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Pan-European registry study shows benefits of cancer genome sequencing for children with cancer

No. 37 | 29/05/2020 | by Moos

In some cases, cancer genome analysis can help find a suitable therapy for children with relapsed cancer and delay the progression of the disease. These are the findings of the INFORM registry study conducted by the Hopp Children's Cancer Center Heidelberg (KiTZ), which systematically investigated the benefits of molecular precision oncology in children. The results of the pan-European project are being presented at the conference of the American Society of Clinical Oncology (ASCO), which is being held virtually from 29 to 31 May, and the project recently won the James B. Nachman endowed ASCO award.

Some childhood cancers have characteristic genetic changes.
© S. Gröbner/KiTZ

The "Hopp Children's Cancer Center Heidelberg" (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and Heidelberg University.

In many cases, when cancer comes back in children, there are hardly any treatment options left. The aim of the INFORM study is for children with relapsed malignancies to receive more effective therapies once the standard treatments have been exhausted. "When it comes to precision medicine and the development of new therapies, pediatric oncology lags behind cancer treatment for adults, where there are lots of clinical studies, lots of new biomarkers and lots of new drugs," says pediatric oncologist and KiTZ researcher Cornelis van Tilburg, who presented the new findings at the ASCO conference.

The INFORM study (INdividualized Therapy FOr Relapsed Malignancies in Childhood) was launched in 2015 to identify molecular targets in children with relapsed cancer that could unlock new treatment options. Together with physicians from University Hospital Heidelberg (UKHD) and researchers from the German Cancer Research Center (DKFZ), the KiTZ team developed an algorithm that they used to assign molecular changes in a tumor to one of seven categories, from 'very suitable' to 'unsuitable', depending on their suitability as a therapeutic target structure. For example, genetic changes in the tumor were classed as very suitable if they are very specific to certain forms of cancer that are known to activate biological target structures that can be directly targeted with active pharmaceutical substances and for which drugs have already been approved, or for which clinical trials are already underway.

The attending pediatric oncologists at the 72 centers in eight European countries were then able to use this information to inform their therapy choices. A total of 149 young patients with relapsed cancer received a more targeted treatment based on the INFORM results, for example through inclusion in a clinical trial or through an 'off-label' treatment using a drug that was originally approved for adults. Of these, 20 patients had a 'very suitable' target structure and the progression of the cancer was delayed by three months compared with patients with less suitable target structures. In all, 525 patients were included in the analysis. In eight per cent of brain tumor patients, it was also possible to diagnose the precise tumor form based on the genome analysis.

"The results show that it is possible to identify molecular targets that open up new treatment possibilities for children with relapsed cancer and a very poor prognosis, and make precision oncology possible for children in the first place," says David Jones, coordinator of molecular diagnostics for the INFORM project at KiTZ. Moreover, the results have already led to the launch of several clinical trials to test new biomarkers for cancer in children. The INFORM approach was recently awarded the James B. Nachman endowed award for pediatric oncology by the American Society of Clinical Oncology (ASCO).

The KiTZ researchers aim to open up individual tumor analyses for as many children as possible, thereby offering them a chance of a potentially more effective therapy, for instance within innovative clinical trials. "There are hardly any innovative targeted drugs specifically for children," says KiTZ director Olaf Witt, who is the coordinator of the INFORM registry study and head of the DKFZ's clinical cooperation unit for pediatric oncology, and also works as a pediatric oncologist at University Hospital Heidelberg. "There are very few clinical trials running in Germany to test new treatment approaches specifically for children with cancer," he adds. "Our vision for the future is to find a customized therapy for every type of tumor in children."

An image for this press release is available for download at:
www.kitz-heidelberg.de/fileadmin/media/kitz/forschung/PedPanCan_SGroebner_E.jpg

Caption:
Some childhood cancers have characteristic genetic changes.

Note on use of images related to press releases
Use is free of charge. The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) permits one-time use in the context of reporting about the topic covered in the press release. Images have to be cited as follows: "Source: S. Gröbner/KiTZ".
Distribution of images to third parties is not permitted unless prior consent has been obtained from DKFZ's Press Office (phone: ++49-(0)6221 42 2854, E-mail: presse@dkfz.de). Any commercial use is prohibited.

The Hopp Children's Cancer Center Heidelberg (KiTZ)
The „Hopp Children's Cancer Center Heidelberg" (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital and Heidelberg University. As the National Center for Tumor Diseases (NCT), which focusses on adult oncology, the KiTZ is based on the US model of so-called "Comprehensive Cancer Centers" (CCC). As a therapy and research center for oncologic and hematologic diseases in children and adolescents, the KiTZ is committed to scientifically exploring the biology of childhood cancer and to closely linking promising research approaches with patient care– from diagnosis to treatment and aftercare. Children suffering from cancer, especially those with no established therapy options, are given an individual therapy plan in the KiTZ, which is created by interdisciplinary expert groups in so-called tumor boards. Many young patients can participate in clinical trials which ensures access to new therapy options. Thus, the KiTZ is a pioneering institution for transferring research knowledge from the laboratory to the clinic.
While the KiTZ focuses on pediatric oncology, the focus of the National Center for Tumor Diseases (NCT), founded in 2004, is adult oncology. Both facilities in Heidelberg are based on the US model of so-called "Comprehensive Cancer Centers" (CCC).

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

Heidelberg University Hospital and Medical Faculty
Internationally recognized patient care, research, and teaching
Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 13,000 employees, training and qualification is an important issue. Every year, around 65,000 patients are treated on an inpatient basis, 56,000 cases on a day patient basis and more than 1,000,000 cases on an outpatient basis in more than 50 clinics and departments with almost 2,000 beds. Jointly with the German Cancer Research Center (DKFZ) and German Cancer Aid, Heidelberg University Hospital has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. Currently, about 3,700 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. www.klinikum.uni-heidelberg.de

Press contact:
Dr. Alexandra Moosmann
Press and Public Relations KiTZ
Hopp Children's Cancer Center Heidelberg (KiTZ)
Im Neuenheimer Feld 130.3 / 7.320
D-69120 Heidelberg
T: +49 (0) 6221 56 36434
a.moosmann@kitz-heidelberg.de
presse@kitz-heidelberg.de

Dr. Sibylle Kohlstädt
Communications and Marketing
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2843
F: +49 6221 42 2968
S.Kohlstaedt@dkfz.de
presse@dkfz.de

Doris Rübsam-Brodkorb
Corporate Communications Heidelberg University Hospital and Medical Faculty
Im Neuenheimer Feld 672
D-69120 Heidelberg
T: +49 6221 56-5052
F: +49 6221 56-4544
doris.ruebsam-brodkorb@med.uni-heidelberg.de

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