B rain metastases (BMs) are the most common intracranial tumors in adults, occurring in 20%-40% of cancer patients. 26 Their incidence has been increasing due to both prolonged systemic control and improved detection, making BMs a growing cause of mortality and morbidity.14,31 Magnetic resonance imaging is currently the standard of care for the diagnosis of BMs because its sensitivity is superior to CT,22,32 and refinements in MRI techniques allow the modality to detect metastases that are not seen with routine image-acquisition protocols. The abbreviatioNs BM = brain metastasis; GRE = gradient echo; SRS = stereotactic radiosurgery. obJective Contrast-enhanced MRI is the preeminent diagnostic test for brain metastasis (BM). Detection of BMs for stereotactic radiosurgery (SRS) planning may improve with a time delay following administration of a high-relaxivity agent for 1.5-T and 3-T imaging systems. Metastasis detection with time-delayed MRI was evaluated in this study. methods Fifty-three volumetric MRI studies from 38 patients undergoing SRS for BMs were evaluated. All studies used 0.1-mmol/kg gadobenate dimeglumine (MultiHance; Bracco Diagnostics) immediately after injection, followed by 2 more axial T1-weighted sequences after 5-minute intervals (final image acquisition commenced 15 minutes after contrast injection). Two studies were motion limited and excluded. Two hundred eighty-seven BMs were identified. The studies were randomized and examined separately by 3 radiologists, who were blinded to the temporal sequence. Each radiologist recorded the number of BMs detected per scan. A Wilcoxon signed-rank test compared BM numbers between scans. One radiologist determined the scan on which BMs were best defined. All confirmed, visible tumors were contoured using iPlan RT treatment planning software on each of the 3 MRI data sets. A linear mixed model was used to analyze volume changes. results The interclass correlations for Scans 1, 2, and 3 were 0.7392, 0.7951, and 0.7290, respectively, demonstrating excellent interrater reliability. At least 1 new lesion was detected in the second scan as compared with the first in 35.3% of subjects (95% CI 22.4%-49.9%). The increase in BM numbers between Scans 1 and 2 ranged from 1 to 10. At least 1 new lesion was detected in the third scan as compared with the second in 21.6% of subjects (95% CI 11.3%-35.3%). The increase in BM numbers between Scans 2 and 3 ranged from 1 to 9. Between Scans 1 and 3, additional tumors were seen on 43.1% of scans (increase ranged from 1 to 14). The median increase in tumor number for all comparisons was 1. There was a significant increase in number of BMs detected from Scan 1 to Scan 2 (p < 0.0367) and from Scan 1 to Scan 3 (p < 0.0264). In 34 of the 51 subjects (66.7%), the radiologist selected the third scan as the one providing the clearest tumor definition. There was an average 25.4% increase in BM volume between Scans 1 and 2 (p < 0.0001) and a 9% increase in BM volume between Scans 2 and 3 (p = 0.0001). coNclusioNs In patients who are ...
Glioblastoma is the most common and aggressive primary brain tumor. Despite standard multimodality therapy, median overall survival remains poor with a 5-year survival rate of approximately 5% in most studies (range 4.7–13.0%). Strong interest in targeting IDH mutations has led to a variety of studies in both hematologic malignancies and solid tumors and to the approval of IDH inhibitors such as ivosidenib, an IDH1 inhibitor, in hematologic malignancies. Here, we present the first case study of a patient with a recurrent IDH1-mutant glioblastoma who experienced improved seizure control and radiographic stable disease for more than 4 years while treated with ivosidenib. Such findings support the further development of IDH inhibitors as single agents and/or in combination for the treatment of IDH-mutant glioma.
Glioblastoma (GBM) carries a poor prognosis despite aggressive multimodality therapy. Oncogenic BRAF mutations are present in < 2% of GBM, along with other glioma types (ganglioglioma, pleomorphic xanthoastrocytoma). Although oral inhibitors of the oncogenic BRAFv600 kinase have demonstrated some efficacy in GBM, several mechanisms mediating resistance to BRAF inhibitors through MAPK reactivation have been described. BRAF inhibitor monotherapy is also associated with an increased risk for hyperproliferative skin lesions. We present a case of a 44-year-old man who initially presented with headaches and seizures and was diagnosed with a left temporal, MGMT unmethylated, BRAF V600E mutant GBM. He underwent gross total resection followed by radiation therapy with concurrent temozolomide, followed by 9 cycles of adjuvant temozolomide. He presented with progression of disease (POD) and subsequently failed treatment with carboplatin after two cycles (first recurrence). He had a repeat resection, and was enrolled in a clinical trial of autologous dendritic cell vaccine and presented with POD after 10 months on this treatment (second recurrence). He was started on another clinical trial of BRAF inhibitor, achieving partial response but developed POD after 7 months on this therapy (third recurrence). He was started on BRAF inhibitor dabrafenib and MEK inhibitor trametinib (D+T), achieving complete response. At the time of this report, 8 months after initiating treatment, the patient remains clinically stable with MRI showing CR. To our knowledge, this is the first report of clinical and radiographic response to combined D+T after BRAF inhibitor failure in BRAF-mutated glioblastoma. Several ongoing trials (NCT01677741, NCT01748149, NCT02124772, NCT02684058, NCT02285439), will elucidate the precise role of these drugs as single agent and in combination in pediatric and adult brain tumors.
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