Faculty Bibliography

Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET, ALK, or ROS1 gene fusion (RET = 32; ALK = 116; ROS1 = 67). Patients with RET+ NSCLC were older at presentation compared to ALK+ and ROS1+ patients (median age: RET = 64 years; ALK = 51 years, p < 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology (RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET+ patients were more likely to be peripheral (RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1+ NSCLC (RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET+ NSCLC shares several distinct radiologic features and metastatic spread with ALK+ and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.

IMPORTANCE:The internet is an important source of medical information for many patients and may have a key role in the education of patients about lung cancer screening (LCS). Although most LCS programs in the United States have informational websites, the accuracy, completeness, and readability of these websites have not previously been studied. OBJECTIVE:To evaluate the informational content and readability of US LCS program websites. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study assessed US LCS program websites identified on September 15, 2018. A standardized checklist was used to assess key informational content of each website, and text was analyzed for reading level, word count, and reading time. Links to US websites of national advocacy organizations with LCS program content were tabulated. All functional LCS program websites in Google internet search engine results using the search terms lung cancer screening, low-dose CT screening, and lung screening were included in the analysis. MAIN OUTCOMES AND MEASURES:Radiologists used a standardized checklist to evaluate content, and readability was assessed with validated scales. Website word count, reading time, and number of links to outside LCS informational websites were assessed. RESULTS:A total of 257 LCS websites were included in the analysis. The word count ranged from 73 to 4410 (median, 571; interquartile range, 328-909). The reading time ranged from 0.3 to 19.6 minutes (median, 2.5; interquartile range, 1.5-4.0). The median reading level of all websites was grade 10 (interquartile range, 9-11). Only 26% (n = 66) of websites had at least 1 web link to a national website with additional information on LCS. There was wide variability regarding reported eligibility age criteria, with ages 55 to 77 years most frequently cited (42% [n = 108]). Only 56% (n = 143) of websites mentioned smoking cessation. The subject of patient cost was mentioned on 75% (n = 192) of websites. Although major LCS benefits, such as detection of lung cancer, were discussed by most (93% [n = 239]) websites, less than half of the websites (45% [n = 115]) made any mention of possible risks associated with screening. CONCLUSIONS AND RELEVANCE:There appears to be marked variability in the informational content of US LCS program websites, and the reading level of most websites is above that recommended by the American Medical Association and the National Institutes of Health. Efforts to improve website content and readability may be warranted.

BACKGROUND:Coronary artery calcification (CAC) is a common and important incidental finding in low-dose computed tomography (LDCT) performed for lung cancer screening (LCS). The impact of these incidental findings on patient management is unclear. PURPOSE/OBJECTIVE:The goals of our study were to determine the impact of reporting CAC on patient management and to determine whether standardized reporting of CAC affects the likelihood of future interventions. METHODS:In this IRB-approved retrospective study, we queried our LCS database for reports of LDCT performed between January 2016 and September 2018. All reports with significant findings of CAC designated with the letter "S" for any Lung-RADS category were selected. The grading of CAC was extracted from the reports. Medical records were reviewed for each patient to determine demographics, clinical history, medications, and cardiac-related diagnostic and interventional procedures. The changes in management after the report of significant CAC on LDCT were documented. Statistical analysis with Student t test and Pearson χ test was performed. RESULTS:A total of 756/3110 patients (mean age: 67±6.4 y; M=466, 61.6%: F=290, 38.4%) were reported to have significant CAC on LDCT for LCS. Of them, 236/756 patients (31.2%) had established coronary artery disease (CAD) at baseline, before the initial LDCT. A change in management was observed in 155/756 patients (20.5%). The most common changes in management included the following: alteration in medication regimen (n=114/155, 73.5%), stress testing (n=65/155, 41.9%), and referral to a cardiologist (36/155, 23.2%). Percutaneous coronary intervention (4, 2.6%) and surgery (3, 1.9%) were uncommon. Changes in management were more common in those without established CAD and in those whose CAC was semiquantitatively graded (35% vs. 25%, P=0.02). CONCLUSION/CONCLUSIONS:CAC is a common significant finding in LDCT for LCS. Reporting of CAC in patients with nonestablished CAD and semiquantitative assessment resulted in changes in management.

