Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases

Abstract

Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8 %) lesions, including 47 (17.3 %) symptomatic cases. 22 of 70 cases (31.4 %) were diagnosed pathologically and 48 (68.6 %) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2 % at 6 months, 17.2 % at 12 months and 34.0 % at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR 2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with radionecrosis risk. This data demonstrates that with close imaging follow-up, radionecrosis after single-fraction SRS for brain metastases is not uncommon. Maximum tumor diameter on pre-treatment MR imaging can provide a reliable estimate of radionecrosis risk prior to treatment planning, with the greatest risk among tumors measuring >1 cm.

DynamicO-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy

“…It has been demonstrated that both larger tumor size and prior WBRT are associated with a higher rate of radionecrosis. 38 On the other hand, it has to be noted that the statistical difference for the higher rate of radiation injury in the group treated with radiosurgery alone is weak (P = .04), and the number of patients in the underlying dataset is too low to derive meaningful conclusions.…”

Institutional experience with SRS VMAT planning for multiple cranial metastases

“…This is higher than for the iPlan plans that have been our clinical standard prior to introducing the VMAT technique but since Gamma Knife plans typically use a PTV D max >140% we accepted this higher inhomogeneity to reduce the GI. The risk of radiation necrosis following cranial SRS has been reported in several studies 13, 14, 15, 16, 17, 18. More data are needed to determine if the difference in dose distribution between the planning techniques have potential clinical consequences.…”

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

“…In the first patient, symptoms developed almost 6 months after the administration of SRS. Although uncommon, it is not impossible to have symptomatic regrowth of lesions-unrelated to tumor recurrence-as early as 6 months after treatment, especially in larger lesions (5). However, given the initial size of the metastatic lesion in this patient, the temporal relationship with pembrolizumab administration, and the more typical delayed development of radiographic and clinical changes following SRS, it is thought that immunotherapy likely played an important role in the pathogenesis of this patient's post-SRS lesions.…”

“…Radiographic changes-unrelated to tumor after stereotactic radiosurgery (SRS) for brain metastasis are well documented (1)(2)(3)(4)(5). Classically, these changes manifest clinically months to years after SRS (5,6).…”

“…Classically, these changes manifest clinically months to years after SRS (5,6). The addition of immune-modulating therapies to systemic treatment paradigms is becoming standard of care in some malignancies that tend to metastasize to the brain, in particular melanoma and non-small cell lung cancer (NSCLC; refs.…”