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Background Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers' average AUC improved from 0.82 to 0.89 with CAD (

In this work, we study the survival outcomes of patients with lung adenocarcinoma in four independent cohorts. By classifying patients with KRAS mutations into three subgroups based on their mutation status of TP53 and SMARCA4, our analysis indicates that patients harboring both KRAS and SMARCA4 mutations do not benefit from the treatment with nonimmunotherapy or immune checkpoint inhibitor‐based immunotherapy. Alternative treatment strategy is requested for this subset of patients., KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin‐remodeling gene SMARCA4 is comutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4 mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in four independent cohorts totaling 564 patients: KRAS‐mutant patients with LUAD who received nonimmunotherapy treatment from (a) The Cancer Genome Atlas (TCGA) and (b) the MSK‐IMPACT Clinical Sequencing (MSK‐CT) cohorts; and KRAS‐mutant patients with LUAD who received immune checkpoint inhibitor‐based immunotherapy treatment from (c) the MSK‐IMPACT (MSK‐IO) and (d) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving nonimmunotherapy treatment, in the TCGA cohort (n = 155), KRAS‐mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome [P = 6e‐04 for disease‐free survival (DFS) and 0.031 for overall survival (OS), respectively], compared to KRAS‐TP53 comutant (KP) and KRAS‐only mutant (K) patients; in the MSK‐CT cohort (n = 314), KS patients also exhibited shorter OS than KP (P = 0.03) or K (P = 0.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression‐free survival (PFS; P = 0.0091) in the MSK‐IO (n = 77), and the shortest PFS (P = 0.0026) and OS (P = 0.0014) in the WFBCCC (n = 18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor leading to adverse clinical outcome in lung adenocarcinoma treated by either nonimmunotherapy or immunotherapy.

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed. Objectives: To develop and validate a deep learning method to improve the management of IPNs. Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions. Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4–90.7%) and 91.9% (95% CI, 88.7–94.7%), compared with 78.1% (95% CI, 68.7–86.4%) and 81.9 (95% CI, 76.1–87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts. Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

Treatment decisions for brain metastatic disease rely on knowledge of the primary organ site and are currently made with biopsy and histology. Here, we develop a deep-learning approach for accurate non-invasive digital histology with whole-brain magnetic resonance imaging (MRI) data. Contrast-enhanced T1-weighted and fast spoiled gradient echo brain MRI exams (n = 1,582) were preprocessed and input to the proposed deep-learning workflow for tumor segmentation, modality transfer, and primary site classification into one of five classes. Tenfold cross-validation generated an overall area under the receiver operating characteristic curve (AUC) of 0.878 (95% confidence interval [CI]: 0.873,0.883). These data establish that whole-brain imaging features are discriminative enough to allow accurate diagnosis of the primary organ site of malignancy. Our end-to-end deep radiomic approach has great potential for classifying metastatic tumor types from whole-brain MRI images. Further refinement may offer an invaluable clinical tool to expedite primary cancer site identification for precision treatment and improved outcomes.

Background: Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means of a spoon-shaped applicator placed on the patient's tongue is a newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism of action of tumour-specific AM RF EMF is largely unknown. Methods: Whole body and organ-specific human dosimetry analyses were performed. Mice carrying human HCC xenografts were exposed to AM RF EMF using a small animal AM RF EMF exposure system replicating human dosimetry and exposure time. We performed histological analysis of tumours following exposure to AM RF EMF. Using an agnostic genomic approach, we characterized the mechanism of action of AM RF EMF. Findings: Intrabuccal administration results in systemic delivery of athermal AM RF EMF from head to toe at levels lower than those generated by cell phones held close to the body. Tumour shrinkage results from differentiation of HCC cells into quiescent cells with spindle morphology. AM RF EMF targeted antiproliferative effects and cancer stem cell inhibiting effects are mediated by Ca2+ influx through Cav3·2 T-type voltage-gated calcium channels (CACNA1H) resulting in increased intracellular calcium concentration within HCC cells only. Interpretation: Intrabuccally-administered AM RF EMF is a systemic therapy that selectively block the growth of HCC cells. AM RF EMF pronounced inhibitory effects on cancer stem cells may explain the exceptionally long responses observed in several patients with advanced HCC. Fund: Research reported in this publication was supported by the National Cancer Institute's Cancer Centre Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Centre (BP) and by funds from the Charles L. Spurr Professorship Fund (BP). DWG is supported by R01 AA016852 and P50 AA026117. Keywords: Advanced hepatocellular carcinoma, T-type voltage gated calcium channels, Calcium influx, Cav 3·2, CACNA1H, Amplitude-modulated, Radiofrequency, Electromagnetic fields, AM RF EMF

The ACR Incidental Findings Committee presents recommendations for managing incidentally detected lung findings on thoracic CT. The Chest Subcommittee is composed of thoracic radiologists who endorsed and developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus. The recommendations address commonly encountered incidental findings in the lungs and are not intended to be a comprehensive review of all pulmonary incidental findings. The goal is to improve the quality of care by providing guidance on management of incidentally detected thoracic findings.

BackgroundKRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 was co-mutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4 mutations in LUAD.MethodsThe association of SMARCA4 mutations with survival outcomes was interrogated in 4 independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received non-immunotherapy treatment from 1) The Cancer Genome Atlas (TCGA) and 2) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from 3) the MSK-IMPACT (MSK-IO) and 4) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts.ResultsOf the patients receiving non-immunotherapy treatment, in the TCGA cohort (n=155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome (P=6e-04 for disease-free survival (DFS) and .031 for overall survival (OS), respectively), compared to KRAS-TP53 co-mutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n=314), KS patients also exhibited shorter OS than KP (P=.03) or K (P=.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P=.0091) in the MSK-IO (n=77), and the shortest PFS (P=.0026) and OS (P=0.0014) in the WFBCCC (n=18) cohorts, respectively.Conclusionsmutations of SMARCA4 represent a genetic factor that lead to adverse clinical outcome in lung adenocarcinoma treated by either non-immunotherapy or immunotherapy.

Soon after the National Lung Screening Trial, organizations began to endorse low-dose computed tomography (LCDT) screening for lung cancer in high-risk patients. Concerns about the risks versus benefits of screening, as well as the logistics of identifying and referring eligible patients, remained among physicians. This study aimed to examine primary care physicians' knowledge, attitudes, referral practices, and associated barriers regarding LDCT screening. We administered a national survey of primary care physicians in the United States between September 2016 and April 2017. Physicians received up to 3 mailings, 1 follow-up email, and received varying incentives to complete the survey. Overall, 293 physicians participated, for a response rate of 13%. We used weighted descriptive statistics to characterize participants and their responses. Over half of the respondents correctly reported that the US Preventive Services Task Force recommends LDCT screening for high-risk patients. Screening recommendations for patients not meeting high-risk criteria varied. Although 75% agreed that the benefits of LDCT screening outweigh the risks, fewer agreed that there is substantial evidence that screening reduces mortality (50%). The most commonly reported barriers to ordering screening included prior authorization requirements (57%), lack of insurance coverage (53%), and coverage denials (31%). The most frequently cited barrier to conducting LDCT screening shared decision making was patients' competing health priorities (42%). Given the impact of physician recommendations on cancer screening utilization, further understanding of physicians' LDCT screening attitudes and shared decision-making practices is needed. Clinical practice and policy changes are also needed to engage more patients in screening discussions., Highlights • Most physicians had five or less lung cancer screening referrals in the past year • Recommendation strategies varied, but often aligned with USPSTF or NCCN guidelines • Physicians were uncertain about the efficacy and cost-effectiveness of screening • Insurance coverage and costs were commonly cited as barriers to screening referral • A common barrier to performing SDM was patients' competing health priorities

A significant reduction in lung cancer specific mortality rate was demonstrated by the National Lung Screening Trial (NLST) in participants who had annual low-dose computed tomography (LDCT) screening. In addition to early detection of lung cancer, lung cancer screening (LCS) provides an opportunity to detect cardiovascular disease, pulmonary disease (such as chronic obstructive pulmonary disease and interstitial lung disease), and extrapulmonary neoplasms, such as thyroid, breast, kidney, liver, esophageal, pancreatic and mediastinal tumors. Considering the fact that 22.3% of the certified deaths in the computed tomography (CT) arm of the NLST trial were due to extrapulmonary malignancies, compared to 22.9% of deaths from lung cancer, it is possible that early diagnosis and treatment of clinically significant incidental findings may further decrease morbidity and mortality in screening participants. In this article we review prevalence, clinical relevance and management of incidentally detected extrapulmonary malignancies.

Despite the promising results of the National Lung Screening Trial in reducing lung cancer mortality among high risk smokers, several challenges remain to be addressed. These include the high false positive rates and the large number of smokers screened in order to prevent one lung cancer death. In addition, host genetic susceptibility has not been integrated into selection of who should be screened. These challenges highlight the need to develop robust ways to identify susceptible smokers for appropriate screening.We used the cytokinesis block micronucleus (CBMN) assay to assess smoking induced genetic instability among NLST participants. Blood cultures were prepared at time of entry into the screening study and DNA damage was recorded as the frequency of binucleated nucleoplasmic bridges and micronuclei. Low dose CT (LDCT) and chest X-ray (CXR) image findings were available upon unblinding of the NLST study and imaging data were merged with blood marker data for statistical analysis.A total of 641 participants were included in this study. The frequency of the CBMN endpoints at time of entry into the study was significantly higher among study participants who had a positive finding during the 3-year screening or reported lung cancer at the end of the follow-up period as compared to participants who were negative. Growth curve models were used to compare trajectories of change in CBMN endpoints between entry into the study and end-of-screening period. A statistically significant increase was predicted for CBMN endpoints among the study participants who were positive versus those who remained negative at the end-of-screening period (P

Although the primary results of the National Lung Screening Trial (NLST) were published only 7 years ago, lung cancer screening today is rapidly advancing (1). In this issue of Translational Lung Cancer Research ( TLCR ) dedicated to CT screening for lung cancer, we include reviews of many of those advances—some already in clinical use, and some still in development.

