Clinical application of CTC detection in the adjuvant diagnosis of early-stage tumours

Malignant tumors are one of the major killers affecting human health. In addition to the increasing morbidity rate year by year, the low rate of early diagnosis of malignant tumors is also a key factor affecting the survival of patients. Research shows that the 5-year survival rate of early-stage tumor patients is significantly higher than that of late-stage tumor patients, while most of the tumor patients are already in advanced stage when they are diagnosed at the first stage, losing the best chance of treatment.

Therefore, early diagnosis and treatment of tumors is decisive for improving the overall prognosis of patients. Circulating tumor cells (CTC), as a novel tumor marker, exists in the blood of patients with early-stage tumors, and its detection is non-invasive, convenient, and repeatable, which plays an important role in the early auxiliary diagnosis of tumors.

一、Interpretation of Clinical Literature on CTC and Early Tumor Auxiliary Diagnosis

Literature 1: Diagnostic efficacy of circulating blood tumor cells combined with CT in the nature of small nodular lung lesions

Journal Article：Chinese Contemporary Medicine

Unit：Shenzhen Baoan District Central Hospital

Objective: To investigate the diagnostic efficacy of circulating tumor cells (CTC) combined with CT in the nature of pulmonary nodular lesions.

Subjects: 82 patients with suspected pulmonary nodular lesions.

CTC detection: CTC was separated and enriched by CTCBIOPSY system.?

Using histopathological examination as the "gold standard", the diagnosis rate of pulmonary nodular lesions was 74.39% (61/82), of which 16 were benign nodules and 45 were malignant nodules; of these, CT examination confirmed the diagnosis of pulmonary nodular lesions in 50 cases, of which 15 were benign nodules and 35 were malignant nodules (Table 1);

CTC examination confirmed the diagnosis of small nodular lesions in the lungs in 54 cases, 16 benign nodules and 38 malignant nodules (Table 2);

CTC combined with CT examination confirmed the diagnosis of small nodular lesions in the lungs in 57 cases, 20 benign nodules and 37 malignant nodules (Table 3);

The accuracy of CTC combined with CT examination in confirming the diagnosis of pulmonary nodular lesions was 85.37% (P<0.05), the diagnostic sensitivity was 86.89% (53/61), the specificity was 80.95% (17/21), the positive predictive value was 92.98% (53/57), and the negative predictive value was 68% (17/25), with an AUC of 0.894 (Table 4, Figure 1).

?Conclusion:

CTC has a high detection rate in small nodular lung lesions, which is more accurate than CT imaging results, and the combined examination of the two can improve the diagnostic efficacy and provide a reference basis for clinical diagnosis and treatment.

Literature 2: Exploring the role of peripheral blood CTC count in screening and diagnosis of benign and malignant pulmonary nodules

Journal Published: Proceedings of the 2021 China Tumor Marker Conference and the 15th Tumor Marker Young Scientist Forum

Unit：Shenzhen Baoan District Central Hospital

Objective: To explore the role of CTC counting in the benign and malignant screening diagnosis of pulmonary nodular lesions.

Subjects: 27 patients with lung nodules detected by low-dose spiral CT and no malignant tumors of other organs found on physical examination.

CTC detection: CTC isolation and enrichment was performed using the CTCBIOPSY system, and cytomorphology was used to identify CTCs and CTM (circulating tumor microemboli).

Findings:

Sputum and alveolar lavage cytology, biopsy or histopathologic findings of single-port thoracoscopic surgical resection were used as the gold standard validation. The results showed that CTC/CTM was detected in 14 cases, of which 13 were pathologically confirmed to be malignant, and CTC/CTM was not detected (including suspects) in a total of 13 cases, of which 1 was pathologically confirmed to be malignant. Analysis showed that the sensitivity of determining the benign or malignant nature of lung nodules by CTC count was 92.86% and the specificity was 92.30%. (Specific CTC/CTM detection and pathologic verification were as follows)

● 4 cases with undetected CTC/CTM, all without positive case finding and without progression on CT follow-up for 15-21 months;

● 8 cases of suspected CTC, of which 1 case was pathologically confirmed carcinoma in situ with microinfiltration, and the remaining 7 cases had no pathologically confirmed lung cancer;

● 1 case of suspected CTM with a proposed clinical diagnosis of peripheral lung cancer bone metastasis without pathologic confirmation;

● 14 cases with detected CTC/CTM, of which 12 cases were pathologically confirmed as lung cancer and 2 cases were not pathologically confirmed;

Research Conclusion:

The sensitivity and specificity of peripheral blood CTC count in screening benign and malignant lesions of lung nodules are high, and its application as a marker for early screening of lung cancer has a high prospect.

二、Introduction of expert consensus on the application of CTC and early tumor auxiliary diagnosis

With the accumulation of CTC-related clinical research, more and more clinical expert consensus recommends that CTC detection has an important role in early cancer diagnosis. At present, the clinical expert consensus of lung cancer, liver cancer, colorectal cancer and pancreatic cancer has incorporated CTC as an indicator for early tumor auxiliary diagnosis.

CTC applied in early tumor auxiliary diagnosis for the applicable population

The application of CTC in early tumor auxiliary diagnosis is not for all healthy people, but for patients with abnormal occupying foci, such as lung nodules, breast nodules, gastrointestinal polyps, ovarian cysts, hepatic hemangiomas, and thyroid nodules, etc., and patients with urgent needs for benign and malignant auxiliary diagnosis of high-risk foci. When the abnormal space-occupying lesions in the body are relatively small, such as small lung nodules with a diameter of less than 10 mm, according to the latest Chinese Expert Consensus on Early-Stage Lung Cancer Diagnosis (2023 Edition), transcoronary lung puncture biopsy should be used mainly for the puncture and biopsy of peripheral lung lesions, especially peripheral lung nodules, and the expert panel does not recommend its use for intrapulmonary nodules with a diameter of <10 mm.

For the difficulty of using invasive biopsy for benign and malignant determination, short-term follow-up observation is often performed according to different risk levels. During the follow-up process, some patients' nodules may increase in size or show a high risk of malignancy such as lobulation, burr and pleural depression signs, and some patients may miss the opportunity for early intervention. By collecting peripheral blood to detect CTC, combined with CT examination to confirm the benign and malignant nature of lung nodules, it is possible to screen out patients with high-risk lung nodules, and then clinicians can carry out early interventions (surgery, radiotherapy, interventional therapy, etc.), which can ultimately improve the cure rate and survival of patients with malignant tumors.

Introduction of the process of CTC test for early tumor auxiliary diagnosis

CTCBIOPSY system has accumulated tens of thousands of clinical test data through 8 years of clinical application in more than 100 large tertiary hospitals, and has established the process of CTC detection for early tumor auxiliary diagnosis

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References:

[1] Chuan-Bin Xu,Ling Bai,Zedi Huang,et al. Diagnostic efficacy of circulating blood tumor cells combined with CT in the nature of pulmonary nodule lesions[J]. China Contemporary Medicine, 2022, 29(26):4.

[2] BAI Ling;XU Chuanbin;WU Chun,et al. Exploring the role of peripheral blood CTC counts in the diagnosis of benign and malignant screening of lung nodules[J].Proceedings of the 2021 China Tumor Marker Academic Conference and the Fifteenth Tumor Marker Young Scientist Forum.

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