Caregiver survey in glioblastoma focused on cognitive dysfunction: development and results from a multicenter study.

Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.

Glioblastoma (GBM) is a very aggressive brain cancer. People who have GBM have trouble remembering things and are unable to do things they used to do. These changes can be very hard. Researchers are trying to better understand what it is like for people who take care of people with GBM (or caregivers). In this study, researchers created a new survey for caregivers. The survey included questions about what caregivers see happening in their loved one with GBM. Caregivers said that memory problems were common. Also, when the patient had more problems the caregiver had a harder time, too. Researchers hope to improve the survey and use it in the future for more studies.

The Role of Dual-Phase FDG PET/CT in the Diagnosis and Follow-Up of Brain Tumors.

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 (SUVmax) was measured in the lesions, contralateral white matter (CWM), contralateral caudate nucleus head, and ipsilateral cerebellar cortex (CC). Lesion-to-CWM SUVmax, lesion-to-contralateral caudate nucleus head SUVmax, and lesion-to-ipsilateral CC SUVmax 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 SUVmax at time 1, 7.20 (sensitivity, 89.2%; specificity, 85.7%); lesion SUVmax at time 2, 7.80 (sensitivity, 97.3%; specificity, 71.4%); lesion-to-CWM SUVmax at time 1, 2.05 (sensitivity, 78.4%; specificity, 92.9%); and lesion-to-CWM SUVmax at time 2, 2.36 (sensitivity, 81.1%; specificity, 85.7%). CONCLUSION. Dual-phase FDG PET/CT improves lesion detection and diagnostic accuracy in malignant brain tumors.

Evolving Strategies to Potentially Further Optimize Surgical Interventions in Brain Cancer.

PURPOSE OF REVIEW: Provide an overview, the indications for use, and a synopsis of current literature regarding two evolving neurosurgical interventions-GammaTile therapy (GTT) and laser interstitial thermal therapy (LITT). RECENT FINDINGS: GTT delivers immediate, uniform, high-dose radiation with avoidance of direct brain-to-seed contact. Innate properties of the novel carrier system and cesium-131 source may explain lower observed rate of radiation-induced necrosis (RIN) and support use in larger and previously irradiated lesions. LITT delivers focal laser energy to cause heat-generated necrosis. Case series suggest use in difficult-to-access lesions and treatment of RIN. Collaboration among subspecialties and remaining up-to-date on evolving technology is critical in developing individualized treatment plans for patients with brain cancer. While patients should be thoroughly counseled that these interventions are not standard of care, in optimal clinical scenarios, GTT and LITT could extend quantity and quality of life for patients with few remaining options. Prospective studies are needed to establish specific treatment parameters.

Comparison of peripheral leukocyte parameters in patients receiving conventionally and hypofractionated radiotherapy schemes for the treatment of newly diagnosed glioblastoma.

Introduction: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown. Methods: To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment. Results: This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy. Discussion: Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.

GammaTile® brachytherapy in the treatment of recurrent glioblastomas.

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 postsurgery (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.

Ethics consultations in neuro-oncology.

BACKGROUND: Management of patients with brain tumors can lead to ethical and decisional dilemmas. The aim of this study was to characterize ethical conflicts encountered in neuro-oncologic patients. METHODS: Retrospective review of ethics consultations performed upon patients with primary and metastatic brain tumors at a tertiary cancer center. An ethics consultation database was examined to characterize ethical conflicts, contextual factors, and interventions by the consultation team. RESULTS: Fifty consultations were reviewed; 28 (56%) patients were women, median age 54 (range 4-86); 27 (54%) patients had a primary central nervous system malignancy; 20 (40%) had brain metastasis. At the time of consultations, 41 (82%) patients lacked decisional capacity; 48 (96%) had a designated surrogate decision maker; 3 (6%) had an advance directive outlining wishes regarding medical treatment; 12 (24%) had a Do Not Attempt Resuscitation (DNAR) order. Ethical conflicts centered upon management of end-of-life (EOL) circumstances in 37 (72%) of cases; of these, 30 did not have decisional capacity. The most common ethical issues were DNAR status, surrogate decision making, and request for nonbeneficial treatment. Consultants resolved conflicts by facilitating decision making for incapacitated patients in 30 (60%) cases, communication between conflicting parties in 10 (20%), and re-articulation of patients' previously stated wishes in 6 (12%). CONCLUSIONS: Decisional capacity at EOL represents the primary ethical challenge in care of neuro-oncologic patients. Incomplete awareness among surrogate decision makers of patients' prognosis and preferences contributes to communication gaps and dilemmas. Early facilitation of communication between patients, caregivers, and medical providers may prevent or mitigate conflicts and allow the enactment of patients' goals and values.

