Cancer cells differ from normal cells, which is reflected by changes in their genome. In the case of lung cancer, many such mutations have been characterized. Some of them have direct therapeutic relevance, as there is a treatment available that targets this difference. This is why genotyping of cancer patients is so important: In a significant number of cases, it offers valuable molecular information about the tumour and a direct path to a personalised treatment.
The Network Genomic Medicine utilizes next-generation sequencing (NGS-) based molecular multiplex diagnostics (see infobox) to look for these genomic aberrations with potential therapeutic relevance.
A vital feature of the initiative is the cooperation with community hospitals and private practices. Interested referring doctors send routine tissue diagnostic samples of patients with advanced lung cancer to the centralised platform in Cologne, where this analysis is conducted free of charge. Referring doctors directly benefit from participation, as they are advised regularly concerning the use of new drugs based on molecular findings. This information is kept up to date by regularly updating the diagnostic panel. Molecular aberrations and outcome of targeted treatments are documented in the central NGM database in Cologne.
The network grew constantly and currently includes about 300 referring institutions from all over Germany. We were the first to demonstrate already in 2013 a substantial overall survival benefit of about two years for patients in our network in the case of EGFR or ALK mutations (see Infobox) compared to chemotherapy. In the meantime, based on the availability of next-generations inhibitors and sequential targeted therapies, the outcome again has substantially improved and we see median overall survival times in these subgroups of about 5 years. Based on these observations, molecular multiplex testing is routinely reimbursed now in our network within an integrated care contract with the major German health insurance companies (among others AOK, BEK, TKK). To date, more than 5.000 lung cancer patients (about 10% of the German lung cancer patients) are genotyped annually.
In order to find the best possible treatment for all targetable mutations, clinical trials with cancer patients are needed. To study rare genetic subgroups, recruiting enough patients with the corresponding mutations can be a challenge. Our high throughput molecular diagnostics approach allows routine testing of many patients and enabled us to competitively participate in global practice changing trials, but also to initiate own multicenter trials. We established a personalised early proof of concept clinical trial platform including clinical trials for all targetable mutations.
In addition, rebiopsy programs have been implemented in clinical routine and foster molecularly guided treatment in relapse as well as a deeper understanding of the molecular mechanisms of relapse.
Initial funding was provided by the Ministry for Innovation, Northrhine-Westfalia and the Federal Ministry of Education and Research, Germany (BMBF).
© Universitätsklinik Köln
“Implementing personalised lung cancer into broad clinical routine in Germany will substantially prolong survival of these patients.”
Prof. Dr. Jürgen Wolf, Prof. Dr. Reinhard Büttner, Speaker, Network Genomic Medicine at University Hospital of Cologne
Nationwide expansion of the NGM experience: the national Network Genomic Medicine (nNGM) Lung Cancer
Following these encouraging experiences in the Cologne network, the initiative of the national Network Genomic Medicine (nNGM) Lung Cancer was started in 2018, and funded by the German Cancer Aid (DKH). Initially consisting of 15 Oncology Centers of Excellence, the nNGM has grown to 17 diagnostic centers until now. The idea of nNGM is to extend the NGM model nationwide and thus, to create access to highly innovative molecular diagnostics and innovative therapy for preferably all patients with advanced lung cancer in Germany. According to the guiding principle “Centralized testing, counselling and evaluation – decentralized treatment”, the nNGM unifies molecular multiplex diagnostics, consultation, trial allocation and evaluation across different diagnostic centers, while treatments (except early phase trials) may take place close to home. One first success of nNGM was to extend the integrated care contracts of NGM with the major health insurance companies nationwide, thus, currently, NGS- based molecular diagnostics is already covered for 65% of the German patients with advanced lung cancer. We are convinced that nNGM represents a best practice example now for rapid implementation of innovative genomic cancer medicine in clinical routine in a complex and diversified health care system.