Risk of malignancy in pulmonary nodules: A validation study of four prediction models.

OBJECTIVES: Clinical prediction models assess the likelihood of malignancy in pulmonary nodules detected by computed tomography (CT). This study aimed to validate four such models in a UK population of patients with pulmonary nodules. Three models used clinical and CT characteristics to predict risk (Mayo Clinic, Veterans Association, Brock University) with a fourth model (Herder et al. [4]) additionally incorporating (18)Fluorine-Fluorodeoxyglucose (FDG) avidity on positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS: The likelihood of malignancy was calculated for patients with pulmonary nodules (4-30mm diameter) and data used to calculate the area under the receiver operating characteristic curve (AUC) for each model. The models were used in a restricted cohort of patients based on each model's exclusion criteria and in the total cohort of all patients. RESULTS: Two hundred and forty-four patients were studied, of whom 139 underwent FDG PET-CT. Ninety-nine (40.6%) patients were subsequently confirmed to have malignant nodules (33.2% primary lung cancer, 7.4% metastatic disease). The Mayo and Brock models performed similarly (AUC 0.895 and 0.902 respectively) and both were significantly better than the Veterans Association model (AUC 0.735, p<0.001 and p=0.002 respectively). In patients undergoing FDG PET-CT, the Herder model had significantly higher accuracy than the other three models (AUC 0.924). When the models were tested on all patients in the cohort (i.e. including those outside the original model inclusion criteria) AUC values were reduced, yet remained high especially for the Herder model (AUC 0.916). For sub-centimetre nodules, AUC values for the Mayo and Brock models were 0.788 and 0.852 respectively. CONCLUSIONS: The Mayo and Brock models showed good accuracy for determining likelihood of malignancy in nodules detected on CT scan. In patients undergoing FDG PET-CT for nodule evaluation, the highest accuracy was seen for the model described by Herder et al. incorporating FDG avidity.

Adequacy of endobronchial ultrasound transbronchial needle aspiration samples in the subtyping of non-small cell lung cancer.

INTRODUCTION: The histological subtyping of non small cell lung cancer (NSCLC) is important in the selection of the optimal treatment for patients with advanced disease. There are now important differences in the chemotherapy regimens used for squamous and non-squamous cancers. Non-squamous cancers (particularly adenocarcinomas) are also suitable for targeted therapy if the epidermal growth factor receptor (EGFR) genetic mutation is present. Diagnosis is frequently made by fine needle aspiration from lymph node metastases. We have evaluated the adequacy of material obtained by EBUS-TBNA for subtyping of NSCLC. METHODS: All EBUS-TBNA procedures performed at Leeds Teaching Hospitals between February 2009 and November 2011 were analysed. Data was collected on the indication, final cytological diagnosis and whether EGFR mutation testing was possible. We analysed the data to establish our rate of NSCLC-NOS diagnoses and to determine the technical success of EGFR testing. RESULTS: Data from 391 procedures was analysed. The indication was staging of malignancy in 345 patients and suspected non-malignant disease in 48 patients. Malignant disease was diagnosed in 204 patients (53.7%), small cell 43, squamous cell 64, adenocarcinoma 40, adenosquamous 2, large cell 12, NSCLC-NOS 31 and malignant disease of non-lung primary 12. EBUS-TBNA identified 149 patients with NCSLC. Subtyping could be obtained in 118 (79.2%). The number of patients with a diagnosis of NSCLC NOS on EBUS-TBNA was 31 (20.8%, 95% CI 15-28%). Of the 204 specimens with a malignant diagnosis immunohistochemistry was performed in 149 (73.0%). It was not performed in 52 (25.5%) cases and there was insufficient material available in 3 (1.5%) cases. EGFR testing was requested in 36 patients. Our test success rate for EGFR mutation testing on EBUS-TBNA samples was 88.8% (95%CI 74.7-95.6%). CONCLUSION: EBUS-TBNA samples when made into cell blocks and subjected to a panel of immunohistochemical stains returned adequate tissue for cytological analysis in over 97% of cases, with an NOS rate of 20.8%. We have also shown that cytology specimens are adequate for EGFR mutation testing in over 88% of cases. We conclude that EBUS-TBNA is an accurate diagnostic test both for determining NSCLC subtype and performing EGFR mutation analysis to tailor treatment in lung cancer patients.