Expression of LKB1 (STK11) and Its Prognostic and Therapeutic Implications in Non-Small Cell Lung Cancer: A Retrospective Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) of first-line systemic therapy stratified by STK11/LKB1 mutation status
研究概览
简要总结
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:
- Does LKB1 mutation status independently predict clinical outcomes, including overall survival and progression-free survival, in patients with NSCLC?
- Does LKB1 alteration modify the predictive value of PD-L1 expression and determine differential responses to immunotherapy, chemotherapy, and targeted therapy?
- Do distinct genomic backgrounds defined by LKB1, KRAS, KEAP1, and TP53 co-mutation patterns represent biologically and clinically meaningful subgroups with different therapeutic vulnerabilities?
- 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.
详细描述
The goal of this observational study is to investigate the clinical and biological significance of LKB1 (STK11) alterations in patients with non-small cell lung cancer (NSCLC) and to determine whether LKB1 mutation status, together with co-occurring genomic alterations, can predict therapeutic response and survival outcomes across different treatment strategies.
The main question this study aims to answer is whether LKB1-driven molecular subgroups can define distinct clinical behaviors, immune phenotypes, and treatment vulnerabilities in NSCLC patients.
Participants included in this study are adult patients diagnosed with NSCLC who have available tumor tissue samples, genomic sequencing data, PD-L1 immunohistochemical evaluation, and clinical follow-up information. Approximately 300 patients with NSCLC will be retrospectively enrolled. Clinical characteristics, including age, sex, smoking history, pathological subtype, TNM stage, treatment history, and survival outcomes, will be collected from medical records.
Tumor tissue samples will be analyzed using targeted next-generation sequencing to identify genomic alterations involving LKB1 (STK11), KRAS, KEAP1, TP53, and other cancer-related genes. Immunohistochemistry will be performed to evaluate LKB1 protein expression and PD-L1 expression levels. Genomic profiles will be integrated with clinical characteristics and treatment information, including chemotherapy, targeted therapy, immune checkpoint inhibitor therapy, and combination treatment regimens.
The study will classify patients according to biologically relevant genomic backgrounds, with LKB1 mutation as the primary molecular factor and KRAS, KEAP1, and TP53 alterations considered as important co-molecular modifiers. Different genomic subgroups will be compared to determine their associations with PD-L1 expression patterns, treatment responses, and long-term clinical outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Crossover
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 45 Years 至 94 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
- •Patients who received first-line systemic therapy, including chemotherapy, targeted therapy, immune checkpoint inhibitor therapy, or combined treatment.
- •Available clinicopathologic data, including TNM stage, treatment information, and follow-up records.
- •Available tumor tissue samples or clinically validated molecular testing results for assessment of STK11/LKB1 status and co-mutation profiles, including KRAS, KEAP1, and TP
- •Available PD-L1 immunohistochemistry (IHC) results or sufficient tumor tissue for PD-L1 TPS assessment, when applicable.
排除标准
- •Pathological diagnosis of small cell lung cancer or mixed small cell/non-small cell lung cancer tumors.
- •Insufficient tumor tissue or unavailable testing results that prevent assessment of STK11/LKB1 status, co-mutation profiles, or PD-L1 expression.
- •Missing key clinical information, treatment records, or follow-up data required for survival analysis.
- •Patients who did not receive first-line systemic therapy.
结局指标
主要结局
Progression-Free Survival (PFS) of first-line systemic therapy stratified by STK11/LKB1 mutation status
时间窗: 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.
次要结局
- Overall Survival (OS) stratified by STK11/LKB1 mutation and co-mutation profiles(1year)
- PD-L1 TPS distribution in STK11/LKB1-mutant and wild-type molecular subgroups(3months)
- Correlation between STK11/LKB1 mutation status and clinicopathological features of NSCLC(3months)
研究者
Ling Zhiqiang
Prof., M.D., PhD,
Zhejiang Cancer Hospital