakaryoblastic, Acute genetics, Neoplasms genetics
- Abstract
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia but is approximately 500 times more likely to develop in children with Down syndrome (DS) through transformation of transient abnormal myelopoiesis (TAM). This study investigates the clinical significance of genomic heterogeneity of AMKL in children with and without DS and in children with TAM. Genomic evaluation of nine patients with DS-related TAM or AMKL, and six patients with non-DS AMKL, included conventional cytogenetics and a comprehensive next-generation sequencing panel for single-nucleotide variants/indels and copy-number variants in 118 genes and fusions involving 110 genes. Recurrent gene fusions were found in all patients with non-DS, including two individuals with complex genomes and either a NUP98-KDM5A or a KMT2A - MLLT6 fusion, and the remaining harbored a CBFA2T3-GLIS2 fusion, which arose from both typical and atypical cytogenetic mechanisms. These fusions guided treatment protocols and resulted in a change in diagnosis in two patients. The nine patients with DS had constitutional trisomy 21 and somatic GATA1 mutations, and those with DS-AMKL had two to four additional clinically significant somatic mutations. Comprehensive genomic characterization provides critical information for diagnosis, risk stratification, and treatment decisions for patients with AMKL. Continued genetic and clinical characterization of these rare cancers will aid in improving patient management., (© 2021 Lalonde et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2021
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7. RNA Dysregulation: An Expanding Source of Cancer Immunotherapy Targets.
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Pan Y, Kadash-Edmondson KE, Wang R, Phillips J, Liu S, Ribas A, Aplenc R, Witte ON, and Xing Y
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- Humans, Immunotherapy, Proteome, Transcriptome, Neoplasms genetics, Neoplasms therapy, RNA genetics
- Abstract
Cancer transcriptomes frequently exhibit RNA dysregulation. As the resulting aberrant transcripts may be translated into cancer-specific proteins, there is growing interest in exploiting RNA dysregulation as a source of tumor antigens (TAs) and thus novel immunotherapy targets. Recent advances in high-throughput technologies and rapid accumulation of multiomic cancer profiling data in public repositories have provided opportunities to systematically characterize RNA dysregulation in cancer and identify antigen targets for immunotherapy. However, given the complexity of cancer transcriptomes and proteomes, important conceptual and technological challenges exist. Here, we highlight the expanding repertoire of TAs arising from RNA dysregulation and introduce multiomic and big data strategies for identifying optimal immunotherapy targets. We discuss extant barriers for translating these targets into effective therapies as well as the implications for future research., Competing Interests: Declaration of Interests Y.X. is a scientific cofounder of Panorama Medicine and consulted for PACT Pharma. O.N.W. currently has consulting, equity, and/or board relationships with Trethera Corporation, Kronos Biosciences, Sofie Biosciences, Breakthrough Properties, Vida Ventures, Nammi Therapeutics, Two River, Iconovir, Appia BioSciences, Neogene Therapeutics, and Allogene Therapeutics. A.R. has received honoraria from consulting with Amgen, Bristol-Myers Squibb, Chugai, Genentech, Merck, Novartis, and Roche and is or has been a member of the scientific advisory board and holds stock in Advaxis, Arcus Biosciences, Bioncotech Therapeutics, Compugen, CytomX, Five Prime, FLX-Bio, ImaginAb, Isoplexis, Kite-Gilead, Lutris Pharma, Merus, PACT Pharma, Rgenix, and Tango Therapeutics. None of these companies contributed to or directed the writing of this review article., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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8. Delayed cancer diagnoses and high mortality in children during the COVID-19 pandemic.
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Ding YY, Ramakrishna S, Long AH, Phillips CA, Montiel-Esparza R, Diorio CJ, Bailey LC, Maude SL, Aplenc R, Batra V, Reilly AF, Rheingold SR, Lacayo NJ, Sakamoto KM, and Hunger SP
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- Betacoronavirus, COVID-19, Child, Fear, Humans, Italy, SARS-CoV-2, Coronavirus Infections, Neoplasms diagnosis, Neoplasms epidemiology, Pandemics, Pneumonia, Viral epidemiology
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- 2020
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9. Development and Clinical Validation of a Large Fusion Gene Panel for Pediatric Cancers.
