Genomic ancestry and cancer among Latin Americans.

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

Estandarización de requerimientos mínimos para la formación de centro de detección temprana de cáncer de pulmón en América Latina / Standardization of Minimum Requirements for the Formation of an Early Detection Center for Lung Cancer in Latin America

Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.

Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.

The role of angiogenesis inhibitors associated with tyrosine kinase inhibitors in the first-line treatment for EGFR-mutated advanced lung cancer.

Tyrosine kinase inhibitors (TKIs) are the standard treatment for epidermal growth factor receptor mutant (EGFRm) advanced non-small cell lung cancer (NSCLC). Combining TKIs with an angiogenesis inhibitor has shown promise in pre-clinical studies. A systematic search of clinical trials found that combining erlotinib (a first-generation TKI) with bevacizumab or ramucirumab (angiogenesis inhibitors) improved progression-free survival (PFS) in EGFRm advanced NSCLC patients compared to TKI alone. However, no significant benefit in overall survival (OS) was observed in trials. Similar efficacy was seen in patients with specific EGFR mutations. Third generation TKIs were used as second-line therapy for patients with the T790M mutation. The combination treatment was associated with a higher incidence of severe adverse events. Overall, combining erlotinib or another TKI with an angiogenesis inhibitor is a safe and effective alternative for first-line treatment in EGFRm advanced NSCLC, particularly in countries without access to osimertinib and for patients with the EGFR L858R mutation.

Impact of Concurrent Genomic Alterations on Clinical Outcomes in Patients With ALK-Rearranged NSCLC.

INTRODUCTION: ALK tyrosine kinase inhibitors have exhibited promising activity against advanced ALK-rearranged NSCLC. However, co-occurring genetic alterations, such as CDKN2A/B or TP53, may negatively affect the efficacy of targeted therapies. METHODS: From December 2017 to December 2022, this study cohort analyzed next-generation sequencing data of 116 patients with metastatic ALK-rearranged NSCLC from five Latin American cancer centers. Clinicopathologic and molecular features were associated with clinical outcomes and risk of brain metastasis (BrM) in patients with and without concurrent somatic alterations. RESULTS: All patients (N = 116) received a second-generation ALK tyrosine kinase inhibitor, and alectinib was selected in 87.2% of cases. Coalterations occurred in 62% of the cases; the most frequent were TP53 mutations (27%) and CDKN2A/B loss (18%). The loss of CDKN2A/B was associated with an increased risk of BrM, with a cumulative incidence of 33.3% versus 7.4% in the non-coaltered subgroup. Compared with patients without coalterations, patients with concurrent CDKN2A/B loss (n = 21) had a shorter median progression-free survival (10.2 versus 34.2 mo, p < 0.001) and overall survival (26.2 versus 80.7 mo, p < 0.001). In the multivariate analysis, co-occurring CDKN2A/B loss was associated with poorer progression-free survival and OS despite the presence of other somatic coalterations, TP53 mutations, BrM, and Eastern Cooperative Oncology Group Performance Status. CONCLUSIONS: This study confirmed the worse prognostic value, which depicted co-occurring alterations in patients with ALK rearrangement. CDKN2A/B loss was substantially associated with worse outcomes and a higher risk of brain metastases. The evidence presented in our study may help select patients with ALK-positive tumors suitable for treatment escalation and closer brain follow-up.

Perilesional edema diameter associated with brain metastases as a predictive factor of response to radiotherapy in non-small cell lung cancer.

