Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

Abstract

IntroductionBrain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear.MethodsThis single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher’s exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure.ResultsA total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure.DiscussionAn optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy.

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

“…In the abovementioned study of Leu et al [18], the overall incidence of radionecrosis cohort was 22.27% (and about 40% of them asymptomatic). The median time to development of radionecrosis was 221 days.…”

“…Leu et al [18] retrospectively examined 107 patients with 256 brain metastases of various histologies (mainly NSCLC). At multivariate analyses, NSCLC histology (hazard ratio 0.23, 95% CI 0.09–0.58, P = 0.0018) and concurrent ICI (hazard ratio 0.31, 95% CI 0.12–0.81, P = 0.0159) were associated with a lower risk of local failure, while male sex and increased tumor volumes were associated with an increased risk of local failure.…”

Advances in Neuro-Oncological Imaging: An Update on Diagnostic Approach to Brain Tumors

“…As new treatments emerge for cancer patients, new imaging tools must be used to better differentiate between cancerous tissue and recovering tissue. One such field is stereotactic radiosurgery, wherein surgeons irradiate specific brain tissues in a targeted manner, avoiding injury to surrounding healthy tissue [9]. Various studies assessing post-treatment tumor recurrence have been conducted, and one emerging radiotracer that has proven successful is an amino acid radiotracer known as [11C] Methionine, which is discussed further in the following section [10].…”