Polimorfismos genéticos asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab / Genetic polymorphisms associated with the response of head and neck carcinoma to cetuximab

Objetivo: Exponer los principales polimorfismos genéticos que han sido asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab. Método: Se realizó una revisión no exhaustiva de artículos publicados en el período de enero de 2000 a diciembre de 2022, para ello se emplearon las bases de datos Medline (vía Pubmed) y Science Direct. En la evaluación de la calidad metodológica de los artículos incluidos se utilizó la guía para los estudios de asociación genética (Q-Genie). Resultados: Se identificaron un total de 206 artículos, de los cuales 12 cumplieron con los criterios para el análisis final. Se reportaron varios polimorfismos, tales como: EGFR-R521K (AA/GA), FcγRIIIa (158VV) y FcγRIIa (131HH), KRASLCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 en sus variantes mutadas, HIF-1α (CT/TT) y XRCC5 (GG/AA) que se asociaron con las variables de supervivencia, riesgo de progresión, tiempos hasta la progresión de la enfermedad, así como toxicidad cutánea. Conclusiones: Varios polimorfismos pueden asociarse con la respuesta del carcinoma de cabeza y cuello al tratamiento con cetuximab, siendo EGFR-R521K y FcγR IIIa-V158F los más estudiados. La enorme incertidumbre de los resultados alcanzados no permite alcanzar conclusiones firmes sobre la influencia de los polimorfismos genéticos en la respuesta al cetuximab; sin embargo, pueden convertirse en biomarcadores farmacogenéticos en la práctica clínica como una valiosa herramienta en la medicina personalizada, para predecir la respuesta medicamentosa. Para ello se requiere la realización de ensayos controlados con estratos por genotipo, con asignación aleatoria del tratamiento y el análisis de otras variables con valor pronóstico conocido.(AU)

Objective: To present the main genetic polymorphisms that have been associated with the response of head and neck carcinoma to cetuximab. Method: A non-exhaustive review of articles published in the period from January 2000 to December 2022 was carried out, for this purpose the Medline (via Pubmed) and Science Direct databases were used. The guide for genetic association studies (Q-Genie) was used to evaluate the methodological quality of the included articles. Results: A total of 206 articles were identified, of which 12 met the criteria for the final analysis. Several polymorphisms were reported, such as: EGFR-R521K (AA/GA), FcγRIIIa (158VV) and FcγRIIa (131HH), KRAS-LCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 in its mutated variants, HIF- 1α (CT/TT) and XRCC5 (GG/AA) that were associated with survival variables, risk of progression, times to disease progression, as well as skin toxicity. Conclusions: Several polymorphisms can be associated with the response of head and neck carcinoma to treatment with cetuximab, being EGFR-R521K and FcγR IIIa-V158F the most studied. The enormous uncertainty of the results obtained does not allow firm conclusions to be reached about the influence of genetic polymorphisms on the response to cetuximab; however, they can become pharmacogenetic biomarkers in clinical practice as a valuable tool in personalized medicine, to predict drug response. This requires carrying out controlled trials with strata by genotype, with random assignment of treatment and the analysis of other variables with known prognostic value.(AU)

Endoscopic versus open surgery in patients with malignant sinonasal tumours and brain invasion. A case series study.

OBJECTIVES: To determine the safety, effectiveness and perioperative costs of endonasal endoscopic approach in brain invasive malignant sinonsal tumours patients. MATERIALS AND METHODS: This was a case series bidirectional study; that included 30 brain invasive malignant sinonsal tumours patients treated by endonasal endoscopic approach (2015-2017) and 53 by open surgery (2010-2015). Propensity score matching was used to compensate the prognostic factors; in a sample of 50 patients (25 per group). Primary response variables was local control and 3-years overall survival. Perioperative cost variables were analyzed. RESULTS: A number of 50 patients were included after matching (25 in each therapeutic group). The age average was 55 years and male proportion was 62%. Squamous cell carcinoma and grade II lesions were the most represented in the sample. Endonasal endoscopic approach reduced surgical time in 1 h 20 min, transfusion needs in 5.5 fold and hospitalization in 19 days; in comparison with open technique. Oncologic control based on surgical free margins, local control, overall survival and progression free survival after three years was higher when the resection was performed endoscopically. Functional status was enhanced and complications diminished by using endoscopic approach. Saving was estimated in $7 355.18 per patient. CONCLUSIONS: Endonasal endoscopic approach represents a safe, effective and economic procedure in selected patients with malignant sinonasal tumors and brain invasion.

