Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC) moves to Grand Rapids, Michigan May 2, 2011

Dr Sholler completed medical school at New York Medical College, in Valhalla, NY. She was a resident in pediatrics and a fellow in pediatric hematology/oncology at Brown University before moving to the University of Vermont in 2005. Her research focuses on new therapies for neuroblastoma and medulloblastoma.

She describes her transition to new her position at Van Andel Research Institute (VARI) in an interview at AACR:

1.  Would you describe your new role at VARI, and continuing responsibilities at the University of Vermont and the NCI?

I will be Pediatric Oncologist, Spectrum Health Medical Group, Helen DeVos Children’s Hospital, Directing the Pediatric Oncology Therapeutic Discovery Clinic, focusing on NB and MB patients enrolling on our NMTRC trials and profiling all patients diagnosed with cancer and all relapses; Co-Director of the VARI/TGen Pediatric Oncology Research Program; and Associate Professor of the Neuroblastoma Translational Research Laboratory at Van Andel Research Institute. I will have a faculty appointment within Michigan State University’s College of Human Medicine.  I will continue as adjunct faculty at University of Vermont to continue key collaborations studying genomic profiles in neuroblastoma patients (with Jeff Bond) and work in Phage-display creating individualized antibodies (with David Krag).  I will continue as a Guest Researcher in the Pediatric Oncology Branch at the NCI where we will open the molecularly-guided protocol and I will be seeing NB patients in clinic monthly.

2.  How will this move enhance your goals for your research?
The Van Andel Research Institute is providing significant support and infrastructure to our research and consortium with a 5 year commitment.  The resources and collaboration at the Van Andel (with Craig Webb) and NCI (with Javed Khan and Melinda Merchant) has allowed this research to move forward, especially in the area of molecularly-guided therapy. I am thankful to have such a great team around us and this move will allow the research to flourish at an even faster rate.  Our goal are to bring understanding to each patients tumor and direct therapies to them as well as making promising new drugs available to kids with NB and MB.

3. During your time in Vermont, much has been accomplished. What is the most satisfying to you?
During my time in Vermont I have seen the creation of a new consortium  and the  bringing together of families and researchers for a common goal. It has been incredible to be a part of this evolving from nothing and out of many people caring about these children.  I am most satisfied to have been able to help many children in bringing them new therapies, I know that from this we will be able to improve the lives of kids with neuroblastoma.

4.  How will your move to VARI affect the operations of the NMTRC?
The Van Andel will now be the lead administrative site for the NMRTC, providing us with significant infrastructure which was minimal before and supported by family foundations. Now that money can go directly to supporting new research and trials. Dr. Jeff Trent, President and Research Director fo the Van Andel Research Instittue and TGen is devoted to making a difference in pediatric cancer and with his support and guidance I am excited about the possibilities of what we can do.

5.  Could you provide an update on the personalized medicine program you initiated?
We have completed our pilot study of molecularly-guided therapeutics showing it is possible in real-time to perform a biopsy, run a gene chip, analyze this using computer algorithms, hold a national tumor board to discuss the patient and create individual treatment plans in less than 2 weeks. We now have FDA approval for  a treatment study and IRB approval at 5 centers (DeVos Children’s Hospital, NCI, St. Louis Univeristy, Levine Children’s, and MDAnderson Orlando) and will be opening this trial in May 2011 when I arrive at the Van Andel.

Symposium for parents and researchers June 23 at VARI

Van Andel Research Institute and the NMTRC welcome all parents, foundations, scientists, and on physicians to attend the third symposium for progress and project updates on June 23rd, 2011 and more details will be forthcoming on the NMTRC site.

Poster presentation by Dr Sholler and colleagues at AACR 2011:

A pilot trial testing the feasibility of using molecular-guided therapy in patients with refractory or recurrent neuroblastoma

The American Association for Cancer Research (AACR) is the oldest and largest scientific organization in the world focused on every facet of cancer research. AACR was founded in 1907 by 11 physicians and scientists interested in research with the goal to “to further the investigation and spread the knowledge of cancer.” Since then, the AACR has grown to 33,000 members and publishes seven peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research, and launched a new journal in 2010, Cancer Discovery.

AACR’s mission is to accelerates progress toward the prevention and cure of cancer by promoting research, education, communication, and collaboration.

The 102nd Annual Meeting 2011 begins April 2 in Orlando FL and will feature over 6000 abstracts presented by basic science, translational, and clinical researchers. Over 17,000 attendees and presenters will learn in a variety of settings: plenary lectures, symposia, minisymposia, workshops, poster sessions, and other formats.

A selection of neuroblastoma-related presentations

Several presentations and posters on neuroblastoma are of interest. Click on the title to see the abstract on AACR site.

4336/4 – Oncolytic reovirus as a novel therapy for neuroblastoma Amelia Kellar, Nicole Redding, Karen Blote, Qiao Shi, Jason Spurrell, Paul Beaudry, Don Morris. University of Calgary, Calgary, AB, Canada Poster Session

4340/8 – Sorafenib induces growth arrest and apoptosis in neuroblastoma cells via inhibition of JAK2/STAT3 and MEK1/2/MAPK (p44/42) signaling pathways Fan Yang¹, Veronica Jove¹, Ralf Buettner¹, Hong Xin¹, Sangkil Nam¹, Tasnim Ara², Yves A. DeClerck², Robert C. Seeger², Hua Yu¹, Richard Jove¹. ¹City of Hope, Duarte, CA; ²The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA Poster Session

4346/14 – Differential response of a novel protein kinase C-iota inhibitor (ICA-1) on neuroblastoma cells Prajit P. Pillai, Mildred Acevedo-Duncan. Univ. of South Florida, Tampa, FL Poster Session

954 – ABCC/MRP multidrug transporters contribute to neuroblastoma biology, pathogenesis and clinical outcome, independently of any role in cytotoxic drug efflux Murray D. Norris¹, Michelle J. Henderson¹, Antonio Porro², Marcia Munoz¹, Nunzio Iraci², Chengyuan Xue¹, Jayne Murray¹, Claudia Flemming¹, Jamie Fletcher¹, Samuele Gherardi², Alan Kwek¹, Amanda Russell¹, Wendy B. London³, Allen B. Buxton³, Lesley Ashton¹, Alan C. Sartorelli⁴, Susan L. Cohn⁵, Manfred Schwab⁶, Glenn M. Marshall¹, Giovanni Perini², Michelle Haber¹. ¹Children’s Cancer Institute Australia, Sydney, Australia; ²University of Bologna, Bologna, Italy; ³University of Florida and Children’s Oncology Group Statistics and Data Center, Gainesville, FL; ⁴Yale University School of Medicine, New Haven, CT; ⁵University of Chicago, Chicago, IL; ⁶German Cancer Research Center, Heidelberg, Germany Minisymposium

4758 – Inhibition of checkpoint kinase 1 (Chk1) as a potential therapeutic for pediatric neuroblastoma Mike R. Russell, Kristina A. Cole, John M. Maris. Children’s Hospital of Philadelphia, Philadelphia, PA Minisymposium

