Comprehensive molecular analysis in cancer of unknown primary can improve cancer therapy

Joint press release by the NCT/UCC Dresden and the NCT Heidelberg

A considerable proportion of patients suffering from cancer of unknown primary (CUP) could benefit from comprehensive molecular analysis and molecularly-informed targeted therapies. These are the findings of a study by a team of researchers from the German Cancer Research Center (DKFZ), University Hospital Carl Gustav Carus Dresden and the National Center for Tumor Diseases (NCT) in Dresden and Heidelberg. The results from the DKFZ/NCT/DKTK MASTER program have been published in Nature Communications. Other ongoing studies involving researchers at the DKFZ and NCT aim to pave the way for molecular diagnostics and targeted therapies to be established for CUP and for the costs to be covered by statutory health insurance schemes.

The NCT is a cross-site cooperation between the German Cancer Research Center (DKFZ) and the Heidelberg University Hospital (UKHD) in Heidelberg, as well as the DKFZ, the University Hospital Carl Gustav Carus Dresden, the Carl Gustav Carus Faculty of Medicine at TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) in Dresden.

CUP accounts for around two to four percent of all cancer cases, affecting around 10,000 people in Germany each year. In these cases, metastases are detected but no primary tumor. Since this means that the cancer has already spread to other parts of the body and is therefore advanced and usually aggressive, the prognosis is generally poor. There is an urgent need for new therapeutic options.
The number of possible genetic alterations that can play a role in oncogenesis and affect treatment is particularly high compared with other types of cancer. In this study involving 70 patients, researchers therefore examined the disease using the most comprehensive molecular analysis to date. This analysis included sequencing the entire tumor genome or exome (the protein-coding part of the genome, in which the majority of known disease-causing variants are to be found), the tumor RNA (transcriptome), certain chemical changes in the DNA (methylome) and a search for hereditary cancer risk factors. For 80 percent of patients, a molecular tumor board – an interdisciplinary team with expertise in oncology, pathology, molecular biology, bioinformatics and human genetics – was able to use this analysis to recommend targeted therapies based on specific genetic changes. 35 percent of patients were treated in line with the recommendation and showed improved disease control compared with the previous therapy. The mean ratio of the progression-free survival (PFS) of targeted therapy to the PFS of the last prior systemic therapy (PFS ratio) was 3.6.

Hanno Glimm, member of the managing directorate of NCT/UCC Dresden and head of department at the DKFZ, explains: “Our study combines the broadest molecular analysis of CUP to date with consistent recommendation and implementation of targeted therapies. The results show that a significant proportion of patients can benefit from this approach, even in late stages of the disease or after several previous therapies.” Stefan Fröhling, Managing Director of NCT Heidelberg and head of department at the DKFZ, says: “The results of the study clearly show that every CUP patient should be offered molecular analysis that is as comprehensive as possible, and that the current therapy standard, which usually comprises chemotherapy treatment, needs to be revised. We recommend that all CUP patients attend a specialized cancer center to explore the possibilities offered by broad molecular analysis and targeted therapy.”

The plan now is for further trials involving the NCT to create the basis for ensuring that, as a rule, the costs of molecular diagnostics and targeted therapies for CUP patients are covered by the statutory health insurance schemes. Lino Möhrmann, the lead author of the study and a clinician scientist at NCT/UCC Dresden, who is funded by the Else Kröner Forschungskolleg (EKFK), says: “We are very happy that we are already able to offer broad molecular diagnostics to all CUP patients at the NCT sites. We are also able to enroll a large number of patients in trials. Moreover, we have instituted a dedicated outpatient clinic for CUP patients at the NCT sites, where we can focus on weighing up, discussing and implementing existing options with patients.”

MASTER program

The study was conducted within MASTER, a precision oncology program involving the eight partner sites of the German Cancer Consortium (DKTK) as well as the DKFZ and the NCT sites in Heidelberg and Dresden. The program identifies new therapeutic options for patients with rare types of cancer or who have developed cancer at an unusually early age, based on comprehensive molecular analyses. Since, in the case of rare cancers, the patient groups at individual cancer centers are usually too small for meaningful research, the organizations involved in the MASTER program work closely with more than 100 partners across Germany. Between 2012, when the program started, and 2021, it had enrolled more than 3,500 patients.

Contact for patients and referring physicians to obtain a second opinion or request an assessment for potential enrollment in a trial:
For patients (NCT/UCC Dresden): www.nct-dresden.de/zweitmeinung
For referring physicians (NCT/UCC Dresden): www.nct-dresden.de/patientenanmeldung
For patients and referring physicians (NCT Heidelberg): Send an email to master(at)nct-heidelberg.de

Publication:
L. Möhrmann, M. Werner, M. Oleś, A. Mock, S. Uhrig et al. Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity. Nat Commun 13, 4485 (2022). https://doi.org/10.1038/s41467-022-31866-4 ; Full text: https://rdcu.be/cST00

A photo to accompany the press release is available free of charge from:
https://www.nct-dresden.de/fileadmin/media/nct-dresden/das-nct/newsroom/pressemitteilungen/CUP-Analyse.jpg
Caption: A physician and a bioinformatician evaluate the results of the molecular analysis of a patient with CUP. © Uniklinikum Dresden/Kirsten Lassig

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Press contact:

Dr Anna Kraft
National Center for Tumor Diseases Dresden (NCT/UCC)
Press and public relations
Phone: +49 (0)351 458-5548
Email: www.nct-heidelberg.de www.nct-dresden.de

Dr. Martin Staiger
National Center for Tumor Diseases (NCT) Heidelberg
Communication and events
In Neuenheimer Feld 460
69120 Heidelberg
Phone: +49 6221 42-1755
Email: martin.staiger@nct-heidelberg.de
www.nct-heidelberg.de

National Center for Tumor Diseases Dresden (NCT/UCC)
The National Center for Tumor Diseases Dresden (NCT/UCC) is a joint institution of the German Cancer Research Center, the University Hospital Carl Gustav Carus Dresden, the Carl Gustav Carus Faculty of Medicine at TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).
The NCT has made it its duty to closely link research and patient care wherever possible. That is why cancer patients at the NCT sites can be treated based on the latest research results. At the same time, the proximity of laboratory and clinic provides researchers with important impulses for their practice-oriented research. The NCT sites share the common goal of developing the NCT into a top international center for patient-oriented cancer research. The Dresden center draws on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. Since 2007, the UCC has been honored by the German Cancer Aid e.V. (DKH) as a "Top Oncological Center" on a continuous basis.

National Center for Tumor Diseases (NCT) Heidelberg
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ), the Heidelberg University Hospital (UKHD), the Medical Faculty of the University of Heidelberg and the German Cancer Aid. The aim of the NCT is to transfer promising approaches from cancer research to the clinic as quickly as possible and thus to benefit the patients. This applies to diagnosis as well as treatment, follow-up care or prevention. The tumor outpatient clinic is the heart of the NCT. Here, the patients benefit from an individual therapy plan drawn up by interdisciplinary panels of experts, the so-called tumor boards. Participation in clinical studies opens up access to innovative therapies. The NCT is thus a trend-setting platform for transferring new research results from the laboratory to the clinic. The NCT cooperates with self-help groups and supports them in their work. The NCT Heidelberg has had a partner location in Dresden since 2015. The Hopp Children's Cancer Center (KiTZ) was founded in Heidelberg in 2017. The pediatric oncologists at the KiTZ work together with the NCT Heidelberg in joint structures.