This Week in Pediatric Oncology
children
Episodes
Monday Feb 10, 2014
Monday Feb 10, 2014
October
03, 2013
Dr. Joseph Neglia (University of Minnesota) is
nationally and internationally recognized for his contributions to the field of
childhood cancer long-term effects. He is the featured guest in this week's
podcast episode, and answers questions from host Dr. Tim Cripe (Nationwide
Children’s Hospital), and co-hosts Dr. Robyn Dennis (Nationwide Children’s
Hospital), Dr. Andy Kolb (AI DuPont), and Donna Ludwinski (Solving Kids’
Cancer), about late effects and the risk of secondary cancers among childhood
cancer survivors.
Monday Feb 10, 2014
Monday Feb 10, 2014
March
06, 2012
Dr. Tim Cripe welcomes Dr. Andy Kolb from AI
DuPont in this episode of TWiPO, and special guest Dr. Andromachi Scaradavou,
the Medical Director of New York Blood Center's National Cord Blood Program.
NYBC is the world's oldest and largest public
cord blood bank, and collects, processes, tests and stores cord blood that
mothers donate shortly after birth. The cord blood is for children and adults
with no related donor available who need a hematopoietic stem cell transplant
for life-threatening illnesses. More than 60,000 units are stored at NYBC and
more than 4500 units have been provided for transplants worldwide. The variety
of ethic groups represented is much higher in cord blood banking than in bone
marrow donor programs. The percentage of use is climbing significantly for
pediatric transplants partly because of the small dose required.
Discussants cover many aspects of this
fascinating subject: background and uses of cord blood, logistics of
collecting, processing, storing, and selecting units for transplants, as well
as the advantages and challenges currently faced in this field. For more on
NYBC seehttp://www.nationalcordbloodprogram.org/
We welcome all questions or comments at
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
October
30, 2011Several just-published papers in the literature
relate to recent podcast episodes, and host Dr. Tim Cripe and co-host Dr. Lionel Chow review these interesting
developments.
0:55 Hedgehog Signaling: Recent papers
discussing this pathway in neuroblastoma and rhabdomyosarcoma are discussed,
with implications for treatment in these tumor types with itraconozole.
6:40 Cell phone and brain tumor risk: The
controversy concerning criticism by the Environmental Health Trust of a study
showing that cell phone use does not increase risk of brain tumors in children
is explored.
Accelerated approval of cancer drugs by the FDA
and implications for pediatric cancers.
15:30 Brentuximab for two types of lymphoma
21:20 Vemurafenib for melanoma
28:30 Crizotinib for non-small cell lung cancer
(and potential use in neuroblastoma)
42:30 Response to email regarding personalized
medicine TWiPO episode #17 and lab blog for Dr Charles Keller at OHSU
References:
Pediatr Blood Cancer. 2011 Dec 1;57(6):930-8.
doi: 10.1002/pbc.23174. Hedgehog pathway activity in
pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: a report
from the Children's Oncology Group.
Int J Oncol. 2011 Oct;39(4):899-906. doi:
10.3892/ijo.2011.1076. Pharmacological inhibition of
the Hedgehog pathway preventshuman rhabdomyosarcoma cell growth.
Cancer Lett. 2011 Nov 28;310(2):222-31. Inhibition of the sonic hedgehog
pathway by cyplopaminereduces the CD133+/CD15+ cell compartment and the in
vitrotumorigenic capability of neuroblastoma cells.
Cell Phone Study Was Flawed, Say Some Experts by
Roxanne Nelson Medscape Oncology News.
The JNCI Study by Aydin et al on Risk of Childhood Brain Cancer from
Cellphone Use Reveals Serious Health Problems, Environmental Health Trust.
N Engl J Med. 2010 Nov 4;363(19):1812-21. Brentuximab
vedotin (SGN-35) for relapsed CD30-positive lymphomas.
FDA Approves Brentuximab for Two Lymphomas By:
ELIZABETH MECHCATIE, Oncology Report Digital Network.
Clin Cancer Res. 2011 Oct
15;17(20):6428-36. Brentuximab Vedotin (SGN-35).
FDA Approves Vemurafenib for Advanced Melanoma.
By: JANE SALODOF MACNEIL, Oncology Report Digital Network.
N Engl J Med. 2011 Jun
30;364(26):2507-16. Improved survival with
vemurafenib in melanoma with BRAFV600E mutation.
N Engl J Med. 2011 Jun 30;364(26):2547-8. Been
there, not done that--melanoma in the age of molecular therapy. http://www.ncbi.nlm.nih.gov/pubmed/21639809
Biochem J. 2011 Aug 15. Activating ALK mutations found in neuroblastoma are inhibited by
Crizotinib and NVP-TAE684.
N Engl J Med. 2010 Oct
28;363(18):1693-703. Anaplastic lymphoma kinase inhibition in non-small-cell
lung cancer.
Nature. 2007 Aug 2;448(7153):561-6. Epub 2007
Jul 11. Identification of the transforming EML4-ALK fusion gene in non-small-cell
lung cancer.
Science. 1994 Mar 4;263(5151):1281-4. Fusion of a kinase gene, ALK, to
a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
Monday Feb 10, 2014
Monday Feb 10, 2014
October
18, 2011
Host Dr. Tim Cripe and co-host Dr. Lionel Chow
welcome special guest Dr. Jeff Toretsky on TWiPO to discuss his clinical and
research interest in Ewing's sarcoma. Dr. Toretsky explains the challenges of
developing a clinical grade drug from a small molecule for a specific target
such as EWS-FLI1. The small market for a disease like Ewing's creates
formidable hurdles for researchers, yet Dr. Toretsky is driven on by the
question "If I don't do this, who will?" (17:54 mins)
Dr. Jeff Toretsky is Professor of Oncology and
Pediatrics at Georgetown University. He graduated with BS in Biochemistry from
University of Wisconsin, Madison, WI, and recieved his MD from University of
Minnesota, Minneapolis, MN. He completed fellowship training at the NCI
Pediatric Branch.
Please send any questions or comments to
twipo@solvingkidscancer.org
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.
Please send questions or comments to
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