title: Serum Transforming Growth Factor-β1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.
authors.affiliation: Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shao-Lun
authors.initials: SL
authors.lastname: Lu
authors.affiliation: Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Hsu
authors.affiliation: Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Tsai
authors.affiliation: Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jian-Kuan
authors.initials: JK
authors.lastname: Wu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Huang
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Koong
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chang
authors.affiliation: Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: jasoncheng@ntu.edu.tw.
authors.forename: Jason Chia-Hsien
authors.initials: JC
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D011014:Pneumonia / Q000209:etiology; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000209:etiology; D043823:Taxoids / Q000008:administration & dosage; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D043823:Taxoids; D053773:Transforming Growth Factor beta1; C080625:taxane; D005472:Fluorouracil