Olfactory Detection of Toluene by Detection Rats for Potential Screening of Lung Cancer

Early detection is critical to successfully eradicating a variety of cancers, so the development of a new cancer primary screening system is essential. Herein, we report an animal nose sensor system for the potential primary screening of lung cancer. To establish this, we developed an odor discrimination training device based on operant conditioning paradigms for detection of toluene, an odor indicator component of lung cancer. The rats (N = 15) were trained to jump onto a floating ledge in response to toluene-spiked breath samples. Twelve rats among 15 trained rats reached performance criterion in 12 consecutive successful tests within a given set, or over 12 sets, with a success rate of over 90%. Through a total of 1934 tests, the trained rats (N = 3) showed excellent performance for toluene detection with 82% accuracy, 83% sensitivity, 81% specificity, 80% positive predictive value (PPV) and 83% negative predictive value (NPV). The animals also acquired considerable performance for odor discrimination even in rigorous tests, validating odor specificity. Since environmental and long-term stability are important factors that can influence the sensing results, the performance of the trained rats was studied under specified temperature (20, 25, and 30 °C) and humidity (30%, 45%, and 60% RH) conditions, and monitored over a period of 45 days. At given conditions of temperature and humidity, the animal sensors showed an average accuracy within a deviation range of ±10%, indicating the excellent environmental stability of the detection rats. Surprisingly, the trained rats did not differ in retention of last odor discrimination when tested 45 days after training, denoting that the rats’ memory for trained odor is still available over a long period of time. When taken together, these results indicate that our odor discrimination training system can be useful for non-invasive breath testing and potential primary screening of lung cancer.

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Multi-Odor Discrimination by Rat Sniffing for Potential Monitoring of Lung Cancer and Diabetes

Sensors ◽

10.3390/s21113696 ◽

2021 ◽

Vol 21 (11) ◽

pp. 3696

Author(s):

Yunkwang Oh ◽

Ohseok Kwon ◽

Sun-Seek Min ◽

Yong-Beom Shin ◽

Min-Kyu Oh ◽

...

Keyword(s):

Lung Cancer ◽

Cost Effective ◽

Performance Criterion ◽

Odor Discrimination ◽

Long Term Stability ◽

Quantitative Measurements ◽

Behavior Response ◽

Odor Monitoring ◽

Sensing Performance

The discrimination learning of multiple odors, in which multi-odor can be associated with different responses, is important for responding quickly and accurately to changes in the external environment. However, very few studies have been done on multi-odor discrimination by animal sniffing. Herein, we report a novel multi-odor discrimination system by detection rats based on the combination of 2-Choice and Go/No-Go (GNG) tasks into a single paradigm, in which the Go response of GNG was replaced by 2-Choice, for detection of toluene and acetone, which are odor indicators of lung cancer and diabetes, respectively. Three of six trained rats reached performance criterion, in 12 consecutive successful tests within a given set or over 12 sets with a success rate of over 90%. Through a total of 1300 tests, the trained animals (N = 3) showed multi-odor sensing performance with 88% accuracy, 87% sensitivity and 90% specificity. In addition, a dependence of behavior response time on odor concentrations under given concentration conditions was observed, suggesting that the system could be used for quantitative measurements. Furthermore, the animals’ multi-odor sensing performance has lasted for 45 days, indicating long-term stability of the learned multi-odor discrimination. These findings demonstrate that multi-odor discrimination can be achieved by rat sniffing, potentially providing insight into the rapid, accurate and cost-effective multi-odor monitoring in the lung cancer and diabetes.

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Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001904 ◽

2021 ◽

Vol 9 (5) ◽

pp. e001904

Author(s):

Javier Ramos-Paradas ◽

Susana Hernández-Prieto ◽

David Lora ◽

Elena Sanchez ◽

Aranzazu Rosado ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Value ◽

Predictive Biomarker ◽

Small Cell ◽

Small Cell Lung ◽

Mutational Burden ◽

Reproducibility Study ◽

Tumor Mutational Burden

BackgroundTumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.MethodsWe evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.ResultsBoth panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N=55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively.ConclusionsBoth panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.

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Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02254-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zhiyu Peng ◽

Huahang Lin ◽

Ke Zhou ◽

Senyi Deng ◽

Jiandong Mei

Keyword(s):

Lung Cancer ◽

Sensitivity Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Value ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Egfr Mutant ◽

Egfr Tkis

Abstract Objective To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. Results Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. Conclusions The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.

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