Neurotoxicity of antibodies in cancer therapy: A review.

The objective of this manuscript is to identify the neurological side effect profile associated with different classes of antibodies used in cancer pharmacotherapy and to estimate the frequency in which these neurotoxicity occurs. A systematic review of the literature was conducted using OVID MEDLINE and EMBASE databases for articles written between January of 2010 till August of 2018. The spectrum of neurotoxicity was searched using expanded terminology, medical subject headings, truncation, spelling variations and database specific controlled vocabulary. 2134 citations were retrieved that were narrowed down to 151 when SORT 1 or SORT 2 critical appraisal tool was applied to articles with human subjects. Meta-analysis using random effect model was done to estimate the prevalence of neurological symptoms per class of antibody described in SORT1 and SORT2 articles. It was found that the most common neurotoxicity per antibody class are as follows; Bi-specific T-cell engagers was headache 38% [35-40%; I2 0%]; anti-CD20, neuropathy, 16% [7-24%, I2 65%]; anti-CD30, neuropathy 57% [46-68%, I2 72%]; anti-CD52, neuropathy 5-15%; anti-CTL4, headache 12% [7-16%, I2 49%]; anti-EGFR, headache 25% [11-38%, I2 92%]; anti-Her2, neuropathy 33% [18-49%, I2 98%]; anti-PD1 and PDL1, headache 3% [2-5%, I2 85%]; and anti-VEGF, headache 25% [16-35%, I2 73%]. Therefore, all classes of antibodies used in cancer pharmacotherapy have associated neurotoxicity with a wide spectrum of effects afflicting the nervous system as a whole. The specific side effects and the frequency at which they occur differ per class of antibody. Broader and more severe symptoms were noted to effect patients with preexisting brain lesions.

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review.

Progressive multifocal leukoencephalopathy (PML) is an uncommon opportunistic infection with high morbidity and mortality. This is an institutional review board-approved retrospective review of medical records identified by diagnostic coding for PML or John Cunningham virus (JCV) from 2000 to 2015. Inclusion criteria were cerebrospinal fluid (CSF) positive for JCV by polymerase chain reaction or brain biopsy-proven PML in non-HIV patients. There were 16 patients, 12 of whom were men (75%); the median age was 56 years (range, 31-71 years). All had hematologic malignancies (5 [31%] had chronic lymphocytic leukemia, 3 [19%] had acute myeloid leukemia, 3 had [19%] mantle cell lymphoma, and 1 patient each had acute lymphoblastic leukemia, Hodgkin lymphoma, myeloma, or B-cell lymphoma). One patient received no cancer-directed therapy. Of the remaining 15 patients, all received conventional chemotherapy, and 9 (60%) underwent transplant. Thirteen patients (87%) received immunomodulating therapy (predominantly rituximab). The median time from cancer diagnosis to PML diagnosis was 48.5 months. PML was diagnosed a median of 2.1 months from symptom onset; however, the median time to PML diagnosis was 5.4 months for the 4 patients presenting with a cerebellar syndrome. PML was diagnosed by CSF in 12 patients and brain biopsy in 4 following negative CSF test results. Median survival from PML diagnosis was 4.3 months for the 11 patients on treatment and 0.87 months for the 5 without treatment. PML still occurs in patients with hematologic malignancies in the absence of treatment. Twenty-five percent of our patients required brain biopsy for diagnosis, and diagnosis was delayed when the clinical presentation was unusual, such as a cerebellar syndrome.

Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma.

BACKGROUND: Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication. METHODS: Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test-Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy-Brain [FACT-Br]). RESULTS: Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment. CONCLUSIONS: Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.

Neurological Complications of Pediatric Cancer.

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.