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Background: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking., Purpose: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models., Methods: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer)., Results: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes., Conclusions: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC)., Methods: We reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors., Results: EGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861-0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042-0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type., Conclusion: Non-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC., (© 2024. The Author(s).)

Background: The timeliness of diagnostic testing after positive screening remains suboptimal because of limited evidence and methodology, leading to delayed diagnosis of lung cancer and over-examination. We propose a radiomics approach to assist with planning of the diagnostic testing interval in lung cancer screening., Methods: From an institute-based lung cancer screening cohort, we retrospectively selected 92 patients with pulmonary nodules with diameters ≥ 3 mm at baseline (61 confirmed as lung cancer by histopathology; 31 confirmed cancer-free). Four groups of region-of-interest-based radiomic features (n = 310) were extracted for quantitative characterization of the nodules, and eight features were proven to be predictive of cancer diagnosis, noise-robust, phenotype-related, and non-redundant. A radiomics biomarker was then built with the random survival forest method. The patients with nodules were divided into low-, middle- and high-risk subgroups by two biomarker cutoffs that optimized time-dependent sensitivity and specificity for decisions about diagnostic workup within 3 months and about repeat screening after 12 months, respectively. A radiomics-based follow-up schedule was then proposed. Its performance was visually assessed with a time-to-diagnosis plot and benchmarked against lung RADS and four other guideline protocols., Results: The radiomics biomarker had a high time-dependent area under the curve value (95% CI) for predicting lung cancer diagnosis within 12 months; training: 0.928 (0.844, 0.972), test: 0.888 (0.766, 0.975); the performance was robust in extensive cross-validations. The time-to-diagnosis distributions differed significantly between the three patient subgroups, p < 0.001: 96.2% of high-risk patients (n = 26) were diagnosed within 10 months after baseline screen, whereas 95.8% of low-risk patients (n = 24) remained cancer-free by the end of the study. Compared with the five existing protocols, the proposed follow-up schedule performed best at securing timely lung cancer diagnosis (delayed diagnosis rate: < 5%) and at sparing patients with cancer-free nodules from unnecessary repeat screenings and examinations (false recommendation rate: 0%)., Conclusions: Timely management of screening-detected pulmonary nodules can be substantially improved with a radiomics approach. This proof-of-concept study's results should be further validated in large programs.

Background: Cancer has become a global health problem, and assessments of cancer mortality are important for effective public health policy-making and adequate resource allocation. In this study, we aimed to predict the mortality rates and numbers of deaths related to four common cancers (lung, liver, stomach, and esophagus) in China from 2020 to 2030 and to estimate the corresponding cancer burden caused by population aging and tobacco smoking., Methods: Cancer mortality data (2004-2017) were extracted from China's death surveillance datasets, and China's population figures (2020-2030) were obtained from the United Nations population projections. Smoking prevalence data were retrieved from a World Health Organization global report, and relative risks of smoking and cancers were derived from large-scale Asian studies. We predicted the deaths related to the four major cancers and age-standardized mortality rates using joinpoint regression and linear regression models. The tobacco smoking-related burden of these four major cancers was estimated using the population attributable fraction., Results: Unlike lung cancer mortality which was predicted to continue to increase, the age-standardized mortality rates for digestive cancers (liver, stomach, and esophageal cancers) are predicted to decline over the next decade. The number of deaths caused by the four major cancers is predicted to increase from 1,490,304 in 2020 to 1,823,960 in 2030. The age-specific mortality rates of the four major cancers are predicted to increase with age after 40-45 years, peaking in the age groups of 80-84 and ≥85 years. In 2030, the combined number of deaths from the four examined cancers among adults aged ≥65 years is predicted to be 1,167,153, accounting for 64% of all deaths from these cancers. Tobacco smoking is predicted to contribute to nearly 29% of deaths from these cancers, corresponding to 527,577 deaths., Conclusions: The overall trend in the combined total mortality from four major cancers is predicted to decline over the next decade; however, the corresponding death toll is expected to surge, in the context of China's population aging and high smoking prevalence. These estimates provide data-driven evidence for China to implement effective cancer control measures in the future., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: Mortality outcomes in trials of low-dose computed tomography (CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect., Methods: A decision tree model with three scenarios (low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort (100,000 smokers aged 45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality (primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables., Results: Among the 100,000 subjects, there were 448, 541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively (17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7 and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, low-dose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths (relative numbers) with low-dose CT screening in the worst and optimal cases were 16 (5.4%) and 288 (40.2%) over no screening, respectively., Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China. However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

Objectives: To portray the stage characteristics of lung cancers detected in CT screenings, and explore whether there's universal stage superiority over other methods for various pathological types using available data worldwide in a meta-analysis approach., Materials and Methods: EMBASE and MEDLINE were searched for studies on lung cancer CT screening in natural populations through July 2015 without language or other filters. Twenty-four studies (8 trials and 16 cohorts) involving 1875 CT-detected lung cancer patients were enrolled and assessed by QUADAS-2. Pathology-confirmed stage information was carefully extracted by two reviewers. Stage I or limited stage proportions were pooled by random effect model with Freeman-Tukey double arcsine transformation., Results: Pooled stage I cancer proportion in CT screenings was 73.2% (95% confidence interval: 68.6%, 77.5%), with a significant rising trend (Ptrend<0.05) from baseline (64.7%) to ≥5 repeat rounds (87.1%). Relative to chest radiograph and usual care, the increased stage I proportions in CT were 12.2% (P>0.05), and 46.5% (P<0.05), respectively. Pathology-specifically, adenocarcinomas (66%) and squamous cell lung cancers (17%) composed the majority of CT-detected lung cancers, and had significantly higher stage I proportions relative to chest radiograph (bronchioloalveolar adenocarcinomas, 80.9% vs 51.4%; other adenocarcinomas, 58.8% vs 38.3%; squamous cell lung cancers, 52.3% vs 38.3%; all P<0.05). However, the percentage of small cell lung cancer was lower using CT than other detection routes, and no significant difference in limited stage proportion was observed (6.8% vs 10.8%, P>0.05)., Conclusion: CT screening can detect more early stage non-small cell lung cancers, but not all of them could be beneficial as there are a considerable number of indolent ones such as bronchioloalveolar adenocarcinomas. Still, current evidence is lacking regarding small cell lung cancers., Competing Interests: The authors have declared that no competing interests exist.

Background: In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated., Methods: Eighty-four individuals referred for lung cancer screening (mean age: 54.5±10.8 years) underwent low-dose computed tomography (LDCT) and ultra-low-dose CT. CT examinations were performed with attenuation-based tube current modulation. Reference tube voltage and current were set to 120kV/25mÅs for LDCT and 80kV/4mÅs for ultra-low-dose CT. CT images were reconstructed with filtered back projection (FBP) for LDCT, and with FBP and IR for ultra-low-dose CT datasets. A reference standard was established by a consensus panel of 2 different radiologists on LDCT. Volume and diameter of the solid nodules were measured on LDCT with FBP and ultra-low dose CT with FBP and IR. Interobserver and interscan variability were analyzed and compared by the Bland-Altman method., Results: A total of 127 nodules were identified, including 105 solid nodules, 15 part solid nodules, 7 ground glass nodules. On ultra-low-dose CT scans, the effective radiation dose was 0.13±0.11mSv. A total of 113 (88.9%) and 110 (86.6%) true-positive nodules with FBP versus 117 (92.1%) and 118(92.9%) with IR were detected by two observers, respectively. The volume and size of the 105 solid nodules were measured, with mean volume/diameter of 46.5±46.6 mm(3)/5.1±1.6mm. There was no significant difference in nodule volume or diameter measurements between ultra-low-dose CT and LDCT protocols for solid nodules., Conclusions: Ultra-low-dose CT with iterative reconstruction has high sensitivity for lung nodule detection without significant difference in nodule size and volume measurement compared to LDCT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Widely used (18)F 2'-deoxy-2'-fluoro-d-glucose (FDG) positron emission tomography (PET) can be problematic with false positives in cancer imaging. This study aims to investigate the diagnostic accuracy of a candidate PET tracer, (18)F 2',3'-dideoxy-3'-fluoro-2-thiothymidine (FLT), in diagnosing pulmonary lesions compared with FDG., Materials and Methods: After comprehensive search and study selection, a meta-analysis was performed on data from 548 patients pooled from 17 studies for evaluating FLT accuracy, in which data from 351 patients pooled from ten double-tracer studies was used for direct comparison with FDG. Weighted sensitivity and specificity were used as main indicators of test performance. Individual data was extracted and patient subgroup analyses were performed., Results: Overall, direct comparisons showed lower sensitivity (0.80 vs. 0.89) yet higher specificity (0.82 vs. 0.66) for FLT compared with FDG (both p<0.01). Patient subgroup analysis showed FLT was less sensitive than FDG in detecting lung cancers staged as T1 or T2, and those ≤2.0 cm in diameter (0.81 vs. 0.93, and 0.53 vs. 0.78, respectively, both p<0.05), but was comparable for cancers staged as T3 or T4, and those >2.0 cm in diameter (0.95 vs. 1.00, 0.96 vs. 0.88, both p>0.05). For benignities, FLT performed better compared with FDG in ruling out inflammation-based lesions (0.57 vs. 0.32, p<0.05), and demonstrated greater specificity regardless of lesion sizes., Conclusions: Although FLT cannot replace FDG in detecting small and early lung cancers, it may help to prevent patients with larger or inflammatory lesions from cancer misdiagnosis or even over-treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)