Glioma is the most common malignant primary brain tumor. Its rapid growth is aided by tumor-mediated glutamate release, creating peritumoral excitotoxic cell death and vacating space for tumor ...expansion. Glioma glutamate release may also be responsible for seizures, which complicate the clinical course for many patients and are often the presenting symptom. A hypothesized glutamate release pathway is the cystine/glutamate transporter System xc (-) (SXC), responsible for the cellular synthesis of glutathione (GSH). However, the relationship of SXC-mediated glutamate release, seizures, and tumor growth remains unclear. Probing expression of SLC7A11/xCT, the catalytic subunit of SXC, in patient and mouse-propagated tissues, we found that ~50% of patient tumors have elevated SLC7A11 expression. Compared with tumors lacking this transporter, in vivo propagated and intracranially implanted SLC7A11-expressing tumors grew faster, produced pronounced peritumoral glutamate excitotoxicity, induced seizures, and shortened overall survival. In agreement with animal data, increased SLC7A11 expression predicted shorter patient survival according to genomic data in the REMBRANDT (National Institutes of Health Repository for Molecular Brain Neoplasia Data) database. In a clinical pilot study, we used magnetic resonance spectroscopy to determine SXC-mediated glutamate release by measuring acute changes in glutamate after administration of the U.S. Food and Drug Administration-approved SXC inhibitor, sulfasalazine (SAS). In nine glioma patients with biopsy-confirmed SXC expression, we found that expression positively correlates with glutamate release, which is acutely inhibited with oral SAS. These data suggest that SXC is the major pathway for glutamate release from gliomas and that SLC7A11 expression predicts accelerated growth and tumor-associated seizures.
Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a ...combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed.
Objective
The purpose of this study was to describe distressed and underprepared family caregiver's use of and interest in formal support services (eg, professional counseling, education, ...organizational assistance).
Method
Cross‐sectional mail survey conducted in communities of 8 cancer centers in Tennessee, Alabama, and Florida (response rate: 42%). Family caregivers of Medicare beneficiaries with pancreatic, lung, brain, ovarian, head and neck, hematologic, and stage IV cancers reported support service use and completed validated measures of depression, anxiety, burden, preparedness, and health.
Results
Caregivers (n = 294) were on average age 65 years and mostly female (73%), White (91%), and care recipients' spouse/partner (60%); patients averaged 75 years were majority male (54%) with lung cancer (39%). Thirty‐two percent of caregivers reported accessing services while 28% were “mostly” or “extremely” interested. Thirty‐five percent of caregivers with high depressive symptoms (n = 122), 33% with high anxiety symptoms (n = 100), and 25% of those in the lowest quartile of preparedness (n = 77) accessed services. Thirty‐eight percent of those with high depressive symptoms, 47% with high anxiety symptoms, and 36% in the lowest quartile of preparedness were “mostly” or “extremely” interested in receiving services. Being interested in support services was significantly associated with being a minority, shorter durations of caregiving, and with higher stress burden.
Conclusions
A large proportion of family caregivers, including those experiencing depression and anxiety symptoms and who were underprepared, are not using formal support services but have a strong interest in services. Strategies to increase service use may include targeting distressed caregivers early in their caregiving experience.
Nearly 3 million U.S. family caregivers support someone with cancer. However, oncology clinic-based service lines that proactively screen, assess, and support cancer caregivers are nearly ...nonexistent.
To examine first-year experiences of a nurse-led clinic-based telehealth support service (FamilyStrong) for family caregivers of patients with recently diagnosed grade IV brain tumors.
This is a retrospective evaluation of operational outcomes from initial implementation of the FamilyStrong Service, developed in partnership with Caregiver and Bereavement Support Services at the University of Alabama at Birmingham (UAB) and the UAB Center for Palliative and Supportive Care. From August 2018 to December 2019, 53 family caregivers were proactively identified and enrolled by a palliative care nurse, working approximately one day/week, who performed monthly caregiver distress thermometer screenings by phone and provided emotional, educational, problem-solving, and referral support.
Enrolled family caregivers were a mean age of 53.5 years and mostly female (62.3%), full- or part-time employed (67.9%), and the patient's spouse/partner (79.3%). Caregivers provided support 6.7 days/week for 11.2 hours/day. The palliative care nurse performed 235 distress screenings and provided support that included 68 documented instances of emotional, problem-solving, and educational support, 41 nurse-facilitated communications with the neuro-oncology team about patient issues, and 24 referrals to UAB and community services (e.g., counseling). The most common problems caregivers wanted assistance with included: managing their relative's health condition and symptoms (51%), coordinating care/services (21%), and planning for the future/advance care planning (17%).
The FamilyStrong Program is among the first "real world" oncology clinic-based formal support services for advance cancer family caregivers.
End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and ...associated Medicare expenditures among older adults with malignant brain tumors.
This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary malignant brain tumor (PMBT) or secondary MBT (SMBT) receiving care within a southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively.
Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n = 383) and 32% of SMBT (n = 940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs 5%, P = 0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (P = 0.003). Nonwhite race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was $-12,138 (95% CI: $-18,065 to $-6210) and with SMBT was $-1,508 (95% CI: $-3,613 to $598).
