Department of Medical Oncology, Radboud university medical center, route 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Medical Oncology, Jeroen Bosch Hospital, P.O. Box 90153, 5200 ME, 's Hertogenbosch, The Netherlands.
Target Oncol. 2019 Aug;14(4):441-451. doi: 10.1007/s11523-019-00656-2.
Everolimus-related interstitial lung disease (ILD) (also: pneumonitis) poses a difficulty for physicians, as it is hard to discriminate ILD from other causes of respiratory symptoms and to decide on safe treatment continuation.
We investigated the capability of pulmonary function tests (PFT), plasma biomarkers, everolimus pharmacokinetics, and FDG-PET to discriminate between everolimus-related ILD and other causes of respiratory problems and to predict the severity of ILD.
Women starting treatment with everolimus plus exemestane for advanced breast cancer were included. At baseline and during the first 3 months, respiratory symptoms, PFT with diffusion capacity of the lungs for carbon monoxide corrected for hemoglobin (DLCOc) and forced vital capacity, serum plasma biomarkers (including SP-D and YKL-40), everolimus trough concentration, and F-FDG-PET were prospectively recorded.
Twenty-seven (out of 29 included) patients were evaluable for analysis. Fifteen patients (56%) developed everolimus-related respiratory signs or symptoms and four patients (15%) needed everolimus discontinuation and received corticosteroids. Change in DLCOc differentiated ILD from alternative diagnoses with 0.91 sensitivity and 0.78 specificity. Decrease in DLCOc (non-significant) was greatest in patients who needed everolimus discontinuation. Serum SP-D and YKL-40 could differentiate ILD from alternative diagnoses with 0.83 and 0.83 sensitivity, and 0.85 and 0.62 specificity, respectively. F-FDG-PET abnormalities did not precede clinical symptoms. No relationship between ILD and everolimus trough concentration was found.
This study shows that everolimus-related ILD occurs frequently. Prospective monitoring of DLCOc in combination with measurement of serum SP-D and YKL-40 appear useful to discriminate ILD from other causes of respiratory symptoms. Clinicaltrials.gov identifier: NCT01978171.
依维莫司相关性间质性肺病（ILD）（也称为肺炎）给医生带来了困难，因为难以将ILD 与其他引起呼吸症状的原因区分开来，也难以确定安全的治疗方案。
我们研究了肺功能检查（PFT）、血浆生物标志物、依维莫司药代动力学、18F-氟脱氧葡萄糖正电子发射断层扫描（18F-FDG-PET）在区分依维莫司相关性ILD 与其他引起呼吸问题的原因，以及预测ILD 严重程度方面的能力。
纳入了开始接受依维莫司联合依西美坦治疗晚期乳腺癌的女性患者。在基线和前 3 个月内，记录了呼吸症状、PFT（包括血红蛋白校正后的一氧化碳弥散量[DLCOc]和用力肺活量）、血清血浆生物标志物（包括 SP-D 和 YKL-40）、依维莫司谷浓度和 18F-FDG-PET。
27 例（共 29 例纳入）患者可进行分析。15 例患者（56%）出现依维莫司相关性呼吸症状或体征，4 例患者（15%）需要停用依维莫司并接受皮质类固醇治疗。DLCOc 的变化可将ILD 与其他诊断区分开来，其敏感性为 0.91，特异性为 0.78。需要停用依维莫司的患者 DLCOc 下降最明显（无统计学意义）。血清 SP-D 和 YKL-40 可分别以 0.83 和 0.83 的敏感性、0.85 和 0.62 的特异性将ILD 与其他诊断区分开来。18F-FDG-PET 异常并未先于临床症状出现。未发现 ILD 与依维莫司谷浓度之间存在相关性。
本研究表明，依维莫司相关性 ILD 较为常见。前瞻性监测 DLCOc 并结合检测血清 SP-D 和 YKL-40 似乎有助于将 ILD 与其他引起呼吸症状的原因区分开来。临床试验注册号：NCT01978171。
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