Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

Michelle A Stinauer,Rene Gonzalez,William Robinson,Brian D Kavanagh,Michael Glode,David Raben,Thomas Flaig,Karl Lewis,Mark Chidel,Tracey E Schefter

doi:10.1186/1748-717x-6-34

Abstract

BackgroundMelanoma 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.MethodsThe 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.ResultsThe 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.ConclusionsAn 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.

Highlights

Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies
We retrospectively reviewed all patients with melanoma and RCC treated with stereotactic body radiation therapy (SBRT) to metastatic sites from October 2004 to November 2009 at the University of Colorado
Seventeen patients had oligometastatic disease at time of treatment with all sites treated with SBRT, and 13 patients had extensive disease in which only selected lesions were treated with SBRT

Summary

Introduction

Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. For at least three decades, renal cell carcinoma (RCC) and melanoma have been considered to be relatively “radioresistant” tumors. In the case of RCC, this opinion was initially based on observations that substantially higher doses of conventionally fractionated radiotherapy (RT) must be employed to achieve the same level of clinical response produced with lower dose for most other histologies [1]. For the case of melanoma, laboratory studies in the early 1970s suggested that higher radiation doses per fraction would be needed to achieve effective cell kill [2]. A dose-response relationship for palliative effect was observed by Onufrey and Mohiuddin among 125 patients treated for metastatic RCC [4], though their results were somewhat at variance with those of Halperin and Harisidias [5]. Multiple melanoma randomized studies were performed both in Europe and in the United States to explore ways to refine the use of RT in that setting: a Danish study found equivalence between 27 Gy in 3 fractions and 40 Gy in 5 fractions, and an RTOG study likewise found equivalence between 50 Gy in 20 fractions and 32 Gy in 4 fractions in terms of response rate [6,7]

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