Background: Our understanding of the interaction between the host immune system and cancer has evolved rapidly over the previous 10 years due to the clinical success induced by checkpoint inhibition. Previous immunologic work can now be realized in combination strategies. Modified Vaccinia Ankara (MVA) offers significant opportunities due to its natural induction of innate and adaptive immunity, large payload, and excellent safety profile. Methods: MVA vectors were administered subcutaneously (SC), intravenously (IV) or intratumorally (IT) into tumor-bearing mice. Cytokine secretion profile in serum was assessed by Luminex analysis. NK and T cell infiltration and activation in various organs and cytolytic activity against target cells were determined by flow cytometrybased assays. PD-1 immune checkpoint blockade (ICB), low dose cyclophosphamide, tumor-targeting Abs or 15 Gy radiotherapy were administered along with IV MVA. Results: Recombinant MVA (rMVA) in which tumor antigens and costimulatory molecules are encoded can be customized for maximal effect by route of administration. rMVA administered intravenously (IV) causes superior induction of antigen specific T cells, cytokines and NK cells than previously seen with subcutaneous or intramuscular routes. Encoding CD40L in addition amplifies the effects and efficacy improves in relevant models. This is dependent on T cells and NK cells, indicating a potential solution to one tumor-resistance mechanism, MHC loss and/or mutation. Furthermore, the combination of rMVA with tumor targeting antibodies, checkpoint inhibition, radiotherapy or chemotherapy often showed additional synergistic therapeutic effects. Administration of MVA alone intratumorally (IT) causes innate immune activation through toll like receptors (TLRs) as well as the cGAS / STING pathway. Recombinant antigen encoding rMVA improves systemic and local antigen-specific T cell responses. These effects can be bolstered by encoding certain costimulatory molecules. Conclusions: IV and IT recombinant MVA may offer off the shelf solutions to resolve many of the host -tumor immunity interactions that result in lack of efficacy of checkpoint inhibition alone in most patients. Bavarian Nordic plans to initiate clinical trials with existing agents in 2019 applied IV and IT and will create novel constructs to maximize clinical effect, planned to initiate in 2020 and beyond. Legal entity responsible for the study: Bavarian Nordic, Inc.
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BACKGROUND
Brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) are considered a major determinant of overall survival (OS). Historically, surgical resection (SR), stereotactic radiosurgery (SRS), or/and whole-brain radiation therapy (WBRT) followed by chemotherapy has been the treatment modalities for BM from lung adenocarcinoma. Recent insights into the biology of adenocarcinoma have led to a wealth of novel therapies, including tyrosine kinase inhibitors (TKIs). Here, we review the pattern of brain metastasis in lung adenocarcinoma patients and management strategies in our centre.
MATERIAL AND METHODS
We performed a single-centre retrospective analysis of patients with lung adenocarcinoma and BM between 2017–2020. Data were collected from electronic medical records, including clinical and histopathological features and outcomes. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test.
RESULTS
We identified 29 patients, 65% male, median age 65 years (range 38–84); 55% ECOG PS 0–1; 59% smokers; 55% had extracranial metastases (ECM) and 66% were symptomatic, 24% were EGFR mutated, the frequency of ALK rearrangement was 14%, in 14% the molecular testing was not performed. We treated 59% with WBRT, 12% with SRS, 11% with SR+WBRT and 4% with SR+SRS; 14% were referred for palliative care. Clinical deterioration during local therapy was observed in 32% of the patients and, consequently, they haven’t undergone systemic treatment. After local treatment, 26% received chemotherapy (CT) and 28% received TKIs therapy. Median OS (mOS) was 11.3 months (95% CI 2.4–20.3) for the CT subgroup; mOS for the TKIs subgroup was not reached, but the 1-year survival rate was 67%.
CONCLUSION
BM confers a worse prognosis in lung adenocarcinoma patients. Currently, targeted systemic treatments in patients with driver mutations improve survival and have demonstrated efficacy in lung adenocarcinoma metastatic to the brain. Further research is needed to find better treatments for BM in NSCLC patients with no driver mutations.
patients had to withdraw owing to financial toxicity while they were still responding with average time to withdrawal being 7.2 months. Conclusions: This observational study depicts the real world scenario of the difficulties in bringing approved regimen into practice with financial toxicity being the reason the non usage in nearly 60% patients. In low income countries, this needs to be addressed if more number of patients are to be benefitted from IO agents in NSCLC.
Introdução: A atividade física (AF) está associada ao melhor desempenho acadêmico, gerando efeitos positivos de aprendizagem, sendo a AF uma intervenção eficaz para aumentar a aprendizagem dos estudantes universitários. Objetivo: Este estudo teve como objetivo investigar os efeitos da atividade física (AF) no desempenho acadêmico dos universitários. Material e métodos: O trabalho foi composto de uma revisão de literatura e utilizou-se das plataformas: PubMed, Cochrane Library, EBESC e Google Acadêmico. Para tanto utilizou-se palavras-chave seguindo o método de busca pelo site DeCS, dos quais nortearam a seleção do material em português, inglês e espanhol. Resultados: Selecionou-se estudos que abordavam sobre a AF como uma ferramenta que contribuiu para o desempenho acadêmico dos uni-versitários, afirmando, nesse caso, que a prática regular pode, também gerar beneficiar que contribuem para as questões psíquicas. A proteção do cérebro (neurogênese hipocampal), em que é importante reforçar que a neurogênese desempenha um papel fundamental na cognição. Aborda-se outros fatores além da AF que podem contribuir (ou prejudicar) o desempenho em sala de aula, referente ao estilo de vida. Conclusão: Diante dos achados, compreen-de-se que o desempenho acadêmico está relacionado com a saúde geral dos universitários. No entanto, destaca-se que a prática regular de AF é um fator chave para proteger o cérebro e dar efeitos imediatos durante a sala de aula, aumentando as notas e as chances de ter um futuro promissor no que se refere a estudos.
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