Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Follow-Up of Patients Diagnosed With Germinal Testicular Tumors (Seminomas and Non-seminomatous) Treated With a Bone Marrow Transplant and a High Dose of Chemotherapy.

INTRODUCTION: Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results. METHODS:  The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens, and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021. RESULTS: A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months. CONCLUSIONS:  These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

INTRODUCTION: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. METHODS: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. RESULTS: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. CONCLUSIONS: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Two thousand years of garden urbanism in the Upper Amazon.

A dense system of pre-Hispanic urban centers has been found in the Upano Valley of Amazonian Ecuador, in the eastern foothills of the Andes. Fieldwork and light detection and ranging (LIDAR) analysis have revealed an anthropized landscape with clusters of monumental platforms, plazas, and streets following a specific pattern intertwined with extensive agricultural drainages and terraces as well as wide straight roads running over great distances. Archaeological excavations date the occupation from around 500 BCE to between 300 and 600 CE. The most notable landscape feature is the complex road system extending over tens of kilometers, connecting the different urban centers, thus creating a regional-scale network. Such extensive early development in the Upper Amazon is comparable to similar Maya urban systems recently highlighted in Mexico and Guatemala.

The impact of earthquakes in Latin America on the continuity of HIV care: A retrospective observational cohort study.

Objectives: As earthquakes occur frequently in Latin America and can cause significant disruptions in HIV care, we sought to analyze patterns of HIV care for adults at Latin American clinical sites experiencing a significant earthquake within the past two decades. Study design: Retrospective clinical cohort study. Methods: Adults receiving HIV care at sites experiencing at least a "moderate intensity" (Modified Mercalli scale) earthquake in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) contributed data from 2003 to 2017. Interrupted Time Series models were fit with discontinuities at site-specific earthquake dates (Sept. 16, 2015 in Chile; Apr. 18, 2014 and Sept. 19, 2017 in Mexico; and Aug. 15, 2007 in Peru) to assess clinical visit, CD4 measure, viral load lab, and ART initiation rates 3- and 6-months after versus before earthquakes. Results: Comparing post-to pre-earthquake periods, there was a sharp drop in median visit (incidence rate ratio [IRR] = 0.79, 95% confidence interval [CI]: 0.68-0.91) and viral load lab (IRR = 0.78, 95% CI: 0.62-0.99) rates per week, using a 3-month window. CD4 measurement rates also decreased (IRR = 0.43; 95% CI: 0.37-0.51), though only using a 6-month window. Conclusions: Given that earthquakes occur frequently in Latin America, disaster preparedness plans must be more broadly implemented to avoid disruptions in HIV care and attendant poor outcomes.

Clinical inertia in newly diagnosed type 2 diabetes mellitus among patients attending selected healthcare institutions in Colombia.

BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.

Economic burden due to COVID-19 in a Colombian Caribbean state, 2020 and 2021.

OBJECTIVE: To estimate the economic burden associated with COVID-19 in Córdoba, Colombia, 2020 and 2021. METHODS: Economic burden study. Direct costs were analyzed from the third-party payer perspective using healthcare administrative databases and interviews from a cohort of confirmed COVID-19 cases from Córdoba. Costing aggregation was performed by the bottom-up method. Indirect costs were estimated using the productivity loss approach. Contrast tests and statistical models were estimated at 5% significance. RESULTS: We studied 1,800 COVID-19 cases. The average economic cost of COVID-19 per episode was estimated at US$ 2,519 (95%CI 1,980;3,047). The direct medical cost component accounted for 92.9% of the total; out-of-pocket and indirect costs accounted for 2% and 5.1%, respectively. CONCLUSION: COVID-19 economic cost was mainly due to direct medical costs. This study provided evidence of the economic burden faced by households due to COVID-19, with the most vulnerable households bearing much of the burden on their income.

Economic burden due to COVID-19 in a Colombian Caribbean state, 2020 and 2021 / Carga económica asociada al COVID-19 en un departamento del Caribe colombiano, 2020 e 2021 / Carga econômica associada à covid-19 em um departamento do Caribe colombiano, 2020 e 2021

Abstract Objective: To estimate the economic burden associated with COVID-19 in Córdoba, Colombia, 2020 and 2021. Methods: Economic burden study. Direct costs were analyzed from the third-party payer perspective using healthcare administrative databases and interviews from a cohort of confirmed COVID-19 cases from Córdoba. Costing aggregation was performed by the bottom-up method. Indirect costs were estimated using the productivity loss approach. Contrast tests and statistical models were estimated at 5% significance. Results: We studied 1,800 COVID-19 cases. The average economic cost of COVID-19 per episode was estimated at US$ 2,519 (95%CI 1,980;3,047). The direct medical cost component accounted for 92.9% of the total; out-of-pocket and indirect costs accounted for 2% and 5.1%, respectively. Conclusion: COVID-19 economic cost was mainly due to direct medical costs. This study provided evidence of the economic burden faced by households due to COVID-19, with the most vulnerable households bearing much of the burden on their income.

