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Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free (“resting”) fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. Results: The study was feasible (74–89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0–100 scale: − 7.9 ± 5.7, effect size [ES] = − 0.9 at mid-intervention; − 4.8 ± 7.3, ES = − 0.5 at post-intervention), CIPN signs (ES = − 1.0 and − 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40–60%) and higher functional connectivity within the salience network (R2 = 20–40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. Trial registration: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174. [ABSTRACT FROM AUTHOR]

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low‐molecular‐weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT. There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants, specifically in brain tumor patients, but they are widely used for venous thromboembolism in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of direct oral anticoagulants in treating venous thromboembolism in patients with brain tumors. [ABSTRACT FROM AUTHOR]

Opinion statement: Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck cancer is a common malignancy frequently treated with chemotherapy and radiotherapy. Studies have shown an increased risk of stroke with the receipt of radiotherapy, but data on stroke-related mortality are limited, particularly in the modern era. Evaluating stroke mortality related to radiotherapy is vital given the curative nature of head and neck cancer treatment and the need to understand the risk of severe stroke in this population. Methods: We analyzed the risk of stroke death among 122,362 patients (83,651 patients who received radiation and 38,711 patients who did not) with squamous cell carcinoma of the head and neck (HNSCC) diagnosed between 1973 and 2015 in the SEER database. Patients in radiation vs. no radiation groups were matched using propensity scores. Our primary hypothesis was that radiotherapy would increase the hazard of death from stroke. We also examined other factors impacting the hazard of stroke death, including whether radiotherapy was performed during the modern era when IMRT and modern stroke care were available as well as increased HPV-mediated cancers of the head and neck. We hypothesized that the hazard of stroke death would be less in the modern era. Results: There was an increased hazard of stroke-related death in the group receiving radiation therapy (HR 1.203, p = 0.006); however, this was a very small absolute increase, and the cumulative incidence function of stroke death was significantly reduced in the modern era (p < 0.001), cohorts with chemotherapy (p=0.003), males (p=0.002), younger cohorts (p<0.001) and subsites other than nasopharynx (p=0.025). Conclusions: While radiotherapy for head and neck cancer increases the hazard of stroke death, this is reduced in the modern era and remains a very small absolute risk. [ABSTRACT FROM AUTHOR]

While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to describe the current state of telemedicine within neuro-oncology. This article will address the development of tele-neuro-oncology over time with a focus on current use and applications of telemedicine within the field. Current modalities and practical considerations for tele-neuro-oncology visits and opportunities for growth will be highlighted. Recent Findings: The use of telemedicine has expanded significantly during the COVID-19 pandemic, particularly within neuro-oncology. The use of telemedicine is widely accepted by neuro-oncologic patients and providers and continues to expand in utilization and scope. The use of tele-neuro-oncology is expected to develop further with opportunities for multidisciplinary and integrated care, clinical trials, research, and education. Summary: Telemedicine provides a unique, patient-centered approach to neuro-oncologic care. Telehealth will remain a valuable tool, and its use and role are expected to expand within neuro-oncology. [ABSTRACT FROM AUTHOR]

The diagnosis of an aggressive, primary brain tumor is life altering for those affected and too often portends a poor prognosis. Despite decades of research, neither a cure nor even a therapy that reliably and dramatically prolongs survival has been found. Fortunately, there are a number of treatments that may prolong the life of select brain tumor patients although the symptom burden can sometimes be high. This article brings together neuro-oncologists, neurologists, and palliative care (PC) physicians to help shine a light on these diseases, their genetics, treatment options, and the symptoms likely to be encountered both from the underlying illness and its treatment. We hope to increase the understanding that PC teams have around these illnesses to improve care for patients and families. [ABSTRACT FROM AUTHOR]

