Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series.

OBJECTIVES: To report on the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma METHODS: Single-center retrospective series of glioma patients treated with olaparib/TMZ September 2018-December 2021 RESULTS: Twenty patients (median age: 42, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of IDH-mutant oligodendroglioma (n=5), IDH-mutant astrocytoma grade 2-3 (n=4), IDH-mutant astrocytoma grade 4 (n=7), or IDH-wildtype glioma (n=4). One patient was treated upfront and 19 at recurrence (median=3). Olaparib 150mg was administered three times/week concurrent with TMZ 50-75mg/m2 daily. Fatigue, gastrointestinal symptoms, and hematologic toxicity were common. 6/20 patients required dose reduction (n=4) or discontinuation (n=2) due to toxicity. Radiographic response was evaluable in 16 and observed (complete + partial) in 4/8 with IDH-mutant grade 2-3 glioma. No responses were seen in patients with grade 4 IDH-mutant astrocytomas (0/5) or IDH-wildtype gliomas (0/3). Progression-free survival was 7.8, 1.3, and 2.0 months, respectively. DISCUSSION: Olaparib/TMZ resulted in objective radiographic response in 50% of evaluable patients with recurrent IDH-mutant grade 2-3 gliomas with encouraging PFS and manageable toxicity. This supports a prospective trial of olaparib/TMZ for this population. CLASSIFICATION OF EVIDENCE: This case series provides Class IV evidence that treatment with olaparib/TMZ may result in radiographic response in patients with glioma.

Mechanical thrombectomy in isolated large vessel posterior cerebral artery occlusions.

PURPOSE: Mechanical thrombectomy (MT) in posterior circulation large vessel occlusion (LVO), including posterior cerebral artery (PCA), has not been validated since all five major MT trials excluded such patients. To evaluate the feasibility and preliminary safety and efficacy of MT in isolated PCA occlusion stroke patients with new-generation MT devices. METHODS: Endovascularly treated acute ischemic stroke (AIS) patients were identified from a prospectively collected database and their baseline characteristics were noted. Clinical outcomes were angiographic recanalization, a favorable clinical outcome at 3 months on modified Rankin Scale (mRS) and visual field (VF) deficit improvement on confrontation test, rate of intracranial hemorrhage (ICH), and mortality at 3 months. RESULTS: A total of 355 AIS patients underwent MT from January 2018 to December 2019. Isolated PCA MT was performed in 15 consecutive patients. The mean age was 64 ± 17 years, and 9(60%) were women. Median presentation NIHSS was 9 (interquartile range 5-15). MT devices used were stent retrievers in 6 patients and combined aspiration and stent retriever in 9 patients. Complete revascularization (TICI 2c or 3) was achieved in 12/15 patients. 3-month VF normalization was seen in 7/12 of the patients. Post-procedure symptomatic ICH occurred in 1/15 of patients. mRS score of 0-2 was achieved in 9/15 of patients but one patient was dead at 3 months post procedure. CONCLUSION: MT is feasible and can achieve successful reperfusion in isolated PCA occlusions and resulted in favorable motor and visual outcomes in this small series of ischemic stroke patients.

Mechanical Thrombectomy for Large Vessel Occlusions in Cocaine Associated Acute Ischemic Stroke: Small Case Series and Review of the Literature.

INTRODUCTION: Cocaine through multifactorial pathogenetic mechanisms causes small and large vessel occlusions (LVO) leading to acute ischemic stroke. The optimal treatment for cocaine related LVO remains unknown. Mechanical thrombectomy (MT) poses a unique challenge, and successful MT are not widely reported. MATERIAL AND METHODS: We report three patients with no other risk factors and a common history of cocaine metabolites found on presentation drug screen who underwent MT for MCA occlusions with subsequent failed recanalization or vessel re-occlusion due to persistent thrombosis and severe vasospasm.Two patients initially had good revascularization but then developed severe vasospasm and reoccluded, and the remaining patient had persistent severe distal vasospasm. Rescue therapy either with balloon angioplasty with stent placement or intraarterial vasodilator was used in all patients and was ineffective. All patient had large hemispheric strokes and developed malignant cerebral edema requiring hemicraniectomy in two of them. We also did literature review and summarized previously reported cases of cocaine associated vasospasm in MT and other endovascular procedures. CONCLUSION: In this case series, cocaine induced vasospasm contributed to unsuccessful recanalization and reocclusion in patients undergoing MT with poor outcomes. Further studies are needed to ascertain strategies for improved outcomes in patients with LVO related to cocaine use.

Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, IDH1-mutant glioblastoma: a case report from a Phase I study.

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.

Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes.

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 being prepared for SRS of BMs, delayed MRI after contrast injection revealed more targets that needed treatment. In addition, apparent treatment volumes increased with a time delay. To avoid missing tumors that could be treated at the time of planned SRS and resultant "treatment failures," the authors recommend that postcontrast MR images be acquired between 10 and 15 minutes after injection in patients undergoing SRS for treatment of BMs.