Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection.

There has been an increase in the use of molecular probe diagnostic techniques for lung cancer, and magnetic resonance imaging (MRI) offers specific advantages for diagnosing pulmonary carcinoma. Furthermore, advancements in near-infrared II (NIR-II) fluorescence have provided a new method for precise intraoperative tumor resection. However, few probes combine preoperative diagnosis with intraoperative imaging. This study aims to fill this research void by employing a dual-modal probe that targets the epidermal growth factor receptor for MR and NIR-II imaging, enabling the preoperative diagnosis of lung cancer using MRI and precise intraoperative tumor localization using NIR-II with a single probe. The imaging effects and targeting ability of the probe were confirmed in cell lines, mouse models, and clinical samples. The MR signal decreased within 24 h in the patient-derived xenograft mouse model. The average signal-to-background ratio of NIR-II reached 3.98 ± 0.27. The clinical sample also showed a decrease in the T2 signal using MRI, and the NIR-II optical signal-to-background ratio was 3.29. It is expected that this probe can improve the diagnostic rate of lung cancer using MRI and enable precise intraoperative tumor resection using NIR-II.

Simultaneous preoperative computed tomography-guided microcoil localizations of multiple pulmonary nodules.

OBJECTIVES: To evaluate retrospectively the feasibility and safety of simultaneous multiple microcoil localizations of multiple pulmonary nodules prior to video-assisted thoracoscopic surgery (VATS). METHODS: This retrospective cohort study enrolled 288 consecutive patients, who underwent computed tomography (CT)-guided microcoil localization and subsequent VATS at our academic hospital between July 2017 and June 2018. Of these patients, 36 with 79 pulmonary nodules undergoing simultaneous multiple microcoil localizations in the ipsilateral lung were designated the multiple localization group; the remaining 252 with 252 pulmonary nodules undergoing single microcoil localization were designated the single localization group. The main outcomes were the technical success and complication rates of the localization procedures. The Student t test and Mann-Whitney U test were used for continuous variables. The chi-squared test and logistic regression analysis were used to assess dichotomous variables. RESULTS: The localization technical success rates of the multiple and single localization groups were 96.2% (76/79) and 98.0% (247/252), respectively (p = 0.326). The rate of any complication (pneumothorax or pulmonary hemorrhage) was significantly higher in the multiple localization than in the single localization group (55.6% vs 21.8%, respectively; p < 0.001). The incidence of pneumothorax was significantly higher in the multiple localization than in the single localization group (p < 0.001). The difference between the incidence of pulmonary hemorrhage in the 2 groups was not significant (p = 0.385). CONCLUSIONS: Although preoperative CT-guided simultaneous microcoil localizations of multiple pulmonary nodules produced a significantly higher incidence of pneumothorax, the localizations were clinically feasible and safe. KEY POINTS: • Simultaneous preoperative CT-guided microcoil localizations of multiple pulmonary nodules are clinically feasible and safe. • Simultaneous microcoil localizations of multiple pulmonary nodules produced a significantly higher incidence of pneumothorax.

Analysis of factors affecting successful microcoil localization for pulmonary nodules.

BACKGROUND: This study aimed to investigate the factors affecting successful microcoil localization for subsequent thoracoscopic resection of pulmonary small nodules and ground-glass nodules. Microcoil has been useful for preoperative localization. Nevertheless, microcoil may dislocate before video-assisted thoracoscopic surgery. METHODS: The medical data of patients with pulmonary solid nodules and ground-glass nodules, who underwent computed tomography-guided microcoil localization before thoracoscopic surgery, were retrospectively reviewed. Factors including clinical data, imaging data, surgical data, and technical data of microcoil localization were collected for stepwise logistic regression analysis. RESULTS: A total of 206 nodules in 192 patients were included in this study. Microcoil dislocation was identified on video-assisted thoracoscopic surgery exploration in six patients (2.9%), resulting in a successful localization rate of 97.1%. The insertion depth of Chiba needle, transfissure needle tract, and pneumothorax after localization were implicated as significant factors for successful microcoil localization. Based on logistic regression, the insertion depth of Chiba needle and pneumothorax after localization were identified as the independent factors for successful microcoil localization. CONCLUSIONS: The insertion depth of Chiba needle and pneumothorax after localization were the independent factors affecting successful microcoil localization for subsequent thoracoscopic resection. Special care should be taken in terms of the sufficient insertion depth of Chiba needle during microcoil localization and the risk of dislocation.

