Harder Eileen M, Park Henry S, Nath Sameer K, Mancini Brandon R, Decker Roy H
Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Department of Therapeutic Radiology Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Pract Radiat Oncol. 2015 Nov-Dec;5(6):e643-9. doi: 10.1016/j.prro.2015.07.003. Epub 2015 Jul 17.
Although angiotensin-converting enzyme (ACE) inhibitor use during conventionally fractionated radiation therapy has been associated with a decreased risk of radiation pneumonitis (RP), a similar effect has not been demonstrated in stereotactic body radiation therapy (SBRT). The purpose of this study was to examine the impact of ACE inhibitor use during SBRT on the risk of symptomatic (grade ≥2) RP.
Patients with at least 1 follow-up treated with SBRT for primary lung cancer were included. ACE inhibitors, angiotensin receptor blockers, statins, nonsteroidal anti-inflammatory drugs, and glucocorticoids were examined. RP was determined from all available medical records, including follow-up appointments with radiation oncology, pulmonology, medical oncology, and hospitalizations. It was scored with the Common Terminology Criteria for Adverse Events, version 4.0. Analysis was performed with Kaplan-Meier and Cox proportional hazards modeling.
A total of 257 patients met inclusion criteria. Seventy (27.2%) used an ACE inhibitor during SBRT. The overall rates of grade ≥2 and ≥3 RP were 19.1% (n = 49) and 7.0% (n = 18), respectively. ACE inhibitor users experienced greater freedom from symptomatic RP on univariate (vs nonusers, 89.8% vs 76.3% at 12 months, P = .029) and multivariate analysis (hazard ratio 0.373, 95% confidence interval 0.156-0.891, P =.026). The volume of normal lung tissue receiving ≥5 Gy, %, ≥10 Gy, ≥20 Gy, and mean lung dose were also significantly associated with RP on univariate and multivariate analysis. ACE inhibitor use was not associated with overall survival. Angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, glucocorticoids, and statin administration were not associated with symptomatic RP or survival.
ACE inhibitor use during SBRT was associated with significantly greater freedom from grade ≥2 RP, even after adjusting for pulmonary dose. Given the data on their protective effect in human and animal models, a prospective evaluation is warranted.
虽然在传统分割放射治疗期间使用血管紧张素转换酶（ACE）抑制剂与放射性肺炎（RP）风险降低相关，但在立体定向体部放射治疗（SBRT）中尚未证实有类似效果。本研究的目的是探讨SBRT期间使用ACE抑制剂对有症状（≥2级）RP风险的影响。
纳入至少接受过1次SBRT治疗原发性肺癌的患者。研究了ACE抑制剂、血管紧张素受体阻滞剂、他汀类药物、非甾体抗炎药和糖皮质激素。通过所有可用的医疗记录确定RP，包括放射肿瘤学、肺病学、医学肿瘤学的随访预约以及住院记录。根据不良事件通用术语标准4.0版进行评分。采用Kaplan-Meier法和Cox比例风险模型进行分析。
共有257例患者符合纳入标准。70例（27.2%）在SBRT期间使用了ACE抑制剂。≥2级和≥3级RP的总体发生率分别为19.1%（n = 49）和7.0%（n = 18）。单因素分析显示，ACE抑制剂使用者出现有症状RP的自由度更高（与未使用者相比，12个月时分别为89.8%和76.3%，P = 0.029），多因素分析也是如此（风险比0.373，95%置信区间0.156 - 0.891，P = 0.026）。在单因素和多因素分析中，接受≥5 Gy、≥10 Gy、≥20 Gy的正常肺组织体积以及平均肺剂量也与RP显著相关。使用ACE抑制剂与总生存期无关。血管紧张素受体阻滞剂、非甾体抗炎药、糖皮质激素和他汀类药物的使用与有症状RP或生存期无关。
即使在调整肺剂量后，SBRT期间使用ACE抑制剂仍与≥2级RP的自由度显著更高相关。鉴于其在人类和动物模型中的保护作用数据，有必要进行前瞻性评估。