Resumen Objetivo: Estimar la carga económica asociada al COVID-19 en Córdoba, Colombia, entre 2020 y 2021. Métodos: Estudio de carga económica. Los costos directos se analizaron desde la perspectiva del tercer pagador usando bases de datos administrativas y entrevistas. La agregación del costeo se realizó por el método de bottom-up. Los costos indirectos se estimaron usando el enfoque de pérdida de productividad. Los test de contraste y modelos estadísticos se estimaron al 5% de significancia. Resultados: Se analizaron 1.800 casos de COVID-19. El costo económico promedio por episodio fue US$ 2.519 (IC95% 1.980;3.047). Los costos directos médicos explicaron el 92,9% del total; el gasto de bolsillo y los costos indirectos un 2% y 5,1%, respectivamente. Conclusión: El costo económico del COVID-19 fue principalmente por el costo directo médico. Este estudio evidenció la carga económica que enfrentan los hogares debido al COVID-19, siendo los más vulnerables quienes asumieron la mayor parte en sus ingresos.

Resumo Objetivo: Estimar a carga econômica associada à covid-19 em Córdoba, Colômbia, entre 2020 e 2021. Métodos: Estudo de avaliação da carga econômica da covid-19. Os custos diretos foram analisados segundo terceiros pagadores, usando-se bases de dados administrativas e entrevistas. A agregação dos custos foi realizada usando-se o método bottom-up. Os custos indiretos foram estimados pela perda de produtividade. Testes de contraste ortogonais e modelos de regressão estatísticos foram estimados com 5% de significância. Resultados: Foram estudadas 1.800 pessoas com covid-19. O custo econômico médio da covid-19 por episódio foi estimado em US$ 2.519 (IC95% 1.980;3.047). O componente de custo médico direto representou 92,9% do total; as despesas diretas e custos indiretos representaram 2,0% e 5,1%, respectivamente. Conclusão: O custo econômico da covid-19 deveu-se principalmente aos custos médicos diretos. Este estudo forneceu avaliações da carga econômica enfrentada pelas famílias devido à covid-19; as mais vulneráveis tiveram grande parte da carga sobre os seus rendimentos.

Actualizaciones en el tratamiento del cáncer de mama - 2 / Updates in the treatment of breast cancer - 2

En el año 2021, la Unidad Funcional de Seno y Tejidos Blandos, junto con la Unidad de Oncología Clínica del Instituto Nacional de Cancerología (INC) de Bogotá, D.C., Colombia, publicamos un suplemento sobre actualizaciones de manejo en tres temas quirúrgicos y tres temas clínicos de cáncer de mama y melanoma, con gran acogida por los colegas cirujanos de mama y oncólogos clínicos de todo el país. A mediados de 2021, planeamos realizar un segundo suplemento de actualizaciones seleccionando cinco temas clínicos, que impactan las conductas terapéuticas en los pacientes con cáncer de mama. Siguiendo la misma metodología utilizada para las anteriores actualizaciones, se realizó la revisión y presentación de la evidencia científica relevante en cada uno de los temas, con actualización de la misma a mayo 2022; dicha revisión fue realizada por dos especialistas en entrenamiento de cada uno de los dos servicios, previa supervisión por alguno de los profesores, junto con el análisis de la experiencia de la Unidad Funcional (información de nuestras publicaciones y de la base de datos de cáncer de mama) y la experiencia del grupo de genética del INC. Este proceso fue seguido por la discusión al interior de los grupos involucrados y, finalmente, se establecieron los cambios de conducta en el abordaje terapéutico de cada uno de los temas evaluados.Los cinco manuscritos incluyen: introducción, definición de conceptos clave, justificación, revisión de la evidencia científica y por último, la conducta clínica adoptada después de la discusión conjunta entre las unidades funcionales involucradas en cada tema, basada en los resultados de los ensayos clínicos y la disponibilidad de recursos de nuestro sistema de salud.

Factores pronósticos de la supervivencia en pacientes con melanoma de piel metastásico, que reciben primera línea de tratamiento con inmunoterapia anti PD-1 o régimen con anti PD-1 y anti CTLA-4, en el Instituto Nacional de Cancerología de Colombia / Prognostic factors for survival in patients with metastatic skin melanoma, receiving first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy regimen at the Instituto Nacional de Cancerología (Bogotá, Colombia)

Introducción. En melanoma metastásico, uno de los estándares de tratamiento es la inmunoterapia anti-PD-1 y anti-CTLA-4. El objetivo de esta investigación fue determinar factores pronósticos asociados con la supervivencia de pacientes con melanoma metastásico, con primera línea con inmunoterapia anti-PD-1 o anti-PD-1 y anti-CTLA-4, en el Instituto Nacional de Cancerología de Colombia.Métodos. Se revisaron 63 historias clínicas del Instituto Nacional de Cancerología de enero de 2016 a abril de 2020. Se realizó un análisis de supervivencia con método de Kaplan-Meier, prueba log-rank y regresión de Cox.Resultados. La mayoría de los pacientes fueron mujeres (58,7%); 47,6% tenían subtipo lentiginoso acral, 17,4% BRAF mutado, 20,6% compromiso en SNC, 50,8% recibieron nivolumab, 41,3% pembrolizumab y 7,9% nivolumab + ipilimumab. La mediana de supervivencia libre de progresión fue de 7,3 meses, con una tasa a 1, 2 y 3 años de 38,0%, 22,0% y 12,0% respectivamente; la mediana de supervivencia global fue 12,2 meses con una tasa a 1, 2 y 3 años de 50,0%, 25,0% y 19,0%. Como factor pronóstico protector para SLP se encontró el recibir nivolumab en comparación con pembrolizumab (HR=0,427; IC95% 0,21-0,86) y para SG el estado funcional al diagnóstico (ECOG 2 HR=12,38; IC95% 2,20-69,45).Conclusión. La SLP y SG fueron menores a la de ensayos clínicos aleatorizados en población caucásica, pero similar a la encontrada en estudios que incluyen mayor proporción del subtipo histológico lentiginoso acral, como la nuestra. Se encontraron como factores pronósticos el tipo de inmunoterapia utilizada y el estado funcional al diagnóstico.

Introduction: In metastatic melanoma, one of the standard treatments is anti-PD-1 and anti-CTLA-4 immunotherapy. This research aimed to determine prognostic factors associated with the survival of patients with metastatic melanoma who started first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy at the Instituto Nacional de Cancerología (INC) (Bogotá, Colombia).Methods: A total of 63 medical records from the INC were reviewed from January 2016 to April 2020. A survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox regression.Results: Most patients were women (58.7%); 47.6% had acral lentiginous subtype, 17.4% BRAF-mutated melanoma, 20.6% CNS involvement, 50.8% received nivolumab, 41.3% pembrolizumab, and 7.9% nivolumab + ipilimumab. Median progression-free survival (PFS) was 7.3 months with a rate at 1, 2, and 3 years of 38%, 22%, and 12%, respectively, while median overall survival (OS) was 12.2 months with a rate of 50%, 25%, and 19% at 1, 2, and 3 years, respectively. A protective prognostic factor for PFS was to receive nivolumab compared to pembrolizumab (HR=0.427; CI95% 0.21-0.86), and for OS, functional status at diagnosis (ECOG 2 HR=12.38; CI95% 2.20-69.45).Conclusion: PFS and OS were lower than those of randomized clinical trials in the Caucasian population, but similar to those found in studies that include a higher proportion of the acral lentiginous histological subtype, such as ours. The type of immunotherapy used and functional status at diagnosis were found as prognostic factors

