Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.
Key Points Immunotherapy for treatment of hematological malignancies is immunosuppressive, and chronic immunosuppression is a risk factor for PML. Early diagnosis is vital for instituting prompt immune reconstitution as treatment; brain biopsy is necessary in suspicious cases.
Purpose It has been reported previously that the combination of bevacizumab with hypofractionated stereotactic re-irradiation (HFSR) with 30Gy (6GyX5 fractions) was safe and efficacious in recurrent glioblastomas and high-grade gliomas (HGG). Because most recurrences are local, developing intensified HFSR dosing schedules remains of interest. We hypothesized that in combination with bevacizumab, HFSR doses could be further escalated, and designed a prospective phase I trial to establish the maximum tolerated dose (MTD) of a 3-fraction HFSR delivered concomitantly with standard doses of bevacizumab. Materials and Methods Patients with recurrent HGG with KPS ≥ 60, history of standard fractionated initial radiation, tumor volume at recurrence ≤ 40cc and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 Phase I dose escalation trial design was utilized, with dose-limiting toxicities (DLT) defined as any grade 3–5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10mg/kg every two weeks. HFSR was initiated after two bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy/fraction. Results A total of 3 patients were enrolled at the 9GyX3 dose level cohort, 5 enrolled in the 10GyX3 cohort and 7 in the 11GyX3 cohort. One DLT of grade 3 fatigue and cognitive deterioration possibly related to HFSR was observed in the 11GyX3 cohort, and this dose was declared the MTD in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival (OS) was 13 months. Conclusions Re-irradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11GyX3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison to our previous 6GyX5 schedule. Promising OS warrants further investigation.
Background:The 2010 American Academy of Neurology guideline for the diagnosis of acute ischemic stroke recommends MRI with diffusion weighted imaging (DWI) over noncontrast head CT. No studies have evaluated the influence of imaging choice on patient outcome. We sought to evaluate the variables that influenced one-year outcomes of stroke and TIA patients, including the type of imaging utilized.Methods:Patients were identified from a prospectively collected stroke and TIA database at a single primary stroke center during a one-year period. Data were abstracted from patient electronic medical records. The primary outcome measure was death, myocardial infarction, or recurrent stroke within the following year. Secondary outcome measures included predictors of getting an MRI study.Results:727 consecutive patients with a discharge diagnosis of stroke or TIA were identified (616 and 111 respectively); 536 had CT and MRI, 161 had CT alone, 29 had MRI alone, and one had no neuroimaging. On multiple logistic regression analysis, there were no differences in primary or secondary outcome measures among different imaging strategies. Predictors of the primary outcome measure included age and NIHSS, while performance of a CT angiogram (CTA) predicted a decreased odds of death, stroke, or MI. The strongest predictor of having an MRI was admission to a stroke unit.Conclusions:These results suggest that long-term (one-year) patient outcomes may not be influenced by imaging strategy. Performance of a CTA was protective in this cohort. A randomized trial of different imaging modalities should be considered.
Background GammaTile® (GT) is a recent U.S. Food and Drug Administration (FDA) cleared brachytherapy platform. Here, we report clinical outcomes for recurrent glioblastoma patients after GT treatment following maximal safe resection. Methods We prospectively followed twenty-two consecutive Isocitrate Dehydrogenase (IDH) wild-type glioblastoma patients (6 O6-Methylguanine-DNA methyltransferase methylated (MGMTm); sixteen MGMT unmethylated (MGMTu)) who underwent maximal safe resection of recurrent tumor followed by GT placement. Results The cohort consisted of 14 second and eight third recurrences. In terms of procedural safety, there was one 30-day re-admission (4.5%) for an incisional cerebrospinal fluid leak, which resolved with lumbar drainage. No other wound complications were observed. Six patients (27.2%) declined in Karnofsky Performance Score (KPS) after surgery due to worsening existing deficits. One patient suffered a new-onset seizure post-surgery (4.5%). There was one (4.5%) 30-day mortality from intracranial hemorrhage secondary to heparinization for an ischemic limb. The mean follow-up was 733 days (range 279-1775) from the time of initial diagnosis. Six-month local control (LC6) and twelve-month local control (LC12) were 86 and 81%, respectively. Median progression-free survival (PFS) was comparable for MGMTu and MGMTm patients (~8.0 months). Median overall survival (OS) was 20.0 months for the MGMTu patients and 37.4 months for MGMTm patients. These outcomes compared favorably to data in the published literature and an independent glioblastoma cohort of comparable patients without GT treatment. Conclusions This clinical experience supports GT brachytherapy as a treatment option in a multi-modality treatment strategy for recurrent glioblastomas.
OBJECTIVE.-FDG PET/CT of brain tumors is limited by background activity. Dual-phase FDG PET/CT can eliminate this limitation and allow discernment of viable tumors. Our aim was to assess the diagnostic capability of dual-phase FDG PET/CT qualitatively and quantitatively and to determine cutoff values for dual-phase FDG PET/CT in brain tumor imaging. MATERIALS AND METHODS.-Retrospectively, 51 malignant brain tumors were evaluated with dual-phase FDG PET/CT in 32 patients. Acquisitions were performed 30 minutes (time 1) and 3 hours (time 2) after administration of 10 mCi (370 MBq) FDG and 6 hours of fasting. Two observers independently and qualitatively evaluated lesions. A weighted Cohen kappa was used to calculate interrater reliability and accuracy. Quantitatively, maximum standardized uptake value (SUV max ) was measured in the lesions, contralateral white matter (CWM), contralateral caudate nucleus head, and ipsilateral cerebellar cortex (CC). Lesion-to-CWM SUV max , lesion-tocontralateral caudate nucleus head SUV max , and lesion-to-ipsilateral CC SUV max ratios at time 1 and time 2 were calculated. ROC analysis was used to determine optimum cutoff values, and AUC ratios were compared among quantitative parameters. Lesion outcome was determined by pathologic results (available in 15 lesions), lesion stability on serial MRI examinations (representing nonviable tumor), or decreased tumor size on serial MRI examinations after new treatment (representing viable tumor).RESULTS.-Thirty-seven viable and 14 nonviable lesions were evaluated. Qualitatively, the diagnostic accuracy (first observer: κ = 0.45 to κ = 0.59; second observer: κ = 0.41 to κ = 0.66) and interrater reliability (at time 1: κ = 0.51; at time 2: κ = 0.83) improved with delayed imaging. AUC and ROC analysis showed comparably high sensitivity, specificity, and accuracy profiles for early and delayed dual-phase FDG PET/CT. Some of the proposed cutoff values were as follows: lesion SUV max at time 1, 7.20 (sensitivity, 89.2%; specificity, 85.7%); lesion SUV max at time 2, 7.80 (sensitivity, 97.3%; specificity, 71.4%); lesion-to-CWM SUV max at time 1, 2.05
Neurologists are often consulted for diagnosis and management of neurologic complications in patients undergoing therapy for cancer. Pediatric patients with cancer, often undergoing the same types of therapy as adults with cancer, may experience different adverse events. The set of neurologic complications in children differs from that in adults and the neurologist must take into account the continuing growth and development of the patient as well as significant differences in primary diagnosis across the population. Correctly recognizing complications and initiating prompt treatment may reduce pain and prevent further progression and permanent deficits. Herein, we review the most recent literature on the neurological complications of cancer therapy organized by frequency in the pediatric population.
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