Dataset Information

Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine.

ABSTRACT:

Purpose

Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called "precision medicine." However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kinases. Kinase activity profiling is therefore theorized to be more reflective of in vivo biology than many current molecular analysis techniques. As a result, this study seeks to prove the feasibility of combining a novel minimally invasive biopsy technique that expands the number of lesions amenable for biopsy with subsequent ex vivo kinase activity analysis.

Methods

Eight patients with lung lesions of varying location and size were biopsied using the novel electromagnetic navigational bronchoscopy (ENB) technique. Basal kinase activity (kinomic) profiles and ex vivo interrogation of samples in combination with tyrosine kinase inhibitors erlotinib, crizotinib, and lapatinib were performed by PamStation 12 microarray analysis.

Results

Kinomic profiling qualitatively identified patient specific kinase activity profiles as well as patient and drug specific changes in kinase activity profiles following exposure to inhibitor. Thus, the study has verified the feasibility of ENB as a method for obtaining tissue in adequate quantities for kinomic analysis and has demonstrated the possible use of this tissue acquisition and analysis technique as a method for future study of lung cancer biomarkers.

Conclusions

We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients.

SUBMITTER: Anderson JC

PROVIDER: S-EPMC4280210 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine.

Anderson Joshua C JC Minnich Douglas J DJ Dobelbower M Christian MC Denton Alexander J AJ Dussaq Alex M AM Gilbert Ashley N AN Rohrbach Timothy D TD Arafat Waleed W Welaya Karim K Bonner James A JA Willey Christopher D CD

PloS one 20141230 12

<h4>Purpose</h4>Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called "precision medicine." However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kin ...[more]

PMID: 25549342

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Project description:Background: Electromagnetic navigational bronchoscopy (ENB) and robotic-assisted bronchoscopy (RB) require a high degree of decision-making and psychomotor skill. Cognitive load theory is the overall effort expended by individuals in response to a task and is closely related to the usability of devices for medical procedures. High cognitive workload leads to poor surgical outcomes and represents a bottleneck for learning that affects performance.Objective: To analyze the cognitive load associated with ENB and RB in experienced ENB practitioners learning RB.Methods: Six experienced ENB bronchoscopists performed ENB and RB on a human cadaver model of peripheral pulmonary nodules. To assess cognitive load, we used the Surgery Task Load Index (SURG-TLX) and biometric changes. The SURG-TLX questionnaire was given to the provider after every peripheral pulmonary nodule biopsy with ENB and RB. Pupillary dilation and screen changes were continuously measured throughout the procedure for each biopsy attempt to collect biometric measures of cognitive load. Procedural time and biopsy outcome were also recorded.Results: Forty procedures (ENB and RB) were analyzed. Task complexity (23%) and mental demand (21.4%) were the highest contributors to cognitive load in ENB and RB. The cumulative SURG-TLX was significantly lower for the RB (69.25 vs. 101.25; P < 0.01). Total procedure time was greater for ENB (6.7 min; SD 1.5) compared with RB (4.4 min; SD 1.5; P = 0.01). Pupillary diameter was similar across the modalities (RB vs. ENB), but the diameter was higher during the biopsy portion (4.25 mm) than the navigation portion (4.01 mm).Conclusion: The intrinsic cognitive load of RB was highly manageable by existing ENB practitioners, and in this study, RB appeared to be less mentally demanding. Future development and training should focus on task complexity and mental demand for RB. The biopsy portion, regardless of bronchoscopic modality, should be a focus for education and training.

Project description:Objectives:Over 25% of the high-risk population screened for lung cancer have an abnormal computed tomography (CT) scan. Conventionally, these lesions have been biopsied with CT guidance with a high diagnostic yield. Electromagnetic navigational bronchoscopy (ENB) with transbronchial biopsy has emerged as a technology that improves the diagnostic sensitivity of conventional bronchoscopic biopsy. It has been used to biopsy lung lesions, due to the low risk of pneumothorax. It is, however, a new technology that is expensive and its role in the diagnosis of the solitary pulmonary nodule (SPN) is yet to be determined. The purpose of this study was to evaluate the diagnostic yield of CT-guided biopsy (CTB) following non-diagnostic ENB biopsy and identify characteristics of the lesion that predicts a low diagnostic yield with ENB, to ensure appropriate use of ENB in the evaluation of SPN. Materials and Methods:One hundred and thirty-five lung lesions were biopsied with ENB from January 2017 to August 2019. Biopsies were considered diagnostic if pathology confirmed malignancy or inflammation in the appropriate clinical and imaging setting. We evaluated lesions for several characteristics including size, lobe, and central/peripheral distribution. The diagnostic yield of CTB in patients who failed ENB biopsies was also evaluated. Logistic regression was used to identify factors likely to predict a non-diagnostic ENB biopsy. Result:Overall, ENB biopsies were performed in 135 patients with solitary lung lesions. ENB biopsies were diagnostic in 52% (70/135) of the patients. In 23 patients with solitary lung lesions, CTBs were performed following a non-diagnostic ENB biopsy. The CTBs were diagnostic in 87% of the patients (20/23). ENB biopsies of lesions <21.5 mm were non-diagnostic in 71% of cases (42/59); 14 of these patients with non-diagnostic ENB biopsies had CTBs, and 86% of them were diagnostic (12/14). ENB biopsies of lesions in the lower lobes were non- diagnostic in 59% of cases (35/59); 12 of these patients with non-diagnostic ENB biopsies had CTBs, and 83% were diagnostic (10/12). ENB biopsies of lesions in the outer 2/3 were non-diagnostic in 57% of cases (50/87); 21 of these patients with non-diagnostic ENB biopsies had CTBs, and 86% were diagnostic (18/21). Conclusion:CTBs have a high diagnostic yield even following non-diagnostic ENB biopsies. Lesions <21.5 mm, in the outer 2/3 of the lung, and in the lower lung have the lowest likelihood of a diagnostic yield with ENB biopsies. Although CTBs have a slightly higher pneumothorax rate, these lesions would be more successfully diagnosed with CTB as opposed to ENB biopsy, in the process expediting the diagnosis and saving valuable medical resources.

Project description:BackgroundSerum steroids are crucial molecules altered in prostate cancer (PCa). Mass spectrometry (MS) is currently the elected technology for the analysis of steroids in diverse biological samples. Steroids have complex biological pathways and stoichiometry and it is important to evaluate their quantitative ratio. MS applications to patient hormone profiling could lead to a diagnostic approach.MethodsHere, we employed the Surface Activated Chemical Ionization-Electrospray-NIST (SANIST) developed in our laboratories, to obtain quantitative serum steroid ratio relationship profiles with a machine learning Bayesian model to discriminate patients with PCa. The approach is focused on steroid relationship profiles and disease association.ResultsA pilot study on patients affected by PCa, benign prostate hypertrophy (BPH), and control subjects [prostate-specific antigen (PSA) lower than 2.5 ng/mL] was done in order to investigate the classification performance of the SANIST platform. The steroid profiles of 71 serum samples (31 controls, 20 patients with PCa and 20 subjects with benign prostate hyperplasia) were evaluated. The levels of 10 steroids were quantitated on the SANIST platform: Aldosterone, Corticosterone, Cortisol, 11-deoxycortisol, Androstenedione, Testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), 17-OH-Progesterone and Progesterone. We performed both traditional and a machine learning analysis.ConclusionWe show that the machine learning approach based on the steroid relationships developed here was much more accurate than the PSA, DHEAS, and direct absolute value match method in separating the PCa, BPH and control subjects, increasing the sensitivity to 90% and specificity to 84%. This technology, if applied in the future to a larger number of samples will be able to detect the individual enzymatic disequilibrium associated with the steroid ratio and correlate it with the disease. This learning machine approach could be valid in a personalized medicine setting.

Dataset Information

Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine.

Purpose

Methods

Results

Conclusions

Publications

Kinomic profiling of electromagnetic navigational bronchoscopy specimens: a new approach for personalized medicine.

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