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Chang F, Lin F, Cao K, Surrey LF, Aplenc R, Bagatell R, Resnick AC, Santi M, Storm PB, Tasian SK, Waanders AJ, Hunger SP, and Li MM
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- Case-Control Studies, Child, Genomics, Humans, Multiplex Polymerase Chain Reaction, Biomarkers, Tumor genetics, High-Throughput Nucleotide Sequencing methods, Neoplasms diagnosis, Neoplasms genetics, Oncogene Proteins, Fusion genetics
- Abstract
Gene fusions are one of the most common genomic alterations in pediatric cancer. Many fusions encode oncogenic drivers and play important roles in cancer diagnosis, risk stratification, and treatment selection. We report the development and clinical validation of a large custom-designed RNA sequencing panel, CHOP Fusion panel, using anchored multiplex PCR technology. The panel interrogates 106 cancer genes known to be involved in nearly 600 different fusions reported in hematological malignancies and solid tumors. The panel works well with different types of samples, including formalin-fixed, paraffin-embedded samples. The panel demonstrated excellent analytic accuracy, with 100% sensitivity and specificity on 60 pediatric tumor validation samples. In addition to identifying all known fusions in the validation samples, three unrecognized, yet clinically significant, fusions were also detected. A total of 276 clinical cases were analyzed after the validation, and 51 different fusions were identified in 104 cases. Of these fusions, 16 were not previously reported at the time of discovery. These fusions provided genomic information useful for clinical management. Our experience demonstrates that CHOP Fusion panel can detect the vast majority of known and certain novel clinically relevant fusion genes in pediatric cancers accurately, efficiently, and cost-effectively; and the panel provides an excellent tool for new fusion gene discovery., (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2019
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10. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy.
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Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nuñez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, and Seidman CE
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- Adult, Aged, Animals, Cardiomyopathies epidemiology, Cohort Studies, Female, Genetic Variation drug effects, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Neoplasms epidemiology, Prospective Studies, Retrospective Studies, Antineoplastic Agents adverse effects, Cardiomyopathies chemically induced, Cardiomyopathies genetics, Genetic Variation genetics, Neoplasms drug therapy, Neoplasms genetics
- Abstract
Background: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM., Methods: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice., Results: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively)., Conclusions: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.
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- 2019
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11. Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events.
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Miller TP, Fisher BT, Getz KD, Sack L, Razzaghi H, Seif AE, Bagatell R, Adamson PC, and Aplenc R
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- Adolescent, Clinical Trials as Topic, Humans, Male, Electronic Health Records, Neoplasms
- Abstract
Background: Adverse events (AEs) on Children's Oncology Group (COG) trials are reported manually by clinical research assistants (CRAs). The Common Terminology Criteria for Adverse Events (CTCAE) was developed to provide standardized definitions for identifying and grading AEs. The CTCAE has expanded significantly over its five versions, but the impact of CTCAE definitional changes has not been examined., Procedure: This study compared AE number and ascertainment among the first four CTCAE versions using a case vignette. Each CTCAE version was used to create a list of AEs and grades by two separate CRAs., Results: The CTCAE expanded from 9 categories and 49 AEs in v1.0 to 26 categories and 790 AEs in v4.0. CRAs independently selected different approaches to AE ascertainment-comprehensive and parsimonious. The number of AEs identified in the parsimonious approach was stable with 10-14 in each CTC version. The comprehensive approach identified 9, 20, 29, and 37 AEs in CTC versions 1.0, 2.0, 3.0, and 4.0, respectively. Only approximately 65% of AEs were conclusively graded in versions 2.0 to 4.0 using the comprehensive approach., Conclusions: CTCAE has increased in complexity. Although this increased complexity allows for more granular AE reporting, these data demonstrate potential unintended negative consequences of increasing CTC AE complexity, including the risk of varying approaches to AE capture. A comprehensive evaluation of CTC AE definitions and CRA reporting practices across COG institutions and AEs are needed to improve the accuracy and efficiency of AE reporting., (© 2019 Wiley Periodicals, Inc.)
