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Introduction: Lung cancer remains a highly fatal disease. Surgical resection has been proven to be the most effective treatment for early-stage lung cancer. The conventional hospital-based pulmonary rehabilitation (PR) is shown to reduce symptoms, improve exercise capacity and impact the quality of life (QoL) for lung cancer patients. To date, scientific evidence on the effectiveness of home-based PR for patients with lung cancer following surgery is scarce. We aim to explore if home-based PR is non-inferior to outpatient PR for patients with lung cancer following surgical resection., Methods and Analysis: This study is a two-arm, parallel-group, assessor-blind, single-centre, randomised controlled trial. Participants will be recruited from West China Hospital, Sichuan University and randomly allocated to either an outpatient group or a home-based group at a ratio of 1:1. The PR programme involves self-management and exercises. The exercise includes warm-up (10 min), aerobic training (20 min), resistance training (15 min) and cool-down (10 min), lasting 4 weeks, with two sessions per week either at home or in the outpatient setting. The intensity will be adjusted according to the modified Borg rating of perceived exertion and heart rate before and after each exercise session. The primary outcome is QoL measured by EORTC QLQ-C30 & LC 13 after an intervention. Secondary outcomes include physical fitness measured by a 6 min walk test and stair-climbing test and symptom severity measured by patient-reported questionnaires and pulmonary function. The main hypothesis is that home-based PR is non-inferior to outpatient PR for patients with lung cancer following surgical resection., Ethics and Dissemination: The trial has been approved by the Ethical Committee of West China Hospital and is also registered with the Chinese Clinical Trial Registry. The results of this study will be disseminated through peer-reviewed publications and presentations at national and international conferences., Trial Registration Number: ChiCTR2100053714., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Whether preoperative localisation is necessary and valuable for the microwave ablation (MWA) of small pulmonary lesions with ground-glass opacity (GGO) remains unclear. This study aimed to explore the role of the Chiba needle and lipiodol localisation techniques in facilitating MWA and biopsy., Methods: This retrospective before-after study included patients with GGOs who underwent conventional MWA and biopsy treatment in our hospital between January 2018 and December 2019 (group A) or who underwent the Chiba needle and lipiodol localisation treatment before MWA and biopsy between January 2020 and December 2020 (group B). The characteristics of each patient and GGO lesion were collected and analysed to evaluate the safety and effectiveness of the localisation technique., Results: A total of 122 patients with 152 GGOs and 131 patients with 156 GGOs underwent MWA and biopsy in groups A and B, respectively. The primary technique efficacy rate of MWA differed significantly between the two groups (A vs. B: 94.1% vs. 99.4%; p = 0.009). The positive biopsy rate in the two groups was determined by the difference (A vs. B: 93.4% vs. 98.1%; p = 0.042). The incidence of complications did not increase in group B., Conclusions: Compared with the unmarked group, the Chiba needle and lipiodol localisation technique improved the positive rate of biopsy and the initial effective rate of MWA, without significantly increasing the complication rate., Key Points: • The localisation of the Chiba needle and lipiodol could improve the positive biopsy rate and the initial effective rate of MWA. • The localisation of the Chiba needle and lipiodol does not affect the subsequent MWA and biopsy and does not increase the incidence of pneumothorax and haemorrhage., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: In the present study, we aim to show the results of microwave ablation (MWA) for medically inoperable stage I non-small cell lung cancers (NSCLCs) with long-term follow-up., Methods: From Feb 2011 to Mar 2016, patients with histologically proven clinical stage I NSCLC were treated with CT-guided MWA and retrospectively analyzed. The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and complications., Results: A total of 105 patients with 105 lesions underwent MWA. The mean age was 70.7 years (range: 40-86 years), and the mean diameter of all lesions was 2.40 cm (range: 0.9-4.0 cm). Adenocarcinoma was the most common histological type (77, 73.3%), followed by squamous cell carcinomas (21, 20%) and undefined NSCLC (7, 6.7%). With a median follow-up of 54.8 months, the median DFS was 36.0 months, and 1-, 3-, and 5-year DFS rates were 89.5%, 49.4%, and 42.7%, respectively. The median CSS and OS were 89.8 and 64.2 months, respectively. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years, while the CSS rates were 99%, 78.9%, and 60.9%, respectively. Patients with stage IB lesions had significant shorter DFS (22.3 months vs. undefined, HR: 11.5, 95%CI: 5.85-22.40) and OS (37.3 vs. 89.8 months, HR: 8.64, 95% CI: 4.49-16.60) than IA disease., Conclusion: MWA is a safe, effective, and potentially curative therapy for medically inoperable stage I NSCLC patients., Key Points: • In this multicenter retrospective study which included 105 patients, we found the median overall survival (OS) was 64.2 months. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years. • Procedures were technically successful and well tolerated in all patients. Most MWA complications were mild or moderate., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Immunometabolic reprogramming due to adenosine produced by CD73 (encoded by the 5'-ectonucleotidase gene NT5E ) is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered human NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells in a model of non-small-cell lung cancer, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This resulted in a 'single agent' immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73 + tumors and enhancing intratumoral activation., Competing Interests: AC, KL, JW, JC, SU, NL, VB, SJ, SP, ST, BE, SM No competing interests declared, (© 2022, Chambers et al.)

Background: Patients with pulmonary nodules are treated by minimally invasive surgery, and postoperative symptoms have become the main factors affecting patients' emotion and quality of life. This study aimed to analyze the changes of postoperative symptoms in lung cancer patients with pulmonary nodules., Methods: The clinical data of eighty-eight lung cancer patients admitted to the same medical group of Department of Thoracic Surgery, West China Hospital of Sichuan University from June 2021 to September 2021 were prospectively collected and analyzed. The types and severity of clinical symptoms before operation, on discharge day, 30-day and 90-day after operation were analyzed., Results: The incidence of postoperative symptoms in lung cancer patients was 79.5%, and most patients suffered from mild (54.3%) and moderate (32.9%) symptoms. The main postoperative symptoms of lung cancer patients were pain (55.7%) and cough (37.2%). The incidence of pain at discharge (55.7%) was significantly higher than that at 30-day (23.7%, P=0.01) and 90-day (12.0%, P=0.01) after discharge. The incidence of cough was significantly higher at 30-day (66.1%) and 90-day (66.0%) than that at discharge (37.2%) (P=0.01, P=0.04)., Conclusions: The main postoperative symptoms of lung cancer patients with pulmonary nodules are pain and cough. The incidence and severity of pain decreases with time, and the incidence of cough increases but the severity decreased gradually.

