Lung Cancer Lesions Research Articles

Clinical and molecular characteristics of multiple primaries identified by whole-exome sequencing-based genetic divergence in non-small-cell lung cancer.

e20558 Background: With the recommendation of high-resolution chest computed tomography scan in lung cancer screening, multiple primary lung cancers (MPLC) is gaining more attention. Identifying MPLC from intrapulmonary metastases (IPM) is crucial to the clinical management. The current guidelines for the identification are always based on expert consensus rather than clinical evidence. We aim to develop a reliable identification method and further figure out the clinical and genetic features of MPLC. Methods: We retrospectively screened 305 lung lesions from 131 patients who underwent radical resection for multiple lung carcinomas. To minimize the effect of therapeutic intervention on prognostic outcomes, patients with each single tumor size smaller than 4cm, free of nodal or systemic metastases, and had high-quality whole-exon sequencing (WES) data were included. We selected 11 patients with confirmed intrapulmonary metastases for training. All patients’ follow-up information was collected until disease recurrence or metastases. A WES genetic divergence method for identifying MPLC from IPM was developed. The disease-free survival (DFS) was used as a validation tool for identification reliability. Results: A total of 61 eligible multi-lesion patients with 128 resected non-small cell lung cancer (NSCLC) lesions were finally analyzed. Based on WES genetic divergence identification, 51 MPLC patients were identified, whose DFS was significantly prolonged (HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.02), while other recommended methods for identifying MPLC patients failed to show a DFS advantage. Among MPLC patients, 43.1% (22/51) had a first-degree relatives cancer family history, of whom 54.5% (12/22) had a lung cancer family history. EGFR was still the most common mutation gene (72.5%, 37/51); however, TP53 mutations was less frequent in MPLC (21% vs. 48%, P < 0.05), and tumor mutation burden (TMB) was lower (median, 0.73 muts/Mb vs. 1.15 muts/Mb, P < 0.01). Notably, despite the lack of shared alterations, unique germline variants in cancer-predisposing genes, particularly nonsynonymous SNV in solute carrier gene (SLC) family, were observed in most MPLC patients, rarely overlapping with IPM patients. Conclusions: WES-based genetic divergence clearly distinguishes independent primary tumors from IPM in NSCLC patients. MPLC patients represent a unique population which deserves further study.

Results of intention-to-treat pulmonary metastasectomies in northern Finland revealing significant number of new lung primary carcinomas: time to move on from wedge resections?

A considerable proportion of intended pulmonary metastasectomies is known to turn out as new incidental primary lung cancers in final pathology. We aimed to analyse the trends and results of pulmonary metastasectomies using the intention-to-treat approach with an emphasis on final histopathological findings. All intention-to-treat pulmonary metastasectomies performed in Oulu University Hospital between 2000 and 2020 were included in the study. Long term survival was analysed with the Kaplan-Meier method and log-rank tests. A binary logistic regression analysis was performed to calculate odds ratios for incidental primary lung cancer in final histology. A total of 154 intended pulmonary metastasectomies were performed to 127 individual patients. There was an increasing trend in pulmonary metastasectomies during the study period. Despite the increasing trend in comorbidities of the operated patients, the length of hospital stays decreased, and the postoperative complication rates remained stable. In final pathology reports, 9.7% were new primary lung cancers and 13.0% were benign nodules. A long disease-free interval (≥24 months) and smoking history were associated with incidental primary lung cancer in final histology. The short-term 30- and 90-day mortalities after pulmonary metastasectomy were 0.7%. The 5-year survival after pulmonary metastasectomy from all histologies was 52.8%, and from colorectal cancer metastasectomies (n=34) it was 73.5%. The significant amount of new primary lung cancer lesions in pulmonary metastasectomy specimens highlight the diagnostic importance of pulmonary metastasectomy. A segmentectomy could be considered as a primary procedure in pulmonary metastasectomy in patients with a long disease-free interval and a heavy smoking history.

