Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Safety and efficacy of CT-guided percutaneous microwave ablation for stage I non-small cell lung cancer in patients with comorbid idiopathic pulmonary fibrosis.

OBJECTIVES: To evaluate the safety and efficacy of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: A retrospective single-center cohort study was conducted in patients with clinical stage I NSCLC who underwent CT-guided MWA from Nov 2016 to Oct 2021. The patients were divided into the IPF group and the non-IPF group. The primary endpoints were 90-day adverse events and hospital length of stay (HLOS). The secondary endpoints included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 107 patients (27 with IPF and 80 without IPF) were finally included for analysis. No procedure-related acute exacerbation of IPF or death occurred post-MWA. The rates of adverse events were similar between the groups (48.6% vs. 47.7%; p = 0.998). The incidence of grade 3 adverse events in the IPF group was higher than that in the non-IPF group without a significant difference (13.5% vs. 4.6%; p = 0.123). Median HLOS was 5 days in both groups without a significant difference (p = 0.078). The 1-year and 3-year OS were 85.2%/51.6% in the IPF group, and 97.5%/86.4% in the non-IPF group. The survival of patients with IPF was significantly poorer than the survival of patients without IPF (p < 0.001). There was no significant difference for PFS (p = 0.271). CONCLUSION: MWA was feasible in the treatment of stage I NSCLC in patients with IPF. IPF had an adverse effect on the survival of stage I NSCLC treated with MWA. CLINICAL RELEVANCE STATEMENT: CT-guided microwave ablation is a well-tolerated and effective potential alternative treatment for stage I non-small cell lung cancer in patients with idiopathic pulmonary fibrosis. KEY POINTS: • Microwave ablation for stage I non-small cell lung cancer was well-tolerated without procedure-related acute exacerbation of idiopathic pulmonary fibrosis and death in patients with idiopathic pulmonary fibrosis. • No differences were observed in the incidence of adverse events between patients with idiopathic pulmonary fibrosis and those without idiopathic pulmonary fibrosis after microwave ablation (48.6% vs. 47.7%; p = 0.998). • The 1-year and 3-year overall survival rates (85.2%/51.6%) in the idiopathic pulmonary fibrosis group were worse than those in the non- idiopathic pulmonary fibrosis group (97.5%/86.4%) (p < 0.001).

Automated segmentation of liver and hepatic vessels on portal venous phase computed tomography images using a deep learning algorithm.

BACKGROUND: CT-image segmentation for liver and hepatic vessels can facilitate liver surgical planning. However, time-consuming process and inter-observer variations of manual segmentation have limited wider application in clinical practice. PURPOSE: Our study aimed to propose an automated deep learning (DL) segmentation algorithm for liver and hepatic vessels on portal venous phase CT images. METHODS: This retrospective study was performed to develop a coarse-to-fine DL-based algorithm that was trained, validated, and tested using private 413, 52, and 50 portal venous phase CT images, respectively. Additionally, the performance of the DL algorithm was extensively evaluated and compared with manual segmentation using an independent clinical dataset of preoperative contrast-enhanced CT images from 44 patients with hepatic focal lesions. The accuracy of DL-based segmentation was quantitatively evaluated using the Dice Similarity Coefficient (DSC) and complementary metrics [Normalized Surface Dice (NSD) and Hausdorff distance_95 (HD95) for liver segmentation, Recall and Precision for hepatic vessel segmentation]. The processing time for DL and manual segmentation was also compared. RESULTS: Our DL algorithm achieved accurate liver segmentation with DSC of 0.98, NSD of 0.92, and HD95 of 1.52 mm. DL-segmentation of hepatic veins, portal veins, and inferior vena cava attained DSC of 0.86, 0.89, and 0.94, respectively. Compared with the manual approach, the DL algorithm significantly outperformed with better segmentation results for both liver and hepatic vessels, with higher accuracy of liver and hepatic vessel segmentation (all p < 0.001) in independent 44 clinical data. In addition, the DL method significantly reduced the manual processing time of clinical postprocessing (p < 0.001). CONCLUSIONS: The proposed DL algorithm potentially enabled accurate and rapid segmentation for liver and hepatic vessels using portal venous phase contrast CT images.

Microwave Ablation for Inoperable Stage I Non-Small Cell Lung Cancer in Patients Aged ≥70 Years: A Prospective, Single-Center Study.

PURPOSE: To evaluate the safety and survival outcomes of computed tomography-guided microwave ablation (MWA) for medically inoperable Stage I non-small cell lung cancer (NSCLC) in patients aged ≥70 years. MATERIALS AND METHODS: This study was a prospective, single-arm, single-center clinical trial. The MWA clinical trial enrolled patients aged ≥70 years with medically inoperable Stage I NSCLC from January 2021 to October 2021. All patients received biopsy and MWA synchronously with the coaxial technique. The primary endpoints were 1-year overall survival (OS) and progression-free survival (PFS). The secondary endpoint was adverse events. RESULTS: A total of 103 patients were enrolled. Ninety-seven patients were eligible and analyzed. The median age was 75 years (range, 70-91 years). The median diameter of tumors was 16 mm (range, 6-33 mm). Adenocarcinoma (87.6%) was the most common histologic finding. With a median follow-up of 16.0 months, the 1-year OS and PFS rates were 99.0% and 93.7%, respectively. There were no procedure-related deaths in any patient within 30 days after MWA. Most of the adverse events were minor. CONCLUSION: MWA is an effective and safe treatment for patients aged ≥70 years with medically inoperable Stage I NSCLC.

Effects of tract embolization on pneumothorax rate after percutaneous pulmonary microwave ablation: a rabbit study.

PURPOSE: To determine the effects of tract embolization with gelatin sponge particles on the prevention of pneumothorax after percutaneous microwave ablation (MWA) in rabbit lungs. MATERIALS AND METHODS: Twenty-four New Zealand white rabbits were randomly divided into Group A (MWA followed by tract embolization with gelatin sponge particles, n = 12) and Group B (MWA without tract embolization, n = 12). For each group, CT images were reviewed for the occurrence of pneumothorax within 30 min after MWA. The rate of pneumothorax was compared by Chi-square Test. Lung tissue around the needle tract was harvested after the rabbits were euthanized, and histopathological examinations were performed and studied with hematoxylin and eosin stains. RESULTS: Twenty-four animals underwent 47 sessions of MWA (24 sessions in Group A and 23 sessions in Group B). Group A had a statistically lower rate of pneumothorax than Group B (25.0 vs. 56.5%; p = 0.028). The pathological examinations of both groups demonstrated thermal injury of the needle tract characterized by a rim of the coagulated lung parenchyma, which might be responsible for pneumothorax after MWA. Gelatin sponge particles could be arranged in irregular flakes densely to effectively seal the needle tract, thus reducing the occurrence of pneumothorax. The gelatin sponge particles could be almost completely absorbed about 14 days later. CONCLUSION: Results of the present study showed needle tract embolization with gelatin sponge particles after CT-guided pulmonary MWA can significantly reduce the incidence of pneumothorax. Gelatin sponge particles can effectively seal the needle tract after ablation and can be completely absorbed in the body with good safety.

Synchronous percutaneous core-needle biopsy and microwave ablation for stage I non-small cell lung cancer in patients with Idiopathic pulmonary fibrosis: initial experience.

