This Week in Pediatric Oncology
2014-02
Episodes
Monday Feb 10, 2014
Monday Feb 10, 2014
October
13, 2011
Host Dr. Tim Cripe and co-hosts Dr. Lars Wagner
and Dr. Lionel Chow welcome guest Dr. Giselle Sholler on this episode of TWiPO.
Dr. Sholler gives the background to her current research interest in
neuroblastoma, and describes her nifurtimox trials and how she formed the
Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC).
The physicians also discuss the specifics of the personalized medicine
feasibility trial now open for neuroblastoma.
Dr. Sholler is a Pediatric Oncologist with
Spectrum Health Medical Group, Helen DeVos Childrens Hospital, and directs the
Pediatric Oncology Therapeutic Discovery Clinic. She is also Co-Director of the
VARI/TGen Pediatric Oncology Research Program, and Associate Professor of the
Neuroblastoma Translational Research Laboratory at Van Andel Research
Institute. She has a faculty appointment within Michigan State University's
College of Human Medicine, and continues as adjunct faculty at University of
Vermont. Dr. Sholler is also a Guest Researcher in the Pediatric Oncology Branch
at the NCI.
References:
J Clin Oncol. 2010 Nov 20;28(33):4877-83. Epub
2010 Oct 4. Pilot study using molecular profiling of patients' tumors to find
potential targets and select treatments for their refractory cancers.
Science 16 Sept 2011: Vol. 333 no. 6049 pp.
1569-1571. Pushing the Envelope in Neuroblastoma Therapy
Mol Cancer Ther August 2011 10; 1311. A Pilot
Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with
Advanced Cancer
Monday Feb 10, 2014
Monday Feb 10, 2014
October
07, 2011
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.
Please send questions or comments to twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
September
28, 2011
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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twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
August
24, 2011
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
Monday Feb 10, 2014
Monday Feb 10, 2014
August
19, 2011
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
Monday Feb 10, 2014
Monday Feb 10, 2014
August
05, 2011
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. Identification of novel cluster
groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with
gene expression profiling: correlation with genome-wide DNA copy number
alterations, clinical characteristics, and outcome
Blood. 2011 Jun 16. [Epub ahead of print] Key pathways are frequently mutated in high risk childhood
acute lymphoblastic leukemia: a report from theChildren's Oncology Group
Please send all questions or comments to
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
July
12, 2011
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
Monday Feb 10, 2014
Monday Feb 10, 2014
July
07, 2011
"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 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.
Please email questions or comments to
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
June
16, 2011
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
Monday Feb 10, 2014
Monday Feb 10, 2014
June
09, 2011
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