Receiving late or no hospice care was common among older patients with malignant brain tumors and was significantly associated with increased total Medicare expenditures for patients with PMBT.
Low-grade gliomas cause significant neurological morbidity by brain invasion. There is no universally accepted objective technique available for detection of enlargement of low-grade gliomas in the ...clinical setting; subjective evaluation by clinicians using visual comparison of longitudinal radiological studies is the gold standard. The aim of this study is to determine whether a computer-assisted diagnosis (CAD) method helps physicians detect earlier growth of low-grade gliomas.
We reviewed 165 patients diagnosed with grade 2 gliomas, seen at the University of Alabama at Birmingham clinics from 1 July 2017 to 14 May 2018. MRI scans were collected during the spring and summer of 2018. Fifty-six gliomas met the inclusion criteria, including 19 oligodendrogliomas, 26 astrocytomas, and 11 mixed gliomas in 30 males and 26 females with a mean age of 48 years and a range of follow-up of 150.2 months (difference between highest and lowest values). None received radiation therapy. We also studied 7 patients with an imaging abnormality without pathological diagnosis, who were clinically stable at the time of retrospective review (14 May 2018). This study compared growth detection by 7 physicians aided by the CAD method with retrospective clinical reports. The tumors of 63 patients (56 + 7) in 627 MRI scans were digitized, including 34 grade 2 gliomas with radiological progression and 22 radiologically stable grade 2 gliomas. The CAD method consisted of tumor segmentation, computing volumes, and pointing to growth by the online abrupt change-of-point method, which considers only past measurements. Independent scientists have evaluated the segmentation method. In 29 of the 34 patients with progression, the median time to growth detection was only 14 months for CAD compared to 44 months for current standard of care radiological evaluation (p < 0.001). Using CAD, accurate detection of tumor enlargement was possible with a median of only 57% change in the tumor volume as compared to a median of 174% change of volume necessary to diagnose tumor growth using standard of care clinical methods (p < 0.001). In the radiologically stable group, CAD facilitated growth detection in 13 out of 22 patients. CAD did not detect growth in the imaging abnormality group. The main limitation of this study was its retrospective design; nevertheless, the results depict the current state of a gold standard in clinical practice that allowed a significant increase in tumor volumes from baseline before detection. Such large increases in tumor volume would not be permitted in a prospective design. The number of glioma patients (n = 56) is a limitation; however, it is equivalent to the number of patients in phase II clinical trials.
The current practice of visual comparison of longitudinal MRI scans is associated with significant delays in detecting growth of low-grade gliomas. Our findings support the idea that physicians aided by CAD detect growth at significantly smaller volumes than physicians using visual comparison alone. This study does not answer the questions whether to treat or not and which treatment modality is optimal. Nonetheless, early growth detection sets the stage for future clinical studies that address these questions and whether early therapeutic interventions prolong survival and improve quality of life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bevacizumab is widely used for treatment of high-grade gliomas and other malignancies. Because bevacizumab has been shown to be associated with neurocognitive decline, this study is designed to ...investigate whether prolonged treatment with bevacizumab is also associated with brain atrophy. We identified 12 high-grade glioma patients who received bevacizumab for 12 months at the first recurrence and 13 matched controls and blindly compared the volumes of the contralateral hemispheres and contralateral ventricle in these two groups at baseline and after 12 ± 2 months of the baseline scan by two independent analyses. The volumes of the contralateral hemispheres and ventricles did not differ significantly between the two groups at baseline. Whereas, in the control group the volumes of the contralateral hemisphere changed subtly from baseline to follow-up (p = 0.23), in the bevacizumab-treated group the volumes significantly decreased from baseline to follow-up (p = 0.03). There was significant increase in the contralateral ventricle volume from base line to follow-up scans in both the control group (p = 0.01) and in the bevacizumab group (p = 0.005). Both the absolute and the percentage changes of contralateral hemisphere volumes and contralateral ventricular volumes between the two patient groups were statistically significant (p < 0.05). Results of this study demonstrate prolonged treatment with bevacizumab is associated with atrophy of the contralateral brain hemisphere.
Highlights • The early development of NCS and EMG was linked to the discovery of electricity. • Research in the topic was heralded by physiologists then undertaken by neurologists. • World War II ...played a mixed role in the evolution of research and technology.
Intrasellar rhabdomyosarcoma is rare, and when arising in collusion with an unrelated entity, can present a diagnostic pitfall. We describe a case of a 56-year-old woman who presented with right eye ...ptosis and a pituitary mass, which was resected and diagnosed as atypical pituitary adenoma. Because of residual disease and atypical pathology, the patient received adjuvant radiation. Tumor recurrence was noted after 5 months, and a second resection was performed. Nests of atypical pituitary adenoma cells within an exuberant spindle cell stroma were noted, with areas of presumed radiation necrosis. A second recurrence prompted a third resection. After expert consultation and additional immunohistochemical stains for muscle markers, a diagnosis was rendered of primary rhabdomyosarcoma arising in association with a pituitary adenoma. Despite its rarity, a high index of suspicion for rhabdomyosarcoma arising within a pituitary adenoma should be maintained in cases of atypical pituitary adenoma with a stromal response.
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