Patient-Derived Tumor Organoids Combined with Function-Associated ScRNA-Seq for Dissecting the Local Immune Response of Lung Cancer.

In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient-derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function-associated single-cell RNA sequencing (FascRNA-seq) platform allowing both phenotypic evaluation and scRNA-seq at single-organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA-seq data of individual pLCOs with their responses to anti-PD-1 (αPD-1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti-tumor immunity, to identify potential tumor-reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA-seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

[Application of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of isolated mediastinal lesions].

OBJECTIVE: To evaluate the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of isolated mediastinal lesions. METHODS: A retrospective study was conducted of 73 consecutive patients with isolated mediastinal lesions of unknown origin without parenchymal lung abnormalities, who underwent EBUS-TBNA from September 2009 to April 2011. The patients who were nondiagnostic with EBUS-TBNA subsequently underwent surgical biopsies and a minimum of 6 months'clinical and radiologic follow-up. RESULTS: EBUS-TBNA achieved definitive diagnoses in 60 patients of the 73 patients (82.2%, 60/73). Malignancies were diagnosed in 23 patients and benignancies in 37. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing malignant mediastinal lesions were 95.8%(23/24), 100%(49/49) and 98.6%(72/73), respectively. EBUS was well tolerated by all of the patients with no complications. CONCLUSION: EBUS-TBNA of isolated mediastinal lesions is a minimally invasive and safe diagnostic technique with high yield.

Segmentectomy and Wedge Resection for Elderly Patients with Stage I Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Considerable controversies exist regarding the efficacies of segmentectomy and wedge resection for elderly patients with early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to solve these issues. METHODS: We searched the online databases PubMed, Web of Science, EMBASE, and Cochrane Library to identify eligible studies. Elderly patients were defined as ≥65 years. Early-stage NSCLC was defined as stage I based on TNM systems. The primary endpoints were survival outcomes (overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS)) and recurrence patterns. The second endpoints were perioperative morbidities. The hazard rate (HR) and odds ratio (OR) were effect sizes. RESULTS: Sixteen cohort studies (3140 participants) and four database studies were finally included. Segmentectomy and lobectomy showed no significant difference in OS (cohort studies HR 1.00, p = 0.98; database studies HR 1.07, p = 0.14), CSS (HR 0.91, p = 0.85), or DFS (HR 1.04, p = 0.78) in elderly patients with stage I NSCLC. In contrast, wedge resection showed inferior OS (HR 1.28, p < 0.001), CSS (HR 1.17, p = 0.001) and DFS (HR 1.44, p = 0.042) compared to lobectomy. Segmentectomy also showed comparable local recurrence risk with lobectomy (OR 0.98, p = 0.98), while wedge resection showed increased risk (OR 5.46, p < 0.001). Furthermore, sublobar resections showed a decreased risk of 30/90-day mortality, pneumonia, and leak complications compared to lobectomy. CONCLUSION: Segmentectomy is promising when applied to elderly patients with stage I NSCLC, while wedge resection should be limited. Randomized controlled trials are warranted to validate these findings.

A fully automated noncontrast CT 3-D reconstruction algorithm enabled accurate anatomical demonstration for lung segmentectomy.

