A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

OBJECTIVES: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. METHODS: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. RESULTS: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). CONCLUSIONS: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

A Novel Radiopathological Grading System to Tailor Recurrence Risk for Pathologic Stage IA Lung Adenocarcinoma.

To validate the efficiency of pathologic grading system in pathologic stage IA lung adenocarcinoma (LUAD), and explore whether integrating preoperative radiological features would enhance the performance of recurrence discrimination. We retrospectively collected 510 patients with resected stage IA LUAD between January 2012 and December 2019 from Guangdong Provincial People's Hospital (GDPH). Pathologic grade classification of each case was based on the International Association for the Study of Lung Cancer (IASLC) pathologic staging system. Kaplan-Meier curves was used to assess the power of recurrence stratification. Concordance index (C-Index) and receiver operating characteristic curves (ROC) were used for evaluating the clinical utility of different grading systems for recurrence discrimination. Patients of lower IASLC grade showed improved recurrence-free survival (RFS) (P < 0.0001) where numerically difference was found between grade II and grade III (P = 0.119). By integrating the IASLC grading system and radiological feature, we found the RFS rate decreased as the novel radiopathological (RP) grading system increased (P < 0.0001). The difference of RFS curves between any 2 groups as per the RP grading system was statisticallysignificant (RP grade I vs RP grade II, p = 0.007; RP grade I vs RP grade III, P < 0.0001; RP grade II vs RP grade III, P = 0.0003). Compared with the IASLC grading system, the RP grading system remarkably improved recurrence survival discrimination (C-index: 0.822; area under the curve, 0.845). Integrating imaging features into pathologic grading system enhanced the efficiency of recurrence discrimination for resected stage IA LUAD and might help conduct subsequent management.

ITHscore: comprehensive quantification of intra-tumor heterogeneity in NSCLC by multi-scale radiomic features.

OBJECTIVES: To quantify intra-tumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) from computed tomography (CT) images. METHODS: We developed a quantitative ITH measurement-ITHscore-by integrating local radiomic features and global pixel distribution patterns. The associations of ITHscore with tumor phenotypes, genotypes, and patient's prognosis were examined on six patient cohorts (n = 1399) to validate its effectiveness in characterizing ITH. RESULTS: For stage I NSCLC, ITHscore was consistent with tumor progression from stage IA1 to IA3 (p < 0.001) and captured key pathological change in terms of malignancy (p < 0.001). ITHscore distinguished the presence of lymphovascular invasion (p = 0.003) and pleural invasion (p = 0.001) in tumors. ITHscore also separated patient groups with different overall survival (p = 0.004) and disease-free survival conditions (p = 0.005). Radiogenomic analysis showed that the level of ITHscore in stage I and stage II NSCLC is correlated with heterogeneity-related pathways. In addition, ITHscore was proved to be a stable measurement and can be applied to ITH quantification in head-and-neck cancer (HNC). CONCLUSIONS: ITH in NSCLC can be quantified from CT images by ITHscore, which is an indicator for tumor phenotypes and patient's prognosis. KEY POINTS: • ITHscore provides a radiomic quantification of intra-tumor heterogeneity in NSCLC. • ITHscore is an indicator for tumor phenotypes and patient's prognosis. • ITHscore has the potential to be generalized to other cancer types such as HNC.

Sublobectomy for stage IA1-2 invasive lung adenocarcinoma with consolidation tumor ratio ≤ 0.25.

BACKGROUND: Sublobectomy for early-stage non-small cell lung cancer (NSCLC) remains a matter of debate. This study aimed to discuss the feasibility of sublobectomy in patients with pathological-stage IA1-2 confirmed as pathologically invasive but radiologically noninvasive adenocarcinoma. METHODS: From 2011 to 2019, we screened clinical stage IA1-IA2 lung cancer patients who underwent surgery at the Guangdong Provincial People's Hospital (GDPH). Inclusion criteria were maximum tumor diameter of 2.0 cm or less, consolidation tumor ratio (CTR) ≤ 0.25, and pathologically confirmed invasive adenocarcinoma. Sublobectomy (segmentectomy and wedge resection) and lobectomy groups were created, and propensity scores were computed. The primary endpoints were lung cancer-specific overall survival (LCSS) and LCS- relapse-free survival (LCS-RFS) after adjusting propensity scores. RESULTS: A total of 1731 patients were screened, and 100 patients were enrolled. The lobectomy group had 51 patients and the limited resection group had 49. No cases relapsed, and two patients died from nontumor causes. For the entire cohort, the 5-year LCSS and 5-year LCS-RFS were 100% in the lobectomy and limited resection groups. When propensity scores matched, there were no differences in LCSS and LCS-RFS between the two groups (LCSS:100%, LCS-RFS 100% in lobectomy and limited resection, respectively). DISCUSSION: Sublobectomy may be curative for pathologically invasive but radiologically noninvasive adenocarcinoma at pathological stage IA1-2.

Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis.

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

Dynamic 18 F-FDG PET/CT can predict the major pathological response to neoadjuvant immunotherapy in non-small cell lung cancer.

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18 F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty-four patients with stage II-III non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18 F-FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non-MPR using logistic regression. Receiver-operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti-PD-1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non-MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.

Identification of heritable rare variants associated with early-stage lung adenocarcinoma risk.

Background: In East Asia, the number of patients with adenocarcinoma, especially those presenting with ground-glass nodules (GGNs), is gradually increasing. Family aggregation of pulmonary GGNs is not uncommon; however, genetic predisposition in these patients remains poorly understood and identification of genes involved in the cause of these early-stage lung cancers might contribute to understanding of the underlying mechanisms and potential prevention strategies. Methods: Fifty patients with early-stage lung adenocarcinoma (LUAD) presenting as GGNs and a first-degree family history of lung cancer (FHLC) from 34 independent families were enrolled into this study. Germline mutations of these patients were analyzed with whole exome sequencing (WES) and compared with age- and sex-matched 39 patients with sporadic lung cancer and 689 local healthy people. We used a stepwise variant filtering strategy, gene-based burden testing, and enrichment analysis to investigate rare but potentially pathogenic heritable mutations. Somatic tumor mutations were analyzed to consolidate germline findings. Results: In total, 1,571 single nucleotide variants (SNVs) and 238 frameshifts with a minor allele frequency (MAF) <0.01, which were rare, recurrent, and potentially damaging candidates, were finally identified through the filtering in the GGN cohort. Pathway analysis showed the extracellular matrix to be the top dysregulated pathway. Gene-based burden testing of these highly disruptive risk-conferring heritable variants showed that MSH5 [odds ratio (OR), 9.28, 95% confidence interval (CI): 2.49-35.87], MMP9 (OR, 8.11, 95% CI: 2.22-28.43), and CYP2D6 (OR, 8.09, 95% CI: 2.68-24.92) were significantly enriched in our cohort (P<0.05). The number of rare damaging germline variants in non-smoking patients was significantly higher than that of smoking-affected patients (Spearman's ρ=-0.39, P=0.02). Conclusions: Heritable, potentially deleterious, and rare candidate variants of MSH5, MMP9 and CYP2D6 were significantly associated with early-stage LUAD presenting with GGNs. Nonsmoking patients likely have a higher genetic predisposition to this type of cancer than smoking-affected patients. These results have extended our understanding of the underlying mechanisms of early-stage LUAD.

Neoadjuvant Therapy for Locally Advanced Esophageal Cancers.

Esophageal carcinoma is one of the most aggressive malignant diseases. At present, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy are regarded as the standard modalities for the treatments of locally advanced esophageal cancers based on several landmark trials. However, the optimal regimen, radiation dose, and surgical intervals are uncertain and the rate of recurrence after neoadjuvant therapy is high. Patients receiving neoadjuvant therapy and reaching a pathological complete response have been reported to have a better survival benefit and a fewer recurrence risk than those non-pathological complete responses. Nevertheless, less than half of patients will reach a pathological complete response after neoadjuvant therapy, and the methods to evaluate the efficacy after neoadjuvant therapy accurately are limited. Immune checkpoint inhibitors have been recommended for the treatments of advanced esophageal cancers. Recently, research has been beginning to evaluate the safety and efficacy of immunotherapy combined with neoadjuvant therapy. Here, we will review and discuss the development of the neoadjuvant therapy of locally advanced esophageal cancers and unsolved clinical problems.

Quantifying invasiveness of clinical stage IA lung adenocarcinoma with computed tomography texture features.

OBJECTIVES: The study objectives were to establish and validate a nomogram for pathological invasiveness prediction in clinical stage IA lung adenocarcinoma and to help identify those potentially unsuitable for sublobar resection-based computed tomography texture features. METHOD: Patients with clinical stage IA lung adenocarcinoma who underwent surgery at Guangdong Provincial People's Hospital between January 2015 and October 2018 were retrospectively reviewed. All surgically resected nodules were pathologically classified into less-invasive and invasive cohorts. Each nodule was manually segmented, and its computerized texture features were extracted. Clinicopathological and computed tomographic texture features were compared between 2 cohorts. A nomogram for distinguishing the pathological invasiveness was established and validated. RESULTS: Among 428 enrolled patients, 249 were diagnosed with invasive pathological subtypes. Smoking status (odds ratio, 2.906; 95% confidence interval, 1.285-6.579; P = .011), mean computed tomography attenuation value (odds ratio, 1.005, 95% confidence interval, 1.002-1.007; P < .001), and entropy (odds ratio, 8.536, 95% confidence interval, 3.478-20.951; P < .001) were identified as independent predictors for pathological invasiveness by multivariate logistics regression analysis. The nomogram showed good calibration (P = .182) with an area under the curve of 0.849 when validated with testing set data. Decision curve analysis indicated the potentially clinical usefulness of the model with respect to treat-all or treat-none scenario. Compared with intraoperative frozen-section, the nomogram performed better in pathological invasiveness diagnosis (area under the curve, 0.815 vs 0.670; P = .00095). CONCLUSIONS: We established and validated a nomogram to compute the probability of invasiveness of clinical stage IA lung adenocarcinoma with great calibration, which may contribute to decisions related to resection extent.

Watershed analysis of the target pulmonary artery for real-time localization of non-palpable pulmonary nodules.

BACKGROUND: Some pulmonary nodules are not suitable for computed tomography-guided percutaneous localization. This study aimed to investigate the feasibility and safety of real-time localization for these non-palpable pulmonary nodules using watershed analysis of the target pulmonary artery during thoracoscopic wedge resection. METHODS: Watershed analysis is a novel technique that can be used to create a specific area on the lung surface for nodule localization. This analysis is performed by temporarily blocking the target pulmonary artery and using indocyanine green fluorescence during surgery. In our study, the surgery was simulated and evaluated preoperatively using a high-precision three-dimensional reconstruction model obtained by multidetector spiral computed tomography. The lung was observed using an infrared thoracoscopy system after an intravenous injection of indocyanine green (2.5 mg/mL), and the white-to-blue transitional zone was marked using electrocautery, after which a wedge resection was performed. RESULTS: A total of 25 out of 26 patients underwent successful wedge resection. The mean tumor size and depth based on computed tomography scans were 13.2±6.4 and 12.2±7.8 mm, respectively. The mean operation duration was 142.6±52.8 min. The mean bleeding volume during surgery was 12.9±9.7 mL. The mean drainage tube indwelling time was 35.6±20.0 h, and the median length of postoperative stay was 3 days (range, 2-6 days). CONCLUSIONS: Our experience showed that the watershed analysis of the target pulmonary artery for nodule localization was safe and feasible. It may become an effective and attractive alternative method for localizing non-palpable pulmonary nodules in selected patients undergoing thoracoscopic wedge resection.

Timing and Origins of Local and Distant Metastases in Lung Cancer.

INTRODUCTION: Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. METHODS: We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. RESULTS: There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. CONCLUSIONS: Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.

Precise resection of multiple pulmonary nodules using a three-dimensional reconstruction model: A case report.

A 48-year-old woman presented to our department and chest computed tomography (CT) revealed five pulmonary nodules, two of which were in the left upper lobe of the lung and three in the superior segment of the left lower lobe., All the lesions were resected for comprehensive histological assessment in order to distinguish synchronous multiple primary lung cancers (SMPLCs) from intrapulmonary metastases. The nodules were all successfully removed by minimally invasive surgery under the guidance of three dimensional (3D) reconstruction, in order to preserve as much lung function for the patient as possible. Postoperative histopathological examination demonstrated the presence of SMPLC. The patient was discharged from hospital on postoperative day 4 without any complications.

A New Prognostic Index Combines the Metabolic Response and RECIST 1.1 to Evaluate the Therapeutic Response in Patients With Non-Small Cell Lung Cancer.

Aim: Response Evaluation Criteria in Solid Tumors (RECIST) is occasionally insufficient for evaluation. We proposed a new prognostic index (NPI) that combines the standardized uptake value (SUV), metabolic tumor volume (MTV), and RECIST. Methods: In total, 116 patients with lung cancer who underwent consecutive positron emission tomography-computed tomography prior to and after the initial treatment were included. We formulated the NPI by estimating the hazard ratios of overall survival for ΔMTV, ΔSUVmax, and ΔD (tumor size based on RECIST). Progression-free survival (PFS) and overall survival (OS) were compared between RECIST and the NPI. Results: ROC curve analysis identified two cutoff values based on the NPI (≤ -49.3% and ≥43.4%) to discriminate partial remission (NPR), stable disease (NSD) and progressive disease (NPD). Based on RECIST, survival analysis did not discriminate significantly on either PFS or OS between the PR, SD, and PD groups. However, according to the NPI, PFS and OS differed significantly between the NPR, NSD, and NPD groups (training set: PFS, p = 0.048; OS, p = 0.026; validation set: PFS, p = 0.004; OS, p = 0.023). Moreover, therapeutic response based on NPI was independent prognostic factor for both PFS [NPR as reference, NSD: hazard ratio (HR) 2.04; 95% confidence interval (95% CI) 1.35-3.08; p = 0.001; NPD: HR 6.87; 95% CI 3.03-15.57; p < 0.001] and OS (NPR as reference, NSD: HR 1.64; 95% CI 1.05-2.57; p = 0.031; NPD: HR 3.56; 95% CI 1.59-7.95; p = 0.002). Conclusion: The NPI showed superiority for evaluation of the therapeutic response and survival for patients with non-small cell lung cancer, overcoming the limitations of RECIST.

Achievements and futures of immune checkpoint inhibitors in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has been threatening human health for years. Cytotoxicity-based chemotherapy seems to reach plateau in NSCLC treatment. Immunotherapy with immune checkpoint inhibitors (ICIs) against programmed cell death 1 (PD-1/L1) axis are to provide long-term survival benefits for wild-type advanced NSCLC patients with acceptable adverse effects. Though beneficiary population is limited from monotherapy, combination strategies are expanding indicators. Retrospective evidences suggested ICIs are also potentially useful for brain metastasis. Furthermore, the combination of ICIs and surgery are to prolong progression free survival time for local advanced patients. Additionally, novel agents targeting in immune checkpoints other than PD-1/L1 demonstrated potential values in anticancer immunity. Herein, we summarize the novel therapies of checkpoint inhibitors in NSCLC treatment and some other potential immunotherapy to provide a conspectus for novel immunotherapy in NSCLC and perspective for the future in anti-cancer treatment.

Compromised Air Quality and Healthcare Safety from Smoking inside Hospitals in Shantou, China.

Achieving smoke-free healthcare facilities remains a great challenge in countries with a high smoking prevalence and weak regulation. Assessment of the impact of environmental tobacco smoke (ETS) and its constituent PM2.5 on the air quality in Chinese hospitals has not been reported. In this study, we conducted air quality surveys by measuring real-time PM2.5 concentrations with Dylos Air Quality Monitors in five tertiary hospitals in Shantou, China during summer (July-August 2016) and winter (November-February 2017). Twenty-eight-day surveys inside the hospitals showed median PM2.5 concentrations above the China Air Quality Standard in elevator lobbies (51.0 µg/m3, IQR 34.5-91.7), restrooms (40.2, 27.1-70.3), and corridors (36.5, 23.0-77.4). Evidence of tobacco smoking was significantly associated with PM2.5 spikes observed in all the survey locations, contributing to the air quality undesirable for health in 49.1% of total survey hours or 29.3% of summer and 75.4% of winter survey hours inside the buildings, and 33.5%, 25.7%, and 6.8% of survey hours in doctor offices, nurse stations, and patient rooms, respectively. In conclusion, smoking inside hospitals induces PM2.5 spikes that significantly compromise the air quality and impose significant health risk to the hospital inhabitants. Reinforcing comprehensive smoking ban with the vested interest of all stakeholders followed by creative disciplinary actions are suggested to ensure healthcare safety.