The consideration of surgery on primary lesion of advanced non-small cell lung cancer

BackgroundNumerous reports have shown that medical treatment confers excellent survival benefits to patients with advanced stage IV non-small cell lung cancer (NSCLC). However, the implications of surgery for primary lesions as palliative treatment remain inconclusive.MethodsWe retrospectively extracted clinical data from the Surveillance, Epidemiology, and End Results Program (SEER) database and selected patients with stage IV NSCLC. Patients were classified into non-surgery and surgery groups, and propensity score matching (PSM) analysis was performed to balance the baseline information. Patients in the surgery group, whose overall survival (OS) was longer than the median survival time of those in the non-surgery group, were deemed to benefit from surgery. We evaluated the efficacy of three surgical techniques, namely, local destruction, sub-lobectomy, and lobectomy, on the primary site in the beneficial population.ResultsThe results of Cox regression analyses revealed that surgery was an independent risk factor for both OS (hazard ratio [HR]: 0.441; confidence interval [CI]: 0.426–0.456; P < 0.001) and cancer-specific survival (CSS) (HR: 0397; CI: 0.380–0.414; P < 0.001). Notably, patients who underwent surgery had a better prognosis than those who did not (OS: P < 0.001; CSS: P < 0.001). Moreover, local destruction and sub-lobectomy significantly compromised survival compared to lobectomy in the beneficial group (P < 0.001). After PSM, patients with stage IV disease who underwent lobectomy needed routine mediastinal lymph node clearing (OS: P = 0.0038; CSS: P = 0.039).ConclusionBased on these findings, we recommend that patients with stage IV NSCLC undergo palliative surgery for the primary site and that lobectomy plus lymph node resection should be conventionally performed on those who can tolerate the surgery.

Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience.

The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution. This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0-60.0) was delivered using 10.0-15.0 Gy per fraction. The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity. SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.

Inhalable Biomineralized Liposomes for Cyclic Ca2+-Burst-Centered Endoplasmic Reticulum Stress Enhanced Lung Cancer Ferroptosis Therapy

Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+-burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy. Equipped with excellent nebulization properties, about 6.80-fold higher lung lesions drug accumulation than intravenous injection made the proposed inhalable LDM an ideal nanoplatform for lung cancer treatment. The Fenton-like reaction mediated by DHA with peroxide bridge structure could contribute to intracellular ROS production and induce ferroptosis. Assisted by DHA-mediated sarco-/endoplasmic reticulum calcium ATPase (SERCA) inhibition, the initial Ca2+ burst caused by CaP shell degradation triggered the Ca2+-mediated intense ER stress and subsequently induced mitochondria dysfunction to further boost ROS accumulation, which strengthens ferroptosis. The second Ca2+ burst occurred as a result of Ca2+ influx through ferroptotic pores on cell membranes, thus sequentially constructing the lethal "Ca2+ burst-ER stress-ferroptosis" cycle. Consequently, the Ca2+-burst-centered ER stress enhanced ferroptosis process was confirmed as a cell swelling and cell membrane disruption process driven by notable intracellular ROS and LPO accumulation. The proposed LDM showed an encouraging lung retention property and extraordinary antitumor ability in an orthotropic lung tumor murine model. In conclusion, the constructed ferroptosis nanoinducer could be a potential tailored nanoplatform for nebulization-based pulmonary delivery and underscore the application of Ca2+-burst-centered ER stress enhanced lung cancer ferroptosis therapy.

Whole-lesion histogram analysis of multiple diffusion metrics for differentiating lung cancer from inflammatory lesions.

