Latin American Patients Research Articles

Performance of the 2020 ACC/AHA and 2023 ESC risk stratification scales for primary prevention of sudden cardiac death in a Latin American population with hypertrophic cardiomyopathy

Abstract Background Identifying patients with hypertrophic cardiomyopathy (HCM) who are at high risk of sudden cardiac death (SCD) is essential for managing this condition. The American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) guidelines help assess and stratify the risk of determining which patients would benefit from primary prevention with an implantable cardioverter-defibrillator (ICD). Objective The study aims to evaluate the performance of the 2020 AHA/ACC and 2023 ESC risk stratification scales (AHA/ACC-rss; ESC-rss) for the primary prevention of SCD in Latin-American patients diagnosed with HCM. Methods A retrospective cohort of HCM from a single-center was analyzed. The inclusion criteria were individuals aged 16 years or older, without a history of SCD, and who had not undergone any treatment such as myomectomy or septal ablation with alcohol (Figure 1). The primary outcome was the identification of SCD or an equivalent event (successful resuscitation after cardiac arrest or appropriate therapy from the ICD). Results One hundred twenty patients were included (mean age 46.2 years old) and the mean follow-up duration was 61.1 months. From the total sample, 10 patients (8.3%) experienced an equivalent SCD event; 7 patients (5.8%) were ICD-protected and 3 (2.5%) required external defibrillation. The ESC-rss showed a greater area under the ROC curve (AUC, 0.79; 95% CI 0.62-0.94 vs AUC, 0.63; 95% CI 0.49-0.78) and specificity (85%; 95% CI 63-92 vs 51%; 95% CI 37.3-64.5). Sensitivity was similar between both scales (AHA/ACC-rss: 77%; 95% CI 50-100 vs ESC-rss: 73%; 95% CI 43-100). Remarkably, 2.5% of the patients who experienced an equivalent of SCD were incorrectly identified as low-risk individuals by either the AHA/ACC-rss, ESC-rss, or both (Table 1). Conclusion The SCD risk stratification recommended by the ESC-rss demonstrated a more effective identification of Latin American patients with HCM for ICD placement because the area under the curve was more significant than those of the AHA/ACC-rss. This single-center study highlights the need for a multicenter prospective study in Latin America.

Morphological characterization of the hippocampus: a first database in Ecuador

IntroductionThe hippocampal volume is a well-known biomarker to detect and diagnose neurological, psychiatric, and psychological diseases. However, other morphological descriptors are not analyzed. Furthermore, not available databases, or studies, were found with information related to the hippocampal morphology from Latin-American patients living in the Andean highlands.MethodsThe hippocampus is manually segmented by two medical imaging specialists on normal brain magnetic resonance images. Then, its morphological qualitative and quantitative descriptors (volume, sphericity, roundness, diameter, volume-surface ratio, and aspect ratio) are computed via 3D digital level-set-based mathematical representation. Furthermore, other morphological descriptors and their possible correlation with the hippocampal volume is analyzed.ResultsWe introduce a first database with the hippocampus’ morphological characterization of 63 patients from Quito, Ecuador, male and female, aged between 18 and 95 years old.DiscussionThis study provides new research opportunities to neurologists, psychologists, and psychiatrists, to further understand the hippocampal morphology of Andean and Latin American patients.

Factors predictive of severe thrombocytopenia and its impact on poor outcomes in Latin American patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort

ObjectiveTo examine the predictors of the occurrence of severe thrombocytopenia and its impact on damage accrual and mortality in SLE patients. MethodsFactors associated with time to severe thrombocytopenia (platelet count ≤20,000/mm3) occurring from the onset of SLE symptoms were assessed by Cox proportional hazards regressions. The association of severe thrombocytopenia with mortality was evaluated by logistic regression analyses while its impact on damage was by negative binomial regression. ResultsOf 1,217 patients, 33 (2.7%) developed severe thrombocytopenia over a mean (SD) follow-up time of 5.9 (3.6) years. The median time from the onset of SLE symptoms to severe thrombocytopenia occurrence was 22 months (IQR 8.7–62.0). Mestizo (60.6%) was the predominant ethnic group, followed by Caucasian (27.3%), while African Latin American exhibited the lowest frequency (12.1%). By multivariable analysis, Mestizo ethnicity (HR 2.67, 95% CI 1.12–6.37, p = 0.027), and autoimmune hemolytic anemia (AIHA) at baseline (HR 3.99; 95% CI 1.05–15.19, p = 0.042) were associated with a shorter time to the occurrence of severe thrombocytopenia while middle/high socioeconomic status (HR 0.23; 95% CI 0.08–0.69, p = 0.008) was associated with a longer time. Severe thrombocytopenia contributed neither to damage nor to mortality. ConclusionsSevere thrombocytopenia occurs during the early course of SLE. Mestizo ethnicity and AIHA at baseline emerged as independent predictors of a shorter time to severe thrombocytopenia occurrence while a middle/high socioeconomic status seems to be protective against its occurrence. Damage and mortality did not seem to be impacted by the occurrence of severe thrombocytopenia.

Active surveillance of papillary thyroid carcinoma in Latin America: a scoping review.

Thyroid nodules are a very common finding and have a malignancy rate of 7%-15%. Some malignant nodules have an indolent behavior and may not affect mortality if left untreated. Active surveillance (AS) is a strategy to prevent overtreatment in patients with papillary thyroid microcarcinomas (PTMCs). This review was conducted to evaluate the status of AS for low-risk PTMC in Latin America, including cultural and logistical challenges, disease progression data, and financial viability. We searched PubMed (MEDLINE), SciELO, LILACS, and Web of Science for articles published after 2014 and enrolling adult Latin American patients. Articles cited in the selected studies were also retrieved. We analyzed the AS protocols, technical or logistical challenges, patient adherence, reasons for AS interruption, surgical conversion rates, duration of AS, and disease progression during AS in our region. Three articles were included in the analysis, all of which considered AS a viable option and reported tumor progression and outcomes similar to those reported in other countries. Neck ultrasound and serum levels of thyroglobulin, thyroid-stimulating hormone (TSH), thyroxine (T4), and antithyroglobulin antibodies were included in the follow-up. No cases of new distant metastases were reported, and the outcomes were favorable when surgery was required. Anxiety was the main reason for AS interruption. We conclude that AS can be an acceptable approach and is safe and effective in Latin America, although more prospective studies are needed to consolidate this strategy in our region. Adequate infrastructure, follow-up, and patient education, as well as multidisciplinary healthcare teams trained in conducting AS must be ensured for successful results.

The real-world applicability of the 2023 international myelin oligodendrocyte glycoprotein antibody-associated disease criteria in a Latin American cohort.

The diagnostic criteria for myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) were published in 2023. We aimed to determine the performance of the new criteria in Latin American (LATAM) patients compared with the 2018 criteria and explore the significance of MOG-IgG titers in diagnosis. We retrospectively reviewed the medical records of LATAM (Argentina, Chile, Brazil, Peru, Ecuador, and Colombia) adult patients with one clinical MOGAD event and MOG-IgG positivity confirmed by cell-based assay. Both 2018 and 2023 MOGAD criteria were applied, calculating diagnostic performance indicators. Among 171 patients (predominantly females, mean age at first attack = 34.1 years, mean disease duration = 4.5 years), 98.2% patients met the 2018 criteria, and of those who did not fulfill diagnostic criteria (n = 3), all tested positive for MOG-IgG (one low-positive and two without reported titer). Additionally, 144 (84.2%) patients met the 2023 criteria, of whom 57 (39.5%) had MOG-IgG+ titer information (19 clearly positive and 38 low-positive), whereas 87 (60.5%) patients had no MOG-IgG titer. All 144 patients met diagnostic supporting criteria. The remaining 27 patients did not meet the 2023 MOGAD criteria due to low MOG-IgG (n = 12) or lack of titer antibody access (n = 15), associated with the absence of supporting criteria. The 2023 MOGAD criteria showed a sensitivity of 86% (95% confidence interval = 0.80-0.91) and specificity of 100% compared to the 2018 criteria. These findings support the diagnostic utility of the 2023 MOGAD criteria in an LATAM cohort in real-world practice, despite limited access to MOG-IgG titration.

