title: Correlation of clinical and dosimetric factors with adverse pulmonary outcomes in children after lung irradiation.
abstract: OBJECTIVE
  To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation.
  
  
  METHODS
  We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period.
  
  
  RESULTS
  We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V22 (volume of lung exposed to a radiation dose ≥22 Gy) and V30 (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and Vdose (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01).
  
  
  CONCLUSIONS
  Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California, USA. rvenkatramani@chla.usc.edu
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatramani
authors.forename: Sunil
authors.initials: S
authors.lastname: Kamath
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wong
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Olch
authors.forename: Jemily
authors.initials: J
authors.lastname: Malvar
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Fariba
authors.initials: F
authors.lastname: Goodarzian
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Keens
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003371:Cough / Q000453:epidemiology / Q000209:etiology; D003520:Cyclophosphamide / Q000009:adverse effects; D004417:Dyspnea / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D010102:Oxygen Inhalation Therapy / Q000706:statistics & numerical data; D011014:Pneumonia / Q000453:epidemiology / Q000209:etiology; D017564:Radiation Pneumonitis / Q000453:epidemiology / Q000209:etiology; D011879:Radiotherapy Dosage; D012129:Respiratory Function Tests; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D003520:Cyclophosphamide