Geographic differences in therapy for stage I non-small-cell lung cancer in older adults.

BACKGROUND: Geographic and socioeconomic factors impact patient treatment choices for certain cancers. Whether they impact treatment in older adults with lung cancer is unknown. We investigated geographic differences in treatment for stage I non-small-cell lung cancer (NSCLC) in older adults in the United States. METHODS: Using the Surveillance, Epidemiology and End Results Database 18th submission, a cohort of stage I NSCLC patients ≥60-years-old was created. Treatment differences (surgery or radiation alone) by geographic location and socioeconomic factors were analyzed. RESULTS: Forty-three thousand three hundred and eighty-seven stage I NSCLC patients were analyzed. Demographics and socioeconomic factors varied across all 13 states (p < 0.001). Surgery was the most common treatment in all states (range 58.6% in AK to 86.5% in CT) (all p < 0.001). Our multivariable analysis found older individuals had higher odds of getting radiation as compared to surgery (odds ratio [OR]: 1.22 for 65-69 years-old to OR: 8.95 for 85+ years-old; p < 0.001). Multiple states (LA, HI, IA, MI, WA, NM) were associated with increased odds of radiation use (vs. surgery alone) (all p < 0.05). People with lower education level (OR: 0.98) and median income (OR: 0.99) and non-Black race (OR: 0.52 for "other" to OR: 0.68 for "White" race with respect to Black race) were associated with lower odds of radiation (p < 0.05). CONCLUSIONS: Our study identified treatment differences for stage I NSCLC patients in the United States related to demographics, socioeconomic factors, and geographic location.

Preserving NLST mortality benefits and acceptable morbidity for lung cancer surgery in a community hospital.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate whether academic thoracic surgeons could achieve morbidity and mortality rates in community hospitals equivalent to those seen in National Lung Screening Trial (NLST). METHODS: This was a retrospective review of community hospital lung cancer procedures for clinical Stage I-III non-small-cell lung cancers from 2007 through 2014. Variables include age, comorbidities, computed tomography (CT) characterization, and operative techniques. RESULTS: There were 177 patients who had lung cancers removed by a minimally invasive approach (79%), including lobectomy in 127 (72%), segmentectomy in 4 (2%), and wedge-resections in 46 (26%). The median patient age was 71 years (interquartile range [IQR], 63-76). The cohort was primarily female (58%), clinical Stage I (82%), with a median tumor size of 2.3 cm (IQR, 1.5-3.3). The median length of stay was 6 days (range: 1-35). Complications were experienced by 78 (44.1%) patients, most commonly atrial fibrillation in 20 (11.3%) followed by air-leak in 19 (10.7%). There were no in-hospital deaths. Tumor location and extent of resection were associated with complications, while larger tumor size, margin contour, and resection method were associated with air-leak (all p < 0.05). Higher clinical stage and larger tumor size were associated with occult Stage III disease (both p < 0.05). CONCLUSIONS: The low morbidity and mortality rates from the NLST were achievable in a community setting for early-stage lung cancer. Characterization of cancers using CT imaging identified factors most commonly associated with postoperative complications and the presence of occult Stage III disease.

Performance of Lung Nodule Management Algorithms for Lung-RADS Category 4 Lesions.

PURPOSE: To test the performance of the American College of Chest Physicians (ACCP) and British Thoracic Society (BTS) algorithms to stratify high-risk nodules identified at lung cancer screening. METHOD AND MATERIALS: Patients with Lung-RADS category 4 nodules identified on lung cancer screening computed tomography (CT) between March 2014 and August 2018 were identified, and a subset of 150 were randomly selected. Nodule characteristics and, if available, fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)-CT scan were recorded. Radiologists blinded to final diagnosis and downstream testing performed five-point visual assessment score for probability of nodule malignancy; their accuracies are averaged below. Probabilities of malignancy according to Brock and Herder models were calculated. ACCP and BTS algorithms were applied to the nodules. RESULTS: Final diagnosis of malignancy was made in 65/150 (43%) of patients. The sensitivity, specificity and accuracy for nodule malignancy were: radiologist visual score (92%, 85%, 88%); BTS (76%, 91%, 85%); ACCP (63%, 89%, 78%); and Brock calculator (77%, 71%, 73%). The sensitivity, specificity, and accuracy for nodule malignancy in patients with FDG PET-CT scan (n = 78) were: FDG uptake (91%, 64%, 83%); Herder probability (91%, 68%, 83%); radiologist visual score (93%, 69%, 86%); BTS (84%, 64%, 78%); Brock probability (82%, 50%, 72%); and ACCP (68%, 59%, 65%). CONCLUSION: Thoracic radiologist visual analysis yielded the greatest accuracy for nodule triage in the entire cohort. BTS performed better than ACCP guidelines and both performed better than the Brock model alone.

Cost-Effectiveness of Follow-Up for Subsolid Pulmonary Nodules in High-Risk Patients.

OBJECTIVE: To evaluate the cost-effectiveness of a number of follow-up guidelines and variants for subsolid pulmonary nodules. METHODS: We used a simulation model informed by data from the literature and the National Lung Screening Trial to simulate patients with ground-glass nodules (GGNs) detected at baseline computed tomography undergoing follow-up. The nodules were allowed to grow and develop solid components over time. We tested the guidelines generated by varying follow-up recommendations for low-risk nodules, that is, pure GGNs or those stable over time. For each guideline, we computed average US costs and quality-adjusted life-years (QALYs) gained per patient and identified the incremental cost-effectiveness ratios of those on the efficient frontier. In addition, we compared the costs and effects of the most recently released version of the Lung Computed Tomography Screening Reporting and Data System (Lung-RADS), version 1.1, with those of the previous version, 1.0. Finally, we performed sensitivity analyses of our results by varying several relevant parameters. RESULTS: Relative to the no follow-up scenario, the follow-up guideline system that was cost-effective at a willingness-to-pay of $100,000/QALY and had the greatest QALY assigned low-risk nodules a 2-year follow-up interval and stopped follow-up after 2 years for GGNs and after 5 years for part-solid nodules; this strategy yielded an incremental cost-effectiveness ratio of $99,970. Lung-RADS version 1.1 was found to be less costly but no less effective than Lung-RADS version 1.0. These findings were essentially stable under a range of sensitivity analyses. CONCLUSIONS: Ceasing follow-up for low-risk subsolid nodules after 2 to 5 years of stability is more cost-effective than perpetual follow-up. Lung-RADS version 1.1 was cheaper but similarly effective to version 1.0.

Determinants of Chest X-Ray Sensitivity for COVID- 19: A Multi-Institutional Study in the United States.

PURPOSE: To evaluate the sensitivity, specificity, and severity of chest x-rays (CXR) and chest CTs over time in confirmed COVID-19+ and COVID-19- patients and to evaluate determinants of false negatives. METHODS: In a retrospective multi-institutional study, 254 RT-PCR verified COVID-19+ patients with at least one CXR or chest CT were compared with 254 age- and gender-matched COVID-19- controls. CXR severity, sensitivity, and specificity were determined with respect to time after onset of symptoms; sensitivity and specificity for chest CTs without time stratification. Performance of serial CXRs against CTs was determined by comparing area under the receiver operating characteristic curves (AUC). A multivariable logistic regression analysis was performed to assess factors related to false negative CXR. RESULTS: COVID-19+ CXR severity and sensitivity increased with time (from sensitivity of 55% at ≤2 days to 79% at >11 days; p<0.001 for trends of both severity and sensitivity) whereas CXR specificity decreased over time (from 83% to 70%, p=0.02). Serial CXR demonstrated increase in AUC (first CXR AUC=0.79, second CXR=0.87, p=0.02), and second CXR approached the accuracy of CT (AUC=0.92, p=0.11). COVID-19 sensitivity of first CXR, second CXR, and CT was 73%, 83%, and 88%, whereas specificity was 80%, 73%, and 77%, respectively. Normal and mild severity CXR findings were the largest factor behind false-negative CXRs (40% normal and 87% combined normal/mild). Young age and African-American ethnicity increased false negative rates. CONCLUSION: CXR sensitivity in COVID-19 detection increases with time, and serial CXRs of COVID-19+ patients has accuracy approaching that of chest CT.

Translation of adapting quantitative CT data from research to local clinical practice: validation evaluation of fully automated procedures to provide lung volumes and percent emphysema.

Current clinical chest CT reporting includes limited qualitative assessment of emphysema with rare mention of lung volumes and limited reporting of emphysema, based upon retrospective review of CT reports. Quantitative CT analysis performed in COPDGene and other research cohorts utilize semiautomated segmentation procedures and well-established research method (Thirona). We compared this reference QCT data with fully automated QCT analysis that can be obtained at the time of CT scan and sent to PACS along with standard chest CT images. 164 COPDGene® cohort study subjects enrolled at Brigham and Women's Hospital had baseline and 5-year follow-up CT scans. Subjects included 17 nonsmoking controls, 92 smokers with normal spirometry, 15 preserved ratio impaired spirometry (PRISm) patients, 12 GOLD 1, 20 GOLD 2, and 8 GOLD 3-4. 97% ( n = 319 ) of clinical reports did not mention lung volumes, and 14% ( n = 46 ) made no mention of emphysema. Total lung volumes determined by the fully automated algorithm were consistently 47 milliliters (ml) less than the Thirona reference value for all subjects (95% confidence interval - 62 to - 32 ml ). Percent emphysema values were equivalent to the Thirona reference values. Well-established research reference data can be used to evaluate and validate automated QCT software. Validation can be repeated as software is updated.

Cumulative nonsmoking risk factors increase the probability of developing lung cancer.

BACKGROUND: It is estimated that 20% of lung cancer cases in the United States are among never smokers, yet current screening recommendations only include a small subset of high-risk patients. In this study, 2 models were used to predict the risk of developing lung cancer in subgroups of never smoking patients with additional risk variables. METHODS: The Liverpool Lung Project (LLP) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were 2 models used to calculate risk of developing lung cancer. Risk was calculated as a function of age for developing lung cancer within the next 5 to 10 years. RESULTS: PLCO estimated a peak risk of 16.20% at age 75 for 30-pack-year smokers with a first-degree relative with lung cancer. LLP estimated a peak risk of 7.3% over the next 5 years at age 79 for men with 30-pack-year and a first-degree relative with early-onset lung cancer (<60 years). Female never smokers with cumulative variables other than smoking had a peak risk of 3.40% for age 74 to 75 years. In contrast, women with only 30-pack-year smoking history and no other variable had a peak risk of 2.20% at age 74 to 75 years. CONCLUSIONS: Models such as LLP and PLCO might be used to identify risk for patients who would otherwise not receive lung cancer screening. These individual risk assessments can be used by patients and providers to assess if one is at substantial risk for developing lung cancer.

Visual Estimate of Coronary Artery Calcium Predicts Cardiovascular Disease in COPD.

