vom 04.06.2019

Stomach and colorectal cancer: Identifying patients at an early stage who are suitable for artificial intelligence immunotherapy.

Joint press release of the Uniklinik RWTH Aachen and NCT Heidelberg.

Tissue from a patient (a) with microsatellite instability (MSI) and a patient (b) with microsatellite stability (MSS). Image source: Jakob Nikolas Kather
Tissue from a patient (a) with microsatellite instability (MSI) and a patient (b) with microsatellite stability (MSS). Image source: Jakob Nikolas Kather

Changes in certain sections of the genetic material of cancer cells, so-called microsatellites, can provide an important indication of whether immunotherapy may be successful in a patient with stomach or colorectal cancer. Scientists from Uniklinik RWTH Aachen, the German Cancer Research Center (DKFZ), the German Cancer Consortium (DKTK) and the National Center for Tumor Diseases Heidelberg (NCT) have developed an adaptive algorithm that can predict instability in microsatellites based directly on images of tissue samples. This could help to potentially identify patients at an early stage who could benefit from immunotherapy. The research results were published in the journal Nature Medicine.

The National Center for Tumor Diseases Heidelberg (NCT) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD), and German Cancer Aid.


Only a small number of patients with stomach or colorectal cancer respond to immunotherapy. Some tumors lead to changes in the genetic material, and this can cause mutations in the sections of the genome, referred to as “microsatellites”, that are frequently replicated. This microsatellite instability (MSI) is a characteristic for distinguishing between different cancers of the gastrointestinal tract and determines whether patients with these diseases are able to respond well to immunotherapy with checkpoint inhibitors. Detecting these properties usually requires a genetic or immunohistochemical test, which requires additional costs and is not always automatically performed for every patient in clinical practice.

The scientists in Aachen and Heidelberg, in collaboration with international colleagues, showed that a computer-aided adaptable algorithm, based on the concept of “deep learning”, enables MSI to be directly diagnosed based on routinely available images of tissue samples without the need for additional laboratory tests. “With our approach, we have the potential to test any patient with colorectal cancer for MSI automatically and cost-effectively, which allows us to provide the option of immunotherapy to a larger group of colorectal cancer patients,” says Jakob Nikolas Kather, physician and scientist at the Clinic for Gastroenterology, Metabolic Diseases and Internal Intensive Care (Medical Clinic III) at Uniklinik RWTH Aachen and member of staff at DKFZ and NCT Heidelberg. “This makes it possible to identify patients who may otherwise never be considered for immunotherapy. However, this approach must be reviewed in prospective studies,” adds Dirk Jäger, Medical and Executive Director of the Department of Medical Oncology at NCT Heidelberg.    

Immunotherapy for cancer
Cancer immunotherapies with so-called checkpoint inhibitors, which can be seen as active agents that release the “brakes” of the immune system, have attracted considerable attention in recent years. For colorectal cancer, however, checkpoint inhibitors have thus far only been successful in “microsatellite instable” tumors. In the more common “microsatellite stable” cases of colorectal cancer, checkpoint inhibitors have not shown objective response rates in previous studies. It remains challenging to predict which patients can benefit from immunotherapy in daily practice. This makes it all the more important to identify patients at an early stage who could benefit from immunotherapy in day-to-day clinical treatment.

Artificial intelligence in medicine
Artificial intelligence and adaptable algorithms are becoming increasingly prominent in medicine. Technological support has been required for a long time. The relevant data are entered into the applications, thereby training the algorithm to analyze large amounts of data and medical images to enable more efficient and more accurate treatments, such as the automatic detection of cancer cells.

