Rowena Yip

Solitary and multiple resected adenocarcinomas after CT screening for lung cancer: Histopathologic features and their prognostic implications

PURPOSE To study the histopathologic features of CT screen-detected Stage IA adenocarcinomas to determine whether survival differed by the proportion of bronchioloalveolar component (BAC) or by the presence of multiple lesions in node-negative patients. METHODS Five pathologists with expertise in pulmonary pathology examined 279 resected cases of adenocarcinomas, 30 mm or less in length diagnosed by CT screening for lung cancer. The panel determined the consensus diagnosis for each case, identified additional cancers, and classified each case as solitary or non-solitary. The presence and proportion of BAC was also documented. RESULTS Of the cases of adenocarcinoma, 20 (7%) were BAC subtype, 246 (88%) mixed subtype and 13 (5%) adenocarcinoma-OTHER. BAC cases manifested as non-solid and part solid nodules, mixed as solid and part-solid, and other as solid only. Kaplan-Meier 10-year survival rates were 100% for BAC and adeno-MIXED with 90-99% BAC cases, 95% for mixed with 1-90% BAC, 90% for those without a BAC component, and 75% for other cases. Fifty (18%) cases were non-solitary carcinomas and 44 of these were node negative; the non-solitary node-negative cases had the same excellent prognosis as solitary node-negative cases. CONCLUSIONS The proportion of BAC component was a positive prognostic factor and correlated with CT consistency. Contrary to staging predictions, cases of non-solitary node-negative adenocarcinoma had the same excellent prognosis as solitary node-negative cases, suggesting that most of the small, node-negative multiple carcinomas probably represent multiple primaries rather than intrapulmonary metastasis.

Ordinal Scoring of Coronary Artery Calcifications on Low-Dose CT Scans of the Chest is Predictive of Death from Cardiovascular Disease

PURPOSE To assess the usefulness of ordinal scoring of the visual assessment of coronary artery calcification (CAC) on low-dose computed tomographic (CT) scans of the chest in the prediction of cardiovascular death. MATERIALS AND METHODS All participants consented to low-dose CT screening according to an institutional review board-approved protocol. The amount of CAC was assessed on ungated low-dose CT scans of the chest obtained between June 2000 and December 2005 in a cohort of 8782 smokers aged 40-85 years. The four main coronary arteries were visually scored, and each participant received a CAC score of 0-12. The date and cause of death was obtained by using the National Death Index. Follow-up time (median, 72.3 months; range, 0.3-91.9 months) was calculated as the time between CT and death, loss to follow-up, or December 31, 2007, whichever came first. Logistic regression analysis was used to determine the risk of mortality according to CAC category adjusted for age, pack-years of cigarette smoking, and sex. The same analysis to determine the hazard ratio for survival from cardiac death was performed by using Cox regression analysis. RESULTS The rate of cardiovascular deaths increased with an increasing CAC score and was 1.2% (43 of 3573 subjects) for a score of 0, 1.8% (66 of 3569 subjects) for a score of 1-3, 5.0% (51 of 1015 subjects) for a score of 4-6, and 5.3% (33 of 625 subjects) for a score of 7-12. With use of subjects with a CAC score of 0 as the reference group, a CAC score of at least 4 was a significant predictor of cardiovascular death (odds ratio [OR], 4.7; 95% confidence interval: 3.3, 6.8; P < .0001); when adjusted for sex, age, and pack-years of smoking, the CAC score remained significant (OR, 2.1; 95% confidence interval: 1.4, 3.1; P = .0002). CONCLUSION Visual assessment of CAC on low-dose CT scans provides clinically relevant quantitative information as to cardiovascular death.

Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules

OBJECTIVES A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. METHODS We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. RESULTS Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). CONCLUSIONS Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer.

Lung Cancers Diagnosed at Annual CT Screening: Volume Doubling Times

PURPOSE To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. MATERIALS AND METHODS All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. RESULTS The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). CONCLUSION Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

Emphysema Scores Predict Death From COPD and Lung Cancer

OBJECTIVE Our objective was to assess the usefulness of emphysema scores in predicting death from COPD and lung cancer. METHODS Emphysema was assessed with low-dose CT scans performed on 9,047 men and women for whom age and smoking history were documented. Each scan was scored according to the presence of emphysema as follows: none, mild, moderate, or marked. Follow-up time was calculated from time of CT scan to time of death or December 31, 2007, whichever came first. Cox regression analysis was used to calculate the hazard ratio (HR) of emphysema as a predictor of death. RESULTS Median age was 65 years, 4,433 (49%) were men, and 4,133 (46%) were currently smoking or had quit within 5 years. Emphysema was identified in 2,637 (29%) and was a significant predictor of death from COPD (HR, 9.3; 95% CI, 4.3-20.2; P < .0001) and from lung cancer (HR, 1.7; 95% CI, 1.1-2.5; P = .013), even when adjusted for age and smoking history. CONCLUSIONS Visual assessment of emphysema on CT scan is a significant predictor of death from COPD and lung cancer.

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds

PURPOSE To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. MATERIALS AND METHODS A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. RESULTS A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). CONCLUSION Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.

CT Screening for Lung Cancer: Alternative Definitions of Positive Test Result Based on the National Lung Screening Trial and International Early Lung Cancer Action Program Databases

PURPOSE To determine the usefulness of alternative nodule size thresholds in a population undergoing computed tomographic (CT) screening for lung cancer and to compare the reported International Early Lung Cancer Action Program ( I-ELCAP International Early Lung Cancer Action Program ) results with the National Lung Screening Trial ( NLST National Lung Screening Trial ) results. MATERIALS AND METHODS The institutional review board approved this retrospective analysis. Informed consent was obtained according to HIPAA compliance. Findings in the CT cohort in the NLST National Lung Screening Trial of 25 813 participants who underwent baseline CT in 2002-2004 were reviewed. The frequency of solid and part-solid pulmonary nodules and the lung cancer diagnoses using an alternative nodule threshold of 5.0, 6.0, 7.0, 8.0, and 9.0 mm were determined. Proportional reduction in the frequency of positive results and their 95% confidence intervals using each of the alternative thresholds were calculated. RESULTS The frequency of positive results in the baseline round in the CT arm of the NLST National Lung Screening Trial using the definition of a positive result of any parenchymal, solid or part-solid, noncalcified nodule of 5.0 mm or larger was 15.8% (4080 of 25 813). Using alternative thresholds of 6.0, 7.0, 8.0, and 9.0 mm, the frequencies of positive results were 10.5% (2700 of 25 813, 7.2% (1847 of 25 813), 5.3% (1362 of 25 813), and 4.1% (1007 of 25 813), respectively, and the corresponding proportional reduction in additional CT scans would have been 33.8% (1380 of 1480), 54.7% (2233 of 4080), 66.6% (2718 of 4080), and 73.8% (3013 of 4080), respectively. Concomitantly, the proportion of lung cancer diagnoses determined within the first 12 months would be delayed up to 9 months for 0.9% (two of 232), 2.6% (six of 232), 6.0% (14 of 232), and 9.9% (23 of 232) of the patients, respectively. CONCLUSION The NLST National Lung Screening Trial results are similar to those previously reported for the I-ELCAP International Early Lung Cancer Action Program and suggest that, even for high-risk participants in the NLST National Lung Screening Trial , higher thresholds of nodule size should be considered and prospectively evaluated.

