The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases

Abstract

Object. Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2-5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation.Methods. The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2-5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery.Results. There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83-6.91, p = 0.032).Conclusions. Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions. (http://thejns.org/doi/abs/10.3171/2013.8.JNS122177) KEy wOrdS • brain metastases • local control • radioresistance • stereotactic radiosurgery • oncology 1131Abbreviations used in this paper: IQR = interquartile range; OS = overall survival; WBRT = whole-brain radiation therapy.

High-dose and fractionation effects in stereotactic radiation therapy: Analysis of tumor control data from 2965 patients

“…DAICc = 0 for the best-fitting model, and models with large DAICc values (>6) have much poorer support from the data. Details are discussed in the main text and in Appendix B. no support for the hypothesis that single-fraction regimens are inherently more effective than multiple fractions [14][15][16][17], and at a biologically plausible a/b ratio of 10 Gy there was some support for higher effectiveness of multiple fractions.…”

“…Clinical results, even for some non-standard scenarios (hyperfractionation [5], high-vs. low dose-rate brachytherapy [6], prostate hypofractionation [7]) were consistent with LQ predictions. In contrast to earlier approaches [8][9][10], there have been no major failures.Some investigators have argued that tumor eradication by large doses/fraction is dominated by distinct biological phenomena (e.g., damage to the tumor vasculature) that are qualitatively different from those operating at lower doses, and therefore are not accounted for by the LQ model [11][12][13][14][15][16][17]. By contrast, others argue [18,19] that SRT effectiveness is sufficiently explained by increased tumor doses, which destroy tumors largely through the same mechanisms that operate at lower doses.…”

Local control after fractionated stereotactic radiation therapy for brain metastases

“…With regard to histology, approximately 5 % of patients enrolled on the RTOG 95-08 and EORTC prospective trials had melanoma [2,3], which is significantly lower than in the present study, and this histology has been linked to greater radioresistance [23], though not in all studies [1,4], and was not associated with more aggressive local progression in our study. A recent study found that while local control after singlefraction SRS was similar between classically radiosensitive versus radioresistant brain metastasis histologies, SRT for radioresistant histologies demonstrated worse local control than for radiosensitive histologies, with an odds ratio of 5.37 (95 % CI 3.83-6.91; p = 0.032) [24].…”

Unexpected Daily Changes in Tumor Volume during Fractionated Gamma Knife Radiosurgery for Solitary Intraventricular Metastatic Renal Cell Carcinoma: A Case Report

“…Fractionated SRS has become a common treatment for large tumors or lesions located near radiosensitive structures [1-6]. Although it is widely performed, an optimal uniform time interval between fractionations has not yet been established, and daily imaging is also not routinely performed during fractionated GKRS treatment [4, 5].…”

“…Fractionated stereotactic radiosurgery (SRS) is being increasingly used for large tumors or other lesions, especially those located near radiosensitive structures [1-6]. However, standard interval times between each fractionated radiosurgery have not yet been established [5].…”