Precision Diagnosis for Intraoperative Frozen Section of Early Stage Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is: To establish a set of diagnostic criteria of intraoperative frozen section of early stage lung adenocarcinoma, including clinicopathologic and molecular characteristics. To assess its clinical usefulness in guiding surgical procedure for early stage lung adenocarcinoma.

Detailed Description
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The detection rate of small pulmonary nodules is increasing due to the widespread use of high-resolution computed tomography (CT) screening in clinical practice. These minute pulmonary nodules are suggestive of atypical adenomatous hyperplasia (AHH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma. Hence, the precision diagnosis of intraoperative frozen section is particularly imperative for its fundamental role in assess indeterminate lung lesions and guide the extent of subsequent surgical procedure. However, it is still difficult for the surgical pathologist to apply the various features according to the newly revised WHO classification of lung adenocarcinoma (2015) to guide surgical management due to their unascertained accuracy or heterogeneity of lung cancer or technique problem. Therefore, the establishment and assessment for a set of diagnostic criteria of intraoperative frozen section of early stage lung adenocarcinoma are our primary aim in this study.

Official Title
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Establishment and Evaluation for Pathological Diagnostic Criteria of Intraoperative Frozen Section of Early Stage Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Device: microscope
* Other: immunostaining
* Device: NGS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with suspected pulmonary nodules (5 20 mm) by chest CT scan; Patients received surgical operation. Exclusion Criteria: Patients compliance is poor and cannot accept follow-up; Patients nursing or pregnant; Patients with a history of any cancer; Patients with confirmed pathological diagnosis or received radiotherapy or chemotherapy or target therapy preoperatively.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Diagnostic
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OCT treatment<br>Randomly assigned patients whose small pulmonary nodules are inflated with the diluted OCT medium (2:3) used for frozen section, and then detected under microscope for their histopathological characteristics, by immunostaining for specific protein expression, by NGS (next-generation sequencing) for driver mutations. | Device: microscope<br>* Detection of of histopathological characteristics of OCT treatment or OCT free samples from patients .<br>Other: immunostaining<br>* Detection of CD31/CD34, D2-40, Ki67 and p53 immunostaining of OCT treatment or OCT free samples from patients .<br>Device: NGS<br>* The investigators used the device to detect the gene mutations of OCT treatment or OCT free samples obtained from part of the patients.<br>* Other names: Illumina Nexseq500;|
| Experimental: OCT free<br>Randomly assigned patients whose small pulmonary nodules are uninflated with OCT used for frozen section, and then detected under microscope for their histopathological characteristics, by immunostaining for specific protein expression, by NGS for driver mutations. | Device: microscope<br>* Detection of of histopathological characteristics of OCT treatment or OCT free samples from patients .<br>Other: immunostaining<br>* Detection of CD31/CD34, D2-40, Ki67 and p53 immunostaining of OCT treatment or OCT free samples from patients .<br>Device: NGS<br>* The investigators used the device to detect the gene mutations of OCT treatment or OCT free samples obtained from part of the patients.<br>* Other names: Illumina Nexseq500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of histopathological characteristics between intraoperative frozen section and paraffin section for patients with early stage lung adenocarcinoma |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of CD31/CD34, D2-40, Ki67 and p53 among different subtypes of early stage lung adenocarcinoma by immunohistochemical (IHC) analysis |  | 6 months | 
| Comparison of mutation profiles among different subtypes of early stage lung adenocarcinoma by tissue microdissection and subsequent next generation sequencing (NGS) |  | 6 months | 
| Verification of the driver mutations from NGS results using droplet digital PCR (ddPCR) in early stage lung adenocarcinoma. |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early stage lung adenocarcinoma, Intraoperative frozen section, Diagnostic criteria