Application of Detecting Circulating Tumor Cells in the Accurate Treatment of Early Stage Lung Adenocarcinoma

Study Overview
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Brief Summary
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In 2015-2016, 224,390 cases were newly diagnosed with lung cancer in USA. Of all the cases, 83% are non-small cell lung cancer (NSCLC). Currently, the 5-year survival rate of NSCLC patients is 21%, and more than 25% of early stage NSCLC patients, who have undergone surgical treatment, will have a relapse or progression. Circulating tumor cells (CTCs), which shed from the primary tumor into the vasculature or lymphatics, can be regarded as a new prognostic factors of metastatic process. Thus far, CTCs-detection technologies can be divided into epithelial cell adhesion molecule (EpCAM)-based detection methods, e.g., the widely used CellSearch® and Adnatest®,and EpCAM-independent detection methods, e.g., ISET® and ScreenCell®. Herein, the investigators used a newly established approach, i.e., CanPatrolTM to detect CTCs in early stage lung Adenocarcinoma cases. The investigator aim to explore whether CTCs detection prior to surgery can be contributive to the early diagnosis, or may help to predict the prognosis and guide the treatment strategy of early stage lung Adenocarcinoma.

Official Title
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Application of Detecting Circulating Tumor Cells in the Accurate Diagnosis and Treatment of Early Stage Lung Adenocarcinoma

Conditions
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Lung Adenocarcinoma, Stage I, Diagnoses Diseases, Circulating Tumor Cells, Treatment

Intervention / Treatment
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* Procedure: lobectomy
* Procedure: segmentecomy
* Drug: chemotherapy（pemetrexed+CISPLATIN）
* Procedure: Lymphadenectomy
* Other: CanPatrolTM to detect CTCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stage I lung adenocarcinoma Exclusion Criteria: cases with any new adjuvant treatment prior to surgery

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IA-CTC-High-enhance<br>IA lung adenocarcinoma cases with high abundant CTCs prior to operation will undergo lobectomy&lymphadenectomy plus adjuvant chemotherapy. Postoperative CTC monitoring will be conducted. | Procedure: lobectomy<br> <br> Drug: chemotherapy（pemetrexed+CISPLATIN）<br> <br> Procedure: Lymphadenectomy<br>* Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.<br>Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|
| Placebo Comparator: IA-CTC-High-controls<br>IA lung adenocarcinoma cases with high abundant CTCs prior to operation will only undergo lobectomy&lymphadenectomy. Postoperative CTC monitoring will be conducted. | Procedure: lobectomy<br> <br> Procedure: Lymphadenectomy<br>* Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.<br>Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|
| Placebo Comparator: IA-CTC-low-controls<br>IA lung adenocarcinoma cases with low abundant CTCs prior to operation will only undergo segmentectomy. Postoperative CTC monitoring will be conducted. | Procedure: segmentecomy<br> <br> Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|
| Active Comparator: IB-CTC-High-enhance<br>IB lung adenocarcinoma cases with high abundant CTCs prior to operation will undergo lobectomy&lymphadenectomy plus adjuvant chemotherapy. Postoperative CTC monitoring will be conducted. | Procedure: lobectomy<br> <br> Drug: chemotherapy（pemetrexed+CISPLATIN）<br> <br> Procedure: Lymphadenectomy<br>* Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.<br>Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|
| Placebo Comparator: IB-CTC-High-controls<br>IB lung adenocarcinoma cases with high abundant CTCs prior to operation will undergo lobectomy&lymphadenectomy. Postoperative CTC monitoring will be conducted. | Procedure: lobectomy<br> <br> Procedure: Lymphadenectomy<br>* Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.<br>Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|
| Placebo Comparator: IB-CTC-low-controls<br>IB lung adenocarcinoma cases with low abundant CTCs prior to operation will undergo lobectomy&lymphadenectomy. Postoperative CTC monitoring will be conducted. | Procedure: lobectomy<br> <br> Procedure: Lymphadenectomy<br>* Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.<br>Other: CanPatrolTM to detect CTCs<br>* CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-μm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | From date of diagnosis until the date of first documented progression or date of cancer related death , whichever came first, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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circulating tumor cells, lung adenocarcinoma, treatment, early diagnosis