title: Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.
abstract: OBJECTIVE
  To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery.
  
  
  METHODS
  Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors.
  
  
  RESULTS
  Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving > or = 5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses > or = 5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses > or = 5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005).
  
  
  CONCLUSIONS
  Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of > or = 5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shu-lian
authors.initials: SL
authors.lastname: Wang
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Ara A
authors.initials: AA
authors.lastname: Vaporciyan
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Helen
authors.initials: H
authors.lastname: Liu
authors.forename: Xiong
authors.initials: X
authors.lastname: Wei
authors.forename: Stephen
authors.initials: S
authors.lastname: Swisher
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
mesh_terms: D000704:Analysis of Variance; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D007902:Length of Stay; D016015:Logistic Models; D008168:Lung / Q000528:radiation effects*; D008297:Male; D011014:Pneumonia / Q000209:etiology*; D011183:Postoperative Complications / Q000209:etiology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D012189:Retrospective Studies; D012737:Sex Factors; D018709:Statistics, Nonparametric
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin