Socioeconomic disparities and health literacy: Unraveling the impact on diagnostic and cancer care in Uruguay.

BACKGROUND: Disparities in the timely diagnosis and care of cancer patients, particularly concerning geographical, racial/ethnic, and economic factors, remain a global health challenge. This study explores the multifaceted interplay between socioeconomic status, health literacy, and specific patient perceptions regarding care access and treatment options that impact cancer care in Uruguay. METHODS: Using the Cancer Health Literacy Test, Spanish Version (CHLT-30-DKspa), and a highly comprehensive questionnaire, we dissected the factors influencing the pathway to diagnosis and route of cancer care. This was done to identify delays by analyzing diverse socioeconomic and sex subgroups across multiple healthcare settings. RESULTS: Patients with lower income took longer to get an appointment after showing symptoms (p = 0.02) and longer to get a diagnosis after having an appointment (p = 0.037). Race/ethnicity also had a significant impact on the length of time from symptoms to first appointment (p =0.019), whereas employment status had a significant impact on patients being susceptible to diagnostic delays beyond the advocated 14-day window (p = 0.02). Higher educational levels were positively associated with increased cancer health literacy scores (p = 0.043), revealing the potential to mitigate delays through health literacy-boosting initiatives. Women had significantly higher self-reported symptom duration before seeking an intervention (p = 0.022). We also found many other significant factors effecting treatment delays and cancer health literacy. CONCLUSIONS: While affirming the global pertinence of socioeconomic- and literacy-focused interventions in enhancing cancer care, the findings underscore a complex, gendered, and perceptually influenced healthcare navigation journey. The results highlight the urgent necessity for strategically crafted, globally relevant interventions that transcend equitable access to integrate literacy, gender sensitivity, and patient-perception alignments in pursuit of optimized global cancer care outcomes.

Detection of NTRK gene fusions in solid tumors: recommendations from a Latin American group of oncologists and pathologists.

NTRK gene fusions have been detected in more than 25 types of tumors and their prevalence is approximately 0.3% in solid tumors. This low prevalence makes identifying patients who could benefit from TRK inhibitors a considerable challenge. Furthermore, while numerous papers on the evaluation of NTRK fusion genes are available, not all countries have guidelines that are suitable for their setting, as is the case with Latin America. Therefore, a group of oncologists and pathologists from several countries in Latin America (Argentina, Chile, Ecuador, Mexico, Peru and Uruguay) met to discuss and reach consensus on how to identify patients with NTRK gene fusions in solid tumors. To do so, they developed a practical algorithm, considering their specific situation and limitations.

Assessing Adherence to Adjuvant Hormone Therapy in Breast Cancer Patients in Routine Clinical Practice.

Background: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). A lack of adherence to adjuvant endocrine therapy is common, 31.0-73.0% of women discontinue endocrine treatment before 5 years. The aim of the study was to assess adherence to HT in routine clinical practice in patients assisted at the Clinical Oncology Department of the Hospital de Clinicas - Universidad de la Republica, Uruguay. Methods: Patients treated with HT for stage 0-III BC between 2017 and 2019 were included. The medication possession (MPR) rate was calculated using pharmacy records, and the Morisky-Green Scale was applied to assess adherence. Adherent patients were those with MPR ≥ 0.80 and who correctly answered the Morisky-Green treatment adherence questionnaire. The association of adherence with polypharmacy, treatment, and patient characteristics was assessed using simple logistic models. The associations between qualitative variables and adherence were assessed using simple logistic regression model or Fisher's exact test. The association between quantitative variables and adherence was assessed using the Student's t-test. The odds ratio (OR) for non-adherence to treatment and its 95% confidence interval were estimated. Results: Totally, 118 patients were included; 65.2% were treated with aromatase inhibitors (AIs), 36.0% presenting polypharmacy. The adherence rate at the end of 2 years was 81.0 %; and it was associated with age (P = 0.03, OR = 0.96 for non-adherence), with adherent and non-adherent patients having a mean age of 65.0 and 60.3 years, respectively; however, adherence was not associated with polypharmacy, territory of origin, marital status, living alone, level of education, occupation, or stage. The adherence profile was similar for both drugs, but homemakers and retired women showed greater adherence to AI. Conclusions: Adherence to HT was assessed in real life, with 19.0% of the patients not adhering to the treatment, despite the known benefit for OS, being a well-tolerated treatment, and being provided free of charge. Older patients were associated with being more adherent. The results show the need of the Pharmacy Service and Department of Clinical Oncology Medical Oncology combining efforts to develop coordinated strategies and interventions to increase adherence, given the impact that this may have on patients' OS.