LB-312/3 – Methylated RASSF1a is the first specific DNA marker for minimal residual disease testing in neuroblastoma Janine Stutterheim, Fatima Ait Ichou, Emmy Den Ouden, Rogier Versteeg, Huib N. Caron, Godelieve A.M. Tytgat, C. Ellen Van der Schoot. Sanquin, Amsterdam, Netherlands, Academic Medical Center, Amsterdam, Netherlands

4563/5 – Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma Erica L. Carpenter¹, Elizabeth A. Haglund¹, Adrian K. Chow¹, Andrew C. Wood¹, Lili T. Belcastro¹, James G. Christensen², Marc Vigny³, John M. Maris¹, Mark A. Lemmon⁴, Yael P. Mosse¹. ¹Children’s Hospital of Philadelphia, Philadelphia, PA; ²Pfizer Global Research and Development, La Jolla, CA; ³INSERM, Paris, France; ⁴University of Pennsylvania, Philadelphia, PA Poster Session

LB-366/11 – Patient-derived EBV-immortalized B-lymphocytes are a dominant contaminant of in vitro cultured human neuroblastoma tumor-initiating cells isolated from bone marrow. Sven Påhlman, Sofie A. Johnsson, Alexander Pietras, Caroline Wigerup, Ingrid Øra, Michael Andäng, Kenneth Nilsson, Tor Olofsson, David Gisselsson. Lund Univ., Malmö, Sweden, Lund Univ., Lund, Sweden, Karolinska Institute, Stockholm, Sweden, Uppsala Univ., Uppsala, Sweden Late-Breaking Poster Session

742/26 – Mechanisms of resistance to small molecule inhibition of anaplastic lymphoma kinase in human neuroblastoma Erica L. Carpenter¹, Elizabeth A. Haglund¹, Adrian K. Chow¹, James G. Christensen², John M. Maris¹, Yael P. Mosse¹. ¹Children’s Hospital of Philadelphia, Philadelphia, PA; ²Pfizer Global Research and Development, La Jolla, CA Poster Session

3942/29 – A pilot trial testing the feasibility of using molecular-guided therapy in patients with refractory or recurrent neuroblastoma Giselle L. Saulnier Sholler¹, Javed Kahn², William Ferguson³, Genvieve Bergendahl¹, Erika Currier¹, Shannon Lenox¹, Jeffrey Bond¹, William Roberts⁴, Deanna Mitchell⁵, Don Eslin⁶, Jacqueline Kraveka⁷, Joel Kaplan⁸, Nehal Parikh⁹, Suman Malempati¹⁰, Gina Hanna¹¹, Barton Kamen¹², Craig Webb¹³. ¹University of Vermont, Burlington, VT; ²National Institute of Health, Bethesda, MD; ³St. Louis University School of Medicine, St. Louis, MO; ⁴University of California San Diego School of Medicine, San Diego, CA; ⁵Michigan State University, Grand Rapids, MI; ⁶MD Anderson Cancer Center Orlando, Orlando, FL; ⁷Medical University of South Carolina, Charleston, SC; ⁸Levine Children’s Hospital, Charlotte, NC; ⁹Connecticut Children’s Medical Center, Hartford, CT; ¹⁰Oregon Health & Science University, Portland, OR; ¹¹Inova Fairfax Hospital for Children and Women, Falls Church, VA; ¹²Cancer Institute of New Jersey, New Brunswick, NJ; ¹³Van Andel Research Institute, Grand Rapids, MI Poster Session

1558/6 – Paracrine signaling through Mycn enhances tumor-vascular microenvironment in neuroblastoma Yvan H. Chanthery, W. Clay Gustafson, William A. Weiss. UCSF, San Francisco, CA Poster Session

4350/18 – Translating diagnostic gene expression profiles for pediatric solid tumors Daniel H. Wai¹, Michele R. Wing², Kelley Kneile², Yvonne Moyer², Jonathan D. Buckley³, Robert C. Seeger⁴, Douglas S. Hawkins⁵, Stephen X. Skapek⁶, Timothy J. Triche⁴. ¹Center for Personalized Medicine, Los Angeles, CA; ²The Research Institute at Nationwide Children’s Hospital, Columbus, OH; ³University of Southern California, Los Angeles, CA; ⁴Children’s Hospital Los Angeles, Los Angeles, CA; ⁵Seattle Children’s Hospital, Seattle, WA; ⁶University of Chicago, Chicago, IL Poster Session

5237/25 – Development of organ-selective neuroblastoma cell lines to identify genes mediating bone marrow and liver colonization Zillan Neiron¹, Kacper Jankowski¹, Jayne Murray¹, Sophia Champion², Murray D. Norris¹, Michelle Haber¹, Jamie I. Fletcher¹. ¹Children’s Cancer Institute Australia, Randwick, NSW, Australia; ²University of New South Wales, Kensington, NSW, Australia Poster Session

130/14 – MiR-204 acts as a tumor suppressor in neuroblastoma through down-regulation of the neurotrophic receptor TrkB Jacqueline M. Ryan¹, Amanda Tivnan¹, Isabella Bray¹, Joanna Fay¹, Andrew M. Davidoff², Lorraine Tracey², Raymond Stallings¹. ¹Royal College of Surgeons in Ireland & National Children’s Research Centre, Dublin, Ireland; ²St. Jude Children’s Research Hospital, Memphis, TN Poster Session

4685 – Mechanistic guidance of ALK inhibition for the treatment of neuroblastoma Scott C. Bresler¹, Andrew Wood², Elizabeth Haglund², James Christensen³, John M. Maris², Mark A. Lemmon¹, Yael P. Mosse². ¹University of Pennsylvania School of Medicine, Philadelphia, PA; ²Children’s Hospital of Philadelphia, Philadelphia, PA; ³Pfizer Inc., La Jolla, CA Minisymposium

1808/28 – Neuroblastoma cell lines established from progressive disease that exhibit partial or multi drug resistance are highly sensitive to chimeric receptor scFv(ch14.18)-zeta mediated NK cell killing Diana Seidel¹, Anastasia Shibina², C. Patrick Reynolds², Winfried S. Wels³, Holger N. Lode¹, Nicole Huebener¹. ¹University Medicine Greifswald, Greifswald, Germany; ²Texas Tech University Health Sciences Center, Lubbock, TX; ³Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt, Germany Poster Session

508/4 – Signal transduction and activator of transcription (STAT) 3 is necessary for environment-mediated drug resistance Tasnim Ara¹, Rie Nakata¹, Hiroyuki Shimada¹, Ralf Buettner², Robert C. Seeger¹, Hua Yu², Richard Jove², Yves A. DeClerck¹. ¹USC/Children’s Hospital Los Angeles, Los Angeles, CA; ²Beckman Research Institute/City of Hope, Duarte, CA Poster Session

