Purpose: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non–small cell lung cancer (NSCLC). Experimental Design: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I–III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. Results: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). Conclusions: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.

IMPORTANCEIt is important to develop a surgical technique to reduce dissemination of tumor cells into the blood during surgery.OBJECTIVE To compare the outcomes of different sequences of vessel ligation during surgery on the dissemination of tumor cells and survival in patients with non-small cell lung cancer. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, randomized clinical trial was conducted from December 2016 to March 2018 with patients with non-small cell lung cancer who received thoracoscopic lobectomy in West China Hospital, Daping Hospital, and Sichuan Cancer Hospital. To further compare survival outcomes of the 2 procedures, we reviewed the Western China Lung Cancer database (2005-2017) using the same inclusion criteria.INTERVENTIONS Vein-first procedure vs artery-first procedure. MAIN OUTCOMES AND MEASURESChanges in folate receptor-positive circulating tumor cells (FR + CTCs) after surgery and 5-year overall, disease-free, and lung cancer-specific survival.RESULTS A total of 86 individuals were randomized; 22 patients (25.6%) were younger and 64 (74.4%) older than 60 years. Of these, 78 patients were analyzed. After surgery, an incremental change in FR + CTCs was observed in 26 of 40 patients (65.0%) in the artery-first group and 12 of 38 (31.6%) in the vein-first group (P = .003) (median change, 0.73 [interquartile range (IQR), −0.86 to 1.58] FU per 3 mL vs −0.50 [IQR, −2.53 to 0.79] FU per 3 mL; P = .006). Multivariate analysis confirmed that the artery-first procedure was a risk factor for FR + CTC increase during surgery (hazard ratio [HR], 4.03 [95% CI,]; P = .005). The propensity-matched analysis included 420 patients (210 with vein-first procedures and 210 with artery-first procedures). The vein-first group had significantly better outcomes than the artery-first group for 5-year overall survival (73.6% [95% CI, 64.4%-82.8%] vs 57.6% [95% CI, 48.4%-66.8%]; P = .002), disease-free survival (63.6% [95% CI, 55.4%-73.8%] vs 48.4% [95% CI, 40.0%-56.8%]; P = .001), and lung cancer-specific survival (76.4% [95% CI, 67.6%-85.2%] vs 59.9% [95% CI, 50.5%-69.3%]; P = .002). Multivariate analyses revealed that the artery-first procedure was a prognostic factor of poorer 5-year overall survival (HR, 1.65 [95% CI, 1.07-2.56]; P = .03), disease-free survival (HR, 1.43 [95% CI, 1.01-2.04]; P = .05) and lung cancer-specific survival (HR = 1.65 [95% CI, 1.04-2.61]; P = .03). CONCLUSIONS AND RELEVANCELigating effluent veins first during surgery may reduce tumor cell dissemination and improve survival outcomes in patients with non-small cell lung cancer.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03436329

BackgroundMassive bleeding caused by vascular injury is considered the most troublesome and dangerous complication during video-assisted thoracoscopic surgery (VATS) pulmonary resection and is an important reason for emergency conversion to thoracotomy. The purpose of this paper was to show the suction-compressing angiorrhaphy technique (SCAT) for troubleshooting this problem without conversion.MethodsA total of 414 consecutive VATS anatomic pulmonary resections were performed between May 2006 and July 2011, among which 17 operations (4.11 %) encountered unexpected vascular injury. The procedure for troubleshooting vascular injury included bleeding control and angiorrhaphy. Bleeding was first controlled through side compression of the injured site with an endoscopic suction. Angiorrhaphy was then performed with running 5-0 Prolene suture using different procedures according to the size and location of the injuries, including direct suture upon suction compression, suture after substituting suction compression with clamping of the injured site, or suture after attaining proximal cross-clamping of the main pulmonary artery. Detailed information of these patients was carefully reviewed. The reasons for conversion to thoracotomy also were revealed.ResultsFifteen cases (15/17, 88.24 %) were successfully managed without conversion. Two cases of left main pulmonary artery injury were converted to thoracotomy due to difficulties in proximal cross-clamping of the injured vessel. Blood loss of the 17 patients ranged from 60–935 (median, 350) ml. Two patients were administered with allogeneic blood. The postoperative chest CT scan showed normal blood flow on the injured vessels. The total conversion rate was 2.66 % (11/414). The most common reason for conversion was hilar lymphadenopathy.ConclusionsThe SCAT is an effective procedure for managing vascular injury during VATS anatomic pulmonary resection. In most cases, bleeding control and angiorrhaphy could be achieved using this method with acceptable blood loss, thereby avoiding emergency conversion to thoracotomy.