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- 2019
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12. Clinical utility of custom-designed NGS panel testing in pediatric tumors.
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Surrey LF, MacFarland SP, Chang F, Cao K, Rathi KS, Akgumus GT, Gallo D, Lin F, Gleason A, Raman P, Aplenc R, Bagatell R, Minturn J, Mosse Y, Santi M, Tasian SK, Waanders AJ, Sarmady M, Maris JM, Hunger SP, and Li MM
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- Child, DNA, Neoplasm chemistry, Genetic Testing standards, High-Throughput Nucleotide Sequencing standards, Humans, Neoplasms genetics, Sequence Analysis, DNA standards, DNA, Neoplasm genetics, Genetic Testing methods, High-Throughput Nucleotide Sequencing methods, Neoplasms diagnosis, Sequence Analysis, DNA methods
- Abstract
Background: Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers., Methods: Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed., Results: NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration., Conclusions: Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.
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- 2019
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13. An overview of disparities in childhood cancer: Report on the Inaugural Symposium on Childhood Cancer Health Disparities, Houston, Texas, 2016.
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Scheurer ME, Lupo PJ, Schüz J, Spector LG, Wiemels JL, Aplenc R, Gramatges MM, Schiffman JD, Pombo-de-Oliveira MS, Yang JJ, Heck JE, Metayer C, Orjuela-Grimm MA, Bona K, Aristizabal P, Austin MT, Rabin KR, Russell HV, and Poplack DG
- Subjects
- Adolescent, Child, Child, Preschool, Congresses as Topic, Female, Humans, Infant, Infant, Newborn, Male, Risk Factors, Texas, Delivery of Health Care, Neoplasms epidemiology, Neoplasms therapy
- Abstract
The Inaugural Symposium on Childhood Cancer Health Disparities was held in Houston, Texas, on November 2, 2016. The symposium was attended by 109 scientists and clinicians from diverse disciplinary backgrounds with interests in pediatric cancer disparities and focused on reviewing our current knowledge of disparities in cancer risk and outcomes for select childhood cancers. Following a full day of topical sessions, everyone participated in a brainstorming session to develop a working strategy for the continued expansion of research in this area. This meeting was designed to serve as a springboard for examination of childhood cancer disparities from a more unified and systematic approach and to enhance awareness of this area of need.
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- 2018
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14. The impact of chemotherapy shortages on COG and local clinical trials: a report from the Children's Oncology Group.
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G Salazar E, Bernhardt MB, Li Y, Aplenc R, and Adamson PC
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- Child, Humans, Pharmacists, Antineoplastic Agents supply & distribution, Clinical Trials as Topic, Neoplasms drug therapy
- Abstract
Background: Oncology drug shortage is associated with increased patient adverse events and decreased enrollment on clinical trials for adult patients; however, the impact of oncology drug shortages has not been well studied in children with cancer., Procedure: The Children's Oncology Group (COG) distributed a 5-item survey to 226 COG site-specific principal investigators (PI's) and 14-item survey to 161 COG pharmacists to gather data the impact of chemotherapeutic shortages on clinical trials and patient care., Results: The response rate was 66.4% (150/226) for PI's and 29.8% (48/161) for pharmacists. COG PI's reported daunorubicin (73%), methotrexate (56%), asparaginase/PEG-asparaginase (42%), doxorubicin (26%), thiotepa (21%), and cytarabine (20%) were most commonly in shortage, while COG pharmacists reported daunorubicin (80%), methotrexate (66%), vincristine (21%), thiotepa (41%), asparaginase/PEG-asparaginase (34%), and cytarabine (34%) were most commonly in shortage over the past two years. Pharmacists were twice as likely to report a shortage compared with PI's (OR 2.1, 95% CI: 1.6-2.7, P < 0.0001). Fifty percent (74/147) of COG PI's reported at least one patient enrolled on a clinical trial was impacted by drug shortage, and 66% (98/148) of COG PI's reported at least one patient had clinical care impacted by drug shortage., Conclusions: Chemotherapy shortages remain widespread across institutions, hinder clinical trials, and may contribute to adverse events in children with cancer. The increased frequency of chemotherapy shortages reported by pharmacists suggests that pharmacist efforts may mitigate negative impact chemotherapy shortages. Over half of pediatric institutions are implementing recommendations to address shortages, such as cross-institutional collaboration and center-level guidelines., (© 2015 Wiley Periodicals, Inc.)
