ABSTRACT
Resumen Introducción : El objetivo del trabajo es evidenciar la necesidad de aplicar una metodología de evaluación en el Trastorno por Déficit de Atención e Hiperactividad (TDAH) por la falta de acuerdo entre padres y profesores en los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición (DSM-5). Métodos : Se trata de un estudio descriptivo retros pectivo de tres años y diez meses. La muestra se extrajo de 640 sujetos evaluados y diagnosticados de TDAH, con edades comprendidas entre 8 y 16 años, y un Cociente Intelectual Total (CIT) entre 80 y 120. A los sujetos se les aplicó una evaluación neuropsicológica. Se tuvieron en cuenta determinadas escalas de los cuestionarios: Siste ma de Evaluación de Niños y Adolescentes (SENA) y Eva luación Conductual de la Función Ejecutiva-2 (BRIEF-2), ambos cumplimentados por padres, y los criterios del DSM-5 contestados por padres y profesores. Resultados : Como resultado se observa una baja con cordancia entre las observaciones obtenidas del DSM-5 entre padres y profesores.
Abstract Introduction : The aim of the study is to demonstrate the need to apply an assessment methodology in At tention Deficit Hyperactivity Disorder (ADHD) due to the lack of agreement between parents and teachers on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Methods : This is a retrospective descriptive study of three years and ten months. The sample was drawn from 640 subjects assessed and diagnosed with ADHD, aged between 8 and 16 years, and with a Total Intellectual Quotient (TQ) between 80 and 120. Subjects underwent a neuropsychological assessment. Certain scales of the questionnaires: Child and Adolescent Assessment Sys tem (SENA) and Behavioural Assessment of Executive Function-2 (BRIEF-2), both completed by parents, and the DSM-5 criteria answered by parents and teachers were taken into account. Results : As a result, a low concordance was observed between the observations obtained from the DSM-5 between parents and teachers.
ABSTRACT
RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.
ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.
ABSTRACT
INTRODUCTION: The aim of the study is to demonstrate the need to apply an assessment methodology in Attention Deficit Hyperactivity Disorder (ADHD) due to the lack of agreement between parents and teachers on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). METHODS: This is a retrospective descriptive study of three years and ten months. The sample was drawn from 640 subjects assessed and diagnosed with ADHD, aged between 8 and 16 years, and with a Total Intellectual Quotient (TQ) between 80 and 120. Subjects underwent a neuropsychological assessment. Certain scales of the questionnaires: Child and Adolescent Assessment System (SENA) and Behavioural Assessment of Executive Function-2 (BRIEF-2), both completed by parents, and the DSM-5 criteria answered by parents and teachers were taken into account. RESULTS: As a result, a low concordance was observed between the observations obtained from the DSM-5 between parents and teachers.
Introducción: El objetivo del trabajo es evidenciar la necesidad de aplicar una metodología de evaluación en el Trastorno por Déficit de Atención e Hiperactividad (TDAH) por la falta de acuerdo entre padres y profesores en los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición (DSM-5). Métodos: Se trata de un estudio descriptivo retrospectivo de tres años y diez meses. La muestra se extrajo de 640 sujetos evaluados y diagnosticados de TDAH, con edades comprendidas entre 8 y 16 años, y un Cociente Intelectual Total (CIT) entre 80 y 120. A los sujetos se les aplicó una evaluación neuropsicológica. Se tuvieron en cuenta determinadas escalas de los cuestionarios: Sistema de Evaluación de Niños y Adolescentes (SENA) y Evaluación Conductual de la Función Ejecutiva-2 (BRIEF-2), ambos cumplimentados por padres, y los criterios del DSM-5 contestados por padres y profesores. Resultados: Como resultado se observa una baja concordancia entre las observaciones obtenidas del DSM-5 entre padres y profesores.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Child , Adolescent , Humans , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/psychology , Retrospective Studies , Neuropsychological Tests , Surveys and Questionnaires , Diagnostic and Statistical Manual of Mental DisordersABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Anaplastic Lymphoma Kinase/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Protein Kinase Inhibitors/therapeutic use , GenomicsABSTRACT
The introduction of immunotherapy has brought about a paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). It has not only significantly improved the prognosis of patients but has also become a cornerstone of treatment, particularly in those without oncogenic driver mutations. Immune checkpoint inhibitors (ICIs) play a crucial role in the treatment of lung cancer and can be classified into two main groups: Anti-cytotoxic T lymphocyte antigen-4 (Anti-CTLA-4) and anti-T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti-PD-L1). Certainly, the landscape of approved first line immunotherapeutic approaches has expanded to encompass monotherapy, immunotherapy-exclusive protocols, and combinations with chemotherapy. The complexity of decision-making in this realm arises due to the absence of direct prospective comparisons. However, a thorough analysis of the long-term efficacy and safety data derived from pivotal clinical trials can offer valuable insights into optimizing treatment for different patient subsets. Moreover, ongoing research is investigating emerging biomarkers and innovative therapeutic strategies that could potentially refine the current treatment approach even further. In this comprehensive review, our aim is to highlight the latest advances in immunotherapy for advanced NSCLC, including the mechanisms of action, efficacy, safety profiles, and clinical significance of ICI.