BACKGROUND: Three-dimensional reconstruction of chest computerized tomography (CT) excels in intuitively demonstrating anatomical patterns for pulmonary segmentectomy. However, current methods are labor-intensive and rely on contrast CT. We hereby present a novel fully automated reconstruction algorithm based on noncontrast CT and assess its performance both independently and in combination with surgeons. METHODS: A retrospective pilot study was performed. Patients between May 2020 to August 2020 who underwent segmentectomy in our single institution were enrolled. Noncontrast CTs were used for reconstruction. In the first part of the study, the accuracy of the demonstration of anatomical variants by either automated or manual reconstruction algorithm were compared to surgical observation, respectively. In the second part of the study, we tested the accuracy of the identification of anatomical variants by four independent attendees who reviewed 3-D reconstruction in combination with CT scans. RESULTS: A total of 20 cases were enrolled in this study. All segments were represented in this study with two left S1-3, two left S4 + 5, one left S6, five left basal segmentectomies, one right S1, three right S2, 1 right S2b + 3a, one right S3, two right S6 and two right basal segmentectomies. The median time consumption for the automated reconstruction was 280 (205-324) s. Accurate vessel and bronchial detection were achieved in 85% by the AI approach and 80% by Mimics, p = 1.00. The accuracy of vessel classification was 80 and 95% by AI and manual approaches, respectively, p = 0.34. In real-world application, the accuracy of the identification of anatomical variant by thoracic surgeons was 85% by AI+CT, and the median time consumption was 2 (1-3) min. CONCLUSIONS: The AI reconstruction algorithm overcame defects of traditional methods and is valuable in surgical planning for segmentectomy. With the AI reconstruction, surgeons may achieve high identification accuracy of anatomical patterns in a short time frame.

AI-based chest CT semantic segmentation algorithm enables semi-automated lung cancer surgery planning by recognizing anatomical variants of pulmonary vessels.

Background: The recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)-based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons' performance. Methods: The semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons' judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT. Results: A total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons. Conclusion: The semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.

Learning curves and long-term outcome of simulation-based thoracentesis training for medical students.

BACKGROUND: Simulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures. METHODS: Fifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participant's performance was assessed by performance score (PS), procedure time (PT), and participant's confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator. RESULTS: Significant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05). CONCLUSIONS: This study demonstrates that simulation-based thoracentesis training can significantly improve an individual's performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.

[Establishment of a mathematical prediction model to evaluate the probability of malignancy or benign in patients with solitary pulmonary nodules].

OBJECTIVE: To evaluate the clinical factors affecting the definite pathological diagnosis of solitary pulmonary nodules (SPN) with multivariate Logistic regression analysis, and to build the clinical prediction model to estimate the probability of malignancy. METHODS: A retrospective cohort study in our institution included 371 patients (197 males and 174 females) with definite pathological diagnosis of solitary pulmonary nodules from Jan 2000 to Sep 2009 (group A). Clinical data included age, gender, course of disease, symptoms, history and quantity of smoking history, history of tumor, family history of tumor, site, diameter, calcification, speculation, border, lobulation, traction of pleural, vascular convergence sign, and cavity. The independent predictors of malignancy were estimated with multivariate analysis, then the clinical prediction model was built. Other 62 SPN patients (group B) with definite pathological diagnosis in our institute from Oct 2009 to Mar 2010, were used to validate value of this clinical prediction model. RESULTS: 53.1% of the nodules were malignant, and 46.9% were benign in goup A. Logistic regression analysis showed that seven clinical characteristics [age of patient (OR: 1.073), diameter (OR: 1.966), border (OR: 0.245), calcification (OR: 0.199), spiculation (OR: 2.088) and the family history of tumor (OR: 3.550)] were independent predictors of malignancy in patients with SPN (P<0.05). The cut-off value was 0.463. The sensitivity in group B was 92.5%, specificity 81.8%, positive predictive value 90.2%, and negative predictive value 85.7%. The area under the ROC curve for our model was 0.888±0.054. CONCLUSION: Age of patient, diameter, border, calcification, spiculation and the family history of tumor are independent predictors of malignancy in patients with SPN. Our prediction model is accurate and sufficient to estimate the malignancy of patients with SPN.

Escalated grades of complications correlate with incremental costs of video-assisted thoracoscopic surgery major lung resection for lung cancer in China.