Prognostic impact of nectin-like molecule-5 (CD155) expression in non-small cell lung cancer

BackgroundCD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population.MethodsTissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS).Resultsthe cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06–4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07– 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98–5.83]; p = 0.058).ConclusionCD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

Efficacy of First-Line Nivolumab Plus Ipilimumab in Unresectable Pleural Mesothelioma: A Multicenter Real-World Study (ImmunoMeso LATAM)

BackgroundThe phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population. MethodsThis retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method. ResultsFrom June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; P = .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event. ConclusionsThis multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings.

Evolution of Proliferative Lupus Nephritis with Focal Extracapillary Proliferation in Latin American Patients with Lupus

Evolution of Proliferative Lupus Nephritis with Focal Extracapillary Proliferation in Latin American Patients with Lupus

Navigation and Robotic Single-Position Prone LLIF: First Cases in Brazil

has been rapid technological advancement in navigation-guided minimally invasive surgery over the past two decades, making these advancements an invaluable aid for surgeons by essentially providing real-time virtual reconstruction of patient anatomy. The objectives of these navigation- and robot-guided procedures are to reduce the likelihood of neural and vascular injury, minimize hospitalization time, decrease bleeding and postoperative pain, shorten healing time, and lower infection rates. A unicentric, retrospective cohort study was conducted to evaluate the preoperative and postoperative clinical and radiographic outcomes of the first Latin American patients diagnosed with lumbar degenerative disease who underwent lumbar interbody fusion at the L4-L5 level via prone-position lateral lumbar interbody fusion-single position prone access. A total of 80 patients (40 assisted by fluoroscopy, 40 assisted by robotics) with 320 percutaneous pedicle screws were evaluated. The primary outcomes analyzed and compared were radiation exposure per screw (seconds), skin-to-skin operative time (minutes), and recovery time (days). Secondary outcomes included lumbar pain intensity (visual analog scale), reported functional disability (Oswestry Disability Index), and any potential complications. All secondary outcomes were collected at the postoperative time. Comparing minimally invasive spine interventions with free-hand instrumentation and robotic instrumentation, a statistically significant difference was identified in radiation exposure per screw and surgical time. The literature on Cirq Robotic is limited; however, minimally invasive spine surgery with robotic assistance appears advantageous in terms of radiation exposure and surgical time.

Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil.

There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

Nasal filling guided by high frequency ultrasound: Reducing risks.

Given the significant increase in the quantity of cosmetic procedures utilizing hyaluronic acid fillers, including in the nasal region, the initial evaluation of patients using high frequency ultrasound becomes a crucial instrument in evaluating and handling nonsurgical rhinoplasty. The aim of this article is to introduce an assessment methodology for nasal filling guided by high frequency ultrasound. A prospective and single-center study was conducted with 12 Latin American patients. The patients underwent nasal filling with hyaluronic acid following high power ultrasound mapping. In the evaluation of the GAIS scale, all patients reported improvement with the treatment. No infections, nodules, ischemia, or other relevant adverse effects were noted. Real-time ultrasound-guided filler techniques have been developed to reduce the risk of vascular compromise, confirming the distribution pattern of blood vessels. It's also crucial to visualize the cannula at the same moment as the vessels, even if the previous vascular mapping was performed. Therefore, the utilization of high frequency ultrasound can act as a pivotal tool in augmenting procedure safety.

Proximal Jejuno-Ileal Bypass as Revision of Roux-en-Y Gastric Bypass.

Bariatric surgery is established as a possibility for the treatment of obesity, allowing weight reduction and remission of obesity comorbidities. Reported suboptimal clinical response rates are as high as 30-60% (insufficient weight loss or gain, defined as BMI greater than 35kg/m2 or excess weight loss less than 50%). Proximal jejuno-ileal bypass (PJIBP) is a promising option when re-intervention is required. To describe the standardization of a proprietary technique of modified PJIBP as a management procedure in patients with post-gastric bypass recurrent weight gain or insufficient post-intervention weight loss. This study evaluated a case series of 10 Latin American patients requiring post-bariatric re-intervention, between February 2018 and 2023, in a single-metabolic surgery center in Cali-Colombia. Median age was 45years (26-70 RIC), 60% female, and 40% male. Mean BMI at conversion was 36.7kg/m2 (6.4 SD). Median follow-up was 22months (RIC 16-30). Mean percentage of excess weight lost was 78% (22.4 SD). One hundred percent achieved glycemia control, only one patient persisted with dyslipidemia, and no patient presented hypoalbuminemia. At the end of follow-up, 100% received vitamin supplementation. PJIBP could be an effective procedure, associated with positive results in relation to weight loss and resolution of obesity comorbidities. Deficiencies of fat-soluble vitamins and protein malnutrition represent the main concern in the long term, so multidisciplinary management and continuous follow-up are required.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0) and5.0 (3.0-8.0)years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Advanced signet ring cell type gastroesophageal cancers in Latin American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.

e16069 Background: Gastric Cancer mortality rates in Latin American countries of Central and South America (LA) are among the highest in the world. After observing multiple cases of advanced gastric adenocarcinoma (GA) with signet ring cell differentiation in young immigrants from LA, we sought to understand the prevalence and demographics of young-onset gastric cancer at our institution. Methods: We used the Inova Fairfax Hospital cancer registry to perform a retrospective cohort study by identifying all patients ≤ 40 from 2013-2022 with 1) GA, and 2) all cancers, and comparing the percentage of LA patients in each group. We noted a trend towards high rates of GC in young immigrants of LA six years ago, and now provide an updated analysis. We then reviewed phenotypic characteristics of each tumor, including signet ring cell differentiation, Her-2/Neu overexpression, and H. Pylori status and the time interval between diagnosis and death. Results: From 2013-2022, 21/37 patients (56.8%) ≤ 40 with GA were from LA (Table 1), with the majority from El Salvador. 95% (20/21) of LA patients had tumors with signet ring cell morphology, 88% (14/16) of non-LA patients had tumors with signet ring cell morphology. In comparison, patients that self-identified as “Hispanic/Spanish” made up 8.1% of subjects ≤ 40 with all cancers during the same time period. Conclusions: At our tertiary care center, Stage IV signet ring cell gastric cancer is highly prevalent in young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]

Abstract PS18-04: Racial disparities in breast cancer and effect of obesity: MammaPrint, BluePrint and whole transcriptome analyses of tumors in Latin American patients in FLEX trial

