The ChiLTERN project has some big goals. Finding the
best individual treatment for paediatric liver cancer and creating the
world's largest pediatric clinical trial are just a few behind
these goals are the people who work tirelessly to keep
things on track make new discoveries share results and most
importantly build a better world for children suffering from liver
cancer. To understand the importance of the whole, one must
understand the significance of the individual parts.
Let us introduce them and their field of work to
you Hello.
I'm Keith Wheatley. I'm professor of clinical trials at the
University of Birmingham in the UK. I'm the project coordinator
for ChiLTERN so I have overall responsibility for the project. I'm
also the lead for two of the work packages one
One on project management and another on communication and dissemination. ChiLTERN
is the most ambitious research project ever undertaken on
children and young adults with liver cancer. So the project
requires robust management including financial oversight.
And that's something that we undertake here in Birmingham. I'm
Bruce Morland and I lead the work package two
of the ChiLTERN project. This is the PHITT Trial and the
PHITT Trial is really the glue that binds all of the
study together. In order for us to undertake research
on patients, entry into a clinical trial is
an absolute requirement. Setting up the PHITT Trial has been
an immense effort across the whole of Europe. It means
that at this time over 130 patients have now been
recruited into the trial. We've recruited from over 12 countries
and it's involved over a hundred individual hospitals - a truly
massive effort. Beyond that we've had collaboration from our colleagues
in Japan and in the United States all of whom
are also recruiting patients into the PHITT Trial and globally
over 350 patients have now been entered. What's the motivation
for us doing all of this. Well it's quite simple.
What we want to do is to be able to
improve the outcomes for our patients. For those patients who
already have good survival this means reducing their side effects.
For those patients who have poor survival the hope is
we can improve their outcome. Alongside that is all of
the research that we're doing trying to understand more about
this rare type of liver cancer in children and hopefully
have some plans for discovering new science that may lead
to better treatments in the future.
Hi, I am Càrol, Germans Trias i Pujol Research
Institute. My work package within the ChiLTERN project has two
main objectives: first to collect biological samples from children with
liver cancer that I enroll in the PHITT Clinical
Trial that is in work package two, and second to
a study the biology and the pathology of these rare tumors.
Up to now we have established the most complete worldwide
collection of biological samples that includes blood, tissue and urine
and we have also defined new biological molecular tools that
increase the prognostic and diagnostic accuracy. The final aim
is to use these tools to increase the survival of
the patients with liver cancer. I have dedicated my whole
career of 20 years to the study of childhood liver
cancer. To have the chance to participate in the ChiLTERN
Project and the PHITT trial with the top experts in the
field is like a dream for me.
In the PHITT study, risk stratification is used to assign
patients to the best therapy for them. This is based
on many criteria. A first step to verify this is
to look at the studies with patients who had hepatoblastoma.
We check there whether the risks stratification used
would have correctly classified them. First results show that the
used stratification allows a good classification. I would like
children with this rare disease to receive a therapy that
is increasingly better adapted to them and their needs.
The work package five is the surgical work package within ChiLTERN.
Our main question is to answer whether to perform resection
or liver transplantation in patients with advanced hepatoblastoma and to
define factors in order to answer this question.
For this we have developed a software processing tool together
with our industrial partner MeVis in Bremen which uses
the preoperative imaging analysis through CT scan or MRI scan
for processing. We have a panel of experts which contributes
to our work and which helps defining the factors to
answer the question. Every center worldwide could participate and can
participate if they want to. If they have cases every
child with a PRETEXT 3 or 4 hepatoblastoma
is susceptible to participate in our study. With this
part of the ChiLTERN project we are analyzing one of
the most innovative systems that is currently available for preoperative
imaging processing and planning of surgery in children with advanced
hepatoblastoma. Our focus so far was to adopt the
system that we analyzed for the use in children. For
this we first standardized the protocols for CT and MRI
imaging to be universally used worldwide and to make it
user independent in order to achieve the highest quality of
data to be processed. We then created a web based
platform together with our partner Cineca in Bologna, Italy
in order to enable the expert panel to access the data
from wherever they are and in order to perform the
necessary analysis. Data collection has started. With this we were
a little bit delayed caused by the late start of
the PHITT study but we are currently making good progress
and then collecting a good amount of patients in our study.
We had a lot of energy to put into the
into the acquiring of ethical approval which we did locally and the
ethical standards in Germany are very restrictive so this was
a high achievement. We have good feedback from colleagues that
have been using the system already and we are confident
that this innovative tool will be answering the question in
a very very satisfying way. In Tübingen we
one of the few reference centers for pediatric surgical oncology
in Germany and liver tumors are one of the main
topics of our daily work. Personally I am involved with
liver tumors since the early days of my medical career
and I also did my habilitation on that topic. The
question of whether to perform extreme resection or transplantation in
children with extended or advanced hepatoblastoma as one of
the most important and surgical questions that is currently in
the different studies that are out there. And we did
some research on this and we shared our results and
relevant publications already. But we experienced that in order to
have more information on this we would need to analyze
a bigger cohort and analyze it together with international experts.
And that was the motivation to perform this analyses together
with the ChiLTERN project. Our ultimate goal is to contribute to
improve treatment results for affected children to make surgery safer
and as safe as possible to put as little burden
on the patients as possible and to contribute to shape
the quality of life of the patients and the families
as much as possible.
The work of my research team on the ChiLTERN project
involves understanding why we may see differences in the way
that different patients respond to chemotherapy. In terms of both
efficacy but also in terms of the side effects of
the chemotherapy. So by understanding differences in the way that
drugs are handled also genetic differences between patients which may
predispose them to certain side effects of chemotherapy may allow
us to tailor treatment for individual patients in the future
and therefore optimize chemotherapy. The work carried out so far
on the ChiLTERN project has involved the development of assays
for measuring drug levels to the required level of accuracy
and precision and also the development of novel assays for
measuring biomarker proteins that may predict both cardio toxicity and
renal toxicity in patients on the clinical trial. For me
the ChiLTERN project is a great example of how working
together at a European level we can improve the lives
of childhood cancer patients worldwide.
We also want to see the results from the different
work packages made widely available - not just to the scientific
community but to the public at large. We've also set
up a patient and public involvement group to find out
what the patients with liver cancer and their families would
like to get out of a project such as ChiLTERN.
Everyone involved with ChiLTERN hopes that it will lead to
major improvements in our understanding of liver cancer in young
people and through improvements in treatment as well.
ChiLTERN is a joint effort.
The value of each partner across Europe and the world
contributes to the whole thus giving the children with liver
cancer and their families a glimmer of hope for a
brighter future ChiLTERN is: Quite simply collaboration. All of the
efforts that we've had collaborating with our international colleagues with
a range of clinicians, surgeons, oncologists, radiologists, pathologists, biologists, nurses
has been fantastic. But the biggest collaboration of all is
the collaboration we've had with our patients and our families
without whom none of this would be possible.
ChiLTERN is science for the benefit of the kids.
ChiLTERN shows that many countries can work together to achieve
improvement for children with this rare disease.
ChiLTERN is the first true global liver tumour study
and thus a huge opportunity for physicians and children all
over the world. Is a great example of how working
together at a European level we can improve the lives
of childhood cancer patients worldwide.
ChiLTERN is the most ambitious research project ever undertaken
on children and young adults with liver cancer.