926 – Whole genome and transcriptome sequencing defines the spectrum of somatic changes in high-risk neuroblastoma Olena Morozova¹, Inanc Birol¹, Richard Corbett¹, Karen Mungall¹, Edward F. Attiyeh², Shahab Asgharzadeh³, Yongjun Zhao¹, Richard A. Moore¹, Martin Hirst¹, Steven Jones¹, Michael D. Hogarty², Sharon Diskin², Yael P. Mosse², Maura Diamond², Richard Sposto³, Lingyun Ji³, Daniela S. Gerhard⁴, Malcolm A. Smith⁴, Javed Khan⁴, Robert C. Seeger³, Marco A. Marra⁵, John M. Maris², the NCI TARGET Initiative. ¹Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; ²Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA; ³Children’s Hospital of Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA; ⁴National Cancer Institute, Bethesda, MD; ⁵Genome Sciences Centre, BC Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Minisymposium

1800/20 – 4-HPR (fenretinide) sensitizes human neuroblastoma cells for antibody-independent and ch14.18-mediated NK cell killing Anastasia Shibina¹, Diana Seidel², Srinivas Somanchi³, Holger N. Lode², Dean A. Lee³, C.Patrick Reynolds¹, Nicole Huebener². ¹Texas Tech Univ. Health Sciences Ctr., Lubbock, TX; ²University Medicine Greifswald, Pediatric Hematology/Oncology, Greifswald, Germany; ³The University of Texas MD Anderson Cancer Center, Houston, TX Poster Session

1423/15 – Effects of DFMO-based combination therapy in advanced stage neuroblastoma Dana-Lynn T. Koomoa, Ingo Lange, Andre S. Bachmann. University of Hawaii, College of Pharmacy, Hilo, HI Poster Session

TARGET Project Team Highlights: Neuroblastoma Javed Khan. National Insts. of Health, Bethesda, MD NCI/NIH-Sponsored Session

NIH15. The NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative: Using Large-Scale Genomics to Identify Novel Therapeutic Targets for Childhood Cancers

Towards a personalized approach to pediatric cancer management: Neuroblastoma as an example John M. Maris. Children’s Hospital of Philadelphia, Philadelphia, PA Major Symposium
Recent Findings from Genomic Analyses of Tumors

5359/30 – Cytotoxicity of MLN8237 and SAHA in pediatric cancer cell lines Jodi Muscal¹, Kathy Scorsone¹, Jeffrey Ecsedy², Stacey Berg¹. ¹Baylor College of Medicine, Houston, TX; ²Millenium Pharmaceuticals, Inc., Cambridge, MA Poster Session

4756 – Exome sequencing of 81 neuroblastomas identifies a wide diversity of somatic mutation Trevor J. Pugh¹, Michael Lawrence¹, Carrie Sougnez¹, Gad Getz¹, Edward Attiyeh², Michael Hogarty², Sharon Diskin², Mosse Yael², Maura Diamond², Shahab Asgharzadeh³, Richard Sposto³, Jun S. Wei⁴, Thomas Badgett⁴, Wendy B. London⁵, Julie Gastier-Foster⁶, Malcolm A. Smith⁴, Daniela S. Gerhard⁴, Robert Seeger³, Javed Khan⁴, Matthew L. Meyerson¹, John M. Maris², NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative. ¹The Broad Institute of MIT and Harvard, Cambridge, MA; ²Children’s Hospital of Philadelphia, Philadelphia, PA; ³Children’s Hospital of Los Angeles, Los Angeles, CA; ⁴National Cancer Institute, Bethesda, MD; ⁵Dana-Farber Cancer Institute and Children’s Oncology Group Statistic and Data Center, Boston, MA; ⁶Nationwide Children’s Hospital, Columbus, OH Minisymposium

Overview of environment: Mediated drug resistance Yves A. DeClerck. USC/Children’s Hospital Los Angeles, Los Angeles, CA Educational Session

New clinical trials using oncolytic viruses for pediatric solid tumors

Solving Kids’ Cancer hosted a fantastic webinar on oncolytic viruses for children with solid tumors January 25, 2011.

All four principal investigators of five trials for children presented–starting with an overview given by Dr Tim Cripe:

• Dr Michael Burke on Seneca Valley virus (NTX-101/SVV-001)
• Dr Timothy Cripe on herpes simplex (HSV1716) and vaccinia (JX-594)
• Dr Corey Raffel on modified measles (MV-CEA)
• Dr E. Anders Kolb on reovirus (Reolysin)

The meeting was recorded and the video is 1 hour and 40 minutes long.

Nearly 100 parents and researchers participated in this live event.

These novel, low-toxicity therapies are advancing quickly and present great promise– perhaps one day children with cancer will be cured without chemotherapy!

Oncolytic Virotherapy for Pediatric Solid Tumors from D Ludwinski on Vimeo.

Paediatric Oncology in Developing Countries (PODC)

Opening Keynote Lecture: Cancer Survival Need Not Be Determined by Income: Lessons from Developing Countries and Focusing on Children ~ Felicia Knaul, United States

Dr Knaul’s talk was extremely eye-opening. She detailed cancer survival rates as a function of per capital income and health spending among developed, developing, and undeveloped countries. What was universally surprising was that the graphs were not at all linear or correlated as expected but rather looked like a scatter plot in each case. There was as much as a 50% spread in survival for the same middle expenditure levels, indicating that although the same resources exist to pay for cancer treatment, some countries perform much better than others. A 2008 BBC news article decried this fact in the UK, citing research on 2 million cancer patients worldwide published in The Lancet.[1]

Nevertheless, looking at the lowest expenditures in undeveloped countries, survival rates were dismal as expected. Elizabeth Van Dyne, a pediatric resident from LA wrote an excellent three part series for The Lancet Student on the PODC presentations (quote includes her original references): [2] [3] [4]

According to the World Health Organization, cancer is the leading cause of death worldwide; it kills more people than tuberculosis, malaria, or HIV/AIDS [1]. The number of annual deaths from cancer is projected to increase by 45% over the next two decades to reach 12 million by 2030 [1]. In 2005, 70% of those who died from cancer lived in middle- or low-income countries [1]. It is particularly difficult to treat cancer in these settings due to the overall lack of resources, which translates into poor diagnostic facilities and late diagnoses, poor pain control, inadequate supportive care, malnutrition, high rates of abandonment of treatment, and infection.

“No child should suffer.” “No child should die unnecessarily.” [2] The undeniable truths professed by Eden Tim on the last day of the SIOP’s 2010 Congress should guide us through strategic execution toward increased rates of cancer survival and effective palliative care. Currently however, whereas survival rates are approximately 75% in high-income countries, less than 20% of children with cancer in middle- or low-income countries typically survive [3]. Furthermore, many of the estimated 100,000 children who die without treatment also suffer without any palliative and analgesic care [3].

Nonetheless, there have been remarkable successes over the last 10 years. Endemic Burkitt lymphoma is treated in Malawi with 4 weeks of chemotherapy (cyclophosphamide and intrathecal methotrexate) that costs in total less than US$ 50, leading to a 48% cure rate [4]. The National Cancer Institute Columbia and Dana-Farber Cancer Institute/Children’s Hospital Boston have focused on having permanent social services, overnight doctor coverage and updated protocols with reduced intensity chemotherapy [6]. These measures dramatically decreased mortality rates during initial treatment [6]. In Recife, Brazil, the 5-year event-free survival rate for acute lymphoblastic leukemia has doubled from 32% to 63% [7].

After attending several presentations in the PODC track, I am left with two powerful impressions:

1.       70% of the world’s children with cancer receive either very substandard care or none at all.

