LKB1 Expression and Clinical Outcomes in Non-Small Cell Lung Cancer: A Retrospective Cohort Study

Condition(s) studied

Study summary

The goal of this observational study is to investigate whether LKB1 alterations can serve as a clinically meaningful biomarker for predicting therapeutic response and survival outcomes in patients with non-small cell lung cancer (NSCLC), and to determine how LKB1 mutation status together with co-occurring genomic alterations influences treatment sensitivity across different therapeutic strategies.

This study will include adult patients diagnosed with NSCLC who underwent surgical resection or tumor biopsy, genomic profiling, PD-L1 immunohistochemical evaluation, and clinical follow-up. Tumor samples from approximately 300 patients will be analyzed for genomic alterations involving LKB1 (STK11), KRAS, KEAP1, TP53, and other cancer-related genes. Clinical characteristics, including age, sex, smoking history, TNM stage, treatment modalities (chemotherapy, targeted therapy, immunotherapy), and survival outcomes will be collected and integrated for comprehensive analysis.

The main questions this study aims to answer are:

1. Does LKB1 mutation status independently predict clinical outcomes, including overall survival and progression-free survival, in patients with NSCLC?
2. Does LKB1 alteration modify the predictive value of PD-L1 expression and determine differential responses to immunotherapy, chemotherapy, and targeted therapy?
3. Do distinct genomic backgrounds defined by LKB1, KRAS, KEAP1, and TP53 co-mutation patterns represent biologically and clinically meaningful subgroups with different therapeutic vulnerabilities?
4. Can an LKB1-centered genomic classification model improve patient stratification and provide a more accurate framework for personalized treatment selection in NSCLC?

The primary outcome measures will include overall survival (OS) and progression-free survival (PFS). Secondary outcome measures will include objective response rate (ORR), disease control rate (DCR), treatment-specific clinical benefit, and the association between genomic alterations, PD-L1 expression, and therapeutic outcomes.

Eligibility

Primary outcome measure(s)

• Progression-Free Survival (PFS) of first-line systemic therapy stratified by STK11/LKB1 mutation status — 1 year
  Progression-free survival (PFS), measured in months, is defined as the time from initiation of first-line systemic therapy to the first documented disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by retrospective review of radiologic imaging reports and medical records, using RECIST v1.1 criteria when available or treating physician-documented progression in routine clinical practice. LKB1 expression status will be assessed by immunohistochemistry (IHC) using archived tumor tissue and categorized as LKB1-low/loss versus LKB1-preserved/high expression according to the study-defined cutoff. PFS will be summarized according to LKB1 expression status and first-line treatment category.

Trial sites (1)

Other trials for the same condition