PURPOSE: Previous studies have shown that FISH testing significantly increases the detection of lung cancer over routine cytology alone, especially for peripheral nodules. We investigated whether patients could be stratified based on their risk of developing lung malignancy after a negative initial bronchoscopic evaluation, using clinical and radiologic characteristics and FISH abnormalities.
METHODS: A retrospective review was performed to identify patients with indeterminate peripheral lung nodules who had undergone a negative initial bronchoscopic evaluation that included bronchial brushings for routine cytology and FISH testing. Patients without evidence of lung cancer at baseline were included in this study (N=228 specimens from 221 patients). FISH testing was performed on residual cytology specimens diagnosed as negative (n=201), atypical (n=18) or suspicious (n=9). FISH results included polysomy (n=30) and negative (n=198). The primary outcome was time to diagnosis of lung cancer and pathology confirmation or clinical/radiologic indication of disease progression during follow-up were considered evidence of malignancy. The median time to last follow-up was 75 days (SD: 212, range 1-821). Hazard ratios (HR) for test results and clinical features were calculated using Cox proportional hazards regression model analyses where P values <0.05 were considered statistically significant.
RESULTS: The mean age of the 221 patients was 66.7 years and 129 (58%) were males. Most patients (79%) were current/former smokers having 33.4 mean pack years (SD: 32.7 range 0-200). After multivariate analysis, polysomy FISH (HR=3.32, CI=1.87-5.88, P<0.0001), pack years (HR=1.03 per pack year up to 50, CI=1.01-1.04, P=0.0014), age (HR=1.04, CI=1.01-1.06, P=0.0061), atypical or suspicious cytology (HR=2.02, CI=1.1-3.69, P=0.023) and spiculation (HR=2.35, CI=1.33-4.14, P=0.0031) were independent predictors of malignancy over time and were used to create a prediction model (C-statistic=0.78).
CONCLUSIONS: FISH, age, spiculation, pack years and cytology were found to be independent predictors of lung cancer after a negative bronchoscopic examination and this multivariate model may help predict a patient’s risk of malignancy during follow-up.
CLINICAL IMPLICATIONS: Further studies are needed to validate this model prior to clinical use.
DISCLOSURE: Kevin Halling: Other: Dr. Kevin Halling and Mayo Clinic receive royalties from the sale of the FISH probes discussed in the study.
The following authors have nothing to disclose: Seher Iqbal, Jesse Voss, Fabien Maldonado, Sarah Jenkins, Michael Henry, Amy Clayton
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