Whole-lesion histogram analysis can provide comprehensive assessment of tissues by calculating additional quantitative metrics such as skewness and kurtosis; however, few studies have evaluated its value in the differential diagnosis of lung lesions. To compare the diagnostic performance of conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) in differentiating lung cancer from focal inflammatory lesions, based on whole-lesion volume histogram analysis. Fifty-nine patients with solitary pulmonary lesions underwent multiple b-values DWIs, which were then postprocessed using mono-exponential, bi-exponential and DKI models. Histogram parameters of the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f), apparent diffusional kurtosis (Kapp) and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the lung cancer and inflammatory lesion groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance. The ADCmean, ADCmedian, D mean and D median values of lung cancer were significantly lower than those of inflammatory lesions, while the ADCskewness, Kapp mean, Kapp median, Kapp SD, Kapp kurtosis and Dapp skewness values of lung cancer were significantly higher than those of inflammatory lesions (all p < 0.05). ADCskewness (p = 0.019) and D median (p = 0.031) were identified as independent predictors of lung cancer. D median showed the best performance for differentiating lung cancer from inflammatory lesions, with an area under the ROC curve of 0.777. Using a D median of 1.091 × 10-3 mm2/s as the optimal cut-off value, the sensitivity, specificity, positive predictive value and negative predictive value were 69.23%, 85.00%, 90.00% and 58.62%, respectively. Whole-lesion histogram analysis of DWI, IVIM and DKI parameters is a promising approach for differentiating lung cancer from inflammatory lesions, and D median shows the best performance in the differential diagnosis of solitary pulmonary lesions.

Relationship of Tumor Necrosis Factor Alpha, Monocyte-Lymphocyte Ratio, and Neutrophil-Lymphocyte Ratio of Bronchial Washing Fluid with Histopathology, Stage, and Bronchoscopic Lesions of Non-Small Cell Carcinoma Lung Cancer

Background: Chronic inflammation has been shown to be closely associated with immunosuppressive conditions that support the microenvironment for tumorigenesis, tumor progression, and metastasis. The aim of this study was to assess the relationship of inflammatory cytokine levels TNF-a , neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) with histopathology, stage, and bronchoscopic features of non-small cell carcinoma lung cancer (NSCLC). Methods: This study was an analytical observational study with a cross-sectional design at the Prof. Dr. I.G.N.G Ngoerah Central General Hospital in January 2023 – September 2023. Data analysis was performed using the Mann-Whitney, Kruskal-Wallis and 2 independent sample t test. Results: There were 23 samples that met the inclusion criteria. The mean NLR, MLR, and TNF-a in this study were 8.939, 0.095, and 129.46 respectively. NLR was associated with KPKBSK histopathology (p = 0.026), KPKBSK stage (p = 0.003), tumour size classification (T) (p = 0.001) and metastasis (M) (p = 0009). MLR was associated with KPKBSK histopathology (p = 0.035). Smoking status had an influence on the relationship between MLR and KPKBSK histopathology (p = 0.032). TNF-a value was not associated with KPKBSK histopathology, bronchoscopic lesions, and stage. Smoking status had an influence on the bronchoscopic lesions of KPKBSK (p = 0.04). Conclusion: There are associations between MLR and NLR with histopathology of non-small cell carcinoma lung cancer. There is a relationship between NLR and the stage of non-small cell carcinoma lung cancer.

Pafolacianine: A Diagnostic Agent to Identify Lung Cancer Lesions in Adults with Known or Suspected Lung Cancer

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Performance and Prospects of [68Ga]Ga-FAPI PET/CT Scans in Lung Cancer.

Fibroblast activation protein (FAP) could be a promising target for tumor imaging and therapy, as it is expressed in &gt;90% of epithelial cancers. A high level of FAP-expression might be associated with worse prognosis in several cancer types, including lung cancer. FAPI binds this protein and allows for labelling to Gallium-68, as well as several therapeutic radiopharmaceuticals. As FAP is only expressed at insignificant levels in adult normal tissue, FAPI provides a highly specific tumor-marker for many epithelial cancers. In this review, current information on the use of [68Ga]Ga-FAPI PET/CT in lung cancer is presented. [68Ga]Ga-FAPI shows a high uptake (standardized uptake value = SUVmax) and tumor-to-background ratio (TBR) in primary lung cancer lesions, as well as in metastatic lesions of other tumor types located in the lung and in lung cancer metastases located throughout the body. Where a comparison was made to [18F]FDG PET/CT, [68Ga]Ga-FAPI showed a similar or higher SUVmax and TBR. In brain and bone metastases, [68Ga]Ga-FAPI PET/CT outperformed [18F]FDG PET/CT. In addition to this strong diagnostic performance, a possible prognostic value of [68Ga]Ga-FAPI PET/CT in lung cancer is proposed.

Pulmonary function changes after sublobar resection in patients with peripheral non-subpleural nodules

BackgroundIn the treatment of peripheral early-staged lung cancer and benign lesions, segmentectomy and wedge resection are both reliable treatment methods. It is debatable that how much pulmonary function will be lost after different sublobar resection in the treatment of early-staged deep-located peripheral NSCLC (non-small cell lung cancer). The purpose of this study was to explore postoperative pulmonary function changes of sublobar resection in enrolled patients with non-subpleural peripheral nodules.MethodsWe collected clinical data of patients undergoing VATS (video-assisted thoracoscopic surgery) segmentectomy or wedge resection for single nodule. These nodules were confirmed as peripheral non-subpleural nodules by preoperative 3D imaging. Patients were divided into two groups according to the operation procedure. Demographic characteristics, pulmonary function, postoperative outcomes, and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. Outcomes after wedge resection were compared with those after segmentectomy resection.ResultsA total of 88 patients were included in this study, including 46 patients with VATS wedge resection and 42 patients with VATS segmentectomy. No difference was detected when comparing FEV1 (forced expiratory volume in 1 s) loss between these two groups (17.6 ± 2.1%, wedge resection vs. 19.4 ± 5.4%, segmentectomy, P = 0.176). FVC (forced vital capacity) loss (8.7 ± 2.3%, wedge resection vs. 17.1 ± 2.2%, segmentectomy, P < 0.001) and MVV (maximum ventilatory volume) loss (11.5 ± 3.1%, wedge resection vs. 20.6 ± 7.8%, segmentectomy, P < 0.001) in segmentectomy group was significantly higher than those in wedge resection group. Discrepancies were investigated when comparing duration of surgery (70 ± 22 min, wedge resection vs. 111 ± 52 min, segmentectomy, P = 0.0002), postoperative drainage (85 ± 45 mL, wedge resection vs. 287 ± 672 mL, segmentectomy, P = 0.0123), and treatment hospitalization expenses [35148 ± 889CNY, wedge resection vs. 52,502 (38,276–57,772) CNY, segmentectomy, P < 0.0002]. No significant difference was found between air leak time (1.7 ± 0.7 days, wedge resection vs. 2.5 ± 1.7 days, segmentectomy, P = 0.062) and hospitalization time (2.7 ± 0.7 days, wedge resection vs. 3.5 ± 1.7 days, segmentectomy, P = 0.051).ConclusionsFor patients with peripheral non-subpleural nodules, we observed that patients who underwent wedge resection had less lung function loss than those who underwent segmentectomy when their lung function was reviewed at the 6th month after surgery. Patients undergoing wedge resection had partial advantages over patients with segmental resection in terms of hospitalization cost, operation time and postoperative drainage, etc. Wedge resection, as a treatment for peripheral non-subpleural pulmonary nodules, seemed to have more advantages in preserving patients’ pulmonary function.

An Effective Method for Lung Cancer Diagnosis from CT Scan Using Deep Learning-Based Support Vector Network.

The diagnosis of early-stage lung cancer is challenging due to its asymptomatic nature, especially given the repeated radiation exposure and high cost of computed tomography(CT). Examining the lung CT images to detect pulmonary nodules, especially the cell lung cancer lesions, is also tedious and prone to errors even by a specialist. This study proposes a cancer diagnostic model based on a deep learning-enabled support vector machine (SVM). The proposed computer-aided design (CAD) model identifies the physiological and pathological changes in the soft tissues of the cross-section in lung cancer lesions. The model is first trained to recognize lung cancer by measuring and comparing the selected profile values in CT images obtained from patients and control patients at their diagnosis. Then, the model is tested and validated using the CT scans of both patients and control patients that are not shown in the training phase. The study investigates 888 annotated CT scans from the publicly available LIDC/IDRI database. The proposed deep learning-assisted SVM-based model yields 94% accuracy for pulmonary nodule detection representing early-stage lung cancer. It is found superior to other existing methods including complex deep learning, simple machine learning, and the hybrid techniques used on lung CT images for nodule detection. Experimental results demonstrate that the proposed approach can greatly assist radiologists in detecting early lung cancer and facilitating the timely management of patients.

Artificial intelligence neural network analysis and application of CT imaging features to predict lymph node metastasis in non-small cell lung cancer.

Computed tomography (CT) is important in the diagnosing of lung cancer. The combination of CT features and artificial intelligence algorithm have been used in the diagnosis of various lung diseases. However, limited studies focused on the relationship between the combination of CT features and artificial intelligence algorithm and lymph node metastasis in non-small cell lung cancer (NSCLC). This study developed an algorithm for lung cancer CT image segmentation based on an artificial neural network model and investigated the role of a nomogram model based on CT images for predicting lymph node metastasis in lung cancer. Wiener filtering and fuzzy enhancement were first used to suppress image noise and improve image contrast. Next, texture features and fractal features were extracted. In the third step, the artificial neural network model was trained and tested according to the best parameters of the network. The area under the curve (AUC) of the constructed nomogram model on the training set and the test set were 0.859 (sensitivity, 0.810; specificity, 0.773) and 0.864 (sensitivity, 0.820; specificity, 0.753), respectively. The decision curve indicated that the model had good clinical application value. The lung cancer CT images contained 13 significant regional features of cancer. The best classification function obtained from training and testing data was Levenberg-Marquardt backpropagation. The sensitivity, specificity, and accuracy in the training stage could reach 98.4%, 100%, and 98.6%, respectively, and the corresponding indexes in the test stage reached 90.9%, 100%, and 95.1%, respectively. The image segmentation algorithm based on the artificial neural network model could extract CT lung cancer lesions efficiently and quasi-determinately, which could be used as an effective tool for radiologists to diagnose lung cancer. The nomogram model based on CT image features and related clinical indicators was an effective method for noninvasive prediction of lymph node metastasis in lung cancer.

Mechanics of lung cancer: A finite element model shows strain amplification during early tumorigenesis.

Early lung cancer lesions develop within a unique microenvironment that undergoes constant cyclic stretch from respiration. While tumor stiffening is an established driver of tumor progression, the contribution of stress and strain to lung cancer is unknown. We developed tissue scale finite element models of lung tissue to test how early lesions alter respiration-induced strain. We found that an early tumor, represented as alveolar filling, amplified the strain experienced in the adjacent alveolar walls. Tumor stiffening further increased the amplitude of the strain in the adjacent alveolar walls and extended the strain amplification deeper into the normal lung. In contrast, the strain experienced in the tumor proper was less than the applied strain, although regions of amplification appeared at the tumor edge. Measurements of the alveolar wall thickness in clinical and mouse model samples of lung adenocarcinoma (LUAD) showed wall thickening adjacent to the tumors, consistent with cellular response to strain. Modeling alveolar wall thickening by encircling the tumor with thickened walls moved the strain amplification radially outward, to the next adjacent alveolus. Simulating iterative thickening in response to amplified strain produced tracks of thickened walls. We observed such tracks in early-stage clinical samples. The tracks were populated with invading tumor cells, suggesting that strain amplification in very early lung lesions could guide pro-invasive remodeling of the tumor microenvironment. The simulation results and tumor measurements suggest that cells at the edge of a lung tumor and in surrounding alveolar walls experience increased strain during respiration that could promote tumor progression.