Background: Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD). Aim: The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT. Methods: Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively. Results: Minor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26-10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7-4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4-3.3); p = 0.001]. Conclusion: Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

Genomic Landscape of Primary Resistance to Osimertinib Among Hispanic Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): Results of an Observational Longitudinal Cohort Study.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been proven safe and effective, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib. Nonetheless, some patients will present with or develop EGFR-TKI resistance mechanisms. OBJECTIVE: We characterized the genomic landscape of primary resistance to osimertinib among Hispanic patients with EGFR-mutant NSCLC. METHODS: An observational longitudinal cohort study was conducted with two groups of patients, those with intrinsic resistance (cohort A) and those with long-term survival (cohort B). All patients were treated and followed between January 2018 and May 2022. All patients were assessed for Programmed Cell Death Ligand 1 (PD-L1) expression and Bcl-2-like protein 11 (BIM)/AXL mRNA expression before starting TKI. After 8 weeks of treatment, a liquid biopsy was performed to determine the presence of circulating free DNA (cfDNA), and next-generation sequencing (NGS) was used to identify mutations at the time of progression. In both cohorts, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: We found a homogeneous distribution of EGFR-sensitizing mutations in both cohorts. For cohort A, exon 21 mutations were more common than exon 19 deletions (ex19dels) for cohort B (P = 0.0001). The reported ORR for osimertinib was 6.3% and 100% for cohorts A and B, respectively (P = 0.0001). PFS was significantly higher in cohort B (27.4 months vs. 3.1 months; P = 0.0001) and ex19del patients versus L858R (24.5 months, 95% confidence interval [CI] 18.2-NR), vs. 7.6 months, 95% CI 4.8-21.1; P = 0.001). OS was considerably lower for cohort A (20.1 months vs. 36.0 months; P = 0.0001) and was better for patients with ex19del, no brain metastasis, and low tumor mutation burden. At the time of progression, more mutations were found in cohort A, identifying off-target alterations more frequently, including TP53, RAS, and RB1. CONCLUSION: EGFR-independent alterations are common among patients with primary resistance to osimertinib and significantly impact PFS and OS. Our results suggest that among Hispanic patients, other variables associated with intrinsic resistance include the number of commutations, high levels AXL mRNA, and low levels of BIM mRNA, T790M de novo, EGFR p.L858R presence, and a high tumoral mutational burden.

Efectividad de la intervención de Enfermería sobre promoción de salud en brigadistas sanitarias / Effectiveness of the Nursing Intervention in Health Promotion among Health Brigade Members

Introducción: En un estudio exploratorio previo se constataron insuficientes conocimientos sobre promoción de salud en brigadistas sanitarias de la Federación de Mujeres Cubanas y se detectaron regularidades en la preparación de técnicas participativas. Objetivo: Evaluar la efectividad de la intervención de Enfermería sobre promoción de salud en brigadistas sanitarias. Métodos: Investigación cuantitativa cuasi-experimental sin grupo control en brigadistas sanitarias del municipio San José de las Lajas, provincia Mayabeque, Cuba, en el período septiembre-diciembre de 2021. En un universo de 469 participantes, se aplicó una encuesta descriptiva y se calculó el coeficiente Alfa de Cronbach para medir su confiabilidad. Se utilizaron distribuciones de frecuencias absolutas y porcentajes y la asociación entre variables se obtuvo con la prueba no paramétrica de rangos con signo de Wilcoxon. Resultados: Según el modelo de Nola J. Pender, después de la intervención, se elevaron los beneficios percibidos de la acción (85,71 por ciento), las barreras percibidas a la acción (87,84 por ciento), la autoeficacia percibida (95,94 por ciento), el afecto relacionado con la actividad (90,40 por ciento) y las influencias interpersonales y situacionales (98,93 por ciento) en las brigadistas sanitarias. Conclusiones: La intervención de Enfermería sobre promoción de salud en brigadistas sanitarias fue efectiva, con significación estadística en los aspectos evaluados(AU)

