To address the error introduced by computed tomography (CT) scanners when assessing volume and unidimensional measurement of solid tumors, we scanned a precision manufactured pocket phantom ...simultaneously with patients enrolled in a lung cancer clinical trial. Dedicated software quantified bias and random error in the X,Y, and Z dimensions of a Teflon sphere and also quantified response evaluation criteria in solid tumors and volume measurements using both constant and adaptive thresholding. We found that underestimation bias was essentially the same for X,Y, and Z dimensions using constant thresholding and had similar values for adaptive thresholding. The random error of these length measurements as measured by the standard deviation and coefficient of variation was 0.10 mm (0.65), 0.11 mm (0.71), and 0.59 mm (3.75) for constant thresholding and 0.08 mm (0.51), 0.09 mm (0.56), and 0.58 mm (3.68) for adaptive thresholding, respectively. For random error, however, Z lengths had at least a fivefold higher standard deviation and coefficient of variation than X and Y. Observed Z-dimension error was especially high for some 8 and 16 slice CT models. Error in CT image formation, in particular, for models with low numbers of detector rows, may be large enough to be misinterpreted as representing either treatment response or disease progression.
BackgroundWith the increasing use of CT screening for lung cancer and the advances in imaging and surgical techniques, as well as the improved understanding of the relationship between imaging ...features and pathology/prognosis of lung cancer, there is a need to reevaluate and tailor the surgical approach for treating early-stage lung cancer. The decision between lobectomy and sublobar resection depends on various factors, and surgical decision-making process is multifaceted, involving patient characteristics, clinical factors, surgeon factors, and hospital settings. Recent studies have shown that sublobar resection may be a viable alternative to lobectomy. Precision medicine aims to identify the most effective treatments and tailor the treatment strategy to individual patients, which will not only improve quality of care and long-term outcomes but also reduce unnecessary workups and treatments. ObjectiveThis dissertation research focuses on understanding the complex surgical decision-making process for early-stage lung cancer treatment, particularly in the context of sublobar resection versus lobectomy, as well as how one could improve the process by introducing objectivity with considerations of potential heterogeneous treatment effects in subgroups of early-stage lung cancer patients. This dissertation is divided into three objectives: 1) to examine the underlying latent constructs of tumor aggressiveness and surgical invasiveness, 2) to explore the factors involved in the decision between lobectomy and sublobar resection, including tumor aggressiveness, patient and surgeon characteristics, and nodule features, and 3) to explore how treatment effects on lung cancer-specific survival may vary between different subgroups of early-stage lung cancer patients.Methods In the first part of the analysis, using data from a prospective cohort of 578 patients who enrolled in the Initiative for Early Lung Cancer Research on Treatment (IELCART) project and underwent surgery for clinical stage IA NSCLC at the Mount Sinai Health System (MSHS) between 2016-2022, the study utilized exploratory and confirmatory factor analyses to examine the underlying latent constructs of tumor aggressiveness and surgical invasiveness, and a multiple-indicator, multiple-cause model to elucidate the relationship between tumor aggressiveness and surgical invasiveness, and how this relationship is modified by other patient and surgeon characteristics and nodule features. In the last part of our dissertation research, using data from 746 participants enrolled in the International Early Lung Cancer Action Program (I-ELCAP) between 1992-2022 who underwent surgical resection for first primary clinical stage IA (≤3cm) non-small cell lung cancer, we explored how treatment effects on lung cancer-specific survival may vary between different subgroups of early-stage lung cancer patients using machine learning based approaches under the counterfactual framework.ResultsUsing exploratory factor analysis and confirmatory factor analysis on data from IELCART-MSHS, this research identified two one-factor latent structures with acceptable fit: one characterizing tumor aggressiveness and another characterizing surgical invasiveness (CFI=0.99, TLI=0.98, RMSEA=0.032, SRMR=0.038). Using a MIMIC model, we found that tumor aggressiveness was positively associated with surgical invasiveness, but that this relationship was modified by patient and surgeon characteristics, as well as by other nodule features. Younger patients (β=-0.214, p=0.017), those with lower BMI (β =-0.181, p=0.049), those with tumors in the right lung (β=0.21, p=0.022), and those treated by male surgeons (β =0.274, p=0.019) were more likely to receive more invasive surgery. In the last part of our dissertation research, we deployed machine learning based approaches and revealed notable treatment effects heterogeneity of sublobar resection vs. lobectomy on lung cancer-specific survival, which varied based on sex, smoking status, comorbidity CT evidence of emphysema, and nodule consistency. Among males, there was no difference in median lung cancer-specific survival between sublobar resection and lobectomy (1.0, 95% CI: 0.99, 1.02), while females had longer median survival with sublobar resection (1.14, 95% CI: 1.13, 1.15). Our study also found that sublobar resection was favored for females, regardless of the presence of CT evidence of emphysema, and that former and never smokers benefited more from sublobar resection than current smokers. The benefit of sublobar resection was also found to be greater for solid tumors (1.24, 95% CI: 1.21, 1.26) than part-solid tumors (1.14, 95% CI: 1.07, 1.22) in female former/never smokers without CT evidence of emphysema. In male patients with self-reported history of diabetes or cardiovascular diseases, the comparison of lung cancer-specific survival between sublobar resection and lobectomy yielded inconclusive results. Lobectomy provided better outcomes in male patients who were current smokers, had no history of cardiovascular disease, but had CT evidence of emphysema (0.93, 95% CI: 0.87-0.99), while sublobar resection resulted in longer median lung cancer survival than lobectomy in male patients who were former or never smokers, had no history of cardiovascular disease or diabetes, and did not show CT evidence of emphysema (1.10, 95% CI: 1.07, 1.13), particularly in those with part-solid tumors (1.04, 95% CI: 1.03, 3.14).ConclusionsThis dissertation research reveals the complexity of surgical decision-making in early-stage lung cancer treatment. Our research not only provides the first examination of tumor aggressiveness as a latent factor involved in decision making network, but also provides important information regarding the magnitude and extent of factors involved in surgical decision making for early-stage lung cancer treatment. Our study provides valuable insights into the potential benefits of sublobar resection in specific patient populations, such as female patients, those with specific comorbidities, smoking status and nodule consistency on CT. Further research is needed to confirm these findings. Overall, the findings underscore the importance of personalized medicine, allowing for targeting of interventions to subgroup of patients where the treatment is more likely to be beneficial and improve treatment efficiency.
Low-dose computed tomography screening for lung cancer can reduce mortality among high-risk persons, but "false-positive" findings may result in unnecessary evaluations with attendant risks. The ...effect of alternative thresholds for defining a positive result on the rates of positive results and cancer diagnoses is unknown.
To assess the frequency of positive results and potential delays in diagnosis in the baseline round of screening by using more restrictive thresholds.
Prospective cohort study.
Multi-institutional International Early Lung Cancer Action Program.
21 136 participants with baseline computed tomography performed between 2006 and 2010.
The frequency of solid and part-solid pulmonary nodules and the rate of lung cancer diagnosis by using current (5 mm) and more restrictive thresholds of nodule diameter.
The frequency of positive results in the baseline round by using the current definition of positive result (any parenchymal, solid or part-solid, noncalcified nodule ≥5.0 mm) was 16% (3396/21 136). When alternative threshold values of 6.0, 7.0, 8.0 and 9.0 mm were used, the frequencies of positive results were 10.2% (95% CI, 9.8% to 10.6%), 7.1% (CI, 6.7% to 7.4%), 5.1% (CI, 4.8% to 5.4%), and 4.0% (CI, 3.7% to 4.2%), respectively. Use of these alternative definitions would have reduced the work-up by 36%, 56%, 68%, and 75%, respectively. Concomitantly, lung cancer diagnostics would have been delayed by at most 9 months for 0%, 5.0% (CI, 1.1% to 9.0%), 5.9% (CI, 1.7 to 10.1%), and 6.7% (CI, 2.2% to 11.2%) of the cases of cancer, respectively.
This was a retrospective analysis and thus whether delays in diagnosis would have altered outcomes cannot be determined.
These findings suggest that using a threshold of 7 or 8 mm to define positive results in the baseline round of computed tomography screening for lung cancer should be prospectively evaluated to determine whether the benefits of decreasing further work-up outweigh the consequent delay in diagnosis in some patients.
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.
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.
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.
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.
Growth assessment for pulmonary nodules is an important diagnostic tool; however, the impact on prognosis due to time delay for follow-up diagnostic scans needs to be considered.
Using the data ...between 2003 and 2019 from the International Early Lung Cancer Action Program, a prospective cohort study, we determined the size-specific, 10-year Kaplan-Meier lung cancer (LC) survival rates as surrogates for cure rates. We estimated the change in LC diameter after delays of 90, 180, and 365 days using three representative LC volume doubling times (VDTs) of 60 (fast), 120 (moderate), and 240 (slow). We then estimated the decrease in the LC cure rate resulting from time between computed tomography scans to assess for growth during the diagnostic workup.
