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      Encefalitis autoinmune por pembrolizumab en anciano con carcinoma no microcítico avanzado de pulmón. Caso clínico Translated title: Pembrolizumab-associated autoimmune encephalitis in an elderly patient with advanced non-small cell lung cancer. A clinical case

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          Resumen

          Los objetivos terapéuticos en el paciente geriátrico son la mejora de su calidad de vida y de su capacidad funcional frente al mero incremento de su supervivencia. En patología neoplásica, la decisión de iniciar tratamiento curativo, especialmente inmunoterapia, debe realizarse tras una completa valoración de los riesgos potenciales. El paciente geriátrico es más susceptible a desarrollar reacciones adversas y de mayor gravedad que el paciente más joven.

          Se presenta el caso de un anciano octogenario con carcinoma no microcítico pulmonar que desarrolló toxicidad neurológica tras tratamiento con pembrolizumab. Se realiza un diagnóstico diferencial de encefalitis y una revisión de los casos de encefalitis autoinmune por pembrolizumab para mejorar nuestro conocimiento de esta infrecuente toxicidad. El trabajo interdisciplinar y la valoración geriátrica integral son elementos esenciales para prevenir el deterioro funcional del anciano.

          Abstract

          Therapeutic objectives for the geriatric patient are improvement of quality of life and functional capacity rather than a mere increase in survival. In neoplastic disease, the decision to initiate administration of curative therapies, especially immunotherapy, should be taken only after any potential risks have been taken into account. Geriatric patients are more susceptible to developing more serious adverse reactions than the younger population.

          We report the case of an octogenarian patient with non-small cell lung cancer who developed neurologic toxicity following pembrolizumab therapy. We carry out a differential diagnosis of encephalitis and provide a literature review of pembrolizumab-associated autoimmune encephalitis cases in order to improve our knowledge of this unusual toxicity. An interdisciplinary approach and comprehensive geriatric assessment are essential components to prevent functional decline in the elderly.

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          Most cited references19

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          Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

          Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
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            Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept.

            Geriatricians have embraced the term "geriatric syndrome," using it extensively to highlight the unique features of common health conditions in older people. Geriatric syndromes, such as delirium, falls, incontinence, and frailty, are highly prevalent, multifactorial, and associated with substantial morbidity and poor outcomes. Nevertheless, this central geriatric concept has remained poorly defined. This article reviews criteria for defining geriatric syndromes and proposes a balanced approach of developing preliminary criteria based on peer-reviewed evidence. Based on a review of the literature, four shared risk factors-older age, baseline cognitive impairment, baseline functional impairment, and impaired mobility-were identified across five common geriatric syndromes (pressure ulcers, incontinence, falls, functional decline, and delirium). Understanding basic mechanisms involved in geriatric syndromes will be critical to advancing research and developing targeted therapeutic options, although given the complexity of these multifactorial conditions, attempts to define relevant mechanisms will need to incorporate more-complex models, including a focus on synergistic interactions between different risk factors. Finally, major barriers have been identified in translating research advances, such as preventive strategies of proven effectiveness for delirium and falls, into clinical practice and policy initiatives. National strategic initiatives are required to overcome barriers and to achieve clinical, research, and policy advances that will improve quality of life for older persons.
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              Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era.

              Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.
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                Author and article information

                Journal
                An Sist Sanit Navar
                An Sist Sanit Navar
                assn
                Anales del Sistema Sanitario de Navarra
                Gobierno de Navarra. Departamento de Salud
                1137-6627
                2340-3527
                15 June 2021
                May-Aug 2021
                : 44
                : 2
                : 291-297
                Affiliations
                [1 ] originalServicio de Geriatría. Complejo Hospitalario de Navarra. Pamplona. orgdiv1Servicio de Geriatría orgnameComplejo Hospitalario de Navarra Pamplona,
                [2 ] originalServicio de Neurología. Complejo Hospitalario de Navarra. Pamplona. orgdiv1Servicio de Neurología orgnameComplejo Hospitalario de Navarra Pamplona,
                [3 ] originalServicio de Oncología Médica. Complejo Hospitalario de Navarra. Pamplona. orgdiv1Servicio de Oncología Médica orgnameComplejo Hospitalario de Navarra Pamplona,
                [4 ] originalServicio de Radiología. Complejo Hospitalario de Navarra. Pamplona. orgdiv1Servicio de Radiología orgnameComplejo Hospitalario de Navarra Pamplona,
                Author notes
                [Correspondencia: ] Francisco Javier Alonso Renedo. Servicio de Geriatría, Complejo Hospitalario de Navarra, Irunlarrea, 3, 31008 Pamplona, España. E-mail: javier.alonso.renedo@ 123456navarra.es
                Article
                10.23938/ASSN.0948
                10019544
                34132243
                fda84c63-fde7-43ea-b6e2-2c78484cc2e2

                Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons

                History
                : 13 October 2020
                : 02 February 2021
                : 26 February 2021
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 16, Pages: 07
                Categories
                Notas Clínicas

                inhibidores del punto de control inmunitario,pembrolizumab,valoración geriátrica integral,encefalitis,anciano,immune checkpoint inhibitors,comprehensive geriatric assessment,encephalitis,elderly

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