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Background
The national Network Genomic Medicine (nNGM) Lung Cancer provides comprehensive and high-quality multiplex molecular diagnostics and standardized personalized treatment recommendation for patients with advanced non-small cell lung cancer (aNSCLC) in Germany. The primary aim of this study was to investigate the effectiveness of the nNGM precision medicine program in terms of overall survival (OS) using real-world data (RWD).
Methods
A historical nationwide cohort analysis of patients with aNSCLC and initial diagnosis between 04/2019 and 06/2020 was conducted to compare treatment and OS of patients with and without nNGM-participation. Patients participating within the nNGM (nNGM group) were selected based on a prospective nNGM database. The electronic health records (EHR) of the prospective nNGM database were case-specifically linked to claims data (AOK, German health insurance). The control group was selected from claims data of patients receiving usual care without nNGM-participation (non-nNGM group). The minimum follow-up period was six months.
Findings
Overall, n = 509 patients in the nNGM group and n = 7213 patients in the non-nNGM group met the inclusion criteria. Patients participating in the nNGM had a significantly improved OS compared to the non-nNGM group (median OS: 10.5 months vs. 8.7 months, p = 0.008, HR = 0.84, 95% CI: 0.74–0.95). The 1-year survival rates were 46.8% (nNGM) and 41.3% (non-nNGM). The use of approved tyrosine kinase inhibitors (TKI) in the first-line setting was significantly higher in the nNGM group than in the non-nNGM group (nNGM: 8.4% (43/509) vs. non-nNGM: 5.1% (366/7213), p = 0.001). Overall, patients receiving first-line TKI treatment had significantly higher 1-year OS rates than patients treated with PD-1/PD-L1 inhibitors and/or chemotherapy (67.2% vs. 40.2%, p < 0.001).
Interpretation
This is the first study to demonstrate a significant survival benefit and higher utilization of targeted therapies for aNSCLC patients participating within nNGM. Our data indicate that precision medicine programs can enhance collaborative personalized lung cancer care and promote the implementation of treatment innovations and the latest scientific knowledge into clinical routine care.
Funding
The study was funded by the AOK Federal Association Germany.
Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, Ptpn6) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2, Ptpn11) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate. Here, we analyzed the role of the constitutively active SHP2-D61Y-mutant in T cell activation using knock-in mice expressing the mutant form Ptpn11D61Y
in T cells. We observed reduced numbers of CD8+ and increased numbers of CD4+ T cells in the bone marrow and spleen of young and aged SHP2-D61Y-mutant mice as well as in Influenza A Virus (IAV)-infected mice compared to controls. In addition, we found elevated frequencies of effector memory CD8+ T cells and an upregulation of the programmed cell death protein 1 (PD-1)-receptor on both CD4+ and CD8+ T cells. Functional analysis of SHP2-D61Y-mutated T cells revealed an induction of late apoptosis/necrosis, a reduced proliferation and altered signaling upon TCR stimulation. However, the ability of D61Y-mutant mice to clear viral infection was not affected. In conclusion, our data indicate an important regulatory role of SHP2 in T cell function, where the effect is determined by the kinetics of SHP2 phosphatase activity and differs in the presence of the permanently active and the temporally regulated phosphatase. Due to interaction of SHP2 with the PD-1-receptor targeting the protein-tyrosine phosphatase might be a valuable tool to enhance T cell activities in immunotherapy.
Purpose
Patient-reported outcome (PRO) measures are increasingly important in evaluating medical care. The increased integration of technology within the healthcare systems allows for collection of PROs electronically. The objectives of this study were to Ashley et al. J Med Internet Res (2013) implement an electronic assessment of PROs in inpatient cancer care and test its feasibility for patients and Dawson et al. BMJ (2010) determine the equivalence of the paper and electronic assessment.
Methods
We analyzed two arms from a study that was originally designed to be an interventional, three-arm, and multicenter inpatient trial. A self-administered questionnaire based on validated PRO-measures was applied and completed at admission, 1 week after, and at discharge. For this analysis — focusing on feasibility of the electronic assessment — the following groups will be considered: Group A (intervention arm) received a tablet version, while group B (control arm) completed the questionnaire on paper. A feasibility questionnaire, that was adapted from Ashley et al. J Med Internet Res (2013), was administered to group A.
Results
We analyzed 103 patients that were recruited in oncology wards. ePRO was feasible to most patients, with 84% preferring the electronic over paper-based assessment. The feasibility questionnaire contained questions that were answered on a scale ranging from “1” (illustrating non achievement) to “5” (illustrating achieving goal). The majority (mean 4.24, SD .99) reported no difficulties handling the electronic tool and found it relatively easy finding time for filling out the questionnaire (mean 4.15, SD 1.05). There were no significant differences between the paper and the electronic assessment regarding the PROs.
Conclusion
Results indicate that electronic PRO assessment in inpatient cancer care is feasible.