OBJECTIVE: Few studies have focused on factors associated with the incremental cost of video-assisted thoracoscopic surgery (VATS) in China. We aim to systematically classify the complications after VATS major lung resection and explore their correlation with hospital costs. METHODS: Patients with pathologically stage I-III lung cancer who underwent VATS major lung resections from January 2007 to December 2018 were included. The Thoracic Mortality and Morbidity (TM&M) Classification system was used to evaluate postoperative complications. Grade I and II complications, defined as minor complications, require no therapy or pharmacologic intervention only. Grade III and IV complications, defined as major complications, require surgical intervention or life support. Grade V results in death. A generalized linear model was used to explore the correlation of incremental hospital costs and complications, as well as other clinicopathologic parameters between 2013 and 2016. RESULTS: A total of 2881 patients were enrolled in the first part, and the minor and major complications rates were 24.3% (703 patients) and 8.3% (228 patients), respectively. Six hundred and eighty-two patients were enrolled in the second part. The complications grade II (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.05-1.2, p = 0.0005), grade III (OR 1.55, 95% CI 1.26-1.9, p < 0.0001), grades IV and V (OR 1.09, 95% CI 1.04-1.13, p = 0.0002), diffusion capacity of carbon dioxide (OR 0.998, 95% CI 0.997-1.000, p = 0.004), and duration of chest drainage (OR 1.03, 95% CI 1.02-1.04, p < 0.001) and were independent risk factors for the increase in in-hospital costs of VATS major lung resections. CONCLUSIONS: The severity of complications graded by the TM&M system was an independent risk factor for increased in-hospital costs.

Different pathologic types of early stage lung adenocarcinoma have different post-operative recurrence patterns.

OBJECTIVES: To accurately describe the pattern, timing and predictors of disease recurrence after curative resection for different types of early-stage lung adenocarcinoma (LUAD). METHODS: A total of 1962 patients with early-stage LUAD were included. The presence of micropapillary, solid components or poorly differentiated cancer as a clinical variable was named "high-grade" adenocarcinoma (HGADC), while others were classified as "low-grade" adenocarcinoma (LGADC). Predictive factors for specific recurrence patterns were assessed by univariate and multivariate analyses using Cox-proportional hazard regression models. Event dynamics, based on the hazard rate, were evaluated. RESULTS: At a median follow-up of 36.0 months, 137 (6.98%) of 1962 patients suffered from recurrence. Multivariable Cox analysis revealed that HGADC was an independent predictor for overall recurrence (hazard ratio [HR] 3.08, 95% confidence interval [CI] 2.09-4.52, p < 0.001), local recurrence (HR 2.77, 95% CI 1.38-5.55, p < 0.001), distant metastasis (HR 3.22, 95% CI 2.03-5.11, p < 0.001), chest recurrence (HR 2.80, 95% CI 1.65-4.75, p < 0.001) and brain recurrence (HR 4.11, 95% CI 1.83-9.22, p < 0.001). However, HGADC (HR 1.56, 95% CI 0.63-3.86, p = 0.335 in univariate analysis) was not a risk factor for bone recurrence. The hazard curve of the whole group presented a double-peaked pattern. Different types of LUAD had different hazard curves. HGADC patients exhibited higher hazard rates than LGADC patients during the whole follow-up. In addition, the recurrence hazard curve in HGADC patients showed a typical "double-peaked" pattern, while the curve in LGADC patients displayed a smooth curve after surgery. CONCLUSIONS: Different postoperative recurrence patterns were seen in HGADC and LGADC. Site-specific recurrence patterns were also different in HGADC and LGADC types.

Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week.

While the potential of patient-derived organoids (PDOs) to predict patients' responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.

Comparison of the autofluorescence bronchoscope and the white light bronchoscope in airway examination.