Using a regression model of the 10-year LC survival rates on LC diameter, the estimated LC cure rate of a 4.0 mm LC with fast (60-d) VDT is 96.0% (95% confidence interval CI: 95.2%–96.7%) initially, but it would decrease to 94.3% (95% CI: 93.2%–95.0%), 92.0% (95% CI: 90.5%–93.4%), and 83.6%(95% CI: 80.6%–86.6%) after delays of 90, 180, and 365 days, respectively. A 20.0-mm LC with the same VDTs has a lower LC cure rate of 79.9% (95% CI: 76.2%–83.5%) initially and decreases more rapidly to 71.5% (95% CI: 66.4%–76.7%), 59.8% (95% CI: 52.4%–67.1%), and 17.9% (95% CI: 3.0%–32.8%) after the same delays of 90, 180, and 365 days, respectively.
Time between scans required to measure growth of lung nodules affects prognosis with the effect being greater for fast growing and larger cancers. Quantifying the extent of change in prognosis is required to understand efficiencies of different management protocols.
The purpose of this study was to determine the frequency of coronary artery calcification (CAC) in high-risk people undergoing computed tomography (CT) screening for lung cancer.
Between 1999 and ...2004, we performed CT screening for lung cancer on 4250 participants, all without documented prior cardiovascular disease, using multidetector-row (MD) CT. Of the patients, 1102 underwent imaging with a four-detector-row CT at 120 kVp and 40 mA, with pitch 1.5 and collimation of 2.5 mm in a single breath hold of 15–20 seconds, and 3148 did with an eight-detector-row CT at the same kVp, mA, and pitch settings but with collimation of 1.25 mm. Visualized CACs in each coronary artery (main, left anterior descending, circumflex, and right) were scored separately as 0 (
absent), 1 (
mild), 2 (
moderate), or 3 (
severe), yielding a possible score of 0–12 for each person. Frequency distributions by gender, age, and pack-years of smoking were determined. Odds ratios (ORs) were calculated using logistic regression analysis of the prevalence of CAC as a joint function of gender, age, pack-years of smoking, and presence of diabetes.
Among the subjects younger than 50 years, positive CAC scores were three times more frequent for men than for women (22% vs. 7%); among those older than 50 years, the frequency increased for both men and women but the increase for women was greater than that for men. The frequency of positive CAC scores increased with increasing pack-years of smoking; it was always higher for men than for women. The ORs were 2.6 for male gender (
P<.0001), 3.7 and 9.6 for ages 60–69 years and 70 years or older, respectively, for increasing age (
P<.0001 for both), 1.6 and 2.3 for 30–59 pack-years and 60 pack-years or longer, respectively, for increasing pack-years of smoking (
P<.0001 for both), and 1.6 for having diabetes (
P=.016).
The CAC score can be derived from ungated low-dose MDCT images. This information can contribute to risk stratification and management of coronary artery disease.
Purpose
Summarise survival of patients with resected lung cancers manifesting as part-solid nodules (PSNs).
Methods
PubMed/MEDLINE and EMBASE databases were searched for all studies/clinical trials ...on CT-detected lung cancer in English before 21 December 2015 to identify surgically resected lung cancers manifesting as PSNs. Outcome measures were lung cancer-specific survival (LCS), overall survival (OS), or disease-free survival (DFS). All PSNs were classified by the percentage of solid component to the entire nodule diameter into category PSNs <80% or category PSNs ≥80%.
Results
Twenty studies reported on PSNs <80%: 7 reported DFS and 2 OS of 100%, 6 DFS 96.3-98.7%, and 11 OS 94.7-98.9% (median DFS 100% and OS 97.5%). Twenty-seven studies reported on PSNs ≥80%: 1 DFS and 2 OS of 100%, 19 DFS 48.0%-98.0% (median 82.6%), and 16 reported OS 43.0%-98.0% (median DFS 82.6%, OS 85.5%). Both DFS and OS were always higher for PSNs <80%.
Conclusion
A clear definition of the upper limit of solid component of a PSN is needed to avoid misclassification because cell-types and outcomes are different for PSN and solid nodules. The workup should be based on the size of the solid component.
Key points
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Lung cancers manifesting as PSNs are slow growing with high cure rates
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Upper limits of the solid component are important for correct interpretation
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Consensus definition is important for the management of PSNs
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Median disease
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free
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survival
(
DFS
)
increased with decreasing size of the nodule
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