ABSTRACT
Resumen Tanto el Trastorno por Déficit de Atención e Hiperactividad (TDAH) como la ansiedad son dos de los trastornos que más se evidencian en la población infanto-juvenil existiendo una correlación entre ambos tal y como se recoge en numerosos estudios. La combinación de ambos trastornos afecta a los procesos de enseñanza-aprendizaje del niño provocando dificultades de aprendizaje (DA) en el mismo. Los objetivos del presente trabajo se basaron en valorar los criterios que evidencian padres y profesores en niños con TDAH para caracterizar el grado de adecuación de la percepción y evaluar si esta se ajusta a la realidad o es insuficiente, si existen diferencias en dicha percepción entre padres y docentes; analizar la conciencia que tienen sobre las posibles DA que puedan presentar, para así aportar orientaciones adecuadas que permitan una favorable inter vención y evolución. La muestra se compone de 137 sujetos con edades comprendidas entre 9 y 15 años con un Coeficiente Intelectual Total (CIT) de entre 80 y 120. Los instrumentos que se utilizaron fueron: la escala de inteligencia de Wechsler para niños-V (WISC-V), el Cuestionario de Ansiedad Estado-Rasgo en Niños(STAI-C), el Sistema de Evaluación de Niños y Adolescentes(SENA) y el Inventario de Problemas en la Escuela (IPE). Como resultado se observa que la ansiedad percibida por estos niños no está relacionada con la que aprecian padres y profesores, sin embargo, estos últimos sí que coinciden en su apreciación.
Abstract Both Attention Deficit Hyperactivity Disorder (ADHD) and anxiety are two of the disorders that are most evident in the infant-juvenile population and there is a correlation between the two, as shown in numerous studies. The combination of both disorders affects the child's teaching-learning processes, causing learning difficulties (LD). The aims of the present study were based on assessing the criteria evidenced by parents and teachers in children with ADHD to characterize the degree of adequacy of perception and to evaluate whether this is in line with real ity or insufficient, whether there are differences in this perception between parents and teachers, and to analyze their awareness of the possible AD they may present, in order to provide appropriate guidelines for favourable intervention and evolution. The sample consisted of 137 subjects aged between 9 and 15 years with a Total IQ (TIQ) between 80 and 120. The instruments used were: the Wechsler Intelligence Scale for Children-V (WISC-V), the State-Trait Anxiety Questionnaire for Children (STAI-C), the Child and Adolescent Assessment System (SENA) and the Inventory of Problems at School (IPE). As a result, it is observed that the anxiety perceived by these children is not related to the anxiety perceived by parents and teachers, although the latter do coincide in their assessment.
ABSTRACT
Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.
ABSTRACT
Both Attention Deficit Hyperactivity Disorder (ADHD) and anxiety are two of the disorders that are most evident in the infant-juvenile population and there is a correlation between the two, as shown in numerous studies. The combination of both disorders affects the child's teaching-learning processes, causing learning difficulties (LD). The aims of the present study were based on assessing the criteria evidenced by parents and teachers in children with ADHD to characterize the degree of adequacy of perception and to evaluate whether this is in line with reality or insufficient, whether there are differences in this perception between parents and teachers, and to analyze their awareness of the possible AD they may present, in order to provide appropriate guidelines for favourable intervention and evolution. The sample consisted of 137 subjects aged between 9 and 15 years with a Total IQ (TIQ) between 80 and 120. The instruments used were: the Wechsler Intelligence Scale for Children-V (WISCV), the State-Trait Anxiety Questionnaire for Children (STAI-C), the Child and Adolescent Assessment System (SENA) and the Inventory of Problems at School (IPE). As a result, it is observed that the anxiety perceived by these children is not related to the anxiety perceived by parents and teachers, although the latter do coincide in their assessment.
