Performance monitoring of EBUS for the staging and diagnosis of lung cancer: auditing the Greater Manchester EBUS service against new national standards.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a pivotal test in lung cancer staging and diagnosis, mandating robust audit and performance monitoring of EBUS services. We present the first regional cancer alliance EBUS performance audit against the new National EBUS specification. METHODS: Across the five EBUS centres in the Greater Manchester Cancer Alliance, data are recorded at the point of procedure, when pathological results are available and at 6 months postprocedure to review any further pathological sampling (eg, at surgical resection) and the outcome of clinical-radiological follow-up. Outcomes across all five centres were compared with national standards for all lung cancer EBUS procedures from 01 January 2017 to 31 December 2018. RESULTS: 1899 lung cancer staging or diagnostic EBUS procedures were performed across the five centres during the study period; 1309 staging EBUS procedures and 590 diagnostic EBUS procedures. Major complications were seen in six cases (<1%). All five trusts demonstrated performance above that set national standards in key metrics for both staging and diagnostic EBUS, however the provision of adequate tissue for predictive marker testing was below national standards at one trust. Across Greater Manchester, 72% and 64% of patients had their EBUS procedure performed within 7 days of referral in 2017 and 2018, respectively. Only one out of five trusts met the national targets of >85% of procedures performed within 7 days of referral. CONCLUSION: The National EBUS service specification is an important framework to drive the quality of EBUS services across the UK. Our data provide assurance of appropriate performance and safety while also highlighting specific areas for attention that can be addressed with the support of the cancer alliance.

Validation of ROS1 by immunohistochemistry against fluorescent in situ hybridisation on cytology and small biopsy samples in a large teaching hospital.

OBJECTIVE: Rearranged ROS1, present in 1%-2% of non-small cell lung cancer (NSCLC) patients, usually young, never or light smokers, is assessed by fluorescence in situ hybridization (FISH) to determine eligibility for tyrosine kinase inhibitors (TKI). Immunohistochemistry (IHC) for the protein product of ROS1 rearrangement, a cost-effective alternative, is validated on cytology and small biopsy samples. METHODS: From 1 March to 31 December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion next generation sequencing (NGS) panel. RESULTS: In a prospective population of 95 cases, 91 were negative and two were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another two cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation, whilst that of FISH was 9 to 42 days at a cost of £51 and £159 respectively. CONCLUSION: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good negative predictive value, faster turnaround time and is cost effective, with proven technical and clinical validation.

Predicting survival following surgical resection of lung cancer using clinical and pathological variables: The development and validation of the LNC-PATH score.

INTRODUCTION: The aim of this study was to develop and validate a simple prognostic scoring system using readily available clinical and pathological variables that could stratify patients according to the risk of death following lung cancer resection. We hypothesized that by using additional pathological variables not accounted for by pathological stage alone coupled with markers of overall fitness a new prognostic tool could be developed. METHODS: Multivariable logistic regression analysis of pathological and other clinical variables from patients undergoing surgical resection of non-small cell lung cancer (NSCLC) were used to determine factors independently associated with 2-year overall survival and so derive the scoring system. The model was then validated in an external multi-centre dataset. RESULTS: Using multivariable logistic regression on a large dataset (n = 1,421) the 'LNC-PATH' (Lymphovascular invasion, N-stage, adjuvant Chemotherapy, Performance status, Age, T-stage, Histology) prognostic score was devised and then validated using an external dataset (n = 402). This can be used to risk stratify patients into low, moderate and high-risk groups with a statistically significant difference between the three groups in their survival distributions. 83.8% of patients in the low-risk group survived two years after surgery compared to 55.6% in the moderate-risk group and 26.2% in the high-risk group. The score was shown to perform moderately well with an Area Under the Receiver Operating Characteristic curve (AUROC) value of 0.76 (95% CI: 0.73-0.79) and 0.70 (95% CI: 0.64-0.76) in the derivation and validation cohorts respectively. DISCUSSION: The LNC-PATH score predicts 2-year overall survival after surgery for NSCLC. This may allow the development of risk stratified follow-up protocols in survivorship clinics which could be the subject of future prospective studies.

Prevalence of nodal metastases in lymph node stations 8 & 9 in a large UK lung cancer surgical centre without routine pre-operative EUS nodal staging.

INTRODUCTION: Endoscopic ultrasound (EUS) allows access to the inferior mediastinal lymph node stations (8 and 9) which are beyond the reach of endobronchial ultrasound (EBUS). The addition of EUS to EBUS procedures requires cost and resource investment. This study sought to describe the prevalence of station 8/9 nodal metastases from intra-operative lymph node sampling in a UK region where routine pre-operative EUS is not available. METHODS: A retrospective review of all lung cancer resections at the University Hospital South Manchester from 2011 to 2014. Surgical variables, pre-operative PET variables and survival outcomes were collected and analysed. RESULTS: 1421 surgical resections were performed in the study period. Lymph node stations 8 and/or 9 were sampled in 52% (736/1421) of patients. Overall, there were 34 patients with lymph node metastases at station 8/9. This represents 2.4% of the study populations and 4.6% of patients in whom stations 8/9 were sampled intra-operatively. Of those patients with station 8/9 metastases, 65% (22/34) had multi-station N2 disease and the majority of the additional N2 disease was present in EBUS-accessible areas (lymph node stations 2, 4 and 7). Two percent (16/736) of patients in whom station 8/9 lymph nodes were sampled intra-operatively had N2 disease that was only accessible endoscopically with EUS. There was no significant difference in overall survival in patients with pathological N2 disease stratified according to whether stations 8/9 were involved or not. CONCLUSIONS: The prevalence of lymph node metastases in stations 8/9 in this UK surgical centre where routine pre-operative EUS is not performed is low at approximately 5%. Given the identification of N2 disease in two-thirds of these patients can potentially be achieved through EBUS alone, this questions whether the resource implications of EUS are justified by the impact on patient management.