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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668596

ChiLTERN Newsletter

March 2017
Welcome to ChiLTERN's first newsletter, a monthly publication sent to the whole network. This is aimed at keeping everyone updated with the progress of the Project. With over 20 collaborators across the United Kingdom, Belgium, Spain, Italy, Switzerland, Germany, Poland, France, Norway, Sweden, Ireland and the Czech Republic, our comprehensive research programme is connected to single largest clinical trial ever undertaken amongst the paediatric population. Ultimately, ChiLTERN will aim to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.
Meet the Leads
I'm Keith Wheatley and I'm the ChiLTERN Project Co-ordinator and also the lead for Work Pages 1 and 7. I'm based in the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham where I am Professor of Clinical Trials and CRCTU Scientific Director. I've been working on clinical trials for over 30 years now, mostly in cancer where areas of particular interest include leukaemia, skin cancer and, since CRCTU took over as the UK lead trials unit for paediatric oncology in 2010, a range of children's cancers. I've also had excursions into other disease areas such as renal disease and Parkinson's. The move into children's cancer has involved the development of novel designs for trials in rare diseases - including the PHITT trial - and I am the Lead Investigator for the BEACON-Neuroblastoma and Euro-EWING 2012 trials. I also have an interest in research associated with clinical trials, such as meta-analysis and biomarker studies
I am Bruce Morland, paediatric oncologist at Birmingham Children’s Hospital and Honorary Professor at the University of Birmingham. I am currently the Chairman of the International Society of Paediatric Oncology Epithelial Liver Tumour group, SIOPEL. My main research interests include liver tumours, drug development and sarcomas. I am currently Vice President of the Innovative Therapies for Children with Cancer, ITCC network of early phase clinical trial centres. In Birmingham we are fortunate to have a specialised surgical service for liver tumours, including transplantation which results in our centre receiving approximately two-thirds of all hepatoblastoma cases in the UK for their surgical management. Our multidisciplinary team therefore has a lot of experience in the clinical management of this rare tumour. The ChiLTERN project was initiated by me as a result of our extensive collaborative links within Europe, and the development of the PHITT trial with our partners in the USA and Japan. It is always exciting for me to see these large collaborative projects take shape and evolve and as the lead for Work Package 2, I am looking forward to getting the PHITT trial launched and to see our first patients treated within the Project.
I am Carolina Armengol, head of the Childhood Liver Oncology group at the Germans Trias i Pujol Research Institute (IGTP). Our group’s line of research is mainly focused on establishing a collection of biological samples from paediatric, but also adult patients with liver cancer, to establish new experimental models and identify new biomarkers and signalling pathways for improving the clinical management and prognosis of these patients. I am leading Work Package 3 that aims to establish a European collection of biological samples from PHITT patients from which we aim to identify biological and pathological parameters in order to improve clinical stratification.  We also will perform a comprehensive molecular study of rare and highly aggressive forms of paediatric liver tumours including HCC to increase current knowledge and provide new biomarkers and therapeutic targets by using the latest omics and sequencing technologies.
I am Beate Häberle, consultant for pediatric surgery at the University of Munich. I have been involved in the German national pediatric liver tumor trials since 1999. Together with an international team from Europe, United States and Japan we established the “Children’s Hepatic tumor International Collaboration” (CHIC). The CHIC team could develop a new risk-stratified staging system in pediatric hepatoblastoma. I am leading Work Package 4, focused on the validation of this newly developed staging system with independent datasets and within the new international trial PHITT. 
My name is Steven Warmann, I am Associate Professor and consultant for Pediatric Surgery and Pediatric Urology at the University Children’s Hospital in Tuebingen, Germany. Our department (Director: Prof. Joerg Fuchs) is currently reference center for Pediatric liver tumors, renal tumors, neuroblastoma and soft tissue sarcoma within the Society of Pediatric Oncology and Hematology (GPOH). Also, we are members of the surgical panels of the SIOP trials on liver tumors (SIOPEL) and renal tumors (SIOP-RTSG). Our main clinical research activities in liver tumors focus on resectability, management of large vessels as well as local treatment of metastases (especially single step procedures of tumor surgery and metastases resections).

Heading the Work Package 5 of the ChiLTERN project, our main aim is to investigate factors contributing to the decision making process of surgical strategies (extended resection versus liver transplantation) in POST-TEXT III and IV Hepatoblastoma. Together with our partner MeVis Medical Soluitons AG (Bremen, Germany) we adapted a specific tool for processing of cross section imaging data for the use in children with complex liver tumors. This tool delivers a virtual imaging analysis including 3-dimensional reconstruction of liver, tumor and vessels as well as a virtual resection assessment with anatomical approach and volumetries of resected and remaining liver. In an expert panel consisting of pediatric surgeons and radiologists we will evaluate the possible impact of this innovative tool on surgical strategies in affected children in order to eventually formulate surgical recommendations for these complex  clinical conditions.

I am Gareth Veal, head of the Newcastle Cancer Centre Pharmacology Group at Newcastle University. I manage an active research group working on clinical pharmacology studies in both childhood and adult cancers. I will be leading on ChiLTERN Work Package 6, focused on ‘pharmacokinetics, pharmacogenetics and toxicity biomarker studies’. This will involve studies investigating the pharmacokinetics of cisplatin, the quantification of potential toxicity biomarkers and pharmacogenetics studies.

WP3 meeting (Paris, 2017) by Carolina Armengol

On 17 January 2017, all beneficiaries involved in the biological and pathological studies of the ChiLTERN project met in Paris for the second WP3 meeting. The main objectives of this meeting were to define the biological and pathological aspects – including ethics – of the upcoming PHITT trial and their integration with the ChiLTERN aims. The most important issue that came up was the importance of obtaining enough biological material from diagnostic biopsies for assuring one of the most comprehensive biomarker studies ever performed in paediatric patients with liver cancer. Moreover, the need for access to the diagnostic clinical data at the time of receiving the biological material for research was underlined. Without this, it will be impossible to select the ideal cases for establishing experimental in vivo and in vitro models, as well as for selecting the highly-aggressive tumours that will be included in the planned high-throughput molecular studies. Also, part of the meeting was focused on the different possibilities for the workflow of material, data and documents among partners. CINECA, one of the beneficiaries of the consortium, has recently opened their website tools to ensure coordination between local hospital staff and CLCN bio-repositories (Spain and Germany) as well as among ChiLTERN beneficiaries. A further meeting was agreed in order to move forward on the definition of the electronic questionnaires for PHITT and ChiLTERN. In summary, it was a very useful and productive meeting for understanding the requirements of all WP3 partners and their thoughts about key aspects of the project.
Dates for the diary
  • The next ChiLTERN Internal Project Board meeting will take place on Thursday 6th April 2017, 11:00 - 13:00 at the Institut Curie, Paris. 
  • There will be a ChiLTERN/ PHITT update at the SIOPEL Spring meeting 2017. This will be during the afternoon of 6th April as part of the Update on Clinical Trials
  • There will be a full ChiLTERN meeting in the Autumn. The date and venue is to be decided and information will be posted in the Meetings section of the project website.  
  • The EU Reporting Period 1 ends on 30th June 2017. 
PHITT Update
The trial has been submitted to the UK authorities. We would for approval by end of April 2017, with the first UK sites opening to recruitment in May. The PHITT trial team will distribute relevant trial documents to each country, and once UK approval is granted, each country can submit for approval (i.e. in May 2017). For more information, contact
If you have any news that you would like to be included in the next ChiLTERN newsletter, please get in touch with Louise Woodall by email at by Monday 20th March 2017.

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