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

A new trial opens: prolonged use of isotretinoin

Aflac ST1001 Prolonged Isotretinoin

Neuroblastoma bits from November 2010

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NCI featured article on ALK inhibitor Crizotinib

While encouraging responses are being seen in lung cancer patients with ALK mutation, drug resistance is expected to be a problem.

Crizotinib Continues to Show Promise for Some Lung Tumors, Faces Challenge of Drug Resistance

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FDA discusses Crizotinib pediatric trial design

Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee (ODAC) Nov 30, 2010

“If the current COG Phase I/II studies evaluating crizotinib in refractory pediatric solid tumors or ALCL shows promising activity in neuroblastoma, should crizotinib be evaluated in the post-transplant relapsed/refractory setting or should a randomized trial in a less heavily treated population be considered? If the former population (i.e., post-transplant relapsed or refractory) is a more appropriate setting, please discuss whether Progression Free Survival (PFS) is an adequate endpoint.”

Committee discussion questions

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Insight Genetics Awarded Qualifying Therapeutic Discovery Program Grant

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http://www.eurojournals.com/ejsr_40_1_15.pdf

www.eurojournals.com

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Scientific American describes the recent advances in viruses that kill cancer — now available to children this year for the first time –

Cancer Therapy Goes Viral: Progress Is Made Tackling Tumors with Viruses: Scientific American

“A new generation of oncolytic viruses are entering late-stage clinical trials, repurposing smallpox and herpesvirus to take on tough tumors.”

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Search goes on for toxins to kill neuroblastoma

“Luesch is experimenting with toxins—drawn from several species of cyanobacteria—on several types of cancer, including neuroblastoma, a childhood disease that attacks nerve cells. In July 2009, he launched a four-year, $1.2 million NCI-funded study, part of which entails… largazole testing on mice.”

Why Scientists Are Searching for Cures Underwater – Newsweek

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Childhood cancer survival in Australia

“Survival outcomes using the period method for 11903 children diagnosed with cancer between 1983 and 2006 and prevalent at any time between 1997 and 2006. The overall relative survival was 90.4% after 1 year,  79.5% after 5 years and 74.7% after 20 years.”

Population-based survival estimates for childhood cancer in Australia during the period 1997–2006

www.nature.com

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Accutane (cis-retinoic acid or isotretinoin) and depression?

A child with neuroblastoma is far more more often a preschooler than a teen. So the risk of suicide and depression is unlikely with such small children. It is a concern with the few teens and young adults with neuroblastoma on this drug, especially since the dosing is 2 to 10 times higher than what is prescribed for acne, and the lower dose is the basis for all the previous studies looking at incidence of depression and suicide. This small study gives important evidence that the drug may not contribute entirely to increased risk:

Severe Acne Linked to Suicide Risk Even Before Treatment Is Started

cme.medscape.com

In a retrospective Swedish cohort, suicide attempts were associated with severe acne even before treatment with isotretinoin was started.

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C10 (p. 80) “Late effects in neuroblastoma”

Dr Lisa Diller (Boston Children’s/Dana-Farber Cancer Institute) reviewed recent published data on late effects and presented new data in the Neuroblastoma Update Course on June 21st, 2010 at the Advances in Neuroblastoma Research meeting in Stockholm, Sweden. The session was organized by Sue Cohn and Andrew Pearson and chaired by Sue Cohn and Rani George.

The Childhood Cancer Survivor Study provided long-term survivorship data for those treated for neuroblastoma between 1970 and 1986, and results on 954 5-year survivors were published in Journal of the National Cancer Institute August 2009.[1]

Of the 954 children, 832 records were abstracted, and only about 10% were stage 4 survivors, so the vast majority (~90%) of the survivor data most likely represented low and intermediate risk survivors.  Only 38% of the survivors had surgery + chemotherapy + radiation.  Of all the survivors, at least 90% had 15 years of follow-up. Of 1358 there were 84 deaths (41 recurrences)  and higher risk of death if diagnosed over the age of 5 and had multimodal therapy. The children treated for neuroblastoma were compared to a cohort of 3899 siblings to determine if there was a higher incidence of health problems. There was a higher incidence of chronic health conditions involving the neurological, sensory, endocrine, and musculoskeletal systems in children treated for neuroblastoma.