Introduction: A previous exploratory study found insufficient knowledge on health promotion among health brigade members from the Cuban Women Federation and permitted to identify regularities in the preparation of participatory techniques. Objective: To evaluate the effectiveness of nursing intervention on health promotion among health brigade members. Methods: A quantitative quasiexperimental research without a control group was carried out with health brigade members from San José de las Lajas Municipality, Mayabeque Province, Cuba, in the period September-December 2021. A study universe of 469 was applied a descriptive survey and Cronbach's alpha coefficient was calculated to measure its reliability. Absolute frequency distributions and percentages were used, and the association between variables was obtained with the nonparametric Wilcoxon signed-rank test. Results: According to Nola J. Pender's model, the intervention permitted to evaluate the perceived benefits of action (85.71 percent), the perceived barriers to action (87.84 percent), the perceived self-efficacy (95.94 percent), the activity-related affect (90.40 percent), as well as the interpersonal and situational influences (98.93 percent), among the health brigade members. Conclusions: The nursing intervention on health promotion among health brigade members was effective, with statistical significance in the evaluated aspects(AU)

The Armed Conflict and the Impact on Patients With Cancer in Ukraine: Urgent Considerations.

On February 24, 2022, a war began within the Ukrainian borders. At least 3.0 million Ukrainian inhabitants have already fled the country. Critical infrastructure, including hospitals, has been damaged. Children with cancer were urgently transported to foreign countries, in an effort to minimize interruption of their life-saving treatments. Most adults did not have that option. War breeds cancer-delaying diagnosis, preventing treatment, and increasing risk. We project that a modest delay in care of only 4 months for five prevalent types of cancer will lead to an excess of over 3,600 cancer deaths in the subsequent years. It is critical that we establish plans to mitigate that risk as soon as possible.

STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

BACKGROUND: Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. METHODS: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). RESULTS: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. CONCLUSIONS: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.

Uniting Latin America Through Research: How Regional Research Can Strengthen Local Policies, Networking, and Outcomes for Patients With Lung Cancer.

Lung cancer represents a considerable global health threat, leading the list in terms of cancer-related deaths worldwide. An important proportion of lung cancer cases occur within Latin America, and current projections show that over the next decade, the number of deaths due to lung cancer will double in the region, underscoring the need to implement evidence-based interventions to improve outcomes. Several challenges have limited the progress in lung cancer research in Latin America for many years, though recently the surge of multidisciplinary, transnational, and transcultural research groups have overcome many of these limitations. The increase in region-specific knowledge has improved cancer care in the area, providing clinicians with a specific demographic and molecular profile for Hispanic patients with lung cancer; as a result, the implementation of precision oncology has benefited from a profound knowledge of the patient profile. Nonetheless, there are still challenges to improve research in Latin America, including stabilizing funding sources to continue independent research, supporting mentoring programs and an early immersion in clinical research for early career fellows, and overcoming barriers for publishing.

Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

Factores de riesgo y prevalencia de osteopenia y osteoporosis en mujeres posmenopáusicas diagnosticadas por densitometría ósea / Risk factors and prevalence of osteopenia and osteoporosis in postmenopausal women diagnosed by bone densitometry

Resumen Objetivo: Determinar la prevalencia de la osteoporosis en mujeres costarricenses posmenopáusicas, atendidas en el Hospital San Juan de Dios de la Caja Costarricense del Seguro Social, y relacionar con características clínicas y de estilo de vida. Métodos. Estudio transversal. Se analizó un total de 923 estudios de densitometría ósea de mujeres con edad entre los 45 y 80 años, en etapa posmenopáusica; se registró un valor de T-score obtenido por densitometría ósea para columna lumbar y cadera; se documentó las variables como la edad, el índice de masa corporal, tabaquismo y otros reconocidos factores de riesgo; se estimó la prevalencia y se analizó la relación con los factores. Resultados. A partir de 923 estudios y los factores de riesgo comúnmente asociados con la enfermedad, fueron estadísticamente significativos los siguientes: la edad (p<0,001), la edad en la menarquia (p = 0,001), la cantidad de años transcurridos desde la menopausia (p<0,001) y el antecedente familiar de fractura de cadera (p = 0,01). Otros factores no resultaron significativos. Conclusiones. Para la población estudiada, se demostró una prevalencia de 47% para osteopenia y de 39% para osteoporosis en mujeres posmenopáusicas. No se logró establecer una relación en las variables de estilo de vida, tales como tabaquismo, alcoholismo, actividad física y consumo de lácteos. Se deben realizar otras investigaciones con un mayor control sobre estas variables para conocer su riesgo relacionado con la enfermedad.

