This Week in Pediatric Oncology

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  1. TWiPO #13 ~ Updates, epidemiology of CNS tumors, birth order, and cell phone risks

    10 februari 2014 · 51 min

    Afspelen
    August
    19, 2011
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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. MAGE-A1, MAGE-A3, and NY-ESO-1 can be upregulated on neuroblastoma cells
    to facilitate cytotoxic-T lymphocyte-mediated tumor cell killing,
    K Lucas

    9:50 Discussion of Rosenberg paper on
    immunotherapy in solid tumors; Nat Rev Clin Oncol. 2011 Aug 2. doi:
    10.1038/nrclinonc.2011.116. Cell transfer immunotherapy for
    metastatic solid cancer-what clinicians need to know.
    Rosenberg SA

    13:00 Birth anomolies in CNS pediatric tumors

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

    31:51 Birth order and risk of
    pediatric cancers

    42:30 Mobile phone use and incidence
    of pediatric CNS tumors.

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

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

  2. TWiPO #12 ~ ALL: Anti-CD19 BiTE and Genetic Risk Groups

    10 februari 2014 · 46 min

    Afspelen
    August
    05, 2011
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    Host Dr. Tim Cripe and co-host Maureen O’Brien
    discuss recent papers on immunotherapy and DNA sequencing studies revealing new
    potential targets in acute lymphoblastic leukemia (ALL).

    1:45 min. Results
    on use of BiTE antibody (Bi-specific T-cell engaging) blinatumomab in adults
    with lymphoma and leukemia:

    Exp Cell Res. 2011 May 15;317(9):1255-60. Epub
    2011 Mar 16. Immunomodulatory therapy of
    cancer with T cell-engaging BiTE antibody blinatumomab

    J Clin Oncol. 2011 Jun 20;29(18):2493-8. Epub
    2011 May 16. Targeted therapy with the
    T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal
    residual disease in B-lineage acute lymphoblastic leukemia patients results in
    high response rate and prolonged leukemia-free survival.

    Use of blinatumomab in pediatrics was recently
    reported in Germany, and an international phase I/II trial for pediatrics is
    due to begin accruing this year.

    Leukemia. 2011 Jan;25(1):181-4. Epub 2010 Oct
    14. Complete remission after
    blinatumomab-induced donor T-cell activation in three pediatric patients with
    post-transplant relapsed acute lymphoblastic leukemia.

    23:00 min. Recent
    findings from the TARGET Initiative (Therapeutically Applicable Research to
    Generate Effective Treatments) http://target.cancer.gov/

    Through NIH's TARGET initiative, scientists
    sequenced 120 candidate genes in 187 high-risk childhood B-precursor acute
    lymphoblastic leukemias (HR B-ALL) and normal tissues and combined the results
    with data from previous studies using microarry and gene copy number studies.
    Sorting through this massive amount of information revealed a high frequency of
    recurrent genetic alterations in several specific cancer signaling pathways.
    The information appears to be useful to stratify these patients into
    subcategories, some of whom do much better than others. These data highlight
    potential new therapeutic targets in certain subsets of childhood ALL.

    Blood. 2010 Dec 2;116(23):4874-84. Epub 2010
    Aug 10. Identificat…

  3. TWiPO #11 ~ BuMel SIOP results and MIBG transplant with Dr Brian Weiss

    10 februari 2014 · 30 min

    Afspelen
    July
    12, 2011
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    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

    Please send questions and comments to
    twipo@solvingkidscancer.org

  4. TWiPO #10 ~ Interview with Dr Robert Seeger

    10 februari 2014 · 28 min

    Afspelen
    July
    07, 2011
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    "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-everamplification 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 Scho…

  5. TWiPO #9 ~ Interview with Dr Peter Adamson

    10 februari 2014 · 41 min

    Afspelen
    June
    16, 2011
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    Host Dr. Tim Cripe of "This Week in
    Pediatric Oncology" podcast interviews Dr. Peter Adamson, new Chair of the
    Children's Oncology Group (COG). 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, 2005http://www.iom.edu/Reports/2005/Making-Better-Drugs-for-Children-with-Cancer.aspx

    Please send questions or comments to
    twipo@solvingkidscancer.org

  6. TWiPO #8 ~ Seneca Valley virus and medulloblastoma

    10 februari 2014 · 19 min

    Afspelen
    June
    09, 2011
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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

  7. TWiPO #7 ~ Interview with E. Anders Kolb and Andrew Napper on drug development

    10 februari 2014 · 31 min

    Afspelen
    June
    02, 2011
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    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)

    Please send questions and comments to
    twipo@solvingkidscancer.org

  8. TWiPO #6 ~ Interview with Dr Archie Bleyer

    10 februari 2014 · 33 min

    Afspelen
    May
    26, 2011
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    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

  9. TWiPO #5 ~ Hedgehog Signaling and Itraconazole

    10 februari 2014 · 29 min

    Afspelen
    May
    19, 2011
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    Discussion of the role of hedgehog signaling
    and repositioning of drugs for pediatric cancers such as anti-fungal drug
    itraconazole

    In this fifth episode, hosts Dr. Tim Cripe and
    Dr. Maureen O'Brien discuss the role of targeting of hedgehog signaling in
    diffuse intrinsic pontine glioma (DIPG) and the use of drugs designed for other
    uses -- designed for other uses -- such as itraconazole, an anti-fungal drug
    found to suppress hedgehog signaling -- as a possible treatment for
    medulloblastoma.