BACKGROUND: COPD is associated with cardiovascular disease (CVD), and coronary artery calcification (CAC) provides additional prognostic information. With increasing use of nongated CT scans in clinical practice, this study hypothesized that the visual Weston CAC score would perform as well as the Agatston score in predicting prevalent and incident coronary artery disease (CAD) and CVD in COPD. METHODS: CAC was measured by using Agatston and Weston scores on baseline CT scans in 1,875 current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study. Baseline cardiovascular disease and incident cardiac events on longitudinal follow-up were recorded. Accuracy of the CAC scores was measured by using receiver-operating characteristic analysis, and Cox proportional hazards analyses were used to estimate the risk of incident cardiac events. RESULTS: CAD was reported by 133 (7.1%) subjects at baseline. A total of 413 (22.0%) and 241 (12.9%) patients had significant CAC according to the Weston (≥ 7) and Agatston (≥ 400) scores, respectively; the two methods were significantly correlated (r = 0.84; P < .001). Over 5 years of follow-up, 127 patients (6.8%) developed incident CVD. For predicting prevalent CAD, c-indices for the Weston and Agatston scores were 0.78 and 0.74 and for predicting incident CVD, they were 0.62 and 0.61. After adjustment for age, race, sex, smoking pack-years, FEV1, percent emphysema, and CT scanner type, a Weston score ≥ 7 was associated with time to first acute coronary event (hazard ratio, 2.16 [95% CI, 1.32 to 3.53]; P = .002), but a Agatston score ≥ 400 was not (hazard ratio, 1.75 [95% CI, 0.99-3.09]; P = .053). CONCLUSIONS: A simple visual score for CAC performed well in predicting incident CAD in smokers with and without COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Computed Tomography Scanning for Early Detection of Lung Cancer.

Parallel and often unrelated developments in health care and technology have all been necessary to bring about early detection of lung cancer and the opportunity to decrease mortality from lung cancer through early detection of the disease by computed tomography. Lung cancer screening programs provide education for patients and clinicians, support smoking cessation as primary prevention for lung cancer, and facilitate health care for tobacco-associated diseases, including cardiovascular and chronic lung diseases. Guidelines for lung cancer screening will need to continue to evolve as additional risk factors and screening tests are developed. Data collection from lung cancer screening programs is vital to the further development of fiscally responsible guidelines to increase detection of lung cancer, which may include small groups with elevated risk for reasons other than tobacco exposure.

Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD: a cohort study.

BACKGROUND: Hypoxemia is a major complication of COPD and is a strong predictor of mortality. We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort. However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline. We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD METHODS: We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline. Development of resting hypoxemia was defined as an oxygen saturation ≤88% on ambient air at rest during follow-up. Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia. RESULTS: Forty-six participants (7%) developed resting hypoxemia at follow-up. Enrollment at Denver (OR 8.30, 95%CI 3.05-22.6), lower baseline oxygen saturation (OR 0.70, 95%CI 0.58-0.85), self-reported heart failure (OR 6.92, 95%CI 1.56-30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95%CI 1.17-6.74), and prior severe COPD exacerbation (OR 3.31, 95%CI 1.38-7.90) were independently associated with development of resting hypoxemia. Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up. CONCLUSIONS: Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation. Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia. TRIAL REGISTRATION: COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008).

Recent trends in surgical research of cancer treatment in the elderly, with a primary focus on lung cancer: Presentation at the 2015 annual meeting of SIOG.

Surgical research concentrating on cancer in the elderly has changed from small single institution outcome studies of carefully selected patients to larger studies that test specific aspects of surgical selection, treatment, and outcome. The purpose of this paper is to review major new trends in surgical geriatric oncology research within the last decade. Reviewing PubMed listings of the last 10years reveals several identifiable areas of particular concentration. Although we use specific studies primarily from lung cancer treatment, the generalizations can be seen across the spectrum of geriatric cancers. These trends include screening for disease that can be successfully treated, integration of operative and non-operative therapies that are changing the indications for surgery, the use of prehabilitation to allow more borderline frail patients to be treated surgically, the use of rehabilitation to facilitate rapid and complete recovery, prevention and treatment of common morbidities, with a special recent focus on delirium and cognitive impairment. New areas of surgical research include research on team building in the OR and ICU. Recent surgical research is becoming quantitative and multi-institutionally based. Overall surgical mortality has dropped over the past 25years in both academic and community hospitals. Prevention of morbidity and loss of functional status is a major focus of research. Funding for new Quality Assurance Projects for elderly patients has been awarded to the American College of Surgeons, and should provide multi-institutional quality outcome data within 5years.