Background: Tumor-related epilepsy (TRE) is the most common cause of hospitalizations in patients with malignant gliomas leading to increased distress and decreased quality of life (QOL) for patients and caregivers.Purpose: We sought to determine the feasibility of incorporating a structured TRE-specific education intervention into clinical practice while assessing effect on distress and TRE knowledge.Methods: We prospectively enrolled glioma patients and their caregivers on an IRB-approved study. Subjects underwent a pre-test to assess baseline knowledge regarding seizure management. A neuro-oncology provider guided subjects through a presentation focused on safety and home management of seizures. Seizure-related distress was measured before and after the educational intervention using a distress thermometer. A post-test was completed. At 2 and 6 months, distress was re-assessed and post-tests were repeated. Subject satisfaction was assessed.Results: Fifty subjects (23 patients, 27 caregivers) were enrolled. Median age was 59. Fifty-seven percent of patients had TRE. Median time to completion was 21.5 min. Median baseline distress scores were 2/10 for patients and 5/10 for caregivers. Distress scores decreased by a mean of 1.5 points and TRE knowledge increased by 2 points for all subjects between the initial and 2-month visit. Ninety-eight percent of subjects strongly agreed that the education was helpful and informative. Caregivers reported more distress despite better baseline seizure knowledge than patients.Conclusion: Structured TRE education is feasible in patients with gliomas and their caregivers and may be effective in reducing distress. Further prospective studies are warranted to assess effects on hospitalizations, cost, and QOL. [ABSTRACT FROM AUTHOR]

Background: Glioma patients make frequent decisions regarding treatment and end-of-life care despite cognitive limitations. We evaluated the feasibility of incorporating the Macarthur Competence Assessment Tool for Treatment (MacCAT-T) to assess decision-making ability in glioma patients. Methods: High-grade glioma patients were consented to an IRB-approved prospective study at one of three treatment decision time points. Patients completed the Montreal Cognitive Assessment (MoCA) and providers informally assessed patient decision-making ability based on neurologic examination. The MacCAT-T, designed to assess patient decision-making domains, was administered by a research assistant. MoCA, provider assessment, and MacCAT-T results were compared to determine whether the MacCAT-T provided additional information. To assess feasibility, we measured administration time and obtained qualitative patient feedback. Results: Eleven patients (median age = 68 years, median Karnofsky Performance Status [KPS] = 80–90) were enrolled. MacCAT-T administration averaged 18.5 minutes. Ninety percent of patients reported "increased knowledge of their treatment options" after taking the MacCAT-T. Clinicians deemed 10 patients to possess sufficient decision-making ability, yet, 6 of them demonstrated impairments in reasoning on the MacCAT-T. Seven patients yielded discordant MOCA and MacCAT-T data, five patients with MOCA score ≥26 showed qualitative MacCAT-T impairments in Reasoning and five patients who scored <21 were within nonimpaired ranges for three of four decision-making domains. Conclusion: MacCAT-T administration was feasible and informative to patients but findings were discordant from MOCA and informal provider assessments. The MacCAT-T may help in identifying mild Reasoning impairments related to patients' initial treatment decisions and should be studied further to determine its role in clinical practice. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 68% of patients who receive neurotoxic chemotherapy and lasts at least 6 months post-chemotherapy in approximately 30% of individuals. CIPN is associated with decreased quality of life and functional impairments. Evidence suggests that CIPN symptoms are caused, in part, by enhanced excitability and impaired inhibition in the central nervous system. Transcutaneous electrical nerve stimulation (TENS) decreases pain by counteracting both of these mechanisms and is efficacious in other conditions associated with neuropathic pain. This single-arm study (n = 29) assessed the feasibility of investigating TENS for CIPN after chemotherapy completion using a wireless, home-based TENS device. Eighty-one percent of eligible patients who were approached enrolled, and 85% of participants who received the TENS device completed the primary (6-week) study term. Qualitative interview data suggest that use of the device on the continuous setting that automatically alternates between 1-h stimulation and rest periods for 5 h/day would be acceptable to most participants. Significant (i.e., p < 0.05) improvements were observed with the EORTC-CIPN20 (percent change from baseline: 13%), SF-MPQ-2 (52%), numeric rating scale of pain (38%), tingling (30%), numbness (20%), and cramping (53%), and UENS large fiber sensation subscore (48%). Preliminary data that support the reliability and construct validity of the UENS for CIPN in cancer survivors are also provided. Together these data suggest that it is feasible to evaluate TENS for CIPN using a wireless, home-based device and that further evaluation of TENS for CIPN in a randomized clinical trial is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms.Methods: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness.Results: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076).Conclusions: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients.Trial Registration: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

