Endobronchial ultrasound in the management of lung cancer: integration of a new technology into clinical care
AuthorSteinfort, Daniel Paul
AffiliationMedicine, Dentistry & Health Sciences - Medicine (RMH & WH)
Document TypePhD thesis
CitationsSteinfort, D. P. (2012). Endobronchial ultrasound in the management of lung cancer: integration of a new technology into clinical care. PhD thesis, Medicine, Dentistry & Health Sciences - Medicine (RMH & WH), The University of Melbourne.
Access StatusOpen Access
© 2012 Dr. Daniel Paul Steinfort
Previous studies have described technical aspects of endobronchial ultrasound (both radial & linear). These included performance of the techniques and diagnostic accuracy, though notably early experience was confined to several centres with extensive & experienced interventional bronchoscopy services. Integration of new technology can evolve rapidly, preceding a more complete understanding of potential limitations and complications. The body of work presented in this thesis was commenced at a time where endobronchial ultrasound was being used more frequently in an increasing number of centres worldwide. There remained a number of outstanding questions regarding the optimal performance of the techniques and their safety profile. This thesis attempts to address several such issues to more clearly define how endobronchial ultrasound (EBUS) is best performed and best incorporated into routine clinical care. Radial EBUS has been demonstrated to have utility in assessment of peripheral lung lesions, though no comparison with alternate diagnostic procedures had previously been undertaken. I performed a prospective randomized pragmatic trial to determine the comparative effectiveness of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) and CT-guided percutaneous needle biopsy (CT-PNB) for the investigation of PPL. Overall complication rates were higher in those undergoing CT-PNB (27% v 3%, p=0.03), while diagnostic accuracy of EBUS-TBLB was shown to be non-inferior to that of CT-PNB. Expected diagnostic accuracy and complication rates are likely to differ for individual patients on the basis of specific complex clinicoradiologic factors, which will influence the comparative effectiveness and cost-utility between EBUS-TBLB and CT-PNB for individual patients. Decision tree analysis is suited to applying clinical research findings to broader patient populations however more accurate understanding of diagnostic performance of EBUS-TBLB was required. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. Meta-analysis demonstrated that EBUS is a safe and relatively accurate (point sensitivity of 0.73, 95%CI 0.70–0.76) tool in investigation of PPLs. Diagnostic sensitivity of EBUS-TBLB may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) with CT-guided percutaneous needle biopsy (CT-PNB). The costs of EBUS-TBLB and CT-PNB to evaluate PPL appear to be equivalent. Specific factors known to influence procedural outcomes will influence cost-benefit outcomes. Consideration of disutility did not significantly alter cost outcomes. Issues regarding safety and tolerability of EBUS-guided transbronchial needle aspiration were undertaken. Incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. EBUS-TBNA may safely be performed under conscious intravenous sedation. Such practice is associated with very high levels of patient satisfaction. Both malignancy and granulomatous disease may be diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Demonstration of granulomas by lymph node EBUS-TBNA in the staging of NSCLC is of uncertain significance. Studies demonstrated that sarcoidal reactions are seen in 4.3% of all patients with NSCLC. Metastatic involvement by NSCLC is not seen in lymph nodes exhibiting sarcoidal granulomatous reactions. No NSCLC patients with sarcoidal granulomas in regional lymph nodes experienced disease recurrence. Case control matching was performed indicating a significantly higher rate of disease recurrence in control subjects (0% v. 44%. p=0.044, X to the power of 2=4.051). Sarcoidal reactions within regional lymph nodes of NSCLC patients predicts a lower rate of disease recurrence following definitive surgical resection. Sarcoidal reactions may represent an effective anti-tumour immunity. Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), conventional TBNA and surgical mediastinoscopy. Findings indicated that EBUS-TBNA was the most cost-beneficial approach (in comparison to traditional surgical techniques) for mediastinal staging of NSCLC patients across all studied parameters. Diagnostic accuracy of EBUS-TBNA in the evaluation of suspected lymphoma remained uncertain. A retrospective review of a prospectively recorded database of consecutive patients with suspected lymphoma who underwent EBUS-TBNA was examined. Findings indicated that diagnostic accuracy of EBUS-TBNA for lymphoma is lower than that for lung cancer staging. Small volume biopsies may be subject to significant interobserver variability in subtype determination. Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens.
Keywordsendobronchial ultrasound; comparative effectiveness research; cost effectiveness
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