Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach

Abstract

BackgroundWe retrospectively report treatment results of our single-centre experience with hypofractionated stereotactic radiotherapy (hfSRT) of limited brain metastases in primary and recurrence disease situations. Our aim was to find the most effective and safe dose concept.MethodsFrom 04/2006 to 12/2010, 75 patients, with 108 intracranial metastases, were treated with hfSRT. 52 newly diagnosed metastases (48%), without up-front whole brain radiotherapy (WBRT), received hfSRT as a primary treatment. 56 metastases (52%) received a prior WBRT and were treated in this study in a recurrence situation. Main fractionation concepts used for primary hfSRT were 6-7x5 Gy (61.5%) and 5x6 Gy (19.2%), for recurrent hfSRT 7-10x4 Gy (33.9%) and 5-6x5 Gy (33.9%).ResultsMedian overall survival (OS) of all patients summed up to 9.1 months, actuarial 6-and 12-month-OS was 59% and 35%, respectively. Median local brain control (LC) was 11.9 months, median distant brain control (DC) 3.9 months and intracranial control (IC) 3.4 months, respectively. Variables with significant influence on OS were Gross Tumour Volume (GTV) (p = 0.019), the biological eqivalent dose (calculated on a 2 Gy single dose, EQD2, α/β = 10) < and ≥ median of 39 Gy (p = 0.012), extracerebral activity of the primary tumour (p < 0.001) and the steroid uptake during hfSRT (p = 0.03). LC was significantly influenced by the EQD2, ≤ and > 35 Gy (p = 0.004) in both uni- and multivariate Cox regression analysis. Median LC was 14.9 months for EQD2 >35 Gy and 3.4 months for doses ≤35 Gy, respectively. Early treatment related side effects were usually mild. Nevertheless, patients with a EQD2 >35 Gy had higher rates of toxicity (31%) than ≤35 Gy (8.3%, p=0.026).ConclusionComparing different dose concepts in hfSRT, a cumulative EQD2 of ≥35 Gy seems to be the most effective concept in patients with primary or recurrent limited brain metastases. Despite higher rates of only mild toxicity, this concept represents a safe treatment option.

Local control after fractionated stereotactic radiation therapy for brain metastases

“…Of the studies that looked at different dosing regimens, Aoyama et.al reported an association between the isocenter dose \35 Gy or peripheral dose \32 Gy with lower local control in univariate analysis, though this factor was no longer significant in their multivariate analysis [41]. OS overall survival, LC local control, LR local recurrence, HR hazard ratio, WBRT whole brain radiotherapy, SRT stereotactic radiotherapy, Gyn gynecologic, GI gastrointestinal, Gy gray, fx fractions EQD 2 [35 Gy had superior local control to those who did not (57 vs. 22 % at 1 year), though there was no significant difference in local control between the different dose concepts they examined [37]. However, in two additional studies in which several SRT doses were used, radiation dose was not associated with local control or survival [31,33].…”

“…At our institution, we use 25 Gy in 5 fractions most commonly, which is the most commonly used SRT fractionation regimen used in the United States according to a national survey of radiation oncologists who treat brain metastases with SRS/SRT [28]. The average reported local control rate after SRT is approximately 78 % (range 52-100 %) [15,[29][30][31][32][33][34][35][36][37][38][39][40], though many of the studies did not specifically isolate patients who did and did not receive WBRT. Two studies directly compared SRS with SRT, and there was no significant difference in local control or survival [31,32].…”

“…In our results, we found local control estimates to be significantly lower (56 % at 1 year) if we censored at the time of death using the Kaplan-Meier method, as compared to local control rates when treating death as a competing risk (71 % at year). It is not always clear which type of analyses were performed in previous SRT studies; some have relatively clear descriptions of the use of Kaplan-Meier methods for the assessment of local control where death is presumably censored in a noninformative manner [37,41]. Others may report response rates [30], which have results more like competing risk models, as stable disease at 3 months followed by death at 4 months would count as stable disease with no time component and overestimate local control relative to Kaplan-Meier.…”

Adjuvant therapy after resection of brain metastases

“…However, it is difficult to compare the results of these studies due to the large hetereogeneity of the fractionation regimens. A recent report comparing different dose concepts in SHRT showed that EQD2s of ≥35 Gy seem to be the most effective concept in patients with primary or recurrent limited primary brain metastases [14]. We compared SRS to different hypofractionated regimens and failed to find any fractionation-associated differences in LC due to the high diversity of dose concepts.…”

Streamlining the Workflow of Stereotactic Radiosurgery (SRS) on Tomotherapy: Experience from a Tertiary Care Centre from India

“…Metastatic brain tumors comprise of nearly 20-40% of all patients diagnosed with cancer [3][4]. As per current evidence, the primary treatment approaches for metastatic brain tumors include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS) [3][4][5]. WBRT has remained the primary treatment for patients presenting with high intracranial tumor burden.…”