BACKGROUND:ROS proto-oncogene 1 (ROS1) rearrangements are a known molecular target in non-small-cell lung cancer (NSCLC). Our goal was to determine whether ROS1-rearranged NSCLC has imaging features and patterns of metastasis, which differ from those of anaplastic lymphoma kinase (ALK)-rearranged or epidermal growth factor receptor (EGFR)-mutant NSCLC. PATIENTS AND METHODS:We retrospectively identified patients with metastatic ROS1-rearranged, ALK-rearranged, or EGFR-mutant NSCLC from January 2014 to June 2018 and included those with pretreatment imaging studies available. We assessed the imaging features of the primary tumor and the distribution of metastases in these patients. The Wilcoxon rank-sum test and Fisher exact test were used to compare the imaging features. RESULTS:We identified 257 patients (167 women and 90 men; median age, 56 years; range, 19-90 years) with metastatic NSCLC (ROS1, 53; ALK, 87; EGFR, 117). Compared with ALK-rearranged or EGFR-mutant NSCLC, ROS1-rearranged NSCLC was less likely to present with extrathoracic metastases (ROS1, 49%; ALK, 75%; EGFR, 72%; P < .01), including brain metastases (ROS1, 9%; ALK, 25%; EGFR, 40%; P < .04). Compared with EGFR-mutant NSCLC, ROS1-rearranged tumors were more likely to exhibit imaging features of lymphangitic carcinomatosis (ROS1, 42%; EGFR, 12%; P < .01) and less likely to have air bronchograms in the primary tumor (ROS1, 2%; EGFR, 28%; P < .01). ROS1-rearranged tumors were also more likely to present with distant nodal metastases (ROS1, 15%; EGFR, 2%; P < .01) and sclerotic-type bone metastases (ROS1, 17%; EGFR, 6%; P < .01). CONCLUSION:Although considerable overlap exists in the imaging features of ROS1-rearranged, ALK-rearranged, and EGFR-mutant NSCLC, we found that ROS1-rearranged NSCLC has certain distinct imaging features and patterns of spread.

PURPOSE/OBJECTIVE:The aims of this study were to determine the prevalence and outcomes of extrapulmonary malignancies identified on lung cancer screening (LCS) and to determine the cost associated with the investigation of these lesions. METHODS:This retrospective study included 7,414 low-dose CT studies performed between June 2014 and December 2019 on 4,160 patients as part of an established LCS program. Patients with indeterminate extrapulmonary lesions were identified, and the diagnostic workup, management, and outcomes of the lesions were determined. Costs related to diagnostic evaluation were estimated using 2020 total facility relative value units and the 2020 Medicare conversion factor. Out-of-pocket costs were extracted from billing records. RESULTS:There were 20 extrapulmonary malignancies among 241 reported lesions in 225 patients (mean age, 66.1 ± 6.4 years; 109 men, 116 women). The prevalence of extrapulmonary malignancy was 20 of 4,160 (0.48%). Early-stage cancers were detected in 13 of 20 (65%). No cancer-specific mortality was observed. The predictive value for malignancy varied by organ (P = .03) and was highest in the chest wall and axilla (36.4%), followed by bone (25%). The average cost on the basis of Medicare reimbursement for diagnosis of an extrapulmonary malignancy on LCS was $1,316.03 ($6.33 per participant and $109.21 per indeterminate incidental lesion). Most patients (203 of 225 [90.2%]) did not have out-of-pocket costs related to diagnostic workup. In those who did, the median cost was $160.60 (range, $75-$606.76). CONCLUSIONS:Low-dose CT for LCS detects extrapulmonary malignancy with high predictive value for certain locations. There is cost associated in the workup related to these incidental lesions, but most malignancies are detected at early stages and have good outcomes.