Wenjia Yang

Prognostic significance and adjuvant chemotherapy survival benefits of a solid or micropapillary pattern in patients with resected stage IB lung adenocarcinoma

Objective: To evaluate the prognostic significance and beneficiaries of adjuvant chemotherapy (ACT) in various histological patterns of stage IB lung adenocarcinoma according to the 8th tumor‐node‐metastasis (TNM) classification. Methods: A total of 1131 patients with pathological stage IB lung adenocarcinoma according to the 8th TNM classification who underwent lobectomy or segmentectomy were enrolled in this study. Based on the proportion of solid/micropapillary components, the patients were classified into 3 groups: solid/micropapillary‐negative (SMPN) (n = 719; median survival, 49.7 months; interquartile range [IQR]. 35.1‐67.0 months), solid/micropapillary‐minor (SMPM; >5% but not predominant) (n = 272; median survival, 38.8 months; IQR, 26.6‐51.5 months) and solid/micropapillary‐predominant (SMPP; >5% and the most dominant) (n = 140; median survival, 39.6 months; IQR, 26.8‐52.5 months). The predictors of disease‐specific survival and recurrence‐free survival were investigated. To reduce selection bias, propensity score‐matching analysis was implemented before survival data were compared. Results: Our data show significant differences in survival rates based on the proportion of solid/micropapillary patterns. The SMPM group had significantly higher cumulative incidences of lung cancer–specific death (P = .000) and recurrence (P = .000) compared with the SMPN group, so did the SMPP group when compared with SMPM patients (P = .000 for both). Multivariate analysis showed that the SMPM and SMPP patterns were poor prognostic factors for disease‐specific survival (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.12‐3.09 and HR, 4.56; 95% CI, 2.69‐7.71, respectively) and recurrence‐free survival (HR, 1.64; 95% CI, 1.20‐2.24 and HR, 2.43; 95% CI, 1.64‐3.60, respectively), as were older age, male sex, smoking history, larger tumor size, necrosis, and abnormal pulmonary function. Survival analysis stratified by histological pattern showed that patients with the SMPP pattern who received ACT had obviously lower cumulative incidences of lung cancer–specific death (HR, 0.46; 95% CI, 0.22‐0.93; P = .031) and recurrence (HR, 0.48; 95% CI, 0.26‐0.88; P = .017). Conclusions: Solid/micropapillary patterns were associated with poor prognosis, even if they were not predominant. ACT contributed to survival benefits in the SMPP subgroup of patients with stage IB lung adenocarcinoma.

Adjuvant chemotherapy may improve prognosis after resection of stage I lung cancer with lymphovascular invasion

Objectives This study explored the prognostic significance and adjuvant chemotherapy benefits in resected patients with stage I non–small cell lung cancer with lymphovascular invasion. Methods A total of 2633 patients who received complete resection with pathologic stage I non–small cell lung cancer in the Shanghai Chest Hospital (2008‐2012) were enrolled in the study, of whom 222 were diagnosed with lymphovascular invasion. By using the Kaplan–Meier method and Cox proportional hazard regression model, we explored the impact of lymphovascular invasion on prognosis and determined if the use of adjuvant chemotherapy is associated with improved outcomes in patients with lymphovascular invasion. A propensity score–matched analysis was implemented to reduce the selection bias. Results Patients with lymphovascular invasion had an unfavorable overall survival and recurrence‐free survival in stage I non–small cell lung cancer. Multivariate Cox analysis indicated that lymphovascular invasion was an independent poor prognostic factor for recurrence‐free survival (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.58‐2.71; P < .001) and overall survival (HR, 2.04; 95% CI, 1.45‐2.87; P < .001) in patients with stage I. After using propensity score–matched pairs, analysis of 65 pairs of patients with lymphovascular invasion indicated a beneficial recurrence‐free survival (HR, 0.33; 95% CI, 0.16‐0.67; P = .002) and overall survival (HR, 0.30; 95% CI, 0.12‐0.74; P = .009) from adjuvant chemotherapy. Conclusions Lymphovascular invasion was correlated with poor prognosis in patients with stage I non–small cell lung cancer. For such patients, adjuvant chemotherapy was associated with improved survival. Our study suggests that adjuvant chemotherapy might be an appropriate option for patients with stage I non–small cell lung cancer with lymphovascular invasion.

Community-based lung cancer screening with low-dose CT in China: Results of the baseline screening

OBJECTIVES To investigate whether low-dose computed tomography (LDCT) screening is capable of enhancing the detection rate of early-stage lung cancer in high-risk population of China with both smoking and non-smoking related factors. METHODS From 2013-2014, eligible participants with high-risk factors of lung cancer were randomly assigned to a screening group or a control group with questionnaire inquiries. Any non-calcified nodules or masses with longest diameters of ≥4 mm identified on LDCT images were considered as positive. RESULTS A total of 6717 eligible participants were randomly enrolled to a study group (3550 to LDCT screening and 3167 to standard care). 3512 participants (98.9%) underwent LDCT screening, and 3145 participants (99.3%) received questionnaire inquiries. A positive screening result was observed in 804 participants (22.9%). In the two-year follow-up period, lung cancer was detected in 51 participants (1.5%) in the LDCT group versus 10 (0.3%) in the control group (stage I: 48 vs 2; stage II to IV or limited stage: 3 vs 8), respectively. Early-stage lung cancer was found in 94.1% vs 20%, respectively. CONCLUSIONS Compared to usual care, LDCT led to a 74.1% increase in detecting early-stage lung cancer. This study provides insights about the non-smoking related risk factors of lung cancer in the Chinese population.

Coexistence of sensitive and resistant epidermal growth factor receptor (EGFR) mutations in pretreatment non-small cell lung cancer (NSCLC) patients: First or third generation tyrosine kinase inhibitors (TKIs)?

OBJECTIVES Occasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients. MATERIALS AND METHODS From January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed. RESULTS 16,842 individuals were screened during the study period with 5900 positive patients identified. Sixty-one patients were confirmed to have primary 20 T790M/insertion plus sensitive mutations (1% of all EGFR-mutant patients, 95% CI, 0.8%-1.3%). Among them, 31 eligible patients were included for survival analyses. The median progression-free survival (PFS) of the 15 osimertinib-treated patients was 18.0 months (95% CI, 15.1-20.9 months), which was greatly longer than the 16 patients who were treated with first generation TKIs (1.2 months, 95% CI, 0.9-1.6, P < 0.001). Similar results were also observed in overall survival (OS) with 25.1 months (95% CI, not calculable) in the osimertinib group and 17.3 months (95% CI, 9.3-25.4 months) in the first generation TKI group (P = 0.02). CONCLUSIONS For patients harboring primary resistant and sensitive mutations detected by routine clinical methods, first generation TKIs are ineffective even with the presence of sensitive mutations. However, osimertinib shows great survival benefit, and thus, should be considered during the whole clinical management.

Screening for early stage lung cancer and its correlation with lung nodule detection

Currently, the most effective way of reducing lung cancer mortality is early diagnosis of lung cancer. The National Lung Screening Trial has proved the efficacy of lung cancer screening using low-dose computed tomography to reduce lung cancer mortality. However, many questions remain surrounding lung cancer screening implementation, among which include how to select the optimal risk population, the personalized screening interval based different levels of risk, methods to improve diagnostic discrimination between malignant and benign disease in detected lung nodules, and the roles of biomolecular markers in stratifying risk and in guiding the management of indeterminate nodules. This review concentrates on the latest developments of lung cancer screening and provides an overview of the main unanswered questions on lung nodule detection.

Predicting malignancy of pulmonary ground-glass nodules and their invasiveness by random forest

Background The purpose of this study was to develop a predictive model that could accurately predict the malignancy of the pulmonary ground-glass nodules (GGNs) and the invasiveness of the malignant GGNs. Methods The authors built two binary classification models that could predict the malignancy of the pulmonary GGNs and the invasiveness of the malignant GGNs. Results Results of our developed model showed random forest could achieve 95.1% accuracy to predict the malignancy of GGNs and 83.0% accuracy to predict the invasiveness of the malignant GGNs. Conclusions The malignancy and invasiveness of pulmonary GGNs could be predicted by random forest.

High-resolution Computed Tomography Features Distinguishing Benign and Malignant Lesions Manifesting as Persistent Solitary Subsolid Nodules

Introduction We retrospectively investigated the high‐resolution computed tomography features that distinguish benign lesions (BLs) from malignant lesions (MLs) appearing as persistent solitary subsolid nodules (SSNs). Materials and Methods In 2015, the data from patients treated in our department with persistent solitary SSNs 5 to 30 mm in size were analyzed retrospectively. The demographic data and HRCT findings were analyzed and compared between those with BLs and MLs. Results Of the 1934 SSNs, 94 were BLs and 1840 were MLs. One half of the MLs (920 SSNs) were randomly selected and analyzed. The BLs were classified into 2 subgroups: 28 pure ground‐glass nodules (pGGNs) and 66 part‐solid nodules (PSNs). After matching in each group, 56 pGGNs and 132 PSNs in the ML group were selected. In the pGGN subgroup, multivariate analysis found that a well‐defined border (odds ratio [OR], 4.320; 95% confidence interval [CI], 1.534‐12.168; P = .006; area under the curve, 0.705; 95% CI, 0.583‐0.828; P = .002) and a higher average CT value (OR, 1.007; 95% CI, 1.001‐1.013; P = .026; area under the curve, 0.715; 95% CI, 0.599‐0.831; P = .001) favored the diagnosis of malignancy. In the PSN subgroup, multivariate analysis revealed that a larger size (OR, 1.084; 95% CI, 1.015‐1.158; P = .016), a well‐defined border (OR, 3.447; 95% CI, 1.675‐7.094; P = .001), and a spiculated margin (OR, 2.735; 95% CI, 1.359‐5.504; P = .005) favored the diagnosis of malignancy. Conclusion In pGGNs, a well‐defined lesion border and a larger average CT value can be valuable discriminators to distinguish between MLs and BLs. In PSNs, a larger size, well‐defined border, and spiculated margin had greater predictive value for malignancy. Micro‐Abstract A pulmonary subsolid nodule (SSN) is a nonspecific finding on computed tomography and often presents a diagnostic challenge to clinicians. The present study found some valuable morphologic discriminators to distinguish malignant SSNs from benign SSNs after investigating the high‐resolution computed tomography features of 1014 SSNs. The use of these morphologic discriminators might help reduce the overdiagnosis and overtreatment of pulmonary SSNs.

Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously untreated advanced lung adenocarcinomas.

Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown.