Segmentectomy Versus Lobectomy for Lung Adenocarcinoma ≤ 2cm

Comparison of Segmentectomy Versus Lobectomy for Lung Adenocarcinoma ≤ 2cm With Micropapillary and Solid Subtype Negative by Intraoperative Frozen Sections: A Prospective and Multi-center Randomized Controlled Trial Study

This study aims to evaluate the non-inferiority in recurrence-free survival and overall survival of segmentectomy compared with lobectomy in patients with lung adenocarcinoma ≤ 2 cm with micropapillary and solid subtype negative by intraoperative frozen sections.

Study Overview

• Status: Recruiting
• Conditions: Lung Adenocarcinoma
• Intervention / Treatment: Procedure: Segmentectomy with systemic lymph node dissection; Procedure: Lobectomy with hilar and mediastinal lymph node dissection

Detailed Description

At present, the technology of intraoperative frozen section has gradually matured, which can diagnose the benign and malignant tumors and guide the resection strategy for peripheral small-sized lung adenocarcinoma. Travis et al. reported high specificity of intraoperative frozen section in the identification of micropapillary components, confirming that intraoperative frozen section may guide the selection of surgical procedures. However, there is still little evidence weather segmentectomy is appropriate for invasive adenocarcinoma without micropapillary patterns. This prospective and multi-center study was aimed to evaluate the non-inferiority in recurrence free survival and overall survival of segmentectomy compared with lobectomy in patients with lung adenocarcinoma (≤ 2 cm) not including micropapillary components.

• Study Type: Interventional
• Enrollment (Estimated): 690
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hang Su; Phone Number: +86 13917810850; Email: dreamsuhang@163.com
• Study Contact Backup: Name: Chang Chen, MD, PhD; Phone Number: +86 021-65115006; Email: chenthoracic@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Chest Hospital
      • Contact: Ning Xu
    • Hefei, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Mingran Xie
  • Henan
    • Nanyang, Henan, China
      • Recruiting
      • Nanyang Central Hospital
      • Contact: Xinwei Dong
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
      • Recruiting
      • Affiliated Hospital Of Nantong University
      • Contact: Honggang Ke
    • Nantong, Jiangsu, China, 216002
      • Recruiting
      • The Sixth People's Hospital of Nantong
      • Contact: Xuedong Zhang
    • Xuzhou, Jiangsu, China
      • Recruiting
      • Affiliated Hospital of Xuzhou Medical University
      • Contact: Hao Xu
    • Yancheng, Jiangsu, China
      • Recruiting
      • Yancheng First People's Hospital
      • Contact: Jian Sun
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Public Health Clinical Center
      • Contact: Feng Jin
      • Sub-Investigator: Yunzeng Zhang
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Chang Chen, MD, PhD; Phone Number: 2074 +86-021-65115006; Email: chenthoracic@163.com
    • Shanghai, Shanghai, China
      • Recruiting
      • Huadong Hospital
      • Contact: Xiaoyong Shen
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated Hospital Zhejiang University School of Medicine
      • Contact: Junqiang Fan
    • Huzhou, Zhejiang, China
      • Recruiting
      • Huzhou Central Hospital
      • Contact: Qibin Shen
    • Ningbo, Zhejiang, China
      • Recruiting
      • Ningbo First Hospital
      • Contact: Xinjian Li
    • Ningbo, Zhejiang, China
      • Recruiting
      • Ningbo No.2 Hospital
      • Contact: Guofang Zhao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged 20-79 years old, both male or female;
• Tumor size <= 2cm on preoperative CT scan;
• Peripheral solitary nodule or the associated lesion is MIA or less invasive lesion;
• Preoperative CT indicated that the nodules were non-pure glass nodules (consolidation to tumor ratio >= 0.25);
• Intraoperative frozen section confirmed invasive lung adenocarcinoma with micropapillary and solid subtype negative (<= 5%);
• Intraoperative frozen section indicated the resection margins was free of tumor cells;
• Lung function could withstand both lung segmentectomy and lobectomy (FEV1 > 1.5L or FEV1% >= 60%);
• Eastern Cooperative Oncology Group, 0 to 2;
• Volunteer to participate the trial and sign the informed consent, able to comply with the follow-up plan and other program requirements.

