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Dr Tim Cripe and co-hosts Dr Lionel Chow and Dr Lars Wagner welcome special guest Dr Stephen Lessnick for an in-depth discussion on the progress to date in understanding the genetics of Ewing’s sarcoma. The challenges of interpreting the gene expression data as well as the ethics of collecting tumor specimens for research purposes are also explored.

Dr. Stephen Lessnick is a Professor of Pediatrics and Oncological Sciences at the University of Utah, where he also serves as an Attending Physician in Pediatric Hematology/Oncology at Primary Children’s Medical Center in Salt Lake City, UT. He received his PhD in Molecular Biology from UCLA in 1994, and his MD from UCLA in 1996, followed by a residency at Children’s Hospital in Boston, and a fellowship at the Dana-Farber Cancer Institute and Children’s Hospital.  Currently, Dr. Lessnick is the Director of the Center for Children’s Cancer Research at Huntsman Cancer Institute, a Jon and Karen Huntsman Presidential Professor in Cancer Research at the University of Utah, and is the Vice Chair for Biology of the Bone Tumor Committee in the Children’s Oncology Group.

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Join host Dr Tim Cripe with his co-hosts  Drs Jim Geller, Lionel Chow, and Lars Wagner in a robust discussion with special guest Dr Kathryn Wikenheiser-Brokamp on the implications of DICER1, rare tumor registries, and difficult issues surrounding genetic counseling.

Kathryn A. Wikenheiser-Brokamp, MD, PhD, is an Associate Professor in Pathology and Pulmonary Biology at Cincinnati Children’s Hospital Medical Center. Her research is focused on pediatric and adult lung diseases, including cancer. She seeks to determine the molecular mechanisms underlying Rb/p16, p53, and Dicer1 pathway function in lung development and the pathogenesis of lung disease. Dr Wikenheiser-Brokamp holds a PhD in Developmental Biology, Developmental Biology and an MD from University of Cincinnati.

Papers discussed:

DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011 Apr;48(4):273-8.

Extending the Phenotypes Associated with DICER1 Mutations. Hum Mutat. 2011 Aug 31. doi: 10.1002/humu.21600.

Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol. 2011 Aug;122(2):246-50.

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In this enlightening interview with Dr Kate Matthay, a reknown leader in the neuroblastoma research community, host Dr Tim Cripe draws out the inspiration for her early interest in medicine and why her career grew with a focus on neuroblastoma. Dr Matthay explains the history and challenges of clinical research for neuroblastoma:

10:00 challenges in planning and conducting the CCG-3891 double randomized trial questioning the need for transplant and cis-retinoic acid

15:00 discussion of the COG-A3973 trial questioning the need for purged stem cells

15:50 rationale for the COG-ANBL0532 single versus tandem transplant trial

16:13 discussion of the COG-ANBL0032 ch14.18 with cytokines trial

18:00 MIBG COG pilot trial

22:00 work with SIOP and NB protocol development for children in Morocco (N Africa)

Please send any questions or comments to twipo@solvingkidscancer.org

TWiPO Episode 14

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Host Dr Tim Cripe and co-hosts Dr Lionel Chow and Dr Jim Geller discuss updates to previous TWiPO episodes reporting on recent press coverage and publications of BiTE antibodies and modified T-cell approaches, and then discuss recent studies on birth defects, birth order, and cell phone use and possible link to risk of childhood cancers.

N Engl J Med. 2011 Aug 10. Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia.

Sci Transl Med 10 August 2011:  T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia; Vol. 3, Issue 95, p. 95ra73

7:40 Decitabine upregulation of NY-ESO-1 and MAGE family expression in NB. Cancer Immunol Immunother. 2011 May 28. MAGE-A1, MAGE-A3, and NY-ESO-1 can be upregulated on neuroblastoma cells to facilitate cytotoxic T lymphocyte-mediated tumor cell killing Bao L, Dunham K, Lucas K.

9:50 Discussion of Rosenberg paper on immunotherapy in solid tumors; Nat Rev Clin Oncol. 2011 Aug 2.  Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know. Rosenberg SA

13:00 Birth anomolies in CNS pediatric tumors, Pediatrics. 2011 Aug 8

29:00 Absolute risk is small; will this lead to genome-wide association studies?

31:51 Birth order and risk of pediatric cancers, Int J Cancer. 2011 Jun 1;128(11):2709-16

42:30 Mobile phone use and incidence of pediatric CNS tumors. J Natl Cancer Inst. 2011 Aug 17;103(16):1264-76. Epub 2011 Jul 27.

46:47 Listener question about time elapse of planning clinical trials to opening.

Please send any comments or questions to twipo@solvingkidscancer.org

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SIOP’s BuMel results discussed, implications for COG

In this eleventh episode of “This Week in Pediatric Oncology” hosts Dr Tim Cripe and Dr Lars Wagner discuss with guest Dr Brian Weiss (Cincinnati Children’s Hospital) the implications of the recent results comparing two chemotherapy combinations for transplant regimens in children with high-risk neuroblastoma in Europe. The BuMel (busulfan, melphalan) regimen resulted in better survival and lower toxicity than CEM (carboplatin, etoposide, melphalan), a regimen used for transplant in the COG for a decade.