Estudios de extensión para la estadificación del cáncer de mama infiltrante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Extension studies for the staging of infiltrating breast cancer. Review of evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La estadificación del cáncer de mama tiene como objetivo determinar la extensión de la enfermedad, definir el tratamiento y el pronóstico de la misma. La American Joint Committee on Cancer(AJCC) ha asignado el estadio utilizando el tamaño del tumor (T), la presencia de compromiso ganglionar (N), y la presencia o ausencia de metástasis a distancia (M). Con el advenimiento de la biología molecular, se integra a la estadificación anatómica la información pronóstica con el grado histológico, el estado de los receptores hormonales y el resultado del receptor de HER2. En el Instituto Nacional de Cancerología (INC), la incorporación del TNM pronóstico trajo consigo un aumento de estadio en el 14,47% de los casos y una disminución en el 40,3%; este resultado se atribuyó en parte al mayor porcentaje de tumores localmente avanzados dentro de la institución. Por subtipo biológico, los tumores luminales presentan mayor riesgo de metástasis óseas, los tumores triple negativo a pulmón y sistema nervioso central; y los tumores HER2 a SNC, hígado y pulmón. Teniendo en cuenta este compromiso a distancia, los métodos de estadificación comúnmente utilizados son gammagrafía ósea (GO), radiografía de tórax (RxT), ecografía hepática (UH) y/o tomografía computarizada (TC). En el caso de identificar hallazgos sospechosos en estos exámenes o si el cuadro clínico del paciente lo sugiere, se realizan estudios adicionales como TC o resonancia magnética nuclear (RMN). Los cambios en la estadificación clínica y la biología del cáncer de mama motivaron a las Unidades de Seno y Tejidos Blandos y Oncología Clínica del Instituto Nacional de Cancerología a revisar la evidencia científica disponible para recomendar la pertinencia de los estudios de extensión.

The staging of breast cancer has the objective to determine the extent of the disease, define treatment and prognosis. The American Joint Committee on Cancer (AJCC) has assigned the stage using the size of the tumor (T), the presence of lymph node involvement (N), and the presence or absence of distant metastases (M). With the advent of molecular biology, prognostic information with histological grade, hormone receptor status, and HER2 receptor is integrated with anatomic staging. In the National Institute of Cancerology (INC) the incorporation of TNM brought with it an increase in stage in 14.47% of cases and a decrease in 40.3%; this result was attributed in part to the higher percentage of locally advanced tumors within the institution. By biological subtype, luminal tumors have a higher risk of bone metastases, triple negative tumors to the lung and central nervous system; and HER2 tumors to CNS, liver and lung. Taking this distant involvement into account, the commonly used staging methods are bone scan (BS), chest radiography (CXR), liver ultrasound (UH) and/or computed tomography (CT) scans. In the case of identifying suspicious findings in these tests or if the patient's clinical condition suggests it, additional studies such as CT or magnetic resonance imaging (MRI) are performed. Changes in the clinical staging and biology of breast cancer motivated the Breast and Clinical Oncology Functional Unit of the National Cancer Institute to review the available scientific evidence to recommend the relevance of extension studies.

Seguimiento de la paciente con diagnóstico de cáncer de mama. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacionalde Cancerología - Colombia / Follow-up of the patient with breast cancer history. Review of the evidence and approach at the Instituto Nacional de Cancerología - Colombia

Los supervivientes de cáncer se definen como aquellos individuos que han completado su tratamiento inicial y no tienen evidencia de la enfermedad. Para el caso de las pacientes supervivientes de cáncer de mama, el seguimiento involucra no sólo la vigilancia de la recaída locorregional y a distancia, así como la tamización de segundos primarios mamarios, sino también la evaluación de los efectos relacionados con las terapias recibidas. Hoy en día, existe controversia sobre cuál debe ser el método, la frecuencia, la duración y tipo de personal de la salud que realice el seguimiento de estas pacientes. Las guías de las distintas sociedades científicas muestran una variabilidad importante en las recomendaciones a este respecto. Este documento pretende revisar la mejor evidencia disponible sobre los procedimientos para la detección de la recaída locorregional, de las metástasis a distancia, de un segundo cáncer de mama contralateral y de los eventos adversos relacionados con los tratamientos para el cáncer de mama. Adicionalmente, se examinan los porcentajes y sitios de recidiva tumoral con relación al estadio clínico y a la biología tumoral

Cancer survivors are defined as those individuals who have completed their initial treatment and have no evidence of disease. In the case of breast cancer survivors, follow-up involves not only surveillance of locoregional and distant relapse, as well as screening for second primary breast cancers, but also evaluation of the effects related to the therapies received. Nowadays, there is controversy about what should be the method, the frequency, the duration and the type of health personnel that carry out the follow-up of these patients. The guides of the different scientific societies show a significant variability in the recommendations in this regard. This document aims to review the best available evidence on procedures for the detection of locoregional relapse, distant metastases, contralateral second breast cancer, and adverse events related to breast cancer treatments. Additionally, the percentages and sites of tumor recurrence are examined in relation to clinical stage and tumor biology

