Department of Radiation Oncology, Emory University, Atlanta, Georgia, USA.
Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Cancer. 2023 Dec 15;129(24):3971-3977. doi: 10.1002/cncr.34983. Epub 2023 Aug 10.
Increasingly, early-stage non-small cell lung cancer (NSCLC) is treated with stereotactic body radiation therapy (SBRT). Although treatment is generally effective, a small subset of tumors will recur because of radioresistance. Preclinical studies suggested PI3K-AKT-mTOR activation mediates radioresistance. This study sought to validate this finding in tumor samples from patients who underwent SBRT for NSCLC.
Patients with T1-3N0 NSCLC treated with SBRT at our institution were included. Total RNA of formalin-fixed paraffin-embedded tumor biopsy specimens (pretherapy) was isolated and analyzed using the Clariom D assay. Risk scores from a PI3K activity signature and four published NSCLC signatures were generated and dichotomized by the median. Kaplan-Meier curves and Cox regressions were used to analyze their association with recurrence and overall survival (OS). The PI3K signature was also tested in a data set of resected NSCLC for additional validation.
A total of 92 patients were included, with a median follow-up of 18.3 months for living patients. There was no association of any of the four published gene expression signatures with recurrence or OS. However, high PI3K risk score was associated with higher local recurrence (hazard ratio [HR], 11.72; 95% CI, 1.40-98.0; p = .023) and worse disease-free survival (DFS) (HR, 3.98; 95% CI, 1.57-10.09; p = .0035), but not OS (p = .49), regional recurrence (p = .15), or distant recurrence (p = .85). In the resected NSCLC data set (n = 361), high PI3K risk score was associated with decreased OS (log-rank p = .013) but not DFS (p = 0.54).
This study validates that higher PI3K activity, measured by gene expression, is associated with local recurrence and worse DFS in early-stage NSCLC patients treated with SBRT. This may be useful in prognostication and/or tailoring treatment, and merits further validation.
越来越多的早期非小细胞肺癌（NSCLC）采用立体定向体放射治疗（SBRT）进行治疗。尽管治疗通常是有效的，但一小部分肿瘤由于放射抵抗而复发。临床前研究表明，PI3K-AKT-mTOR 激活介导放射抵抗。本研究旨在验证这一发现在接受 NSCLC SBRT 治疗的患者的肿瘤样本中的发现。
纳入在我院接受 SBRT 治疗的 T1-3N0 NSCLC 患者。使用 Clariom D 检测从福尔马林固定石蜡包埋肿瘤活检标本（治疗前）中分离并分析总 RNA。使用中位数对 PI3K 活性特征和四个已发表的 NSCLC 特征的风险评分进行分类。使用 Kaplan-Meier 曲线和 Cox 回归分析来分析它们与复发和总生存（OS）的关系。PI3K 特征还在切除 NSCLC 的数据集进行了进一步验证。
共纳入 92 例患者，生存患者的中位随访时间为 18.3 个月。四个已发表的基因表达特征均与复发或 OS 无关联。然而，高 PI3K 风险评分与更高的局部复发（风险比 [HR]，11.72；95%CI，1.40-98.0；p=0.023）和更差的无病生存（DFS）（HR，3.98；95%CI，1.57-10.09；p=0.0035）相关，但与 OS（p=0.49）、区域复发（p=0.15）或远处复发（p=0.85）无关。在切除的 NSCLC 数据集（n=361）中，高 PI3K 风险评分与 OS 降低相关（对数秩 p=0.013），但与 DFS 无关（p=0.54）。
本研究验证了在接受 SBRT 治疗的早期 NSCLC 患者中，通过基因表达测量的更高的 PI3K 活性与局部复发和更差的 DFS 相关。这可能有助于预后和/或调整治疗方案，值得进一步验证。