BACKGROUND AND OBJECTIVE: The sensitivity and accuracy of white light bronchoscopy (WLB) in airway examination are low. Autofluorescence bronchoscope (AFB) can determine early lesions in bronchial mucosa more sensitively, but it has seldom performed in China. To assess the clinical value of the AFB in airway examination, we compared the sensitivity and specificity of the AFB and WLB in detecting cancer of the airway mucosa. METHODS: Between September 2009 and May 2010, bronchoscope examinations using both the AFB and WLB were performed on 136 patients, 95 men and 41 women with a median age of 61.5 years (ranged from 25 to 84 years). There were 46 lesions located in the central airway, 84 in the peripheral lung parenchyma, and 6 in the mediastinal region. All patients received local and general anesthesia and were subsequently examined with the WLB and AFB in tandem. All procedures were completed safely. Abnormal visual findings were recorded, and biopsies of the affected regions were collected for pathologic examination. RESULTS: Of 241 regions sampled for biopsy, 76 sites contained malignant lesions, whereas 165 sites contained benign lesions. The AFB detected 72 of the 76 malignant lesions, but the WLB detected only 50. The sensitivities of the AFB and WLB were 94.7% and 65.8%, respectively, and the specificities were 57.0% and 83.6%, respectively. The negative predictive values of the AFB and WLB were 95.9% and 84.1%, respectively. CONCLUSIONS: The AFB is more sensitive than the WLB in detecting cancerous lesions in the mucosa, and is an effective airway examination.

Comparative study on preoperative localization techniques using microcoil and hookwire by propensity score matching.

BACKGROUND: The purpose of this study was to compare the efficacy and safety of two preoperative pulmonary nodule localization techniques using microcoil and hookwire. METHODS: A total of 307 patients with 324 pulmonary nodules were included in the study from March 2012 to October 2016 in two medical centers. Baseline data, positioning operation data, success rate, complications, surgery and pathological results were statistically analyzed. Complications were used as the dependent variables, whereas others were used as covariates for the propensity score matching of the two groups. Statistical analyses were performed to compare the success rate and complication rate of the matched groups. RESULTS: There were 218 lesions in the microcoil group and 106 nodules in the hookwire group. There were no significant differences in gender, age and the location of nodules between the two groups. The diameters of the nodules were smaller (8.2 ± 3.5 mm vs. 10.7 ± 4.3 mm) and solid nodules were fewer (11.5% vs. 26.4%) in the microcoil group. The complication rate of the two groups was not statistically significant. After propensity score matching, 71 patients in each group were successfully matched. We found that the success rate was higher (97.2% vs. 94.4%) and the incidence of complications was lower (31% vs. 15.5%) in the microcoil group. CONCLUSIONS: Both techniques have been shown to be effective in preoperative localization of tiny pulmonary nodules. The method of microcoil localization has more advantages in clinical application. KEY POINTS: Comparison of the efficacy and safety of two methods in preoperative pulmonary nodule localization in order to determine the optimal method.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Is video-assisted thoracoscopy a sufficient approach for mediastinal lymph node dissection to treat lung cancer after neoadjuvant therapy?

BACKGROUND: The role of video-assisted thoracoscopic surgery (VATS) in mediastinal lymph node dissection (MLND) for non-small cell lung cancer (NSCLC) following neoadjuvant therapy remains controversial. The aim of this study was to demonstrate the sufficiency of VATS by evaluating perioperative and long-term outcomes. METHODS: Patients with locally advanced NSCLC and treated with radical surgery after neoadjuvant therapy were identified in our database. The thoroughness of MLND was compared by approach. Multivariable logistic regression analysis was used to evaluate predictors of sufficient MLND. Propensity score matching was performed. Kaplan-Meier and Cox proportional hazard analyses were used to assess long-term survival. RESULTS: Of the 127 enrolled patients, 56 underwent attempted VATS and 71 underwent thoracotomy. Multivariable logistic regression analysis revealed that approach was not a predictor of sufficient MLND (odds ratio 0.81, 95% confidence interval [CI] 0.364-1.803; P = 0.606). After matching, 28 pairs of patients were selected from the two groups. There was no significant difference between the numbers of dissected lymph nodes (15 vs. 20; P = 0.191) and nodal stations (7 vs. 7; P = 0.315). Recurrence-free (log-rank P = 0.613) and overall survival (log-rank P = 0.379) was similar in both groups. Multivariable Cox proportional hazards model analysis indicated that VATS was not an independent predictor of recurrence-free (hazard ratio 0.955, 95% CI 0.415-2.198; P = 0.913) or overall survival (hazard ratio 0.841, 95% CI 0.338-2.093; P = 0.709). CONCLUSION: Compared to thoracotomy, VATS is a sufficient approach for MLND to treat locally advanced NSCLC following neoadjuvant therapy without compromising long-term survival.

Effects of primary tumor resection on the survival of patients with stage IV extrathoracic metastatic non-small cell lung cancer: A population-based study.

BACKGROUND: Selected non-small cell lung cancer (NSCLC) patients with extrathoracic metastases might benefit from surgical intervention; however, the evidence is limited. We investigated the benefit of surgery in these patients regarding the extent of the metastatic disease. METHODS: Patients with extrathoracic metastatic NSCLC were identified in the US National Cancer Institute Surveillance, Epidemiology, and End Results database (2010-2015). Survival was compared before and after matching. Multivariate Cox regression models were built to identify factors associated with survival and to adjust for covariates in subgroup analysis. RESULTS: Of the 39,655 patients, 1206 underwent primary tumor resection, and 630 patients were identified 1:1 in surgical and nonsurgical groups after matching. In the entire cohort, patients who underwent surgery had significant prolonged overall survival (OS) in both unmatched (median survival time, [MST]: 14 vs. 6 months, p < 0.001) and matched (MST: 11 vs. 7 months, p < 0.001) cohorts. In the highly selected surgery-recommended cohort, surgical group still had a significantly longer OS (MST: 14 vs. 6 months, p < 0.001). Multivariate regression showed that surgery was independently associated with improved OS and lung cancer-specific mortality (LCSM) (OS: hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.56-0.64, p < 0.001; LCSM: subhazard ratio [SHR]: 0.61, 95% CI: 0.57-0.66, p < 0.001). Subgroup analysis showed that surgery was an independent favorable predictor to survival in all cohorts except patients with N3 disease, and patients with single-organ metastasis were associated with the most prominent survival benefit from surgery. CONCLUSIONS: Primary tumor resection was associated with improved survival in extrathoracic metastatic NSCLC patients, particularly for those with single-organ metastasis.

Primary tumour resection in non-small-cell lung cancer patients with ipsilateral pleural dissemination (M1a): a population-based study.

OBJECTIVES: Non-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination (M1a) are generally contraindicated for surgery. However, several small-sample studies have demonstrated that they might benefit from surgery. We investigated the effects of primary tumour resection on survival in these patients. METHODS: Stage IV NSCLC patients with ipsilateral pleural dissemination were identified from the US National Cancer Institute Surveillance, Epidemiology and End Results database entries from 2010 to 2015. Survival analysis was performed before and after matching. Multivariable regression models were built to identify prognostic factors. RESULTS: Of the 5513 patients with ipsilateral pleural dissemination, 309 underwent primary tumour resection. In the entire cohort, surgery was associated with improved overall survival (OS) in both the unmatched and matched cohorts (both log rank, P < 0.001). In the surgery-recommended cohort, patients treated with surgery also had significantly longer OS before and after matching. Multivariable regression models showed that surgery was an independent favourable prognostic factor for OS [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.48-0.65; P < 0.001] and lung cancer-specific mortality (subhazard ratio 0.60, 95% CI 0.51-0.70; P < 0.001). Surgery was independently associated with improved survival in all subgroups except for those with pericardial effusion (P = 0.065) or N3 disease (P = 0.17). In the surgical cohort, patients who underwent lobe/bilobectomy had significantly better OS than those who underwent sublobar resection (log rank, P < 0.001). CONCLUSIONS: Inclusion of primary tumour resection in multimodal therapy of NSCLC was associated with improved survival in selected patients with ipsilateral pleural dissemination, except for those with pericardial effusion or N3 disease.