Purpose: To reveal the survival and safety of percutaneous microwave ablation (MWA) combined with chemoradiotherapy (CRT) in treating small cell lung cancer (SCLC)., Materials and Methods: Clinical data of 48 SCLC patients who underwent MWA were retrospectively collected; survival and incidence of major complications were analyzed., Results: Totally, 48 SCLC patients underwent 51 MWA procedures. The median overall survival (OS) for all SCLC was 27.0 months (95% confidence interval 22.4-31.6 months). The OS of limited-stage (LS-SCLC) was longer than the extensive-stage (ES-SCLC) (median 48.0 months vs. 25.0 months, P = 0.022). The OS of SCLC with tumor diameter ≤3.0 cm was longer than that of tumor diameter >3.0 cm (median 48.0 months vs. 27.0 months, P = 0.041). For LS-SCLC, the 1-, 2-, 3-, and 5-year survival rate was 91.67%, 72.22%, 66.67%, and 61.11%, respectively. For ES-SCLC, the 1-, 2-, and 3-year survival rates were 83.33%, 50.0%, and 8.33%. Major complications included pneumothorax needing tube placement (29.4%), rarely arrhythmia (2.0%), empyema (2.0%), pulmonary fungal infection (2.0%), and shingles (2.0%)., Conclusion: For SCLC patients, who received MWA combined with CRT, OS of LS-SCLC and tumor diameter ≤3.0 cm was better than that of the ES-SCLC and tumor diameter >3.0 cm. For inoperable SCLC, MWA was safe., Competing Interests: None

Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients. Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing. Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients. Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Wei, Cheng, Huang, Zong, Meng, Li, Han, Xu, Wang, Jing, Li, Cao, Ni, Sun, Yang and Ye.)

Background: Computed tomography (CT)-guided percutaneous microwave ablation (MWA) is a very common ablation method that shows a good local tumor control rate in primary and secondary lung tumors. At present, few reports have explored the safety and efficacy of MWA for lung metastases from breast cancer., Methods: From January 2012 to January 2018, 32 breast cancer patients with 46 pulmonary metastases received CT-guided percutaneous MWA. The study was approved by the local institutional review board. The clinical efficacy and complications of MWA were investigated., Results: The median follow-up time was 32 months and the main effective rate was 97.8% (45/46). Five of 46 lesions had local progression (10.9%), with a median progression time of 10 months. The 1-, 3-, and 5-year overall survival (OS) rates were 96.9%, 53.3%, and 17.8%, respectively. The median OS time was 36 months. Among 46 MWA treatments, 11 (23.9%) had massive pneumothorax, two (4.3%) had massive pleural effusion, and two (4.3%) had a pulmonary infection., Conclusion: CT-guided percutaneous MWA may be safe and effective for treating lung metastases from breast cancer., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the efficacy of microwave ablation (MWA) and MWA plus monochemotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC)., Material and Methods: Patients with advanced NSCLC aged ≥70 years were retrospectively enrolled. MWA was performed at the primary tumor site. The end points included progression-free survival (PFS), response to MWA and overall survival (OS)., Results: Fifty-four patients were enrolled; of these, 36 received monochemotherapy. Complete ablation was achieved in 42 patients (77.8%). The median PFS and OS were 4.9 months and 21.8 months, respectively. Univariate analyses showed that female patients had superior PFS (31.9 months [95% confidence interval (CI): 0.8-63.0]) vs. 5.0 months in male patients (95% CI: 2.0-8.0), p  = .002). Female sex was associated with better OS (not reached vs. 10.8 months, 95% CI: 9.3-12.3, p  = .003). Moreover, patients with primary tumor size <3.5 cm had better OS than those with tumor size ≥3.5 cm (not reached vs. 10.9 months, 95% CI: 8.2-13.6, p  = .006). Multivariate analyses showed that no characteristics were independent prognostic factors of PFS, but sex and primary tumor size were independent prognostic factors of OS., Conclusion: MWA was effective in the treatment of elderly patients with advanced NSCLC.

Epithelial-mesenchymal transition (EMT) has been shown to be linked to a poor prognosis, particularly in patients with non-small-cell lung cancer. Nevertheless, little is known regarding the existence of EMT-related gene signatures and their prognostic values in lung adenocarcinoma (LUAD). In the current study, we systematically profiled the mRNA expression data of patients with LUAD in The Cancer Genome Atlas and Gene Expression Omnibus databases using a total of 1,184 EMT-related genes. The prognostic values of the EMT-related genes used to develop risk score models for overall survival were determined using LASSO and Cox regression analyses. A prognostic signature that consisted of nine unique EMT-related genes was generated using a training set. A nomogram, incorporating this EMT-related gene signature and clinical features of patients with LUAD, was constructed for potential clinical use. Calibration plots, decision-making curves, and receiver operating characteristic curve analysis showed that this model had a good ability to predict the survival of patients with LUAD. The EMT-associated gene signature and prognostic nomogram established in this study were reliable in predicting the survival of patients with LUAD. Thus, we first identified a novel EMT-related gene signature and developed a nomogram for predicting the prognosis of patients with LUAD.

Epigenetic factors play crucial roles in carcinogenesis by modifying chromatin architecture. Here, we established an epigenetic biosignature-based model for examining survival in patients with lung adenocarcinoma (LUAD). We retrieved gene-expression profiles and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus and clustered the data into training ( n = 490) and Validation ( n = 226) datasets, respectively. To establish an epigenetic model, we identified prognostic epigenetic regulation-related genes by LASSO and Cox regression analyses, and established a novel 11-gene signature, including EPC1, GADD45A, HCFC2, RCOR1, SMARCAL1, TLE2, TRIM28, and ZNF516 , for predicting LUAD overall survival (OS). The biosignature performed optimally in both the training and validation sets according to receiver operating characteristic and calibration plots. Moreover, the biosignature classified patients into high- and low-risk clusters with distinct survival times, with Cox regression analysis revealing the biosignature as an independent LUAD prognostic index. Furthermore, the generated nomogram integrating the prognostic gene biosignature and clinical indices predicted LUAD OS with high efficiency and outperformed tumor-node-metastasis staging in LUAD survival prediction. These results demonstrated the efficacy of the epigenetic signature prognostic nomogram for reliably predicting LUAD OS and its potential application for informing clinical decision making and individualized treatment.

MYB Proto-Oncogene Like 2 (MYBL2) is a highly conserved member of the Myb family of transcription factors and plays a critical role in regulating cell proliferation and survival. Here we show that overexpression of MYBL2 is frequently observed in lung adenocarcinoma (LUAD) and significantly correlates with advanced stage and poor patient survival. Knockdown of MYBL2 induced apoptosis in lung cancer cells and resulted in significant inhibition of cell proliferation, migration, and invasion. Notably, we identified Non-SMC Condensin I Complex Subunit H (NCAPH) gene as a direct target of MYBL2. NCAPH expression is highly correlated with that of MYBL2 in LUAD cases and is tightly affected by MYBL2 knockdown or overexpression in vitro. Chromatin immunoprecipitation (ChIP) assays also showed that MYBL2 directly binds to the transcription start site (TSS) of NCAPH. Moreover, we provided evidence that NCAPH functions as an oncogene in lung cancer and overexpression of NCAPH could partially rescue cell death and migration blockage induced by MYBL2 knockdown. Together, these results suggest that overexpression of MYBL2 promotes proliferation and migration of lung cancer cells via upregulating NCAPH, establishing their roles as novel prognostic biomarkers as well as potential therapeutic targets for the disease.

Objectives: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone., Materials and Methods: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported., Results: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups., Conclusions: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone., Key Points: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

Aims: Local therapy including surgery or radiotherapy has been reported for the treatment of non-small cell lung cancer (NSCLC) with synchronous solitary metastasis, while studies with other local ablative treatment are rare. Here, we summarized our single-center experience of microwave ablation (MWA) for both primary and metastatic lesions in NSCLC patients with synchronous solitary extracranial metastases., Patients and Methods: We retrospectively screened our institute database from January 2014 to Jun 2019. NSCLC patients with synchronous extracranial solitary metastasis with primary and metastatic lesions that were treated with MWA were identified and analyzed., Results: Of the 1472 stage IV NSCLC patients found, 38 were diagnosed with synchronous extracranial solitary metastasis and 29 of them received MWA for primary and metastatic lesions. The most common distant metastases were contralateral lung metastases (14 cases), followed by bone (6), liver (4), adrenal gland (3) and pleura metastases (1). Median OS and PFS was 21.5 and 12.5 months, respectively. Patients with N0 had significantly longer PFS (median 18.5 vs. 8.0 months) and OS (median 42.7 vs. 19.0 months). In addition, systemic therapy was showed to be a prognostic factor for better PFS (12.9 vs. 7.5 months). Clinical pathological factors including age, histology, T stage, PS score, and metastasis locations are not significantly associated with survival., Conclusions: MWA may serve as an alternative treatment for NSCLCs with synchronous solitary extracranial metastases.

Objectives: Evidence from multiple clinical trials showed that local consolidative therapy (LCT) improved survival in oligometastatic non-small cell lung cancer (NSCLC) patients. In the present study, we aim to explore the potential role of microwave ablation (MWA) as LCT for epidermal growth factor receptor (EGFR)-mutant advanced NSCLC patients with extracranial oligometastasis., Materials and Methods: From January 2015 to December 2018, a total of 86 EGFR-mutant stage IIIB or IV NSCLC patients with extracranial oligometastasis were enrolled for retrospective analysis. MWA was used as LCT for all oligometastatic lesions and/or primary tumors in 34 patients without progression after first-line EGFR-TKIs therapy (consolidation group), while the other 52 patients received only TKIs until disease progression (monotherapy group). We calculated and compared the progression-free survival (PFS) and overall survival (OS) of the two groups., Results and Conclusion: Patients with MWA consolidation therapy had significantly improved PFS (median 16.7 vs. 12.9 months, HR 0.44, 95% CI 0.22-0.88, P = 0.02) and OS (median: 34.8 vs. 22.7 months, HR 0.45, 95% CI 0.24-0.88, P = 0.04) than monotherapy group. MWA for LCT was identified as the independent predictive factor for better PFS (HR 0.46, 95% CI 0.37-0.82, P < 0.01) and OS (HR 0.57, 95% CI 0.33-0.91, P = 0.02). Most toxicities were mild and well tolerated. No patient had to discontinue EGFR-TKIs because of MWA complications. These findings suggest that MWA as local consolidative therapy after first-line EGFR-TKIs treatment leads to better disease control and survival than TKIs monotherapy in EGFR-mutant advanced NSCLC patients with extracranial oligometastasis. MWA as a novel option of LCT might be considered for clinical management of these patients.

Purpose: The present study retrospectively evaluated the feasibility, safety, and short-term efficacy of computed tomography (CT)-guided percutaneous microwave ablation (MWA) to treat multiple synchronous ground-glass opacities (GGOs) of the lung. Materials and Methods: From October 2016 to May 2019, 33 patients (9 males and 24 females, mean age: 59.6 ± 10.0 years) with multiple GGOs (103 GGOs with mean size 12.3 ± 6.3 mm) were enrolled in this study. Patients underwent 66 procedures of CT-guided percutaneous MWA. The feasibility, safety, local progression-free survival, and overall survival were evaluated. Results: The technical success and technique efficacy rate were 100% and no MWA procedure-related deaths were reported. The median follow-up period was 18.1 (range: 6.8-37.7) months. Major complications included pneumothorax (11/66, 16.7%), pleural effusion (2/66, 3.0%), pneumonia (3/66, 4.5%), and nerve injury (1/66, 1.5%), which were well controlled by appropriate treatment. Minor complications included pneumothorax (38/66, 57.6%), pleural effusion (43/66, 65.2%), hemoptysis (13/66, 19.7%), subcutaneous emphysema (4/66, 6.1%), and hemothorax (2/66, 3.0%). Currently, all patients are alive without local progression or tumor recurrence, despite the relatively insufficient follow-up time. Conclusion: CT-guided percutaneous MWA for the treatment of multiple synchronous lung GGOs is feasible, safe, and efficacious over short-term follow-up. It may also be employed as an alternative approach for nonsurgical candidates. A longer follow-up is warranted to evaluate the oncologic outcomes.

Background: Previous studies have documented the therapeutic value of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for early-stage non-small cell lung cancer (NSCLC). However, few studies have focused on patients aged 80 years and older. This retrospective study aimed to evaluate the safety and clinical outcomes of CT-guided percutaneous MWA in patients aged 80 years and older with early-stage peripheral NSCLC., Methods: A retrospective analysis of 63 patients aged 80 years and older with cT1a-2bN0M0 peripheral NSCLC who underwent CT-guided percutaneous MWA was performed between January 2008 and January 2018 at 11 hospitals in Shandong Province, China., Results: The median follow-up time was 21.0 months. The overall median survival time was 50 months. The cancer-specific median survival time was not reached in five years. The one-, two-, three-, four-, and five-year overall survival rates were 97.1%, 92.6%, 63.4%, 54.4%, and 32.6%, respectively. The one-, two-, and three-year cancer-specific survival (CSS) rates were 97.9%, 97.9%, and 69.4%, respectively. The four- and five-year CSS rates were not achieved. A total of 14 patients (22.2%) had local progression. The one-, two-, three-, four-, and five-year local control rates were 88.8%, 78.8%, 70.3%, 63.9%, and 63.9%, respectively. The mortality rate was 0% within 30 days after the procedure. Major complications included pneumothorax requiring drainage (21.1%), pulmonary infection (4.2%), and pleural effusions requiring drainage (2.8%)., Conclusions: CT-guided percutaneous MWA is a safe and effective modality for treating patients aged 80 years and older with early-stage peripheral NSCLC., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) mutation is considered a subgroup of lung cancer sensitive to EGFR-targeted tyrosine kinase inhibitors. We aimed to develop and validate a computed tomography (CT)-based radiomics signature for prediction of EGFR mutation status in LADC appearing as a subsolid nodule., Materials and Methods: A total of 467 eligible patients were divided into training and validation cohorts ( n = 306 and 161, respectively). Radiomics features were extracted from unenhanced CT images by using Pyradiomics. A CT-based radiomics signature for distinguishing EGFR mutation status was constructed using the random forest (RF) method in the training cohort and then tested in the validation cohort. A combination of the radiomics signature with a clinical factors model was also constructed using the RF method. The performance of the model was evaluated using the area under the curve (AUC) of a receiver operating characteristic curve., Results: In this study, 64.2% (300/467) of the patients showed EGFR mutations. L858R mutation of exon 21 was the most common mutation type (185/301). We identified a CT-based radiomics signature that successfully discriminated between EGFR positive and EGFR negative in the training cohort (AUC = 0.831) and the validation cohort (AUC = 0.789). The radiomics signature combined with the clinical factors model was not superior to the simple radiomics signature in the two cohorts ( p > .05)., Conclusion: As a noninvasive method, the CT-based radiomics signature can be used to predict the EGFR mutation status of LADC appearing as a subsolid nodule., Implications for Practice: Lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) mutation is considered a subgroup of lung cancer that is sensitive to EGFR-targeted tyrosine kinase inhibitors. However, some patients with inoperable subsolid LADC are unable to undergo tissue sampling by biopsy for molecular analysis in clinical practice. A computed tomography-based radiomics signature may serve as a noninvasive biomarker to predict the EGFR mutation status of subsolid LADCs when mutational profiling is not available or possible., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Lung cancer is the leading cause of cancer mortality worldwide. Approximately 85% of all lung cancer cases are classified as non‑small cell lung cancer (NSCLC). Currently, there is no standard method to predict the survival of patients with NSCLC. Insulin‑like growth factor‑binding proteins (IGFBPs) function as modulators of IGF signaling and are attracting increasing attention for their role in NSCLC. However, the prognostic values of individual IGFBPs in NSCLC, particularly at the mRNA level, remain unknown. In the present study, the distinct expression patterns and prognostic values of IGFBP family members in patients with NSCLC through bioinformatics analysis were reported using a series of databases, including Gene Expression Profiling Interactive Analysis, Kaplan‑Meier Plotter, cBioPortal, GeneMANIA, and the Database for Annotation, Visualization and Integrated Discovery. In patients with NSCLC, IGFBP2 and IGFBP3 were significantly upregulated, while IGFBP6 was downregulated. High IGFBP1/2/4 expression was correlated with poor overall survival (OS) in all NSCLC types, especially adenocarcinoma; however, high IGFBP2/5 expression was significantly correlated with favorable OS only in patients with squamous cell carcinoma. In addition, aberrant IGFBP1/2/3/4/5 mRNA levels were associated with the prognosis of subsets of NSCLC with different clinicopathological features. These results indicated that various IGFBPs can serve as useful prognostic biomarkers and as potential targets for NSCLC therapies.

Background: Most epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs) experience oligoprogressive disease. Local ablation for isolated resistant sites continued with the original EGFR-TKI showed good efficacy in these patients. We conducted this multicenter retrospective study to investigate the potential benefit of thermal ablation in NSCLC patients that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment., Methods: A total of 71 EGFR-mutant patients treated with EGFR-TKIs were identified. Progression-free survival 1 (PFS1) was calculated from the initiation of TKI treatment to first progression. Patients with metastatic sites ≤ 3 in less than 3 extra-CNS organs suitable for local ablation therapy received either radiofrequency ablation or microwave ablation to these sites and continued on the original TKIs. PFS2 was defined from the first progression to second progression after ablation., Results: The median PFS1 for all patients was 11.8 months. Eighty extra-CNS oligoprogressive lesions in 71 patients were ablated. Thirty-six of 71 patients progressed after thermal ablation and 31 of whom died during the study period. The median PFS2 after thermal ablation was 10.0 months, and the median overall survival was 26.4 months. PFS1 and PFS2 were highly correlated with OS, whereas PFS1 was not correlated with PFS2. The numbers of oligoprogressive lesions were significantly and independently associated with PFS2., Conclusion: Local thermal ablation for the oligoprogressive lesions with continuous EGFR-TKI treatment is associated with additional 10 months of disease control and should be recommended in TKI acquired resistant-NSCLC patients.

Purpose: Patients with oligometastatic non-small-cell lung cancer (NSCLC) benefit from local control treatments such as surgery or irradiation. The efficacy and safety of microwave ablation (MWA) in these patients was unknown. Material and methods: Between January 2011 and April 2018, eligible patients were retrospectively enrolled. MWA was conducted for both primary lesions and metastatic lesions in patients with synchronous metastases and in metastatic lesions for patients with metachronous metastases. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), technical success, technique efficacy, and complications. Results: Seventy-nine patients with 103 oligometastatic lesions were enrolled. A total of 20 primary lesions and 96 metastatic lesions were treated with MWA during 101 procedures. Technical success was achieved in all patients. Technique efficacy was achieved in 72 patients (91.1%). The median PFS and OS were 14.0 and 47.8 months, respectively. Forty-four patients (55.7%) developed complications with 21 (29.6%) of these patients developing major complications. All complications were resolved via appropriate medical treatments, and no MWA-related deaths occurred. Conclusion: MWA was safe and effective for patients with oligometastatic NSCLC.

Background: Camrelizumab is a promising anti-programmed cell death-1 agent for non-small cell lung cancer (NSCLC) and induces reactive capillary hemangiomas (RCHs). Routine clinical management of this unique and prevalent toxicity has been summarized in previous studies. The objective of this study was to provide evidence of apatinib as a salvage therapy for RCHs., Materials and Methods: In this single-center, observational study, patients with NSCLC who were over 18 years of age and treated with camrelizumab were enrolled. The incidence of RCHs, onset and duration time, severity, evolution, and clinical practices, especially with apatinib, for their management and impact on quality of life, were recorded during a 6-month follow-up., Results: A total of 28 patients were included. The incidence of RCHs was 28.6% (8/28). The median onset and duration time were 6 weeks and 8 weeks, respectively. Six (21.4%) patients had mild and moderate RCHs and four (9.3%) patients achieved a rapid regression of RCHs with the application of apatinib. The impact of the RCHs on quality of life was limited and assessed with Dermatology Life Quality Index scores. No treatment-associated termination was observed., Conclusion: The combination of camrelizumab and apatinib in the treatment of NSCLC reduced the incidence of RCHs. Apatinib appeared to be a salvage therapy of RCHs, which leads to rapid regression of RCHs with no impairment on the quality of life., Competing Interests: None

Aim: The present study evaluated the safety and efficacy of camrelizumab (a programmed death-1 antibody) in combination with microwave ablation (MWA) in advanced non-small cell lung cancer (NSCLC)., Materials and Methods: A total of 21 patients were prospectively enrolled. MWA was performed in 25 pulmonary lesions during 21 sessions. Camrelizumab was administered 5-7 days after MWA as a dose of 200 mg, which was repeated every 2 weeks until disease progression or intolerable toxicities. The primary endpoints were safety and the objective response rate (ORR). Other endpoints included progression-free survival (PFS) and overall survival (OS)., Results: The technical success rate was 100%. No treatment-associated deaths were identified. Major complications, minor complications, and side effects of MWA were observed in 9, 8, and 14 patients, respectively. The main major complications included pneumothorax, pneumonia, hemorrhage, and pleural effusion. The adverse events of camrelizumab included reactive skin capillary hyperplasia (n = 9), hypothyroidism (n = 5), pneumonia (n = 4), fatigue (n = 2), leukopenia (n = 1), and neutropenia (n = 1). Grade 2 and 3 camrelizumab adverse events were identified in eight and three patients, respectively. The ORR was 33.3%, with two patients achieving complete response and five patients achieving partial response. The median PFS was 5.1 months and OS was not reached., Conclusions: Camrelizumab administration combined with MWA was safe in the treatment of advanced NSCLC, and the combination improved the ORR of camrelizumab alone compared to previous reports., Competing Interests: None

Objectives: The objective of this study is to determine the diagnostic ability of percutaneous core biopsy immediately after microwave ablation (MWA) for lung ground-glass opacity (GGO)., Materials and Methods: Seventy-four patients with 74 lung GGOs were enrolled and treated with MWA. A percutaneous core needle biopsy was performed pre- and immediately post-MWA. All biopsy specimens were histologically examined by hematoxylin and eosin staining and immunostaining. Histologically, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (AC) were identified as positive, while chronic inflammation or normal lung tissue was identified as negative., Results: The outcomes of pre-MWA histological diagnosis were AAH (n = 4), AIS (n = 16), MIA (n = 14), AC (n = 29), chronic inflammation (n = 2), and lung tissue (n = 9) with an 85.1% (63/74) positive diagnosis rate. The outcomes of the immediately post-MWA histological diagnosis were AAH (n = 5), AIS (n = 10), MIA (n = 11), AC (n = 29), chronic inflammation (n = 1), and lung tissue (n = 18) with a 74.3% (55/74) positive diagnosis rate. There was no significant difference in the positive diagnosis rate between the pre- and immediately post-MWA groups (P = 0.10). The outcomes of the combined diagnosis of pre- and immediately post-MWA were AAH (n = 4), AIS (n = 16), MIA (n = 16), AC (n = 31), chronic inflammation (n = 2), and lung tissue (n = 5) with a positive diagnosis rate of 90.5% (67/74), which was higher than that by pre-MWA biopsy (P < 0.05). The main complications were pneumothorax (n = 45, 60.8%), hemoptysis (n = 24, 32.4%), pleural effusion (n = 39, 52.7%), and pulmonary infection (n = 10, 13.5%)., Conclusions: Immediately post-MWA core biopsy has promising efficacy for histological diagnosis of lung GGOs., Competing Interests: None

Objectives: Pulmonary granulomatous nodule (GN) with spiculated or lobulated appearance are indistinguishable from solid lung adenocarcinoma (SADC) based on CT morphological features, and partial false-positive findings on PET/CT. The objective of this study was to investigate the ability of quantitative CT radiomics for preoperatively differentiating solitary atypical GN from SADC., Methods: 302 eligible patients (SADC = 209, GN = 93) were evaluated in this retrospective study and were divided into training (n = 211) and validation cohorts (n = 91). Radiomics features were extracted from plain and vein-phase CT images. The L1 regularized logistic regression model was used to identify the optimal radiomics features for construction of a radiomics model in differentiate solitary GN from SADC. The performance of the constructed radiomics model was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC)., Results: 16.7% (35/209) of SADC were misdiagnosed as GN and 24.7% (23/93) of GN were misdiagnosed as lung cancer before surgery. The AUCs of combined radiomics and clinical risk factors were 0.935, 0.902, and 0.923 in the training cohort of plain radiomics(PR), vein radiomics, and plain and vein radiomics, and were 0.817, 0835, and 0.841 in the validation cohort of three models, respectively. PR combined with clinical risk factors (PRC) performed better than simple radiomics models (p < 0.05). The diagnostic accuracy of PRC in the total cohorts was similar to our radiologists (p ≥ 0.05)., Conclusions: As a noninvasive method, PRC has the ability to identify SADC and GN with spiculation or lobulation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The study was conducted to retrospectively evaluate the safety and effectiveness of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for peripheral non-small cell lung cancer (NSCLC) in 11 patients with a single lung after pneumonectomy., Methods: From May 2011 to March 2015, 11 single-lung patients (8 men and 3 women; mean age 60.3 years, range 46-71) with peripheral NSCLC underwent 12 sessions of MWA. Eleven tumors measuring 13-52 mm (mean 30.2 mm) were treated. Follow-up was performed via CT scan at 1, 3, 6, 12, 18, and 24 months after the procedure and annually thereafter. Clinical outcomes were evaluated and complications after MWA were summarized., Results: At a median follow-up period of 20 months (range 6-38), four patients showed evidence of local recurrence at a rate of 36.4% (4/11). Median overall survival was 20 months. The overall survival rates at one, two, and three years after MWA were 88.7%, 63.6%, and 42.3%, respectively. Complications after MWA included pneumothorax (33.3%), hemoptysis (33.3%), intrapulmonary bleeding (25%), pleural effusion (16.7%), and pulmonary infection (8.3%). None of the patients died during the procedure or in the 30 days after MWA., Conclusion: CT-guided percutaneous MWA is safe and effective for the treatment of peripheral NSCLC in patients with a single lung after prior pneumonectomy., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Many major diseases, including various types of cancer, are increasingly threatening human health. However, the mechanisms of the dynamic processes underlying these diseases remain ambiguous. From the holistic perspective of systems science, complex biological networks can reveal biological phenomena. Changes among networks in different states influence the direction of living organisms. The identification of the kernel differential subgraph (KDS) that leads to drastic changes is critical. The existing studies contribute to the identification of a KDS in networks with the same nodes; however, networks in different states involve the disappearance of some nodes or the appearance of some new nodes. In this paper, we propose a new topology-based KDS (TKDS) method to explore the core module from gene regulatory networks with different nodes in this process. For the common nodes, the TKDS method considers the differential value (D-value) of the topological change. For the different nodes, TKDS identifies the most similar gene pairs and computes the D-value. Hence, TKDS discovers the essential KDS, which considers the relationships between the same nodes as well as different nodes. After applying this method to non-small cell lung cancer (NSCLC), we identified 30 genes that are most likely related to NSCLC and extracted the KDSs in both the cancer and normal states. Two significance functional modules were revealed, and gene ontology (GO) analyses and literature mining indicated that the KDSs are essential to the processes in NSCLC. In addition, compared with existing methods, TKDS provides a unique perspective in identifying particular genes and KDSs related to NSCLC. Moreover, TKDS has the potential to predict other critical disease-related genes and modules.

Purpose: The purpose of the study is to retrospectively evaluate the safety and efficacy of microwave ablation (MWA) for the treatment of ground-glass opacity (GGO)-lung adenocarcinoma., Materials and Methods: From December 2013 to June 2017, a total of 51 patients (22 males and 29 females, mean age of 69.4 ± 10.1 years) were included in this study, with 51 lung adenocarcinoma lesions showing GGO (mean long-axis diameter of 18.7 ± 6.05 mm). They received a total of 52 sessions of percutaneous computed tomography-guided (CT-guided) MWA. First, lung adenocarcinoma with GGO was histologically defined by needle biopsy under the guidance of CT. Second, the efficacy of CT-guided MWA was analyzed, including the feasibility, safety, 3 years local progression-free survival (LPFS), 3 years disease-specific survival, and 3 years overall survival (OS). Final, complications after MWA were also summarized., Results: The technical success rate was 100%, without MWA procedure-related death. At the median follow-up period (27.02, range: 7-45 months), the rates of 3 years LPFS, cancer-specific survival, and OS were 98%, 100%, and 96%, respectively. The complications after MWA included pneumothorax (48.1%, 25/52), hemoptysis (28.8%, 14/52), pleural effusion (23.1%, 12/52), and pulmonary infection (7.7%, 4/52)., Conclusions: CT-guided percutaneous MWA was a feasible, safe, and effective therapeutic approach for treating GGO-lung adenocarcinoma., Competing Interests: There are no conflicts of interest

Background: To evaluate the efficacy and safety of microwave ablation (MWA) followed by immediate biopsy in the treatment of non-small cell lung cancer (NSCLC) and to clarify whether pathology changes can predict treatment responses and patient survival., Methods: Patients with pathologically confirmed NSCLC pre-ablation were treated with MWA, and immediate biopsy was carried out right after ablation in one procedure. Pathology changes were categorized according to the pre- and postablation pathology: Group A, same histology type; Group B, paired histology type with burning degeneration; Group C, no definite histology type; Group D, no definite cancer cells. The internal correlations between pathology changes and baseline characteristics, responses to MWA and survival were evaluated., Results: A total of 68 patients were enrolled in the study, of which 19, 28, 11 and 10 patients were classified into Group A, Group B, Group C and Group D, respectively. In total, 85.3 and 69.1% patients were diagnosed with malignant tumors and the same pathology type, respectively. No significant difference in clinical-pathologic characteristics or response to MWA between the groups was observed. Upon combining Groups A, B and C, Group D exhibited longer progression-free survival (PFS) (Groups A + B + C versus Group D, 11.7 months, 95% CI 9.6-13.7 versus 26.6 months, 95% CI 19.0-34.2, p = .253) and overall survival (OS) (15.9 months, 95% CI 14.2-17.5, versus 29.8 months, 95% CI, 24.3-35.3, p = .395), although no significant differences were observed. Complications were identified in 63 (92.6%), of which 17 (25.0%) patients had major complications., Conclusions: Immediate biopsy post-MWA can distinguish cancer cells or histology types in most cases of NSCLC. However, pathology changes pre- and postablation could not predict the response to MWA and patient survival.

Background: Programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) were associated with non-small cell lung cancer (NSCLC). We conducted this study to evaluate the correlation between PD-L1 or CD8+ TILs expression and MWA or survival in advanced NSCLC patients treated with microwave ablation (MWA) plus chemotherapy., Methods: Previously untreated, pathologically verified advanced NSCLC patients with adequate tissues for the analysis of PD-L1 expression and the presence of CD8+ TILs were retrospectively enrolled. None of the patients had sensitive mutations, and therefore, they were treated with MWA of the primary tumors followed by chemotherapy., Results: A total of 51 patients were enrolled. PD-L1 expression and the presence of CD8+ TILs were identified in 31 (60.8%) and 9 (17.6%) patients, respectively. PD-L1 expression and CD8+ TILs had no correlation with baseline characteristics, the response to chemotherapy or MWA. Patients with PD-L1 expression had similar progression-free survival (PFS: 7.9 months for PD-L1-positive vs. 5.8 months for PD-L1-negative; p = .660) and overall survival (OS: 18.7 months for PD-L1-positive vs. 15.2 months for PD-L1-negative; p = .901). Patients with CD8+ TIL expression did not show superior PFS (CD8+ TIL vs. CD8- TIL, 8.0 vs. 6.2 months, p = .435) or OS (CD8+ TIL vs. CD8- TIL, 20.5 vs. 16.9 months, p = .653)., Conclusion: PD-L1 expression and the presence of CD8+ TILs could predict neither the patients' response to chemotherapy or MWA nor survival in advanced NSCLC patients treated with MWA plus chemotherapy.

Objectives: To verify the association between EGFR status and clinical response to microwave ablation (MWA) and survival., Methods: NSCLC patients with known EGFR status and treated with MWA in combination with chemotherapy were retrospectively enrolled in the study., Results: A total of 61 patients were recruited. EGFR mutations were found in 28 patients (39.4 %), and were more common in women (67.7 %) and nonsmokers (74.1 %). Complete ablation was achieved in 69.7 % of patients with EGFR mutant tumours and in 82.1 % of patients with EGFR wild-type tumours (p = 0.216). The median progression-free survival (PFS) and overall survival (OS) were 8.3 months and 27.2 months in patients with an EGFR mutant tumour. The corresponding values were 5.4 months (p = 0.162) and 17.8 months (p = 0.209) in patients with an EGFR wild-type tumour. Patients with complete ablation had longer PFS (7.8 months vs. 4.2 months, p = 0.024) and OS (28.1 months vs. 12.6 months, p = 0.001) than those with incomplete ablation. Multivariate analyses also showed that response to MWA was an independent prognostic factor for OS, but EGFR status was not, and that neither response to MWA nor EGFR status was a prognostic factor for PFS., Conclusions: The EGFR status was not related to response to MWA, and response to MWA was a predictor of survival., Key Points: • EGFR mutations were commonly seen in women and in nonsmokers • EGFR status had no correlation with the response to MWA, PFS and OS. • The response to MWA could predict PFS and OS.

Curcumin (Cur) is a promising photosensitizer that could be used in photodynamic therapy. However, its poor solubility and hydrolytic instability limit its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) in order to improve its therapeutic activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using an emulsification and low-temperature solidification method. The functions of Cur and Cur-SLNs were studied on the non-small cell lung cancer A549 cells for photodynamic therapy. The results revealed that Cur-SLNs induced ~2.27-fold toxicity higher than free Cur at a low concentration of 15 μM under light excitation, stocking more cell cycle at G2/M phase. Cur-SLNs could act as an efficient drug delivery system to increase the intracellular concentration of Cur and its accumulation in mitochondria; meanwhile, the hydrolytic stability of free Cur could be improved. Furthermore, Cur-SLNs exposed to 430 nm light could produce more reactive oxygen species to induce the disruption of mitochondrial membrane potential. Western blot analysis revealed that Cur-SLNs increased the expression of caspase-3, caspase-9 proteins and promoted the ratio of Bax/Bcl-2. Overall, the results from these studies demonstrated that the SLNs could enhance the phototoxic effects of Cur., Competing Interests: The authors report no conflicts of interest in this work.

The non-small cell lung cancer (NSCLC) patients that experienced good clinical response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) will ultimately develop acquired resistance. This retrospective study was performed to explore the potential survival benefit of microwave ablation (MWA) therapy in epidermal growth factor receptor (EGFR)-mutant NSCLC that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment.We retrospectively analyzed 54 NSCLC patients with EGFR mutations who showed a clinical benefit from initial EGFR-TKI therapy and developed extra-CNS oligoprogressive disease at our institutions. Twenty eight patients received MWA as a local therapy for the metastatic sites and continued on the same TKIs (MWA group). The following 26 patients received systemic chemotherapy after progression (chemotherapy group). The progression-free survival (PFS1) was calculated from initiation of targeted therapy to first progression. Progression-free survival (PFS2) was defined from first progression to second progression after MWA or chemotherapy. Overall survival (OS) was calculated from the time of diagnosis to the date of last follow-up or death.The median PFS1 for both groups was similar (median 12.6 vs. 12.9 months, HR 0.63). However, the MWA group patients had a significantly longer PFS2 (median 8.8 vs. 5.8 months, hazards ratio [HR] 0.357) and better OS (median 27.7 vs. 20.0, HR 0.238) in comparison with chemotherapy group. Multivariate analysis and the internal validation identified MWA as the main favorable prognostic factor for PFS2 and OS. In the MWA group, the median PFS2 for complete ablation was significantly longer than that for incomplete ablation (11 vs. 4.2 months, HR 0.29, P < 0.05).MWA with continued EGFR inhibition might be associated with favorable progression-free survival (PFS) and OS in patients with extra-CNS oligometastatic disease. MWA as a local therapy for extra-CNS oligometastatic disease should be considered for NSCLC with acquired resistance to EGFR-TKIs., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To retrospectively evaluate the efficacy and safety of microwave ablation (MWA) combined with osteoplasty in lung cancer patients with painful extraspinal bone metastases., Materials and Methods: From January 2011 to July 2014, 26 lung cancer patients with 33 painful extraspinal bone metastases underwent percutaneous MWA combined with osteoplasty. Effectiveness was evaluated by visual analog scale (VAS) and daily morphine dose with a follow-up of 6-months. Complications were also recorded., Results: Mean VAS score and morphine dose pre-procedure were 7.4 ± 1.6 (range, 5-10) and 47.7 ± 30.1 mg (range, 20-120 mg), respectively. Technical success and pain relief were achieved in all patients. Mean VAS scores and daily morphine doses post-procedure were as follows: 48 h, 1.7 ± 1.2 (p < 0.001) and 29.6 ± 16.1 mg (p = 0.003); 7 days, 1.9 ± 1.7 (p < 0.001) and 16.1 ± 12.0 mg (p < 0.001); 1 month, 1.5 ± 0.9 (p < 0.001) and 10.8 ± 10.9 (p < 0.001); 3 months, 0.9 ± 0.7 (p < 0.001) and 8.4 ± 9.2 mg (p < 0.001); and 6 months, 1.2 ± 0.8 (p < 0.001) and 9.2 ± 12.3 mg (p < 0.001). Complications were observed in eight patients (28%); among these, major complications were reported in two (7.7%) patients, one with local infection and the other with a bone fracture. The minor complication rate was 23.1% (6/26)., Conclusion: MWA combination with osteoplasty appeared to be an effective and safe treatment for lung cancer patients with painful extraspinal bone metastases.

Purpose: To verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy., Methods: Thirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0)., Results: MWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00-9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5-11.9). The median overall survival time was 21.3 months (95 % CI 17.0-25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients., Conclusions: Patients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

The aim of the study was to determine survival benefit of the microwave ablation (MWA)/chemotherapy combination compared with chemotherapy alone. Patients with untreated, stage IIIB or IV NSCLC and at least one additional measurable site other than the ablative site were enrolled. They were divided into MWA/chemotherapy group and chemotherapy group. The primary endpoint was progression-free survival (PFS); secondary endpoints included response, time to local progression (TTLP), overall survival (OS), and adverse events (AEs). Forty-six and twenty-eight patients were enrolled in the MWA/chemotherapy group and chemotherapy group, respectively. Complete ablation was observed in 84.8 % patients in the MWA/chemotherapy group. Median TTLP was 27.0 months. Objective response rate and disease control rate in MWA/chemotherapy group were 21.7 and 76.1 %, and in the chemotherapy group were 32.1 % (p = 0.320) and 75.0 % (p = 0.916), respectively. MWA/chemotherapy combination prolonged PFS [MWA/chemotherapy group 10.9 (95 % CI 5.1-16.7) ms vs. chemotherapy group 4.8 (95 % CI 3.9-5.8) ms, p = 0.001] and tended to improve OS [MWA/chemotherapy group 23.9 (95 % CI 15.2-32.6) ms vs. chemotherapy group 17.3 (95 % CI 15.2-19.3) ms, p = 0.140]. Multivariate analyses showed that MWA was an independent prognostic factor of PFS and primary tumor size was an independent prognostic factor of OS. AEs of MWA were observed in 67.4 % patients. Chemotherapy-associated AEs were observed in 39.1 and 53.6 % of patients in the MWA/chemotherapy and chemotherapy group, respectively. MWA/chemotherapy combination improved PFS of advanced NSCLC compared to chemotherapy alone, and the combination did not increase the adverse events of chemotherapy.

Purpose: To retrospectively evaluate safety and effectiveness of CT-guided percutaneous microwave ablation (MWA) in 47 patients with medically inoperable stage I peripheral non-small cell lung cancer (NSCLC)., Methods: From February 2008 to October 2012, 47 patients with stage I medically inoperable NSCLC were treated in 47 MWA sessions. The clinical outcomes were evaluated. Complications after MWA were also summarized., Results: At a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, 5 years after MWA were 96%, 64%, and 48%, respectively. The median cancer-specific and median overall survivals were 47.4 and 33.8 months. The overall survival rates at 1, 2, 3, and 5 years after MWA were 89%, 63%, 43%, and 16%, respectively. Tumors ≤3.5 cm were associated with better survival than were tumors >3.5 cm. The complications after MWA included pneumothorax (63.8%), hemoptysis (31.9%), pleural effusion (34%), pulmonary infection (14.9%), and bronchopleural fistula (2.1%)., Conclusions: MWA is safe and effective for the treatment of medically inoperable stage I peripheral NSCLC., (© 2014 Wiley Periodicals, Inc.)

Objective: To study the effect of dihydroartemisinin (DHA) combined irradiation on the apoptosis of human lung cancer GLC-82 cells and to study its mechanism., Methods: The growth inhibition rate of GLC-82 cells acted by different concentrations DHA was detected using MTT assay at 24, 48, and 72 h, respectively. Clone forming test was used. With multi-target single-hit model, the radiosensitization effect was assessed by calculating sensitizing enhancement ratio (SER).The effect of DHA combined irradiation on the apoptosis of GLC-82 cell cycle distribution and apoptosis were measured by flow cytometry. The protein expression of p53, p21, Bcl-2, and Bax were detected by Western blot., Results: Different concentrations DHA (4, 8, 16, 32, 64, and 128 μg/mL) had cytotoxicity on GLC-82 cells. The IC50 for 24, 48, and 72 h was 38.25,20.58, and 10.36 μg/mL, respectively, in obvious dose- and time-dependent manner. The growth inhibition rate was more significantly increased than that of the blank control group (P < 0.01, P<0.05). DHA had sensitization enhancement effect on GLC-82 cells, with SER of 1.4. DHA combined irradiation could obviously change the structure of GLC-82 cells cell cycle and induce apoptosis (with the apoptosis rate of 21.5%), which was significantly different from that of the blank control group (P < 0.05). Western blot showed the expression of p53 and p21 protein could be increased by DHA combined irradiation, and the expression of Bcl-2 protein down-regulated (P <0.01, P <0. 05)., Conclusions: DHA had stronger cytotoxicity and radiosensitization on GLC-82 cells. Its mechanisms might lie in making the arrest of GLC-82 cells' growth at G0/G1 phase, decreasing the ratio of cells at S phase, restoring the function of p53, decreasing the expression of Bcl-2 protein, and inducing apoptosis in GLC-82 cells.

Three cases are reported of invasive pulmonary aspergillosis (IPA) occurring after microwave ablation (MWA) for lung tumours. This is a rare complication that has not previously been described in the literature. The diagnosis of IPA was based on the following factors: host factors, clinical manifestations and mycological findings. The first case was a 63-year-old man treated for primary lung squamous carcinoma. Significant tumour regression was achieved by 18 days after MWA, medical treatment with itraconazole for 6 weeks, and postural drainage. The second case, a 65-year-old man, was confirmed with primary lung squamous cell carcinoma. Voriconazole administration using intravenous infusion combined with intracavitary lavage was therapeutically effective after MWA at 1 year follow-up. The third case was a 61-year-old woman with primary lung adenocarcinoma. Delayed pneumothorax and bronchopleural fistula secondary to IPA persisted. The patient died from secondary multiple organ function failure. Despite its very low incidence, the significance of early diagnosis and early administration of antifungal therapy should be highlighted because of the relentless severity of IPA in patients undergoing MWA.

Purpose: To investigate the expression of hypoxia-inducible factor prolyl hydroxylase 3 (HIFPH3) in non-small cell lung cancer (NSCLC) and explore the correlation of HIFPH3 expression with lymph node metastasis and microvessel density (MVD)., Materials and Methods: A total of 73 cases of NSCLC specimens, 24 cases of para- cancerous tissues, and 20 normal pulmonary tissues were collected for HIFPH3 and CD31 immunohistochmical (IHC) study. Microvessel density (MVD) of the NSCLC tissues was also determined based on the expression of CD31., Results: The expression of HIFPH3 in carcinoma tissue was statistically higher than para-cancerous and normal pulmonary tissues (χ2=48.806, p<0.05). Compared withthe negative lymph node metastasis group, the lymph node metastasis group showed significantly higher HIFPH3 expression (χ2=6.300, p<0.05). The strong HIFPH3+group displayed a significantly higher MVD than weak HIFPH3+ and HIFPH3- groups (p<0.05). No differences in positive HIFPH3 expression were noted regarding the tumor diameter, age, smoking status, gender of NSCLC patients, tumor size, histopathology, or differentiation., Conclusions: HIFPH3 expression in human NSCLC lesions is significantly higher than that in para-cancerous and normal lung tissues and is positively associated with lymph node metastasis and MVD.