PURPOSE: This study aimed to retrospectively evaluate the safety and feasibility of computed tomography (CT)-guided synchronous percutaneous core-needle biopsy (CNB) and microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: From January 2019 to January 2023, nineteen stage I NSCLC patients with IPF underwent CT-guided synchronous percutaneous CNB and MWA in this study. The technical success rate, complications, local tumor progression (LTP) and overall survival (OS) were observed, and the effect of synchronous percutaneous CNB and MWA were evaluated. RESULTS: The technical success rate of synchronous percutaneous CNB and MWA was 100%. With a median follow-up time of 20.36 months, the median OS was 25 months (95% CI: 21.79, 28.20). The six-, twelve- and eighteen-month OS rates were 94.73%, 89.47% and 57.89%, respectively. The six-, twelve- and eighteen-month LTP rates were 0%, 10.52% and 31.57%, respectively. Major complications including pneumothorax, bronchopleural fistula and pneumonia occurred in 26.32% (5/19) patients. None of the patients died during the procedure. CONCLUSIONS: According to the results of the current study, CT-guided synchronous percutaneous CNB and MWA appears to be a safe and effective for stage I NSCLC in patients with IPF and providing an alternative therapeutic option for local control of pulmonary malignancy in high-risk patients.

Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report.

BACKGROUND: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. CASE PRESENTATION: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1ß isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. CONCLUSIONS: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.

Nerve Injury and Regeneration after Neurolysis: Ethanol Alone versus Ethanol with Brachytherapy in Rabbits.

PURPOSE: This study aimed to prove the hypothesis that neurolysis based on ethanol injection in combination with iodine-125 (125I) radioactive seed implantation could prolong the nerve regeneration time compared with that based on ethanol injection alone. The grade of nerve injury was assessed for both methods. MATERIALS AND METHODS: Twenty female rabbits (mean weight, 2.8 kg ± 0.2) were randomly assigned to group A (neurolysis of the left brachial plexus nerve based on ethanol injection in combination with 125I radioactive seed implantation, n = 10) and group B (neurolysis using ethanol injection alone, n = 10). The right brachial plexus nerve was used as a control. Injury and regeneration of the brachial plexus nerve were analyzed using electromyography. Statistical tests were performed using the Mann-Whitney U test and repeated-measures analysis of variance. The results were verified with histopathological examinations. RESULTS: The overall postprocedural amplitude was significantly lower in group A than in group B (P = .01), particularly in the second month after the procedure (P = .036). However, no statistical difference in latency was observed between the 2 groups (P = .103). Histopathological examination of both groups revealed Sunderland third-degree peripheral nerve injury (PNI), which was mainly characterized by axonal disintegration. The degree of nerve regeneration was significantly lower in group A than in group B. CONCLUSIONS: Neurolysis based on ethanol injection in combination with 125I radioactive seed implantation can prolong the nerve regeneration time compared with that based on ethanol injection alone, although both methods resulted in Sunderland third-degree PNI.

Correlations of RENAL, PADUA and NePhRO Scores With Complications and Outcomes in Patients After CT-Guided Microwave Ablation of Renal Tumors.

OBJECTIVE: This retrospective study aimed to access the correlations of RENAL, PADUA and NePhRO scores with operative complications, chronic kidney disease (CKD) upstaging, and oncologic outcomes after CT-guided percutaneous Microwave Ablation (MWA) of renal tumors in order to determine their status as independent predictors of outcomes after MWA. This study also aimed to generally evaluate the efficacy of MWA in treating renal tumors. METHODS: From January 2017 to December 2019, 18 patients with 27 renal tumors who had undergone simultaneous biopsy and MWA were recruited in this single-center retrospective study. Data collection included tumor characteristics, procedural protocols, complications, CKD upstaging data, local tumor control data and overall survival. All lesions were evaluated using RENAL, PADUA and NePhRO scores, and further analysis was performed to determine whether the scores were correlated with operative complications, CKD upstaging, local tumor control and overall survival. RESULTS: The minor and major complication rates were 16.7% and 0%, respectively. Two patients with solitary kidney experienced CKD upstaging. Local tumor recurrence was identified in one type of tumor (3.7%) in the first year of follow-up. L. parameter (P = .031), longitudinal (polar) location score (P = .011), Ne. parameter (P = .036), number of kidneys (P = .005), and number of lesions (P = .008), were predictive factors significantly associated with the occurrence of complications. Besides, CKD upstaging was associated with A. parameter (P = .032) and urinary collecting system score (P = .028). RENAL, PADUA, and NePhRO scores were significantly correlated with complications, overall survival, and CKD upstaging, respectively (P < .05). CONCLUSION: CT-guided percutaneous MWA was found to be a valuable alternative in the treatment of renal tumors for selected patients. Furthermore, RENAL, PADUA and NePhRO scores were not independent predictors of outcomes of MWA.