This SIOP trial was one of the plenary presentations at ASCO in June 2011.  In this lively and informative discussion, Dr Brian Weiss explains the COG response to these results due to the difference in induction regimens. The BuMel regimen will be used in the upcoming MIBG frontline pilot that Dr Weiss is leading as principal investigator.

Dr Weiss and TWiPO hosts also discussed the recent paper Safety and efficacy of tandem (131) I-metaiodobenzylguanidine infusions in relapsed/refractory neuroblastoma authored by Johnson et al in Pediatr Blood Cancer. 2011 Apr 14

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Top neuroblastoma researcher discusses career, advances in research

“This Week in Pediatric Oncology” podcast host Dr Tim Cripe interviewed Dr Robert Seeger from CHLA (Children’s Hospital of Los Angeles) about his contributions to improvements in treating neuroblastoma as well as his vision for future advances.

Dr Seeger’s career has been remarkable in that he began with an interest in immunotherapy and neuroblastoma as an intriguing model for this approach, and has consequently been involved in every major advance in treating neuroblastoma, including the pivotal 1984 discovery of the first-ever amplification of an oncogene for any cancer – MYCN and the 1985 demonstration that MCYN could be used to predict survival. Authoring over 180 publications, Dr Seeger has made a significant contribution to every step toward developing better therapies for neuroblastoma, including induction therapy, myeloablative therapy, immunotherapy with anti-GD2 antibody and cytokines, maintenance therapy with retinoids, and most recently, work in tumor microenvironment and developing reproducible biomarkers for detecting minimal residual disease. At the beginning of Dr Seeger’s career, survival for high-risk neuroblastoma was abysmal at about 5%, and now survival is about 45%. Dr Seeger has been a leader in the NANT consortium (New Approaches to Neuroblastoma Therapy) and involved in planning the early phase clinical trials conducted by this 15-member consortium.

When questioned about current challenges in his research, Dr Seeger mentioned the increased regulatory burdens associated with developing new treatments, and also discussed the need for preclinical (mouse) models that are predictive and well-validated. Dr Seeger believes that improvements can be made in functional imaging, including developing pharmacodynamic markers to detect impact of therapy on tumor.

Dr Seeger is Professor and Division Head for Basic and Translational Research at Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles/USC School of Medicine in Los Angeles, CA. His research interests are neuroblastoma risk assessment by gene expression profiling at diagnosis; evaluating response to treatment by quantifying rare neuroblastoma cells in blood and bone marrow; immunotherapy of neuroblastoma (natural killer cells, anti-tumor antibodies, tumor associated macrophages). Dr Seeger is a reviewer for several high-impact oncology journals, and is a member of the COG NB steering committee. He earned his MD at Oregon Health Sciences University School of Medicine in Portland and completed pediatric internship and residency at the University of Minnesota Medical School in Minneapolis. Additionally, Dr Seeger obtained research fellowship training at the National Cancer Institute (NCI) and the ICRF Tumor Immunology Unit at University College London, UK.

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Chair of Children’s Oncology Group (COG) discusses career, drug development

Host Dr Tim Cripe of  ”This Week in Pediatric Oncology” podcast interviews Dr Peter Adamson, new COG Chair. Co-hosts for this episode are Dr Jim Geller, Dr Raj Nagarajan, and Dr Lionel Chow. This conversation includes Dr Adamson’s background and interest in pediatric oncology, and openly addresses the much-needed advances in drug development for pediatric tumors that are distinct from adult tumors.  On the heels of the remarkable ch14.18 development story in neuroblastoma, Dr Adamson explains the need for a “virtual” drug company that consists of a public-private partnership to develop drugs in a similar narrow venue, which is underway.

Reference:

Making Better Drugs for Children with Cancer. Institute of Medicine Consensus Report. Peter C. Adamson, Susan L. Weiner, Joseph V. Simone, and Hellen Gelband, Editors. April 18, 2005

Background:

Dr Adamson was elected by principal investigators of more than 200 Children’s Oncology Group sites. COG includes more than 5,000 experts in childhood cancer at leading children’s hospitals, universities and cancer centers across North America, Australia, New Zealand and Europe.

In 1999 Dr. Adamson came to The Children’s Hospital of Philadelphia (CHOP) from the National Cancer Institute (NCI), and is the director of Clinical and Translational Research and chief of the Division of Clinical Pharmacology and Therapeutics at Children’s Hospital. He also is a professor of Pediatrics and Pharmacology at the University of Pennsylvania School of Medicine. He remains on the staff of Children’s Hospital and on the Penn faculty while serving as Children’s Oncology Group chair.

Dr. Adamson’s previous roles at COG include leading the 21-site phase 1 consortium. During the eight years that Dr. Adamson led this effort, the collaborating sites conducted more than 25 studies designed to test the safety of novel anticancer drugs.

Says Dr Adamson, “I hope to fully leverage the emerging discoveries being made at a rapid pace by transforming how research moves from the bench to the bedside in a very large collaboration.”

Dr. Adamson received his MD from Cornell University and completed his residency at CHOP in 1987. He then spent 10 years at the NCI where he finished his fellowship in Pediatric Hematology/Oncology and Biotechnology, and worked as an investigator and an attending physicians before coming to CHOP.

Please send questions or comments to twipo@solvingkidscancer.org

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An oncolytic virus for a common childhood brain tumor

In this eighth episode of “This Week in Pediatric Oncology” podcast hosts Dr Tim Cripe, Dr Lars Wagner and Dr Lionel Chow discuss a recent publication by researchers at Baylor/Texas Children’s in Houston that shows remarkable results of Seneca Valley virus SVV-001 on orthotopic mouse models of medulloblastoma.

The TWiPO hosts raise many interesting points about this research and highlight the strengths as well as limitations of this work. This exciting research provides new evidence of promise for oncolytic virus therapy for childhood tumors.

For more information about oncolytic virus trials for pediatric cancers, see a recent webinar “Oncolytic Virotherapy for Pediatric Solid Tumors” presented by the principal investigators of five clinical trials in children and sponsored by Solving Kids’ Cancer.

The article discussed in this episode can be found here:

A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models. Yu L, Baxter PA, et al. Neuro Oncol. 2011 Jan;13(1):14-27. Epub 2010 Nov 12.

Another related article by the same group:

Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus. Wadhwa L, Hurwitz MY, et al. Cancer Res. 2007 Nov 15;67(22):10653-6. [fulltext]

Please send questions or comments to twipo@solvingkidscancer.org

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Advances in Target Discovery and Drug Development in Pediatric Cancers

In this seventh episode of “This Week in Pediatric Oncology” TWiPO podcast, host Dr Tim Cripe interviews Dr E. Anders Kolb and Dr Andrew Napper from Nemours in Wilmington, Delaware.

This informative discussion covers the strategies, scope, and challenges of target discovery, drug development, and preclinical testing for pediatric cancers, a complex process that has been accelerated by high throughput screening technology that has only recently become available in academic settings.

Dr Kolb is the Director of Blood and Bone Marrow Transplantation at Alfred I. duPont Hospital for Children, and Head of the Cancer Therapeutics Laboratory at Nemours Biomedical Research. He is also a Principal Investigator in the Pediatric Preclinical Testing Program (PPTP), a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models.

Dr Andrew Napper joined the research team at the Nemours Center for Childhood Cancer Research (NCCCR) in 2009 to establish its High Throughput Screening and Drug Discovery Laboratory. Dr. Napper came to Nemours from the University of Pennsylvania, where he was the Director of High Throughput Screening for the Penn Center for Molecular Discovery, one of the original ten centers established as part of the National Institutes of Health’s Roadmap initiative to discover drugs for neglected diseases.

For more information on this program and technology:

Lab Offer Hope for Kids with Cancer, Wilmington News Journal (8/24/09)

Academic screening goes high-throughput, Nature Methods 7, 787–792 (2010)

This podcast is sponsored by Solving Kids’ Cancer. Please send questions and comments to twipo@solvingkidscancer.org

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An icon in pediatric oncology: Dr Archie Bleyer interviewed on TWiPO

In this sixth episode of TWiPO, Dr Tim Cripe interviews Dr Archie Bleyer about his career and research interest in improving survival rates in adolescents and young adults (AYA) affected by cancer.

Dr Bleyer  is the Medical Director of , Clinical Research at St. Charles Cancer Care in Bend, Oregon and a Clinical Research Professor at Oregon Health & Sciences University in Portland. He also is a Professor of Pediatrics at The University of Texas Medical School at Houston and Senior Advisor of the Aflac/CureSearch Adolescent and Young Adult Cancer Research, and founding member of the LiveStrong Young Adult Alliance.

Dr. Bleyer chaired the Children’s Cancer Group for 10 years, then the world’s largest pediatric cancer research organization, and the Department and Division of Pediatrics at the University of Texas MD Anderson Cancer Center.  He was the American Cancer Society Professor of Clinical Oncology and in charge of the cancer curriculum in the University of Washington School of Medicine. During the past three decades, Dr. Bleyer was awarded research grants totaling more than $75 million as a principal investigator from the National Institutes of Health, the American Cancer Society, and the Leukemia Society of America. His research has been published in more than 300 peer-reviewed articles, chapters, and books.

This is an inspiring and enlightening discussion of the progress and challenges of the past 3 decades of treating children and young adults with cancer, and an optimistic view of future improvements in survival, quality of life, and reducing late effects in survivors. Listeners are welcome to send thoughts and comments to twipo@solvingkidscancer.org