Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

Abstract

Background: The role of circulating tumor cells (CTCs) for predicting the recurrence of cancer in lung cancer patients after surgery remains unclear. Methods: A negatively selected protocol of CTC identification was applied. For all the enrolled patients, CTC testing was performed before and after surgery on the operation day (day 0), postoperative day 1, and day 3. The daily decline and trend of CTCs were analyzed to correlate with cancer relapse. The mixed model repeated measures (MMRM) adjusted by cancer characteristics was applied for statistical significance. Results: Fifty patients with lung mass undergoing surgery were enrolled. Among 41 primary lung cancers, 26 (63.4%) were pathological stage Tis and I. A total of 200 CTC tests were performed. MMRM analysis indicated that surgery could contribute to a CTC decline after surgery in all patients with statistical significance (p = 0.0005). The daily decrease of CTCs was statistically different between patients with and without recurrence (p = 0.0068). An early rebound of CTC counts on postoperative days 1 and 3 was associated with recurrence months later. Conclusion: CTC testing can potentially serve as a tool for minimal residual disease detection in early-staged lung cancer after curative surgery.

Liquid Biopsy Analysis of Circulating Tumor Biomarkers in Lung Cancer

“…Increased CTCs in PV were reported to associate with patients' poor prognosis [103,105]. Similar to association of post-surgical hepatocellular carcinoma (HCC) CTCs with cancer relapse [38], detection of CTCs in PV during operation or in post-surgical peripheral blood also enables early detection of lung cancer recurrence, particularly in the post-resected lung cancer patients [37,[106][107][108].…”

The Evolving Concept of Complete Resection in Lung Cancer Surgery

“…However, blood samples are the ones most commonly utilized. The determination of biomarkers in liquid biopsy is useful in early diagnosis of lung cancer [ 64 , 65 ], in monitoring patients and genetic alterations during therapy [ 63 , 66 ], in characterizing molecular tumor profile [ 66 , 67 ], in assessing prognosis [ 68 ] and in detecting minimal residual disease in early stage lung cancer after curative resection [ 69 ]. Regarding the latter, Wu et al determined the circulating tumor cell count before and after resection on the day of surgery, and on postoperative days 1 and 3 in 41 patients with lung cancer, 30 (80%) adenocarcinomas.…”

“…Regarding the latter, Wu et al determined the circulating tumor cell count before and after resection on the day of surgery, and on postoperative days 1 and 3 in 41 patients with lung cancer, 30 (80%) adenocarcinomas. The count dropped on postoperative day 1, but a rise in count on day 3 in 11 patients was associated with recurrence [ 69 ]. Chaudhuri et al determined circulating tumor DNA in 40 patients before and after intended curative treatment with radiotherapy, chemotherapy and/or surgery for stage I to III lung cancer.…”

Liquid biopsies to distinguish malignant from benign pulmonary nodules

“…53 The CTC count has been proven to be a promising biomarker for the diagnosis, prognosis and monitoring of therapeutic response in lung cancer. [54][55][56] The biggest challenge for CTC application in the early detection of cancer is the enrichment of very few CTC cells, which usually exist as single tumor cell in the context of millions of blood cells. 57 The smaller the size of the lesion, the lower the amount of CTCs in the blood, thereby causing low diagnostic sensitivity of CTCs for malignant SPNs.…”