Computed tomography-based 3D convolutional neural network deep learning model for predicting micropapillary or solid growth pattern of invasive lung adenocarcinoma.

PURPOSE: To investigate the value of a computed tomography (CT)-based deep learning (DL) model to predict the presence of micropapillary or solid (M/S) growth pattern in invasive lung adenocarcinoma (ILADC). MATERIALS AND METHODS: From June 2019 to October 2022, 617 patients with ILADC who underwent preoperative chest CT scans in our institution were randomly placed into training and internal validation sets in a 4:1 ratio, and 353 patients with ILADC from another institution were included as an external validation set. Then, a self-paced learning (SPL) 3D Net was used to establish two DL models: model 1 was used to predict the M/S growth pattern in ILADC, and model 2 was used to predict that pattern in ≤ 2-cm-diameter ILADC. RESULTS: For model 1, the training cohort's area under the curve (AUC), accuracy, recall, precision, and F1-score were 0.924, 0.845, 0.851, 0.842, and 0.843; the internal validation cohort's were 0.807, 0.744, 0.756, 0.750, and 0.743; and the external validation cohort's were 0.857, 0.805, 0.804, 0.806, and 0.804, respectively. For model 2, the training cohort's AUC, accuracy, recall, precision, and F1-score were 0.946, 0.858, 0.881,0.844, and 0.851; the internal validation cohort's were 0.869, 0.809, 0.786, 0.794, and 0.790; and the external validation cohort's were 0.831, 0.792, 0.789, 0.790, and 0.790, respectively. The SPL 3D Net model performed better than the ResNet34, ResNet50, ResNeXt50, and DenseNet121 models. CONCLUSION: The CT-based DL model performed well as a noninvasive screening tool capable of reliably detecting and distinguishing the subtypes of ILADC, even in small-sized tumors.

Myeloprotection with trilaciclib in Chinese patients with extensive-stage small cell lung cancer receiving chemotherapy: Results from a randomized, double-blind, placebo-controlled phase III study (TRACES).

INTRODUCTION: Trilaciclib is a transient cyclin-dependent kinase 4/6 inhibitor that decreases the incidence of chemotherapy-induced myelosuppression in extensive-stage small cell lung cancer (ES-SCLC). TRACES study was designed to assess the safety, efficacy and pharmacokinetics (PK) of trilaciclib before chemotherapy in Chinese patients with ES-SCLC. METHODS: The study included an open-label safety run-in part (Part 1) and double-blinded, placebo-controlled part (Part 2) where patients received trilaciclib or placebo before chemotherapy. Treatment-naïve or previously treated ES-SCLC patients received intravenous trilaciclib (240 mg/m2) or placebo before etoposide/carboplatin or topotecan, respectively. Primary endpoints were PK, safety and duration of severe neutropenia (DSN) in Cycle 1 in Part 1 and Part 2. Exploratory endpoints included the effect of trilaciclib on other myeloprotection endpoints, safety and antitumor efficacy. RESULTS: Overall, 95 Chinese patients were enrolled, of which 12 and 83 patients were in Part 1 and Part 2, respectively. In Part 1, trilaciclib was well tolerated. Non-compartmental analysis results revealed no substantial differences in the main exposure parameters. In Part 2, 41 patients received trilaciclib, and 42 received placebo. Patients in trilaciclib arm vs placebo arm had a clinically and statistically significant decrease in DSN (mean [SD]) in Cycle 1 (0 [1.7] vs 2 [3.0] days; P = 0.0003), with improvements in additional neutrophil, red blood cell, and platelet measures. After a median follow-up of 14.1 months, the median overall survival was 12.0 months in trilaciclib arm and 8.8 months in placebo arm (HR, 0.69; 95 % CI: 0.40-1.22). Median progression-free survival was 4.8 months and 4.3 months, respectively (HR, 0.86; 95 % CI: 0.53-1.39). Trilaciclib had a well-tolerated safety profile. CONCLUSIONS: Trilaciclib in the Chinese population demonstrated a similar PK and safety profile as seen in other global trials. There was significant reduction of DSN in Cycle 1, thereby substantiating the myeloprotective effects of trilaciclib in Chinese ES-SCLC patients.

Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial.

This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Eligible patients received unecritinib 100, 200, and 300 mg QD, and 200, 250, 300, and 350 mg BID in a 3 + 3 design during dose escalation and 300 and 350 mg BID during expansion. Phase II trial patients received unecritinib 300 mg BID in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) per independent review committee (IRC). Key secondary endpoints included intracranial ORR and safety. The ORR of 36 efficacy evaluable patients in the phase I trial was 63.9% (95% CI 46.2%, 79.2%). In the phase II trial, 111 eligible patients in the main study cohort received unecritinib. The ORR per IRC was 80.2% (95% CI 71.5%, 87.1%) and the median progression-free survival (PFS) per IRC was 16.5 months (95% CI 10.2, 27.0). Additionally, 46.9% of the patients who received recommended phase II dose of 300 mg BID experienced grade 3 or higher treatment-related adverse events. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC.ClinicalTrials.gov identifier: NCT03019276 and NCT03972189.

Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have MET exon 14 (METex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with METex14 skipping mutation-positive (METex14-positive) NSCLC. Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan. Adults with locally advanced or metastatic METex14-positive NSCLC received oral gumarontinib 300 mg once daily in continuous 21-day cycles until disease progression, intolerable toxicity, or withdrawal of consent. Eligible patients had failed one or two prior lines of therapy (not including a MET inhibitor), were ineligible for/refused chemotherapy, and had no genetic alterations targetable with standard therapies. The primary endpoint was objective response rate in patients with a valid baseline tumour assessment, by blinded independent review. The study was registered at ClinicalTrials.gov (NCT04270591). Findings: Between Aug 2, 2019 and Apr 28, 2021, 84 patients were enrolled and received gumarontinib (median follow-up 13.5 months [IQR 8.7-17.1]), at data cut-off (Apr 28, 2022) five patients whose METex14 status could not be confirmed by a central laboratory were excluded from the efficacy analysis. The objective response rate was 66% (95% CI 54-76) overall (n = 79), 71% (95% CI 55-83) in treatment-naïve patients (n = 44), and 60% (95% CI 42-76) in previously-treated patients (n = 35). The most common treatment-related adverse events (any grade) were oedema (67/84 patients, 80%) and hypoalbuminuria (32/84, 38%). Grade ≥3 treatment-emergent adverse events occurred in 45 (54%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 8% (7/84) of patients. Interpretation: Gumarontinib monotherapy had durable antitumour activity with manageable toxicity in patients with locally advanced or metastatic METex14-positive NSCLC when used in first line or later. Funding: Haihe Biopharma Co., Ltd. Supported in part by grants from the National Science and Technology Major Project of China for "Clinical Research of Gumarontinib, a highly selective MET inhibitor" (2018ZX09711002-011-003); the National Natural Science Foundation of China (82030045 to S.L. and 82172633 to YF.Y); Shanghai Municipal Science & Technology Commission Research Project (19411950500 to S.L.); Shanghai Shenkang Action Plan (16CR3005A to S.L.) and Shanghai Chest Hospital Project of Collaborative Innovation (YJXT20190105 to S.L.).

A CT-based nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodule according to the 2021 WHO classification.

PURPOSE: To establish a nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodules (SSNs) according to the 2021 WHO classification. METHODS: A total of 656 patients who underwent SSNs resection were retrospectively enrolled. Among them, 407 patients were assigned to the derivation cohort and 249 patients were assigned to the validation cohort. Univariate and multi-variate logistic regression algorithms were utilized to identity independent risk factors of adenocarcinomas. A nomogram based on the risk factors was generated to predict the risk of adenocarcinomas. The discrimination ability of the nomogram was evaluated using the concordance index (C-index), its performance was calibrated using a calibration curve, and its clinical significance was evaluated using decision curves and clinical impact curves. RESULTS: Lesion size, mean CT value, vascular change and lobulation were identified as independent risk factors for adenocarcinomas. The C-index of the nomogram was 0.867 (95% CI, 0.833-0.901) in derivation cohort and 0.877 (95% CI, 0.836-0.917) in validation cohort. The calibration curve showed good agreement between the predicted and actual risks. Analysis of the decision curves and clinical impact curves revealed that the nomogram had a high standardized net benefit. CONCLUSIONS: A nomogram for predicting the risk of adenocarcinomas in patients with SSNs was established in light of the 2021 WHO classification. The developed model can be adopted as a pre-operation tool to improve the surgical management of patients.

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.

Importance: Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. Objective: To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. Design, Setting, and Participants: This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Interventions: Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. Main Outcomes and Measures: The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results: Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Conclusions and Relevance: Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT04063163.

Reconstruction-Assisted Feature Encoding Network for Histologic Subtype Classification of Non-Small Cell Lung Cancer.

