Comparison of Segmentectomy Versus Lobectomy for Lung Adenocarcinoma 2 - 3cm With IASLC Grade 1 - 2 by Intraoperative Frozen Sections: A Prospective and Multi - Center Randomized Controlled Trial Study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 587
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study is a prospective, multicenter randomized controlled trial (RCT) designed to compare the efficacy of segmentectomy and lobectomy for invasive lung adenocarcinoma with a diameter of 2-3 cm and intraoperative frozen section-confirmed IASLC pathological new grade 1-2. The non-inferiority of segmentectomy is primarily evaluated by 5-year relapse-free survival (RFS) and overall survival (OS) after surgery, while secondary endpoints include pulmonary function preservation, perioperative complications, etc. With a planned enrollment of 587 patients over a 3-year recruitment period and a 5-year follow-up, this study aims to identify an optimized surgical approach.
详细描述
Lung cancer is the most prevalent and lethal malignant tumor worldwide. Surgical resection remains the most effective treatment for early-stage lung cancer, with lobectomy historically serving as the standard procedure. Recent studies have demonstrated that segmentectomy can achieve comparable outcomes to lobectomy for tumors ≤2 cm and those with ground-glass opacity dominance (CTR ≤0.5). However, for invasive lung adenocarcinomas measuring 2-3 cm with solid predominance (CTR >0.5), high-level evidence supporting segmentectomy as an alternative to lobectomy is lacking. The 2020 International Association for the Study of Lung Cancer (IASLC) proposed a new grading system for invasive adenocarcinoma, which stratifies prognosis based on histologic subtypes. Tumors with IASLC Grade 1-2 (≤20% high-grade components) have better outcomes, but their optimal surgical approach (segmentectomy vs. lobectomy) in solid-predominant lesions (2-3 cm) remains unproven. Intraoperative frozen section has shown high accuracy in diagnosing IASLC grades, enabling real-time surgical decision-making. The primary objective of this study is to evaluate whether segmentectomy is non-inferior to lobectomy in terms of 5-year relapse-free survival (RFS) and overall survival (OS) for patients with 2-3 cm lung adenocarcinomas confirmed as IASLC Grade 1-2 by intraoperative frozen section.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Initial Registration (1.1) Inclusion Criteria:
- •Aged 20 to 79 years, regardless of gender.
- •Preoperative CT or PET-CT suggests: ① Imaging diameter of 2-3 cm.
- •Suspicion of non-small cell lung cancer (NSCLC).
- •Solitary nodule or concomitant lesions with microinvasion or below.
- •Primary tumor not located in the middle lobe.
- •No suspected lymph node involvement.
- •Preoperative CT lung window (window level -700HU, window width 1500HU) indicates the nodule is predominantly solid, i.e., the consolidation-to-tumor ratio (CTR) is greater than 0.5 (CTR > 0.5).
- •4. Good lung function (FEV1 > 1.5 L or FEV1% ≥ 60%), tolerable for both segmentectomy and lobectomy.
- •5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Voluntary participation with signed informed consent, able to comply with study visit plans and other protocol requirements.
- •7. No history of ipsilateral thoracotomy; video-thoracoscopic examination meets the criteria.
- •8. No history of chemotherapy or radiotherapy, including treatment for other cancers. Eligible if more than 5 years have passed since completion of perioperative adjuvant chemotherapy. Eligible if there is a history of or ongoing hormone therapy.
- •9. All the following laboratory test results are eligible (all laboratory tests use the latest results within 28 days before initial registration; laboratory tests on the same day within 4 weeks before initial registration are allowed):
- •White blood cell count ≥ 3000/mm³.
- •Hemoglobin ≥ 8.0 g/dL (without blood transfusion within 28 days before initial registration).
- •Platelet count ≥ 10×10⁴/mm³.
- •AST ≤ 100 IU/L.
- •⑤ ALT ≤ 100 IU/L.
- •⑥ Total bilirubin ≤ 2.0 mg/dL.
- •⑦ Serum creatinine ≤ 1.5 mg/dL.
- •The patient has signed a written informed consent. (1.2)
排除标准
- •Active bacterial or fungal infection (confirmed by imaging diagnosis or bacteriological examination with fever >38°C).
- •Multiple active cancers (synchronous or metachronous multiple primary cancers, excluding in situ carcinoma or intramucosal cancer lesions considered cured by local treatment; such lesions are not included in active multiple cancers).
- •Patients with severe impairment of cardiac, hepatic, or renal function (cardiac function grade 3-4; ALT and/or AST more than 3 times the upper limit of normal; Cr exceeding the upper limit of normal).
- •Patients with concomitant other malignant tumors or hematological diseases.
- •Pregnant, planning to become pregnant, or lactating female patients (diagnosed with early pregnancy when urine HCG >2500 IU/L).
- •Any form of antitumor therapy before tumor resection, including interventional chemotherapy embolization, ablation, radiotherapy, chemotherapy, and molecular targeted therapy.
- •Patients who participated in other tumor-related clinical trials within the past three months.
- •Preoperative CT suggests ground-glass predominant nodules (CTR < 0.5).
- •Patients with positive lymph nodes indicated by preoperative imaging or lymph node puncture (clinical N stage = 1 or 2).
- •Patients with tumors near the hilum who cannot undergo segmentectomy.
- •Patients deemed unsuitable for enrollment by the investigator.
- •Intraoperative Secondary Registration (2.1) Inclusion Criteria:
- •Intraoperative frozen section indicates invasive lung adenocarcinoma with International Association for the Study of Lung Cancer (IASLC) grade 1-2 (<20% pathological high-grade subtypes).
- •2. Intraoperative frozen section shows negative surgical margins.
- •Intraoperative exploration reveals no severe adhesions or lymph node inflammatory changes (adhesions of pulmonary vessels or bronchi), confirming feasibility for both lobectomy and segmentectomy.
- •(2.2) Exclusion Criteria:
- •Patients with IASLC grade 3 (≥20% pathological high-grade subtypes) indicated by intraoperative frozen section.
- •Patients confirmed with in situ carcinoma or microinvasive adenocarcinoma by intraoperative frozen section.
- •Patients with preoperative findings of distant metastasis or pleural/ascitic effusion.
结局指标
主要结局
Overall Survival (OS)
时间窗: 5 years
Overall Survival (OS) is defined as the time from the date of surgery to death from any cause. For surviving patients, survival time is censored at the last date when survival was confirmed; the study allows telephone confirmation of survival status, provided that medical records are available. For lost-to-follow-up patients, survival time is censored on the last date when survival was confirmed before the loss of follow-up. For patients diagnosed with non-malignant tumors, the date of surgery is used as the censorship point.
Recurrence-Free Survival (RFS)
时间窗: 5 years
Recurrence-Free Survi refers to the time from the date of surgery to the diagnosis of recurrence or death from any cause, whichever occurs first. "Recurrence" includes both cases confirmed by imaging diagnosis and clinical exacerbation (symptomatic aggravation) not confirmed by imaging diagnosis. For the former, the day of imaging examination is regarded as the recurrence date, while for the latter, the day of diagnosing symptomatic deterioration is considered the recurrence date. An increase in tumor marker values alone is not considered an RFS event. When recurrence is confirmed based on the pathological results of a biopsy specimen, if the patient had already been clinically diagnosed with recurrence before, the endpoint is the date of clinical diagnosis; otherwise, it is the biopsy date. The occurrence of other primary cancers is not considered an endpoint, and RFS continues until other events are identified.
次要结局
- Postoperative Respiratory Function(12 months)
- Hospitalization Duration(1 month)
- Chest Tube Placement Time(1 month)
- Surgical Time(1 day)
- Blood Loss(1 day)
研究者
Chang Chen
Professor at Tongji University School of Medicine and Chief Physician of the Department of Thoracic Surgery at Shanghai Pulmonary Hospital
Shanghai Pulmonary Hospital, Shanghai, China