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- 2015
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15. Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer.
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de Blank P, Zaoutis T, Fisher B, Troxel A, Kim J, and Aplenc R
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- Adolescent, Child, Child, Preschool, Clostridium Infections epidemiology, Cohort Studies, Cross Infection epidemiology, Databases, Factual, Female, Hospitals, Pediatric, Humans, Incidence, Infant, Male, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Risk Factors, United States epidemiology, Clostridioides difficile, Clostridium Infections etiology, Cross Infection etiology, Neoplasms complications
- Abstract
Objectives: To study the trend of Clostridium difficile infection (CDI) and risk factors for hospital acquired CDI (HA-CDI) among children with cancer., Study Design: We analyzed 33 095 first pediatric hospitalizations for malignancy among 43 pediatric hospitals between 1999 and 2011. The effect of demographics, disease characteristics, and weekly drug exposure (antibiotics, antacids, and chemotherapy) on HA-CDI was assessed with multivariate Cox regression. CDI was defined by the combination of International Classification of Diseases, 9th edition-Clinical Modification (ICD-9CM), CDI diagnostic assay billing code, and concurrent administration of a CDI-active antibiotic. HA-CDI was defined as CDI with assay occurring after the sixth hospital day., Results: A total of 1736 admissions with CDI were identified, of which 380 were HA-CDI. CDI incidence increased from 1999-2006 (P = .01); however, CDI testing frequency and disease decreased from 2006-2010 (P < .05). Admissions with HA-CDI had longer lengths of stay compared with those without HA-CDI (35 days vs 12 days, P < .01) and greater risk of inpatient mortality (relative risk 2.3, P < .01). Increased risk of HA-CDI (hazard ratio [95% CI]) was seen after exposure to the following drugs: aminoglycoside (1.357 [1.053-1.749]), third generation cephalosporin (1.518 [1.177-1.959]), cefepime (2.383 [1.839-3.089]), and proton pump inhibiting agent (1.398 [1.096-1.784]) in the prior week, and chemotherapy (1.942 [1.491-2.529]) in the 8-14 days prior to HA-CDI onset. Histamine-2 receptor antagonist exposure in the prior week was associated with decreased risk of HA-CDI (0.730 [0.584-0.912])., Conclusions: Despite an apparent decrease in CDI incidence from 2006-2010, HA-CDI remains prevalent and morbid among children with cancer. Recent exposure to chemotherapy, proton pump inhibitor, and certain antibiotics were independent risk factors for HA-CDI., (Copyright © 2013 Mosby, Inc. All rights reserved.)
- Published
- 2013
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16. The use of palliative chemotherapy in pediatric oncology patients: a national survey of pediatric oncologists.
