Significance of Pathologic Response in Patients With Early and Locally Advanced Breast Cancer Treated With Neoadjuvant Chemotherapy in a Middle-Income Country. A Real-World Historical Cohort.

PURPOSE: Breast cancer (BC) is the most frequent neoplasm in women in Colombia and is associated with a higher mortality rate than in other countries and regions. Neoadjuvant chemotherapy (NACT) has become a standard treatment in locally advanced BC and provides an opportunity to improve clinical outcomes in BC. This study aims to describe characteristics, treatment patterns, and outcomes after NACT in a cohort of Colombian patients with BC. METHODS: We performed a retrospective cohort study. We included adult patients with BC treated with NACT. Clinical charts were retrospectively reviewed. Descriptive statistics and time to event for overall survival analyses were performed. Recursive partitioning was performed for survival curves to assess the complex relationship between survival times and other variables. RESULTS: Three hundred and fourteen patients were included for analysis. The pathologic complete response after neoadjuvant chemotherapy (ypCR) rate was 34.4%, with a higher ypCR in triple-negative BC (TNBC; 46.9%) and human epidermal growth factor receptor 2-positive BC (72.7%). Those who did not achieve ypCR had a higher percentage of death and relapse. The median follow-up was 4.9 years, with an 88.2% 5-year overall survival (OS). CONCLUSION: A total of 62.6% of the total patients identified were not treated with NACT, indicating a low utilization. Our global ypCR rate was higher when compared with similar studies in Colombia, likely because of differences in the NACT treatment regimens. ypCR was only associated with OS in the TNBC subgroup, emphasizing the importance of pursuing ypCR in these patients. We consider the use of NACT a valuable opportunity to implement innovative treatment approaches that improve outcomes in Colombian patients with BC.

Altering the substitution and cross-linking of glucuronoarabinoxylans affects cell wall architecture in Brachypodium distachyon.

The Poaceae family of plants provides cereal crops that are critical for human and animal nutrition, and also, they are an important source of biomass. Interacting plant cell wall components give rise to recalcitrance to digestion; thus, understanding the wall molecular architecture is important to improve biomass properties. Xylan is the main hemicellulose in grass cell walls. Recently, we reported structural variation in grass xylans, suggesting functional specialisation and distinct interactions with cellulose and lignin. Here, we investigated the functions of these xylans by perturbing the biosynthesis of specific xylan types. We generated CRISPR/Cas9 knockout mutants in Brachypodium distachyon XAX1 and GUX2 genes involved in xylan substitution. Using carbohydrate gel electrophoresis, we identified biochemical changes in different xylan types. Saccharification, cryo-SEM, subcritical water extraction and ssNMR were used to study wall architecture. BdXAX1A and BdGUX2 enzymes modify different types of grass xylan. Brachypodium mutant walls are likely more porous, suggesting the xylan substitutions directed by both BdXAX1A and GUX2 enzymes influence xylan-xylan and/or xylan-lignin interactions. Since xylan substitutions influence wall architecture and digestibility, our findings open new avenues to improve cereals for food and to use grass biomass for feed and the production of bioenergy and biomaterials.

Concordance between 21-gene recurrence score assay and clinicopathological predictive models in early-breast cancer patients cared for at a cancer center in Colombia.

INTRODUCTION: The genomic-based 21-gene recurrence score assay (21-GRSA) allows to determine the usefulness of adjuvant chemotherapy in patients with luminal-type early breast cancer (LTEBC). Additional predictive models have also been developed, such as Magee equations (ME), the Predict model (PM), and the Tennessee nomogram score (TNS). OBJECTIVE: To evaluate the concordance between 21-GRSA, ME, PM and TNS. METHODS: Patients with unifocal LTEBC and 21-GRSA, ME, PM and TNS results were included. A subgroup analysis of women older than 50 years was carried out. Concordance between the models and 21-GRSA was evaluated using Cohen's kappa index (KI). RESULTS: One-hundred and twenty-two women were included. Concordance between 21-GRSA and ME (KI = 0.35) and PM (KI = 0.24) was fair (p < 0.001). Concordance between 21-GRSA and TNS was inferior (KI = 0.16, p = 0.04). Eighty patients older than 50 years with sufficient data to calculate all three predictive models were included. Concordance was found between the low-risk classification on 21-GRSA and all three combined models in 36/37 patients (negative predictive value of 97.3%). CONCLUSION: 21-GRSA can be omitted in women older than 50 years with LTEBC classified with low risk scores on all three predictive models.