2.       Impressive improvement in care and cures have resulted with training (“Twinning” programs matching hospitals in developed countries with Third World hospitals) using crude adaptations for care, and limited resources.

Nevertheless, a difficult ethical question must be addressed. Why spend limited resources on a “few” children with cancer if there are many children dying of malaria and malnutrition? The surprising answer was not so intuitive for me. Where the most rudimentary cancer care for children has been introduced, the level of basic care for children with other diseases has been dramatically improved. Local institutions are better supported by their governments, and they can attract funds from more sources when they begin to focus on the most curable cancers like Wilm’s tumor and ALL. It is a matter of great prestige for these institutions to be able to offer treatments (however basic) for children with cancer. I was surprised to learn in follow-up discussions with the Director of Outreach at St Jude’s, Dr Scott Howard, that most of the money raised to support newly established programs is raised locally.

In Malawi they measure response to chemo with a tape measure around the abdomen! But the nutritional status of all children in the region has been improved since local doctors have begun to tackle cancer. St Jude’s launched a twinning program where hospitals in US team up with a hospital in a developing country and they send nurses and pediatric oncologists back and forth for training and have weekly tumor boards via skype/teleconferences. Other countries are doing this as well – we heard about a Swedish hospital that teamed up with a hospital in Vietnam. Right now the educational resource cure4kids.org has 24,000 health professionals using it in 175 countries. They also set up a free database for registries to track diagnosis and survival called POND4kids.org. In North Africa a focus on neuroblastoma and retinoblastoma has been added to the study group. Dr Kate Matthay is a key participant in the French-African Pediatric Oncology Group, and she recently spent a year on sabbatical in France and North Africa developing protocols for neuroblastoma.

Twinning sites are shown in this slide (presentation by Dr Quintana at the UICC World Cancer Congress in Shenzhen, China, August 2010): [5]

In the 2009 report on activities of the International Outreach Program at St Jude’s tangible results in increased cure rates are detailed:

The mission of the International Outreach Program (IOP) at St. Jude Children’s Research Hospital is to improve the survival rate of children with cancer and other catastrophic diseases worldwide through the sharing of knowledge, technology and organizational skills. There are an estimated 160,000 newly diagnosed cases of childhood cancer worldwide each year, making cancer the leading cause of childhood death in developing regions of Asia, South and Central America, Africa and the Middle East. During the past 30 years, improvements in therapy have dramatically increased survival rates for children with cancer, yet more than 70 percent of the world’s children with cancer still do not have access to modern treatment. St. Jude strives to address the needs of children with cancer in countries that lack sufficient resources and to help these countries effectively manage their burden of cases. One of the key accomplishments of the IOP in 2009 was the inauguration of a new state-of-the-art children’s cancer center in Guatemala. The Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City was opened at a cost of $4.1 million U.S. through the efforts of the local supporting foundation Ayúdame a Vivir, local government leaders, volunteers, local industry and the IOP. The new center provides 40 inpatient beds, more than doubling the previous capacity. The UNOP anticipates seeing approximately 300 new patients per year and will treat more than 100 patients each day in the outpatient clinic. Since the IOP partnership was initiated in 2000, the survival rate in Guatemala City has greatly improved from 28 percent to 75 percent. The achievement of the Guatemalan program is emblematic of the success that other IOP partner sites may achieve in the future. [6]

Since SIOP represents pediatric oncology worldwide, there was understandably widespread interest at the meeting in advances in care for 70% of the world’s children who do not reside in developed countries. A little goes a long way in these countries. One reason is that the pay for medical professionals and supportive staff is very low. For example, a social worker in India with a Master’s Degree in SW typically earns $250 per month. Treatments are very inexpensive. An allogeneic transplant costs $12,000 in Pakistan (now used primarily for thalassemia), $120,000 in Italy, and $360,000+ in the US.

To summarize, there was a sense of optimism about the efforts underway to improve care and save lives for the vast numbers of children who will benefit greatly from modest investments of time and resources from the resource-rich countries.

It reminds me of the story:

A little boy went out on a beach after a great storm. There were piles of starfish as far as the eye could see. The boy began throwing them back in the water, one by one, as fast as he could. A man standing on the dunes above saw the boy and perceived the futility of the boy’s efforts. He screamed to the boy below him on the shore: “THERE ARE TOO MANY! YOU’LL NEVER MAKE A DIFFERENCE!” and the boy yelled back as he threw another starfish in the ocean: “IT WILL … FOR THIS ONE!”

[2] Van Dyne E, Congress of the International Society of Paediatric Oncology Part 1: “No child should die of cancer!” Lancet Student, November 15, 2010 [link]

[3] Van Dyne E, Congress of the International Society of Pediatric Oncology Part 2: The Strategies and Successes of The “Incurable” Third World. Lancet Student, November 17, 2010 [link]

[4] Van Dyne E, Congress of the International Society of Paediatric Oncology Part 3: HIV-related Malignancies in Children. Lancet Student, November 18, 2010 [link]

5.  St. Jude Children’s Research Hospital International Outreach Program, presentation by Dr Quintana at the UICC World Cancer Congress, Shenzhen, China, August 19, 2010 [slides]

6. International Outreach Program Report of Activities 2009 [link]

Presentations with implications for neuroblastoma

Antiangiogentic agents

Rakesh Jain, Raghu Kalluri, and Marsha Moses talked about angiogenesis and why metastases are promoted when giving antiangiogenetic agents. The agents create hypoxia in the tumor and an interesting series of experiments they performed support the theory that hypoxia drives metastases. Candidate biomarkers have been proposed SDF1-alpha and receptor CXCR4 to help determine which patients may benefit from antiangiogenetic agents and who should not get these agents. In the second presentation they showed a model of how they induced metastases in mice – providing a better understanding of mechanism so it can be blocked. They can induce metastases with both hypoxia-dependent mechanism and hypoxia-independent mechanism.

Validation of survivin as target

Fieke Lamers (Netherlands) gave an interesting presentation on validation of survivin as therapeutic target. They have a drug YM155 by Astellas pharmaceuticals that suppresses survivin, which is highly expressed in most neuroblastomas. They had 24 NB cell lines, some were resistant to YM155 and they found that cyclosporin will sensitize NB lines that show MDR1 resistance to YM155, and then NB will undergo apoptosis in presence of YM155.

The neuroblastoma oral papers (OP2) presented on Friday October 22, 2010 at SIOP in Boston covered a range of topics including prognostic factors, targets, and stem cell contamination. This report will focus on the presentation on prognostic significance of segmental alterations in neuroblastoma tumors.

Accumulation of segmental alterations determines progression in neuroblastoma (O024)

Neuroblastoma tumor biology has long been an intense subject of study because of the heterogeneous nature of this disease. Looking at macro, micro, and genetic features reveals the differences in tumors, and why some children with neuroblastoma survive without treatment and others do poorly with the most intense treatments conceived. Now that technology is accessible to analyze genetic profiles, more precise risk can be assigned, and appropriate treatment given. Further, this analysis allows for understanding the evolution of tumor genetics as relapse and progression occurs.