Background. The utilization of inpatient medical services by patients with glioblastoma (GBM) is not well studied. We sought to describe causes, frequency, and outcomes of acute care visits in GBM. Methods. We conducted a retrospective study of 158 GBM patients at the University of Rochester over 5 years. Electronic medical records were reviewed to identify all local and outside acute care visits. Acute care visits were defined as any encounter resulting in an emergency department visit or inpatient admission. Results. Seventy-one percent (112/158) of GBM patients had 235 acute care visits corresponding to 163 hospitalizations (69%) and 72 emergency department visits (31%). Sixty-three percent of patients had multiple visits. Admission diagnoses were seizure (33%), neurosurgical procedure (15%), infection (12%), focal neurologic symptoms (9%), and venous thromboembolism (VTE, 9%). Forty-six patients had 1 or more visits for seizures. Median time to first acute care visit was 65.6 days and 22% of patients had an acute care visit within 30 days of diagnosis. Median length of stay was 5 days. Thirty-five percent of admitted patients were discharged home; 62% required a higher level of care than prior to admission (23% were discharged home with services, 17% to a nursing facility, 16% to hospice, 6% to acute rehab) and 3% died. Thirty-eight percent of patients had ACV within 30 days of death. Median survival was 14 months for patients who had acute care visits and 22.2 months for patients who did not. Conclusion. The majority of GBM patients utilize acute care, most commonly for seizures. The high number of emergency department visits, short length of stay, and many patients discharged home suggest that some acute care visits may be avoidable. [ABSTRACT FROM AUTHOR]

Background. American Society for Clinical Oncology (ASCO) quality measures for terminal cancers recommend early advance care planning and hospice at the end of life. We sought to evaluate adherence to 5 palliative care quality measures and explore associations with patient outcomes in glioblastoma. Methods. This is a retrospective analysis of 117 deceased glioblastoma patients over 5 years. Records were reviewed to describe adherence to palliative care quality measures and patient outcomes. Data regarding emotional assessments, advance directives, palliative care consultation, chemotherapy administration, hospice, location of death, and overall survival were collected. Results. Median overall survival was 12.9 months. By the second oncology visit, 22.2% (26/117) had an emotional assessment completed. Advance directives were documented for 52.1% (61/117) by the third neuro-oncology visit (30/61 health care proxy), yet 26.5% (31/117) did not have any advance directive before the last month of life. With regard to other ASCO quality measures, 36.8% (43/117) had a palliative care consult; 94.0% (110/117) did not receive chemotherapy in the last 14 days of life; 59.8% (70/117) enrolled in hospice >7 days before death; and 56.4% (66/117) died in a home setting. Patients who enrolled in hospice >7 days before death were 3.56 times more likely to die in a home setting than patients enrolled <7 days before death or with no hospice enrollment (P = .002, [OR 3.56; 95% CI, 1.57-8.04]). Conclusions. Late advance directive documentation, minimal early palliative care involvement, and the association of early hospice enrollment with death in a home setting underscore the need to improve care and better define palliative care quality measures in glioblastoma. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6 % in cases and 27.5 % in controls, whereas SSRIs were used in 16.9 % of cases and 17.3 % of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with 'any SSRI use' among breast cancer patients (OR = 1.73, 95 % CI = 0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that ABT-888 (velparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent TMZ refractory glioblastoma patients. The combination regimen (TMZ/ABT-888) was tested using two randomized schedules (5 vs. 21 days), with 6-month progression free survival (PFS6) as the primary endpoint. The maximum tolerated dose (MTD) for TMZ using the 21 day of 28 TMZ schedule, in concert with 40 mg BID ABT-888 was determined in a phase I portion of this study, and previously reported to be 75 mg/m (arm1). The MTD for ABT-888 (40 mg BID) and the 5 of 28 day TMZ (150-200 mg/m) schedule was known from prior trials (arm2). Two cohorts were studied: bevacizumab (BEV) naïve (n = 151), and BEV refractory (n = 74). Overall ten patients were ineligible. The incidence rate of grade 3/4 myelosuppression over all was 20.0 %. For the BEV refractory cohort, the PFS 6 was 4.4 %; for the BEV naïve cohort, PFS6 was 17 %. Overall survival was similar for both arms in both the BEV naïve [median survival time (MST) 10.3 M; 95 % CI 8.4-12] and BEV refractory cohort (MST 4.7 M; 95 %CI 3.5-5.6). The median PFS was essentially the same for both arms and both cohorts at ~2.0 M (95 % CI 1.9-2.1). [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients. [ABSTRACT FROM AUTHOR]

