Mediastinal Staging Accuracy of a Selective Lymphadenectomy Strategy in Early Stage NSCLC (ECTOP-1003)

Lymph Node Metastases Clinical Trial

Official title:

Evaluation of the Mediastinal Staging Accuracy of a Selective Lymphadenectomy Strategy Based on Tumor Location, Ground Glass Opacity Component and Frozen Section Diagnosis in Peripheral cT1N0M0 Invasive Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03216551
• Other study ID #: SASLND
• Status: Completed
• Start date: March 14, 2019
• Est. completion date: May 30, 2022

Study information

• Verified date: July 2023
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a clinical trial from Eastern Cooperative Thoracic Oncology Project (ECTOP), numbered as ECTOP-1003. Systemic mediastinal lymphadenectomy is deemed indispensable in lung cancer surgery for accurate staging and complete resection. However, extensive lymphadenectomy in patients without nodal metastasis may not improve survival and would increase operative duration and cause damage to mediastinal structures.Therefore the precise selection of patients without mediastinal nodal metastasis is the key to avoid unnecessary lymphadenectomy.The investigator's previous retrospective study shows tumor location, ground glass opacity component and histological subtypes are important predictors of negative nodal status in specific mediastinal regions. The current prospective observational study is to further verify the mediastinal staging accuracy of this selective lymphadenectomy strategy.

Description:

Background:

Complete lung cancer lymphadenectomy in patients without nodal metastasis may not improve survival and would increase operative duration and cause damage to mediastinal structures.The investigator's previous retrospective study of 2749 invasive NSCLC patients showed none of the 151 tumors with consolidation tumor ratios ≤ 0.5 had N2 disease. Tumors with lepidic predominant adenocarcinoma (LPA) histology had zero mediastinal nodal involvement. Tumors in the apical segment of upper lobes had zero inferior mediastinal nodal (IMLN) involvement. Only seven out of 740 (0.9%) peripheral upper lobe tumors had IMLN metastasis. Interestingly, all these seven tumors showed visceral pleural invasion. Among patients with left lower lobe tumors, if hilar nodes were negative, station 4L lymph node metastasis was not found in superior and basal segment tumors, and station 5/6 lymph node involvement was always absent in basal segment tumors.

The current prospective, multi-center, observational study is to verify the staging accuracy of a selective mediastinal lymphadenectomy strategy based on tumor location, ground glass opacity component and intraoperative histological subtyping by frozen section in patients with peripheral clinical T1N0M0 invasive non-small cell lung cancer.

Objectives:

Primary: To determine the mediastinal staging accuracy of the selective mediastinal lymphadenectomy strategy.

Secondary:

1. To determine the diagnostic accuracy of intraoperative adenocarcinoma histologic subtyping, N1 nodes metastasis and visceral pleural invasion by frozen section.

2. To determine the mediastinal lymph node metastasis rate in peripheral clinical T1N0M0 lung cancer with different histologic subtypes.

3. To evaluate the pattern of mediastinal nodal involvement of tumors in different lung segments.

4. To determine the mediastinal nodal status of tumors with different radiological features (pure ground glass opacity, mixed ground glass opacity and solid nodules).

Outlines:

1. All recruited patients will undergo systematic mediastinal lymph node dissection (lung resection can be segmentectomy, lobectomy, bilobectomy or pneumonectomy). For tumors in the left lungs, removal of mediastinal nodal stations 4, 5,6,7 and 8 are required. For tumors in the right lungs, removal of mediastinal nodal stations 2,4,7 and 8 are required. For lower lobe tumors, station 9 should also be removed. Stations 10/11/12 should routinely be dissected.

2. Stations 10/11 are subclassified as follows: Station 10a (the anterior region of the pulmonary veins), Station 10s (between azygos vein and the right upper lobe bronchus), Station 10p (in the posterior region of the right main bronchus for right-side tumors or between left main pulmonary artery and left main bronchus for left-side tumors), Station 11s (between right upper lobe bronchus and the intermediate bronchus), and Station 11i (between right middle lobe bronchus and right lower lobe bronchus).

3. Intraoperative frozen section analysis should determine whether the tumor is lepidic predominant adenocarcinoma, whether there are N1 nodes involvement (lymph nodes adjacent to the tumor should be sent to intraoperative frozen section), and whether there is viceral pleural invasion. However, intraoperative frozen section results will not affect the surgical predure. Every patient will receive systematic lymph node dissection.

4. By the assumed selective lymph node dissection strategy, patients with consolidation tumor ratios ≤ 0.5 tumors will be considered to have negative mediastinal metastasis. Patients with intraoperative LPA diagnosis will be considered to have negative mediastinal metastasis. Patients with an apical tumor will be considered to have negative IMLN metastasis. If both N1 nodes and visceral pleural invasion are negative, patients with peripheral non-apical-segment upper lobe tumors will be considered to have negative IMLN metastasis. If N1 nodes are negative, patients with left superior segment tumors will be considered to have negative 4L lymph node metastasis, and patients with left basal segment tumors will be considered to have negative superior mediastinal lymph node metastasis. The virtual mediastinal staging results of this selective lymph node dissection strategy will then be compared with the final staging results by the complete lymphadenectomy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1076
• Est. completion date: May 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Informed consent must be signed

• Peripheral clinical stage T1N0M0

• Invasive non-small cell lung cancer as determined preoperatively or intraoperatively, excluding AIS/MIA

• Can be completely resected

• If there are multiple nodules, except the predominant nodule, other nodules should be pure GGO

Exclusion Criteria:

• Previous malignancy or lung surgery

• Previous induction therapy for the disease

• Intolerable to the surgery

• Incomplete mediastinal lymph node dissection or lymph node sampling

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Lymph Node Metastases
• Lymphatic Metastasis
• Non-small Cell Lung Cancer Stage I

Intervention

Diagnostic Test:
• Intra-operative frozen section
Tumor histologic subtypes (whether it is lepidic predominant adenocarcinoma), N1 nodes metastasis (lymph nodes adjacent to the tumor will be sent to frozen section) and visceral pleural invasion will be determined by the intra-operative frozen section.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mediastinal staging accuracy of the assumed selective lymph node dissection strategy	To compare the mediastinal staging results by the assumed selective lymph node dissection strategy and the final staging results by systematic lymph node dissection.	2-3 weeks after the surgery until the final pathology results are reported.
Secondary	The accuracy of determining lepidic predominant adenocarcinoma, N1 nodes metastasis and viceral pleural invasion by frozen section	The concordance rate of intraoperative histologic subtypes, N1 node metastasis and visceral pleural invasion compared to the final pathology.	2-3 weeks after the surgery until the final pathology results are reported.
Secondary	The nodal metastasis pattern of tumors in different lung segments.	The mediastinal nodal metastasis pattern of tumors in different lung segments.	2-3 weeks after the surgery until the final pathology results are reported.
Secondary	The nodal status of tumors with various CT appearance	The nodal status of tumors with CT appearance of pure ground glass opacity, sub-solid and solid nodules.	2-3 weeks after the surgery until the final pathology results are reported.
Secondary	The lymph node metastasis rate of different histologic subytpes.	The lymph node metastasis rate of different adenocarcinoma subytypes, squmous cell carcinoma, etc.	2-3 weeks after the surgery until the final pathology results are reported.