Exclusion Criteria:

• Radiological pure ground glass nodules (consolidation to tumor ratio < 0.25);
• The nodule is close to the lung hilus and is unable to perform segmentectomy;
• Intraoperative frozen section confirmed with micropapillary and solid subtype positive (> 5%);
• Intraoperative frozen section confirmed adenocarcinoma in situ and minimally invasive adenocarcinoma;
• Preoperative imaging examination or EBUS indicated lymph node positive metastasis;
• Preoperative imaging examination revealed distant metastasis;
• Patients with severe damage to heart, liver and kidney function (grade 3 ~ 4, ALT and/or AST over 3 times the normal upper limit, Cr over the normal upper limit);
• Patients with other malignant tumors;
• Pregnant, planned pregnancy and lactating female patients (urine HCG>2500IU/L is diagnosed as early pregnancy);
• Prior chemotherapy, radiation therapy or any other therapies were performed; 12 participated in other tumors within three months of relevant clinical subjects;
• Those who have participated in other tumor-related clinical trials within three months;
• Those are not suitable for participating in trials according to investigator's assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Segmentectomy with systemic lymph node dissection; Segmentectomy with hilar and mediastinal lymph node dissection is performed. If the tumor located at inter-segment plane and without sufficient resection margin distance, a combined segmentectomy will be performed after a comprehensive evaluation. As with lobectomy, systemic or selective lymph node dissection is mandatory, and nodal sampling is not allowed. At least three stations of mediastinal lymph node from 2R, 4R, 7, 8, 9 for the right side and 5, 6, 7, 8, 9 for the left side, respectively. The distance from the dissection margin to the tumor edge must be evaluated in the same manner as with lobectomy. When lymph node metastasis is present or resection margin is not cancer-free, the surgical procedure must be converted to a lobectomy.	Procedure: Segmentectomy with systemic lymph node dissection; Segmentectomy with hilar and mediastinal lymph node dissection is performed. If the tumor located at inter-segment plane and without sufficient resection margin distance, a combined segmentectomy will be performed. Systemic or selective lymph node dissection is mandatory, and nodal sampling is not allowed. At least three stations of mediastinal lymph node from 2R, 4R, 7, 8, 9 for the right side and 5, 6, 7, 8, 9 for the left side, respectively. The distance from the dissection margin to the tumor edge must be evaluated intra-operatively. If the distance is either less than the maximum tumor diameter or 20 mm, the absence of cancer cells in the resection margin must be histologically or cytologically confirmed before finishing surgery.
Active Comparator: Lobectomy with systemic lymph node dissection; lobectomy with hilar and mediastinal lymph node dissection is performed. Systemic or selective lymph node dissection is mandatory, and nodal sampling is not allowed. At least three stations of mediastinal lymph node from 2R, 4R, 7, 8, 9 for the right side and 5, 6, 7, 8, 9 for the left side, respectively. The distance from the dissection margin to the tumor edge must be evaluated intraoperatively. If the distance is either less than the maximum tumor diameter or ,20 mm, the absence of cancer cells in the resection margin must be histologically or cytologically confirmed before finishing surgery.	Procedure: Lobectomy with hilar and mediastinal lymph node dissection; Lobectomy with hilar and mediastinal lymph node dissection is performed. Segmentectomy with hilar and mediastinal lymph node dissection is performed. Systemic or selective lymph node dissection is mandatory, and nodal sampling is not allowed. At least three stations of mediastinal lymph node from 2R, 4R, 7, 8, 9 for the right side and 5, 6, 7, 8, 9 for the left side, respectively. The distance from the dissection margin to the tumor edge must be evaluated intra-operatively. If the distance is either less than the maximum tumor diameter or 20 mm, the absence of cancer cells in the resection margin must be histologically or cytologically confirmed before finishing surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrence-free survival rate	Recurrence-free survival (RFS) was defined as the time from surgery until recurrence or death from any cause	5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	Overall survival (OS) was defined as the time from surgery until death from any cause	5 year
Operation time	The surgery time in both groups.	24 hours
Blood loss	Intraoperative blood loss in total.	24 hours
Incidence of operative complications	Any intraoperative complications related to the surgery.	1 month
Post-operative respiratory function	The post-operative respiratory function will be evaluated by FEV1% and FVC.	6 months

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Principal Investigator: Chang Chen, MD, PhD, Shanghai Pulmonary Hospital, School of Medicine, Tongji University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 24, 2021
• First Submitted That Met QC Criteria: June 21, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung
• Other Study ID Numbers: STAR001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No