Some individuals experience cancer recurrence when they enter adolescence or adulthood after they have been successfully treated for cancer in childhood while others don’t. But why is this? This is the core question being considered in a research project directed by the University Medical Center of Johannes Gutenberg University Mainz (JGU). The German Federal Ministry of Education and Research (BMBF) and the Federal Ministry for the Environment, Nature Conservation, Building, and Nuclear Safety (BMUB) are funding the project with a total of around EUR 3.8 million through the Basic Energy Research 2020+ funding program. The purpose of research in this area is to help identify in future those patients who may have a particular individual susceptibility to radiation so that the treatment they receive can be modified accordingly. The joint research project on “Intrinsic radiotherapy: the identification of biological and epidemiological long-term effects” (ISIBELa) is being coordinated by the Institute of Medical Biostatistics, Epidemiology, and Informatics (IMBEI) at the Mainz University Medical Center in close cooperation with the on-site Department of Radiation Oncology and Radiation Therapy. Further involved in the collaborative research project ISIBELa are the German Childhood Cancer Registry, the Institute of Molecular Genetics, Genetic Security Research, and Consulting (IMSB) at Mainz University, the Molecular Epidemiology Unit of the Leibniz Institute for Prevention Research and Epidemiology – BIPS GmbH, and the Biological Radiation research team at TU Darmstadt.
The ISIBELa joint research project is to determine the risk of secondary cancer in later life following successful therapy in childhood. Approximately five to ten percent of all former patients subsequently redevelop cancer. “One of the core aspects we are considering within ISIBELa is whether the cells of various individuals react differently to the ionizing radiation from radiotherapy,” explained the IMBEI Director and Coordinator of the research cooperative, Professor Maria Blettner. Questions of this complexity can today only be resolved by research groups in which there is interdisciplinary collaboration between those involved in fundamental research and clinicians with various specializations. Hence, the work being undertaken by physicians, biologists, epidemiologists, and mathematicians is closely meshed within the ISIBELa project.
In the first part of this multi-phase project, the researchers will initially identify and statistically analyze all cases with secondary cancer after childhood cancer in Germany. During the further course of the project, they will examine how patients with or without secondary cancer differ with regard to various factors, such as the type of primary disease and the treatment received. Patients will be asked to provide a tissue sample. The tissue samples are examined for evidence of possible genetic and epigenetic causes of cancer using state-of-the-art laboratory techniques. For example, the Institute of Molecular Genetics of JGU is employing the latest methods of high-throughput genome and transcriptome sequencing to look for differences between the patient groups.
“Thanks to the progress made in treatment in recent years, the prognosis for recovery from many types of cancer has significantly improved. We now consider it feasible that we will be able to provide cancer patients with the same life expectancy as healthy persons of the same age. Hence, greater emphasis is being placed on late adverse effects. And this is exactly the area being considered by the new collaborative research project ISIBELa. Our expected results should hopefully enable us to develop methods with which we can fairly reliably identify, before treatment, which patients are particularly susceptible to radiation so that that we can optimize their therapy accordingly,” stated Professor Heinz Schmidberger, Director of the Department of Radiation Oncology and Radiation Therapy at the Mainz University Medical Center, Professor Thomas Hankel of the Institute of Molecular Genetics at the Mainz University Medical Center, and Dr. Manuela Marron, epidemiologist and study coordinator at BIPS, representing all involved researchers.
It is mainly attributable to the significant improvements in the diagnosis and treatment of childhood cancer that the probability of survival of, for example, leukemia patients today is now 80 percent compared to just two percent in the 1960s. Radiotherapy was developed as a major means of treating cancer in the 1970s and still remains one of the cornerstones of cancer treatment. In radiotherapy, targeted ionizing radiation is used to eliminate tumor cells.
The ISIBELa collaborative research project is part of the University Center for Tumor Diseases (UCT) at the Mainz University Medical Center. The individualization of cancer therapy is one of the research goals of the UCT. The translational research on long-term effects of treatment should also enhance the international reputation of the UCT. It is to be hoped that collaboration between ISIBELa and UCT will soon lead to the development of less aggressive forms of treatment.
Johannes Gutenberg-Universität Mainz