Optimal Extent of Pulmonary Resection in Clinical Stage IA Non-Small Cell Lung Cancer (OREX-IA)

A Prospective Study to Optimize the Extent of Pulmonary Resection According to the Decision-Making Algorithm in Patients With Clinical Stage IA Non-Small Cell Lung Cancer

The investigatros hypothesized that selection of surgical procedure according to the pre-defined institutional decision-making algorithm will not compromise the treatment outcomes including overall survival and disease-free survival in participants with clinical stage IA non-small cell lung cancer.

The purpose of this study is to determine the outcome of participants with clinical stage IA NSCLC treated by 3 types of surgical resection (wide wedge resection, segmentectomy, or lobectomy) according to the institutional decision-making algorithm

The investigators are planning to enroll 1,000 participants who meet the pre-defined eligibility criteria over 5 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage IA Non-small Cell Lung Cancer
• Intervention / Treatment: Procedure: Extent of pulmonary resection

Detailed Description

1. Background

   • The standard extent of pulmonary resection for non-small cell lung cancer (NSCLC) is still lobectomy. However, recent advances in imaging technology and staging modalities and the widespread use of computed tomography (CT) screening have greatly increased the probability of detecting small-sized tumors, especially with ground-glass opacity (GGO) feature. Adenocarcinoma with GGO feature generally has a good prognosis due to its minimally invasive nature. Many studies have shown that these pathologically less invasive subtypes are associated with better prognoses compared with other subtypes such as acinar, papillary, micropapillary, and solid predominant invasive adenocarcinoma.
   • This recent change in the disease pattern of NSCLC from locally advanced and solid tumors to early and less invasive tumors with GGO features have led to a resurgence of interest in sublobar resection. Several retrospective studies have been conducted to compare the early and late outcomes including long-term survival between patients who underwent lobectomy and those who underwent sublobar resection.
   • Multiple reports have suggested that small-sized peripheral lung adenocarcinoma can be treated by sublobar resection, yielding survival rates similar to those of lobectomy. Lobectomy is considered to be too much for these less invasive tumors and sublobar resection would be sufficient for these tumors. If sublobar resection is equivalent to lobectomy in terms of their oncologic efficacy for the surgical treatment of NSCLC, the potential benefits of sublobar resection include (1) the preservation of vital lung parenchyma and pulmonary function, which may lead to improved early morbidities and mortalities and then late quality of life and (2) a chance for a second resection with a subsequent primary NSCLC.
   • However, when considering the published evidence for sublobar resection, its interpretation needs to be cautious. Since most studies were non-randomized, there may also have been selection bias in terms of preoperative patient risk factors (intentional vs. compromised sublobar resection), tumors of various histological subtypes or different tumor size in the study arms. Therefore, the results from two randomized trials of lobectomy versus sublobar resection for small-sized lung cancer currently ongoing in Japan (Japan Clinical Oncology Group [0802]) and in the United States (Cancer and Leukemia Group B [140503]) need to be awaited.
   • Based on these clinical circumstances and the published evidence, the investigators developed the decision-making algorithm regarding the surgical treatment for clinical stage IA NSCLC.
2. Hypothesis The investigators hypothesized that selection of surgical procedure according to the pre-defined institutional decision-making algorithm will not compromise the treatment outcomes including overall survival and disease-free survival in patients with clinical stage IA non-small cell lung cancer.
3. Purpose The purpose of this study is to determine the outcome of participants with clinical stage IA NSCLC treated by 3 types of surgical resection (wide wedge resection, segmentectomy, or lobectomy) according to the institutional decision-making algorithm
4. Study plan The investigators are planning to enroll 1,000 participants who meet the pre-defined eligibility criteria over 5 years.

• Study Type: Observational
• Enrollment (Actual): 1018

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who are planned to undergo surgery for clinical stage IA non-small cell lung cancer

Description

Inclusion Criteria:

1. The following features should be fulfilled at preoperative thin-section CT scans

   • Solitary lung nodule
   • Lesion size is 3cm or less in its maximal dimension of the entire tumor
   • The center of the tumor is located in the outer third of the lung field in either the transverse, coronal, or sagittal plane
   • Lung cancer is suspected (or NSCLC if tissue diagnosis already obtained)
2. Clinical stage T1a-bN0M0 (according to 7th AJCC staging system)
3. Absence of proximal segmental or lobar bronchial involvement.
4. NSCLC must be confirmed in intraoperative frozen section biopsies or postoperative pathologic examinations if the lesion was not histologically confirmed before operation.
5. Age ≥ 18 years and < 75 years.
6. ECOG performance status 0-1.
7. The patient should have adequate cardiopulmonary reserve to tolerate lobectomy (ppo FEV1 > 40% and ppo DLCO > 40% or VO2 max > 15ml kg-1 min-1)
8. No prior chemotherapy or thoracic radiotherapy for any malignancy.
9. No prior malignancy within 5 years from study entry (except for non-melanoma skin cancer, superficial bladder cancer, thyroid cancer or carcinoma in situ of the uterine cervix).
10. The patient agrees to participate in the study and signs the informed consent form.

Exclusion Criteria:

1. Histologic diagnosis other than NSCLC (such as small cell lung cancer, carcinoid, pulmonary lymphoma, or other benign lung disease, etc).
2. Hilar or mediastinal lymph node metastasis suspected on imaging studies (CT or PET/CT) or confirmed preoperatively by EBUS or mediastinoscopy.
3. Parietal pleura, chest wall, or mediastinal invasion is confirmed intraoperatively or postoperatively.
4. M1a disease is confirmed intraoperatively or postoperatively.
5. Bilobectomy, sleeve resection, pneumonectomy, concomitant wedge resection, or concomitant thoracic procedure (including cardiac surgery) is performed.
6. Synchronous or metachronous multiple cancers (within the past 5 years).
7. Interstitial lung disease or severe pulmonary emphysema which makes it impossible to tolerate either lobectomy or sublobar resection.
8. Active bacterial or fungal infection.
9. Uncontrolled systemic disease which makes the patient medically unfit for thoracic surgery such as unstable angina, recent myocardial infarction, congestive heart failure, or end-stage renal or liver disease.
10. Serious mental illness or psychosis.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lobectomy; Lobectomy will be chosen as the extent of pulmonary resection according to the institutional decision-making algorithm
Segmentectomy; Segmentectomy will be chosen as the extent of pulmonary resection according to the institutional decision-making algorithm	Procedure: Extent of pulmonary resection; Extent of pulmonary resection selected based on the institutional decision-making algorithm
Wide wedge resection; Wide wedge resection will be chosen as the extent of pulmonary resection according to the institutional decision-making algorithm	Procedure: Extent of pulmonary resection; Extent of pulmonary resection selected based on the institutional decision-making algorithm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	the time from the date of the operation until the first recurrence or the last follow-up.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	the interval between the date of the operation and the date of death from any cause or the last follow-up	5 years
Rate of loco-regional recurrence	Loco-regional recurrence means tumor recurrence within the ipsilateral hemithorax and mediastinum	5 years
Rate of systemic recurrence	Systemic recurrence means tumor recurrence outside the bilateral hemithorax or mediastinum except for lung-to-lung metastasis	5 years
Postoperative FEV1 (Forced expiratory volume in 1 second; Liter)	the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity. This value reflects the pulmonary function of participants	6 months, 12 months, 24 months, 36 months, 48 months, 60 months after operation date
Postoperative DLco (Diffusing capacity of the lung for carbon monoxide; mL/mmHg/min)	the extent to which oxygen passes from the air sacs of the lungs into the blood. This value is also related to the pulmonary function of participants	6 months, 12 months, 24 months, 36 months, 48 months, 60 months after operation date
C/T ratio at thin section CT scans	C/T ratio is the consolidation/tumor ratio, which can be measured by the maximum diameter of consolidation to the maximum tumor diameter. Pathologic invasiveness of tumors can be predicted by this value.	within 2 months prior to operation date
Postoperative pathologic subtypes	(according to the 2015 WHO classification of lung tumors)	1 month after operation date
Incidence of lymph node metastasis	The investigators will check the incidence of lymph node metastasis from the permanent pathology report.	within 1 month after operation date

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Hong Kwan Kim, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Wedge resection; Segmentectomy; Lobectomy; Clinical stage IA non-small cell lung cancer; Sublobar resection; Limited resection
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 2016-12-116

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