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Kang TI, Hexem K, Localio R, Aplenc R, and Feudtner C
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- Adult, Aged, Child, Female, Humans, Male, Middle Aged, Medical Oncology, Neoplasms drug therapy, Palliative Care
- Abstract
Background: Many children continue receiving chemotherapy after there is no realistic hope for cure. One factor that influences parental decisions to pursue medical therapies is physician preference. To date, no studies have described pediatric oncologists' perspectives and practices regarding palliative chemotherapy (PC)., Procedure: We surveyed via email pediatric oncologists practicing in the U.S who are members of the Children's Oncology Group to achieve the following objectives: (1) Describe pediatric oncologists treatment considerations regarding the use of PC. (2) Assess treatment considerations that influenced pediatric oncologists' therapy recommendations for their most recent patient receiving PC. There were 422 participants (40.8%) who completed the survey., Results: The most important factors considered by pediatric oncologists when prescribing PC were the toxicity of the chemotherapy (4.90 mean SD = 0.36 utilizing 5 point scale with 1 = not important to 5 = very important), the preferences of the family (4.57; SD = 0.60), and the potential to decrease symptoms arising from tumor burden (4.42; SD = 0.65). These treatment considerations were not as important when PC was prescribed for their most recent patient. Similarly, the chief aims in prescribing PC were not achieved for recent patients receiving PC. For their most recent patient who received PC, 40.8% believe this treatment was primarily for parental wishes., Conclusion: According to 80.2% of pediatric oncologists completing the survey, some patients receive chemotherapy beyond medical benefit and 40.8% of these oncologists have prescribed PC for the purpose of parental wishes to a recent patient. The chief aims in prescribing palliative chemotherapy were not achieved for recent patients., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2013
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17. Acceptability and feasibility of family use of The Cellie Cancer Coping Kit.
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Marsac ML, Hildenbrand AK, Clawson K, Jackson L, Kohser K, Barakat L, Kassam-Adams N, Aplenc R, Vinsel A, and Alderfer MA
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- Adult, Child, Feasibility Studies, Female, Humans, Male, Neoplasms therapy, Pilot Projects, Stress, Psychological prevention & control, Adaptation, Psychological, Neoplasms psychology, Parents psychology, Patient Acceptance of Health Care psychology, Stress, Psychological therapy
- Abstract
Purpose: This study aims to examine the acceptability and feasibility of child and parent use of The Cellie Cancer Coping Kit (Cellie Kit). The Cellie kit is designed to promote coping and decrease distress in children undergoing pediatric cancer treatment. It includes a plush toy, coping cards, and book for caregivers., Methods: In study 1, 15 children (ages 6-12) undergoing cancer treatment and their parents reviewed the Cellie Kit materials and provided feedback on its acceptability and perceived feasibility of use. In study 2, 15 additional children (ages 6-12) and their parents participated in a pilot intervention of the Cellie Kit and completed follow-up interviews and a satisfaction measure., Results: In study 1, all parents reported that they could understand the book and enact its coping tips and that the Cellie Kit was relevant to their families' cancer experience. Children explained they would use the Cellie Kit for emotional expression, fun, and comfort. The Cellie Kit was revised after study 1 to integrate additional material suggested by families. In study 2, all families completing follow-up assessments reported utilizing the Cellie Kit. A majority (86 % of children and 100 % of parents) indicated that they would recommend the Cellie Kit to others, and most (64 % of children and 93 % of parents) reported learning new information and/or skills from the Cellie Kit., Conclusions: The Cellie Kit is an engaging, helpful, and easy-to-use coping tool for families facing pediatric cancer treatment. Future research should examine the efficacy of brief interventions using the Cellie Kit to promote adjustment to pediatric cancer.
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- 2012
- Full Text
- View/download PDF
18. Merging of the National Cancer Institute-funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group.
- Author
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Aplenc R, Fisher BT, Huang YS, Li Y, Alonzo TA, Gerbing RB, Hall M, Bertoch D, Keren R, Seif AE, Sung L, Adamson PC, and Gamis A
- Subjects
- Adolescent, Child, Child, Preschool, Cooperative Behavior, Costs and Cost Analysis, Female, Hospitals, Pediatric, Humans, Infant, Male, Medical Oncology economics, Medical Oncology organization & administration, Medical Oncology standards, Medical Oncology statistics & numerical data, Medical Records Systems, Computerized economics, Medical Records Systems, Computerized standards, Medical Records Systems, Computerized statistics & numerical data, National Cancer Institute (U.S.), Organizational Objectives, Outcome and Process Assessment, Health Care, United States, Young Adult, Child Health Services economics, Child Health Services standards, Child Health Services statistics & numerical data, Clinical Trials, Phase III as Topic economics, Clinical Trials, Phase III as Topic standards, Clinical Trials, Phase III as Topic statistics & numerical data, Comparative Effectiveness Research, Medical Oncology trends, Medical Record Linkage, Medical Records Systems, Computerized trends, Neoplasms economics, Neoplasms mortality, Neoplasms therapy
- Abstract
Purpose: The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions., Methods: COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data., Results: Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described., Conclusions: These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy., (Copyright © 2012 John Wiley & Sons, Ltd.)
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- 2012
- Full Text
- View/download PDF
19. Pediatric phase I trial and pharmacokinetic study of dasatinib: a report from the children's oncology group phase I consortium.
- Author
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Aplenc R, Blaney SM, Strauss LC, Balis FM, Shusterman S, Ingle AM, Agrawal S, Sun J, Wright JJ, and Adamson PC
- Subjects
- Administration, Oral, Adolescent, Child, Child, Preschool, Dasatinib, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Hematologic Neoplasms diagnosis, Hospitals, Pediatric, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Maximum Tolerated Dose, Neoplasms pathology, Patient Selection, Pediatrics, Philadelphia, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Pyrimidines adverse effects, Risk Assessment, Thiazoles adverse effects, Treatment Outcome, Young Adult, Hematologic Neoplasms drug therapy, Neoplasms drug therapy, Pyrimidines administration & dosage, Pyrimidines pharmacokinetics, Thiazoles administration & dosage, Thiazoles pharmacokinetics
- Abstract
Unlabelled: PURPOSE Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-β receptor. Dasatinib was found to have selective activity in several tumor models in the Pediatric Preclinical Testing Program. PATIENTS AND METHODS A phase I study of dasatinib in pediatric patients with refractory solid tumors or imatinib-refractory, Philadelphia chromosome-positive leukemia was performed. Dose levels of 50, 65, 85, and 110 mg/m²/dose, administered orally twice daily for 28 days, with courses repeated without interruption, were studied. Pharmacokinetic studies were performed with the initial dose., Results: A total of 39 patients (solid tumors, n = 28; chronic myeloid leukemia [CML], n = 9; acute lymphoblastic leukemia, n = 2) were enrolled. No dose-limiting toxicities (DLTs) were observed at the 50, 65, and 85 mg/m² dose levels. At 110 mg/m², two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m²), grade 3 diarrhea (85 mg/m²), and grade 2 creatinine elevation (50 mg/m²) were observed. DLT in later courses included pleural effusions, hemangiomatosis, and GI hemorrhage. There were three complete cytogenetic responses, three partial cytogenetic responses, and two partial/minimal cytogenetic responses observed in evaluable patients with CML. CONCLUSION Overall, drug disposition and tolerability of dasatinib were similar to those observed in adult patients.
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- 2011
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20. Survival by race among children with extracranial solid tumors in the United States between 1985 and 2005.
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Johnson KA, Aplenc R, and Bagatell R
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, SEER Program, Survival Rate, Young Adult, Neoplasms ethnology, Neoplasms mortality, Racial Groups statistics & numerical data
- Abstract
Background: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was used to compare survival rates by race among children with common extracranial solid tumors between 1985 and 2005., Procedure: Diagnosis and outcome data were obtained from SEER. Five-year survival probabilities were calculated using the Kaplan-Meier method. Survival hazard ratios were calculated using the Cox proportional hazards model. Survival probabilities were compared among Whites, Blacks, American Indians/Alaskan Natives, and Asians/Pacific Islanders., Results: Five-year survival probabilities were higher for White children than for children belonging to other racial groups (77% vs. 71% for Blacks, 72% for American Indian/Alaskan Native, 72% for Asian/Pacific Islander). Male non-White children had worse 5-year survival than male White children while there were no differences in survival among females across racial groups. There was no difference when survival probabilities for Hispanic and non-Hispanic children were compared. Overall, Black children had a higher risk of death compared to White children (1.31, P < 0.05). Black children had a higher risk of death from germ cell tumors, hepatoblastoma and non-rhabdomyosarcoma soft tissue sarcomas. Asian/Pacific Islander children also had a higher risk of death overall (1.34, P < 0.05) and a higher risk of death from germ cell tumors, hepatocellular carcinoma, neuroblastoma, and Wilms tumor compared to White children., Conclusions: Male children from minority groups have poorer survival from extracranial solid malignancies than White male children. Future efforts should be directed at understanding the causes of these differences and at developing practical clinical interventions to eliminate them., (© 2010 Wiley-Liss, Inc.)
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- 2011
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- View/download PDF
21. A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors.
- Author
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Fox E, Aplenc R, Bagatell R, Chuk MK, Dombi E, Goodspeed W, Goodwin A, Kromplewski M, Jayaprakash N, Marotti M, Brown KH, Wenrich B, Adamson PC, Widemann BC, and Balis FM
- Subjects
- Administration, Oral, Adolescent, Antineoplastic Agents adverse effects, Area Under Curve, Child, Female, Humans, Male, Maximum Tolerated Dose, Quinazolines adverse effects, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacokinetics, Neoplasms drug therapy, Quinazolines administration & dosage, Quinazolines pharmacokinetics
- Abstract
Purpose: To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors., Patients and Methods: Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m(2)/d resulted in de-escalation to 8 mg/m(2)/d and subsequent re-escalation to 12 and 17 mg/m(2)/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria., Results: Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m(2)/d. Subsequently, 8 mg/m(2)/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m(2)/d; one had DLT (grade 3 diarrhea). At 17 mg/m(2)/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non-dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m(2)/d (adult fixed dose equivalent, 20 mg). At 12 mg/m(2)/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC(0-∞)) was 900 ng·h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma., Conclusion: The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m(2)/d administered orally, once daily, continuously. A phase II study is in development.
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- 2010
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22. Pre-transplant lung function is predictive of survival following pediatric bone marrow transplantation.
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Ginsberg JP, Aplenc R, McDonough J, Bethel J, Doyle J, and Weiner DJ
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Predictive Value of Tests, Respiratory Function Tests, Retrospective Studies, Survival Rate, Treatment Outcome, Young Adult, Bone Marrow Transplantation, Lung physiopathology, Neoplasms physiopathology, Neoplasms therapy
- Abstract
