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.

Taxanes for the treatment of breast cancer during pregnancy: an international cohort study.

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.

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.

Shifts in bacterioplankton community structure between dry and wet seasons in a tropical estuary strongly affected by riverine discharge.

Estuaries are among the most productive ecosystems in the world and are highly dynamic due to the interaction of freshwater and seawater, which results in strong spatial gradients in physico-chemical conditions. Bacterioplankton play a central role in these systems, driving the fluxes of carbon and energy, and being central for contaminant removal in human-impacted areas. Most studies on bacterioplankton dynamics have been carried out in temperate estuaries, and they show that salinity is a major factor driving bacterioplankton distribution. Tropical estuaries, although largely understudied, experience drastic variations in river discharge between the dry and the rainy seasons, influencing the spatial distribution of the salinity gradient and thus likely impacting bacterioplankton communities. Using Illumina sequencing of the 16S rRNA gene, here we studied bacterial communities from the Nicoya's Gulf (Costa Rica), a large tropical estuary characterized by high riverine discharge during the rainy season, to explore seasonal changes in the spatial distribution and connectivity of these communities along the Gulf. Our results show pronounced differences in bacterial diversity and community structure between seasons and zones within the estuary (the shallow upper Gulf, the middle zone and the lower zone, located in the marine end of the estuary). Bacterial communities from the different regions were more similar during the rainy season, suggesting a larger degree of microbial connectivity likely driven by the fast water circulation fueled by the riverine discharge. In the dry season, Enterobacteriales and Cyanobacteria dominated bacterial communities, whereas in the rainy season Alphaproteobacteria was the dominant group. These contrasting seasonal trends were consistent with the seasonal variations observed in bacterial assemblages during a year at a single station in the upper region of the Gulf. We conclude that the Gulf is highly dynamic in both the spatial and temporal scale and that bacterioplankton communities are strongly influenced by the riverine and tidal inputs during both seasons. This study sheds light on the sources of variability in the structure of bacterial communities in tropical estuarine systems, an understudied type of aquatic ecosystem, and sets the basis to design further comprehensive studies on their microbial diversity.

High-Dose vs. Low-Dose Dexamethasone in Patients With COVID-19: A Cohort Study in Rural Central America.

To compare the clinical outcomes of a low dose dexamethasone strategy vs. a high-dose dexamethasone strategy in hypoxemic COVID-19 patients. A retrospective observational study comparing low-dose (8 mg) and high-dose dexamethasone (24 mg) of COVID-19 patients admitted from September 1, 2020 to October 31, 2020 in a hospital in Honduras. We included 81 patients with confirmed COVID-19 who required oxygen therapy. The mean age was similar between groups (57.49 vs. 56.95 years). There were more male patients in the group of 24 mg ( p = 0.01). Besides, patients on the 24 mg dose had more prevalence of hypertension ( p = 0.052). More patients in the 24 mg group had a higher rate of invasive mechanical ventilation (15.00% vs. 2.56%, p = 0.058). When evaluating the association between the high dose group and outcomes, we find no significant association with mortality, nosocomial infections, high flow mask, invasive mechanical ventilation, or the need for vasopressors. We find no significant differences in the Kaplan-Meier analysis regarding the survival (log-rank p -value = 0.315). We did not find significant differences between the use of 24 mg and 8 mg of dexamethasone in hypoxemic COVID-19 patients.

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.

Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP).

Objectives: To compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American. Methods: A multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1-49%, and <1%). Results: For the entire population (N=125), the overall response rate (ORR) was 57.6% (N=72), and 18.4% (N=25) achieved stable disease. OS was 26.3 months (95%CI 23.9-28.6), and PFS was 20.5 months (95%CI 18.0-23.0). PFS assessed by ethnicity showed a median for the Hispanic population of 19.4 months (95%CI 16.4-22.5) and 21.2 months (95%CI 17.2-23.3; p=0.76) for the NHW group. OS by race showed a significant difference in favor of the NHW group, with a median OS of 27.7 months (95%CI 24.6-30.9) vs. 20.0 months (95%CI 16.4-23.5) for Hispanics. (P=0.032). Unadjusted 12-month and 24-month OS was 86.6% (95%CI 79.9-88.0) and 46.6% (95%CI 40.2-48.3) for NHW compared to 82.5% (95%CI 77.1-84.2) and 17.5% (95%CI 15.6-24.5) in Hispanics. NHW had an EE factor of 0.78 and Hispanics had 0.58, showing a reduction in survival versus NHW and PACIFIC of 20% and 42%, respectively. HR for the OS among NHWs and Hispanics was 1.53 (95%CI 1.12-1.71; P=0.052) and 2.31 (95%CI 1.76-2.49; P=0.004). Fifty-six patients (44.8%) had some degree of pneumonitis due to cCRT plus durvalumab. There was no difference in the proportion of pneumonitis according to race (P=0.95), and the severity of pneumonitis was not significantly different between Hispanics and NHWs (P=0.41). Conclusions: Among patients with LA stage III NSCLC, NHW had better survival outcomes when compared to Hispanics, with an OS that seems to favor the NHW population and with an EE factor that shows a shorter survival in Hispanics compared with NHW and with the PACIFIC trial group.

Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP).

INTRODUCTION: Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M mutations and evidence of relapse of the disease. Effectiveness and safety of this drug have been studied in multiple clinical trials and observational studies, however, information regarding outcomes among Hispanic patients treated with Osimertinib is scarce. The objective of this study was to examine real-world effectiveness and safety of first-line Osimertinib in a cohort of Hispanic patients with NSCLC, emphasizing post-progression outcomes. METHODS: This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC. Patients with a confirmed diagnosis of metastatic EGFR-mutated NSCLC who received Osimertinib (80mg/day until evidence of disease progression or presence of intolerable adverse effects) were identified and included. NGS was performed in tumor samples or liquid biopsies among patients who had disease progression. The primary outcome was progression-free survival, and the secondary outcome was post-progression survival. RESULTS: A total of 94 patients from Mexico, Argentina, Costa Rica, Colombia, Panama, Chile and the USA were included, with a median age of 59 years. Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4-18.2 months). Lung/pleura and lymph nodes were the most common sites of progression. Median post-progression survival was 7.73 months (95%CI 4.07 months-Not reached). Factors which negatively affected PFS included presence of liver metastases at diagnosis and a tumor mutational burden > 5 mut/Mb. CONCLUSION: Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC. Liver metastases and a higher tumor mutation burden were associated with a lower PFS. Despite effectiveness, different mechanisms of resistance were identified among the patients in this cohort, including mutations which can be targeted by other therapeutic options.

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.

p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics.

BACKGROUND: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. METHODS: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. RESULTS: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27-9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1-16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7-8.2%) and Bolivar with 2.4% (95%CI 0-7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. CONCLUSIONS: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

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.

Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The PI3K/AKT and androgen-receptor pathways are dysregulated in metastatic castration-resistant prostate cancers (mCRPCs); tumours with functional PTEN-loss status have hyperactivated AKT signalling. Dual pathway inhibition with AKT inhibitor ipatasertib plus abiraterone might have greater benefit than abiraterone alone. We aimed to compare ipatasertib plus abiraterone with placebo plus abiraterone in patients with previously untreated mCRPC with or without tumour PTEN loss. METHODS: We did a randomised, double-blind, phase 3 trial at 200 sites across 26 countries or regions. Patients aged 18 years or older with previously untreated asymptomatic or mildly symptomatic mCRPC who had progressive disease and Eastern Collaborative Oncology Group performance status of 0 or 1 were randomly assigned (1:1; permuted block method) to receive ipatasertib (400 mg once daily orally) plus abiraterone (1000 mg once daily orally) and prednisolone (5 mg twice a day orally) or placebo plus abiraterone and prednisolone (with the same dosing schedule). Patients received study treatment until disease progression, intolerable toxicity, withdrawal from the study, or study completion. Stratification factors were previous taxane-based therapy for hormone-sensitive prostate cancer, type of progression, presence of visceral metastasis, and tumour PTEN-loss status by immunohistochemistry. Patients, investigators, and the study sponsor were masked to the treatment allocation. The coprimary endpoints were investigator-assessed radiographical progression-free survival in the PTEN-loss-by-immunohistochemistry population and in the intention-to-treat population. This study is ongoing and is registered with ClinicalTrials.gov, NCT03072238. FINDINGS: Between June 30, 2017, and Jan 17, 2019, 1611 patients were screened for eligibility and 1101 (68%) were enrolled; 554 (50%) were assigned to the placebo-abiraterone group and 547 (50%) to the ipatasertib-abiraterone group. At data cutoff (March 16, 2020), median follow-up duration was 19 months (range 0-33). In the 521 (47%) patients who had tumours with PTEN loss by immunohistochemistry (261 in the placebo-abiraterone group and 260 in the ipatasertib-abiraterone group), median radiographical progression-free survival was 16·5 months (95% CI 13·9-17·0) in the placebo-abiraterone group and 18·5 months (16·3-22·1) in the ipatasertib-abiraterone group (hazard ratio [HR] 0·77 [95% CI 0·61-0·98]; p=0·034; significant at α=0·04). In the intention-to-treat population, median progression-free survival was 16·6 months (95% CI 15·6-19·1) in the placebo-abiraterone group and 19·2 months (16·5-22·3) in the ipatasertib-abiraterone group (HR 0·84 [95% CI 0·71-0·99]; p=0·043; not significant at α=0·01). Grade 3 or higher adverse events occurred in 213 (39%) of 546 patients in the placebo-abiraterone group and in 386 (70%) of 551 patients in the ipatasertib-abiraterone group; adverse events leading to discontinuation of placebo or ipatasertib occurred in 28 (5%) in the placebo-abiraterone group and 116 (21%) in the ipatasertib-abiraterone group. Deaths due to adverse events deemed related to treatment occurred in two patients (<1%; acute myocardial infarction [n=1] and lower respiratory tract infection [n=1]) in the placebo-abiraterone group and in two patients (<1%; hyperglycaemia [n=1] and chemical pneumonitis [n=1]) in the ipastasertb-abiraterone group. INTERPRETATION: Ipatasertib plus abiraterone significantly improved radiographical progression-free survival compared with placebo plus abiraterone among patients with mCRPC with PTEN-loss tumours, but there was no significant difference between the groups in the intention-to-treat population. Adverse events were consistent with the known safety profiles of each agent. These data suggest that combined AKT and androgen-receptor signalling pathway inhibition with ipatasertib and abiraterone is a potential treatment for men with PTEN-loss mCRPC, a population with a poor prognosis. FUNDING: F Hoffmann-La Roche and Genentech.