Tratamiento sistémico para el cáncer de mama HER2 positivo avanzado. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Systemic treatment for advanced HER2 positive breast cancer. Review of the evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

El cáncer de mama es la neoplasia más frecuente y de mayor mortalidad en las mujeres en todo el mundo. El receptor 2 del factor de crecimiento epidérmico humano (HER2) se sobreexpresa en aproximadamente el 20% de las pacientes con cáncer de mama y se asocia a mayor riesgo de recidiva tumoral y mortalidad. Antes del desarrollo de los anticuerpos monoclonales dirigidos contra HER2, el cáncer de mama HER2 positivo estaba asociado con un pronóstico desfavorable. El uso de las terapias dirigidas anti HER2 ha mejorado significativamente las tasas de supervivencia global tanto en el escenario adyuvante como en la enfermedad metastásica. En los últimos años han surgido nuevos medicamentos que bloquean esta vía de señalización, lo cual ha permitido establecer varias líneas de tratamiento con terapia anti HER2 en las pacientes con enfermedad metastásica. Por esta razón, las unidades funcionales de Oncología Clínica/Seno y Tejidos Blandos tomaron la decisión de realizar una revisión de la evidencia científica disponible a octubre de 2021, para establecer las recomendaciones en el abordaje terapéutico de las pacientes con cáncer de mama metastásico HER2 positivo en el Instituto Nacional de Cancerología (INC).

Breast cancer is the most common neoplasm and the one with the highest mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of breast cancer patients and is associated with an increased risk of tumor recurrence and mortality. Before the development of monoclonal antibodies directed against HER2, HER2-positive breast cancer was associated with a poor prognosis. The use of anti-HER2 targeted therapies has significantly improved overall survival rates both in the adjuvant setting and in metastatic disease. In recent years, new drugs have emerged that block this signaling pathway, which has made it possible to establish several lines of treatment with anti-HER2 therapy in patients with metastatic disease. For this reason, the clinical oncology/breast and soft tissue functional units made the decision to conduct a review of the available scientific evidence as of October 2021 to establish recommendations for the therapeutic approach to patients with HER2-positive metastatic breast cancer in the National Cancer Institute (INC).

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Criterios para la identificación de síndromes de cáncer de mama hereditarios. Revisión de la literatura y recomendaciones para el Instituto Nacional de Cancerología - Colombia / Criteria for the identification of hereditary breast cancer syndromes. Review of the literature and recommendations for the Instituto Nacional de Cancerología - Colombia

Introducción. Los síndromes de cáncer de mama hereditario (SCMH) corresponden a un 5% a 10% de todos los casos de la enfermedad, en su mayoría explicados por mutaciones en los genes BRCA1 y BRCA2. Se han publicado múltiples guías y recomendaciones internacionales actualizadas, con el fin de dar lineamientos para seleccionar los casos con sospecha de un SCMH. Como antecedentes locales, el Instituto Nacional de Cancerología de Colombia cuenta con un "Programa institucional para la identificación y manejo de familias con sospecha de cáncer hereditario", con fines asistenciales, dentro del cual el cáncer de mama es la patología más remitida al servicio de genética (55%; 540/986). En el 21% de los casos con cáncer de mama que cumplieron criterios NCCN se diagnosticó un SCMH, la mayoría asociados a mutaciones en los genes BRCA1 y BRCA2 (12,3%) y en menor proporción a otros genes de susceptibilidad al cáncer de mama (8,6%).Objetivo. Identificar los criterios de selección más implementados para diagnosticar los casos de cáncer de mama hereditarios a través de una revisión de la literatura, y realizar un consenso Institucional sobre las indicaciones de remisión a consejería genética y solicitud de pruebas para fines diagnósticos y de tratamiento sistémico con iPARP. Materiales y métodos. Se realizó una revisión narrativa de la literatura científica publicada en los últimos 10 años, al 30 de agosto del 2021, sobre la prevalencia de mutaciones germinales en los genes BRCA1 y BRCA2, y en otros genes no BRCA, en pacientes con cáncer de mama, obteniéndose en total 146 y seleccionándose un total de 41 artículos. En el interior de las unidades funcionales de mama y tejidos blandos, genética y oncología clínica, se presentó la evidencia disponible, realizando una discusión amplia entre las tres unidades y finalmente se definieron las indicaciones para remisión a genética, para solicitar estudios genéticos y de tratamiento sistémico con iPARP.Resultados. Según lo reportado en la literatura, los principales criterios de sospecha de un SCMH deben incluir: el subtipo triple negativo, la presentación bilateral, la edad muy temprana de diagnóstico y los antecedentes familiares (AF) de cáncer de mama antes de los 50 años o cáncer de ovario a cualquier edad.Conclusiones. Se adoptan las recomendaciones de la NCCN para la remisión a consejería genética y solicitud de estudios genéticos para identificar cáncer de mama hereditario, y se establecen los criterios del estudio OlympiA para la solicitud de estudios genéticos con el fin de guiar el tratamiento sistémico con iPARP en el Instituto Nacional de Cancerología. Lo anterior permitirá que desde nuestra Institución se ofrezca adecuadamente este servicio a la población colombiana.

