Patient and Clinician Preferences for Genetic and Genomic Testing in Non-Small Cell Lung Cancer: A Discrete Choice Experiment.

Precision (personalised) medicine for non-small cell lung cancer (NSCLC) adopts a molecularly guided approach. Standard-of-care testing in Australia is via sequential single-gene testing which is inefficient and leads to tissue exhaustion. The purpose of this study was to understand preferences around genetic and genomic testing in locally advanced or metastatic NSCLC. A discrete choice experiment (DCE) was conducted in patients with NSCLC (n = 45) and physicians (n = 44). Attributes for the DCE were developed based on qualitative interviews, literature reviews and expert opinion. DCE data were modelled using a mixed multinomial logit model (MMNL). The results showed that the most important attribute for patients and clinicians was the likelihood of an actionable test, followed by the cost. Patients significantly preferred tests with a possibility for reporting on germline findings over those without (ß = 0.4626) and those that required no further procedures over tests that required re-biopsy (ß = 0.5523). Physician preferences were similar (ß = 0.2758 and ß = 0.857, respectively). Overall, there was a strong preference for genomic tests that have attribute profiles reflective of comprehensive genomic profiling (CGP) and whole exome sequencing (WES)/whole genome sequencing (WGS), irrespective of high costs. Participants preferred tests that provided actionable outcomes, were affordable, timely, and negated the need for additional biopsy.

Activin A is essential for neurogenesis following neurodegeneration.

It has long been proposed that excitotoxicity contributes to nerve cell death in neurodegenerative diseases. Activin A, a member of the transforming growth factor-beta superfamily, is expressed by neurons following excitotoxicity. We show for the first time that this activin A expression is essential for neurogenesis to proceed following neurodegeneration. We found that intraventricular infusion of activin A increased the number of newborn neurons in the dentate gyrus, CA3, and CA1 layers of the normal adult hippocampus and also, following lipopolysaccharide administration, had a potent inhibitory effect on gliosis in vivo and on microglial proliferation in vivo and in vitro. Consistent with the role of activin A in regulating central nervous system inflammation and neurogenesis, intraventricular infusion of follistatin, an activin A antagonist, profoundly impaired neurogenesis and increased the number of microglia and reactive astrocytes following onset of kainic acid-induced neurodegeneration. These results show that inhibiting endogenous activin A is permissive for a potent underlying inflammatory response to neurodegeneration. We demonstrate that the anti-inflammatory actions of activin A account for its neurogenic effects following neurodegeneration because co-administration of nonsteroidal anti-inflammatory drugs reversed follistatin's inhibitory effects on neurogenesis in vivo. Our work indicates that activin A, perhaps working in conjunction with other transforming growth factor-beta superfamily molecules, is essential for neurogenesis in the adult central nervous system following excitotoxic neurodegeneration and suggests that neurons can regulate regeneration by suppressing the inflammatory response, a finding with implications for understanding and treating acute and chronic neurodegenerative diseases.