Background: Pulmonary toxicity is well described in recipients of bone marrow transplants (BMT), and accounts for a sizeable proportion of post-transplant mortality. The majority of the data on post-transplant pulmonary function is from adults, although several small pediatric case series have been described. In adults, pre-transplant lung function has been predictive of post-transplant respiratory failure and mortality. This use of pulmonary function testing, that is, for pre-transplant risk counseling, is novel but has never been applied to pediatric patients. We hypothesized that in children, as in adults, pre-transplant pulmonary function would also be predictive of outcome post-transplantation morbidity., Procedure: Retrospective database analysis of pulmonary function tests of patients undergoing first myeloablative BMT at two large children's hospitals., Results: Two hundred seventy-three subjects had at least one pre-transplant PFT, and 317 subjects had at least one post-transplant PFT available for analysis. While the majority of patients had normal or mildly reduced pre-transplant flows and lung volume, 25% had moderately or severely reduced diffusion. All lung function parameters decreased post-transplant with a slow improvement over ensuing years. The Lung Function Score, a combined measurement of FEV(1) and DLCO, was highly associated with post-transplant survival. Hazard ratios for mortality (compared to the best LFS) ranged from 1.654 to 2.454., Conclusions: Lung function prior to bone marrow transplant, especially diffusing capacity, is frequently abnormal. Lung function frequently decreases shortly post-transplant and tends to improve over time, but frequently remains abnormal even years after transplant. Post-transplant survival is related to pre-transplant lung function., (Copyright 2009 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
23. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy
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Garcia-Pavia, P, Kim, Y, Restrepo-Cordoba, MA, Lunde, IG, Wakimoto, H, Smith, AM, Toepfer, CN, Getz, K, Gorham, J, Patel, P, Ito, K, Willcox, JA, Arany, Z, Li, J, Owens, AT, Govind, R, Nuñez, B, Mazaika, E, Bayes-Genis, A, Walsh, R, Finkelman, B, Lupon, J, Whiffin, N, Serrano, I, Midwinter, W, Wilk, A, Bardaji, A, Ingold, N, Buchan, R, Tayal, U, Pascual-Figal, DA, De Marvao, A, Ahmad, M, Garcia-Pinilla, JM, Pantazis, A, Dominguez, F, John Baksi, A, O'Regan, DP, Rosen, SD, Prasad, SK, Lara-Pezzi, E, Provencio, M, Lyon, AR, Alonso-Pulpon, L, Cook, SA, DePalma, SR, Barton, PJR, Aplenc, R, Seidman, JG, Ky, B, Ware, JS, Seidman, CE, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Wellcome Trust, Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Imperial College London (Reino Unido), Fondation Leducq, British Heart Foundation, National Institutes of Health (Estados Unidos), Howard Hughes Medical Institute, Fundación ProCNIC, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Department of Health, Royal Brompton & Harefield NHS Foundation Trust, Imperial College Healthcare NHS Trust- BRC Funding, Rosetrees Trust, and The Academy of Medical Sciences
- Subjects
CARDIOTOXICITY ,cardiomyopathies ,Adult ,Male ,Cardiac & Cardiovascular Systems ,FAMILIAL DILATED CARDIOMYOPATHY ,Antineoplastic Agents ,Mice, Transgenic ,TITIN ,1117 Public Health and Health Services ,Cohort Studies ,Mice ,Neoplasms ,A-BAND TRUNCATION ,Animals ,Humans ,genetics ,titin ,Prospective Studies ,AMERICAN SOCIETY ,1102 Cardiorespiratory Medicine and Haematology ,POLYMORPHISMS ,Aged ,Retrospective Studies ,Science & Technology ,CONGESTIVE-HEART-FAILURE ,MUTATIONS ,Genetic Variation ,1103 Clinical Sciences ,CHEMOTHERAPY ,Middle Aged ,medical oncology ,drug therapy ,Mice, Inbred C57BL ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,Female ,ECHOCARDIOGRAPHY ,Cardiomyopathies ,Life Sciences & Biomedicine - Abstract
BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P
- Published
- 2019
24. Merging of NCI-Funded Cooperative Oncology Group Data with an Administrative Data Source to Develop a More Effective Platform for Clinical Trial Analysis and Comparative Effectiveness Research: A Report from the Children’s Oncology Group
- Author
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Aplenc, R, Fisher, BT, Huang, YS, Li, Y, Alonzo, TA, Gerbing, RB, Hall, M, Bertoch, D, Keren, R, Seif, AE, Sung, L, Adamson, PC, and Gamis, A
- Subjects
Male ,Comparative Effectiveness Research ,Adolescent ,Medical Records Systems, Computerized ,Child Health Services ,Infant ,Hospitals, Pediatric ,Medical Oncology ,Article ,National Cancer Institute (U.S.) ,United States ,Young Adult ,Outcome and Process Assessment, Health Care ,Clinical Trials, Phase III as Topic ,Child, Preschool ,Neoplasms ,Costs and Cost Analysis ,Humans ,Organizational Objectives ,Female ,Medical Record Linkage ,Cooperative Behavior ,Child - Abstract
The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions.COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data.Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described.These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy.
- Published
- 2012
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