ntroduction: Hereditary breast and ovarian cancer syndromes (HBOC) represents 5% to 10% of all breast cancer cases, and BRCA1andBRCA2 explain most of these syndromes. Multiple guidelines and updated recommendations have been published to define which patients should be selected for genetic testing based on a clinical suspicion of a HBOC syndrome. For context, the Instituto Nacional de Cancerología from Colombia developed an "Institutional Program for the identification and management of families with suspected hereditary cancer" for healthcare purposes, within which breast cancer is the most referred pathology to the genetics service (55%; 540/986). Inherited cancer was diagnosed in 21% of the patients with breast cancer who met NCCN criteria; most of these were associated with BRCA1 and BRCA2 mutations (12.3%) and to a lesser extent to other breast cancer susceptibility genes (8.6%).Objective: To identify the most implemented selection criteria to diagnose inherited breast cancer cases, through a review of the literature, and to achieve an institutional consensus on the indications for referral to genetic counseling and genetic testing for diagnostic and systemic treatment with PARPi.Materials and methods: A narrative review of the scientific literature published in the last 10 years as of August 30, 2021 on the prevalence of germline mutations in the BRCA1 and BRCA2 genes, and in other non-BRCA genes, in patients with breast cancer was carried out. Overall, 146 articles were first identified but only 41 were selected. Within the functional units of breast and soft tissue, genetics and clinical oncology, the available evidence was presented and a broad discussion was carried out; finally the indications for referral to genetic counseling, for genetic testing and for systemic treatment with PARPi were defined.Results: As reported in the literature, clinical criteria for HBOC syndrome should include: triple negative subtype, bilateral presentation, very early age of diagnosis and family history (FH) of breast cancer before 50 years of age or ovarian cancer at any age. Conclusions: The NCCN recommendations for referral to genetic counseling and ordering genetic testing to diagnose HBOC cases are adopted at the Instituto Nacional de Cancerología from Colombia, as well as the OlympiA study criteria for ordering genetic testing to guide systemic PARPi therapy. This will allow our Institution to adequately offer this service to the Colombian population.

Eventos tromboembólicos sintomáticos después de artroscopia de rodilla / Symptomatic thromboembolic events after knee arthroscopy

Introducción: La artroscopia de rodilla es usualmente un procedimiento seguro con pocas complicaciones. El objetivo de este estudio es calcular la incidencia de eventos tromboembólicos sintomáticos: trombosis venosa profunda y tromboembolismo pulmonar, asociados a artroscopia de rodilla y los posibles factores de riesgo relacionados. Materiales and Métodos: Cohorte retrospectiva que incluyó todos los pacientes llevados a artroscopia de rodilla entre Enero 2011 y Diciembre 2015 en un hospital universitario. El seguimiento fue de 30 días después de la cirugía. Se registraron datos demográficos, los eventos de interés, el tipo de cirugía y los posibles factores de riesgo. Resultados: 1,097 artroscopias de rodilla se hicieron en los 5 años. El 100% tuvieron seguimiento de 10 días mínimo, 90.5% alcanzaron el seguimiento de 30 días. El tiempo promedio de seguimiento fue 15.1 meses. El porcentaje de eventos tromboembólicos fue de 1.4% (n = 14). Se encontraron dos factores de riesgo asociados: eventos tromboembólicos previos (p = 0.013) y uso de anticoagulantes previo a la cirugía (p=0.001). La edad promedio fue mayor en los pacientes con eventos tromboembólicos comparado con los que no tuvieron eventos (58 vs 46 años), p = 0.009. Discusión: La incidencia de eventos tromboembólicos sintomáticos tras artroscopia de rodilla es bajo. El uso rutinaio de profilaxis tromboembólica no se recomienda. En los pacientes con historia de eventos tromboembólicos previos o que estpan anticoagulados en el momento de la cirugía, si se recomienda. Además, en los pacientes mayores de 50 años, debería considerarse su uso. Nivel de Evidencia: III, Estudio de Cohorte Restrospectiva.