Magnetic resonance tomography of the lungs with paramagnetic contrast enhancement in dynamic follow-up control of treatment of lung cancer in radiophobic patient: a case report

Till now the facilities of MRI with paramagnetic contrast enhancement (CE-MRI) in detection of lung tumors remain underused and almost ignored. A clinical case of primary detection and prospective follow-up of lung cancer in a patient whose MRI of the chest revealed a tumor lesion — a central cancer of the left lung, in particular a lesion of the bronchus of the lower lobe of the left lung. MRI of the chest with paramagnetic contrast enhancement was carried out as part of the whole body CE-MRI study after the complex therapy of breast cancer, and both the primary lung tumor and metastatic lesion of mediastinal — subbifurcation lymph nodes were revealed. With a transbronchial biopsy, the diagnosis of lung cancer was verified. Chemotherapy (ChT) was started using the vinorelbin/ carboplatin regimen. After this, the CE-MRI has been carried out during the whole period of followup of anti-cancer chemotherapy. At the CE-MRI during the first course of ChT visually the complete regression of the disease, also with clinical remission was achieved. However, the ChT scheme was not fully completed due to the patient’s departure for urgent private reasons. Two months later, the patient was examined again according to the same CE-MRI protocol, while a relapse of the disease was detected with a more pronounced lesion of the mediastinal lymph nodes than during the initial treatment. ChT with vinorelbine/carboplatin was again carried out under the control CE-MRI, this time completely. According to the chest CE-MRI, visual remission was achieved, with the disappearance of nodular tumor at the site of the previously identified primary tumor of lung cancer and metastatic lesions of lymph nodes. Thus, it was the CE-MRI which provided the early diagnosis and adequate control of treatment of the lung cancer with extensive local lymph nodes spread. After this CE-MRI, the whole body PET with 18F-fluorodeoxyglucose (FDG) was also performed and no signs of relapse or continued tumor growth were revealed. Five months after this stage, the patient did persist to stay completely preserved clinically, at work and socially active. Thus, the chest CE-MRI can be employed for the follow-up of the tumor process in lung cancer, as necessary, without radiation exposure, without limiting the number and frequency of studies.

Determination of breath isoprene in 109 suspected lung cancer patients using cavity ringdown spectroscopy

Background: Lung cancer is one of the most common malignant tumors worldwide. Currently, effective screening methods for early lung cancer are still scarce. Breath analysis provides a promising method for the pre-screening or early screening of lung cancer. Isoprene is a potential and important breath biomarker of lung cancer. Material and Methods: To investigate the clinical value of isoprene for diagnosing lung cancer patients, a cavity ringdown spectroscopy (CRDS) based near-real time, sensitive analysis method of breath isoprene is developed in our lab. In this paper, 92 breath samples from lung cancer patients, 17 breath samples from patients with benign lesions, and 107 breath samples from healthy people were collected. Results: Research indicates that breath isoprene concentration is significantly higher in healthy individuals ([Formula: see text][Formula: see text]ppbv) than in patients with lung cancer ([Formula: see text][Formula: see text]ppbv) and benign lung lesions ([Formula: see text][Formula: see text]ppbv). The result of Receiver Operating Characteristic (ROC) curve suggests that the concentration of isoprene is meaningful for the diagnosis of lung cancer ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). Conclusion: This study demonstrates that the CRDS breath isoprene analysis system can effectively analyze a large sample of human breath isoprene, and preliminarily confirms the use of breath isoprene as a biomarker for lung diseases.

Deep learning-based diagnosis from endobronchial ultrasonography images of pulmonary lesions

Endobronchial ultrasonography with a guide sheath (EBUS-GS) improves the accuracy of bronchoscopy. The possibility of differentiating benign from malignant lesions based on EBUS findings may be useful in making the correct diagnosis. The convolutional neural network (CNN) model investigated whether benign or malignant (lung cancer) lesions could be predicted based on EBUS findings. This was an observational, single-center cohort study. Using medical records, patients were divided into benign and malignant groups. We acquired EBUS data for 213 participants. A total of 2,421,360 images were extracted from the learning dataset. We trained and externally validated a CNN algorithm to predict benign or malignant lung lesions. Test was performed using 26,674 images. The dataset was interpreted by four bronchoscopists. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the CNN model for distinguishing benign and malignant lesions were 83.4%, 95.3%, 53.6%, 83.8%, and 82.0%, respectively. For the four bronchoscopists, the accuracy rate was 68.4%, sensitivity was 80%, specificity was 39.6%, PPV was 76.8%, and NPV was 44.2%. The developed EBUS-computer-aided diagnosis system is expected to read EBUS findings that are difficult for clinicians to judge with precision and help differentiate between benign lesions and lung cancers.

Improved Survival With Surgical Treatment of Primary Lung Lesions in Non-Small Cell Lung Cancer With Brain Metastases: A Propensity‐Matched Analysis of Surveillance, Epidemiology, and End Results Database

ObjectivesNon-small cell lung cancer (NSCLC) with Brain metastases (BM) is an advanced disease with poor prognosis and low survival rate. Our study evaluated the survival benefit of primary lung resection with mediastinal lymph node dissection in NSCLC patients with BM using Surveillance, Epidemiology, and End-result (SEER) databases.MethodsAll cases analyzed were from Surveillance, Epidemiology, and End Results database. The data of the patients with BM of NSCLC from 2010 to 2016 was retrospectively analyzed. Patients (N=203) patients who underwent radical surgical treatment for primary lung lesions and patients (N=15500) who did not undergo surgery were compared. We successfully analyzed patients using propensity score matching (PSM). Kaplan‐Meier and Cox‐ regression analyses were applied to assess prognosis.ResultsThe median survival in the surgery group was longer than in the control group (27 months vs 5 months; P < 0.001) in the overall sample, 21 months longer compared to the control group (27 months vs 6 months; P<0.001) in a PSM cohort. Cox regression analysis showed that underwent surgery patients in the propensity-matched sample had a significantly lower risk of mortality (HR:0.243, 95%CI: 0.162-0.365, P < 0.001) compared with untreated patients. Multivariate analysis identified the following as independent risk factors for NSCLC with BM: no primary resection surgery, age >65 years, worse differentiation, squamous cell carcinoma, lymphatic metastasis, no systemic therapy. Subgroup analysis revealed that radical resection of the primary lung provided a survival benefit regardless of marital status, tumor size, tumor grade, tumor T stage, and mediastinal lymph node metastasis after PSM.ConclusionRadical resection of primary lung can improve the survival of NSCLC patients with BM. Male, age>65years, poorly differentiated tumor, tumor size>5cm, and mediastinal lymph node metastasis were factors for poor survival.

Automated classification of PET-CT lesions in lung cancer: An independent validation study.

IntroductionRecently, a tool called the positron emission tomography (PET)‐assisted reporting system (PARS) was developed and presented to classify lesions in PET/computed tomography (CT) studies in patients with lung cancer or lymphoma. The aim of this study was to validate PARS with an independent group of lung‐cancer patients using manual lesion segmentations as a reference standard, as well as to evaluate the association between PARS‐based measurements and overall survival (OS).MethodsThis study retrospectively included 115 patients who had undergone clinically indicated (18F)‐fluorodeoxyglucose (FDG) PET/CT due to suspected or known lung cancer. The patients had a median age of 66 years (interquartile range [IQR]: 61–72 years). Segmentations were made manually by visual inspection in a consensus reading by two nuclear medicine specialists and used as a reference. The research prototype PARS was used to automatically analyse all the PET/CT studies. The PET foci classified as suspicious by PARS were compared with the manual segmentations. No manual corrections were applied. Total lesion glycolysis (TLG) was calculated based on the manual and PARS‐based lung‐tumour segmentations. Associations between TLG and OS were investigated using Cox analysis.ResultsPARS showed sensitivities for lung tumours of 55.6% per lesion and 80.2% per patient. Both manual and PARS TLG were significantly associated with OS.ConclusionAutomatically calculated TLG by PARS contains prognostic information comparable to manually measured TLG in patients with known or suspected lung cancer. The low sensitivity at both the lesion and patient levels makes the present version of PARS less useful to support clinical reading, reporting and staging.

Vav1 accelerates Ras-driven lung cancer and modulates its tumor microenvironment.

The potential impact of Vav1 on human cancer was only recently acknowledged, as it is detected as a mutant or an overexpressed gene in various cancers, including lung cancer. Vav1, which is normally and exclusively expressed in the hematopoietic system functions as a specific GDP/GTP nucleotide exchange factor (GEF), strictly regulated by tyrosine phosphorylation. To investigate whether Vav1 plays a causative or facilitating role in-vivo in lung cancer development and to examine whether it co-operates with other oncogenes, such as mutant K-Ras, we generated novel mouse strains that express: Vav1 or K-RasG12D in type II pneumocytes, as well as a transgenic mouse line that expresses both Vav1 and K-RasG12D in these cells. Coexpression of Vav1 and K-RasG12D in the lungs dramatically increased malignant lung cancer lesions, and did so significantly faster than K-RasG12D alone, strongly suggesting that these two oncogenes synergize to enhance lung tumor development. Vav1 expression alone had no apparent effects on lung tumorigenesis. The increase in lung cancer in K-RasG12D/Vav1 mice was accompanied by an increase in B-cell, T-cells, and monocyte infiltration in the tumor microenvironment. Concomitantly, ERK phosphorylation was highly elevated in the lungs of K-RasG12 D/Vav1 mice. Also, several cytokines such as IL-4 and IL-13 which play a significant role in the immune system, were elevated in lungs of Vav1 and K-RasG12 D/Vav1 mice. Our findings emphasize the contribution of Vav1 to lung tumor development through its signaling properties.

Effective generation of tumor-infiltrating lymphocyte products from metastatic non-small-cell lung cancer (NSCLC) lesions irrespective of location and previous treatments.

BackgroundNon-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Because current treatment regimens show limited success rates, alternative therapeutic approaches are needed. We recently showed that treatment-naïve, stage I/II primary NSCLC tumors contain a high percentage of tumor-reactive T cells, and that these tumor-reactive T cells can be effectively expanded and used for the generation of autologous tumor-infiltrating T cell (TIL) therapy. Whether these promising findings also hold true for metastatic lesions is unknown yet critical for translation into the clinic.Materials and methodsWe studied the lymphocyte composition using flow cytometry from 27 metastatic NSCLC lesions obtained from different locations and from patients with different histories of treatment regimens. We determined the expansion capacity of TILs with the clinically approved protocol, and measured their capacity to produce the key pro-inflammatory cytokines interferon-γ, tumor necrosis factor and interleukin 2 and to express CD137 upon co-culture of expanded TILs with the autologous tumor digest.ResultsThe overall number and composition of lymphocyte infiltrates from the various metastatic lesions was by and large comparable to that of early-stage primary NSCLC tumors. We effectively expanded TILs from all metastatic NSCLC lesions to numbers that were compatible with TIL transfusion, irrespective of the location of the metastasis and of the previous treatment. Importantly, 16 of 21 (76%) tested TIL products displayed antitumoral activity, and several contained polyfunctional T cells.ConclusionsMetastatic NSCLC lesions constitute a viable source for the generation of tumor-reactive TIL products for therapeutic purposes irrespective of their location and the pre-treatment regimens.