Taking a look at the genes of brain tumors may help making the right therapy decision
Researchers from the „Hopp-Children’s Cancer Center Heidelberg“ (KiTZ) together with colleagues from the US, showed substantial molecular diversity behind seemingly similar embryonal brain tumors in children. The scientists could reveal the impact of identifying this molecular diversity on the diagnosis and treatment approach. The investigations, which were conducted in the context of a clinical study, were supported by the German Cancer Consortium (DKTK).
Diagnosis „primitive neuroectodermal tumor of the CNS“: Tumor cells are small and poorly differentiated.
© Dominik Sturm / KiTZ
The “Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a joint initiative of the German Cancer Research Center (DKFZ), Heidelberg University Hospital and Heidelberg University.
Brain tumors that look similar under the microscope can differ strongly on a molecular level - a distinction that should be considered when making treatment decisions. Children with embryonal brain tumors have to undergo intense and devastating therapies, with an overall limited curative outcome for some tumor subtypes. This holds true for “supratentorial primitive neuroectodermal tumors (sPNETs)”: These tumors derive from immature cells of the central nervous system (CNS), growing particularly fast and aggressively.
The team surrounding Professor Stefan Pfister, KiTZ director, head of the “Pediatric Neurooncology” division of the DKFZ and senior physician at the Heidelberg University Hospital, conducted the study together with colleagues of the Fred Hutchinson Cancer Research Center (Seattle, USA) and the Children’s National Medical Center (Washington DC, USA). Using a state-of-the-art data analysis method, the researchers analyzed chemical gene modifications, so-called DNA methylation, within the patients` tumor tissue in the context of a phase-III clinical trial on sPNETs.
Molecular diagnostic tumor classification prior to treatment could prevent devastating therapies for many children. “An exact diagnosis and prognosis assessment for most children with CNS tumors is possible when histological examinations are combined with methylation analyses of the tumor DNA”, says Professor Pfister, a main author of the study. “We can thus better estimate who would benefit from the intense radiation and chemotherapy and which treatment option should be used. This way we are able to save children from the side-effects of non-beneficial therapies.”
In the context of this study the methylation analysis showed that fewer patients than assumed truly suffered from sPNET, but the majority had other tumor types such as glioblastoma, ependymoma or others that had been misdiagnosed. Accounting for these “false positives”, the prognosis for sPNET is much better than previously assumed, with an increased chance of responding well to chemotherapy.
Since the molecular characterization of embryonal tumors of the central nervous system in children can therefore have a crucial impact on treatment types and therapy success, the researchers recommend to implement this method as a standard-of-care method for diagnosis.
Original publication:
Hwang et al. 2018: Extensive Molecular and Clinical Heterogeneity in Patients With Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children’s Oncology Group Randomized ACNS0332 Trial. DOI: 10.1200/JCO.2017.76.4720. Journal of Clinical Oncology – Online publication on October 17, 2018.
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https://www.dkfz.de/de/presse/pressemitteilungen/2018/bilder/PNET_FOXR2_HE.jpg
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The „Hopp Children's Cancer Center Heidelberg” (KiTZ)
The “Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a joint initiative of the German Cancer Research Center (DKFZ), Heidelberg University Hospital and Heidelberg University. 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 severe blood diseases 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. KiTZ online: www.kitz-heidelberg.de
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 institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
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
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