Incorporation of Multiple Sources into IT - and Data Protection Concepts: Lessons Learned from the FARKOR Project

The IT- and data protection concept of the FAmiliäres Risiko für das KOloRektale Karzinom (FARKOR) project will be presented. FARKOR is a risk adapted screening-project in Bavaria, Germany focusing on young adults with familial colorectal cancer (CRC). For each participant, data from different sources have to be integrated: Treatment records centrally administered by the resident doctors association (KVB), data from health insurance companies (HIC), and patient reported lifestyle data. Patient privacy rights must be observed. Record Linkage is performed by a central independent trust center. Data are decrypted, integrated and analyzed in a secure part of the scientific evaluation center with no connection to the internet (SECSP). The presented concept guarantees participants privacy through different identifiers, separation of responsibilities, data pseudonymization, public-private key encryption of medical data and encrypted data transfer

Data for the elaboration of the CIPROS checklist with items for a patient registry software system: Examples and explanations

The data presented relates to the publication “Enhancing Requirements Engineering for Patient Registry Software Systems with Evidence-based Components” (Lindoerfer and Mansmann, 2017) [1], which describes the strategy behind the development of the CIPROS checklist. This manuscript also compares CIPROS with general requirements specification templates, and standards. The data is shortly described in Section 2.4 and presented in Appendix A. The examples represent the material extracted from the literature used in qualitative analysis. The explanations summarize the example contents from which the CIPROS checklist was created. Patient registries are a crucial part of medical research. High quality registries use efficient information systems software selected from a wide variety of existing software solutions. An efficient selection process requires focused selection criteria. The evidence-based CIPROS checklist [2] accelerates this requirements engineering process. CIPROS was developed in a multistep procedure: (1) A systematic literature review provided an exhaustive collection of relevant publications (64 articles), (2) a catalogue of relevant criteria was derived by a qualitative content analysis, and (3) the checklist containing 72 items was composed which provides a minimal appraisal standard. The data presented per checklist item provide the relevant textual information (examples) and a first qualitative summary (explanation). The examples and explanations provide the background information on CIPROS. They elucidate how to implement the checklist items in other projects. The literature list and the selected texts serve as a reference for scientists and system developers

Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models

BACKGROUND The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms. METHODS We analyzed 21 KRAS, NRAS, BRAF, and PI3K wildtype CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity. Furthermore, 31 anti-EGFR SR tumors were generated via chronic in vivo treatment with cetuximab. A multi-omics approach was employed to address molecular primary and secondary resistance mechanisms. Gene set enrichment analyses were used to uncover SR pathways. Targeted therapy of SR PDX models was applied to validate selected SR pathways. RESULTS In vivo anti-EGFR SR could be established with high efficiency. Chronic anti-EGFR treatment of CRC PDX tumors induced parallel evolution of multiple resistant lesions with independent molecular SR mechanisms. Mutations in driver genes explained SR development in a subgroup of CRC PDX models, only. Transcriptional reprogramming inducing anti-EGFR SR was discovered as a common mechanism in CRC PDX models frequently leading to RAS signaling pathway activation. We identified cAMP and STAT3 signaling activation, as well as paracrine and autocrine signaling via growth factors as novel anti-EGFR secondary resistance mechanisms. Secondary resistant xenograft tumors could successfully be treated by addressing identified transcriptional changes by tailored targeted therapies. CONCLUSIONS Our study demonstrates that SR PDX tumors provide a unique platform to study molecular SR mechanisms and allow testing of multiple treatments for efficient targeting of SR mechanisms, not possible in the patient. Importantly, it suggests that the development of anti-EGFR tolerant cells via transcriptional reprogramming as a cause of anti-EGFR SR in CRC is likely more prevalent than previously anticipated. It emphasizes the need for analyses of SR tumor tissues at a multi-omics level for a comprehensive molecular understanding of anti-EGFR SR in CRC