Accurate histological subtype classification between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using computed tomography (CT) images is of great importance to assist clinicians in determining treatment and therapy plans for non-small cell lung cancer (NSCLC) patients. Although current deep learning approaches have achieved promising progress in this field, they are often difficult to capture efficient tumor representations due to inadequate training data, and in consequence show limited performance. In this study, we propose a novel and effective reconstruction-assisted feature encoding network (RAFENet) for histological subtype classification by leveraging an auxiliary image reconstruction task to enable extra guidance and regularization for enhanced tumor feature representations. Different from existing reconstruction-assisted methods that directly use generalizable features obtained from shared encoder for primary task, a dedicated task-aware encoding module is utilized in RAFENet to perform refinement of generalizable features. Specifically, a cascade of cross-level non-local blocks are introduced to progressively refine generalizable features at different levels with the aid of lower-level task-specific information, which can successfully learn multi-level task-specific features tailored to histological subtype classification. Moreover, in addition to widely adopted pixel-wise reconstruction loss, we introduce a powerful semantic consistency loss function to explicitly supervise the training of RAFENet, which combines both feature consistency loss and prediction consistency loss to ensure semantic invariance during image reconstruction. Extensive experimental results show that RAFENet effectively addresses the difficult issues that cannot be resolved by existing reconstruction-based methods and consistently outperforms other state-of-the-art methods on both public and in-house NSCLC datasets. Supplementary material is available at https://github.com/lhch1994/Rafenet_sup_material.

Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC. METHODS: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m2 of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305. FINDINGS: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death). INTERPRETATION: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population. FUNDING: Jiangsu Hengrui Pharmaceuticals.

AIR-Net: A novel multi-task learning method with auxiliary image reconstruction for predicting EGFR mutation status on CT images of NSCLC patients.

Automated and accurate EGFR mutation status prediction using computed tomography (CT) imagery is of great value for tailoring optimal treatments to non-small cell lung cancer (NSCLC) patients. However, existing deep learning based methods usually adopt a single task learning strategy to design and train EGFR mutation status prediction models with limited training data, which may be insufficient to learn distinguishable representations for promoting prediction performance. In this paper, a novel multi-task learning method named AIR-Net is proposed to precisely predict EGFR mutation status on CT images. First, an auxiliary image reconstruction task is effectively integrated with EGFR mutation status prediction, aiming at providing extra supervision at the training phase. Particularly, we adequately employ multi-level information in a shared encoder to generate more comprehensive representations of tumors. Second, a powerful feature consistency loss is further introduced to constrain semantic consistency of original and reconstructed images, which contributes to enhanced image reconstruction and offers more effective regularization to AIR-Net during training. Performance analysis of AIR-Net indicates that auxiliary image reconstruction plays an essential role in identifying EGFR mutation status. Furthermore, extensive experimental results demonstrate that our method achieves favorable performance against other competitive prediction methods. All the results executed in this study suggest that the effectiveness and superiority of AIR-Net in precisely predicting EGFR mutation status of NSCLC.

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.

Urban-Rural Differences in Clinical Characteristics of Prostate Cancer at Initial Diagnosis: A Single-Center Observational Study in Anhui Province, China.

BACKGROUND: People residing in rural areas have higher prostate cancer (PCa) mortality to incidence ratio (M/I) and worse prognosis than those in urban areas of China. Clinical characteristics at initial diagnosis are significantly associated with biochemical recurrence, overall survival, and PCa disease-free survival. OBJECTIVE: This study aimed at investigating the clinical characteristics at initial diagnosis of urban and rural PCa patients and to establish a logistic regression model for identifying independent predictors for high-grade PCa. MATERIALS AND METHODS: Clinical characteristics for PCa patients were collected from the largest prostate biopsy center in Anhui province, China, from December 2015 to March 2019. First, urban-rural disparities in clinical characteristics were evaluated at initial diagnosis. Second, based on pathological findings, we classified all participants into the benign+ low/intermediate-grade PCa or high-grade PCa groups. Univariate and multivariate logistic regression analyses were performed to identify independent factors for predicting high-grade PCa, while a nomogram for predicting high-grade PCa was generated based on all independent factors. The model was evaluated using area under receiver-operating characteristic (ROC) curve as well as calibration curve analyses and compared to a model without the place of residence factor of individuals. RESULTS: Statistically significant differences were observed between urban and rural PCa patients with regard to tPSA, PSA density (PSAD), and Gleason score (GS) (p < 0.05). Logistic regression analysis revealed that tPSA [OR = 1.060, 95% confidence interval (CI): 1.024, 1.098], PSAD (OR = 14.678, 95%CI: 4.137, 52.071), place of residence of individuals (OR = 5.900, 95%CI: 1.068, 32.601), and prostate imaging reporting and data system version 2 (PI-RADS v2) (OR = 4.360, 95%CI: 1.953, 9.733) were independent predictive factors for high-grade PCa. The area under the curve (AUC) of the nomogram was greater than that of the model without the place of residence of individuals. The calibration curve of the nomogram indicated that the prediction curve was basically fitted to the standard curve, suggesting that the prediction model had a better calibration ability. CONCLUSIONS: Compared to urban PCa patients, rural PCa patients presented elevated tPSA, PSAD levels, and higher pathological grades. The place of residence of the individuals was an independent predictor for high-grade PCa in Anhui Province, China. Therefore, appropriate strategies, such as narrowing urban-rural gaps in access to health care and increasing awareness on the importance of early detection should be implemented to reduce PCa mortality rates.

Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706).

INTRODUCTION: Blocking vascular endothelial growth factor pathway can enhance the efficacy of EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC. ACTIVE is the first phase 3 study conducted in the People's Republic of China evaluating apatinib, a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, plus gefitinib as first-line therapy in EGFR-mutant NSCLC. METHODS: Treatment-naive patients with stage IIIB or IV nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and EGFR exon 19 deletion or exon 21 L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/d), plus apatinib (500 mg/d; apatinib [A] + gefitinib [G] group), or placebo (placebo [P] + gefitinib [G] group). Stratification factors were mutation type, sex, and performance status. The primary end point was progression-free survival (PFS) by blinded independent radiology review committee (IRRC). Secondary end points were investigator-assessed PFS, overall survival, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance. RESULTS: A total of 313 patients were assigned to the A + G (n = 157) or P + G group (n = 156). Median IRRC PFS in the A + G group was 13.7 months versus 10.2 months in the P + G group (hazard ratio 0.71, p = 0.0189). Investigator- and IRRC-assessed PFS were similar. Overall survival was immature. The most common treatment-emergent adverse events greater than or equal to grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A + G group and increased alanine aminotransferase (10.4%) and aspartate aminotransferase (3.2%) in the P + G group. QoL in the two groups had no statistical differences. Post hoc analysis revealed PFS benefits tended to favor the A + G group in patients with TP53 exon 8 mutation. CONCLUSIONS: Apatinib + gefitinib as first-line therapy had superior PFS in advanced EGFR-mutant NSCLC versus placebo + gefitinib. Combination therapy brought more adverse events but did not interfere QoL. TRIAL REGISTRATION: NCT02824458.

Association between p73 G4C14-to-A4T14 polymorphism and lung cancer risk: A systematic review and meta-analysis.

OBJECTIVE: This study was conducted to evaluate the relationship between the p73 G4C14-to-A4T14 polymorphism (hereafter, G4C14-to-A4T14) and lung cancer risk. METHODS: The studies on the relationship between G4C14-A4T14 and lung cancer risk published as of November 5, 2018, were comprehensively searched in PubMed, Embase, the Cochrane Library, the Chinese Wanfang database, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM). The last update was on May 24, 2019. Statistical analysis was performed using Stata 12.0. RESULTS: The association between G4C14-A4T14 and lung cancer risk was analyzed in nine studies. The findings indicate no association between G4C14-to-A4T14 and lung cancer risk (allele model: OR = 0.90, 95% CI: 0.73-1.11, I2  = 86.0%, P = .330; dominant model: OR = 0.93, 95% CI: 0.74-1.17, I2  = 82.6%, P = .551; recessive model: OR = 0.75, 95% CI: 0.50-1.13, I2  = 75.2%, P = .165; homozygote model: OR = 0.74, 95% CI: 0.47-1.17, I2  = 79.6%, P = .199; heterozygote model: OR = 0.98, 95% CI: 0.80-1.21, I2  = 75.8%, P = .879). The heterogeneity between subgroups by cancer types and genotyping method was significantly reduced. After the deletion of suspected duplicates, no association was found between G4C14-to-A4T14 and lung cancer susceptibility. CONCLUSION: Our meta-analysis confirms that G4C14-to-A4T14 is not significantly related to lung cancer risk.

Diagnostic Value of Video-assisted Mediastinoscopy and Endobronchial Ultrasound-guided Transbronchial Needle Aspiration for Mediastinal Lymphadenectasis without Pulmonary Abnormalities.

BACKGROUND Mediastinal diseases are difficult to diagnose due to diverse origins and complex anatomical structure of the mediastinal tissues. The prospective study aimed to compare the diagnostic efficiency of video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions without pulmonary abnormalities. MATERIAL AND METHODS We divided 100 mediastinal lymphadenectasis patients without pulmonary abnormalities into a VAM group and an EBUS group. The pathological results of each group were regarded as the endpoints. SPSS19.0 statistical software was used. RESULTS The diagnostic accuracy, sensitivity, and specificity of VAM were 96%, 97.4%, and 100%, respectively; those of EBUS-TBNA diagnosis were 62%, 87.1%, and 100%, respectively. There was a statistically significant difference in the diagnostic sensitivity of benign mediastinal lesions between the 2 groups (P<0.01). Compared with the EBUS group (62%), the accuracy in the VAM group was significantly higher (96%) (P<0.01). CONCLUSIONS We found that the diagnostic accuracy of VAM for mediastinal lymphadenectasis without pulmonary abnormalities is superior to that of EBUS. Therefore, for patients with mediastinal lymphadenectasis or mediastinal mass and without pulmonary abnormalities, mediastinoscopy is recommended as the first choice.