Circulating Tumor Cells from Surgical Manipulation Predict Recurrence and Poor Prognosis in Non-Small Cell Lung Cancer

Background/Objectives: In our previous multicenter prospective controlled study (UMIN000018602), we investigated the impact of surgical manipulation on circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). CTCs were detected after surgery in four patients (4/29, 13.8%), although CTCs were not present before surgery. These four patients had tumor cells leaked into their bloodstream by surgeons’ manipulation. We aimed to clarify long-term outcomes according to the presence of CTCs.
Methods: Patients with cT1b-2N0M0 NSCLC scheduled for lobectomy were enrolled, based on the selection criteria of a consolidation-to-ground-glass opacity ratio (over 50%). Peripheral blood samples (≥3 mL) were collected before surgery (for pre-CTCs), during surgery, and immediately after pulmonary vein dissection (for post-CTCs). CTCs were isolated from these samples using ScreenCell®’s size-selective method.
Results: From July 2015 to January 2016, 29 patients were enrolled, yielding paired pre- and post-CTC samples for all patients. Thirteen patients were pre-CTC positive, and post-CTCs were detected in 17 patients. Survival analysis revealed a statistically significant difference in recurrence-free survival between patients with and without post-CTCs (p = 0.043), while pre-CTCs status had no significant impact on recurrence (p = 0.226). Patients with post-CTCs had a significantly higher recurrence rate than those without (p = 0.043). Half of patients with post-CTCs but without pre-CTCs had recurrence within 5 years after surgery.
Conclusions: Post-CTCs emerged as a significant predictor of recurrence following lobectomy; however, it could be possible for thoracic surgeons to prevent recurrence by improving surgical techniques for NSCLC patients with post-CTCs but without pre-CTCs.
Optimum diagnostic pathway and pathologic confirmation rate of early stage lung cancer: Results from the VIOLET randomised controlled trial

Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial.
Methods: VIOLET compared minimally invasive video-assisted thoracic surgery versus open surgery for known or suspected lung cancer. Diagnostic patient pathways were identified and methods of tissue confirmation were documented. The outcome of inappropriate lobectomy for benign disease or inappropriate wedge resection for primary lung cancer was compared with respect to the pathologic diagnosis.
Findings: From July 2015 to February 2019, 502 patients were randomised and underwent surgery; 262 (52%) had a pre-operative pathologic confirmed diagnosis of primary lung cancer, 205 did not have a pre-operative biopsy and 35 had a non-diagnostic pre-operative biopsy. Of the 240 participants without pre-operative pathologic confirmation of primary lung cancer, intraoperative biopsy and frozen section analysis was undertaken in 144 (60%). The remaining 96 underwent direct surgical resection without tissue confirmation (19% of the entire cohort). Confirmation of histologic diagnosis before surgery was less costly than diagnosis in the operating theatre. The inappropriate surgery rate was 3.6% (18/502 participants, 7 lobectomy for benign disease, 11 wedge resection for lung cancer).
Interpretation: Low levels of inappropriate resection can be achieved at pre-operative tissue confirmation rates of 50% through a combination of intra-operative confirmatory biopsy and correct risk estimation of lung cancer. Practice needs to be monitored to ensure acceptable levels are consistently achieved.
An assessment of diagnostic performance of a filter-based antibody-independent peripheral blood circulating tumour cell capture paired with cytomorphologic criteria for the diagnosis of cancer

Y disruption, autosomal hypomethylation and poor male lung cancer survival.

Cluster circulating tumor cells in surgical cases of lung cancer

Lack of association between Screencell-detected circulating tumour cells and long-term survival of patients undergoing surgery for non-small cell lung cancer: A pilot clinical study.

Prognostic Relevance of Circulating Tumor Cells and Circulating Cell-Free DNA Association in Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab

Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study

Circulating tumor cells and microemboli can differentiate malignant and benign pulmonary lesions

Perioperative detection of circulating tumour cells in patients with lung cancer.