Abstract Aim: To determine the prevalence of osteoporosis in postmenopausal Costa Rican women treated at the San Juan de Dios Hospital of the Costa Rican Social Security Fund, and relate it to clinical and lifestyle characteristics. Methods. Transversal study. A total of 923 bone densitometry studies of postmenopausal women aged between 45 and 80 years were analyzed; A T-score value obtained by bone densitometry was recorded for the lumbar spine and hip; variables such as age, bodymass index, smoking, and other recognized risk factors were documented; the prevalence was estimated and the relationship with the factors was analyzed. Results. From 923 studies and risk factors commonly associated with the disease, the following were statistically significant: age (p<0.001), age at menarche (p = 0.001), number of years since menopause (p<0.001) and family history of hip fracture (p = 0.01). Other factors were not significant. Conclusions. For the population studied, a prevalence of 47% for osteopenia and 39% for osteoporosis in postmenopausal women was demonstrated. It was not possible to establish a relationship in lifestyle variables, such as smoking, alcoholism, physical activity and dairy consumption. Other investigations with greater control over these variables should be carried out to know their risk related to the disease.

COVID-19 Vaccine Intention among Rural Residents in Mexico: Validation of a Questionnaire.

The COVID-19 pandemic forced the scientific community and the pharmaceutical industry to develop new vaccines, in an attempt to reach herd immunity and stop the SARS-CoV-2 from spreading. However, to ensure vaccination among the general population, COVID-19 vaccine intention must be measured. So far, no studies have focused on rural residents in Latin America, which represent approximately 20% of the population of this geographical region. In this study, we present the validation of a self-developed questionnaire, which was validated in a pilot study with 40 Spanish-speaking Mexican rural residents in the state of Guerrero, Mexico. In this study, we describe the chronological validation of the questionnaire, including the assessment of its internal consistency and temporal reliability, which we measured with the Cronbach's alpha and Spearman's rank correlation coefficient, respectively. After the psychometrical analysis, we were able to validate a 20-item questionnaire, which intends to assess vaccine intention among the rural population. Aiming to develop a comprehensive policy and vaccination strategies, we hope this instrument provides valuable insight regarding COVID-19 vaccination willingness across rural communities in Mexico and Latin America. Finally, if we want to reach worldwide herd immunity, it is important to understand rural residents' position towards COVID-19 vaccination.

Validación de un programa educativo para brigadistas sanitarias / Validation of an educative program for members of sanitary brigades

Introducción: Es en la comunidad donde se pueden identificar y priorizar los problemas de salud. Existe la necesidad de preparar las brigadistas sanitarias, para abordar las acciones comunitarias de promoción de los principales problemas de salud. Objetivo: Validar un programa educativo sobre la promoción de salud, para brigadistas sanitarias. Métodos: Se realizó una Investigación de desarrollo tecnológico, desde abril de 2017 a enero del 2020,el universo de estudio estuvo conformado por 469 brigadistas sanitarias, de San José de las Lajas, provincia Mayabeque. Se utilizó el criterio de expertos para el diseño del programa educativo, así como la construcción de criterios de estructura, procesos y resultados, en la validación de su implementación. Resultados: Se obtuvo como tecnología sanitaria un programa educativo con nueve capítulos. En la evaluación de los 11 criterios de medidas que aportó que el 90.9 por ciento fue adecuado. Conclusiones: El resultado de las actividades de promoción de salud, validan la pertinencia y utilidad del programa educativo en el desempeño de las brigadistas sanitarias(AU)