As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial.Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations. Subjects were tracked for lung cancer incidence and mortality. We examined the incidence of new nodules and their associated lung cancer risk by nodule size (i.e., mean diameter).A total of 25,002 subjects underwent the baseline LDCT screening examination and either a T1 or T2 LDCT screen. At both T1 and T2, 2.6% of subjects had new solid nodules. Of the new solid nodules, 53.0% were6 mm, 29.5% were 6 to10 mm, and 17.1% were ≥ 10 mm. Lung cancer risk (defined as diagnosis within 2 years of baseline) increased from 1.1% for nodules4 mm to 24.0% for those ≥ 20 mm. Compared with solid nodules detected at baseline, the cancer risk was higher for new solid nodules that were 4 to6 mm (p0.001) and 6 to8 mm (p0.001) but lower for new nodules ≥ 20 mm (p = 0.03). Cancers associated with new nodules had significantly poorer survival than did those associated with baseline nodules and were significantly less likely to be adenocarcinoma.The incidence of new nodules was 2-3% annually, with the cancer risk increasing by nodule size. New nodules may convey differential lung cancer risks by size, compared with baseline nodules.

In patients with early-stage lung cancer, surgical resection is the treatment of choice. Knowledge of the expected postsurgical changes and awareness of the temporal evolution of these findings as well as potential complications are important in avoiding misinterpretation. We review the surgical techniques used for lung cancer resection, expected postoperative radiologic manifestations, as well as potential early and late postoperative complications in order to improve diagnostic interpretation and optimize patient management.

The National Lung Screening Trial (NLST) demonstrated a reduction in lung cancer and all-cause mortality with low-dose CT (LDCT) screening. The aim of our study was to examine the time to diagnosis (TTD) of lung cancer in the LDCT arm of the NLST and assess its relationship with cancer characteristics and survival. The subjects (N = 462) with a positive baseline screen and subsequent lung cancer diagnosis within 3 years were evaluated by data and image review to confirm the baseline abnormality. The cases were analysed for the relationship between TTD and imaging features, cancer type, stage and survival for 7 years from baseline screen. Cancer was judged to be present at baseline in 397/462 cases. The factors that showed significant association (p value trend less than 0.05) with longer TTD included smaller nodule size, pure ground glass nodules (GGNs), smooth/lobulated margins, stages I/II, adenocarcinoma, and decreasing lung cancer mortality. The logistic regression model for lung cancer death showed significant inverse relationships with size less than 20 mm (OR = 0.32), pure GGNs (OR = 0.24), adenocarcinoma (OR = 0.57) and direct relationship with age (OR = 1.4). TTD after a positive LDCT screen in the NLST showed a strong association with imaging features, stage and mortality. • NLST observed variable time to lung cancer diagnosis from positive baseline screen. • Time to diagnosis was associated with imaging features, cancer type and stage. • In univariate but not multivariate analysis, longer TTD correlated with decreased mortality.

We describe the development and psychometric properties of a new, brief measure of smokers' knowledge of lung cancer screening with low-dose computed tomography (LDCT). Content experts identified key facts smokers should know in making an informed decision about lung cancer screening. Sample questions were drafted and iteratively refined based on feedback from content experts and cognitive testing with ten smokers. The resulting 16-item knowledge measure was completed by 108 heavy smokers in Houston, Texas, recruited from 12/2014 to 09/2015. Item difficulty, item discrimination, internal consistency and test-retest reliability were assessed. Group differences based upon education levels and smoking history were explored. Several items were dropped due to ceiling effects or overlapping constructs, resulting in a 12-item knowledge measure. Additional items with high item uncertainty were retained because of their importance in informed decision making about lung cancer screening. Internal consistency reliability of the final scale was acceptable (KR-20 = 0.66) and test-retest reliability of the overall scale was 0.84 (intraclass correlation). Knowledge scores differed across education levels (F = 3.36, p = 0.04), while no differences were observed between current and former smokers (F = 1.43, p = 0.24) or among participants who met or did not meet the 30-pack-year screening eligibility criterion (F = 0.57, p = 0.45). The new measure provides a brief, valid and reliable indicator of smokers' knowledge of key concepts central to making an informed decision about lung cancer screening with LDCT, and can be part of a broader assessment of the quality of smokers' decision making about lung cancer screening., Highlights • Lung cancer screening with low-dose CT is recommended for high risk smokers. • Smokers must understand harms and benefits in making informed screening decisions. • A brief measure of lung cancer screening knowledge is offered. • The measure assesses key concepts in making informed screening decisions. • It can be part of a broader assessment of the quality of screening decisions.