Gudrun Schleiermacher from France presented on a study of numerical and segmental chromosome alterations in neuroblastoma tumors. This subject was a matter of interest at ANR in Stockholm as well, and this abstract was also presented at ASCO in June.[1]  This topic has been the subject of many abstracts at recent meetings, and several recent publications confirm the importance of this work [2-6].

Prior publication in 2009 from this French group included  a comprehensive overview of the genetic alterations of neuroblastoma and clinical significance. A series of 493 neuroblastoma samples was investigated by array-based comparative genomic hybridization and the analysis identified several types of profiles:

Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.[2]

Caren and collegues (Sweden) also concurred that these studies have:

implications for therapy in different risk groups and stresses that genome-wide microarray analyses should be included in clinical management to fully evaluate risk, aid diagnosis, and guide treatment. [5]

Schleiermacher and colleagues analyzed 394 neuroblastoma tumors with array-based comparative genomic hybridization and linked the results to clinical data for outcomes. The tumor samples included all risk groups, and analysis was performed again in the event of relapse to discover changes in the tumor profile. The study confirmed that neuroblastoma tumors are characterized by two distinct genetic profiles — either numerical or segmental chromosome alterations.

Tumors were first divided into five groups based on genomic aberrations: numerical only, segmental only, MYCN amplified, numerical and segmental, MYCN and numerical. The tumors with only numerical alterations had the best prognosis. No breakpoint pattern was observed in the segmental-only group which contained up to 1000 breakpoints. Seven or more breakpoints portended a worse prognosis, and was an independent factor in multivariate analysis. More breakpoints were correlated with higher age at diagnosis, higher stage of disease, and higher risk of relapse.

Tumors with only numerical alterations at diagnosis frequently acquired segmental alterations upon relapse. This could not be strictly attributed to chemotherapy since tumors treated with surgery only had acquired segmental aberrations. The authors concluded that tumor progression is directly linked to an accumulation of segmental alterations.

References

1. J Clin Oncol. 2010 Jul 1;28(19):3122-30. Epub 2010 Jun 1. Accumulation of Segmental Alterations Determines Progression in Neuroblastoma. PMID: 20516441

2. J Clin Oncol. 2009 Mar 1;27(7):1026-33. Epub 2009 Jan 26.  Overall genomic pattern is a predictor of outcome in neuroblastoma. PMID: 19171713

3. British Journal of Cancer (2007) 97, 238–246.  Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification. [free fulltext]

4. Am J Pathol. 2010 Jun;176(6):2616-25. Epub 2010 Apr 15. 2p24 Gain region harboring MYCN gene compared with MYCN amplified and nonamplified neuroblastoma: biological and clinical characteristics. PMID: 20395439

5. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4323-8. Epub 2010 Feb 9.  High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset. [free fulltext]

6. N Engl J Med 2005; 353:2243-2253.  Chromosome 1p and 11q Deletions and Outcome in Neuroblastoma. [free fulltext]

Travel to this meeting was supported by:

• Lighthouse Laboratories
• Max’s Ring of Fire
• Magic Water
• Friends of Will
• Solving Kids’ Cancer
• Children’s Neuroblastoma Cancer Foundation

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Swedish researchers share the prize at SIOP for winning posters on neuroblastoma

Drs Fredrik Hedborg (Uppsala University) and Catarina Trägar (Karolinska Institute) shared the top prize for neuroblastoma research poster at SIOP 2010.

PH036 Age dependent genotypes in high-risk neuroblastoma: MYCN amplification is a fast track to aggressive disease whereas segmental deletion of 11q implies a more complex, multi-step tumor evolution (p. 896)

Dr Hedborg and colleagues explored the age-dependence of the genetics of aggressive disease in 30 high-risk and 4 intermediate-risk children. MYCN amplification was present in all but one of the 12 youngest children (mean age 29.6 months, range 4 – 30 months) and MYCN amplification was absent in all but one of the 11 oldest (mean age 65.6 months, range 57 – 169 months), and 12/18 of these had 11q loss. This age differential was confirmed by the Swedish Childhood Cancer Registry where mean ages at diagnosis were 29.4 months for MYCN amplified (n=65)  and 54.8 months for MYCN-non-amplified (n=46). Significantly more segmental chromosome aberrations were noted in older children with 11q loss, and this data suggest that two major pathways exist in the development of aggressive neuroblastoma. MYCN-amplification tumors in younger children result from fewer but rapid genetic events, whereas tumors in older children with 11q loss are the result of a slower, multi-step process.

PH038 Differences in biological features and survival improvement between genetic subsets of high-risk neuroblastoma indicate the need of adapted treatment (p. 897)

Dr Trägar and colleagues also looked at Swedish registry data and noted older age for 34 children with 11q deletion (median age 41 months) and longer median survival of 40 months compared to children with MYCN-amplified tumors (median age 22.5 months, median survival 16 months), but both groups had similar 8 year overall survival rate of ~35%.

Survival data were reported as follows:
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The researchers concluded that 11q-deletion tumors present later than MYCN-amplified tumors, but noted that prognosis is similar, and suggest further consideration is needed for therapeutic approaches for 11q-deleted tumors since prognosis has not improved for this group since the 1980s.

Both research teams have contributed to increased understanding concerning the relationship between age and biology of neuroblastoma high-risk tumors.

Travel to this meeting was supported by:

• Lighthouse Laboratories
• Max’s Ring of Fire
• Magic Water
• Friends of Will
• Solving Kids’ Cancer
• Children’s Neuroblastoma Cancer Foundation

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“Meet the Experts” session

Drs Huib Caron (The Netherlands) and Suzanne Shusterman (Boston Childrens/DFCI) presented on MIBG therapy in “Meet the Experts” session Friday Oct 22 and Saturday Oct 23, 2010 at the SIOP meeting in Boston.

Completed and ongoing studies

Dr Caron covered the therapeutic considerations, and Dr Shusterman spoke about the practical and logistic issues surrounding the design of MIBG therapy rooms and handling the radioactive material.

MIBG (meta-iodobenzylguanidine) is a synthetic analogue to norepinephrine, developed in the 1970s at University of Michigan as a potential agent for use in hypertension. It is taken up by 90% of neuroblastomas. The compound (also called iobenguane) is useful for both imaging with I-123 isotope which has a shorter half-life of 13 hours and produces better resolution images, and radiation therapy with I-131 which has a longer half-life of 8 days.

The compound with a radioactive isotope of iodine attached (I-131) is taken up in the NB cell but is not lethal to that cell. The beta particles from I-131 decay kills cells up to 2 mm away, and gamma radiation from decay (as in imaging) reaches 2 m or greater distance, but is not lethal to cells in that path. The resulting beta particle decay “cross-fire” is why MIBG radiation therapy appears to be more effective in clumps of disease rather than in diffuse or trace disease. Dr Caron commented in his presentation that this is why he believes using MIBG radiation therapy at the end of induction with minimal or undetectable disease will have questionable efficacy, and why studies in the Netherlands have used double MIBG treatments at the beginning of induction (1989-1999 in 41 children).[1]   Dr Maris countered in a later conversation that there is evidence of efficacy from a double MIBG therapy study where children who respond completely to the first MIBG therapy receive a second MIBG treatment and do well. He also mentioned that it is very common to see much more disease in a post-MIBG therapy scan, revealing that often the imaging dose of MIBG does not show as much disease, and therefore using MIBG therapy at the end of induction even in children with negative MIBG scans may successfully treat undetectable or trace disease. This question (as well as feasibility) will be addressed by the new frontline pilot study now open in several centers using MIBG at the end of induction with CEM transplant for 49 newly diagnosed high-risk NB (see previous article). The German group GPOH is using MIBG therapy in frontline therapy in the ongoing NB2004 study a the end of induction for children who have remaining MIBG positive primary uptake. This study plan is to accrue 360 children.[2]

Other completed and ongoing studies were reviewed, including an ongoing study using MIBG upfront with topotecan in 15 children, a GPOH study using MIBG + gemcitabine phase I/II for refractory and relapsed NB and should finish within the year. The NANT 2007-03 phase I MIBG + vorinostat trial is based on the fact vorinostat (an HDAC inhibitor) increases the norepinephrine transporter expression, and in mice the combination results showed improved response. In 2006 Matthay et al published in JCO the results of the phase I MIBG + CEM transplant in 24 children where the 3-year event-free survival (EFS) was 30% and the 3-year overall survival (OS) was 60% for primary refractory disease. The dose levels from this study were used in the phase II which was recently completed and preliminary results were presented at ANR in June 2010 in Stockholm by Dr Greg Yanik (OR58). MIBG has been tested at 8 to 18 mCi in various trials. In 2007 a Phase II was published in JCO showing promising effectiveness in 164 relapsed or refractory patients with a median of 3 prior regimens (range 1 – 13).[3]  A study in the UK planned to use topotecan with MIBG for relapsed or refractory NB closed before it accrued. Another NANT phase I study N2004-06 used MIBG with irinotecan and vincristine, and results are pending. In Sweden a study using haploidentical donor transplant with MIBG was completed in 5 children.[4] In France a study is ongoing using topotecan with MIBG in relapsed and refractory children.

Approval status for 131-I MIBG

131-I MIBG is made by Draximage (a division of Draxis Health) in Canada, and another company Molecular Insights makes Azedra (Ultratrace MIBG with no cold contaminants). 131-I MIBG is approved for treatment of neuroblastoma in Europe, but still an investigational new drug (IND) in the US.

Future focus

Conclusions drawn from this session include the fact that MIBG therapy is obviously an important agent in the treatment of neuroblastoma, with a long history of studies completed since the 1980s. An important challenge for all researchers involved is figuring out the optimum way to use this agent. An excellent review published in 2008 by Drs Matthay and Dubois provides more information.[5]

References

1. Eur J Cancer. 2008 Mar;44(4):551-6. Epub 2008 Feb 11. Iodine-131-metaiodobenzylguanidine as initial induction therapy in stage 4 neuroblastoma patients over 1 year of age. PMID: 18267358

2.  Randomized Study of Standard Induction Chemotherapy Versus Topotecan Hydrochloride-Containing Induction Chemotherapy Followed by Myeloablative Autologous Stem Cell Transplantation and Consolidation Therapy With Isotretinoin in Pediatric Patients With High-Risk Neuroblastoma GPOH-NB2004-HR

3. J Clin Oncol. 2007 Mar 20;25(9):1054-60. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. PMID: 17369569

4. Biol Blood Marrow Transplant. 2009 Sep;15(9):1077-85. Epub 2009 Jul 8. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. PMID: 19660720

5. Q J Nucl Med Mol Imaging. 2008 Dec;52(4):403-18. Radiolabeled metaiodobenzylguanidine for imaging and therapy of neuroblastoma. PMID: 19088694

Travel to this meeting was supported by:

• Lighthouse Laboratories
• Max’s Ring of Fire
• Magic Water
• Friends of Will
• Solving Kids’ Cancer
• Children’s Neuroblastoma Cancer Foundation

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Dr Frank Saran from The Royal Marsden in the UK presented on neuroblastoma during the Paediatric Radiation Oncology Society (PROS) education session Wednesday October 20 at the SIOP meeting in Boston. Prior to his presentation we heard from other specialists on the challenges of using radiation for poor-prognosis brain tumors, particularly high-grade glioma. Other brain tumors discussed were ependymoma, supratentorial primitive neuroectodermal tumors (sPNET), and the emerging use of proton radiation. The difficulty of minimizing neurocognitive damage and the grim prognosis for some of these tumors are very sobering. There was no discussion in this session of treatment for brain metastases for non-CNS tumors. There was also a presentation on radiation for Wilm’s tumor.

Dr Saran gave a short history of studies showing why today radiation is a part of standard therapy for high-risk neuroblastoma (but use of TBI was not discussed). Local failure accounted for a large percentage of relapses when chemo-only regimens were used. In unpublished data supplied by Dr Andrew Pearson,  40% of all stage 4 over 1 year relapsed at the primary site in the ENSG5 study. By contrast in 2001 Memorial-Sloan Kettering (MSKCC) published a series of 99 children with only 10% local failure rate. MSKCC uses hyperfractionated radiation 21 Gy in 14 fractions, usually given in two fractions per day to primary sites and additional radiation to some metastases.  The current SIOP NB trial uses 21 Gy in 14 fractions given over 3 weeks.

Dr Saran also listed current efforts to determine the optimum way to give 131-I MIBG radiation. Some investigations address maintaining oxygenation, fractionating treatment, using radiosensitizers, use of carrier-free (Ultratrace), and adding chemotherapy. A recent European trial showed good results when MIBG radiation therapy was given concurrently with topotecan. Several combination trials (chemo with MIBG) are ongoing in the US and in Europe.

Travel to this meeting was supported by:

• Lighthouse Laboratories

• Max’s Ring of Fire

• Magic Water

• Friends of Will

• Solving Kids’ Cancer

• Children’s Neuroblastoma Cancer Foundation

The World of Childhood Cancer

This year Boston MA and Dana-Farber/Boston Children’s will host the 42nd Annual Conference of the International Society of Paediatric Oncology (SIOP) October 20 – 24, 2010. This is the first time this meeting has been held in the US in 17 years.

Next week will be my first return to Boston since my son was treated there for neuroblastoma 1991-1993. I am deeply indebted to the foundations (from AUS, US, and UK) who support this endeavor and have generously granted travel scholarships for me to attend and report on this meeting:

• Lighthouse Laboratories
• Max’s Ring of Fire
• Magic Water
• Friends of Will
• Solving Kids’ Cancer
• Children’s Neuroblastoma Cancer Foundation

Last year the meeting was held October 5-9, 2009 in Sao Paulo Brazil. There were 31 symposia lectures, 174 oral presentations, 535 posters, and 40 publications.[1]

The Société Internationale d’Oncologie Pédiatrique (SIOP) has continental branches for Europe, South America (nations south of Mexico), North America, Asia, Australia, and Africa. ESIOP (Europe) conducts large studies on neuroblastoma in 20 countries including UK and Israel. The first annual general meeting was held in Madrid in 1969 and began with a distinct focus on neuroblastoma among other pediatric cancers. St Jude’s cure4kids site provides access to presentations and education books from each SIOP conference.

