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PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P =.17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P =.0004 and 21.7 v 6.4 months, log rank P =.04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS. [ABSTRACT FROM AUTHOR]

Abstract: Understanding how animals perceive, learn and remember stimuli is critical for understanding both how cognition is shaped by natural selection, and how ecological factors impact behaviour. However, the majority of studies on cognition involve captive animals in laboratory settings. While controlled settings are required to accurately measure aspects of cognition, they may not yield realistic estimates of learning performance in natural environments. Wild bees offer a useful system in which to study cognitive ecology and comparative cognition more broadly: they encompass around 20,000 species globally, varying in characteristics such as life‐history strategy, degree of sociality and dietary specialization. Yet, the limited number of protocols currently available for studying insect cognition has restricted research to a few commercially available bee species, in almost exclusively laboratory settings. We present a protocol (Free‐Moving Proboscis Extension Response [FMPER]) to measure wild bees’ colour preferences, learning performance and memory. We first used laboratory‐reared bumblebees Bombus impatiens to establish that FMPER yielded results consistent with learning theory. We then successfully tested wild honeybees Apis mellifera in the laboratory and Bombus vosnesenskii at field sites. Free‐Moving Proboscis Extension Response is straightforward to implement, is low cost, and may be readily adapted to other flower‐visiting insects. We believe it will be useful to a broad range of evolutionary biologists, behavioural ecologists and pollination ecologists interested in measuring cognitive performance in the wild and across a broader range of species. [ABSTRACT FROM AUTHOR]

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs. • Pre-treatment ctDNA features are associated with checkpoint blockade response • Pre-treatment peripheral T cell levels are associated with checkpoint blockade response • Early on-treatment ctDNA dynamics are associated with checkpoint blockade response • Multiparameter noninvasive models can predict checkpoint blockade response in NSCLC Multiparameter noninvasive models that integrate pre-treatment ctDNA and peripheral immune features, together with early on-treatment ctDNA dynamics, show promise in predicting durable clinical response to immune checkpoint blockade treatment in patients with non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: Treatment with PD-(L)1 blockade can produce remarkably durable responses in patients with non-small cell lung cancer (NSCLC). However, a significant fraction of long-term responders ultimately progress and predictors of late progression are unknown. We hypothesized that circulating tumor DNA (ctDNA) analysis of long-term responders to PD-(L)1 blockade may differentiate those who will achieve ongoing benefit from those at risk of eventual progression., Experimental Design: In patients with advanced NSCLC achieving long-term benefit from PD-(L)1 blockade (progression-free survival ≥ 12 months), plasma was collected at a surveillance timepoint late during/after treatment to interrogate ctDNA by Cancer Personalized Profiling by Deep Sequencing. Tumor tissue was available for 24 patients and was profiled by whole-exome sequencing ( n = 18) or by targeted sequencing ( n = 6)., Results: Thirty-one patients with NSCLC with long-term benefit to PD-(L)1 blockade were identified, and ctDNA was analyzed in surveillance blood samples collected at a median of 26.7 months after initiation of therapy. Nine patients also had baseline plasma samples available, and all had detectable ctDNA prior to therapy initiation. At the surveillance timepoint, 27 patients had undetectable ctDNA and 25 (93%) have remained progression-free; in contrast, all 4 patients with detectable ctDNA eventually progressed [Fisher P < 0.0001; positive predictive value = 1, 95% confidence interval (CI), 0.51-1; negative predictive value = 0.93 (95% CI, 0.80-0.99)]., Conclusions: ctDNA analysis can noninvasively identify minimal residual disease in patients with long-term responses to PD-(L)1 blockade and predict the risk of eventual progression. If validated, ctDNA surveillance may facilitate personalization of the duration of immune checkpoint blockade and enable early intervention in patients at high risk for progression., (©2020 American Association for Cancer Research.)