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55–74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9–1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

Context.—Optimal management of the patient with a solitary pulmonary nodule entails early diagnosis and appropriate treatment for patients with malignant tumors, and minimization of unnecessary interventions and procedures for those with ultimately benign nodules. With the growing number of high-resolution imaging modalities and studies available, incidentally found solitary pulmonary nodules are an increasingly common occurrence.Objective.—To provide guidance to clinicians involved in the management of patients with a solitary pulmonary nodule, including aspects of risk stratification, workup, diagnosis, and management.Data Sources.—Data for this review were gathered from an extensive literature review on the topic.Conclusions.—Logical evaluation and management pathways for a patient with a solitary pulmonary nodule will allow providers to diagnose and treat individuals with early stage lung cancer and minimize morbidity from invasive procedures for patients with benign lesions.

Importance Lung cancer screening with low-dose computed tomography lowers lung cancer mortality but has potential harms. Current guidelines support patients receiving information about the benefits and harms of lung cancer screening during decision-making. Objective To examine the effect of a patient decision aid (PDA) about lung cancer screening compared with a standard educational material (EDU) on decision-making outcomes among smokers. Design, Setting, and Participants This randomized clinical trial was conducted using 13 state tobacco quitlines. Current and recent tobacco quitline clients who met age and smoking history eligibility for lung cancer screening were enrolled from March 30, 2015, to September 12, 2016, and followed up for 6 months until May 5, 2017. Data analysis was conducted between May 5, 2017, and September 30, 2018. Interventions Participants were randomized to the PDA videoLung Cancer Screening: Is It Right for Me?(n = 259) or to EDU (n = 257). Main Outcomes and Measures The primary outcomes were preparation for decision-making and decisional conflict measured at 1 week. Secondary outcomes included knowledge, intentions, and completion of screening within 6 months of receiving the intervention measured by patient report. Results Of 516 quit line clients enrolled, 370 (71.7%) were younger than 65 years, 320 (62.0%) were female, 138 (26.7%) identified as black, 47 (9.1%) did not have health insurance, and 226 (43.8%) had a high school or lower educational level. Of participants using the PDA, 153 of 227 (67.4%) were well prepared to make a screening decision compared with 108 of 224 participants (48.2%) using EDU (odds ratio [OR], 2.31; 95% CI, 1.56-3.44;P Conclusions and Relevance In this study, a PDA delivered to clients of tobacco quit lines improved informed decision-making about lung cancer screening. Many smokers eligible for lung cancer screening can be reached through tobacco quit lines. Trial Registration ClinicalTrials.gov identifier:NCT02286713

Introduction In the National Lung Screening Trial (NLST) all cases with a 4-mm nodule (micronodule) and no other findings were classified as a negative study. The prevalence and malignant potential of micronodules in the NLST is evaluated to understand if this classification was appropriate. Methods and Materials In the NLST a total of 53,452 participants were enrolled with 26,722 undergoing low-dose computed tomography (CT) screening. To determine whether a micronodule developed into a lung cancer, a list from the NLST database of those participants who developed lung cancer and had a micronodule recorded was selected. The CT images of this subset were reviewed by experienced, fellowship-trained thoracic radiologists (R.F.M., C.C., P.M.B., and D.R.A.), all of whom participated as readers in the NLST. Results There were 26,722 participants who underwent CT in the NLST, of which 11,326 (42%) participants had at least one CT with a micronodule. Five thousand five hundred sixty (49%) of these participants had at least one positive CT examination, of which 409 (3.6%) subsequently were diagnosed with lung cancer. Of the 409 lung cancer cases with a micronodule recorded, there were 13 cases in which a micronodule developed into lung cancer. Considering the 13 cases, they represent 1.2% (13 of 1089) of the lung cancers diagnosed in the CT arm of the NLST and 0.11% (13 of 11,326) of the total micronodule cases. Additionally they represent 0.23% (13 of 5560) of the micronodule and at least one positive CT examination cases and 3.2% (13 of 409) of the micronodule cases diagnosed with lung cancer. The average size of the nodule at baseline (recorded as maximum diameter by perpendicular diameter) was 3.0 × 2.5 mm (ranges 2 x 4 mm and 2 x 4 mm) and at the positive CT the nodule was 11.1 × 8.6 mm (ranges, 6 x 20 mm and 5 x 14 mm); a difference of average change in size of 8.1 × 6.1 mm. The average number of days from first CT with a micronodule recorded to positive CT was 459 days (range, 338 – 723 days), the mean time from first CT with micronodule to lung cancer diagnosis was 617 days (range, 380 – 1140 days) and the mean time from positive CT to lung cancer diagnosis was 160 days (range, 18 – 417 days). Histologically, there was one small cell carcinoma and 12 non–small cell with stages of IA in 8 (62%), stage IB in 2 (15%), and 1 each stage IIIA, IIIB, and IV. The overall survival of NSCLC cases with a micronodule was not significantly different than the survival of the CT subset diagnosed with NSCL (p = 0.36). Conclusions Micronodules are common among lung cancer–screened participants and are capable of developing into lung cancer; however, following micronodules by annual CT screening surveillance is appropriate and does not impact overall survival or outcome.

Incentive plans are a core component of many radiology positions and are often considered a major factor in the ability to recruit and retain high-performing radiologists. Financial incentives are widely thought to be effective at motivating individuals, but there is considerable evidence to the contrary. In this report, the authors examine basic assumptions about financial incentives and debate the potential negative impact of financial incentive systems on performance at radiology practices.

The incidence and mortality from lung cancer is decreasing in the US due to decades of public education and tobacco control policies, but are increasing elsewhere in the world related to the commencement of the tobacco epidemic in various countries and populations in the developing world. Individual cigarette smoking is by far the most common risk factor for lung carcinoma; other risks include passive smoke inhalation, residential radon, occupational exposures, infection and genetic susceptibility. The predominant disease burden currently falls on minority populations and socioeconomically disadvantaged people. In the US, the recent legalization of marijuana for recreational use in many states and the rapid growth of commercially available electronic nicotine delivery systems (ENDS) present challenges to public health for which little short term and no long term safety data is available.

OBJECTIVE. The effectiveness of lung cancer screening with low-dose CT (LDCT) has been shown by multiple clinical trials, particularly the National Lung Screening Trial. Accurate communication of LDCT results to health care providers is critical to optimal patient care. CONCLUSION. The Lung CT Screening Reporting and Data System (Lung-RADS), a structured decision-oriented reporting system designed to minimize the rate of false-positive results and developed by the American College of Radiology, is recommended for use with all LDCT examinations.

The classification of pulmonary large cell carcinoma has undergone a major revision with the recent World Health Organization (WHO) 2015 Classification. Many large cell carcinomas are now reassigned to either adenocarcinoma with solid pattern or nonkeratinizing squamous cell carcinoma based on immunopositivity for adenocarcinoma markers or squamous cell carcinoma markers, respectively. Large cell carcinomas that are negative for adenocarcinoma and squamous cell carcinoma immunomarkers are now classified as large cell carcinoma with null immunohistochemical features (LCC-N). Although a few studies investigated the mutation profile of large cell carcinomas grouped by immunostain profile before the publication of the new WHO classification, investigation of tumors previously diagnosed as large cell carcinoma and reclassified according to the 2015 WHO classification has not, to our knowledge, been reported.Context.— To determine the mutation profiles of pulmonary large cell carcinomas reclassified by WHO 2015 criteria.Objective.— Archival cases of non–small cell lung carcinoma with large cell carcinoma morphology (n = 17) were reclassified according to 2015 WHO criteria. To determine mutation profile, we employed Ion Torrent (Life Technologies, Carlsbad, California)–based next-generation sequencing (50 genes; more than 2800 mutations) in addition to real-time quantitative reverse transcription polymerase chain reaction for ALK translocation detection.Design.— Two of 17 cases (12%) were reclassified as LCC-N, and both had mutations—BRAF D594N in one case and KRAS G12C in the other case. Seven of 17 cases (41%) were reclassified in the adenocarcinoma with solid pattern group, which showed one KRAS G12C and one EGFR E709K + G719C double mutation in addition to mutations in TP53. Eight of 17 cases (47%) were reclassified in the nonkeratinizing squamous cell carcinoma group, which showed mutations in PIK3CA, CDKN2A, and TP53. No ALK translocations or amplifications were detected.Results.— The adenocarcinoma with solid pattern group showed mutations typical of adenocarcinoma, whereas the nonkeratinizing squamous cell carcinoma group showed mutations typical of squamous cell carcinoma. Both LCC-N cases had mutations associated with adenocarcinoma, supporting the hypothesis that LCC-N is related to adenocarcinoma.Conclusions.—

Lung cancer is the leading cause of cancer-related deaths in the United States. Several surgical techniques are currently used as part of the standard of care for early-stage lung cancer. Differentiating normal postoperative changes from complications is essential in the management of these patients. This article will review the various surgical approaches used, ranging from wedge resection to pneumonectomy, and will outline their expected postsurgical changes. Early and late postsurgical complications will be described, some of which are unique to the type of surgery performed. In addition, local tumor recurrence is a form of postoperative complication and must be distinguished from typical postoperative or postradiation change. Knowledge of both common and uncommon postoperative complications is crucial in the follow-up of lung cancer patients. Summary Statement Familiarity with the appearance of postoperative complications in lung cancer patients is vital to distinguish it from the normal postoperative or postradiation appearance in follow-up imaging.

Purpose Understanding the radiographic appearance and normal rate of fluid accumulation after pneumonectomy is important in order to detect postoperative complications. Methods Upright posterior–anterior chest radiographs of 94 postpneumonectomy patients were assessed for the rate of pleural fluid accumulation as a percentage of hemithorax volume. Results Overall median time to 70% hemithoracic opacification was 3 days and mean time was 27 days. The median time to 100% opacification was 66 days and mean time was 96 days. Conclusion The median time to 70% hemithoracic opacification postpneumonectomy is 3 days, while median time to 100% opacification was 66 days.

Malignancies of the lungs, both primary and metastatic, are the leading cause of death worldwide. Over 1.5 million new cases of primary lung cancer are diagnosed annually worldwide with a dismal five-year survival rate of approximately 15%, which remains unchanged despite major efforts and medical advances. As expected, survival for patients with lung metastases is even worse at about 5%. Early detection and staging are fundamental in improving survival rates and selecting the most effective treatment strategies. Recently, nanoparticles have been developed for imaging and treating various cancers, including pulmonary malignancies. In this work, three different examples of nanoparticle configurations for cancer theranosis are presented, namely conventional spherical polymeric nanoparticles with a diameter of ~ 150 nm; and discoidal mesoporous silicon nanoconstructs and discoidal polymeric nanoconstructs with a diameter of ~ 1,000 nm and a height of 400 and 500 nm, respectively. The spherical nanoparticles accumulate in tumors by means of the well-known enhanced permeation and retention effect, whereas sub-micrometer discoidal nanoconstructs are rationally designed to adhere firmly to the tortuous tumor vasculature. All three nanoparticles are characterized for their in vivo performance in terms of magnetic resonance, positron-emission tomography (PET), and optical imaging. Preliminary data on the in vivo and ex vivo PET/CT imaging of breast cancer metastasis in the lungs using discoidal nanoconstructs is presented. In conclusion, opportunities for nanoparticle-based theranosis in primary lung cancer and pulmonary metastasis are presented and discussed.

The purpose of this study was to reduce the radiation dosage associated with computed tomography (CT) lung cancer screening while maintaining overall diagnostic image quality and definition of ground‐glass opacities (GGOs). A lung screening phantom and a multipurpose chest phantom were used to quantitatively assess the performance of two iterative image reconstruction algorithms (adaptive statistical iterative reconstruction (ASIR) and model‐based iterative reconstruction (MBIR)) used in conjunction with reduced tube currents relative to a standard clinical lung cancer screening protocol (51 effective mAs (3.9 mGy) and filtered back‐projection (FBP) reconstruction). To further assess the algorithms' performances, qualitative image analysis was conducted (in the form of a reader study) using the multipurpose chest phantom, which was implanted with GGOs of two densities. Our quantitative image analysis indicated that tube current, and thus radiation dose, could be reduced by 40% or 80% from ASIR or MBIR, respectively, compared with conventional FBP, while maintaining similar image noise magnitude and contrast‐to‐noise ratio. The qualitative portion of our study, which assessed reader preference, yielded similar results, indicating that dose could be reduced by 60% (to 20 effective mAs (1.6 mGy)) with either ASIR or MBIR, while maintaining GGO definition. Additionally, the readers' preferences (as indicated by their ratings) regarding overall image quality were equal or better (for a given dose) when using ASIR or MBIR, compared with FBP. In conclusion, combining ASIR or MBIR with reduced tube current may allow for lower doses while maintaining overall diagnostic image quality, as well as GGO definition, during CT lung cancer screening. PACS numbers: 87.57.Q‐, 87.57.nf

KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 was co-mutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in 4 independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received non-immunotherapy treatment from 1) The Cancer Genome Atlas (TCGA) and 2) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from 3) the MSK-IMPACT (MSK-IO) and 4) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving non-immunotherapy treatment, in the TCGA cohort (n=155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome (P=6e-04 for disease-free survival (DFS) and .031 for overall survival (OS), respectively), compared to KRAS-TP53 co-mutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n=314), KS patients also exhibited shorter OS than KP (P=.03) or K (P=.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P=.0091) in the MSK-IO (n=77), and the shortest PFS (P=.0026) and OS (P=0.0014) in the WFBCCC (n=18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor that lead to adverse clinical outcome in lung adenocarcinoma treated by either non-immunotherapy or immunotherapy. Citation Format: LIANG LIU, Tamjeed Ahmed, Willam Jeffrey Petty, Stefan Grant, Jimmy Ruiz, Thomas W. Lycan, Umit Topaloglu, Ping-Chieh Chou, Lance D. Miller, Gregory A. Hawkins, Martha A. Alexander-Miller, Stacey S. O’Neill, Bayard L. Powell, Ralph B. D’Agostino, Reginald F. Munden, Boris Pasche, Wei Zhang. SMARCA4 mutations in KRAS-mutant lung adenocarcinoma: A multi-cohort analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3138.

Purpose In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC). Patients and Methods Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. Results Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. Conclusion Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

PURPOSE Diaphragmatic hernia (DH) is an uncommon complication after esophagectomy, with

Results from the National Lung Screening Trial have confirmed that lung cancer mortality is reduced using low-dose CT screening. Opening a lung cancer screening program requires a multidisciplinary approach. While the fundamental aspects of a screening program are similar, such as scheduling, performing, and managing follow-up, there are aspects of a lung cancer screening program that are unique. This article will discuss factors important in establishing a state of the art lung cancer screening program.

Over the last few decades, advances in radiotherapy (RT) technology have improved delivery of radiation therapy dramatically. Advances in treatment planning with the development of image-guided radiotherapy and in techniques such as proton therapy, allows the radiation therapist to direct high doses of radiation to the tumour. These advancements result in improved local regional control while reducing potentially damaging dosage to surrounding normal tissues. It is important for radiologists to be aware of the radiological findings from these advances in order to differentiate expected radiation-induced lung injury (RILD) from recurrence, infection, and other lung diseases. In order to understand these changes and correlate them with imaging, the radiologist should have access to the radiation therapy treatment plans.

Introduction This study's objectives were to determine whether tumor response measured by computed tomography (CT) and evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) correlated with overall survival (OS) in patients with non–small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy and surgical resection. Methods We measured primary tumor size on CT before and after neoadjuvant chemotherapy in 160 NSCLC patients who underwent surgical resection. The relationship between CT-measured response (RECIST) and histopathologic response (⩽ 10% viable tumor) and OS were assessed by Kaplan-Meier survival, univariable, and multivariable Cox proportional hazards regression. Results There was a statistically significant association between CT-measured response (RECIST) and OS ( p = 0.03). However, histopathologic response was a stronger predictor of OS ( p = 0.002), with a more pronounced separation of the survival curves when compared with CT-measured response. In multivariable Cox regression analysis, only pathologic stage and histopathologic response were significant predictors of OS. A 41% overall discordance rate was noted between CT RECIST response and histopathologic response. CT RECIST classified as nonresponders a subset of patients with histopathologic response (8 out of 30 points, 27%) who demonstrated prolonged survival after neoadjuvant chemotherapy. Conclusion We were unable to show that CT RECIST is a reliable predictor of OS in patients with NSCLC undergoing surgical resection after neoadjuvant chemotherapy. The failure of CT RECIST to predict long-term outcome may be because of the inability of CT imaging to consistently identify patients with histopathologic response. CT RECIST may have only a limited role as an efficacy endpoint after neoadjuvant chemotherapy in patients with resectable NSCLC.

The aim of this study was to analyze the impact that a clinical history of an oncologic disease may have on the management decisions for incidentally detected lung nodules on chest computed tomographic (CT) examinations.An electronic survey was sent to all 796 members of the Society of Thoracic Radiology regarding criteria for the management of incidentally detected lung nodules in oncologic patients, as well as recommendations for nodule follow-up. Nodule characteristics and clinical parameters used by respondents were analyzed. Differences between variables were examined using the χ test.Of the 796 Society of Thoracic Radiology members, 178 (22.36%) replied. Most respondents were subspecialized in cardiothoracic imaging (92.70%) and practiced in an "academic or teaching hospital setting" (75.28%) with a "dedicated oncology center" (94.03%). "History of oncologic disease" was the most important factor (98.87%) for management decisions. In patients with such a history, respondents most commonly used "experience and common sense" (56.74%) and reported "all incidentally found lung nodules" (65.73%, P0.0001). "Size" and "shape" were the 2 most important nodule characteristics (33.61% and 27.05%, respectively) used to consider a nodule "clinically relevant," and "size" (44.07%) was also the most important nodule characteristic prompting recommendation for short-term CT follow-up. Follow-up CT examinations in oncologic patients were recommended by 75.84% of respondents.In patients with a history of oncologic disease, radiologists tend to report every detected nodule and to routinely recommend follow-up CT examinations. Although most radiologists rely on "experience and common sense" in managing these nodules, greater standardization of lung nodule management in oncologic patients is needed, ideally through guidelines tailored to this patient population.

Objective The study objective was to establish The American Association for Thoracic Surgery (AATS) lung cancer screening guidelines for clinical practice. Methods The AATS established the Lung Cancer Screening and Surveillance Task Force with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 4 medical oncologists, 1 pulmonologist, 1 pathologist, and 1 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with, and at risk for, lung cancer. The task force reviewed the literature, including screening trials in the United States and Europe, and discussed local best clinical practices in the United States and Canada on 4 conference calls. A reference library supported the discussions and increased individual study across disciplines. The task force met to review the literature, state of clinical practice, and recommend consensus-based guidelines. Results Nine of 14 task force members were present at the meeting, and 3 participated by telephone. Two absent task force members were polled afterward. Six unanimous recommendations and supporting work-up algorithms were presented to the Council of the AATS at the 2012 annual meeting in San Francisco, California. Conclusions Annual lung cancer screening and surveillance with low-dose computed tomography is recommended for smokers and former smokers with a 30 pack-year history of smoking and long-term lung cancer survivors aged 55 to 79 years. Screening may begin at age 50 years with a 20 pack-year history of smoking and additional comorbidity that produces a cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Screening should be undertaken with a subspecialty qualified interdisciplinary team. Patient risk calculator application and intersociety engagement will provide data needed to refine future lung cancer screening guidelines.

Lung cancer screening with LDCT is a complex and controversial topic, with inherent risks and benefits. Results from the large, prospective, randomized NLST show that lung cancer screening with LDCT can decrease lung cancer–specific mortality by 20% and even decrease all-cause mortality by 7%.8 The NLST results indicate that to prevent one death from lung cancer, 320 high-risk individuals must be screened with LDCT. However, the NLST findings have not been replicated yet in a separate cohort. Further analysis of the NLST is underway, including comparative effectiveness modeling. The cost-effectiveness and true benefit-to-risk ratio for lung cancer screening still must be determined. At some point, an acceptable level of risk will have to be deemed appropriate for the benefits of screening. The NCCN Lung Cancer Screening Panel recommends helical LDCT screening for select patients at high risk for lung cancer based on the NLST results, nonrandomized studies, and observational data. These guidelines discuss in detail the criteria for determining which patients are at high risk, and the algorithm provides recommendations for evaluating and following-up nodules detected on LDCT screening (e.g., solid and part-solid nodules). Smokers should always be encouraged to quit smoking tobacco (http://www.smokefree.gov/). Programs using behavioral counseling combined with medications that promote smoking cessation (approved by the FDA) can be very useful (see Treating Tobacco Use and Dependence: Quick Reference Guide for Clinicians; http://www.surgeongeneral.gov/tobacco/tobaqrg.htm). When considering lung cancer screening, it is important to have a full understanding of all risks and benefits related to screening with LDCT. As policies for implementing lung screening programs are designed, a focus on multidisciplinary programs (incorporating primary care doctors, pulmonologists, radiologists, thoracic surgeons, medical oncologists, and pathologists) will be helpful to optimize decision-making and minimize interventions for patients with benign lung disease.

Chest computed tomography is acquired in the axial plane, but sternal injuries may be missed on axial images. This study hypothesized that sagittal sternal reconstruction images improve detection of sternal injury and radiologist's confidence in diagnosis compared to axial images. Five radiologists independently reviewed first axial images and on a different day sagittal images of a retrospective set of trauma cases recording presence/absence of a sternal injury and/or adjacent hematoma. The reviewer's confidence in the presence/absence of a sternal injury was assessed on a 5-point scale. Sagittal reconstructions generally yielded higher interreader agreement and confidence indices on statistical analysis.

Purpose: The development of computer-aided diagnostic (CAD) methods for lung nodule detection, classification, and quantitative assessment can be facilitated through a well-characterized repository of computed tomography (CT) scans. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) completed such a database, establishing a publicly available reference for the medical imaging research community. Initiated by the National Cancer Institute (NCI), further advanced by the Foundation for the National Institutes of Health (FNIH), and accompanied by the Food and Drug Administration (FDA) through active participation, this public-private partnership demonstrates the success of a consortium founded on a consensus-based process. Methods: Seven academic centers and eight medical imaging companies collaborated to identify, address, and resolve challenging organizational, technical, and clinical issues to provide a solid foundation for a robust database. The LIDC/IDRI Database contains 1018 cases, each of which includes images from a clinical thoracic CT scan and an associated XML file that records the results of a two-phase image annotation process performed by four experienced thoracic radiologists. In the initial blinded-read phase, each radiologist independently reviewed each CT scan and marked lesions belonging to one of three categories (" nodule�3 mm," " nodule