Introduction: It is in the community where the health problems can be identified and prioritized. There is a necessity of preparing the members of the sanitary brigades to treat the community actions of promotion of the main health problems. Objective: To validate an educative program about promotion of health for members of sanitary brigades. Methods: A technological development research was carried out, from April, 2017 to January, 2020, the study universe was formed by 469 members of sanitary brigades, from San José de las Lajas, Mayabeque province. Criterion experts was used for the design of the educative program, as well as for the elaboration of criteria about structure, processes, and results, in the validation and its implementation. Results: As sanitary technology an educative program with nine chapters was obtained. In the Evaluation of 11 criteria of the measures it conveyed that the 90.9 per cent was adequate. Conclusions: The result of the health promotion activities, validate the pertinence and utility of the educative program in the performance of the members of the sanitary brigades(AU)

Characteristics and outcomes of thymomas in Latin America: Results from over 10 years of experience (CLICaP-LATimus).

BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.

EGFR Inhibitors Plus Bevacizumab are Superior Than EGFR Inhibitors Alone as First-Line Setting in Advanced NSCLC With EGFR Mutations and BIM Deletion Polymorphisms (BIM-CLICaP).

PURPOSE: BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-triggered apoptosis in EGFR-mutant non-small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS: A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS: Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION: EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy, associated with poor outcomes in patients with metastatic disease (mMCC). Management has been dramatically altered as a result of incorporating immune checkpoint blockade agents. MCC data from Latin America (LATAM) come from case-series or individual records. Regional registries are lacking. A need for better registries to improve current knowledge about MCC is highlighted. Our objectives were to describe a real-world experience with avelumab as a second-line (or first-line in unfit patients) treatment in a subset of LATAM participants enrolled in a global Expanded Access Program (EAP) for patients with mMCC, and to evaluate its contribution to the resolution of the concerns described in a recent regional experts review. MATERIALS AND METHODS: We reviewed data of LATAM participants in an avelumab EAP for mMCC treatment (NCT03089658). EAP patient had unresectable or mMCC with progressive disease after one line of chemotherapy, and were ineligible for clinical trials or unfit for chemotherapy. RESULTS: 46 patients (median age: 71.6 years; 60.9% males; median treatment duration: 7.9 months) were included in the LATAM EAP. Physician-assessed objective responses were available for 19 patients. Complete response rate was 15.8% and partial response rate reached 42.1%, summarizing an objective response rate of 57.9%. Stable disease rate was 10.5%, with a disease control response of 68.4%. CONCLUSION: Avelumab showed robust efficacy and a safety profile consistent with global EAP data. Results are aimed to improve current knowledge about mMCC treatment and access to immunooncologic strategies for treating LATAM patients.

The Role of a Cachexia Grading System in Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy: Implications for Survival.

OBJECTIVE: The association between cancer-induced weight-loss (CIWL) and poor clinical outcomes in patients treated with immunotherapy is scarcely understood. We evaluated the use of a cachexia-grading system in IO-treated non-small cell lung cancer (NSCLC) patients in order to predict clinical outcomes. MATERIALS: 300 patients with NSCLC, who received immunotherapy during any line of therapy, were included. All patients were graded according to a previously validated cachexia scale, which takes into consideration body mass index (BMI) and weight loss, stratifying patients into five risk categories (0 [pre-cachexia] - 4 [refractory cachexia]). Primary endpoint was overall survival (OS). RESULTS: Ninety-one (30.3%) patients were classified in the low risk category, 176 (58.6%) were classified in the intermediate risk category and 33 (11%) were in the high risk category. Patients classified as low-risk had a significantly longer OS compared with those with intermediate or high risk (22.4 mo, [95%CI: 16.6-NR] vs. 17.1 [95%CI: 13.5-22.4] vs. 8.0 [3.9-18.4]; p < 0.001). In the multivariate analysis, after adjusting for age, hemoglobin and ORR, hazard of death increased as per the cachexia risk scale (Hazard ratio: 1.62 [1.22-2.16]; p = 0.001). CONCLUSION: Cachexia is independently associated with worse OS in NSCLC patients who receive immunotherapy, highlighting the role for nutritional assessment.

Nivel de conocimientos sobre promoción de salud en brigadistas sanitarias / Level of knowledge about health promotion in members of sanitary brigades

Introducción: En el sistema social cubano, la labor educativa no puede circunscribirse solo a la escuela, en la educación deben asumir mayores responsabilidades sociales la familia, la comunidad, las demás instituciones y organizaciones; de ahí la participación activa de las brigadistas sanitarias, promotoras voluntarias, en la realización de acciones de promoción salud.Objetivo: Explorar el nivel de conocimiento y la preparación en técnicas de participación de lasbrigadistas sanitarias.Métodos: Se realizó una investigación descriptiva, transversal, desde el primero de enero hasta el 31 de marzo del 2017 en el municipio San José de las Lajas, provincia Mayabeque. El universo de estudio estuvo constituido por 469 federadas. Las variables estudiadas fueron: edad, nivel de escolaridad, estado civil, ocupación, lugar de residencia, conocimiento de losproblemas de salud y de las técnicas participativas. Para la recogida de información se utilizóla entrevista y se utilizaron la frecuencia absoluta y por cientos para el análisis estadístico.Se cumplió con los principios de la ética médica.Resultados: Predominaron las brigadistas de 41 a 50 años de edad en el 31.1 porciento, el nivel medio representado con el 37.5 porciento, casadas y el 84.6 porciento del área urbana. El mayor conocimiento se tuvo sobre la prematuridad en el embarazo con el 92.5 porciento y el debate público como técnicas de participación en las actividades educativas. Conclusiones: Se hace necesario confeccionar un manual de preparación en temáticas de promoción de salud para preparar las brigadistas sanitarias en esta tarea(AU)

Introduction: In the Cuban social system, the educative work cannot be limited only to schools, in education, higher responsibilities should be assumed by the family, the community, the rest of the institutions and organizations; so there is the active participation of the members of the sanitary brigades, voluntary promoters in the performance of actions of health promotion.Objective: To explore the level of knowledge and the preparation in participating techniques of the members of the sanitary brigades.Methods: A descriptive, cross sectional research was carried out, from January 1st to March 31st, 2017 in San José de las Lajas, Mayabeque province. The studied universe was composed by 469 women. The studied variables were: age, scholarship, marital status, occupation, place of residence, knowledge about health problems and participating techniques. For collecting the information an interview was used and absolute and percentages were used for the statistical analysis. The principles of medical ethics were achieved.Results: Members of the sanitary brigades of 41 to 50 years old prevailed with a 31.1 per cent, the mean level was represented with 37.5 per cent, married and the 84.6 per cent from urban areas. The highest knowledge was about prematurity in pregnancy with the 92.5 per cent and the public debate as the participating technique in educative activities.Conclusions: It is necessary elaborate a preparation manual in topics of health promotion for preparing the members of sanitary brigades in this task(AU)

Antibiotics impair immune checkpoint inhibitor effectiveness in Hispanic patients with non-small cell lung cancer (AB-CLICaP).

BACKGROUND: The intestinal microbiota is an important factor in modulating immune-mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments. METHODS: This was a retrospective cohort study. Patients with advanced non-small cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 (PD-L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non-ATB exposed (no-ATB), exposed within 30 days of the first dose of ICI (pre-ICI ATB) and patients receiving ATB concomitantly with ICI (ICI-ATB). Progression-free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed. RESULTS: A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B-lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32-67.7), compared with 20.3 months (95% CI: 12.1-non-reached [NR]) for patients with pre-ICI ATB treatment and 24.7 months (95% CI: 13-NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups. CONCLUSIONS: Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs.