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German cancer registries offer a systematic approach for the collection, storage, and management of data on patients with cancer and related diseases. Much hope in research and healthcare in general is depending on such register-based analyses in order to comprehensively consider the features of a highly diverse population. Next to the data collection the cancer registries are responsible for data protection. To fulfill legal regulations, access to data has to be controlled in a strict way leading to sometimes bureaucratic and slow processes. The situation is especially complicated in Germany, since cancer data is distributed over numerous federal cancer registries. If a nationwide data evaluation is conducted a research team has to negotiate a separate contract with each cancer registry.In a joint work in progress effort of cancer registries, technical, medical, and economical experts we propose a different solution for cooperative data processing. Our approach aims for combining data in a virtual pool based on the selection criteria of individual requests from researchers. To achieve our goal, we adapt the Fraunhofer Medical Data Space as enabling technology. The architecture we propose will allow us to pool data of multiple partners regulated by data access policies. In doing so, each of the data sources can introduce its own rules and specifications on how data is used. Additionally, we add a digital consent management that will allow individual patients to decide how their data is used. Finally, we show the high potential of the cooperative analysis of distributed cancer data supported by the proposed solution in our approach.
In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described.
After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.