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.

Body Composition and Metabolic Dysfunction Really Matter for the Achievement of Better Outcomes in High-Grade Serous Ovarian Cancer.

Although obesity-associated metabolic disorders have a negative impact on various cancers, such evidence remains controversial for ovarian cancer. Here, we aimed to evaluate the impact of body composition (BC) and metabolism disorders on outcomes in high-grade serous ovarian cancer (HGSOC). METHODS: We analyzed clinical/genomic data from two cohorts (PUC n = 123/TCGA-OV n = 415). BC was estimated using the measurement of adiposity/muscle mass by a CT scan. A list of 425 genes linked to obesity/lipid metabolism was used to cluster patients using non-negative matrix factorization. Differential expression, gene set enrichment analyses, and Ecotyper were performed. Survival curves and Cox-regression models were also built-up. RESULTS: We identified four BC types and two clusters that, unlike BMI, effectively correlate with survival. High adiposity and sarcopenia were associated with worse outcomes. We also found that recovery of a normal BC and drug interventions to correct metabolism disorders had a positive impact on outcomes. Additionally, we showed that immune-cell-depleted microenvironments predominate in HGSOC, which was more evident among the BC types and the obesity/lipid metabolism cluster with worse prognosis. CONCLUSIONS: We have demonstrated the relevance of BC and metabolism disorders as determinants of outcomes in HGSOC. We have shone a spotlight on the relevance of incorporating corrective measures addressing these disorders to obtain better results.

Barreras para las actividades de investigación en los programas de residencia: estudio de métodos mixtos / Barriers for research activities in residency programs: A mix-methods study

Introducción Las actividades de investigación tienen un impacto positivo en el rendimiento de los médicos residentes. Falta información sobre investigaciones desarrolladas por residentes de países en vías de desarrollo. Nuestro objetivo fue evaluar las barreras y facilitadores para la investigación en programas de residencia en una Facultad de Medicina de América Latina. Métodos Se llevó a cabo un diseño de estudio de metodología mixta. Utilizamos un enfoque de teoría fundamentada para la fase cualitativa, recopilando los datos a través de entrevistas semiestructuradas y grupos focales con profesores y residentes. Para la fase cuantitativa, se administraron encuestas a residentes y profesores. Para evaluar las propiedades psicométricas de las encuestas utilizamos análisis factorial y scree plot (validez); alfa de Cronbach y coeficiente de Correlación Intraclase (confiabilidad). Resultados Se realizaron grupos focales que incluyeron diez profesores y quince residentes, y se identificaron los siguientes dominios: a) facilitadores para la participación de los residentes, b) barreras, c) estrategias para introducir la investigación en el currículo, d) argumentos que respaldan las actividades de investigación durante la residencia, y e) perfil de los residentes motivados en la investigación. Tanto los residentes como el profesorado identificaron la falta de tiempo protegido y la ausencia de tutoría adecuada como las principales barreras. Se encontró una brecha de género relacionada con las publicaciones internacionales (34% vs 66% mujeres/hombres), las mujeres percibieron que las actividades de investigación 'compiten con otras actividades' (OR: 2.04, IC 95% 1.03 a 4.07). Conclusiones Los residentes y profesores de una universidad latinoamericana de alta productividad valoran mucho la investigación. La presencia de brecha de género, la falta de tiempo protegido y de tutorías destacan como las principales barreras. Las estrategias propuestas para mejorar la investigación dentro de los programas de residencia son: establecer un programa de tutoría interdisciplinario entre residentes e investigadores; promover las rotaciones electivas; y premiar propuestas que consideren la equidad de género.

