title: Dosimetric predictors of radiation-induced lung injury in stereotactic body radiation therapy.
abstract: METHODS
  The aim was to retrospectively investigate correlations between potential predictive parameters and the occurrence of radiation-induced lung injury in patients with primary or secondary lung tumours treated with stereotactic body radiation therapy (SBRT). Sixty patients (63 tumours) underwent SBRT, with a dose of 45 Gy in 3 fractions over 5 days or 26 Gy in single fraction. The following parameters were tested for correlation with Radiation Therapy Oncology Group (RTOG) lung toxicity score: planning target volume (PTV), tumour location, primary vs. metastatic tumour, and Mean Lung Dose (in 2 Gy fractions, MLD2). Normal Tissue Complication Probability (NTCP) values were then estimated.
  
  
  RESULTS
  The median follow-up time was 30.9 months (range 6.7-56.7). RTOG grade 0-1 toxicity was observed in 54/63 (85.7%) and grade 2-3 in 9/63 (14.3%) cases. Mean values of MLD(2) for RTOG grade 0-1 and 2-3 were respectively 11.2 Gy (95% Confidence Interval (CI) 10.1-12.3 Gy) and 20.3 Gy (95% CI 16.6-23.9 Gy). NTCP mean values for RTOG grade 0-1 and 2-3 were respectively 4% (95% CI 2-5.9%) and 37% (95% CI 11.6-62.3%). Univariate analysis, performed with t-Student test, showed a statistically significant difference between MLD(2) values in the two groups (t=5.93 and p < or = 0.001). Logistic regression analysis showed a good correlation between MLD(2) and toxicity scores 2-3 (p=0.008, odds ratio 1.5). From logistic regression relationship between the observed rates of grade 2-3 and MLD(2), a D(50)=19.8 Gy and a gamma50= 2.2 were obtained. From the sigmoid-shaped dose-response relationship between NTCP and MLD(2), a D(50)=22.4 Gy and gamma(50)= 2.2 were derived.
  
  
  CONCLUSIONS
  MLD(2) is strongly associated to the risk of lung injury. Higher NTCP values are associated with a higher risk, but when comparing the expected to the observed toxicity rate, NTCP seems to underestimate the risk.
authors.affiliation: Department of Medical and Surgical Sciences, University of Torino, S. Giovanni Battista Hospital, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Filippi
authors.forename: Alessia
authors.initials: A
authors.lastname: Guarneri
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Giglioli
authors.forename: Cristina
authors.initials: C
authors.lastname: Mantovani
authors.forename: Christian
authors.initials: C
authors.lastname: Fiandra
authors.forename: Silvia
authors.initials: S
authors.lastname: Anglesio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ragona
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000532:radiotherapy* / Q000556:secondary; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index