Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery.

Bariatric surgery is a sustainable weight loss approach, including vertical sleeve gastrectomy (VSG). Obesity exacerbates tumor growth, while diet-induced weight loss impairs progression. It remains unknown how bariatric surgery-induced weight loss impacts cancer progression or alters response to therapy. Using a pre-clinical model of obesity followed by VSG or diet-induced weight loss, breast cancer progression and immune checkpoint blockade therapy were investigated. Weight loss by VSG or weight-matched dietary intervention before tumor engraftment protected against obesity-exacerbated tumor progression. However, VSG was not as effective as diet in reducing tumor burden despite achieving similar weight and adiposity loss. Leptin did not associate with changes in tumor burden; however, circulating IL-6 was elevated in VSG mice. Uniquely, VSG tumors displayed elevated inflammation and immune checkpoint ligand PD-L1+ myeloid and non-immune cells. VSG tumors also had reduced T lymphocytes and markers of cytolysis, suggesting an ineffective anti-tumor microenvironment which prompted investigation of immune checkpoint blockade. While obese mice were resistant to immune checkpoint blockade, anti-PD-L1 potently impaired tumor progression after VSG through improved anti-tumor immunity. Thus, in formerly obese mice, surgical weight loss followed by immunotherapy reduced breast cancer burden. Finally, we compared transcriptomic changes in adipose tissue after bariatric surgery from patients and mouse models. A conserved bariatric surgery-associated weight loss signature (BSAS) was identified which significantly associated with decreased tumor volume. Findings demonstrate conserved impacts of obesity and bariatric surgery-induced weight loss pathways associated with breast cancer progression.

As the number of people classified as obese rises globally, so do obesity-related health risks. Studies show that people diagnosed with obesity have inflammation that contributes to tumor growth and their immune system is worse at detecting cancer cells. But weight loss is not currently used as a strategy for preventing or treating cancer. Surgical procedures for weight loss, also known as 'bariatric surgeries', are becoming increasingly popular. Recent studies have shown that individuals who lose weight after these treatments have a reduced risk of developing tumors. But how bariatric surgery directly impacts cancer progression has not been well studied: does it slow tumor growth or boost the anti-tumor immune response? To answer these questions, Sipe et al. compared breast tumor growth in groups of laboratory mice that were obese due to being fed a high fat diet. The first group of mice lost weight after undergoing a bariatric surgery in which part of their stomach was removed. The second lost the same amount of weight but after receiving a restricted diet, and the third underwent a fake surgery and did not lose any weight. The experiments found that surgical weight loss cuts breast cancer tumor growth in half compared with obese mice. But mice who lost the same amount of weight through dietary restrictions had even less tumor growth than surgically treated mice. The surgically treated mice who lost weight had more inflammation than mice in the two other groups, and had increased amounts of proteins and cells that block the immune response to tumors. Giving the surgically treated mice a drug that enhances the immune system's ability to detect and destroy cancer cells reduced inflammation and helped shrink the mice's tumors. Finally, Sipe et al. identified 54 genes which were turned on or off after bariatric surgery in both mice and humans, 11 of which were linked with tumor size. These findings provide crucial new information about how bariatric surgery can impact cancer progression. Future studies could potentially use the conserved genes identified by Sipe et al. to develop new ways to stimulate the anti-cancer benefits of weight loss without surgery.

The brain tumor not-for-profit and charity experience of COVID-19: reacting and adjusting to an unprecedented global pandemic in the 21st century.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has affected individuals as well as disease-specific brain tumor organizations. These organizations around the world exist to address unmet needs for patients and caregivers they serve. The direct impact of the pandemic on these organizations constitutes significant collateral damage. In order to better understand the effects of the COVID-19 pandemic on brain tumor organizations, the International Brain Tumour Alliance (IBTA) carried out an international survey to identify organizational changes induced by the virus and approaches adopted to address challenges. METHODS: A 37-question online survey consisting of categorical and qualitative questions was developed and circulated to 130 brain tumor organizations across the world. Seventy-seven organizations from 22 countries completed the survey (59% return rate). Descriptive statistics and content analysis were used to present the results. RESULTS: Responses fell into the following 3 categories: (1) organizational characteristics, (2) impact of COVID-19 on services, and (3) COVID-19 impact on financial and human resources within organizations. Although organizational characteristics varied, common concerns reported were activity disruption which impacted organizations' abilities to offer usual services and challenges to sustaining funding. Both financial and human resources were stressed, but integral adaptations were made by organizations to preserve resources during the pandemic. CONCLUSIONS: Although brain tumor organizations have been impacted by the COVID-19 pandemic, organizations quickly adjusted to this unprecedented global healthcare crisis. Nimble reactions and flexibility have been vital to organization sustainability. Innovative approaches are required to ensure organizations remain viable so that needs of brain tumor community at large are met.