Abstract Background: Latin Americans are more likely to be diagnosed with aggressive early-stage breast cancer compared to Non-Hispanic White. Multiple factors may contribute to this, including metabolic factors and ancestry. In a previous study, we identified upregulated immune pathway genes in Luminal B tumors from obese Black patients compared to matched White patients. In this study, we report clinical and transcriptomic profiles of breast tumors from Latin and White patients to enhance understanding of factors contributing to aggressive tumor biology in Latin patients. Methods: We matched 311 Latin and 311 White breast cancer patients enrolled in FLEX by age, T stage, N stage and clinical subtype (ER/PR and HER2 status). FLEX (NCT03053193) is a prospective, observational trial that includes stage I-III breast cancer patients who receive MammaPrint (with or without BluePrint) as standard of care and consent to whole transcriptome and clinical data collection. MammaPrint is a 70-gene risk of distant recurrence signature that classifies patients as Low Risk or High Risk. BluePrint is an 80-gene molecular subtyping signature, categorizes tumors as Luminal-, HER2- or Basal-Type. MammaPrint further groups Luminal into A (Low Risk) and B (High Risk). ImPrint is a 53-gene signature that has been shown to predict the likelihood of achieving pCR with PD1-PDL1 immune checkpoint inhibitors. Statistical analyses on groups were conducted using arsenal R package and p-value < 0.05 was considered significant. Whole transcriptome comparisons were made, using limma R package, between Latin and White patients stratified by BluePrint subtype Luminal and weight categories normal (body-mass-index (BMI) 18.5 to < 25) and obese (BMI ≥30). Significant differentially expressed genes had an adjusted p-value < 0.05. Gene set enrichment analysis (GSEA) was conducted using fgsea R package. Results: Latin patients had significantly higher percentage of type 2 diabetes (23.3% vs 8.5%), BMI obese (49.0% vs 39.4%), BluePrint Basal (14.8% vs 9.3%) and ImPrint Immune Sensitive (12.0% vs 5.1%) compared to matched White patients. When comparing whole transcriptome of tumors from Latin and White patients, only tumors stratified by Luminal B and obesity resulted in differentially expressed genes: Latin patients had higher expression (>2-fold change) of 42 immunoglobulin genes compared to White, with only IGKV6-21 being statistically significant. Additional immune related genes such as IKZF1 and AGER, as well as UTS2 (gene encoding a vasoconstrictor agent and contributor of angiogenesis) were significantly upregulated in Latin patients. Upregulation of immune related pathways such as inflammatory response, interferon alpha/gamma response and downregulation of adipogenesis, oxidative phosphorylation and MYC targets were identified in Latin patients compared to White using GSEA Hallmarks gene sets. Conclusion: There were additional clinical and genomic differences between tumors from Latin and White patients, even when controlling for age, T stage, N stage and clinical subtype. Particularly, there were more type 2 diabetes, BMI obese, BluePrint Basal, and ImPrint Immune Sensitive among Latin patients. In addition, transcriptomic differences between obese Latin and matched White patients were found in Luminal B subgroup that may contribute to the aggressive tumor biology; immunoglobulin genes and immune related pathways were associated with higher expression in Latin patients. This study suggests that biological differences in breast tumors, particularly from obese patients, may result from shared background and reflects the need for inclusion of diverse patient groups in clinical trials. Citation Format: Marcela Mazo-Canola, Virginia Kaklamani, Pooja Advani, Sailaja Kamaraju, Alfredo A. Santillan-Gomez, Robert Maganini, Julie Barone, Sahra Uygun, Lavanya Samraj, William Audeh, Joyce O'Shaughnessy, FLEX Investigators' Group. Racial disparities in breast cancer and effect of obesity: MammaPrint, BluePrint and whole transcriptome analyses of tumors in Latin American patients in FLEX trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS18-04.

Abstract PO1-16-06: LuciA-15 - A real-world prospective study of PARP inhibitors for the treatment of Latin American patients with HER-2 negative metastatic breast cancer with mutation of BRCA1/2 genes or in the Homologous Recombination Repair genes

Abstract Background PARP inhibitors (PARPi) improves progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to physician choice of chemotherapy (CT). The AIM of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population. Methods We analyzed data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA 1 or BRCA 2 or in the Homologous Recombination Repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. From September 2019 and April 2023, we collected baseline characteristics, previous systemic treatments, type and pattern of use, treatment beyond PARPi progression, and patient predisposition. Objective responses, best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analyzed with R software and RStudio version 14.0. Results After a median follow-up of 18.07 months (CI95% 10.53 - 30.07), 51 patients were treated with PARPi. Mean age at start treatment was 47,08 years. 62.7% had ER+ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talalaparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT (PbCT) in the (neo)adjuvant/metastatic setting. 57.5% had visceral metastasis and the median number of metastatic sites were 2 (range 1-4). Median number of lines at the time to start PARPi was 2 (range 0-8), 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively. The rwORR was 47.0%, and the median rwPFS1 was 7.77 months (CI95% 5.67-14.7). There was a tendence of better rwPFS1 in patients without previous CT versus previous CT in the advance setting, 14.30 months (CI95% 6.47-NR) versus 6.37 months (CI95% 5.03-8.73), respectively (p 0.084). The median rwOS was 26.97 months (CI95% 13.50-NR) and higher in the subgroup of patients naïve for CT versus previous exposure to CT in the advance setting, the median rwOS was 32.1 months (CI95% 27.0-NR) versus 13.0 (IC95%10.1-NR), respectively (p 0.022). 23.5% of patients progressed on PARPi during the first 6 months of treatment, 32.4% with visceral compromise, 27.8% with visceral crisis, and 26.5% with ≥2 metastatic sites. CT was the treatment of choice in most patients (55.3%). The medium rwPFS2 (next treatment after PARPi failure) was 4.00 months (CI95% 3.43 – 7.13). Treatment was discontinued for adverse events in 4.0 % of patients. Conclusion This is the first Latin-American evidence that replicate the data already published in randomized clinical trials and other scanty real-world evidence studies in this field, positive results in rwORR and rwPFS, encouraging data in rwOS. Notably, high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, similar rwOS results among subgroups (TNBC versus ER+ve/HER2-ve, talazoparib versus Olaparib, etc). <graphic> Citation Format: Fernando E. Petracci, Cynthia Villarreal-Garza, Facundo Argañaraz, Gonzalo Gómez Abuin, José Peñaloza, Marcos A. Flores, Luciano Piazzoni, Cecilia Riggi, Lucía Fabiano, Lucía González, Belén Cieplinski, Sergio Rivero, Ernesto Korbenfeld, Pablo Mandó. LuciA-15 - A real-world prospective study of PARP inhibitors for the treatment of Latin American patients with HER-2 negative metastatic breast cancer with mutation of BRCA1/2 genes or in the Homologous Recombination Repair genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-06.

A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America.

MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29years (range 31-71) and 49.90years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

Dermoscopic Features of Pigmented Bowen Disease: A Multicenter Study on Behalf of the Ibero-Latin American College of Dermatology (CILAD).

Studies focused on dermoscopic aspects of pigmented Bowen disease (pBD) in Latin American population are scarce and limited to only case reports or small series. To report dermoscopic findings in a large series of 147 pBD diagnosed in Ibero-Latin American population. We conducted a multicentric, retrospective study on 147 histologically proven pBD under the auspices of the Dermoscopy Chapter of the Ibero-Latin American College of Dermatology. The study population consisted of 77 females (52%) and 70 males (48%) with a mean age of 68.6 years. 70.1% of patients had skin phototype 3, 15.6% to skin phototype 2, and 14.3% to skin phototype 4. On clinical examination, near 60% of pBD were flat, 70% presented with scales, and 90% were asymmetric. Under dermoscopy, structureless hypopigmented areas, dots brown and pink color were the most frequently observed. Regarding specific dermoscopic clues to pBD, the most prevalent were structureless hypopigmented areas, vessels arranged in linear fashion at the periphery, and pigmented lines or pigmented dots distributed in a linear fashion. Clustered, coiled, and dotted vessels were observed in 55.8%, 45.6%, and 45.6% of the cases, respectively. We report a large series of cases of pBD in Latin American patients, with most patients being skin phototype 3 and 4. Distinctively in our study, the pigmented structures and the clues derived from the presence of melanin were much more frequent than in previous reports in fair skin.

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.