Original publication
Jakob Nikolas Kather, Alexander T. Pearson, Niels Halama, Dirk Jäger, Jeremias Krause, Sven H. Loosen, Alexander Marx, Peter Boor, Frank Tacke, Ulf Peter Neumann,
Heike I. Grabsch, Takaki Yoshikawa, Hermann Brenner, Jenny Chang-Claude,
Michael Hoffmeister, Christian Trautwein, Tom Luedde (2019) Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer. Nature Medicine, https://www.nature.com/articles/s41591-019-0462-y

An image for the press release is available free of charge on the internet:
https://www.nct-heidelberg.de/fileadmin/media/nct-heidelberg/news/Meldungen/Bilder/Abb_Gewebeproben_von_MSI_und_MSS.jpg
Caption: Tissue from a patient (a) with microsatellite instability (MSI) and a patient (b) with microsatellite stability (MSS).

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The use of images is free of charge. The NCT Heidelberg permits one-time use in connection with coverage of the subject of the press release. Please list the photo credits: “Jakob Nikolas Kather”. The transmission of photographic material to third parties is only permitted after prior consultation with the NCT Press Office (Tel. 06221 56 5930, Email: friederike.fellenberg@nct-heidelberg.de). Use for commercial purposes is prohibited.


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National Center for Tumor Diseases Heidelberg (NCT)
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National Center for Tumor Diseases Heidelberg (NCT)
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital (UKHD) and German Cancer Aid. The NCT’s goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. This is true for both diagnosis and treatment, follow-up care or prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here, the patients benefit from an individual treatment plan prepared in interdisciplinary expert rounds, so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. Since 2015, the NCT Heidelberg has maintained a partner site in Dresden. The Hopp Children’s Cancer Center (KiTZ) was established in Heidelberg in 2017. The pediatric oncologists at KiTZ work together in parallel structures with the NCT Heidelberg.

German Cancer Research Center (DKFZ)
The German Cancer Research Center (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. Together 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.

German Cancer Consortium (DKTK)
The German Cancer Consortium (DKTK) is a joint long-term initiative involving the German Federal Ministry of Education and Research (BMBF), participating German states and the German Cancer Research Center (DKFZ) and was established as one of six German Health Research Centres (DZGs).
As DKTK’s core center the DKFZ works together with research institutions and hospitals in Berlin, Dresden, Essen/Düsseldorf, Frankfurt/Mainz, Freiburg, Munich, Heidelberg and Tübingen to create the best possible conditions for clinically oriented cancer research. The consortium promotes interdisciplinary research at the interface between basic research and clinical research, as well as clinical trials for innovative treatments and diagnostic methods. Another key focus of the consortium’s work is on developing research platforms to speed up the application of personalized cancer treatments and to improve the diagnosis and prevention of cancer.

Heidelberg University Hospital (UKHD)

Heidelberg University Hospital (UKHD) is one of the most important medical centers in Germany; Heidelberg University’s Medical Faculty is one of Europe's most prestigious biomedical research facilities. Their shared objective is the development of innovative diagnostics and treatments and their prompt implementation for the benefit of the patient. The hospital and faculty employ approximately 13,000 individuals and are involved in training and qualification. Every year approximately 65,000 patients are treated as inpatients and 56,000 as day patients in more than 50 specialized clinical departments with around 2,000 beds, with more than 1 million patients being treated as outpatients. Together with the German Cancer Research Center and German Cancer Aid, the Heidelberg University Hospital established The National Center for Tumor Diseases (NCT) Heidelberg as the leading oncology center of excellence in Germany. The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical training in Germany. At present 3,700 aspiring physicians and doctors are studying in Heidelberg.

Uniklinik RWTH Aachen

The Uniklinik RWTH Aachen is a supramaximal care provider that combines patient-oriented medicine and nursing, teaching and research at an international level. With 36 specialist clinics, 25 institutes and five interdisciplinary units, the University Hospital covers the entire medical spectrum. Excellently qualified teams of doctors, nurses and scientists are competently committed to the health of the patients. The bundling of patient care, research and teaching in one central building offers the best conditions for intensive interdisciplinary exchange and close clinical and scientific networking. Around 7.000 employees provide patient-oriented medicine and care according to recognised quality standards. With 1.400 beds, the University Hospital treats around 50.000 inpatient and 200.000 outpatient cases per year.