    1:20 feedback and comments on previous TWiPO
    episode

    2:58 Hedgehog-responsive candidate cell of origin for diffuse intrinsic
    pontine glioma; (fulltext) Proc Natl Acad Sci U S A. 2011
    March 15; 108(11): 4453–4458

    9:22 Itraconazole,
    a commonly used antifungal that inhibits Hedgehog pathway activity and cancer
    growth. Cancer Cell. 2010 Apr 13;17(4):388-99.

  10. TWiPO #4 ~ Meetings Recap and Immunotherapy for Synovial Cell Sarcoma

    10 februari 2014 · 34 min

    Afspelen
    May
    08, 2011
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    In this fourth episode of TWiPO host Dr. Tim
    Cripe and co-host Dr. Jim Geller discuss updates after two recent meetings and
    then discuss an exciting paper just published on "Tumor regression in
    patients with metastatic synovial cell sarcoma and melanoma using genetically
    engineered lymphocytes reactive with NY-ESO-1" J Clin Oncol. 2011 Mar
    1;29(7):917-24. Epub 2011 Jan 31. by Paul Robbins and
    colleagues at the NCI.

    1:23 Conference
    on oncolytic viruses (see recent http://vimeo.com/20002455 webinar on pediatric
    trials).

    7:28 Conference
    on DIPG (Diffuse Intrinsic Pontine Glioma) at Cincinnati Children's; discussion
    on biology, new tumor models, and genetic profiling.

    12:50 Discussion
    on adoptive immunotherapy using tumor-infiltrating lymphocytes in patients with
    metastatic melanoma and synovial cell sarcoma.

    28:28 Listener
    email questions and answers. (send emails to twipo@solvingkidscancer.org)

  11. TWiPO #3 ~ Vincristine Pharmacogenetics, Irinotecan/Temozolomide for Relapsed Neuroblastoma

    10 februari 2014 · 33 min

    Afspelen
    April
    25, 2011
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    In this third episode, host Tim Cripe, MD, PhD,
    asks his co-hosts to discuss two recent papers that provide new information
    about genetic predisposition to increased toxicity to vincristine in some
    children, and the results of a phase II study using a combination therapy
    (irinotecan and temozolomide) in relapsed or refractory neuroblastoma.

    1:24 Maureen
    O'Brien, MD discusses "Increased risk of vincristine neurotoxicity
    associated with low CYP3A5 expression genotype in children with acute
    lymphoblastic leukemia" in Pediatr Blood Cancer. 2011 Mar;56(3):361-7.
    doi: 10.1002/pbc.22845. Epub 2010 Nov 11.http://www.ncbi.nlm.nih.gov/pubmed/21225912

    22:10 Lars
    Wagner, MD discusses "Phase II study of irinotecan and temozolomide in
    children with relapsed or refractory neuroblastoma: a Children's Oncology Group
    study" from J Clin Oncol. 2011 Jan 10;29(2):208-13. Epub 2010 Nov
    29. http://www.ncbi.nlm.nih.gov/pubmed/21115869

  12. TWiPO #2 ~ Interview with Greg Reaman

    10 februari 2014 · 40 min

    Afspelen
    April
    13, 2011
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    In this second episode of TWiPO, host Dr. Tim
    Cripe interviews Dr. Gregory Reaman about his career in pediatric oncology,
    leadership of the COG, challenges, and expectations for the future.

  13. TWiPO #1 ~ Epidemiology of Childhood Cancer

    10 februari 2014 · 44 min

    Afspelen
    April
    11, 2011
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    Solving Kids' Cancer is sponsoring a free
    podcast series for researchers, clinicians, advocates, and others focusing on
    pediatric cancer research, hosted by physician-scientist Dr. Timothy Cripe and colleagues at Cincinnati Children's.
    Podcasts will be published 2 to 4 times per month with discussions on new
    publications, clinical trials, interviews with thought leaders, and more.

    This
    first episode is a discussion among the pediatric oncologists about the
    recently published paper in Journal of Clinical Oncology "Outcomes for
    Children and Adolescents With Cancer: Challenges for the Twenty-First
    Century" (J Clin Oncol 28:2625-2634)