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-ß1 (TGF-ß1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-ß1 concentration (-11,310 vs -5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-ß1 concentration (-37.4% vs -25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-ß1 >7040 pg/mL (P=.014) were independent factors associated with PPCs.Preoperative FVC and decrease in serum TGF-ß1 level after dose-limited CCRT to the lung are associated with the development of PPCs.
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