ABSTRACT
Introduction: The yield of adding plasma-based next-generation sequencing (NGS) to tissue NGS for the detection of actionable aberrations (AAs) has been reported; however, additional studies are needed to determine utility in the clinical setting. In this retrospective data review, we present our real world data on the utilization of liquid biopsies in the routine management of NCSLC patients, in a community setting. Methods: We conducted a retrospective review of 279 consecutive patients with non-small cell lung cancer (NSCLC) in the community setting, who had liquid biopsies performed between the years 2014 and 2019 as part of routine clinical management. Results: Over a period of 5 years, 337 liquid biopsy samples, taken from 279 patients were sent for plasma NGS testing. The median age at diagnosis was 73 years (range 36-93 y, SD 10.4 y), 141, (51%) were men and 138 (49%) were women. The majority were White or Caucasian (80% versus 8% Black or African American versus 12% Multiracial or unknown race) and had a history of smoking (79%). Excluding synonymous mutations and variants of unknown significance, 254 AAs were detected in 106 patients. Commonly detected AAs were EGFR (n = 127, 50%), KRAS (n = 61, 24%), BRAF (n = 24, 9.5%), and MET (n = 23, 9%). Tissue NGS detected AAs in 45 patients, with EGFR (n = 28, 57%) and KRAS (n = 10, 20%) being the most common AAs. Concordance agreement between plasma and tissue NGS modalities was detected in 39 of 45, 87% patients and was demonstrated most commonly in EGFR (n = 25) and KRAS (n = 11). In 44 of 106 (42%) of patients, for whom tissue NGS was not performed, additional precision treatment was guided by the AA detected through liquid biopsy. Conclusions: Integration of liquid biopsy into the routine management of patients with non-small cell lung cancer demonstrated AA detection in 44 additional patients, which comprise a 42% increase in AA detection rate, when tissue NGS was not performed.
ABSTRACT
It is likely that the pathophysiology of exertional heat stroke (EHS) differs from passive heat stroke (PHS), but this has been difficult to verify experimentally. C57Bl/6 mice were instrumented with temperature transponders and underwent 3 wk of training using voluntary and forced running wheels. An EHS group was exposed to environmental temperatures (Tenv) of 37.5, 38.5, or 39.5°C at either 30, 50, or 90% relative humidities (RH) while exercising on a forced running wheel. Results were compared with sham-matched exercise controls (EXC) and naïve controls (NC). In EHS, mice exercised in heat until they reached limiting neurological symptoms (loss of consciousness). The symptom-limited maximum core temperatures achieved were between 42.1 and 42.5°C at 50% RH. All mice that were followed for 4 days survived. Additional groups were killed at 0.5, 3, 24, and 96 h, post-EHS or -EXC. Histopathology revealed extensive damage in all regions of the small intestine, liver, and kidney. Plasma creatine kinase, blood urea nitrogen, alanine transaminase, and intestinal fatty acid binding protein-2 were significantly elevated compared with matched EXC and NC, suggesting multiple organ injury to striated muscle, kidney, liver, and intestine, respectively. EHS mice were hypoglycemic immediately following EHS but exhibited sustained hyperglycemia through 4 days. The results demonstrate unique features of survivable EHS in the mouse that included loss of consciousness, extensive organ injury, and rhabdomyolysis.
