title: Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control.
abstract: BACKGROUND
  Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.
  
  
  METHODS
  The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUVmax) were analyzed.
  
  
  RESULTS
  The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.
  
  
  CONCLUSIONS
  An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.
authors.affiliation: University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Stinauer
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.forename: Tracey E
authors.initials: TE
authors.lastname: Schefter
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Thomas
authors.initials: T
authors.lastname: Flaig
authors.forename: Karl
authors.initials: K
authors.lastname: Lewis
authors.forename: William
authors.initials: W
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: Chidel
authors.forename: Michael
authors.initials: M
authors.lastname: Glode
authors.forename: David
authors.initials: D
authors.lastname: Raben
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000532:radiotherapy; D016634:Radiosurgery / Q000379:methods*; D012189:Retrospective Studies