title: Normal tissue complication probability models for severe acute radiological lung injury after radiotherapy for lung cancer.
abstract: OBJECTIVE
  To derive Normal Tissue Complication Probability (NTCP) models for severe patterns of early radiological radiation-induced lung injury (RRLI) in patients treated with radiotherapy (RT) for lung tumors. Second, derive threshold doses and optimal doses for prediction of RRLI to be used in differential diagnosis of tumor recurrence from RRLI during follow-up.
  
  
  METHODS
  Lyman-EUD (LEUD), Logit-EUD (LogEUD), relative seriality (RS) and critical volume (CV) NTCP models, with DVH corrected for fraction size, were used to model the presence of severe early RRLI in follow-up CTs. The models parameters, including α/β, were determined by fitting data from forty-five patients treated with IMRT for lung cancer. Models were assessed using Akaike information criterion (AIC) and area under receiver operating characteristic curve (AUC). Threshold doses for risk of RRLI and doses corresponding to the optimal point of the receiver operating characteristic (ROC) curve were determined.
  
  
  RESULTS
  The α/βs obtained with different models were 2.7-3.2 Gy. The thresholds and optimal doses curves were EUDs of 3.2-7.8 Gy and 15.2-18.1 Gy with LEUD, LogEUD and RS models, and μd of 0.013 and 0.071 with the CV model. NTCP models had AUCs significantly higher than 0.5. Occurrence and severity of RRLI were correlated with patients' values of EUD and μd.
  
  
  CONCLUSIONS
  The models and dose levels derived can be used in differential diagnosis of tumor recurrence from RRLI in patients treated with RT. Cross validation is needed to prove prediction performance of the model outside the dataset from which it was derived.
authors.affiliation: Medical Physics, CRO Aviano National Cancer Institute, 33081 Aviano, Italy. Electronic address: mavanzo@cro.it.
authors.forename: M
authors.initials: M
authors.lastname: Avanzo
authors.affiliation: Radiation Oncology Department, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Trovo
authors.affiliation: Radiation Oncology Department, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Furlan
authors.affiliation: Medical Physics, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Barresi
authors.affiliation: Institute of Diagnostic Radiology, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Linda
authors.affiliation: MRI Applications and Workflow, General Electric, 78533 Buc, France.
authors.forename: J
authors.initials: J
authors.lastname: Stancanello
authors.affiliation: Radiation Oncology Department, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Andreon
authors.affiliation: Radiation Oncology Department, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Minatel
authors.affiliation: Institute of Diagnostic Radiology, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bazzocchi
authors.affiliation: Radiation Oncology Department, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Trovo
authors.affiliation: Medical Physics, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Capra
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology*; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012306:Risk; D012449:Safety
keywords: IMRT; Lung injury; Lung tumors; NTCP; Tomotherapy