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Stereotactic radiosurgery (SRS) has become a preferred treatment in the initial management of brain metastases (BM). This study reported treatment outcomes and identified the patient, tumour, and treatment-related factors that predict failure, survival, and brain necrosis (BN).
Methods:
We retrospectively reviewed the electronic medical records of all BM patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. All recurrences and BN were defined in the neurooncological tumour board.
Results:
From December 2016 to April 2020, 148 patients were analysed. The median follow-up was 14·8 months (range 6–51). At the time of analyses, 72·3% of the patients were alive. Presence of initial neurological deficit (HR; 2·71 (1·07–6·9); p = 0·036) and prior RT (HR; 2·55 (1·28–5·09); p = 0·008) is associated with worse overall survival. The local recurrence rate was 11·5 %. The distant brain metastasis rate was 53·4 %. Leptomeningeal metastasis was seen in 11 patients (7·4%). Symptomatic BN was seen in 19 patients (12·8 %). Bigger lesions (13 versus 23 mm diameter; p = 0·034) and cavity radiosurgery are associated with more BN (63·2 % versus 36·8%; p: 0·004).
Conclusions:
Distant BM is the leading cause of CNS recurrences and, salvage SRS is possible. Due to the increasing risk of developing BN routine metastasectomy should be made with caution.
Cerebral radionecrosis, a subacute or late effect of radiotherapy, can be debilitating and difficult to treat. Steroids can reduce symptoms, but have significant long-term side effects. Bevacizumab has been shown to reduce edema and other radiologic features associated with radionecrosis and improve patient symptoms. We report our experience using bevacizumab for cerebral radionecrosis.
Methods:
We retrospectively reviewed the charts of all patients treated at our institution with bevacizumab for non-glioma-associated cerebral radionecrosis. We recorded change in symptoms, change in steroids, change in performance status, time to tumor progression, and time to death. We delineated the volume of necrosis pre- and post-bevacizumab on T1-post-gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI scans.
Results:
We identified 15 patients, 8 with brain metastases, 6 with meningioma, and 1 with nasopharyngeal carcinoma. Most received four doses of bevacizumab, 7.5 mg/kg q 3 weeks × 4 doses. Neuroimaging demonstrated a reduced T1 gadolinium-enhancing volume and edema in 14/15 patients (the average reduction in T1-post-gadolinium volume was 3.0 cm3, and average reduction in FLAIR volume was 27.9 cm3). There was no appreciable change in patient performance status. Steroid doses decreased in five of nine patients. There was a high rate (26%) of adverse events, including pulmonary embolism, stroke, and wound dehiscence. The median progression-free survival was 6.5 months.
Conclusion:
Although bevacizumab is commonly prescribed for cerebral radionecrosis, in our retrospective cohort, the clinical benefits were modest and there was significant toxicity.
It has been well established that surgical resection in patients with singular symptomatic brain metastases prolongs survival. However, surgical resection for patients with multiple symptomatic brain metastases is less commonly performed and reported in the literature, and even avoided, for a multitude of reasons. However, the advent of minimally invasive keyhole techniques has allowed for an increased survival benefit from simultaneous resections of multifocal or multiple lesions, without increasing morbidity. These keyhole techniques have improved the quality of life in patients with multiple lesions by increasing the total extent of resection, which has been shown to correlate with overall patient survival, while minimizing recovery and morbidity. This chapter details the patient selection criteria, preoperative planning, surgical technique, steps for complication avoidance, and postoperative considerations necessary for developing an appropriate treatment plan utilizing multiple keyhole craniotomies in a single surgical setting.
To identify prognostic factors and investigate patient survival after whole-brain radiotherapy (WBRT) for initial brain metastases arising from non-small cell lung cancer (NSCLC).
Methods:
Patients diagnosed with NSCLC between 1 January 2010 and 30 September 2019, and who received WBRT upon first developing a brain metastasis, were investigated. Overall survival was determined as related to age, sex, duration between initial examination and brain metastasis detection, stage at the first examination, presence of metastases outside the brain, blood analysis findings, brain metastasis symptoms, radiotherapy dose and completion, imaging findings, therapeutic course of chemotherapy and/or radiation therapy, histological type, and gene mutation status.
Results:
Thirty-one consecutive patients (20 men and 11 women) with a mean age of 63·8 years and median survival of 129 days were included. Multivariate analysis with stepwise testing was performed to investigate differences in survival according to gene mutation status, lactate dehydrogenase (LDH) level, irradiation dose, WBRT completion and Stage status. Of these, a statistically significant difference in survival was observed in patients with gene mutation status (hazard ratio: 0·31, 95% CI: 0·11–0·86, p = 0·025), LDH levels <230 vs. ≥230 IU/L (hazard ratio: 4·08, 95% CI: 1·45–11·5, p < 0·01) received 30 Gy, 30 Gy/10 fractions to 35 Gy/14 fractions, and 37·5 Gy/15 fractions (hazard ratio: 0·26, 95% CI: 0·09–0·71, p < 0·01), and stage IV versus non-stage IV (hazard ratio: 0·13, 95 CI:0·02–0·64, p < 0·01)
Findings:
Gene mutation, LDH, radiation dose and Stage are prognostic factors for patients with initial brain metastases who are treated with WBRT.
Small-cell lung cancer (SCLC) has poor prognosis owing to the high risk of distant metastasis.
Purpose:
To identify the prognosticators of brain metastasis from SCLC treated by whole-brain radiotherapy.
Material and methods:
We evaluated patients diagnosed with primary brain metastasis from SCLC between 1 January 2010 and 30 September 2019. Age, sex, disease stage at the first examination, time to the diagnosis of brain metastasis, state of other lesions at the diagnosis of brain metastasis, haematological parameters, neurologic symptoms, whole-brain radiotherapy dose, imaging findings of the brain metastasis (single or multiple), and chemotherapy and radiotherapy status were investigated for correlations with survival from the diagnosis of brain metastasis.
Results:
A total of 24 participants were evaluated. After radiotherapy, the median survival period was 118·5 (22–998) days, and 21 patients died during the follow-up period. Multivariate stepwise analysis of the four parameters of lactate dehydrogenase (LDH) level (within vs. above the reference value), platelet level (continuous variable), neurologic symptoms (with versus. without), and NSE (neuron-specific enolase) level (continuous variable) identified the following significant differences: neurologic symptoms were 3·81 (95% CI 1·07–13·5, p = 0·04), and NSE was 1·01 (95% CI 1·00–1·01, p = 0·04).
Conclusion:
NSE and neurologic symptoms are prognosticators of brain metastasis from SCLC treated by whole-brain radiotherapy.
While treating brain metastasis with whole-brain radiotherapy incorporating a simultaneous integrated boost (WBRT-SIB), the risk of hippocampus injury is high. The aim of this study is to compare dosimetrically between intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in sparing of hippocampus and organs at risk (OARs) and planning target volume (PTV) coverage.
Methods:
In total, 16 patients presenting with more than one brain metastases were previously treated and then retrospectively planned using VMAT and IMRT techniques. For each patient, a dual-arc VMAT and another IMRT (five beams) plans were created. For both techniques, 30 Gy in 10 fractions was prescribed to the whole brain (WB) minus the hippocampi and 45 Gy in 10 fractions to the tumour with 0·5 cm margin. Dose–volume histogram (DVH), conformity index (CI) and homogeneity index (HI) of PTV, hippocampus mean and maximum dose and other OARs for both techniques were calculated and compared.
Results:
A statistically significant advantage was found in WB-PTV CI and HI with VMAT, compared to IMRT. There were lower hippocampus mean and maximum doses in VMAT than IMRT. The maximum hippocampus dose ranged between 15·5 and 19·2 Gy and between 18·4 and 20·6 Gy in VMAT and IMRT, respectively. The mean dose of the hippocampus ranged between 11·5 and 17·7 Gy and between 13·2 and 18·3 Gy in VMAT and IMRT, respectively.
Conclusion:
Using WBRT-SIB technique, VMAT showed better PTV coverage with less mean and maximum doses to the hippocampus than IMRT. Clinical randomised studies are needed to confirm safety and clinical benefit of WBRT-SIB.