Report to HCA International Foundation

Dr Daniel Morgenstern

Clinical and Research Fellowship in Neuroblastoma

The Hospital for Sick Children, Toronto, ON, Canada

March 2012 – August 2013

Supervisors

1.      Dr Meredith Irwin, Associate Chair of Paediatrics (Research), Scientist SickKids Research Institute and Staff Physician, Division of Haematology/Oncology

2.      Dr Sylvain Barcuhel, Professor of Paediatrics, Staff Physician and Director of the Novel Agent and Innovative Therapy Programme, Division of Haematology/Oncology

Main outputs/achievements

My role at The Hospital for Sick Children (SickKids) was as the inaugural fellow specialising in neuroblastoma – a particular type of childhood cancer. Neuroblastoma has a fascinatingly varied natural history, with disease in infants often regressing spontaneously without the need for chemotherapy (even if metastatic at presentation), whilst the outcomes for children with metastatic disease remain poor despite very intensive multi-modal therapy. The post was part funded by hospital charity funds (Sears Cancer Foundation and Garron Family Cancer Centre) and, in addition, I was successful in obtaining (by competitive application) additional support from the Hospital Research Institute. The support of HCA International Foundation was of particular help in contributing to the costs of relocating to Canada and registering to practice medicine. The Fellowship combined laboratory-based research, with involvement in the NAIT programme for early phase clinical trials and exposure to clinical practice – all with a specific focus on neuroblastoma.

1) Clinical

I participated in a weekly out-patient clinic focussing on neuroblastoma patients, as well as attending weekly solid tumour rounds and neoplastic rounds (multi-disciplinary meetings). These opportunities allowed me to further develop my knowledge of the clinical management of neuroblastoma (particularly low risk patients who are typically managed in the out-patient setting). In addition, through fellow membership of the Childrens’ Oncology Group (COG), I have had the opportunity to become familiar with the North American co-operative group for childhood cancers and, in particular, their concepts for management of neuroblastoma. I was able to attend the Fall meeting of COG in Atlanta in 2012. I also undertook routine ward cover at weekends and participated in various teaching sessions for oncology fellows, all providing an invaluable insight into the approach to healthcare in Canada, the different methods of organising patient care, staffing, training, etc.

2) Laboratory

I have been able to extend my knowledge of the basic biology of neuroblastoma and techniques for identifying and characterising potential new therapeutic agents. I have worked on a number of promising new drugs/signalling pathways and scientific publications relating to this work are in preparation. I presented some of this work at the international Advances in Neuroblastoma Research meeting held (coincidentally) in Toronto in 2012 and at the University of Toronto Department of Paediatrics research day.

3) Experimental therapeutics

Through participation in the Novel Agent and Innovative Therapy (NAIT) programme, I have been exposed to the wide range of early phase studies for paediatric cancers currently open and being developed in North America. I was able to write-up and publish the results of a completed Phase I study of a novel combination of chemotherapy agents and develop the protocol for a follow-up study. This protocol will, hopefully, open across Canada in 2014 and we are currently exploring options to open the study additionally in London to allow access for UK patients. I was able to attend the AGM of the NANT consortium (Novel Approaches to Neuroblastoma Therapy) in Los Angeles at which I presented a trial concept for trial of a novel targeted radiotherapy agent.

4) Additional academic

I undertook a clinical project using data from a large international database to explore outcomes relating to a particular pattern of neuroblastoma metastatic disease, so-called ‘4N disease’. I was selected to present this work as an oral presentation at the ASCO (American Society of Clinical Oncology) AGM in Chicago in 2013 and was additionally awarded the Brigid Leventhal Award for the highest-ranking submission by a trainee in paediatrics.

5) Publications arising out of fellowship

  1. Morgenstern DA, Marzouki M, Bartels U, Irwin MS, Sholler GLS, Gammon J, Yankanah R, Wu B, Samson Y, Baruchel S Phase I study of vinblastine and sirolimus in pediatric patients with recurrent or refractory solid tumors Paediatirc Blood and Cancer (in press)
  2. Morgenstern DA, Baruchel S, Irwin MS Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy. Journal of Pediatric Hematology and Oncology (epub ahead of print)
  3. Morgenstern DA & Irwin MS Neuroblastoma (invited book chapter in Cancer Genomics to be published by Elsevier, in press)
  4. Morgenstern DA, Soh SY, Stavropoulos J, Bodwin S, Baruchel S, Malkin D, Meyn S, Irwin MS Metachronous neuroblastoma in an infant with germline partial trisomy 2p: a role for ALK? (submitted)
  5. Morgenstern DA, London WB, Stephens D, Volchenboum SL, Hero B, Di  Cataldo A, Nakagawara A, Shimada H, Ambros PF, Matthay KK,  Cohn SL,  Pearson ADJ, Irwin MS (2013). Metastatic neuroblastoma confined to distal lymph nodes (stage 4N) to predict outcome in patients with stage 4 disease: A study from the International Neuroblastoma Risk Group (INRG) database. Annual meeting of the American Society of Clinical Oncology (ASCO)

Next steps

In May 2013, I was appointed as a Consultant in Paediatric Oncology at Great Ormond Street Hospital and will be returning to the UK at the end of August to take up this new role. The post will have a particular focus on the management of patients with neuroblastoma and consequently my fellowship at SickKids will be invaluable both in having provided an excellent learning opportunity, but also for providing possibilities of ongoing future collaborations between SickKids and Great Ormond Street Hospital. My hope is that I will be able to bring my familiarity with the North American approach back to my UK practice and that I will be able to encourage and facilitate enhanced trans-Atlantic collaboration for future neuroblastoma trials.

Dr Daniel Morgenstern

11 July 2013

Daniel Morgenstern (left), recipient of the Brigid-Leventhal Award at ASCO 2013