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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

Please send questions and comments to twipo@solvingkidscancer.org

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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.

Please email questions or comments to twipo@solvingkidscancer.org

Milestones and metrics for June 2010 – June 2011

Looking back at the idea formulated in discussions with John Rogers and Graeme Tucker (see About) last June at the Advances in Neuroblastoma Research meeting, I see we have accomplished some of what we set out to do, and come up short in some areas.

Shortcomings and successes

It is harder to write quality, in-depth analysis of current research than I thought.  After ASCO 2010 I had over 70 pages of notes and spent countless hours viewing the virtual meeting presentations, but only managed to post on a few of the topics. Because it is so time-consuming to do literature searches of background publications for reference, the first year total of posts stands at only 61, which is only a little more than once per week. My goal was at least 3 posts per week.

Is there really that much happening in the neuroblastoma research world? You bet! PubMed shows neuroblastoma articles in the last 12 months tops 1260+ publications. That is 24 per week! That does not include interesting industry news, reports on presentations at meetings, or clinical trial openings.

Consequently we have a goal to pick up the pace for year 2. It would be wonderful to have guest writers contribute regularly. (Contact NB Globe if you or anyone you know would like to contribute an article!)

Even with infrequent posts, the response metrics shown by Google analytics has been very encouraging. In the 10.5 months Google analytics has been tracking visitors, there have been 15,740 unique visitors and 57,691 page views and over 50% arrive from search engines.  The US and Canada represent 73% of the visits and 18% are from Europe. Many of the domains of visitors are from universities and research institutions.

Hubspot has a free “website grader” that grades us poorly for the infrequent posts, and thinks the readability level is too high:

E. Readability Level: Advanced / Doctoral Degree

Really? I would love to have feedback on this — is the readability too high?

The opportunity to host the podcast by Dr Tim Cripe for Solving Kids’ Cancer is an exciting development and episode downloads now exceed 950x!

Meeting mania

Is it possible to attend too many meetings? Attended since June 2010:

• ASCO 2010 Chicago June
• ANR 2010 Stockholm June
• CNCF 2010 Chicago July
• FDA patient rep workshop DC Sept
• SIOP 2010 Boston Oct
• NANT 2011 Los Angeles Feb
• AACR 2011 Orlando April
• ASCO 2011 Chicago June

Travel was generously supported by partner foundations, my family, FDA, ASCO, and AACR. In fact, because of this site, I was able to get a press pass to AACR!

The rest of 2011 includes presentations invited to give at:

• UK NB parent meeting in London — on history of NB clinical trials and current research
• APHON (Association of Pediatric Hematology/Oncology Nurses) in Los Angeles — on parent decision making and expectations when enrolling children in phase I and phase II trials
• SIOP in Auckland —  on research news source for parents of children with neuroblastoma

An educational year

I have learned some interesting things along the way. Some information is repeated, repeatedly. I saw three presentations last year on MIBG and Curie scoring at three different meetings, and several variations on the ALK mutation, expression, and inhibition research. Repetition certainly helps me learn incrementally and cements the content in place!

I also found it was essential to explore the bigger picture of pediatric oncology with regard to drug development and regulation, clinical trial design and interpretation, overlap of research in other solid tumors informing different disease groups, bioethics, psycho-oncology, palliative care research, and so many other related topics because they have filled in the gaps of my understanding with my narrow focus on neuroblastoma. It has indeed been an intense education and I am looking forward to year 2.

Caution: good information is not enough

Ultimately, the children who suffer this dread disease are the focus and reason for this work. I believe this is a worthwhile endeavor.

But unfortunately, good information is not enough. Some parents, like me, have an insatiable desire to learn all there is to know about neuroblastoma and its treatment after their child is diagnosed. Sadly, this does not guarantee a good outcome.  A strong caution is offered here: find a medical team you trust.

Being an informed parent will enhance communication with your child’s oncologist and help you provide the best possible care for your child.  My own experience involved a difficult struggle with this issue.  Two years of no sleep after my son relapsed—staying up all hours reading and researching—I was a basket case fighting for his life and stressed to the limit. I was ultimately saved by another parent’s cautionary tale. Their doctor had gently warned them that if they never decided to trust a physician—and took full responsibility upon themselves—the consequences would be severe in blaming themselves if the outcome was not good.

This hit me like a ton of bricks.  I suddenly realized how unrealistic my endeavors and expectations were—I was not and never will be an oncologist. The conscious decision to trust our medical team was made at that moment.  I remained every bit as engaged in care and treatment decisions, of course, but I realized it was not up to me to save my son. We all did our very best. Because of this firm understanding I emphatically believe that my son had the best possible care, and therefore have no regrets.