title: Analysis of Clinical and Dosimetric Factors Influencing Radiation-Induced Lung Injury in Patients with Lung Cancer.
abstract: OBJECTIVE
  Dose escalation of thoracic radiation can improve the local tumor control and surivival, and is in the meantime limited by the occurrence of radiation-induced lung injury (RILI). This study investigated the clinical and dosimetric factors influencing RILI in lung-cancer patients receiving chemoradiotherapy for better radiation planning.
  
  
  METHODS
  A retrospective analysis was carried out on 161 patients with non-small-cell or small-cell lung cancer (NSCLC and SCLC, respectively), who underwent chemoradiotherapy between April 2010 and May 2011 with a median follow-up time of 545 days (range: 39-1453). Chemotherapy regimens were based on the histological type (squamous cell carcinoma, adenocarcinoma, or SCLC), and radiotherapy was delivered in 1.8-3.0 Gy (median, 2.0 Gy) fractions, once daily, to a total of 39-66 Gy (median, 60 Gy). Univariate analysis was performed to analyze clinical and dosimetric factors associated with RILI. Multivariate analysis using logistic regression identified independent risk factors correlated to RILI.
  
  
  RESULTS
  The incidence of symptomatic RILI (≥grade 2) was 31.7%. Univariate analysis showed that V5, V20, and mean lung dose (MLD) were significantly associated with RILI incidence (P=0.029, 0.048, and 0.041, respectively). The association was not statistically significant for histological type (NSCLC vs. SCLC, P = 0.092) or radiation technology (IMRT vs. 3D-CRT, P = 0.095). Multivariate analysis identified MLD as an independent risk factor for symptomatic RILI (OR=1.249, 95%CI=1.055-1.48, P= 0.01). The incidence of bilateral RILI in cases where the tumor was located unilaterally was 22.7% (32/141) and all dosimetric-parameter values were not significantly different (P>0.05) for bilateral versus ipsilateral injury, except grade-1 (low) RILI (P < 0.05). The RILI grade was higher in cases of ipsilateral lung injury than in bilateral cases (Mann-Whitney U test, z=8.216, P< 0.001).
  
  
  CONCLUSIONS
  The dosimetric parameter, MLD, was found to be an independent predictive factor for RILI. Additional contralateral injury does not seem to be correlated with increased RILI grade under the condition of conventional radiotherapy treatment planning.
authors.affiliation: 1. First Clinical Medical School, Wenzhou Medical University, Wenzhou, China ; 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Shuiyun
authors.initials: S
authors.lastname: Han
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Feiying
authors.initials: F
authors.lastname: Gu
authors.affiliation: 1. First Clinical Medical School, Wenzhou Medical University, Wenzhou, China ; 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Yuezhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Zhun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Qingren
authors.initials: Q
authors.lastname: Lin
authors.affiliation: 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Denghu
authors.initials: D
authors.lastname: Weng
authors.affiliation: 1. First Clinical Medical School, Wenzhou Medical University, Wenzhou, China ; 2. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 3. Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Mao
keywords: Dose-volume-histogram; lung cancer; radiation-induced lung injury