Smoking Cessation and Relapse during a Lung Cancer Screening Program

Background: The potential for negative screening to reduce smoking cessation and long-term abstinence is a concern in lung cancer screening. We examine whether consistently negative results during long-term participation in a lung cancer screening program reduce cessation or increase relapse. Methods: Participants (N = 2,078) in the Early Lung Cancer Action Program received annual screenings and periodic smoking behavior surveys over a follow-up period as long as 12 years. Point abstinence and prolonged abstinence were examined among 730 baseline smokers. Relapse was examined among 1,227 former smokers who quit for 1 year or more at enrollment, 121 recent quitters at enrollment, and 155 baseline smokers who quit during follow-up. Abstinence and relapse for participants with consistently negative computerized tomography scan results were compared with those with non-cancer–positive results using stratified Cox models. Results: Baseline smokers with negative computerized tomography scans had a 28% lower likelihood of achieving point abstinence at one or more follow-up assessments compared with those with positive scans (hazard ratio, 0.72; P < 0.0004), but consistently negative scans were not associated with a lower likelihood of prolonged abstinence. A consistently negative scan was not associated with a higher likelihood of relapse back to smoking for long-term former smokers, recent quitters, or those who quit during follow-up. Conclusions: We did not detect a lower long-term smoking abstinence or increased relapse over a 6-year period of follow-up among individuals participating in a lung cancer screening program who have a consistently negative screening compared with those with a positive, but noncancer, screening result. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3476–83)

Assessment of lung-cancer mortality reduction from CT Screening

BACKGROUND CT screening has been shown to increase lung cancer curability and we now assess the corresponding reduction in lung cancer mortality. METHODS Lung-cancer mortality in a cohort of 7995 smokers who underwent CT screening for lung cancer in New York State (NYS) was compared with two unscreened cohorts (CPS-II and CARET). The standardized mortality ratio (SMR) of observed to expected lung cancer deaths for NYS was jointly adjusted for age, sex, and smoking history. As more current NYS smokers might have quit as a result of the screening, thus reducing deaths from lung cancer, another analysis was restricted to those participants smoking at entry and still smoking 6 years later. RESULTS The SMR was 64/99.8=0.64 (P = 0.84 × 10⁻⁴) and 28/77.6=0.36 (P = 0.83 × 10⁻¹⁰), showing a significant reduction in deaths from lung cancer of 36% and 64% for CPS-II and CARET, respectively. Considering participants who were smoking at entry and still smoking 6 years later, the SMR using CPS-II rates was 29/49.1 = 0.59 (P = 0.001) and using CARET rates it was 21/57.4 = 0.37 (P = 0.31 × 10⁻⁷). CONCLUSIONS CT screening significantly reduces lung-cancer mortality.

Internal growth of nonsolid lung nodules: radiologic-pathologic correlation.

PURPOSE To determine whether computed tomographic (CT) attenuation values correlate with the histologic measurements of a lung cancer manifesting as a nonsolid nodule and to quantify the extent to which the tumor replaces the airspace within the nodule. MATERIALS AND METHODS Informed consent was obtained to analyze images from CT and pathologic examination under an institutional review board-approved protocol. Fifteen patients who had undergone resection of nonsolid lung cancer were evaluated. On the basis of the CT attenuation values of nonsolid nodules, nonneoplastic lung, soft tissue, and air, the overall proportion of soft tissue in the nodule and nonneoplastic lung and the difference between these two measures were calculated. The analogous measures were obtained from a representative digitized histologic slide. The area of each nodule and the proportion of air within it were measured, and the proportion of soft tissue in the nodule and nonneoplastic lung and the difference between the two were calculated. The difference between the two proportions at CT and histologic examination are the proportions attributable to the cancer on the basis of CT and histologic examinations, respectively. Linear regression was performed to assess the relationship between these measures. RESULTS The average proportions of soft tissue in the nodule at CT and histologic examination were 48% and 69%, respectively, and they showed significant correlation with each other (P = .02); in addition, each showed significant correlation with the attenuation of the nodule (P < .0001 and P = .02, respectively). The difference between the proportions of soft tissue in nodule and nonneoplastic lung at CT and histologic examination were 37% and 30%, respectively, and both were independent of the tumor diameter (P = .26 and P = .41). CONCLUSION The proportion of soft tissue within a nonsolid nodule is correlated with attenuation at CT. This allows for measurement of change within the nodule. An increase of 100 HU in nodule attenuation represents an approximately 10% increase in tumor volume.