Tanto el Trastorno por Déficit de Atención e Hiperactividad (TDAH) como la ansiedad son dos de los trastornos que más se evidencian en la población infanto-juvenil existiendo una correlación entre ambos tal y como se recoge en numerosos estudios. La combinación de ambos trastornos afecta a los procesos de enseñanza-aprendizaje del niño provocando dificultades de aprendizaje (DA) en el mismo. Los objetivos del presente trabajo se basaron en valorar los criterios que evidencian padres y profesores en niños con TDAH para caracterizar el grado de adecuación de la percepción y evaluar si esta se ajusta a la realidad o es insuficiente, si existen diferencias en dicha percepción entre padres y docentes; analizar la conciencia que tienen sobre las posibles DA que puedan presentar, para así aportar orientaciones adecuadas que permitan una favorable intervención y evolución. La muestra se compone de 137 sujetos con edades comprendidas entre 9 y 15 años con un Coeficiente Intelectual Total (CIT) de entre 80 y 120. Los instrumentos que se utilizaron fueron: la escala de inteligencia de Wechsler para niños-V (WISC-V), el Cuestionario de Ansiedad Estado-Rasgo en Niños(STAI-C), el Sistema de Evaluación de Niños y Adolescentes(SENA) y el Inventario de Problemas en la Escuela (IPE). Como resultado se observa que la ansiedad percibida por estos niños no está relacionada con la que aprecian padres y profesores, sin embargo, estos últimos sí que coinciden en su apreciación.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Adolescent , Humans , Child , Anxiety Disorders , Anxiety , Schools , Perception , ParentsABSTRACT
BACKGROUND: Despite the advances in the management of advanced non-small cell lung cancer (NSCLC), the access to genetic profiling and target therapies remains a challenge in Latin America, even in countries with a higher rate of targetable mutations. The aim of this study is to evaluate the clinical outcomes of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) treatment in a Peruvian real-world setting. METHODS: This is a retrospective study of recurrent or advanced NSCLC EGFR mutated patients diagnosed and treated with anti-EGFR TKI at Instituto Nacional de Enfermedades Neoplásicas (INEN) between January 1, 2015 to December 31, 2020. The outcomes were objective response rate (ORR), progression free survival (PFS), and overall survival (OS). RESULTS: We identify 613 stage IV or recurrent NSCLC patients who were tested for EGFR mutations and found a pathogenic mutation in 39.5% of patients. Only 51.2% of them received anti-EGFR TKI as institutional treatment. ORR was 58%, after median follow-up of 32 months, the estimated median PFS was 13.9 months (11.1-16.7 months), and the estimated median OS was 21.7 months (18.5-24.9 months). No differences were found in PFS according to line of treatment or brain metastases at diagnosis (p = 0.46 and p = 0.07, respectively), respect to OS there were no differences line of treatment (p = 0.12), significant difference were found in presence of brain metastases (p = 0.006). CONCLUSION: Our study demonstrates that erlotinib for advanced NSCLC harboring EGFR-activating mutations is effective even in patients usually excluded from clinical trial, like those previously exposed to one or more lines of chemotherapy or with brain metastases.
Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Peru , Retrospective Studies , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Mutation , Brain Neoplasms/drug therapy , ErbB Receptors/genetics , ErbB Receptors/therapeutic useABSTRACT
Background: The COVID-19 pandemic caused discontinuities in cancer care (CC) in most countries. Here, the authors describe the real-world impacts of implementing a contingency plan employing telemedicine for CC. Methods: A retrospective study of patients who received CC through telemedicine at the Instituto Nacional de Enfermedades Neoplasicas, Peru, from March 2020 to February 2021 was conducted. Impacts were measured by comparing the amount of CC administered during the pandemic versus the prior year. Results: A total of 16,456 telemedicine visits were carried out. An annual comparative analysis showed a gap of 23% and telemedicine accounted for 27.6% of the total CC administered during the pandemic. A high (4.50/5) level of patient satisfaction with telemedicine was reported. Conclusion: Telemedicine is an important tool to facilitate the continuity of CC.
Subject(s)
COVID-19 , Neoplasms , Telemedicine , Humans , Pandemics , COVID-19/epidemiology , Peru/epidemiology , Retrospective Studies , Neoplasms/epidemiology , Neoplasms/therapy , Patient SatisfactionABSTRACT
Background: Lung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients. Methods: Comparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment. Results: Overall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability. Conclusion: NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.
ABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , AMP-Activated Protein Kinase Kinases , B7-H1 Antigen/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Hispanic or Latino/genetics , Humans , Kelch-Like ECH-Associated Protein 1/genetics , Lung Neoplasms/pathology , Mutation , NF-E2-Related Factor 2/genetics , Prognosis , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Registries , Retrospective StudiesABSTRACT
BACKGROUND: Lung cancer is still a prevalent and fatal neoplasm in developing countries. In the last decades, chemotherapy (CHT) maintenance occupied an important role in the treatment, as well as targeted therapies. We aimed to evaluate the survival impact of targeted therapy in advanced lung cancer at a private Peruvian institution (Oncosalud - AUNA). METHODS: We reviewed retrospectively medical records of patients with advanced-stage non-small cell lung cancer (NSCLS) (clinical stage III-IV) who received CHT and maintenance treatment with target therapy (TT) or CHT. The impact was assessed by progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method, and comparisons of survival curves were performed using log-rank or Breslow test and Cox model. RESULTS: The median age of the patients was 65 years. Clinical characteristics, as well as the treatment type, showed no significant difference between the two groups. The maintenance schedule in those receiving CHT was generally pemetrexed (70%) and in those receiving TT was erlotinib (60.7%). In patients receiving TT, the median PFS was 13 months compared to 7 months in those receiving CHT; likewise, the median OS was 45 and 17 months, respectively. The PFS and OS curves showed significant differences (P < .05), achieving a better survival in subjects treated with TT. CONCLUSION: Progression-Free Survival and OS were superior in patients who received targeted therapy than those treated only with CHT, the 2 years rate of PFS and OS was nearly double to those who received only CHT-based treatments.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Peru , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.
Subject(s)
Thymoma/epidemiology , Adult , Aged , Aged, 80 and over , Female , Humans , Latin America , Male , Middle Aged , Time Factors , Treatment Outcome , Young AdultABSTRACT
PURPOSE: BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-triggered apoptosis in EGFR-mutant non-small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS: A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS: Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION: EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Bcl-2-Like Protein 11/genetics , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Adult , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Drug Combinations , ErbB Receptors/antagonists & inhibitors , Female , Gene Deletion , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Neoplasm Staging , Polymorphism, Genetic , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis. METHODS: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method. RESULTS: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival. CONCLUSIONS: The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival. WHAT THIS STUDY ADDS: To determine prognosis factors in TETs.
Subject(s)
Neoplasms, Glandular and Epithelial/epidemiology , Thymus Neoplasms/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Time FactorsABSTRACT
BACKGROUND: The intestinal microbiota is an important factor in modulating immune-mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments. METHODS: This was a retrospective cohort study. Patients with advanced non-small cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 (PD-L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non-ATB exposed (no-ATB), exposed within 30 days of the first dose of ICI (pre-ICI ATB) and patients receiving ATB concomitantly with ICI (ICI-ATB). Progression-free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed. RESULTS: A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B-lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32-67.7), compared with 20.3 months (95% CI: 12.1-non-reached [NR]) for patients with pre-ICI ATB treatment and 24.7 months (95% CI: 13-NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups. CONCLUSIONS: Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs.
Subject(s)
Anti-Bacterial Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/pathology , Male , Retrospective StudiesABSTRACT
OBJECTIVES: The objectives of this study are to evaluate the relationship between authorship networking, socioeconomic factors, and scientific productivity across Latin America. METHODS: In a bibliometric analysis of cancer-related Latin-American publications, the relationship between authorship network indicators, sociodemographic factors, and number of peer-reviewed indexed publications per country was explored. A systematic review of the literature for cancer publications between 2000 and 2018 using the Scopus database limited to Latin-American authors was used for the construction of coauthorship and publication networks and their respective metrics. Sociodemographic variables including percentage of invested gross domestic product in research, population, and cancer incidence were also estimated. Multiple linear regression models were constructed to determine the relationship between productivity and the aforementioned variables. RESULTS: A total of 8,528 articles across nine countries were included. Brazil was the most productive nation with 41.8% of identified references followed by Mexico (16.6%) and Argentina (12.9%). Latin America experienced a 9% growth in number of publications across the studied time frame. After analyzing networking and sociodemographic variables, number of authors in a collaboration network and percentage of invested gross domestic product were associated with high productivity yielding a multiple regression model with an R2 value of 0.983. CONCLUSIONS: This study indicates that extensive authorship networking and a high investment in research strongly predict cancer-related productivity.
Subject(s)
Abstracting and Indexing/statistics & numerical data , Authorship/standards , Peer Review, Research/methods , Publications/statistics & numerical data , Bibliometrics , Data Management , Efficiency , Humans , Incidence , Latin America/epidemiology , Neoplasms/epidemiology , Publications/trends , Socioeconomic FactorsABSTRACT
INTRODUCTION: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. METHODS: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. RESULTS: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. CONCLUSIONS: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.