This Week in Pediatric Oncology

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TWIPO #28 ~ Uniting the Childhood Cancer Community

February 10th, 2014

August 15, 2013

TWIPO host Dr. Tim Cripe (Nationwide Children's) and co-hosts speak with Vickie Buenger from Texas A&M University about her role as a childhood cancer advocate. A founding member of the Coalition Against Childhood Cancer, Buenger discusses the organization's principles and future projects to bring the childhood cancer community together.

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TWIPO #27 ~ Advocating for Better Research for our Kids

February 10th, 2014

August 01, 2013

In this new episode, host Dr. Tim Cripe (Nationwide Children's) and co-host Dr. Jeffrey Auletta (Nationwide Children's) interview Solving Kids' Cancer co-founder and Executive Director Scott Kennedy and co-director of research programs Donna Ludwinski. Both Scott and Donna share their personal stories that led them to Solving Kids' Cancer and their shared passion to improve survival for children with the deadliest childhood cancers through research advocacy.

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TWiPO #26 ~ Killer Immunoglobulin Receptor (KIR) Mismatch in Neuroblastoma

February 10th, 2014

May 07, 2012

In this interesting episode, host Dr. Tim Cripe (Nationwide Children's) and co-hosts Dr. Lionel Chow (Cincinnati Children's), Dr. Andy Kolb (AI DuPont), and Donna Ludwinski (Solving Kids' Cancer) quiz Dr Paul Sondel and Dr. Ken DeSantes (both from University of Wisconsin - Madison) on NK cells and the implications of KIR/KIR-ligand mismatch (killer immunoglobulin-like receptor) with regard to immunotherapy treatment of neuroblastoma.

References:

Delgado DC, Hank JA, Kolesar J, Lorentzen D, et al. Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res. 2010 Dec 1;70(23):9554-61. Epub 2010 Oct 8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999644/

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Venstrom JM, Zheng J, Noor N, Danis KE, et al. KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma. Clin Cancer Res. 2009 Dec 1;15(23):7330-4. Epub 2009 Nov 24. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788079/

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Alderson KL, Sondel PM. Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicity. J Biomed Biotechnol. 2011;2011:379123. Epub 2011 May 24. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110303/

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TWiPO #25 ~ Histones in Pediatric Gliomas

February 10th, 2014

April 05, 2012

Host Dr. Tim Cripe welcomes back co-host Dr. Lionel Chow to discuss somatic mutations in pediatric brain tumors. After recapping the consensus paper on molecular subgroups in medulloblastoma discussed in TWiPO episode 22 (Brain Tumor Round Robin) Dr Chow highlights the significance of the driver mutations in histone H3.3 in pediatric glioblastoma. Results of whole exome sequencing have shown that significantly more somatic mutations are present in adult tumors compared to pediatric tumors. This difference might suggest a reason for better success rates in pediatric tumors and possibly more escape mechanisms in adult tumors. Dr. Chow also discusses a paper published by the Pediatric Cancer Genome Project (a St. Jude Children's Research Hospital–Washington University collaboration) on somatic histone H3 alterations in diffuse intrinsic pontine glioma (DIPG). The findings are significant in showing that this mutation is present in 36% of non-brain stem gliomas and in 78% of brain stem gliomas, but in none of the other pediatric tumor types.

Please send comments and questions to twipo@solvingkidscancer.org

Papers discussed:

Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012 Apr;123(4):465-72. Epub 2011 Dec 2.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306779/

Schwartzentruber J, Korshunov A, Liu XY, Jones DT, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012 Jan 29;482(7384):226-31. doi: 10.1038/nature10833. http://www.ncbi.nlm.nih.gov/pubmed/22286061

Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012 Jan 29;44(3):251-3. doi: 10.1038/ng.1102. St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project.http://www.ncbi.nlm.nih.gov/pubmed/22286216

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TWiPO #24 ~ Cord Blood Banking: Interview with Machi Scaradavou

February 10th, 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

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TWiPO #23 ~ Neuroblastoma Jeopardy 2011

February 10th, 2014

January 26, 2012

In 2011 there were over 1300 new articles published on neuroblastoma in the medical literature.

Join Dr. Tim Cripe and his co-host Dr. Lars Wagner in a fast-paced, in-depth, and comprehensive survey of 18 of the most important papers on neuroblastoma published in 2011. Dr. Cripe and Dr Wagner explore and discuss the compelling evidence reported on a variety of topics, including epidemiology, risk stratification, clinical trials, ALK mutation and expression, new targets, and genetics.

All of the papers discussed are listed HERE with links to PubMed.