Brain tumors and COVID-19: the patient and caregiver experience.

BACKGROUND: Since the COVID-19 pandemic began, thousands of medical procedures and appointments have been canceled or delayed. The long-term effects of these drastic measures on brain tumor patients and caregivers are unknown. The purpose of this study is to better understand how COVID-19 has affected this vulnerable population on a global scale. METHODS: An online 79-question survey was developed by the International Brain Tumour Alliance, in conjunction with the SNO COVID-19 Task Force. The survey was sent to more than 120 brain tumor charities and not-for-profits worldwide and disseminated to pediatric and adult brain tumor patients and caregivers. Responses were collected from April to May 2020 and subdivided by patient versus caregiver and by geographical region. RESULTS: In total, 1989 participants completed the survey from 33 countries, including 1459 patients and 530 caregivers. There were no significant differences in COVID-19 testing rates (P = .662) or positive cases for brain tumor patients between regions (P = .1068). Caregivers were significantly more anxious than patients (P ≤ .0001). Patients from the Americas were most likely to have lost their jobs due to the pandemic, practiced self-isolation, and received telehealth services (P ≤ .0001). Patients from Europe experienced the most treatment delays (P = .0031). Healthcare providers, brain tumor charities, and not-for-profits were ranked as the most trusted sources of information. CONCLUSIONS: As a result of COVID-19, brain tumor patients and caregivers have experienced significant stress and anxiety. We must continue to provide accessible high-quality care, information, and support in the age of COVID-19.

Radiation Therapy for Glioblastoma: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Guideline.

Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy for glioblastoma. Because of its relevance to the ASCO membership, ASCO reviewed the guideline and applied a set of procedures and policies used to critically examine guidelines developed by other organizations. Methods The ASTRO guideline on radiation therapy for glioblastoma was reviewed for developmental rigor by methodologists. An ASCO endorsement panel updated the literature search and reviewed the content and recommendations. Results The ASCO endorsement panel determined that the recommendations from the ASTRO guideline, published in 2016, are clear, thorough, and based on current scientific evidence. ASCO endorsed the ASTRO guideline on radiation therapy for glioblastoma and added qualifying statements. Recommendations Partial-brain fractionated radiotherapy with concurrent and adjuvant temozolomide is the standard of care after biopsy or resection of newly diagnosed glioblastoma in patients up to 70 years of age. Hypofractionated radiotherapy for elderly patients with fair to good performance status is appropriate. The addition of concurrent and adjuvant temozolomide to hypofractionated radiotherapy seems to be safe and efficacious without impairing quality of life for elderly patients with good performance status. Reasonable options for patients with poor performance status include hypofractionated radiotherapy alone, temozolomide alone, or best supportive care. Focal reirradiation represents an option for select patients with recurrent glioblastoma, although this is not supported by prospective randomized evidence. Additional information is available at www.asco.org/glioblastoma-radiotherapy-endorsement and www.asco.org/guidelineswiki .

Central Nervous System Cancers, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.

A new reality: long-term survivorship with a malignant brain tumor.

PURPOSE/OBJECTIVES: To explore the survivor experience of adults who have been diagnosed three years or longer with a primary malignant brain tumor (PMBT). RESEARCH APPROACH: Qualitative using a biographical narrative approach. SETTING: Six sites across the United States. PARTICIPANTS: Survivors of PMBTs (N = 35) and their family caregivers (N = 35). METHODOLOGIC APPROACH: Using a semistructured interview guide, survivors and caregivers were interviewed individually about their lives before and since the PMBT diagnosis. Thematic analysis was performed to identify themes. FINDINGS: Stability in survivor lives disintegrated as a result of the changes experienced related to the tumor and its treatment. Those changes were profound and ultimately contributed to multiple losses in key areas of their lives. Over time, living with the diagnosis and its consequences required survivors and their caregivers to adapt to the new reality of their lives. Through the process of becoming a survivor, individuals were able to take back control of their lives. Adaptation required survivors to use internal and external resources as ways of coping with their new reality. CONCLUSIONS: People with PMBTs require support as they adapt to losses and changes that impact their lives. Assessment of specific changes that impact survivors' lives may be useful in guiding type of support given. Symptom management and mobilization of internal and external resources may lessen the life-changing impact. INTERPRETATION: Nurses should capture symptom meaning during assessments and expand assessments to include social support systems. Instituting measures that facilitate survivor independence may lessen the impact of disability. The significance of symptom worsening over time requires additional research. KNOWLEDGE TRANSLATION: Restoring self-worth and taking control of their lives are critical concerns for survivors of PMBTs.

The influence of caregiver mastery on depressive symptoms.

PURPOSE: The purpose of this study was to explore how the relationship between care recipients' problem behaviors and caregivers' depressive symptoms varies as a function of caregiver mastery, controlling for the effects of caregiver age, gender, and relationship to the care recipient in caregivers of people with primary malignant brain tumor (PMBT). DESIGN: A cross-sectional design was used to gather data via telephone interviews from 95 caregivers of people with primary malignant brain tumor, recruited from 2003 to 2004 from a brain tumor treatment center, two national support groups, and a statewide cancer registry. METHODS: Measures for the study included the Neuropsychiatric Inventory-Questionnaire, Caregiver Mastery, and the Center for Epidemiologic Studies-Depression. A stepwise regression procedure was used to evaluate potential moderating and mediating relationships. FINDINGS: Data did not indicate that caregiver mastery was a moderating variable. The analysis showed caregiver mastery as a partial mediator, with both a direct effect of care recipients' problem behaviors on caregivers' depressive symptoms and an indirect effect through caregiver mastery. Concerning the indirect effect, care recipients' problem behaviors were related to lower levels of caregiver mastery, which in turn were related to more depressive symptoms in caregivers. CONCLUSIONS: Findings showed a link between care recipients' problem behaviors and caregivers' depressive symptoms, a relationship that has not been well established in oncology. This association indicates one mechanism through which problem behaviors in the care recipient might lead to caregiver depressive symptoms.

Predictors of distress in caregivers of persons with a primary malignant brain tumor.

The purpose of this cross-sectional, descriptive study was to identify predictors of distress for family caregivers of persons with a primary malignant brain tumor (PMBT). The effect of the care recipient's functional, cognitive, and neuropsychiatric status on caregiver burden and depressive symptoms was examined through telephone interviews with 95 caregivers. Care recipients' neuropsychiatric status consistently affected caregivers' depressive symptoms and burden, and assisting with activities of daily living affected burden related to caregivers' schedules and health. The care recipient's cognitive status and need for assistance with instrumental activities of daily living did not affect any outcome variable. Results may help identify caregivers at risk for negative outcomes, and suggest interventions to improve caregivers' emotional health.

Symptom management of brain tumor patients.

OBJECTIVES: To review the symptoms frequently observed with brain tumors, focusing on the descriptions, causes, treatments, and nursing implications. DATA SOURCES: Research and review articles and textbooks. CONCLUSION: Patients with brain tumors commonly have symptoms caused by the tumor or treatment. Treatment approaches for these symptoms will help the patient cope with those impairments caused by the symptoms. IMPLICATIONS FOR NURSING PRACTICE: The nurse can help move the patient toward a good quality of life by being aware of the symptoms and setting a plan to manage the symptoms with a patient and caregiver. Periodic reassessment is required to maintain continuity of care.

Caregivers of persons with a brain tumor: a conceptual model.

Researchers have documented negative physical and emotional consequences for both family caregivers of persons with cancer as well as caregivers of persons with a neurologic disorder. However, there is a unique subset of caregivers who must provide care for someone who may suffer from both a short, terminal trajectory of disease, as well as neurological and neuropsychiatric sequelae - the caregiver of a person with a primary malignant brain tumor. The purpose of this article was to describe a conceptual framework for providing care for a person with a primary malignant brain tumor. The demands of this particular care situation are described, as well as potential resources available to the caregiver to meet those demands. Finally, the stress response that results from the balance between care demands and caregiver resources is illustrated. Development of a conceptual framework for this caregiving population is the first step in assisting nurses to identify factors that place caregivers of persons with a primary malignant brain tumor at risk for negative consequences, and to design interventions to improve caregiver health.