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DKFZ/NCT/DKTK-MASTER study: Molecular analysis supports therapy decisions in rare cancers

vom 15.06.2021

DKFZ/NCT/DKTK-MASTER study: Molecular analysis supports therapy decisions in rare cancers

Copyright: NCT Heidelberg / Philip Benjamin

Joint press release of NCT Heidelberg and NCT/UCC Dresden

Rare cancers are often difficult to treat. Scientists from the German Consortium for Translational Cancer Research (DKTK), led by NCT Heidelberg and NCT/UCC Dresden, have demonstrated for the first time that patients with rare tumor diseases benefit from comprehensive molecular analysis. The researchers examined the molecular profiles and clinical data of a total of 1310 patients, around three-quarters of whom suffered from rare cancers. Based on several hundred biomarkers, a team of physicians made evidence-based treatment recommendations in 88 percent of the 1310 cases, some of which included new, experimental therapies. The recommendations were implemented in about one-third of patients, resulting in significantly improved disease control compared with previous treatments.

The NCT is a multi-site collaboration between the German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD) on the one hand, and DKFZ, Carl Gustav Carus University Hospital Dresden, the Medical Faculty of TU Dresden, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR) on the other.

Cancer patients respond very differently to treatments. Precision oncology therefore tries to find out in advance which individually adapted therapy is most promising. To do this, experts analyze the molecular, cellular, and functional properties of human tumors. Some of these characteristics, such as specific changes in the genetic material of the cancer cells, can then serve as biomarkers that indicate the chances of success of certain treatment approaches. On this basis, a so-called molecular tumor board – a team with diverse expertise in oncology, pathology, molecular biology, bioinformatics, and medical genetics – makes individual therapy decisions.

Retrospective analyses show that about one-third of all cancer patients benefit from therapy decisions based on biomarkers. However, for rare cancers, the clinical relevance of precision oncology approaches has not been proven so far. This is mainly because these tumor types are poorly studied and their incidence in individual cancer centers is so low that patient groups are too small for meaningful investigations. In the DKFZ/NCT/DKTK-MASTER program, therefore, centers throughout Germany have joined forces to be able to look at and research larger samples. In fact, rare cancers in their entirety account for up to a quarter of all tumor diseases. And unlike common cancers such as breast, colorectal, or lung cancer, there are usually no or only a few established treatment standards for these rare diseases and thus a considerable unmet medical need.

In the prospective observational study within the DKFZ/NCT/DKTK- MASTER program, scientists have now analyzed the complete molecular profiles and clinical data of 1310 cancer patients. 75.5 percent of them suffered from rare tumors. Based on 472 individual and six composite biomarkers, a multi-institutional molecular tumor board recommended evidence-based treatment with sometimes novel, experimental therapies in 88 percent of the 1310 cases. The respective recommendations were implemented in approximately one-third of these patients and resulted in significantly improved overall response and disease control rates compared with prior therapies.

“Our data demonstrate the utility of so-called molecular stratification in rare cancers. This forms the basis for new clinical trials and facilitates the approval of drugs in this underserved patient population,” said Stefan Fröhling, Managing Director at NCT Heidelberg and one of the study’s leaders.

“Once again, the present study makes it clear that the interaction of multicentre networks such as the DKTK for translational research and the NCT for clinical research can lead to pioneering achievements in the field of personalised oncology in Germany,” adds Hanno Glimm, Managing Director at NCT/UCC Dresden and also one of the study’s leaders. “In total, more than 100 partners have contributed to the success of the program,” said Glimm. These represent all levels of cancer patient care in Germany – from the top centers to the oncologists in private practice.

In addition to the NCT Heidelberg and the NCT/UCC Dresden, six other DKTK partner sites (Berlin, Essen/Düsseldorf, Frankfurt/Mainz, Freiburg, Munich, Tübingen) cooperate in the DKFZ/NCT/DKTK-MASTER program. The program serves the multidimensional characterization of patients with advanced rare cancers and patients diagnosed with incurable cancer at an unusually early age. The participating physicians and researchers are further developing characterization methods at all levels, for example by including proteomic and epigenomic studies. In addition, treatment approaches beyond drug therapy will be included in the future, for example radiotherapy or surgery. A particular focus of the program is the development and conduct of clinical trials to test treatments that address the characteristics of each cancer. These multidisciplinary efforts aim to provide modern, precision oncology treatment to as many patients as possible.

The Heidelberg NCT site plays a pioneering role in this, as is also evident from related programs – such as the DKFZ/NCT/DKTK-INFORM study, which focuses on children with advanced cancers and is being conducted at the KiTZ (Hopp Children’s Tumor Center Heidelberg).

*Molecularly Aided Stratification for Tumor Eradication Research

Original publication
P. Horak, C. Heining, S. Kreutzfeldt et al. (2021) Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Cancer Discovery, a journal of the American Association for Cancer Research. DOI: 10.1158/2159-8290.CD-21-0126

Further information
www.nct-heidelberg.de/master
www.nct-dresden.de/forschung/nct-master-program

Contact for referring physicians and patients: master@nct-heidelberg.de

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Press contact:

Dr. Friederike Fellenberg
National Center for Tumor Diseases Heidelberg (NCT)
Press and Public Relations
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 42-1755
E-mail: friederike.fellenberg@nct-heidelberg.de
www.nct-heidelberg.de

Dr. Anna Kraft
National Center for Tumor Diseases Heidelberg Dresden (NCT/UCC)
Press and Public Relations
Tel.: +49 (0)351 458-5548
E-Mail: anna.kraft@nct-dresden.de
www.nct-dresden.de