The Impact of Surgical Technique on Circulating Tumor DNA in Stage I-III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This clinical trial compares the effect of pulmonary vein-first surgical technique to pulmonary artery-first surgical technique in decreasing circulating tumor cell deoxyribonucleic acid (ctDNA) in patients with stage I-III non-small cell lung cancer. Pulmonary vein first and pulmonary artery first surgical techniques are standard surgical techniques for the division of the blood vessels during lung resection surgery. Pulmonary vein-first surgical technique may reduce the risk of shedding tumor cells during surgery and influence long term overall survival.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the association between sequence of surgical resection and postoperative ctDNA levels at specified time points. SECONDARY OBJECTIVE: I. To determine the associated between sequence of surgical resection and postoperative ctDNA level and clinical oncologic outcomes. II. To assess disease-free survival and the role of circulating tumor DNA in disease recurrence in patients with resectable non-small cell lung cancer. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients undergo pulmonary vein first approach surgical procedure on day of surgery. GROUP II: Patients undergo pulmonary artery first approach surgical procedure on day of surgery. After completion of surgery, patients are followed up at day 1, day 7, days 7-28, 4 months, every 6 months for 2 years, then every 6 months for up to 5 years

Official Title
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The Impact of Surgical Technique on Circulating Tumor DNA in Early-Stage Non-Small Cell Lung Cancer

Conditions
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Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8

Intervention / Treatment
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* Procedure: Pulmonary Artery-First Surgical Technique
* Procedure: Biospecimen Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patients 18 years of age or older with confirmed or suspected early-stage (stage I-III) NSCLC Eligible and scheduled for surgical anatomic lung resection (e.g. lobectomy or segmentectomy) as routine clinical care for their disease Exclusion Criteria: Previous cancer diagnosis within 5 years (except ductal carcinoma in situ [DCIS] of the breast, superficial bladder cancer, non-melanoma skin primary, other malignancy that does not require treatment). Preoperative chemotherapy, immunotherapy, or radiation therapy Receipt of perioperative blood transfusion

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I (pulmonary vein first approach procedure)<br>Patients undergo pulmonary vein first approach surgical procedure on day of surgery. | Procedure: Pulmonary Artery-First Surgical Technique<br>* Undergo pulmonary artery first surgical technique<br>* Other names: Artery-First Ligation;|
| Active Comparator: Group II (pulmonary artery first surgical procedure)<br>Patients undergo pulmonary artery first approach surgical procedure on day of surgery. | Procedure: Biospecimen Collection<br>* Correlative studies<br>* Other names: Specimen Collection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating tumor deoxyribonucleic acid (ctDNA) status | Stratified by surgical vascular division technique. A peripheral blood sample will be taken at the time of surgery to determine baseline ctDNA status. Following surgical resection a blood sample will be taken at specified time points (postoperative day 2; postoperative day 14) to determine ctDNA levels compared to baseline. The difference in the proportion of patients who have positive ctDNA status between those undergoing division/ligation in a pulmonary-vein first technique compared to a pulmonary-artery first technique will be estimated. The risk difference will be estimated along with a 95% confidence interval. | At postoperative day 2 | 
| Circulating tumor deoxyribonucleic acid (ctDNA) status | Stratified by surgical vascular division technique. A peripheral blood sample will be taken at the time of surgery to determine baseline ctDNA status. Following surgical resection a blood sample will be taken at specified time points (postoperative day 2; postoperative day 14) to determine ctDNA levels compared to baseline. The difference in the proportion of patients who have positive ctDNA status between those undergoing division/ligation in a pulmonary-vein first technique compared to a pulmonary-artery first technique will be estimated. The risk difference will be estimated along with a 95% confidence interval. | At postoperative day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival rate | The distribution of survival outcomes will be estimated using the Kaplan-Meier method, stratified by ctDNA status at 2 days and 2 weeks. Key statistics (median survival, 1- and 2-year survival) will be estimated from the curve along with 95% confidence intervals. We will also use a Cox proportional hazard regression model, stratified by stage in the analyses, to estimate the hazard ratio along with a 95% confidence interval. | Up to 5 years | 
| Overall survival rate | The distribution of survival outcomes will be estimated using the Kaplan-Meier method, stratified by ctDNA status at 2 days and 2 weeks. Key statistics (median survival, 1- and 2-year survival) will be estimated from the curve along with 95% confidence intervals. We will also use a Cox proportional hazard regression model, stratified by stage in the analyses, to estimate the hazard ratio along with a 95% confidence interval. | Up to 5 years |