Introduction: Knee arthroscopy is usually a safe procedure with few complications. The objective of this study is to calculate the incidence of symptomatic thromboembolic events: deep vein thrombosis and pulmonary thromboembolism, associated with knee arthroscopy and the possible related risk factors. Materials and Methods: Retrospective cohort that included all patients undergoing knee arthroscopy between January 2011 and December 2015 at a university hospital. Follow-up was 30 days after surgery. Demographic data, events of interest, type of surgery and possible risk factors were recorded. Results: 1,097 knee arthroscopies were performed in the 5 years. 100% had follow-up of at least 10 days, 90.5% reached follow-up of 30 days. The average follow-up time was 15.1 months. The percentage of thromboembolic events was 1.4% (n = 14). Two associated risk factors were found: previous thromboembolic events (p = 0.013) and use of anticoagulants prior to surgery (p = 0.001). The average age was higher in patients with thromboembolic events compared to those without events (58 vs 46 years), p = 0.009. Discussion: The incidence of symptomatic thromboembolic events after knee arthroscopy is low. The routine use of thromboembolic prophylaxis is not recommended. In patients with a history of previous thromboembolic events or who are on anticoagulation at the time of surgery, if recommended. Furthermore, its use should be considered in patients over 50 years of age. Level of Evidence: III, Retrospective Cohort Study.

Los desafíos en la continuidad de atención de personas viviendo con VIH en el Perú durante la pandemia de la COVID-19 / Challenges to the continuity of care of people living with HIV throughout the COVID-19 crisis in Peru

RESUMEN La pandemia por la COVID-19 y las medidas restrictivas de distanciamiento social pueden interactuar con la epidemia de VIH de múltiples formas. Existen aproximadamente 87 000 personas viviendo con VIH (PVV) en el Perú quienes están en riesgo de contraer la COVID-19; 67 000 de ellas que reciben tratamiento antirretroviral (TAR) podrían tener limitaciones en el acceso a sus medicamentos, comprometiendo su adherencia y su salud. Además, el efecto que podría tener la pandemia en la salud mental de PVV en Perú aún no está esclarecido. Este artículo tiene como finalidad describir las implicancias clínicas de la coinfección VIH/SARS-CoV-2; discutir los desafíos en la continuidad de atención de las PVV en el Perú durante la crisis sanitaria por la COVID-19; y comentar las posibles implicancias de las medidas restrictivas sobre la salud mental de las PVV.

ABSTRACT The COVID-19 pandemic and societal response implemented may interact with the ongoing HIV epidemic in multiple ways. There are approximately 87000 people living with HIV (PLWH) who are at risk of developing COVID-19 in Peru and 67,000 of them are on antiretroviral therapy (ART) and at risk of limitations in their access to ART, compromising their adherence and their health during the pandemic. Finally, the potential effect of the pandemic on the mental health of PLWH is not documented. This opinion aims to: describe the clinical implications of the HIV/SARS-CoV-2 coinfection; discuss the challenges to the continuity of care of PLWH in Peru during the COVID-19 crisis; and comment possible implications that the COVID-19 crisis may pose on the mental health of PLWH.

Los desafíos en la continuidad de atención de personas viviendo con VIH en el Perú durante la pandemia de la COVID-19 / Challenges to the continuity of care of people living with HIV throughout the COVID-19 crisis in Peru

RESUMEN La pandemia por la COVID-19 y las medidas restrictivas de distanciamiento social pueden interactuar con la epidemia de VIH de múltiples formas. Existen aproximadamente 87 000 personas viviendo con VIH (PVV) en el Perú quienes están en riesgo de contraer la COVID-19; 67 000 de ellas que reciben tratamiento antirretroviral (TAR) podrían tener limitaciones en el acceso a sus medicamentos, comprometiendo su adherencia y su salud. Además, el efecto que podría tener la pandemia en la salud mental de PVV en Perú aún no está esclarecido. Este artículo tiene como finalidad describir las implicancias clínicas de la coinfección VIH/SARS-CoV-2; discutir los desafíos en la continuidad de atención de las PVV en el Perú durante la crisis sanitaria por la COVID-19; y comentar las posibles implicancias de las medidas restrictivas sobre la salud mental de las PVV.