INTRODUCCIÓN: La prueba genómica de recurrencia de 21 genes (PGR21) permite determinar la utilidad de la quimioterapia adyuvante en pacientes con cáncer de mama temprano luminal (CMTL). Se han desarrollado modelos predictivos adicionales, como las ecuaciones de Magee (EM), el modelo Predict (MP) y la puntuación del nomograma de la Universidad de Tennessee (NT). OBJETIVO: Evaluar la concordancia entre PGR21, EM, MP y NT. MÉTODOS: Se incluyeron pacientes con CMTL unifocal y con resultados de PGR21, EM, MP y NT. Se efectuó subanálisis de mujeres mayores de 50 años. La concordancia se evaluó mediante índice kappa de Cohen (IK). RESULTADOS: Se incluyeron 122 mujeres. La concordancia entre PGR21 y EM (IK = 0.35) y MP (IK = 0.24) fue aceptable (p < 0.001); entre PGR21 y NT fue inferior (IK = 0.16, p = 0.04). Se incluyeron 80 pacientes mayores de 50 años con datos suficientes para calcular los tres modelos. Se encontró concordancia entre la clasificación de bajo riesgo mediante PGR21 y los tres modelos combinados en 36/37 pacientes (valor predictivo negativo de 97.3 %). CONCLUSIÓN: Se puede omitir la PGR21 en las mujeres mayores de 50 años con CMTL que se clasifica de bajo riesgo en los tres modelos predictivos.

Real-world evidence of nivolumab for non-small-cell lung cancer in a developing country.

Nivolumab is a human programmed death receptor-1 blocking antibody, used as treatment option in patients with advanced non-small-cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second-line (2L) or third-line (3L) therapy in patients with advanced NSCLC. This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as 2L or 3L treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) to treatment. OS and PFS were estimated with the Kaplan-Meier method and the differences were evaluated through the log-rank test. Data of 178 patients were included. The median follow-up was 26.8 months (interquartile range (IQR): 20.3-40.4). Nivolumab was commonly used as a 2L treatment (77.5%). The outcomes in this setting (2L) were as follows: ORR was 21.0%, and the median PFS and OS were 5.5 months (95% confidence interval (CI): 4.5-6.5) and 12.4 months (95% CI: 10.8-14.0), respectively. In 3L, the ORR with nivolumab was 15.0%, the median PFS and OS were 4.1 months (95% CI: 3.1-5.1) and 10.1 months (95% CI: 9.4-10.6), respectively. Three patients (1.7%) required discontinuation due to toxicity. Nivolumab effectiveness and safety in this scenario was consistent with that reported by previous trials and other real-world data.

Concordancia entre la prueba de puntuación de recurrencia de 21 genes y modelos clínico-patológicos predictivos en pacientes con cáncer de mama temprano en un centro oncológico en Colombia / Concordance between 21-gene recurrence score assay and clinicopathological predictive models in early-breast cancer patients cared for at a cancer center in Colombia

Resumen Introducción: La prueba genómica de recurrencia de 21 genes (PGR21) permite determinar la utilidad de la quimioterapia adyuvante en pacientes con cáncer de mama temprano luminal (CMTL). Se han desarrollado modelos predictivos adicionales, como las ecuaciones de Magee (EM), el modelo Predict (MP) y la puntuación del nomograma de la Universidad de Tennessee (NT). Objetivo: Evaluar la concordancia entre PGR21, EM, MP y NT. Métodos: Se incluyeron pacientes con CMTL unifocal y con resultados de PGR21, EM, MP y NT. Se efectuó subanálisis de mujeres mayores de 50 años. La concordancia se evaluó mediante índice kappa de Cohen (IK). Resultados: Se incluyeron 122 mujeres. La concordancia entre PGR21 y EM (IK = 0.35) y MP (IK = 0.24) fue aceptable (p < 0.001); entre PGR21 y NT fue inferior (IK = 0.16, p = 0.04). Se incluyeron 80 pacientes mayores de 50 años con datos suficientes para calcular los tres modelos. Se encontró concordancia entre la clasificación de bajo riesgo mediante PGR21 y los tres modelos combinados en 36/37 pacientes (valor predictivo negativo de 97.3 %). Conclusión: Se puede omitir la PGR21 en las mujeres mayores de 50 años con CMTL que se clasifica de bajo riesgo en los tres modelos predictivos.

Abstract Introduction: The genomic-based 21-gene recurrence score assay (21-GRSA) allows to determine the usefulness of adjuvant chemotherapy in patients with luminal-type early breast cancer (LTEBC). Additional predictive models have also been developed, such as Magee equations (ME), the Predict model (PM), and the Tennessee nomogram score (TNS). Objective: To evaluate the concordance between 21-GRSA, ME, PM and TNS. Methods: Patients with unifocal LTEBC and 21-GRSA, ME, PM and TNS results were included. A subgroup analysis of women older than 50 years was carried out. Concordance between the models and 21-GRSA was evaluated using Cohen's kappa index (KI). Results: One-hundred and twenty-two women were included. Concordance between 21-GRSA and ME (KI = 0.35) and PM (KI = 0.24) was fair (p < 0.001). Concordance between 21-GRSA and TNS was inferior (KI = 0.16, p = 0.04). Eighty patients older than 50 years with sufficient data to calculate all three predictive models were included. Concordance was found between the low-risk classification on 21-GRSA and all three combined models in 36/37 patients (negative predictive value of 97.3%). Conclusion: 21-GRSA can be omitted in women older than 50 years with LTEBC classified with low risk scores on all three predictive models.

Breast carcinoma or sweat gland carcinoma? A report of two cases and a comparison with the literature / ¿Carcinoma de mama o carcinoma de glándula sudorípara? Presentación de dos casos y análisis de la literatura.

Primary apocrine carcinoma of the sweat gland is a neoplasm with a very low incidence that may represent a clinical and histological diagnostic challenge, as well as for adequate local, adjuvant, and advanced disease management. The average age of patients is around 67 years with no gender preference. This cancer develops primarily at the axillary and scalp levels and is clinically characterized by slow growth, but can progress aggressively with local, nodal, and metastatic involvement (primarily lung, liver, and bone). The recommended management, once the histology is established, consists of a wide local resection with a clear margin of 1 to 2 cm and regional lymphadenectomy if clinically positive nodes are detected. The adjuvant treatment (radiotherapy or chemotherapy) and for the advanced disease is not established. We report here the cases of two female patients initially diagnosed with breast cancer who were finally diagnosed with apocrine carcinoma of the sweat gland.

El carcinoma apocrino primario de glándula sudorípara es una neoplasia con una muy baja incidencia, que puede representar un reto diagnóstico, clínico e histológico, y un reto terapéutico local, adyuvante y de la enfermedad avanzada. La edad media de los pacientes es de alrededor de 67 años, y no se ha observado preferencia según el sexo. Se presenta con mayor frecuencia en las axilas y en el cuero cabelludo. Se caracteriza clínicamente por un lento crecimiento, aunque puede progresar agresivamente, con compromiso local, ganglionar y metastásico, principalmente, pulmonar, hepático y óseo. El tratamiento recomendado -una vez establecida la histología- consiste en una resección local amplia con un margen claro de 1 a 2 cm y linfadenectomía regional si se detectan ganglios clínicamente positivos. El tratamiento adyuvante (radioterapia o quimioterapia) y de la enfermedad avanzada no está claramente establecido. Se presentan dos pacientes de sexo femenino con sospecha inicial de cáncer de mama, en quienes se diagnosticó finalmente un carcinoma apocrino de glándula sudorípara.