Dr Diller also mentioned evidence from soon-to-be published institutional data that advanced bone age or epiphyseal closure is more common in children treated with cis-retinoic acid than children who did not have cis-retinoic acid. There is a theoretical toxicity proposed related to cis-retinoic acid given with anti-GD2 antibody (ch14.18) because of clearance issues, but this has yet to be verified.[2]

References

1. J Natl Cancer Inst. 2009 Aug 19;101(16):1131-40. Epub 2009 Jul 31. [fulltext]

2. ANR 2010 “Neuroblastoma Update Course” ANR 2010 Abstract Programme, p 80.

Dr Peter Zage from MD Anderson in Houston TX gave a presentation at the Children’s Neuroblastoma Cancer Foundation (CNCF) conference Saturday July 10, 2010 on the 3F8 randomized trial:

A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic Acid (RA) Plus GM-CSF in Primary Refractory Neuroblastoma Patients (NCT00969722)

This trial is funded by United Therapeutics, who recently retained rights to 3F8. This trial is currently open in 15 locations and began accruing in 2009, with a planned accrual of 40 children 18 months to 13 years old. United Therapeutics has also entered into an agreement with Memorial Sloan-Kettering Cancer Center (MSKCC) to exclusively license certain rights to the  antibody 8H9, used for brain relapse of certain tumors, including neuroblastoma.

This phase II randomized trial is a “registration trial” with the goal of gaining FDA approval for 3F8. The objective is to compare response rates in children with primary refractory disease to either 3F8 + GM-CSF or cis-retinoic acid (Accutane) + GM-CSF. Children who do not respond after two cycles may cross over to the other arm for the next two cycles. The children who have primary refractory disease–defined in this case as bone marrow or bone disease after induction or transplant, but no soft tissue disease– represent roughly 10% of all NB high-risk cases, or about 30 per year in the US, according to Dr Zage.  Children are not eligible if they have soft tissue disease, brain metastases, and they cannot have radiation during this trial.

A phase III (non-randomized) registration trial COG-ANBL0931 also opened in January 2010 and will accrue 105 patients: “Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma.”  The purpose of this trial is to gain FDA approval for the ch14.18 antibody.  According to the NIH clinical trials listing it is currently open in 29 locations. This trial also allows residual disease (primary refractory after stem cell transplant) by MIBG scan, CT scan, MRI, bone marrow aspiration, or biopsy.

The landmark phase III study COG-ANBL0032 that revealed efficacy for ch14.18 with IL2 and GM-CSF upon early analysis is also still open in 155 locations, with randomization ceased so all enrolled will receive ch14.18 (with GM-CSF and IL-2). [1]  The trial will accrue a total of 423. This trial also allows primary refractory disease described by the protocol.

Dr Zage gave a brief history of the development, production, and use of monoclonal antibodies in neuroblastoma. [2]

This is the first time 3F8 antibody has been available at an institution other than Memorial-Sloan Kettering in New York or Queen Mary Hospital in Hong Kong.

References

1. J Clin Oncol 27:15s, 2009 (suppl; abstr 10067z)

2. Cancer Biol Ther. 2009 May;8(10):874-82. Epub 2009 May 9. Review. [fulltext]

MIBG non-avid at diagnosis = better outcome?

POC39 (p. 211) Neuroblastomas with non-avid I-123 MIBG scan and negative urinary catecholamine secretion: A single institute’s experience

PL30 (p. 102) Analysis of MIBG scoring as a prognostic indicator in patients with stage 4 neuroblastoma. A Children’s Oncology Group (A3973) report

Dui Yen Soh, Sylvain Baruchel, and Meredith Irwin at Sick Kids in Toronto reviewed 148 children diagnosed between 1999 and 2009 (all stages and risk groups). They confirmed the interesting observation that non-avid MIBG and negative urine catecholamines at diagnosis are associated with low stage and favorable outcome. Of the MIBG non-avid children, 5 were low risk, 3 were intermediate risk, and 3 were high risk. These numbers are too small to confirm better outcome for MIBG non-avid (at diagnosis) high-risk, but Greg Yanik (University of Michigan) mentioned an interesting observation of better survival for those high-risk children who are MIBG non-avid at diagnosis (of n= 280 enrolled in COG-A3973, 29 were MIBG negative at diagnosis) in his presentation on a new scoring method to stratify patients at the end of induction. He presented at ASCO 2010 Chicago, ANR 2010 Stockholm, and will present again next week at the CNCF Parent Conference in Chicago. More on Dr Yanik’s presentation to come.[1]

Any ideas why MIBG non-avid survival might be better? No answers proposed yet.

Tandem transplant in Korea

POC40 (p. 211) Efficacy of tandem high-dose chemotherapy and autologous stem cell rescue in patients with high-risk Neuroblastoma: a preliminary report of NB 2004 study at Samsung Medical Center (Republic of Korea)

Ki Woong Sung and group reported at ANR results of 47 children diagnosed 2004 to 2008 and enrolled on NB 2004.  Of the 44 patients that went through tandem transplant, 36 (82%) remain event-free after median follow-up of 3 years (14-72 months) with probability of 5 year overall and event-free survival determined to be 68% ± 20%  and 67% ±  16%, with no treatment-related deaths.  Another report from the same center in 2007 gave results of 52 children diagnosed from 1997 to 2005 (44 had second SCT with TBI).  That study had 15% treatment-related deaths, 33 (75%) were event-free with median follow-up of 53 months (19-117 mo) from diagnosis.[2]  A retrospective study of 141 patients enrolled 2000 to 2005 from the Korean Society of Pediatric Hematology-Oncology (KSPHO) published May 2010 also showed improved 5-year event-free survival in the tandem group over the single transplant group (51 ±12% vs. 31 ±12%, P=0.030).[3]

Korean single and tandem retrospective study 1997 to 2005

These studies show strikingly comparable results to a larger COG pilot (97 children diagnosed 1994 to 2002) reported in 2006, which was the rationale for the current frontline single-versus-tandem trial in the COG.[4]

Germans report no difference in outcome using cis-retinoic acid (Accutane) or ch14.18/CHO antibody

POC37 (p. 210) Comparison of anti-GD2-antibody ch14.18 and 13-cis-retinoic acid as consolidation therapy for high-risk neuroblastoma. Results of the German NB97 trial

Thorsten Simon and group from GPOH (German pediatric oncology study group) reported retrospectively on two similar—but not randomized groups—showing that the outcome was not statistically different with almost 8 years of median follow-up for 74 children who received only ch14.18 antibody (1997-2002) and 75 children who received only cis-retinoic acid (2002-2004). The 3-year event-free survival from diagnosis was 53% ± 6% and 51% ± 6% (p=.209) respectively. While this result is interesting with regard to single-agent efficacy, it is very important to note that none of the children received both antibodies and cis-retinoic acid, nor were the children given cytokines (IL2 or GM-CSF) with the antibody as in the current COG trial. The GPOH previously reported no advantage to ch14.18 (no cytokines) over oral maintenance chemotherapy.[5]  But at ANR 2008 (Japan) the GPOH group reported no late relapses in the ch14.18 group. At this 2010 ANR they also said they have now seen a difference in the retrospective study after 10 years with statistically significant improved survival for the ch14.18 group. During the Special Clinical Session at ANR on Tuesday Dr Thorsten Simon said the GPOH will be revisiting the question of ch14.18/CHO given the remarkable survival advantage shown in the COG study report from Mar 2009.[6]  They are now considering using subcutaneous administration of IL2 to reduce toxicity (as is SIOP in the UK and the rest of Europe), and exploring the use of other agents such as IL15 or lenalidomide with the antibody.

References

1. J Clin Oncol 28:15s, 2010 (suppl; abstr 9516)
2. Bone Marrow Transplant. 2007 Jul;40(1):37-45. Epub 2007 Apr 30. PMID 17468771
3. J Korean Med Sci. 2010 May;25(5):691-7. Epub 2010 Apr 21. PMID 20436703 [full text]
4. J Clin Oncol. 2006 Jun 20;24(18):2891-6. PMID: 16782928 [full text]
5. J Clin Oncol. 2004 Sep 1;22(17):3549-57. PMID: 15337804
6. J Clin Oncol 27:15s, 2009 (suppl; abstr 10067z)