Please send all comments and questions to twipo@solvingkidscancer.org

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TWiPO #22 ~ Brain Tumor Year-End Round Robin

February 10th, 2014

December 05, 2011

Join Dr. Tim Cripe and his co-host Dr. Lionel Chow for a fast-paced, in-depth, and comprehensive survey of 15 important recent papers on pediatric brain tumor research, addressing medulloblastoma, ependymomas, and gliomas. Dr. Cripe and Dr. Chow explore and discuss the compelling evidence reported on a variety of topics, including viral causes and therapeutic implications, biomarkers, genomics, proteomics, targets, classification, risk stratification, treatment side-effects, proton-beam radiation therapy, and results of recent clinical trials.

This robust review of current research includes all of the following papers [click link], listed by timed location in the podcast.

Please send all comments and questions to twipo@solvingkidscancer.org

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TWiPO #21 ~ Interview with Dr. Beatrice Lampkin

February 10th, 2014

November 29, 2011

Dr. Tim Cripe and co-hosts Dr. Maureen O'Brien and Dr. Raj Nagarajan interview a pediatric hematology/oncology legend, Dr. Beatrice Lampkin, who served as Director of Cincinnati Children's Division of Hematology/Oncology in the 1970’s. This enlightening and inspiring discussion explores her career and her contributions to leukemia therapy and the challenges she faced as an early leader in the field as a female. She describes her experience with polio, paralysis from the neck down, crutches for mobility, and later, her confinement to a wheelchair. Revealing another era in communications with parents and patients in the 1960s and 1970s, she explains how parents were advised to use the term "anemia" to describe their child's condition rather than "leukemia" to to explain why the child would require periodic blood transfusions, in order to prevent shunning by friends and family. Dr. Lampkin also shares her satisfaction in following the earliest survivors of pediatric cancer she treated who are now in their 40s and 50s.

As if all that isn't inspiring enough, she describes her busy retirement in which she continues to teach the Cincinnati Children's Hospital fellows how to examine blood and bone marrow smears under the microscope and her work in the founding of the GLAD House (http://www.gladhouse.org/), a sanctuary to help drug-addicted youth get off the streets.

Please send all comments and questions to twipo@solvingkidscancer.org.

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TWiPO #20 ~ The F-word in Pediatric Cancer Research

February 10th, 2014

November 15, 2011

Today’s episode features an impressive lineup for a hot topic. Host Dr. Tim Cripe warns: “If your blood isn’t boiling by the end, you weren't listening.” Hear Tim and co-host Dr. Lionel Chow discuss pediatric cancer research funding with guests Dr. C. Patrick (Pat) Reynolds, Dr. E. Anders (Andy) Kolb, and parent Joe McDonough.

Dr. Pat Reynolds puts government spending on the number one disease killer of children in the US in perspective, comparing the tiny $200M spent on pediatric cancer research to the foreign aid budget of $22B (less than 1%). For example, $1.6B goes to Egypt alone. The COG budget is a mere $46M. The DOD budget is $700B. See his slides here. Dr. Lionel Chow mentions an enlightening fact – private donations to St Jude exceed $600M per year, on top of the givers’ paying taxes. This is 3 times the entire NCI budget for pediatric cancer research for all institutions in the US.

Spending per Person Years Life Lost is compared for childhood cancers and adult cancers, see graph here.

Dr. C Patrick Reynolds is Director, Cancer Center and Professor of Cell Biology & Biochemistry, Internal Medicine, and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock TX. Dr. E Anders 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, Wilmington, DE. Joe McDonough is father to Andrew, and founder of The Andrew McDonough B+ (Be Positive) Foundation, raising money for families and research.

Please send comments to twipo@solvingkidscancer.org

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TWiPO #19 ~ More on Hedgehog signaling, brain tumor risk from cell phone use, and FDA approval of cancer drugs

February 10th, 2014

October 30, 2011

Several 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.

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TWiPO #18 ~ Targeting EWS-FLI1 in Ewing’s Sarcoma: Interview with Dr Jeff Toretsky

February 10th, 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

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TWiPO #17 ~ Personalized medicine: Interview with Dr Giselle Sholler

February 10th, 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

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TWiPO #16 ~ Genetic Underpinnings of Ewing Sarcoma: Interview with Dr Stephen L. Lessnick

February 10th, 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

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TWiPO #15 ~ MicroRNAs and hereditary cancer

February 10th, 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

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TWiPO #14 ~ Interview with Dr Kate Matthay

February 10th, 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

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

February 10th, 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

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

February 10th, 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

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

February 10th, 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

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TWiPO #10 ~ Interview with Dr Robert Seeger

February 10th, 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

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TWiPO #9 ~ Interview with Dr Peter Adamson

February 10th, 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

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