Inmunoterapia vs. terapia diana en el paciente con melanoma avanzado y mutación BRAF V600, ¿por cuál comenzar? / Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First?

El paciente con melanoma avanzado, metastásico o de alto riesgo, cuenta con opciones de tratamiento sistémico, inmunoterapia y terapias dirigidas, que han mejorado significativamente su supervivencia. El 50% de los pacientes con melanoma presentan mutación del gen BRAF. La toma de decisiones en cuanto a la secuencia óptima de tratamiento sistémico debe tener en cuenta factores relacionados con el medicamento, factores clínicos del paciente, así como los propios del tumor. Aunque la combinación ipilimumab-nivolumab es la que proporciona mejores resultados de supervivencia en todos los pacientes, la toxicidad asociada y el perfil de las terapias diana las puede hacer recomendables como primera línea en pacientes en determinadas situaciones clínicas. El objetivo de esta revisión es proporcionar un algoritmo de toma de decisiones en cuanto a la primera línea de tratamiento sistémico, inmunoterapia vs. terapias dirigidas, en el paciente con melanoma avanzado con mutación BRAF (AU)

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma (AU)

[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? / Inmunoterapia vs. terapia diana en el paciente con melanoma avanzado y mutación BRAF V600, ¿por cuál comenzar?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma (AU)

El paciente con melanoma avanzado, metastásico o de alto riesgo, cuenta con opciones de tratamiento sistémico, inmunoterapia y terapias dirigidas, que han mejorado significativamente su supervivencia. El 50% de los pacientes con melanoma presentan mutación del gen BRAF. La toma de decisiones en cuanto a la secuencia óptima de tratamiento sistémico debe tener en cuenta factores relacionados con el medicamento, factores clínicos del paciente, así como los propios del tumor. Aunque la combinación ipilimumab-nivolumab es la que proporciona mejores resultados de supervivencia en todos los pacientes, la toxicidad asociada y el perfil de las terapias diana las puede hacer recomendables como primera línea en pacientes en determinadas situaciones clínicas. El objetivo de esta revisión es proporcionar un algoritmo de toma de decisiones en cuanto a la primera línea de tratamiento sistémico, inmunoterapia vs. terapias dirigidas, en el paciente con melanoma avanzado con mutación BRAF (AU)

Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? / Inmunoterapia vs. terapia diana en el paciente con melanoma avanzado y mutación BRAF V600, ¿por cuál comenzar?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

Impact of a pulmonary embolism response team initiative on hospital mortality of patients with bilateral pulmonary embolism / Impacto de una iniciativa de equipo de respuesta a la embolia pulmonar en la mortalidad hospitalaria de pacientes con embolia pulmonar bilateral

Introduction Pulmonary embolism (PE) response teams (PERT) for the management of high-risk PE (HR-PE) and intermediate-high risk PE (IHR-PE) are encouraged in PE guidelines. We aimed to assess the impact of a PERT initiative on mortality in these groups of patients, compared with standard care. Methods We conducted a prospective, single-center registry, including consecutive patients with HR-PE and IHR-PE with PERT activation from February-2018 to December-2020 (PERT group, n=78 patients) and compared it with an historic cohort of patients admitted to our hospital in a previous 2-year period (2014–2016), managed with standard of care (SC-group, n=108 patients). Results Patients in the PERT group were younger and less comorbid. The risk profile at admission and the percentage of HR-PE was similar in both cohorts (13% in SC-group and 14% in PERT-group, p=0.82). Reperfusion therapy was more frequently indicated in PERT-group (24.4% vs 10.2%, p=0.01), with no differences in fibrinolysis treatment, while catheter-directed therapy (CDT) was more frequent in PERT group (16.7% vs 1.9%, p<0.001). Reperfusion and CDT were associated with lower in-hospital mortality (2.9% vs 15.1%, p=0.001 for reperfusion and 1.5% vs 16.5%, p=0.001 for CDT). The primary outcome, 12-month mortality, was lower in the PERT-group (9% vs 22.2%, p=0.02), There were no differences in 30-day readmissions. In multivariate analysis PERT activation was associated with lower mortality at 12 months (HR 0.25, 95% confidence interval 0.09–0.7, p=0.008). Conclusion A PERT initiative in patients with HR-PE and IHR-PE was associated with a significant reduction in 12-month mortality compared with standard of care, and also with an increase in the use of reperfusion, especially catheter-directed therapies (AU)

Introducción Las guías de manejo de embolia pulmonar (EP) recomiendan organizar equipos de respuesta a la embolia pulmonar (PERT) para el manejo de la EP de riesgo intermedio-alto (EP-IAR) y de alto riesgo (EP-AR). Nuestro objetivo fue evaluar el impacto de una iniciativa PERT sobre la mortalidad en estos pacientes, en comparación con la atención estándar. Métodos Realizamos un registro prospectivo unicéntrico, incluyendo pacientes consecutivos con EP-IAR y EP-AR con activación del PERT desde febrero de 2018 hasta diciembre de 2020 (grupo PERT, n=78 pacientes) y lo comparamos con una cohorte histórica de pacientes ingresados en nuestro hospital en un período previo de 2 años (2014-2016), manejados con atención estándar (grupo SC, n=108 pacientes). Resultados Los pacientes del grupo PERT eran más jóvenes y con menos comorbilidades. El perfil de riesgo al ingreso y el porcentaje de EP-AR fue similar en ambas cohortes (13% en el grupo SC y 14% en el grupo PERT, p=0,82). La terapia de reperfusión fue más frecuentemente indicada en el grupo PERT (24,4% vs. 10,2%, p=0,01), sin diferencias en el uso de fibrinólisis, mientras que la terapia dirigida por catéter (CDT) fue más frecuente en el grupo PERT (16,7% vs. 1,9%, p<0,001). La reperfusión y la CDT se asociaron con una menor mortalidad hospitalaria (2,9% vs. 15,1%, p=0,001 para reperfusión y 1,5% vs. 16,5%, p=0,001 para CDT). El objetivo primario, la mortalidad a los 12 meses, fue menor en el grupo PERT (9% frente al 22,2%, p=0,02). No hubo diferencias en los reingresos a los 30 días. En el análisis multivariado la activación de PERT se asoció con una menor mortalidad a los 12 meses (hazard ratio 0,25, intervalo de confianza del 95%: 0,09-0,7, p=0,008)(AU)

Impact of a pulmonary embolism response team initiative on hospital mortality of patients with bilateral pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) response teams (PERT) for the management of high-risk PE (HR-PE) and intermediate-high risk PE (IHR-PE) are encouraged in PE guidelines. We aimed to assess the impact of a PERT initiative on mortality in these groups of patients, compared with standard care. METHODS: We conducted a prospective, single-center registry, including consecutive patients with HR-PE and IHR-PE with PERT activation from February-2018 to December-2020 (PERT group, n=78 patients) and compared it with an historic cohort of patients admitted to our hospital in a previous 2-year period (2014-2016), managed with standard of care (SC-group, n=108 patients). RESULTS: Patients in the PERT group were younger and less comorbid. The risk profile at admission and the percentage of HR-PE was similar in both cohorts (13% in SC-group and 14% in PERT-group, p=0.82). Reperfusion therapy was more frequently indicated in PERT-group (24.4% vs 10.2%, p=0.01), with no differences in fibrinolysis treatment, while catheter-directed therapy (CDT) was more frequent in PERT group (16.7% vs 1.9%, p<0.001). Reperfusion and CDT were associated with lower in-hospital mortality (2.9% vs 15.1%, p=0.001 for reperfusion and 1.5% vs 16.5%, p=0.001 for CDT). The primary outcome, 12-month mortality, was lower in the PERT-group (9% vs 22.2%, p=0.02), There were no differences in 30-day readmissions. In multivariate analysis PERT activation was associated with lower mortality at 12 months (HR 0.25, 95% confidence interval 0.09-0.7, p=0.008). CONCLUSION: A PERT initiative in patients with HR-PE and IHR-PE was associated with a significant reduction in 12-month mortality compared with standard of care, and also with an increase in the use of reperfusion, especially catheter-directed therapies.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer.

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability to predict response to treatment of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. Based on their results, a series of recommendations are made to optimize the determination of these biomarkers and thus help standardize the diagnosis and treatment of these tumours.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer / Consenso de Expertos de la Sociedad Española de Patología y la Sociedad Española de Oncología Médica sobre la determinación de biomarcadores en el cáncer de páncreas y vías biliares

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability to predict response to treatment of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. Based on their results, a series of recommendations are made to optimize the determination of these biomarkers and thus help standardize the diagnosis and treatment of these tumours.

El cáncer de páncreas y el de vías biliares son tumores de mal pronóstico. En los últimos años, el desarrollo de nuevas técnicas diagnósticas de biología molecular ha permitido conocer las principales alteraciones génicas implicadas en el desarrollo de estos tumores. Múltiples estudios han evaluado el carácter predictivo de respuesta a tratamiento de determinados biomarcadores, como BRCA en cáncer de páncreas, IDH1 y FGFR2 en tumores de vía biliar; y la inestabilidad de microsatélites y las fusiones de NTRK, para predecir la respuesta al tratamiento. En este consenso, un grupo de expertos seleccionado por la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) ha revisado el papel que desempeñan estas mutaciones en el proceso de carcinogénesis y sus implicaciones clínicas. Como resultado, en este artículo se proponen una serie de recomendaciones para optimizar la determinación de estos biomarcadores, con el fin de fomentar la estandarización en el diagnóstico y el tratamiento de estos tumores.(AU)

[Multidisciplinary consensus on optimizing the detection of NTRK gene alterations in tumours]. / Consenso multidisciplinar para optimizar la determinación de alteraciones del gen NTRK.

The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionized the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children and are either rare tumours with common NTRK fusions that may be diagnostic, or more common tumours with rare NTRK fusions. To assess the currently available evidence, 3key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathology (SEAP) and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical and therapeutic aspects of NTRK-fusion tumours. It also discusses the challenges related to the routine detection of these genetic alterations in a mostly public health care system.

Infecciones en pacientes con tumores sólidos de sistema nervioso central y de cabeza y cuello / Infections in patients with solid tumors of the central nervous system and head and neck

Los tumores sólidos representan el 90% de las patologías oncohematológicas que se diagnostican en Argentina. Las infecciones son una de las complicaciones más frecuentes, causando una importante morbimortalidad, y en muchos casos retrasan la prosecución de los tratamientos específicos. La incidencia y tipo de infección depende del sitio específico del tumor, los fenómenos post obstructivos, el tipo e intensidad del tratamiento que se administre, las comorbilidades del paciente y la epidemiología local, entre otros factores. En forma constante se van incorporando nuevos tratamientos al arsenal terapéutico, tales como nuevos esquemas de quimioterapia, terapias blanco e inmunoterapia, y el manejo de las complicaciones asociadas a los mismos representa un desafío para el equipo tratante.En esta revisión abordamos la epidemiología, prevención y manejo de las complicaciones infecciosas más frecuentes en los pacientes con tumores de sistema nervioso central y de cabeza y cuello

Solid tumours represent 90 percent of the oncohematologic pathologies diagnosed in Argentina. Infections are one of the most frequent complications causing important morbidity and mortality and delay in prosecution of their specific treatment. The type of infection depends on the specific site of the tumour, the presence of post obstructive phenomena, the treatment administered, comorbidity and local epidemiology, among others. New therapies are being continuously incorporated to the armamentarium of cancer treatment such as new chemotherapies regimes, target therapy and immunotherapy. The management of adverse events and infectious complications associated with them are a challenge for the physician in charge of these patients.The epidemiology, prevention and management of the most frequent infectious complications in patients with tumours of the central nervous system and head and neck are reviewed in this paper

Nuevas posibilidades terapéuticas en melanoma metastásico / Novel therapeutics possibilities for metastatic melanoma

El melanoma ha experimentado un aumento constante en su tasa de incidencia en las últimas cinco décadas a nivel mundial. El pronóstico del paciente con melanoma se relaciona con el estadio de la enfermedad al momento del diagnóstico, con una sobrevida global media de 6,2 meses en pacientes con melanoma metastásico. El avance en las investigaciones sobre la biología y el comportamiento tumoral permitió el desarrollo de nuevas terapias con distintos mecanismos de acción y mayor eficacia. En esta revisión se abordan las terapias biológicas en melanoma metastásico, su mecanismo de acción y principales resultados en ensayos clínicos. (AU)

Melanoma has experienced a consistent increase in incidence over the past five decades worldwide. The prognosis of patients with melanoma is related to the stage of disease at diagnosis, with a median overall survival of 6.2 months in metastatic melanoma. Progress in research on tumor biology allowed the development of new therapies with different mechanisms of action and greater efficiency. In this review, biologic therapies in metastatic melanoma, its mechanism of action and main results in clinical trials are discussed. (AU)

[New drugs in the treatment of multiple myeloma]. / Nuevos fármacos en el tratamiento del mieloma múltiple.

Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient.