Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model.

BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and with regard to the underlying mechanisms. RESULTS: Combined treatment with precision RT and checkpoint inhibitor IT achieved control of tumor growth. However, BALB/c mice receiving combined treatment demonstrated changes in measures of anxiety levels, regardless of tumor status. C57BL/6J mice with tumors demonstrated increased anxiety, except following combined treatment. Object recognition memory was impaired in C57BL/6J mice without tumors following combined treatment. All mice with tumors showed impaired object recognition, except those treated with RT alone. Mice with tumors demonstrated impaired amygdala-dependent cued fear memory, while maintaining hippocampus-dependent context fear memory. These behavioral alterations and cognitive impairments were accompanied by increased microglial activation in mice receiving immunotherapy alone or combined with RT. Finally, based on tumor status, there were significant changes in proinflammatory cytokines (IFN-γ, IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic). MATERIALS AND METHODS: Here we test the hypothesis that IT combined with peripheral RT have detrimental behavioral and cognitive effects as a result of an enhanced proinflammatory environment in the brain. BALB/c mice with or without injected hind flank CT26 colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody, and precision CT-guided peripheral RT alone and combined were used to closely model clinical treatment. We assessed behavioral and cognitive performance and investigated the immune environment using immunohistochemistry and multiplex assays to analyze proinflammatory mediators. CONCLUSIONS: Although combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Additional file 1: of Next-generation genotyping of hypervariable loci in many individuals of a non-model species: technical and theoretical implications

Supplementary materials [119]. (DOCX 43 kb

Chemoradiation versus radiation alone in stage IIIB cervical cancer patients with or without human immunodeficiency virus

ObjectiveCervical cancer remains the most common cancer among women in sub-Saharan Africa and is also a leading cause of cancer related deaths among these women. The benefit of chemoradiation in comparison with radiation alone for patients with stage IIIB disease has not been evaluated prospectively in women living with human immunodeficiency virus (HIV). We assessed the survival of chemoradiation versus radiation alone among stage IIIB cervical cancer patients based on HIV status.MethodsBetween February 2013 and June 2018, patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIB cervical cancer with or without HIV and treated with chemoradiation or radiation alone, were prospectively enrolled in an observational cohort study. Overall survival was evaluated using the Kaplan-Meier method. Cox proportional hazards modeling was used to analyze associations with survival.ResultsAmong 187 patients, 63% (n=118) of women had co-infection with HIV, and 48% (n=69) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2 year overall survival compared with those receiving radiation alone (59% vs 41%, p<0.01), even among women living with HIV (60% vs 38%, p=0.02). On multivariable Cox regression analysis, including all patients regardless of HIV status, 2 year overall survival was associated with receipt of chemoradiation (hazard ratio (HR) 0.63, p=0.04) and total radiation dose ≥80 Gy (HR 0.57, p=0.02). Among patients who received an adequate radiation dose of ≥80 Gy, adjusted overall survival rates were similar between chemoradiation versus radiation alone groups (HR 1.07; p=0.90). However, patients who received an inadequate radiation dose of <80 Gy, adjusted survival was significantly higher in chemoradiation versus radiation alone group (HR 0.45, p=0.01).ConclusionsAddition of chemotherapy to standard radiation improved overall survival, regardless of HIV status, and is even more essential in women who cannot receive full doses of radiation