Department of Radiation Oncology, Billerica, MA.
Center for Atmospheric and Environmental Chemistry, Aerodyne Research Inc., Billerica, MA.
J Thorac Oncol. 2014 Jul;9(7):957-964. doi: 10.1097/JTO.0000000000000182.
In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors.
Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters.
Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development.
The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.
在这项前瞻性的初步研究中，我们评估了测量多种呼出气作为接受立体定向消融放疗（SABR）治疗肺部肿瘤的患者放射性肺炎（RP）生物标志物的可行性和潜在效用。
对 26 例接受 SABR 治疗肺部肿瘤的患者进行了呼吸分析。使用实时红外激光光谱法，在每次分割前和分割后立即测量呼出气一氧化氮（eNO）、一氧化碳（eCO）、氧化亚氮（eN2O）和二氧化碳（eCO2）的浓度。将 RP 发展（CTCAE 分级≥2）与基线气体浓度、每次 SABR 分割后气体浓度的急性变化以及剂量学参数相关联。
在可评估的 20 例患者中，有 5 例发生了 RP，发生时间为 SABR 后 5.4 个月。与非 RP 患者相比，RP 患者的 eNO 和 eCO 浓度急性变化（分别为每次分割前后测量值之间的百分比变化）显著较小（p=0.022 和 0.015）。在一项探索性分析中，基线 eNO 大于 24 个部分每十亿和 eCO 急性下降小于 5.5%的联合预测因子与 RP 发生率强烈相关（p=0.0099）。eN2O 和 eCO2 浓度与 RP 发展均无显著相关性。虽然在注定发生 RP 的患者中通常更高，但剂量学参数与 RP 发展无显著相关性。
在这项初步研究中，大多数 SABR 患者能够完成呼出气分析。呼出气成分的基线浓度和浓度的急性变化与 SABR 后 RP 的发生有关。如果我们的发现得到验证，呼出气分析可能成为一种用于非侵入性识别 SABR 后发生 RP 风险最高的患者的有用方法。
