Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):1023-31. doi: 10.1016/j.ijrobp.2015.08.035. Epub 2015 Aug 28.
Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy.
We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically.
Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-β1 (TGF-β1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-β1 concentration (-11,310 vs -5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-β1 concentration (-37.4% vs -25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-β1 >7040 pg/mL (P=.014) were independent factors associated with PPCs.
Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.
本研究旨在探讨新辅助同步放化疗（CCRT）联合手术治疗局部晚期食管鳞癌（ESCC）患者术后肺部并发症（PPC）与临床因素、剂量学参数和生物标志物之间的关系，同时该研究对肺部剂量限制下的 CCRT 和食管切除术进行了严格的限定。
本研究前瞻性纳入 112 例接受三模态治疗（包括放疗[40Gy]、紫杉烷类/5-氟尿嘧啶类同步治疗和根治性食管切除术）的 ESCC 患者。术后 30 天内发生肺炎或急性呼吸窘迫综合征的患者被定义为 PPC 患者。在 CCRT 前和 CCRT 后 1 个月内采集血清样本。通过邻近连接分析（PLA）检测血清生物标志物与 PPC 的相关性，并通过酶联免疫吸附试验（ELISA）进行验证。统计分析临床因素、肺剂量学参数和生物标志物与 PPC 的相关性。
33 例（29.5%）患者发生 PPC。没有一个剂量学参数与 PPC 相关。术前功能肺活量（FVC）与 PPC 显著相关（P=.004）。在 15 种 PLA 筛选的生物标志物中，治疗后转化生长因子-β1（TGF-β1）与 PPC 呈边缘显著相关（P=.087）。与无 PPC 患者相比，PPC 患者 CCRT 后血清 TGF-β1 浓度的下降（-11310 与-5332pg/ml，P=.005）和 CCRT 前后血清 TGF-β1 浓度下降百分比（-37.4%与-25.0%，P=.009）显著更大。多因素分析显示，术前 FVC（P=.003）和 TGF-β1 下降>7040pg/ml（P=.014）是与 PPC 相关的独立因素。
术前 FVC 和肺剂量限制下 CCRT 后血清 TGF-β1 水平的降低与 PPC 的发生有关。
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