Introduction Research activities have a positive impact on the performance of residents. However, information on research conducted by residents from developing countries is scarce. Our study sought to identify the barriers and facilitators for developing research in medical residency programs in a Latin-American faculty of medicine. Methods A mixed methodology study design was carried out. We used a grounded theory approach for the qualitative phase, collecting data through semi-structured interviews and focus groups with faculty and residents. For the quantitative phase, surveys were administered to residents and teachers. We used factor analysis and scree plot (validity), Cronbach's alpha, and Intraclass correlation coefficient (reliability) to evaluate the surveys' psychometric properties. Results Focus groups involving ten faculty members and 15 residents were conducted, and the following domains were identified: a) facilitators for resident participation, b) barriers, c) strategies for introducing research into the curriculum, d) arguments supporting research activities throughout medical residency, and e) profile of research-motivated residents. Both residents and faculty members identified a lack of protected time and adequate mentoring as the major barriers. A gender gap was found related to international publications (34% vs. 66% women/men); women perceived that research activities 'compete with other activities' (OR: 2.04, 95% CI 1.03 to 4.07). Conclusions Research is highly valued by both residents and faculty members at a Latin-American university with a strong academic output. Major barriers to promoting research in this context include lack of protected time and effective mentoring, and gender gaps. Strategies proposed to improve research within medical residency programs include: establishing an interdisciplinary mentoring program between residents and researchers, promoting elective rotations, and rewarding proposals that consider gender equity.

Barriers for research activities in residency programs: A mix-methods study.

Introduction: Research activities have a positive impact on the performance of residents. However, information on research conducted by residents from developing countries is scarce. Our study sought to identify the barriers and facilitators for developing research in medical residency programs in a Latin-American faculty of medicine. Methods: A mixed methodology study design was carried out. We used a grounded theory approach for the qualitative phase, collecting data through semi-structured interviews and focus groups with faculty and residents. For the quantitative phase, surveys were administered to residents and teachers. We used factor analysis and scree plot (validity), Cronbach's alpha, and Intraclass correlation coefficient (reliability) to evaluate the surveys' psychometric properties. Results: Focus groups involving ten faculty members and 15 residents were conducted, and the following domains were identified: a) facilitators for resident participation, b) barriers, c) strategies for introducing research into the curriculum, d) arguments supporting research activities throughout medical residency, and e) profile of research-motivated residents. Both residents and faculty members identified a lack of protected time and adequate mentoring as the major barriers. A gender gap was found related to international publications (34% vs. 66% women/men); women perceived that research activities 'compete with other activities' (OR: 2.04, 95% CI 1.03 to 4.07). Conclusions: Research is highly valued by both residents and faculty members at a Latin-American university with a strong academic output. Major barriers to promoting research in this context include lack of protected time and effective mentoring, and gender gaps. Strategies proposed to improve research within medical residency programs include: establishing an interdisciplinary mentoring program between residents and researchers, promoting elective rotations, and rewarding proposals that consider gender equity.

Introducción: Las actividades de investigación tienen un impacto positivo en el rendimiento de los médicos residentes. Falta información sobre investigaciones desarrolladas por residentes de países en vías de desarrollo. Nuestro objetivo fue evaluar las barreras y facilitadores para la investigación en programas de residencia en una Facultad de Medicina de América Latina. Métodos: Se llevó a cabo un diseño de estudio de metodología mixta. Utilizamos un enfoque de teoría fundamentada para la fase cualitativa, recopilando los datos a través de entrevistas semiestructuradas y grupos focales con profesores y residentes. Para la fase cuantitativa, se administraron encuestas a residentes y profesores. Para evaluar las propiedades psicométricas de las encuestas utilizamos análisis factorial y scree plot (validez); alfa de Cronbach y coeficiente de Correlación Intraclase (confiabilidad). Resultados: Se realizaron grupos focales que incluyeron diez profesores y quince residentes, y se identificaron los siguientes dominios: a) facilitadores para la participación de los residentes, b) barreras, c) estrategias para introducir la investigación en el currículo, d) argumentos que respaldan las actividades de investigación durante la residencia, y e) perfil de los residentes motivados en la investigación. Tanto los residentes como el profesorado identificaron la falta de tiempo protegido y la ausencia de tutoría adecuada como las principales barreras. Se encontró una brecha de género relacionada con las publicaciones internacionales (34% vs 66% mujeres/hombres), las mujeres percibieron que las actividades de investigación 'compiten con otras actividades' (OR: 2.04, IC 95% 1.03 a 4.07). Conclusiones: Los residentes y profesores de una universidad latinoamericana de alta productividad valoran mucho la investigación. La presencia de brecha de género, la falta de tiempo protegido y de tutorías destacan como las principales barreras. Las estrategias propuestas para mejorar la investigación dentro de los programas de residencia son: establecer un programa de tutoría interdisciplinario entre residentes e investigadores; promover las rotaciones electivas; y premiar propuestas que consideren la equidad de género.

Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer.

Chronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise impact of COX-2, encoded by PTGS2, on the immune profile remains unknown. To address this, we performed an integrated bioinformatics analysis using data from the HGSOC cohorts (TCGA-OV, n = 368; Australian cohort AOCS, n = 80; GSE26193, n = 62; and GSE30161, n = 45). Employing Gene Set Variation Analysis (GSVA), MIXTURE and Ecotyper cell deconvolution algorithms, we concluded that COX-2 was linked to immune cell ecosystems associated with shorter survival, cell dysfunction and lower NK cell effector cytotoxicity capacity. Next, we validated these results by characterizing circulating NK cells from HGSOC patients through flow cytometry and cytotoxic assays while undergoing COX-2 and CTLA-4 blockade. The blockade of COX-2 improved the cytotoxic capacity of NK cells against HGSOC cell lines. Our findings underscore the relevance of COX-2 in shaping the TIME and suggest its potential as a prognostic indicator and therapeutic target. Increased COX-2 expression may hamper the effectivity of immunotherapies that require NK cell effector function. These results provide a foundation for experimental validation and clinical trials investigating combined therapies targeting COX-2 and CTLA-4 in HGSOC.

Circulating T regulatory cell subsets in patients with untreated lung cancer

IntroductionRegulatory T Cells (Tregs) play an important role in carcinogenesis and tumor immunoediting by preventing the development of effective antitumor immunity. Several reports showed that circulating Tregs are increased in patients with solid tumors, including lung cancer. Treg population could be categorized into “naive,” “effector,” and “memory” subtypes, bearing potential unique functions. However, the data regarding the prognostic impact of these Tregs subtypes is limited in lung cancer. The aim of this study was to investigate the frequency of different circulating Tregs subtypes in lung cancer and their correlation with clinical outcomes.MethodsWe analyzed the frequency of circulating CD4, CD8 and, Tregs lymphocytes in 66 patients with lung cancer and 32 healthy controls using flow cytometry. Circulating Tregs subtypes: naïve (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO−), memory (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO+) and the expression of the activation marker HLA-DR were correlated with overall survival.ResultsThe percentage and the absolute number of total, memory and activated Tregs was significantly higher in lung cancer patients than healthy controls. Patients with a Tregs percentage higher than 5.4% and higher than 20% of HLA-DR + Tregs had worse overall survival than those with lower levels.ConclusionsCirculating Tregs and activated Tregs are a potential prognostic factor in patients with lung cancer treated with conventional therapy and could be considered a predictive biomarker in patients not eligible for immune blockade treatments. Additionally, it will be interesting to study these Tregs subsets for immune treatments in future clinical trials. (AU)

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.

Circulating T regulatory cell subsets in patients with untreated lung cancer.

INTRODUCTION: Regulatory T Cells (Tregs) play an important role in carcinogenesis and tumor immunoediting by preventing the development of effective antitumor immunity. Several reports showed that circulating Tregs are increased in patients with solid tumors, including lung cancer. Treg population could be categorized into "naive," "effector," and "memory" subtypes, bearing potential unique functions. However, the data regarding the prognostic impact of these Tregs subtypes is limited in lung cancer. The aim of this study was to investigate the frequency of different circulating Tregs subtypes in lung cancer and their correlation with clinical outcomes. METHODS: We analyzed the frequency of circulating CD4, CD8 and, Tregs lymphocytes in 66 patients with lung cancer and 32 healthy controls using flow cytometry. Circulating Tregs subtypes: naïve (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO-), memory (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO+) and the expression of the activation marker HLA-DR were correlated with overall survival. RESULTS: The percentage and the absolute number of total, memory and activated Tregs was significantly higher in lung cancer patients than healthy controls. Patients with a Tregs percentage higher than 5.4% and higher than 20% of HLA-DR + Tregs had worse overall survival than those with lower levels. CONCLUSIONS: Circulating Tregs and activated Tregs are a potential prognostic factor in patients with lung cancer treated with conventional therapy and could be considered a predictive biomarker in patients not eligible for immune blockade treatments. Additionally, it will be interesting to study these Tregs subsets for immune treatments in future clinical trials.

