title: Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases.
abstract: OBJECTIVE
  To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases.
  
  
  METHODS
  From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board-approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm(3) (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm(3) gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping.
  
  
  RESULTS
  Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose-response predictor than the minPTV dose.
  
  
  CONCLUSIONS
  The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose-response outcomes should increase the concordance between the planned and delivered doses.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaminath
authors.affiliation: Department of Medical Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Massey
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Brierley
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rob
authors.initials: R
authors.lastname: Dinniwell
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Radiation Therapy, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Velec
authors.affiliation: Department of Medical Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kristy K
authors.initials: KK
authors.lastname: Brock
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: laura.dawson@rmp.uhn.on.ca.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001943:Breast Neoplasms; D015179:Colorectal Neoplasms; D054893:Cone-Beam Computed Tomography; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000379:methods; D012119:Respiration; D013997:Time Factors; D047368:Tumor Burden