Schmidt Bernd, Beyer Julia, Dietrich Dimo, Bork Ines, Liebenberg Volker, Fleischhacker Michael
Clinic for Internal Medicine I, Department of Pneumology, UKH, Halle/Saale, Germany.
University Hospital Bonn, Institute of Pathology, Bonn, Germany.
PLoS One. 2015 Feb 12;10(2):e0118195. doi: 10.1371/journal.pone.0118195. eCollection 2015.
Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response.
In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2) in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study.
According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Additionally, a Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p ≤ 0.001 (hazard ratio 11.08) providing some evidence for mSHOX2 also being a predictive marker.
The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment.
大多数晚期肺癌患者会在几个月内死亡。为开发新的治疗方案，我们需要更好的方法来评估治疗反应。
在一项前瞻性试点研究中，我们纳入了36例晚期非小细胞肺癌和小细胞肺癌患者（34例IV期，2例IIIB期），其中34例接受了标准的铂类化疗/放疗，2例接受了酪氨酸激酶抑制剂治疗。在治疗前及治疗期间直至重新分期，我们测量了血浆中细胞外甲基化SHOX2 DNA（mSHOX2）的水平。mSHOX2分析对临床数据设盲，使其成为一项观察性研究。
根据31例一线患者的重新分期，19例患者被归类为无反应者，12例患者属于反应者组。我们观察到放射学数据与作为治疗反应等效指标的血浆mSHOX2水平变化之间存在紧密相关性。ROC分析显示，在治疗开始一周后，两组患者均具有较高的鉴别能力（AUC 0.844）。此外，Kaplan-Meier和Cox比例风险分析显示，生存率与血浆mSHOX2值之间存在密切关系，p≤0.001（风险比11.08），这为mSHOX2也是一种预测标志物提供了一些证据。
对细胞外血浆mSHOX2 DNA进行纵向测量可提供有关细胞毒性治疗反应的信息，并能对肺癌患者的治疗反应进行早期评估。如果在更大规模的研究中得到证实，这将是选择和指导细胞毒性治疗的一个有价值的工具。