Infantile/Capillary Hemangioma of the Uterine Corpus: A Rare Cause of Abnormal Genital Bleeding.

BACKGROUND: Infantile hemangiomas are vascular anomalies. However, they rarely cause genital bleeding. Here, we present the case of a young female with an endocavitary hemangioma who presented with abnormal uterine bleeding (AUB). CASE: The patient was an 8-year-old female with genital bleeding. Transabdominal pelvic ultrasound showed a 20-mm highly vascularized focal intrauterine endocavitary lesion. Vascular computerized tomography excluded vascular anomalies. Magnetic resonance imaging suggested a hemangioma. Minimally invasive open surgery was performed to remove the lesion. Subsequent pathology analyses confirmed an infantile/capillary hemangioma. CONCLUSIONS: Infantile hemangiomas are vascular anomalies that should be considered potential causes of AUB in early puberty. The study of these cases should include pelvic ultrasound and vascular magnetic resonance imaging. Experienced surgeons can successfully accomplish fertility-sparing surgical procedures. SUMMARY: We describe an unusual case of peripubertal AUB caused by an endocavitary capillary hemangioma. Management included fertility-sparing surgery and the complete resolution of symptoms.

Real-world evaluation of molecular testing and treatment patterns for EGFR mutations in non-small cell lung cancer in Latin America.

Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first- or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC. These findings underline the unmet needs of ensuring early diagnosis, molecular profiling and use of correct treatment to alleviate NSCLC burden in the region.

Multiplex SuperSelective PCR Assays for the Detection and Quantitation of Rare Somatic Mutations in Liquid Biopsies.

SuperSelective primers, by virtue of their unique design, enable the simultaneous identification and quantitation of inherited reference genes and rare somatic mutations in routine multiplex PCR assays, while virtually eliminating signals from abundant wild-type sequences closely related to the target mutations. These assays are sensitive, specific, rapid, and low cost, and can be performed in widely available spectrofluorometric thermal cyclers. Herein, we provide examples of SuperSelective PCR assays that target eight different somatic EGFR mutations, irrespective of whether they occur in the same codon, occur at separate sites within the same exon, or involve deletions. In addition, we provide examples of SuperSelective PCR assays that detect specific EGFR mutations in circulating tumor DNA present in the plasma of liquid biopsies obtained from patients with non-small-cell lung cancer. The results suggest that multiplex SuperSelective PCR assays may enable the choice, and subsequent modification, of effective targeted therapies for the treatment of an individual's cancer, utilizing frequent noninvasive liquid biopsies.

Cancer of the vagina: 2021 update.

Diagnosis of a primary vaginal cancer is rare, as most vaginal tumors are metastatic from another primary site. Although cancer of the vagina is more common in postmenopausal women, an increase in young women being diagnosed with primary vaginal cancer has been reported, especially in countries with a high HIV prevalence. This is associated with persistence of high-risk HPV infection. The emphasis should be on primary prevention with prophylactic HPV vaccination. Once there is a suspicion of a primary vaginal cancer, this should be confirmed histologically with biopsy. Staging has been done clinically, as with cervical cancer; however, there is a role for imaging in assisting with staging as this is often a difficult assessment. Treatment should be individualized and depends on stage as well as histologic subtype. It is prudent to refer cases to centers of excellence with experience in dealing with this rare gynecological cancer.

Cancer of the vulva: 2021 update.

Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.

Obesity and gynecological cancers: A toxic relationship.

Despite the evidence supporting the relevance of obesity and obesity-associated disorders in the development, management, and prognosis of various cancers, obesity rates continue to increase worldwide. Growing evidence supports the involvement of obesity in the development of gynecologic malignancies. This article explores the molecular basis governing the alteration of hallmarks of cancer in the development of obesity-related gynecologic malignancies encompassing cervical, endometrial, and ovarian cancers. We highlight specific examples of how development, management, and prognosis are affected for each cancer, incorporate current knowledge on complementary approaches including lifestyle interventions to improve patient outcomes, and highlight how new technologies are helping us better understand the biology underlying this neglected pandemic.