ABSTRACT The COVID-19 pandemic and societal response implemented may interact with the ongoing HIV epidemic in multiple ways. There are approximately 87000 people living with HIV (PLWH) who are at risk of developing COVID-19 in Peru and 67,000 of them are on antiretroviral therapy (ART) and at risk of limitations in their access to ART, compromising their adherence and their health during the pandemic. Finally, the potential effect of the pandemic on the mental health of PLWH is not documented. This opinion aims to: describe the clinical implications of the HIV/SARS-CoV-2 coinfection; discuss the challenges to the continuity of care of PLWH in Peru during the COVID-19 crisis; and comment possible implications that the COVID-19 crisis may pose on the mental health of PLWH.

Diagnóstico y tratamiento multidisciplinario de melanoma temprano y localmente avanzado. Consenso de expertos. Asociación Colombiana de Hematología y Oncología (ACHO) / Diagnosis and multidisciplinary treatment of early-stage and locally advanced melanoma: Expert consensus, Colombian Association of Hemato-Oncology (ACHO)

Resumen Introducción: El melanoma ocasiona el 75% de las muertes por cáncer de piel. Según GLOBOCAN, en 2018 se presentaron 287.723 casos nuevos de melanoma, con una mortalidad de 60.712 casos, que equivale al 20% del total de los casos incidentes. Las alternativas para el tratamiento del melanoma se fundamentan en la estatificación de la enfermedad, y en las características moleculares de la enfermedad. Objetivo: Consensuar, por común acuerdo de expertos, sugerencias para el diagnóstico y manejo de melanoma temprano basadas en la evidencia y ajustadas al contexto colombiano. Métodos: Se llevó a cabo un consenso de expertos multidisciplinario, constituido por 19 oncólogos clínicos, 2 cirujanos de mama y tejidos blandos, 2 dermatólogos, 2 patólogos y 2 radioterapeutas, miembros activos de la Asociación Colombiana de Hemato Oncología (ACHO). Este consenso se realizó en 4 etapas: 1. Estructuración de 29 preguntas, que se calificaron de 1 a 9. 2. Reenvío de las preguntas no consensuadas. 3. Análisis y discusión de las respuestas. 4. Las respuestas no consensuadas se llevaron a un consenso nominal. Resultados: Se discutieron 29 preguntas relacionadas con el diagnóstico y tratamiento de melanoma temprano, se construyeron sugerencias basadas en evidencia utilizada por los expertos y en guías de manejo de oncología reconocidas internacionalmente, adaptadas al contexto y realidad colombianos. Conclusiones: Se presentan sugerencias multidisciplinarias para el diagnóstico y tratamiento de melanoma temprano, las cuales debe considerarse para orientar la toma de decisiones y homogenizar la práctica clínica de acuerdo al contexto colombiano y a las características propias del sistema de salud del país. Este es un documento académico y no regulatorio.

Abstract Introduction: Melanoma causes 75% of deaths from skin cancer. In 2018, according to GLOBOCAN, 287,723 new melanoma cases were registered, with a mortality of 60,712 cases, which is equivalent to 20% of all incident cases. Alternatives for the treatment of melanoma are based on disease staging and the molecular characteristics of the disease. Objective: To establish a consensus by common agreement of experts and construct suggestions for the diagnosis and management of early-stage melanoma based on evidence and adjusted to the Colombian context. Methods: A multidisciplinary expert consensus was established, wth the participation of 19 clinical oncologists, 2 soft tissue surgeons, 2 dermatologists, 2 pathologists, and 2 radiotherapists, active members of the Colombian Association of Hemato-Oncology (ACHO). This consensus was carried out in four stages: 1) Structuring of 29 questions, which were scored from 1 to 9; 2) Resubmission of non-consensual questions; 3) Analysis and discussion of responses; and 4) Validation of non-consensual responses by nominal consensus. Results: Twenty-nine questions related to the diagnosis and treatment of early-stage melanoma were discussed in order to construct suggestions based on evidence proven by experts, as well as on internationally recognized oncology management guidelines adapted to the Colombian context and reality. Conclusions: Multidisciplinary suggestions are offered for the diagnosis and treatment of early-stage melanoma, which should be considered in order to guide decision-making and homogenize clinical practice according to the Colombian context and the characteristics of the Colombian health care system. This is an academic and non-regulatory document.