Evaluating the natural growth rate of metastatic cancer to the brain.

BACKGROUND: Brain metastases are becoming increasingly more prevalent as cancer patients survive longer with both improved local and systemic therapy. Little is known, however, of the natural growth rates of brain metastases. This investigation aims to ascertain this growth rate of these lesions before the initiation of any CNS- directed therapy. METHODS: A total of 700 patients were screened, identifying 18 cancer patients (13 breast and 5 lung) with 29 brain metastases that were serially imaged from 2011 to 2017 before treatment for their intracranial metastases. Growth rates were measured by contouring lesions serially across at least two MRI studies in iPlan software by independent raters. These values were then compared between primary (breast and lung) cancer cohorts. RESULTS: The mean age at diagnosis was 53 and 95% were female. The interval between primary cancer diagnosis and brain metastases was 4.6 years and 1.2 years in the breast and lung cancer groups, respectively. Of the breast and lung cancer patients, 23% and 40% were deceased, with respective 5.08 cm3 and 2.44 cm3 initial tumor volumes. The average growth rate of lung and breast tumors was 0.018 and 0.040 cm3/day, respectively, with deceased patients having larger and faster growing tumors. Breast and lung metastases grew 2.39% and 1.14% of their total volumes daily and doubling times were 86 and 139 days, respectively. CONCLUSION: This investigation provides a unique perspective into the biological growth of metastatic brain lesions. It is our hope that this study guides timing of treatment and informs both clinicians and patients of tumor growth kinetics before initiating treatment for intracranial metastases.

Glioblastoma multiforme presenting with an open ring pattern of enhancement on MR imaging.

BACKGROUND: Intracerebral ring enhancing lesions can be the presentation of a variety of pathologies, including neoplasia, inflammation, and autoimmune demyelination. Use of a precise diagnostic algorithm is imperative in correctly treating these lesions and minimizing potential adverse treatment effects. CASE DESCRIPTION: A 55-year-old patient presented to the hospital with complaints of a post-concussive syndrome and a non-focal neurologic exam. Imaging revealed a lesion with an open ring enhancement pattern, minimal surrounding vasogenic edema, and minimal mass effect. Given the minimal mass effect, small size of the lesion, and nonfocal neurological exam, we elected to pursue a comprehensive noninvasive neurologic workup because our differential ranged from inflammatory/infectious to neoplasm. Over the next 8 weeks, the patient's condition worsened, and repeat imaging showed marked enlargement of the lesion with a now closed ring pattern of enhancement with satellite lesions and a magnetic resonance (MR) spectroscopy and perfusion signature suggestive of neoplasm. The patient was taken to surgery for biopsy and debulking of the lesion. Surgical neuropathology examination revealed glioblastoma multiforme. CONCLUSION: The unique open ring enhancement pattern of this lesion on initial imaging is highly specific for a demyelinating process, however, high-grade glial neoplasms can also present with complex and irregular ring enhancement including an open ring sign. Therefore, other imaging modalities should be used, and close follow-up is warranted when the open ring sign is encountered.

Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling.

OBJECTIVE: Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen. METHODS: We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT. RESULTS: 10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively. CONCLUSION: FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose-response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose-response relationship for LC in patients treated with FSRT for brain metastases.

ILAE type 3 hippocampal sclerosis in patients with anti-GAD-related epilepsy.

OBJECTIVE: To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti-glutamic acid decarboxylase (GAD) concentrations. METHODS: Small case series. RESULTS: Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. CONCLUSIONS: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD-related neurologic syndrome in some instances.

Dynamic perfusion MRI characteristics of dural metastases and meningiomas: a pilot study characterizing the first-pass wash-in phase beyond relative cerebral blood volume.

OBJECTIVE: Dural metastases and meningiomas are extraaxial lesions that may be difficult to distinguish using conventional imaging methods. This distinction, however, is clinically important. Perfusion MRI may play a role in preoperative assessment. The aim of this study was to evaluate the utility of perfusion parameters in differentiating between these two entities. In particular, we evaluated two new metrics that reflect the first-pass wash-in characteristics of perfusion. MATERIALS AND METHODS: Patients with intracranial extraaxial masses who underwent perfusion MRI were included. Region-of-interest analysis was performed and several perfusion metrics were calculated including relative cerebral blood volume (rCBV), mean transit time and time to peak (TTP) enhancement from initial bolus enhancement (T0), calculated as TTP-T(0). Two new metrics characterizing first pass wash-in enhancement were also measured: relative wash-in time and wash-in slope. Lesions were divided into two groups: meningioma and metastasis. Comparisons between the two groups were made using Wilcoxon rank sum and Fisher exact tests. RESULTS: Twenty lesions were studied (12 meningioma and 8 metastases). Compared with meningiomas, relative wash-in time was statistically lower in metastases (p < 0.05). No other statistically significant differences were observed. Specifically, there was no difference between the two study groups in rCBV. CONCLUSION: First-pass wash-in characteristics of dural lesions may be useful for evaluating and characterizing lesions. In particular, a metric describing the wash-in phase of perfusion-that is, relative wash-in time-was found to be lower in metastases compared with meningiomas. Contrary to a prior report, we found rCBV to be limited in the evaluation of extraaxial lesions.