Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare.

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests. Simultaneously, Australian Genomics has built national skills, infrastructure, policy, and data resources to enable effective data sharing to drive discovery research and support improvements in clinical genomic delivery.

Performance of somatic structural variant calling in lung cancer using Oxford Nanopore sequencing technology.

BACKGROUND: Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and seven structural variant callers comprised of generic callers (SVIM, Sniffles2, DELLY in generic mode and cuteSV) and somatic callers (Severus, SAVANA, nanomonsv and DELLY in somatic modes). RESULTS: Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short-read sequencing. When compared to somatic structural variants detected with short-read sequencing, more events were detected with long-read sequencing. The mean recall of somatic variant events identified by long-read sequencing was higher for the somatic callers (72%) than generic callers (53%). Among the somatic callers when using the minimap2 aligner, SAVANA and Severus achieved the highest recall at 79.5% and 79.25% respectively, followed by nanomonsv with a recall of 72.5%. CONCLUSION: Long-read sequencing can identify somatic structural variants in clincal samples. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.

World Association for Bronchology and Interventional Pulmonology (WABIP) guidelines on airway stenting for malignant central airway obstruction.

Malignant Central Airway Obstruction (MCAO) encompasses significant and symptomatic narrowing of the central airways that can occur due to primary lung cancer or metastatic disease. Therapeutic bronchoscopy is associated with high technical success and symptomatic relief and includes a wide range of airway interventions including airway stents. Published literature suggests that stenting practices vary significantly across the world primarily due to lack of guidance. This document aims to address this knowledge gap by addressing relevant questions related to airway stenting in MCAO. An international group of 17 experts from 17 institutions across 11 countries with experience in using airway stenting for MCAO was convened as part of this guideline statement through the World Association for Bronchology and Interventional Pulmonology (WABIP). We performed a literature and internet search for reports addressing six clinically relevant questions. This guideline statement, consisting of recommendations addressing these six PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with expert experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique.

Whole Genome Sequencing in Advanced Lung Cancer can be Performed Using Diff-Quik Cytology Smears Derived from Endobronchial Ultrasound, Transbronchial Needle Aspiration (EBUS TBNA).

INTRODUCTION: Maximising alternative sample types for genomics in advanced lung cancer is important because bronchoscopic samples may sometimes be insufficient for this purpose. Further, the clinical applications of comprehensive molecular analysis such as whole genome sequencing (WGS) are rapidly developing. Diff-Quik cytology smears from EBUS TBNA is an alternative source of DNA, but its feasibility for WGS has not been previously demonstrated. METHODS: Diff-Quik smears were collected along with research cell pellets. RESULTS: Tumour content of smears were compared to research cell pellets from 42 patients, which showed good correlation (Spearman correlation 0.85, P < 0.0001). A subset of eight smears underwent WGS, which presented similar mutation profiles to WGS of the matched cell pellet. DNA yield was predicted using a regression equation of the smears cytology features, which correctly predicted DNA yield > 1500 ng in 7 out of 8 smears. CONCLUSIONS: WGS of commonly collected Diff-Quik slides is feasible and their DNA yield can be predicted.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.

Technologies for targeting the peripheral pulmonary nodule including robotics.

Bronchoscopic sampling of PPL was significantly advanced by the development of the endobronchial ultrasound guide sheath method in the 1990s. Since then, a range of technical and procedural techniques have further advanced diagnostic yields. These include the use of thinner bronchoscopes with better working channel diameters, understanding the importance of peripheral transbronchial needle aspiration, and virtual bronchoscopic assistance. These have enabled better sampling of smaller and more technically challenging lesions including ground-glass nodules. Most recently, robotic bronchoscopy has been developed which, among other refinements, allows fine control of visual bronchoscopic navigation by replacing movements directed by the hand with electronic consoles and trackballs, and innovatively integrate virtual with real bronchoscopic pathways. The requirement for PPL diagnosis and treatment is expected to increase with more chest CT performed as part of CT screening programmes.

COVID-19 and the case for global development.

COVID-19 accentuates the case for a global, rather than an international, development paradigm. The novel disease is a prime example of a development challenge for all countries, through the failure of public health as a global public good. The COVID-19 pandemic has highlighted the falsity of any assumption that the global North has all the expertise and solutions to tackle global challenges, and has further highlighted the need for multi-directional learning and transformation in all countries towards a more sustainable and equitable world. We illustrate our argument for a global development paradigm by examining the implications of the COVID-19 pandemic across four themes or 'vignettes': global value chains, digitalisation, debt, and climate change. We conclude that development studies must adapt to a very different context from when the field emerged in the mid-20th century.

Bronchodilator responsiveness as a predictor of success for bronchial thermoplasty.

BACKGROUND AND OBJECTIVE: A characteristic feature of asthma is hypertrophied airway smooth muscle, responsible for bronchoconstriction. This is the target of bronchial thermoplasty (BT). It is known that with increasing time and severity some patients develop remodelled airways with fixed airflow obstruction. The question arises whether these patients will still respond to BT. METHODS: Forty-nine consecutive severe asthmatic patients were prospectively evaluated at baseline and then 6 months after BT. The characteristics recorded included medication usage, exacerbation history, spirometry and the Asthma Control Questionnaire 5-Item Version score (ACQ-5). Seven patients were excluded as they did not demonstrate airflow obstruction at baseline (forced expiratory ratio (forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC)) < 70%). The remaining 42 patients were divided into two cohorts based on their response to bronchodilator. Eighteen patients in whom the FEV1 improved by at least 12% and 200 mL following bronchodilator were allocated to Group 1 (reversible). The remaining patients were allocated to Group 2 (fixed). The outcomes following BT in these two groups were then compared. RESULTS: The patient age was 57.2 ± 12.4 years, the ACQ-5 was 3.2 ± 1.0 and the FEV1 56.0 ± 16.4% predicted. At baseline, the patient cohorts were very similar, save for the response to bronchodilator, which was 28.1 ± 12.5% in Group 1 and 4.1 ± 5.3% in Group 2. Both groups responded to BT equally well, with significant improvements in ACQ-5, salbutamol usage, exacerbation frequency and the weaning of oral corticosteroids. CONCLUSION: In patients with severe asthma, the presence or absence of variable airflow obstruction as measured by spirometry does not appear to influence outcomes from BT.

First Human Use of a New Robotic-Assisted Fiber Optic Sensing Navigation System for Small Peripheral Pulmonary Nodules.

BACKGROUND: We tested a new, investigational robotic-assisted bronchoscope system with a remotely controlled catheter to access small peripheral bronchi with real-time driving under live visualization and distal tip articulation of the catheter. The unique catheter remains stationary once located at the biopsy position. OBJECTIVES: The primary objectives of this study were to evaluate the safety and feasibility of a new shape-sensing robotic bronchoscope system to bronchoscopically approach and facilitate the sampling of small peripheral pulmonary nodules of 1-3 cm. Secondary objectives included evaluating procedural characteristics and early performance trends associated with the use of the new robotic bronchoscope system. METHODS: Subjects were enrolled according to study eligibility criteria at a single center. Navigation pathways were semi-automatically created using pre-procedure CT scans. Simultaneous (real-time) viewing of actual and virtual bronchi was used real time during navigation to the displayed target. An endobronchial ultrasound mini-probe was used to confirm lesion location. Flexible 19- to 23-G needles specifically designed to accommodate tight bend radii in transbronchial needle aspiration were used along with conventional biopsy tools. Enrolled subjects completed follow-up visits up to 6 months after the procedure. RESULTS: The study included 29 subjects with a mean lesion size of 12.2 ± 4.2, 12.3 ± 3.3, and 11.7 ± 4.1 mm in the axial, coronal, and sagittal planes, respectively. The CT bronchus sign was absent in 41.4% of cases. In 96.6% of cases, the target was reached, and samples were obtained. No device-related adverse events and no instances of pneumothorax or excessive bleeding were observed during the procedure. Early performance trends demonstrated an overall diagnostic yield of 79.3% and a diagnostic yield for malignancy of 88%. CONCLUSION: This new robotic-assisted bronchoscope system safely navigated to very small peripheral airways under continuous visualization, and through maintenance of a static position, it provides a unique sampling capability for the biopsy of small solitary pulmonary nodules.

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks.

BACKGROUND: Next-generation sequencing (NGS) in lung cancer specimens from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is usually performed on formalin-fixed paraffin-embedded cell block material. OBJECTIVES: Since DNA can be damaged by this process, we investigated the potential of using DNA extracted from Diff-Quik cytology smears made for rapid on-site evaluation during EBUS-TBNA. METHODS: In a prospective study, 67 patients undergoing diagnostic EBUS-TBNA were ana-lysed. We compared cell blocks and smears for DNA yields and sequencing (TruSeq Amplicon Cancer Panel) outcomes. Smears were also evaluated for tumour cell fraction and overall cellularity (cell count). RESULTS: Primary lung cancer was diagnosed in 64 patients and metastatic malignancy in 3 patients. The DNA yield from smears was significantly higher than that obtained from matched cell blocks (mean 1,740 vs. 434 ng; p = 0.001). For 33 cases with matched smears and cell blocks the mutation profiles were similar. Smears with abundant malignant cells (using a cut-off of > 25% tumour cell fraction and > 1,000 cells) accurately predicted high (> 50 ng) DNA yield and therefore success in triaging samples to sequencing. In terms of tissue workflow, using only smears as source DNA for sequencing was an improvement in the use of only cell blocks (54/67 [80.6%] vs. 41/67 [61.2%]); however, the use of cell blocks when smears were not available or did not yield sufficient DNA further improved the success rate to 62/67 (92.5%) cases. CONCLUSION: We recommend smears in laboratory workflows as the primary source of DNA for NGS following an EBUS procedure.

Bronchial thermoplasty: activations predict response.

BACKGROUND: Bronchial thermoplasty (BT) is an emerging bronchoscopic intervention for the treatment of severe asthma. The predictive factors for clinical response to BT are unknown. We examined the relationship between the number of radiofrequency activations applied and the treatment response observed. METHODS: Data were collected from 24 consecutive cases treated at three Australian centres from June 2014 to March 2016. The baseline characteristics were collated along with the activations delivered. The primary response measure was change in the Asthma Control Questionnaire-5 (ACQ-5) score measured at 6 months post BT. The relationship between change in outcome parameters and the number of activations delivered was explored. RESULTS: All patients met the ERS/ATS definition for severe asthma. At 6 months post treatment, mean ACQ-5 improved from 3.3 ± 1.1 to 1.5 ± 1.1, p < 0.001. The minimal clinically significant improvement in ACQ-5 of ≥0.5 was observed in 21 out of 24 patients. The only significant variable that differed between the 21 responders and the three non-responders was the number of activations delivered, with 139 ± 11 activations in the non-responders, compared to 221 ± 45 activations in the responders (p < 0.01). A significant inverse correlation was found between change in ACQ-5 score and the number of activations, r = -0.43 (p < 0.05). CONCLUSIONS: The number of activations delivered during BT has a role in determining clinical response to treatment.

Thoracic ultrasound recognition of competence: A position paper of the Thoracic Society of Australia and New Zealand.

The ability to perform bedside thoracic ultrasound is increasingly recognized as an essential skill for thoracic clinicians, extending the clinical examination and aiding diagnostic and therapeutic procedures. Thoracic ultrasound reduces complications and increases success rates when used prior to thoracentesis or intercostal chest tube insertion. It is increasingly difficult to defend performing these procedures without real or near-real time image guidance. To assist thoracic physicians and others achieve and demonstrate thoracic ultrasound competence, the Interventional Pulmonology Special Interest Group (IP-SIG) of the Thoracic Society of Australia and New Zealand (TSANZ) has developed a new pathway with four components: (i) completion of an approved thoracic ultrasound theory and hands-on teaching course. (ii) A log of at least 40 relevant scans. (iii) Two formative assessments (following 5-10 scans and again after 20 scans) using the Ultrasound-Guided Thoracentesis Skills and Tasks Assessment Tool (UG-STAT). (iv) A barrier assessment (UG-STAT, pass score of 90%) by an accredited assessor not directly involved in the candidate's training. Upon completion of these requirements a candidate may apply to the TSANZ for recognition of competence. This pathway is intended to provide a regional standard for thoracic ultrasound training.

A combined hands-on teaching programme and clinical pathway focused on pleural ultrasound and procedure supervision transforms pleural procedure outcomes.

BACKGROUND: Management of pleural effusions is a common diagnostic and management problem. AIMS: We reviewed the outcomes from pleural procedures after the instigation of pleural effusion management guidelines, focusing on pleural ultrasound and a hands-on teaching programme followed by procedure supervision that enabled many operators to perform such procedures. METHODS: This is a retrospective analysis of all procedures performed for pleural effusions on medical patients. Outcomes were assessed prior to the instigation of pleural effusion management guidelines (pleural pathway) and hands-on teaching (January 2010 to June 2011) and following these interventions (January 2012 to June 2013). RESULTS: A total of 171 procedures involving 129 patients (pre-pathway group) and 146 procedures involving 115 patients (post-pathway group) was analysed. The rate of complications prior to the pleural pathway was 22.2% (38 of 171 procedures). Following the pathway, the rate of complications declined to 7.5% (11 of 146 procedures, P < 0.003). The use of pleural ultrasound increased dramatically (72.5 vs 90.2%). The number of patients who underwent repeated procedures (defined as ≥3) reduced dramatically (21 vs 7, P < 0.01). This improvement occurred using many supervised operators who completed the hands-on teaching programme (n = 32) and followed the pleural pathway (127 of 146 procedures). CONCLUSION: The instigation of a clinical pathway focused on the use of bedside pleural ultrasound, and teaching of drainage techniques with procedure supervision vastly improved patient outcomes. This not only allowed better quality of care for patients, it also provided the acquisition of new skills to medical staff, not limiting these skills to specialised staff.

Bronchial thermoplasty in severe asthma in Australia.

BACKGROUND: Bronchial thermoplasty (BT) is an approved bronchoscopic intervention for the treatment of severe asthma. However, limited published experience exists outside of clinical trials regarding patient selection and outcomes achieved. AIMS: To evaluate the effectiveness and safety of BT in patients with severe asthma encountered in clinical practice. METHODS: This is a retrospective analysis of the first 'real world' data from Australia. The following outcomes were measured prior to, and 6 months following BT: spirometry, Asthma Control Questionnaire-5 (ACQ-5) score, reliever and preventer medication use and exacerbation history. RESULTS: Twenty patients were treated from June 2014 to December 2015 at three university teaching hospitals. All subjects met the European Respiratory Society/American Thoracic Society definition of severe asthma. Mean pre-bronchodilator forced expiratory volume in 1 s was 62.8 ± 16.6% predicted (range: 33-95%). All patients were being treated with high dose inhaled corticosteroids, long-acting beta2 agonists and long-acting muscarinic antagonists. Ten patients (50%) were taking maintenance oral prednisolone. Most subjects also required at least one of montelukast (65%), omalizumab (30%) and methotrexate (20%). ACQ-5 improved from 3.6 ± 1.1 at baseline to 1.6 ± 1.2 at 6 months, P < 0.001. Short-acting reliever use decreased from a median of 8.0-0.25 puffs/day, P < 0.001, and exacerbations requiring corticosteroids also significantly reduced. Five of 10 patients completely discontinued maintenance oral corticosteroids. Ten patients with a baseline forced expiratory volume in 1 s of <60% predicted significantly improved from 49.2 ± 9.6% to 61.8 ± 17.6%, P < 0.05. Only two procedures required hospitalisation beyond the planned overnight admission. CONCLUSION: BT is a safe procedure which can achieve clinical improvement in those with uncontrolled symptoms and severe airflow obstruction.

Risk stratification in the investigation of pulmonary nodules in a high-risk cohort: positron emission tomography/computed tomography outperforms clinical risk prediction algorithms.

BACKGROUND: Clinical prediction models and 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) are used for the assessment of solitary pulmonary nodules (SPN); however, a biopsy is still required before treatment, which carries risk. AIM: To determine the combined predictive benefit of one such model combined with modern PET/CT data to improve decision-making about biopsy prior to treatment and possibly reduce costs. METHODS: Patients with a SPN undergoing 18F-FDG-PET/CT from January 2011 to December 2012 were retrospectively identified; 143 patients met inclusion criteria. PET/CT studies were rated (5-point visual scale), and CT characteristics were determined. Tissue was obtained by endobronchial ultrasonography with guide sheath (EBUS-GS), CT-guided biopsy and/or surgery. EBUS-transbronchial needle aspiration (TBNA) was used instead of nodule biopsy if there were PET-positive sub-centimetre lymph nodes. RESULTS: The prediction model yielded an area under the receiver operating characteristic curve (AUC-ROC) of 64% (95% confidence interval (CI) 0.55-0.75). PET/CT increased this to 75% (95% CI 0.65-0.84). The 11% improvement is statistically significant. PET/CT score was the best single predictor for malignancy. A PET score of 1-2 had a specificity of 100% (CI 0.73-1.0), whereas a score of 4-5 had a sensitivity of only 76% (CI 0.68-0.84). No significant difference in clinical prediction scores between groups was noted. PET/CT showed the greatest benefit in true negatives and in detecting small mediastinal lymph nodes to allow EBUS-TBNA with a higher diagnostic rate. Cost analysis did not support a policy of resection-without-tissue diagnosis. CONCLUSION: PET/CT improves the clinical prediction of SPN, but its greatest use is in proving benignity. High PET scores had high false positive rates and did not add to clinical prediction. PET should be incorporated early in decision-making to allow for more effective biopsy strategies.

A new instrument to assess physician skill at chest tube insertion: the TUBE-iCOMPT.

Currently no tool exists to assess proceduralist skill at chest tube insertion. As inadequate doctor procedural competence has repeatedly been associated with adverse events, there is a need for a tool to assess procedural competence. This study aims to develop and examine the validity of a tool to assess competency at insertion of a chest tube, using either the Seldinger technique or blunt dissection. A 5-domain 100-point assessment tool was developed inline with British Thoracic Society guidelines and international consensus­the Chest Tube Insertion Competency Test (TUBE-iCOMPT). The instrument was used to assess chest tube insertion in mannequins and live patients. 29 participants (9 novices, 14 intermediate and 6 advanced) were tested by 2 blinded expert examiners on 2 occasions. The tool's validity was examined by demonstrating: (1) stratification of participants according to expected level of expertise (analysis of variance), and (2) test-retest and intertester reliability (intraclass correlation coefficient). The intraclass correlation coefficient of repeated scores for the Seldinger technique and blunt dissection, were 0.92 and 0.91, respectively, for test-retest results, and 0.98 and 0.95, respectively, for intertester results. Clear stratification of scores according to participant experience was seen (p<0.0001). There was no significant difference between scores obtained using mannequins or live patients. This study has validated the TUBE-iCOMPT, which could now be incorporated into chest tube insertion training programmes, providing a way to document acquisition of skill, guide individualised teaching, and assist with the assessment of the adequacy of clinician training.

Comparison of objective criteria and expert visual interpretation to classify benign and malignant hilar and mediastinal nodes on 18-F FDG PET/CT.

BACKGROUND AND OBJECTIVE: There is widespread adoption of FDG-PET/CT in staging of lung cancer, but no universally accepted criteria for classifying thoracic nodes as malignant. Previous studies show high negative predictive values, but reporting criteria and positive predictive values varies. Using Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) results as gold standard, we evaluated objective FDG-PET/CT criteria for interpreting mediastinal and hilar nodes and compared this to expert visual interpretation (EVI). METHODS: A retrospective review of all patients with lung cancer who had both FDG-PET/CT and EBUS-TBNA from 2008 to 2010 was performed. Scan interpretation was blinded to histology. Patients from 2008/2009 were used for the prediction set. The validation set analysed patients from 2010. Objective FDG-PET/CT criteria were SUVmax lymph node (SUVmaxLN), ratio SUVmaxLN/SUVmax primary lung malignancy, ratio SUVmaxLN/SUVaverage liver, ratio SUVmaxLN/SUVmax liver and ratio SUVmaxLN/SUVmax blood pool. A nuclear medicine physician reviewed all scans and classified nodal stations as benign or malignant. RESULTS: Eighty-seven malignant lymph nodes and 41 benign nodes were in the prediction set. All objective FDG-PET/CT criteria analysed were significantly higher in the malignant group (P < 0.0001). EVI correctly classified 122/128 nodes (95.3%). Thirty-four malignant nodes and 19 benign nodes were in the validation set. The new proposed cut-off values of the objective criteria from the prediction set correctly classified 44/53 (83.0%) nodes: 28/34 (82.4%) malignant nodes and 16/19 (84.2%) benign nodes. EVI had 91% accuracy: 33/34 (97.1%) malignant nodes and 15/19 (79.0%) benign nodes. CONCLUSIONS: Objective analysis of 18-F FDG PET/CT can differentiate between malignant and benign nodes but is not superior to EVI.