Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events.

UNLABELLED: : In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended. IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer. Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be life-threatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.

Immunoradiotherapy as An Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent.

Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy.

Immunotherapy, Cancer and Rheumatological Diseases: A Review of the Literature and a Series of Cases in a University Hospital. / Inmunoterapia, cáncer y enfermedades reumatológicas: revisión de la literatura y serie de casos en un hospital universitario.

The appearance in the field of oncology of therapeutic molecules in the form of monoclonal antibodies, whose objective is to stimulate the patient's own immune system to be responsible for destroying cancer cells, has revolutionized the treatment of many cancers in recent years. This type of therapy, called immunotherapy, is also characterized by presenting side effects in the form of autoimmune diseases that we are still beginning to understand. From the point of view of the immune-mediated rheumatological side effects, we can find musculoskeletal manifestations, mechanical, inflammatory or systemic autoimmune diseases. The therapeutic approach to these side effects remains uncertain due to the absence of clinical trials and validated recommendations. The multidisciplinary management is crucial to successfully treat such cases. In the following manuscript, we will describe our case reports of rheumatologic immune-related adverse events in a university hospital.

[High prevalence of hypovitaminosis D in medical students in Gran Canaria, Canary Islands (Spain)]. / Elevada prevalencia de hipovitaminosis D en los estudiantes de medicina de Gran Canaria, Islas Canarias (España).

BACKGROUND: Vitamin D deficiency has been described in many diseases and indeed in the general population. However fewer reports have been published in young and healthy people. Vitamin D deficiency should not be found in medical students of the Canary Islands, because they have all the resources to avoid it. OBJECTIVE: To estimate the prevalence of vitamin D deficiency in a population of medical students of both gender from the University of Las Palmas de Gran Canaria. METHODS: 103 medical students of both genders from the University of Las Palmas de Gran Canaria. They completed a questionnaire and a physical examination. Vitamin D (25- hydroxycholecalciferol [25-HCC]), parathyroid hormone, biochemical markers of bone remodeling and a general biochemical study were performed. Bone mineral density was assessed by dual energy X-ray absorptiometry at the lumbar spine and the proximal femur. Quantitative ultrasounds parameters were measured at the calcaneus. RESULTS: Only 38.8% of the students of Medicine (42.1% of males and 44.9% of females) have 25-HCC values higher than 30 ng/dl as widely recommended nowadays. Vitamin D deficiency (< 20 ng/ml) is observed in 32.6% and vitamin D insufficiency (< 30 ng/ml) in 28.6% of the students of Medicine in Las Palmas de Gran Canaria. CONCLUSION: Although they have optimal conditions for having good levels of vitamin D, near two thirds of the medical students in the Canaries have low values of vitamin D.

Inmunoterapia, cáncer y enfermedades reumatológicas: revisión de la literatura y serie de casos en un hospital universitario / Immunotherapy, cancer and rheumatological diseases: a review of the literature and a series of cases in a university hospital

La aparición en el campo de la oncología de moléculas terapéuticas en forma de anticuerpos monoclonales, cuyo objetivo consiste en estimular el propio sistema inmune del paciente para que sea este el encargado de destruir las células cancerígenas, ha revolucionado el tratamiento de diversos cánceres en los últimos años. Este tipo de terapia, denominada inmunoterapia, se caracteriza además por presentar efectos secundarios en forma de enfermedades autoinmunes que todavía estamos empezando a conocer. Desde el punto de vista de los efectos secundarios inmunomediados reumatológicos, podemos encontrar manifestaciones musculoesqueléticas mecánicas, inflamatorias o enfermedad autoinmune sistémica. El manejo terapéutico de estos efectos secundarios se mantiene variable debido a la ausencia de ensayos clínicos y de recomendaciones validadas, siendo el manejo multidisciplinar fundamental para tratar con éxito dichos casos. En este artículo presentamos nuestra serie de casos clínicos de pacientes en tratamiento con inmunoterapia y efectos secundarios inmunomediados reumatológicos en un hospital universitario

The appearance in the field of oncology of therapeutic molecules in the form of monoclonal antibodies, whose objective is to stimulate the patient's own immune system to be responsible for destroying cancer cells, has revolutionized the treatment of many cancers in recent years. This type of therapy, called immunotherapy, is also characterized by presenting side effects in the form of autoimmune diseases that we are still beginning to understand. From the point of view of the immune-mediated rheumatological side effects, we can find musculoskeletal manifestations, mechanical, inflammatory or systemic autoimmune diseases. The therapeutic approach to these side effects remains uncertain due to the absence of clinical trials and validated recommendations. The multidisciplinary management is crucial to successfully treat such cases. In the following manuscript, we will describe our case reports of rheumatologic immune-related adverse events in a university hospital

Elevada prevalencia de hipovitaminosis D en los estudiantes de medicina de Gran Canaria, Islas Canarias (España) / High prevalence of hypovitaminosis D in medical students in Gran Canaria, Canary Islands (Spain)

Fundamento: Se ha descrito la existencia de deficiencia de vitamina D tanto en la población general como en un gran número de enfermedades. Sin embargo, se han publicado pocos estudios realizados en población joven y sana en España. Teóricamente no debería encontrarse deficiencia de vitamina D entre los estudiantes de Medicina de la Universidad de Las Palmas de Gran Canaria, porque disponen de todos los medios para evitarla. Objetivo: Estimar la prevalencia de deficiencia de vitamina D en una población de estudiantes de Medicina de ambos sexos de la Universidad de Las Palmas de Gran Canaria. Método: Se estudiaron 103 alumnos de Medicina de ambos sexos de la Universidad de Las Palmas de Gran Canaria. A todos se les realizó un cuestionario y una exploración física. Se determinó la vitamina D 25-hidroxicolecalciferol (25-HCC), la hormona paratiroidea, varios marcadores bioquímicos de remodelado óseo y un estudio bioquímico general. Se estimó la densidad mineralósea por absorciometría radiológica dual en la columna lumbar y en la extremidad proximal del fémur. Asimismo, se midieron los parámetros ultrasonográficos en el calcáneo. Resultados: Sólo el 38,8% de los estudiantes de Medicina (el 42,1% de los varones y el 44,9%de las mujeres) presentaron niveles de 25-HCC superiores a 30 ng/dl tal y como se recomienda (..) (AU)

Background: Vitamin D deficiency has been described in many diseases and indeed in the general population. However fewer reports have been published in young and healthy people. Vitamin D deficiency should not be found in medical students of the Canary Islands, because they have all the resources to avoid it. Objective: To estimate the prevalence of vitamin D deficiency in a population of medical students of both gender from the University of Las Palmas de Gran Canaria. Methods: 103 medical students of both genders from the University of Las Palmas de Gran Canaria. They completed a questionnaire and a physical examination. Vitamin D (25- hydroxycholecalciferol [25-HCC]), parathyroid hormone, biochemical markers of bone remodeling and ag eneral biochemical study were performed. Bone mineral density was assessed by dual energyX-ray absorptiometry at the lumbar spine and the proximal femur. Quantitative ultrasounds parameters were measured at the calcaneus. Results: Only 38.8% of the students of Medicine (42.1% of males and 44.9% of females) have25-HCC values higher than 30 ng/dl as widely recommended nowadays. Vitamin D deficiency(< 20 ng/ml) is observed in 32.6% and vitamin D insufficiency (< 30 ng/ml) in 28.6% of the students of Medicine in Las Palmas de Gran Canaria. Conclusion: Although they have optimal conditions for having good levels of vitamin D, near two thirds of the medical students in the Canaries have low values of vitamin D (AU)