Clinical and Molecular Findings in Patients With Cervical/Supraclavicular Metastasis From Non-small-cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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Despite the availability of highly effective endoscopy-based and computed tomography (CT)-based biopsy procedures, up to 50% of patients with advanced lung cancer potentially eligible for targeted therapies or immunotherapy do not have access to a diagnosis or to a thorough molecular profiling for different reasons. Enlarged and/or positron emission tomography (PET) positive cervical/supraclavicular lymph nodes (CSLs) are ideal targets for a minimally invasive diagnosis of lung cancer through a percutaneous ultrasound-guided biopsy (US-NAB). However, the prevalence of metastatic involvement of CSLs in patients with advanced lung cancer was never specifically assessed. Furthermore, the possible association of malignant CSLs involvement with molecular status was never investigated, unlike what was done for several other metastatic sites.

Official Title
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Mutational Profile of Patients With and Without Neck and Supraclavicular Lymph Nodes Metastasis From Advanced Non-squamous Non-small-cell Lung Cancer: a Prospective Cohort Study

Conditions
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Lung Cancer Metastatic

Intervention / Treatment
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* Procedure: Needle or forceps biopsy of cervical and/or supraclavicular lymph nodes
* Procedure: Needle, forceps or surgical biopsy of any lesion other than cervical and/or supraclavicular lymph nodes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years at the time of the procedure; Suspected advanced, treatment naïve non-squamous NSCLC ; Indication to biopsy for diagnosis and/or molecular profiling; Written informed consent to the study participation. Exclusion Criteria: Patients with known non-squamous NSCLC sent for re-biopsy after first or second line treatment; Inability to stop anticoagulant or antiplatelet therapy before the procedure (except acetylsalicylic acid 100 mg/day); Platelet count <50.000 per μL; Inability or unwillingness to provide a written informed consent.

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental group<br>Patients with advanced lung cancer featuring cervical and/or supraclavicular lymph node metastasis | Procedure: Needle or forceps biopsy of cervical and/or supraclavicular lymph nodes<br>* Patients with evidence of enlarged and/or PET positive cervical and/or supraclavicular lymph nodes suspected of being metastasis from lung cancer will be submitted to the biopsy from this location.<br>* Other names: Ultrasound guided biopsy;|
| Control group<br>Patients with advanced lung cancer NOT featuring cervical and/or supraclavicular lymph node metastasis | Procedure: Needle, forceps or surgical biopsy of any lesion other than cervical and/or supraclavicular lymph nodes<br>* Patients without evidence of enlarged and/or PET positive cervical and/or supraclavicular lymph nodes will be submitted to the biopsy considered less invasive and effective based on imaging data and clinical health status.<br>* Other names: Surgical biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of KRAS mutation | Number of participants with KRAS mutation in the 2 groups (patients with and without cervical/supraclavicular lymph node metastasis) | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of EGFR, ALK, ROS1, BRAF, RET, MET, NTRK | Number of participants with EGFR, ALK, ROS1, BRAF, RET, MET, NTRK mutation in the 2 groups (patients with and without cervical/supraclavicular lymph node metastasis) | 2 months | 
| Tumor proportion score of PD-L1 | Number of participants with a tumor proportion score of PD-L1 < 1%; 1-50%; >50% in the two groups (patients with and without cervical/supraclavicular lymph node metastasis) | 2 months | 
| Prevalence of cervical/supraclavicular lymph node metastasis | Number of participants with cervical/supraclavicular lymph node metastasis in the whole cohort of patients with stage IV lung cancer | 2 months | 
| Predictors of cervical/supraclavicular lymph node metastasis | Association between the presence of cervical/supraclavicular lymph node metastasis and the following factors: age, sex, smoking habit, tumor histologic type, central vs peripheral primary tumor, enlarged and/or PET positive N2 or N3 lymph nodes in the middle mediastinum, and molecular profile. | 6 months |