To characterize the overall survival (OS) and cause specific survival (CSS), and variables affecting outcome, in patients with primary spinal cord astrocytoma (SCA) and ependymoma (SCE). About 664 patients with SCA and 1,057 patients with SCE were analyzed using the Surveillance, Epidemiology, and End Results database. For grade 1, 2, 3 and 4 SCA, the 5-year OS was 82, 70, 28 and 14%; the 5-year CSS was 89, 77, 36 and 20%. For SCA, lower grade, younger age, and undergoing resection significantly improved OS and CSS; treatment without radiotherapy was favorable for CSS. Smaller tumor size also improved survival. For grade 1, 2, and 3 SCE, the 5-year OS was 92, 97 and 58%; the 5-year CSS was 100, 98 and 64%. For SCE, lower grade, younger age, and undergoing resection significantly improved OS and CSS; treatment without radiotherapy was favorable for OS. Smaller tumor size did not confer a survival benefit. Patients with resected grade 2 spinal cord glioma who did not receive radiotherapy fared well with respect to OS and CSS. For patients with spinal cord glioma, the variables of histology, grade, age and undergoing resection are significant predictors of outcome. Though treatment with radiotherapy was associated with worse outcomes, this may reflect a bias in that patients who underwent radiotherapy were perhaps more likely to have had adverse risk factors. Given the retrospective nature of this study, specific recommendations about which situations warrant radiotherapy cannot be determined. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is experienced as numbness, tingling, pain, and cramping in the hands and/or feet and can interfere with daily living. Exercise is a promising treatment for CIPN but its underlying mechanisms are understudied. Herein, we discuss potential mechanisms underlying how exercise might treat CIPN (e.g., anti-inflammatory cytokines, self-efficacy, and social support) and what demographic (e.g., age and sex) and clinical characteristics (e.g., body mass index), and exercise routines (e.g., timing, intensity, and type of exercise) may moderate the effects of exercise on relieving CIPN. These details can help clinicians predict who will get CIPN, enable clinicians to tailor exercise programs to patients based on specific characteristics, and inform future research and biomarkers on the relationship between exercise and CIPN. Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it is becoming more critical to develop mechanistic understanding of the effects of exercise in order to tailor it to best treat CIPN symptoms and identify who will benefit most. To address the current lack of clarity around the effect of exercise on CIPN, we reviewed the key potential mechanisms (e.g., neurophysiological and psychosocial factors), mediators (e.g., anti-inflammatory cytokines, self-efficacy, and social support), and moderators (e.g., age, sex, body mass index, physical fitness, exercise dose, exercise adherence, and timing of exercise) that may illuminate the relationship between exercise and CIPN improvement. Our review is based on the studies that tested the use of exercise for patients with CIPN, patients with other types of neuropathies, and healthy adults. The discussion presented herein may be used to (1) guide oncologists in predicting which symptoms are best targeted by specific exercise programs, (2) enable clinicians to tailor exercise prescriptions to patients based on specific characteristics, and (3) inform future research and biomarkers on the relationship between exercise and CIPN. [ABSTRACT FROM AUTHOR]