Incidence of Radionecrosis in Single-Fraction Radiosurgery Compared with Fractionated Radiotherapy in the Treatment of Brain Metastasis

Abstract

Introduction Radiation-induced brain necrosis [“radionecrosis” (rn)] is a relatively uncommon but potentially severe adverse effect of stereotactic radiosurgery (srs) for brain metastasis. Although dose, volume, and hypofractionation have been suggested to affect rn rates, patient and treatment variability in this population make it difficult to clearly delineate the risk. We set out to establish the effect of fractionation on rn rates by reviewing patients receiving simultaneous multi-fraction and single-fraction treatment at our centre.Methods Patients receiving simultaneous (within 1 month) 1-fraction (ssrs) and 3-fraction (fsrs) radiosurgery treatments during 2012–2015 were identified in our institution’s database. Serial post-srs magnetic resonance imaging (mri) was reviewed to determine rn and local recurrence. The effect of maximum dose, volume, whole-brain radiotherapy (wbrt), and fractionation on rn development was assessed using logistic regression for paired data. Results are reported using odds ratios (ors) and corresponding 95% confidence intervals (cis).Results Of 90 patients identified, 22 had at least a 6-month mri follow-up. Median follow-up was 320 days. The most common primary tumour type was non-small-cell lung cancer, followed by breast and rectal cancer. Radionecrosis developed in 16 patients [21 of 62 lesions (34%), with 4 being symptomatic (20%)]. Of the 21 lesions in which rn developed, 11 received 3 fractions, and 10 received 1 fraction. The or for the association between the incidence of rn and maximum dose was 1.0 (95% ci: 0.9 to 1.1); for fractionation it was 1.0 (95% ci: 0.3 to 3.6); for previous wbrt, it was 0.4 (95% ci: 0.2 to 1.2); and for a 10-unit increase in volume, it was 3.1 (95% ci: 1.0 to 9.6). Local recurrence developed in 8 patients (12%), 6 of whom belonged to the ssrs group.Conclusions Our results indicate that patients receiving srs for multiple brain metastases experience a higher rate of rn than is reported in the literature and poorer survival despite having equivalent local control. Maximum dose did not appear to be associated with rn risk in our cohort, but volume was significantly associated with rn risk. Although fractionated treatment did not directly lower the rate of rn in this population, it might have played a role in reducing the magnitude of the rn risk in large-volume lesions. Further investigation will help to delineate optimal dose and fractionation so as to minimize rn while maintaining local control in this group.

FSRT vs. SRS in Brain Metastases—Differences in Local Control and Radiation Necrosis—A Volumetric Study

“…In addition, similarly to the work of Minniti et al radiation necrosis was also markedly reduced in the FSRT arm with a radionecrosis rate of 0% in the FSRT arm compared to 39.8% for the SRS group ( 31 ). In the subgroup of large brain metastases, some negative comparative studies have also been published, which were mainly characterized by small patient numbers ( 32 – 34 ). However, we are unaware of any comparative investigations of FSRT and SRS that demonstrated significantly inferior results for the FSRT group.…”

Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization

“…Several studies seem to support the latter proposal. [9,10,17] As illustrated in this report, progressive extracranial disease remains a major problem for many patients with brain metastatic disease. Promising therapeutic breakthroughs Table 3: Tumor volume dynamics of Met 2 and Met 3 throughout treatment (GKRS1-GKRS3) and during follow-up.…”

One-Day Two-Fraction Radiosurgery for Brain Metastases Using Gamma Knife

“…Other than single-fraction SRS, staged-treatment and fractionated irradiation are also available to reduce the risk of perifocal radiation necrosis [6,7,[11][12][13][15][16][17][18]26]. Fractionated doses help to spare normal tissues by allowing time for the repair of sublethal damage and/or potential lethal damage and enhance tumor cell killing by allowing reoxygenation between doses [27].…”

“…Under in vivo conditions with blood flow, reoxygenation is expected to enhance the effectiveness of irradiation to the target tumor [28]. The optimal dose fractionation for a large brain metastasis not responsive to single-fraction SRS has not been established well [15]. Inoue et al reported the importance of a 14 Gy equivalent dose-volume in five-fraction CyberKnife SRS for large brain metastases [16].…”

“…In addition, even if the size of the lesions is 2 to 4 cm, the single fraction irradiation dose would be decreased so as not to increase the possibility of adverse effects on the surrounding normal brain [5,9,10]. Staged-or hypofractionated-SRS regimens have emerged as an alternative to single-fraction treatment when the target tumors are large [6,7,[11][12][13][14][15][16][17]. Staged-or hypofractionated SRS maintains the stereotactic advantages of precise tumor localization and sharp dose fall-off while using the biologic advantage of fractionation, and might, therefore, improve the therapeutic ratio in selected patients [11].…”