¿Carcinoma de mama o carcinoma de glándula sudorípara? Presentación de dos casos y análisis de la literatura / Breast carcinoma or sweat gland carcinoma? A report of two cases and a comparison with the literature

Resumen El carcinoma apocrino primario de glándula sudorípara es una neoplasia con una muy baja incidencia, que puede representar un reto diagnóstico, clínico e histológico, y un reto terapéutico local, adyuvante y de la enfermedad avanzada. La edad media de los pacientes es de alrededor de 67 años, y no se ha observado preferencia según el sexo. Se presenta con mayor frecuencia en las axilas y en el cuero cabelludo. Se caracteriza clínicamente por un lento crecimiento, aunque puede progresar agresivamente, con compromiso local, ganglionar y metastásico, principalmente, pulmonar, hepático y óseo. El tratamiento recomendado -una vez establecida la histología- consiste en una resección local amplia con un margen claro de 1 a 2 cm y linfadenectomía regional si se detectan ganglios clínicamente positivos. El tratamiento adyuvante (radioterapia o quimioterapia) y de la enfermedad avanzada no está claramente establecido. Se presentan dos pacientes de sexo femenino con sospecha inicial de cáncer de mama, en quienes se diagnosticó finalmente un carcinoma apocrino de glándula sudorípara.

Abstract Primary apocrine carcinoma of the sweat gland is a neoplasm with a very low incidence that may represent a clinical and histological diagnostic challenge, as well as for adequate local, adjuvant, and advanced disease management. The average age of patients is around 67 years with no gender preference. This cancer develops primarily at the axillary and scalp levels and is clinically characterized by slow growth, but can progress aggressively with local, nodal, and metastatic involvement (primarily lung, liver, and bone). The recommended management, once the histology is established, consists of a wide local resection with a clear margin of 1 to 2 cm and regional lymphadenectomy if clinically positive nodes are detected. The adjuvant treatment (radiotherapy or chemotherapy) and for the advanced disease is not established. We report here the cases of two female patients initially diagnosed with breast cancer who were finally diagnosed with apocrine carcinoma of the sweat gland.

Treatment of adults with acute uncomplicated malaria with azithromycin and chloroquine in India, Colombia, and Suriname.

BACKGROUND: To explore the use of azithromycin-chloroquine (AZCQ) for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ) 600 mg base once daily (QD) for 3 days versus atovaquone-proguanil (AP) or chloroquine plus sulfadoxine-pyrimethamine (SPCQ) in adults with acute uncomplicated Plasmodium falciparum malaria. METHODS: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28. RESULTS: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: -22.6, 0.8). In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: -52, -32). A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%. CONCLUSION: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g.

Carcinoma córtico-adrenal: revisión de la literatura / Adrenal-cortical carcinoma: a review of the literature

El carcinoma córtico-adrenal es una entidad que se presenta raras veces; su evolución es agresiva, con una alta probabilidad de recaída y una supervivencia a 5 años que no supera el 60%. El único tratamiento curativo es la cirugía, siempre y cuando esta sea completa y a los pacientes se los diagnostique en estadios tempranos. Otras intervenciones que se pueden brindar son la radioterapia, la quimioterapia y el control de secreción hormonal en el contexto adyuvante o paliativo. En algunos casos (síndrome de Cushing) el bloqueo hormonal previo a la cirugía es imperativo. En esta revisión se describen la patogénesis, el diagnóstico, los factores pronósticos y el tratamiento del carcinoma córtico-adrenal, con el propósito de guiar el enfoque diagnóstico y el tratamiento.

Adrenal-cortical carcinoma is a rarely occurring entity; it evolves aggressively, has a high probability of relapse and survival at 5 years does not surpass 60%. Surgery provides the only curative treatment, but only when it is complete and carried out on patients with early-stage diagnosis. Additional treatments that may be used include radiotherapy, chemotherapy and control of hormonal secretion in an adjuvant or palliative context. In some cases (Cushing´s syndrome), it is imperative to provide hormonal block before surgery. The pathogenesis, diagnosis, prognostic factors and treatment of adrenal-cortical carcinoma are described in this review in order to sharpen the focus on diagnosis and treatment.