Sintilimab plus Bronchial Arterial Infusion Chemotherapy/Drug-Eluting Embolic Chemoembolization for Advanced Non-Small Cell Lung Cancer: A Preliminary Study of 10 Patients.

PURPOSE: To evaluate the short-term efficacy and safety of immunotherapy with sintilimab combined with bronchial arterial infusion (BAI) chemotherapy/drug-eluting embolic (DEE) bronchial arterial chemoembolization (BACE) for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Ten patients with advanced NSCLC were treated with sintilimab plus BAI/DEE-BACE between December 2019 and November 2020 and retrospectively evaluated. The Response Evaluation Criteria in Solid Tumors version 1.1 was applied to evaluate the treatment response. The local tumor control duration, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier analysis. RESULTS: At 30 days after the last multimodal treatment, complete response, partial response, and stable disease were recorded in 1 (10%), 7 (70%), and 2 (20%) patients, respectively, for an objective response rate of 80% and a disease control rate of 100%. No patient experienced progressive disease. The median duration of local tumor control was 8.0 months (95% CI, 6.2-9.7 months). The median PFS and OS were 11.0 months (95% CI, 6.9-15.1 months) and 8.0 months (95% CI, 5.5-10.5 months), respectively. Two cases of Grade III adverse events related to medications were reported. CONCLUSIONS: Sintilimab combined with BAI/DEE-BACE for patients with advanced NSCLC appears to be safe and feasible. Compared with previous studies on BAI/DEE-BACE, the addition of immunotherapy may improve survival.

A Comparative Study of Cavitary and Noncavitary Non-small Cell Lung Cancer Patients Treated with CT-Guided Microwave Ablation.

PURPOSE: To explore the outcomes of computed tomography‒guided microwave (MW) ablation in patients with cavitary non-small cell lung cancer (NSCLC) and to compare the outcomes of cavitary and noncavitary NSCLC treated with MW ablation. MATERIALS AND METHODS: A total of 317 patients with NSCLC (194 men and 123 women) treated with MW ablation were include: 19 patients with cavitary NSCLC and 298 patients with noncavitary NSCLC. Complications, progression-free survival (PFS), and overall survival (OS) were evaluated and compared between the 2 groups. The Kaplan-Meier method was used to investigate the correlation of cavity and OS in patients with NSCLC. RESULTS: A total of 364 MW ablation procedures were performed. Adenocarcinoma was the predominant histopathological subtype in patients with cavitary NSCLC (73.7%). Cavitary NSCLC had an incidence rate of 57.9% in overall complications, which was significantly higher than that of 34.6% for noncavitary NSCLC (P = .040). In a mean follow-up of 27.2 months ± 11.9, the median PFS and OS for cavitary NSCLC were 9.0 months ± 8.5 and 14.0 months ± 10.8, respectively, and those for noncavitary NSCLC were 13.0 months ± 10.7 and 17.0 months ± 10.9, respectively. There was no significant difference in PFS (P = .180) or OS (P = .133) between cavitary and noncavitary NSCLC. In addition, the local recurrence rates for cavitary and noncavitary NSCLC were 15.8% and 21.5%, respectively, and no significant difference was found (P = .765). The Kaplan-Meier method revealed no association between the cavity and OS in patients with NSCLC treated with MW ablation. CONCLUSIONS: MW ablation was an effective and safe approach for cavitary NSCLC treatment. Compared with noncavitary NSCLC, cavitary NSCLC manifested with more complications but a comparable outcome after MW ablation.

Microwave ablation of lung malignancies with coexisting severe emphysema: a retrospective analysis of safety and efficacy in 26 patients.

PURPOSE: This retrospective study aimed to evaluate the safety and efficacy of microwave ablation (MWA) for lung malignancies in patients with severe emphysema. MATERIALS AND METHODS: The clinical records of 1075 consecutive patients treated for malignant lung tumors in our department were retrospectively reviewed. Emphysema was assessed based on standard-dose computed tomography (CT) and was considered severe when it occupied ≥25% of the lung. Overall, 26 patients (24 men and 2 women; mean age ± standard deviation [SD]: 71.23 ± 8.18 years, range: 59-88 years) with severe emphysema underwent CT-guided percutaneous MWA for treating 26 tumors (24: non-small cell lung cancer and 2: metastases). The mean tumor size was 3.0 cm (SD: 1.5, range: 1.2-6.5 cm). Follow-up was performed with CT at 1, 3, 6, 12 months after ablation, and every 6 months thereafter. Complications and efficacy were evaluated. RESULTS: The median follow-up duration in all patients was 17.5 months (range: 5-37 months, interquartile range: 15.8). The mortality rate was 0% within 30 days after ablation. Major complications including pneumonia, lung abscess and refractory pneumothorax occurred in 19.2% (5/26) patients. The technical success and efficacy rates were 88.5% (23/26) and 87.0% (20/23), respectively, and the local tumor progression rate was 30.0% (6/20). CONCLUSION: MWA appears to be a safe and effective therapeutic option for treating lung malignancies in patients with severe emphysema.

Risk prediction of pneumothorax in lung malignancy patients treated with percutaneous microwave ablation: development of nomogram model.

OBJECTIVES: To develop effective nomograms for predicting pneumothorax and delayed pneumothorax after microwave ablation (MWA) in lung malignancy (LM) patients. METHODS: LM patients treated with MWA were randomly allocated to a training or validation cohort at a ratio of 7:3. The predictors of pneumothorax identified by univariate and multivariate analyses in the training cohort were used to develop a predictive nomogram. The C-statistic was used to evaluate predictive accuracy in both cohorts. A second nomogram for predicting delayed pneumothorax was developed and validated using identical methods. RESULTS: A total of 552 patients (training cohort: n = 402; validation cohort: n = 150) were included; of these patients, 27.9% (154/552) developed pneumothorax, with immediate and delayed pneumothorax occurring in 18.8% (104/552) and 9.1% (50/552), respectively. The predictors selected for the nomogram of pneumothorax were emphysema (hazard ratio [HR], 6.543; p < .001), history of lung ablation (HR, 7.841; p= .025), number of pleural punctures (HR, 1.416; p < .050), ablation zone encompassing pleura (HR, 10.225; p < .001) and pulmonary fissure traversed by needle (HR, 10.776; p < .001). The C-statistics showed good predictive performance in the training and validation cohorts (0.792 and 0.832, respectively). Another nomogram for delayed pneumothorax was developed based on emphysema (HR, 2.952; p= .005), ablation zone encompassing pleura (HR, 4.915; p < .001) and pulmonary fissure traversed by needle (HR, 4.348; p = .015). The C-statistics showed good predictive performance in the training cohort, and it had efficacy for prediction in the validation cohort (0.719 and 0.689, respectively). CONCLUSIONS: The nomograms could effectively predict the risk of pneumothorax and delayed pneumothorax after MWA.

Risk prediction of pleural effusion in lung malignancy patients treated with CT-guided percutaneous microwave ablation: a nomogram and artificial neural network model.

OBJECTIVES: To develop an effective nomogram and artificial neural network (ANN) model for predicting pleural effusion after percutaneous microwave ablation (MWA) in lung malignancy (LM) patients. METHODS: LM patients treated with MWA were randomly allocated to either the training cohort or the validation cohort (7:3). The predictors of pleural effusion identified by univariable and multivariable analyses in the training cohort were used to develop a nomogram and ANN model. The C-statistic was used to evaluate the predictive accuracy in both the training and validation cohorts. RESULTS: A total of 496 patients (training cohort: n = 357; validation cohort: n = 139) were enrolled in this study. The predictors selected into the nomogram for pleural effusion included the maximum power (hazard ratio [HR], 1.060; 95% confidence interval [CI], 1.022-1.100, p = 0.002), the number of pleural punctures (HR, 2.280; 95% CI, 1.103-4.722; p = 0.026) and the minimum distance from needle to pleura (HR, 0.840; 95% CI, 0.775-0.899; p < 0.001). The C-statistic showed good predictive performance in both cohorts, with a C-statistic of 0.866 (95% CI, 0.787-0.945) internally and 0.782 (95% CI, 0.644-0.920) externally (training cohort and validation cohort, respectively). The optimal cutoff value for the risk of pleural effusion was 0.16. CONCLUSIONS: Maximum power, number of pleural punctures and minimum distance from needle to pleura were predictors of pleural effusion after MWA in LM patients. The nomogram and ANN model could effectively predict the risk of pleural effusion after MWA. Patients showing a high risk (>0.16) on the nomogram should be monitored for pleural effusion.

Local progression after computed tomography-guided microwave ablation in non-small cell lung cancer patients: prediction using a nomogram model.

OBJECTIVES: To develop an effective nomogram model for predicting the local progression after computed tomography-guided microwave ablation (MWA) in non-small cell lung cancer (NSCLC) patients. METHODS: NSCLC patients treated with MWA were randomly allocated to either the training cohort or the validation cohort (4:1). The predictors of local progression identified by univariable and multivariable analyses in the training cohort were used to develop a nomogram model. The C-statistic was used to evaluate the predictive accuracy in both the training and validation cohorts. RESULTS: A total of 304 patients (training cohort: n = 250; validation cohort: n = 54) were included in this study. The predictors selected into the nomogram for local progression included the tumor subtypes (odds ratio [OR], 2.494; 95% confidence interval [CI], 1.415-4.396, p = 0.002), vessels ≥3 mm in direct contact with tumor (OR, 2.750; 95% CI, 1.263-5.988; p = 0.011), tumor diameter (OR, 2.252; 95% CI, 1.034-4.903; p = 0.041) and location (OR, 2.442; 95% CI, 1.201-4.965; p = 0.014). The C-statistic showed good predictive performance in both cohorts, with a C-statistic of 0.777 (95% CI, 0.707-0.848) internally and 0.712 (95% CI, 0.570-0.855) externally (training cohort and validation cohort, respectively). The optimal cutoff value for the risk of local progression was 0.39. CONCLUSIONS: Tumor subtypes, vessels ≥3 mm in direct contact with the tumor, tumor diameter and location were predictors of local progression after MWA in NSCLC patients. The nomogram model could effectively predict the risk of local progression after MWA. Patients showing a high risk (>0.39) on the nomogram should be monitored for local progression.

Cryoablation, high-intensity focused ultrasound, irreversible electroporation, and vascular-targeted photodynamic therapy for prostate cancer: a systemic review and meta-analysis.

Cryoablation (CA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) have been evaluated as novel strategies for selected patients with prostate cancer (PCa). We aim to determine the current status of literature regarding the clinical outcomes among these minimally invasive therapies. A systematic search of PubMed, EMBASE, and the Cochrane Library for all English literature published from January 2001 to December 2019 was conducted to identify studies evaluating outcomes of CA, HIFU, IRE or VTP on PCa. Proportionality with 95% confidence intervals (CIs) was performed using STATA version 14.0. 56 studies consisting of 7383 participants were found to report data of interest and fulfilled the inclusion criteria in the final meta-analysis. The pooled proportions of positive biopsy after procedure were 20.0%, 24.3%, 24.2%, and 36.2% in CA, HIFU, IRE and VTP, respectively. The pooled proportions of BRFS were 75.7% for CA and 74.4% for HIFU. The pooled proportions of CSS were 96.1%, 98.2%, and 97.9% for CA, HIFU, and IRE, respectively. The pooled proportions of OS were 92.8% for CA and 85.2% for HIFU. The pooled proportions of FFS were 64.7%, 90.4%, and 76.7% for CA, IRE and VTP, respectively. The pooled proportions of MFS were 92.8% for HIFU and 99.1% for IRE. This meta-analysis shows that CA, HIFU, IRE, and VTP are promising therapies for PCa patients with similar clinical outcomes. However, further larger, well-designed randomized controlled trials are required to confirm this assertion.

Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is the key predictor of EGFR tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC). We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations. METHODS: A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system (ARMS). We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate (ORR), disease control rate (DCR) and progression free survival (PFS). RESULTS: Of all patients, EGFR mutation rate was 28.6% (60/210) by direct sequencing and 45.2% (95/210) by ARMS (P<0.001) respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR (48.0% vs. 80.9%, P=0.004) and shorter median PFS (7.4 vs. 10.5 months, P=0.009) as compared with that of EGFR mutation positive patients by both detection methods. CONCLUSIONS: Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.

Accurate Early Detection and EGFR Mutation Status Prediction of Lung Cancer Using Plasma cfDNA Coverage Patterns: A Proof-of-Concept Study.

Lung cancer is a major global health concern with a low survival rate, often due to late-stage diagnosis. Liquid biopsy offers a non-invasive approach to cancer detection and monitoring, utilizing various features of circulating cell-free DNA (cfDNA). In this study, we established two models based on cfDNA coverage patterns at the transcription start sites (TSSs) from 6X whole-genome sequencing: an Early Cancer Screening Model and an EGFR mutation status prediction model. The Early Cancer Screening Model showed encouraging prediction ability, especially for early-stage lung cancer. The EGFR mutation status prediction model exhibited high accuracy in distinguishing between EGFR-positive and wild-type cases. Additionally, cfDNA coverage patterns at TSSs also reflect gene expression patterns at the pathway level in lung cancer patients. These findings demonstrate the potential applications of cfDNA coverage patterns at TSSs in early cancer screening and in cancer subtyping.

Maintenance treatment of immunotherapy after microwave ablation plus drug-eluting bead bronchial arterial chemoembolization for advanced non-small cell lung cancer: a retrospective single-center cohort study.

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

Standard treatment-refractory/ineligible small cell lung cancer treated with drug-eluting beads bronchial arterial chemoembolization: a retrospective cohort study.

Background: Patients with small cell lung cancer (SCLC) are prone to developing refractoriness to standard treatment, and some patients are ineligible for systemic therapy owing to comorbidities or poor pulmonary function. The prognosis of patient with standard treatment-refractory/ineligible (STRI)-SCLC remains poor. This retrospective cohort study aimed to investigate the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for the treatment of SRTI-SCLC and to identify the predictors of overall survival (OS). Methods: A total of 18 patients with STRI-SCLC who received DEB-BACE were included. Treatment response, adverse events, progression-free survival (PFS), and OS were evaluated. Further molecular targeted therapy or immunotherapy was administered as a second-line treatment or beyond for those patients who had not received these regimens previously. Univariate and multivariate Cox analyses were used to explore the predictors of OS for STRI-SCLC treated with DEB-BACE. Results: The overall disease control rate at 3 months after DEB-BACE was 77.8% (14/18); of these patients who experienced disease control, partial response and stable disease were achieved in 2 patients (11.1%) and 12 patients (66.7%), respectively. There were 7 patients (38.9%) who received anlotinib after DEB-BACE. No severe DEB-BACE-related or anlotinib-related adverse events were observed. The median PFS was 5.0 months; the 6- and 12-month PFS rates were 55.6% (10/18) and 11.1% (2/18), respectively. The median OS was 9.0 months; the 6- and 12-month OS rates were 77.8% (14/18) and 33.3% (6/18), respectively. Postoperative anlotinib [hazard ratio: 0.302; 95% confidence interval (CI): 0.098-0.930; P=0.037] was identified as the predictor of OS in patients with STRI-SCLC treated with DEB-BACE. Conclusions: DEB-BACE is an effective and well-tolerated approach for patients with STRI-SCLC. Postoperative anlotinib is the predictor of OS and may indicate a better prognosis for patients with STRI-SCLC.