The meeting program includes parallel tracks of the following affiliated societies:

• International Confederation of Childhood Cancer Parent Organisations (ICCCPO)
• International Society of Paediatric Surgical Oncology – IPSO
• Paediatric Oncology Developing Countries Committee
• Paediatric Radiation Oncology Society
• SIOP Paediatric Psycho-Oncology Committee
• The SIOP Nurses Committee

This year’s meeting will have over 2000 attendees from 95 countries:

A sampling of the interesting presentations are highlighted below, taken from the 58 page program.

Wednesday

Role of Surgical Resection in the Cure of Neuroblastoma ~ Mike La Quaglia, United States

Neuroblastoma ~ Frank Saran, United Kingdom

Thursday

Traumatic Stress as a Model for Understanding Patient and Parent ~ Plenary Discussion,  Andrea Patenaude, United States

Response to Childhood Cancer ~ Sean Phipps and Anne Kazak, United States

Incidents and Complication of Totally Implanted Vascular Access Devices: A Prospective Study (O017) ~ Jean-Marc Joseph, Christophe Gapany, Stephane Tercier, Manuel Diezi, Switzerland

Communication With Patients About Challenging Topics ~ Chair: Gerry Koocher, United States, Lori Wiener, United States, Helena Kondryn, United Kingdom, Tim Eden, United States, Katryn Cantrell, United States

Role of SIOP in Integrating Psychosocial Care into Routine Pediatric Oncology Treatment and Fostering Pediatric Psycho-Oncology Research on a Global Level ~ Jimmie Holland, United States

Friday

Therapeutic MIBG ~ Huib Caron, The Netherlands and Suzanne Shusterman, United States

Update on Children’s Oncology Group (COG) Studies ~ Thomas Merchant, United States

Update on SIOP Studies ~ Roger Taylor, United Kingdom

Neuroblastoma (OP2) ~ Chairs: Angelika Eggert, Germany and Purna Arun Kurkure, India

Accumulation of Segmental Alterations Determines Progression in Neuroblastoma (O024) ~ Gudrun Schleiermacher, Isabelle Janoueix-Lerosey, Agnès Ribeiro, Jerzy Klijanienko, Jerome Couturier, Gaelle Pierron, Veronique Mosseri, Alexander Valent, Nathalie Auger, Dominique Plantaz, Hervé Rubie, Dominique Valteau-Couanet, Franck Bourdeaut, Valerie Combaret, Christophe Bergeron, Jean Michon, Olivier Delattre,  France

Tumor Cell Detection in Autologous Stem Cell Harvests in Patients with High-Risk Neuroblastoma (O025) ~ Janine Stutterheim1, Florentien E.M. Vree1, Barbara Hero2, Lily Zappeij-Kannegieter1, Carlijn Voermans1, Roswitha Schumacher-Kuckelkorn2, Ulrike Koehl2, Johannes H. Schulte2, Felix Niggli3, Michael C. Fruhwald2, Max M. van Noesel1, Charlotte M. Niemeyer1, Udo Bode2, Freimut H. Schilling2, Christian Schultz2, Norbert Graf2, Michaela Nathrath2, Irene Schmid2, Hubert N. Caron1, Ellen C. van der Schoot1, Godelieve A.M. Tytgat1 ~ 1The Netherlands, 2Germany, 3Switzerland

Validation of Survivin as a Therapeutic Target in Neuroblastoma (O026) ~ Fieke Lamers, Fieke Lamers, Linda Schild, Ida van der Ploeg, Marli Ebus, Jan Koster, Rogier Versteeg, Huib Caron, Jan Molenaar, The Netherlands

Identification of New Candidate Genes in Progression of Neuroblastoma Using Omics Analysis (O027) ~ Eiso Hiyama, Naomi Kamei, Arata Kamimatsuse, Yukina Hirai, Keiko Hiyama, Tsutomu Masujima, Japan

Keynote Lecture: Psycho-Oncology Late Effects in Survivors ~ Mark Chesler, United States
Chairs: Carmen Auste, The Phillipines and Benson Pau, China

Opening Keynote Lecture: Cancer Survival Need Not Be Determined by Income: Lessons from Developing Countries and Focusing on Children ~ Felicia Knaul, United States
Chairs: Gabriele Calaminus, Germany and Lisa Diller, United States

Neuroblastoma: A 20-Year Experience in a UK Regional Center (O057) ~ Adeline Salim, Dhanya Mullassery, Barry Pizer, Heather McDowell, Paul Losty, United Kingdom

Opening Plenary Session: What About the Rest of the Family? ~ Chairs: Melanie Goldish, United States and Simon Lala, New Zealand

Doubled and Silenced: Grandparents’ Experiences of Childhood Cancer (ICCCPO001) ~ Nancy Moules, Doug Strother, Catherine Laing, Dianne Tapp, Canada

The Benefits of Group Psychosocial Activities for Siblings of Cancer Patients: Results of a 7 Year Qualitative Study (ICCCPO003) ~ Deborah Berk, United States

Emotional Difficulties Experienced by Childhood Cancer Patients’ Siblings (PS007) ~ Shubha Maudgal, Veena Shukla, Maitreyl Nigwekar, India

Angiogenesis (S5)
Chairs: Mark Kieran, United States and Stefan Pfister, Germany
Anti-Angiogenesis: Emerging Paradigms and Biomarkers
Rakesh Jain, United States

Tumor Microenvironment Controls the Rate of Cancer Progression and Metastasis
Raghu Kalluri, United States

Matrix Metalloproteinases and Associated Proteins as Biomarkers of Angiogenesis, Tumor Growth and Progression
Marsha Moses, United States

Phase II Study of Low Dose Metronomic (LDM) Cyclophosphamide (CTX) and Vinorlebine (VN) for Recurrent or Resistant Pediatric Tumors (O045)
Odile Oberlin, Annie Rey, Gisele Goma, Daniel Orbach, Anne-Sophie Defachelles, Jean-Claude Gentet, Francoise Mechinaud, Claude Linassier, Pascal Chastagner, Didier
Cupissol, Guy Leverger, Christophe Bergeron, France

Transition of AdV-tk Gene Transfer Approach from Adult to Pediatric Oncology (O046)
Laura Aguilar, Andrea Manzanera, Claudia Moran, Mark Kieran, John Goldberg, Jana Portnow, Pamela New, E. Antonio Chiocca, Estuardo Aguilar-Cordova, Jill Brace-O’Neill, United States

Cancer Patients’ and Parents’ Attitudes towards Banking of Tissues for Research (O047) ~ Steven Joffe, Julie Najita, United States

Late Effects ~ Chairs: Louis Constine, United States and Edward Halperin, United States
Lung ~ Giovanni Scarzello, Italy
Endocrinology ~ Laurie Cohen, United States
Fertility ~ Valerie Bernier, France
Neurocognitive Function ~ Laetitia Padovani, France
Second Malignancies ~ Louis Constine, United States

Nurses Oral Papers II: Parental Perspectives – and Listening to Children and Young People
Chairs: Faith Gibson, United Kingdom and Lisa Morrisey, United States

Children, Parents, and Healthcare Professionals Perspectives on Children’s Participation in Shared Decision Making (O089) ~ Imelda Coyne1, Aislinn Amory1, Faith Gibson2, Gemma Kiernan1, 1Ireland, 2United Kingdom

Adolescent-Parent-Clinician Communication Regarding Cancer-Related Symptoms (O090) ~ Christina Baggott, United States

Weblogs of Parents with a Child Treated for Cancer: Their Intentions and Experiences (O091) ~ Veronique Van de Velde, Ilse Demares, Patricia De Vos, Johan De Porre, Barbara De Moerloose, Yves Benoit, Gino Verleye, Belgium

IPSO – Translational Research and Surgical Strategies of Childhood Solid Tumors
Sponsored by Children’s Hospital Boston
Dietrich von Schweinitz, Germany
Chairs: Jan Godzinski, Poland and Robert Shamberger, United States

Accurate Prediction of Neuroblastoma Outcome Based on miRNA Expression Profiles (O099)
Johannes Schulte1, Benjamin Schowe1, Pieter Mestdagh2, Lars Kaderali1, Prabhav Kalaghatgi1, Stefanie Schlierf1, Joelle Vermeulen2, Bent Brockmeyer1, Kristian Pajtler1, Theresa Thor1, Katleen de Preter2, Frank Speleman2, Katharina Marik1, Angelika Eggert1, Jo Vandesompele2, Alexander Schramm1, 1Germany, 2Belgium

Saturday

Therapeutic MIBG ~ Huib Caron, The Netherlands and Suzanne Shusterman, United States

Workshop on Ototoxicity ~ Chairs: Penelope Brock, United Kingdom and Edward Neuwelt, United States

Predictors of Independent Living after Childhood Cancer: A Report from the Childhood Cancer Survivor Study (O104)
Alicia Kunin-Batson, Nina Kadan-Lottick, Liang Zhu, Cheryl Cox, Veronica Bordes, Deo Kumar Srivastava, Lonnie Zeltzer, Leslie Robison, Kevin Krull, United States

Fatigue, Vitality, Sleep and Neurocognitive Functioning in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study (O106)
Nancy Clanton, James Klosky, Zhenyu Pan, E. Brannon Morris, Neelam Jain, Deo Kumar, Srivastava, Daniel Mulrooney, Lonnie Zeltzer, Marilyn Stovall, Leslie Robison, Kevin Krull, United States

Immunotherapy in Solid Tumors (S12)
Co-Sponsored by Texas Children’s Hospital and the Dunbar Foundation
Chairs: Lisa Diller and Robert Seeger, United States

Vaccine Therapy for Neuroblastoma ~ Chrystal Louis, United States

Adoptive Immunotherapy for Neuroblastoma ~ Laurence Cooper, United States

Allogeneic Transplant in Neuroblastoma: Lessons from a Mouse Model ~ Shifra Ash, Israel

Solid Tumors (OP17)
Chairs: Scott Macfarlane, New Zealand and Arthur Zimmermann, Switzerland

Integrating Diversity-Oriented Synthesis and Expression-Based Screening to Identify New Inducers of Neuroblastoma Differentiation (O143)
Stacey Frumm, Zi Peng Fan, Kenneth N. Ross, Supriya Gupta, Lynn VerPlank, Byung-Chul Suh, Jeremy Duvall, Lisa Marcaurelle, Nicola Tolliday, Kimberly Stegmaier
United States

Deep Sequencing Reveals Differential Expression of microRNAs in Favourable Versus Unfavourable Neuroblastoma (O144)
Johannes Schulte1, Tobias Marshall1, Marcel Martin1, Philipp Rosenstiel1, Pieter Mestdagh2, Stefanie Schlierf1, Theresa Thor1, Jo Vandesompele2, Angelika Eggert1, Stefan Schreiber1, Sven Rahmann1, Alexander Schramm1, 1Germany, 2Belgium

High Expression of the ALK Receptor Tyrosine Kinase Precedes Mutation as a Determining Factor of Unfavourable Phenotype in Primary Neuroblastoma (O145)
Johannes Schulte, Hagen Bachmann, Bent Brockmeyer, Sandra Nowacki, Yvonne Kahlert, Andre Oberthur, Katleen de Preter, Kristian Pajtler, Jessica Theissen, Frank Westermann, Frank Speleman, Jo Vandesompele, Frank Berthold, Angelika Eggert, Barbara Hero, Alexander Schramm, Matthias Fischer, Germany

Toxicity and Efficacy of HDC with BU/MEL and HSCT in High-Risk Neuroblastoma Patients: A Single Center Study (O146)
Stephanie Proust-Houdemont, Ellen Benhamou, Christelle Dufour, Gisele Goma, Nathalie Gaspar, Veronique Minard-Colin, Cormac Owens, Olivier Hartmann, Dominique Valteau-Couanet, France

New Drug Development for Children with Cancer
Sponsored by Lucile Packard Children’s Hospital at Stanford
Peter Adamson, United States
Chairs: Darren Hargrave, United Kingdom and Michael Link, United States

Sunday

The Voice of the Invisible – The Experiences and Consequences of
Having a Brother or Sister with Cancer During Childhood
Ulrika Kreicbergs, Sweden
Chairs: Patti Byron, Canada and Barbara Cuccovia, United States

World Child Cancer Report
Chairs: Maarten Egeler, The Netherlands and Raul Ribeiro, United States
World Child Cancer (GL001)
Tim Eden, United Kingdom

Posttraumatic Stress, Depression, and Anxiety among Adult Long Term Survivors of Cancer in Adolescence (O179)
Lutz Goldbeck, Tanja Besier, Klaus-Michael Debatin, Desiree Grabow, Ute Dieluweit, Andreas Hinz, Peter Kaatsch, Diana C. M. Seitz, Germany

Emotional, Behavioral and School Difficulties for Siblings of Children with Cancer: A Comparison with Matched Classmates (O180)
Melissa Alderfer, Caroline Stanley, Robert Noll, United States

Challenges for Solid Tumor Diagnosis in a Resource-Limited Setting (O183)
Mariana Kruger, David Reynders, Fareed Omar, Judy Schoeman, Oloko Wedi, South Africa

President’s Symposium
Genomics: Prospects for Genome-Based Personalized Medicine (S14) ~ Huib Caron, The Netherlands and Todd Golub, United States

Integrative and Functional Studies of Human Genomic Cancer ~ Levi Garraway, United States

Towards Personalized Management of Neuroblastoma ~ John Maris, United States

Ballroom B/C Ethical Challenges in Pediatric Oncology Clinical Research (S15) ~ Tim Eden, United Kingdom and Steven Joffe, United States

Best Practices in Informed Consent ~ Leslie Fallowfield, United Kingdom

Ethical Issues in Clinical Trials in the Developing World ~ Mariana Kruger, South Africa

Assent in Pediatric Research ~ Marion Broome, United States

1. (2009), 41st Annual conference of International Society of Paediatric Oncology SIOP 2009, Sao Paulo, Brazil, October 5–9, 2009. Pediatric Blood & Cancer, 53: 701–915. doi: 10.1002/pbc.22234