Endoscopic versus open surgery in patients with malignant sinonasal tumors and brain invasion. A case series study. / Cirugía endoscópica vs. cirugía abierta en pacientes con neoplasias nasosinusales malignas con invasión cerebral. Estudio de serie de casos.

OBJECTIVES: To determine the safety, effectiveness and perioperative costs of endonasal endoscopic approach in brain invasive malignant sinonsal tumors patients. MATERIALS AND METHODS: This was a case series bidirectional study; that included 30 brain invasive malignant sinonsal tumors patients treated by endonasal endoscopic approach (2015-2017) and 53 by open surgery (2010-2015). Propensity score matching was used to compensate the prognostic factors; in a sample of 50 patients (25 per group). Primary response variables was local control and 3-years overall survival. Perioperative cost variables were analyzed. RESULTS: A number of 50 patients were included after matching (25 in each therapeutic group). The age average was 55 years and male proportion was 62%. Squamous cell carcinoma and grade II lesions were the most represented in the sample. Endonasal endoscopic approach reduced surgical time in 1 hour 20 minutes, transfusion needs in 5.5 fold and hospitalization in 19 days; in comparison with open technique. Oncologic control based on surgical free margins, local control, overall survival and progression free survival after three years was higher when the resection was performed endoscopically. Functional status was enhanced and complications diminished by using endoscopic approach. Saving was estimated in $7 355.18 per patient. CONCLUSIONS: Endonasal endoscopic approach represents a safe, effective and economic procedure in selected patients with malignant sinonasal tumors and brain invasion.

Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.

Satisfacción con los resultados estéticos de la reconstrucción mamaria posmastectomía, en el Instituto Nacional de Oncología y Radiobiología (INOR) de Cuba, mediante el cuestionario BREAST-Q / Satisfaction with the aesthetic results of post-mastectomy breast reconstruction at the Cuban Institute of Oncology (INOR) by using the BREAST-Q questionnaire

INTRODUCCIÓN: El tratamiento quirúrgico del cáncer de mama deja secuelas deformantes, por tanto, la reconstrucción mamaria es considerada parte integral del tratamiento. Evaluar la satisfacción de las pacientes sobre los resultados estéticos de la reconstrucción orienta hacia la efectividad de las técnicas quirúrgicas empleadas. OBJETIVOS: Evaluar la satisfacción con los resultados estéticos de las pacientes reconstruidas posmastectomía, y comparar estos resultados con la simetría frontal mamaria posquirúrgica. MÉTODOS: Se realizó un estudio de serie de casos en 40 pacientes reconstruidas posmastectomía en el periodo 2013-2018 en el Instituto Nacional de Oncología y Radiobiología (INOR) de Cuba. Se evaluó la satisfacción sobre sus resultados estéticos mediante el cuestionario BREAST-Q modificado. El test no paramétrico de Kruskal-Wallis se usó para determinar diferencias de los niveles de satisfacción entre grupos de covariables. Los resultados se correlacionaron con la medida de la simetría frontal global posquirúrgica mediante la correlación de Spearman. RESULTADOS: Se obtuvieron altos niveles satisfacción de las pacientes reconstruidas en las escalas evaluadas, con medianas por encima de 95 puntos. Pacientes entre 35 y 54 años alcanzaron puntuaciones significativamente más altas (p < 0,05). La satisfacción con la apariencia de las mamas correlacionó positiva y significativamente con la simetría frontal posquirúrgica. CONCLUSIONES: Los altos niveles de satisfacción alcanzados sugieren una alta efectividad de las técnicas quirúrgicas reconstructivas empleadas, especialmente con la técnica de dorsal ancho más implante; la correlación positiva entre la satisfacción con la apariencia de las mamas y la simetría global posquirúrgica verifica esta afirmación

INTRODUCTION: The surgical treatment of breast cancer leaves deforming sequelae; therefore, breast reconstruction is considered an integral part of the treatment. Evaluating patient satisfaction with the aesthetic results of reconstruction is one way to assess the effectiveness of the surgical techniques used. OBJECTIVES: To evaluate satisfaction with aesthetic results in patients reconstructed after mastectomy and to compare these results with frontal breast symmetry after surgery. METHODS: A case series study was conducted in 40 reconstructed post-mastectomy patients from 2013-2018 at INOR. Satisfaction with aesthetic results was evaluated using the modified Breast Q survey. Differences in satisfaction levels between groups of covariates were determined by the non-parametric Kruskal-Wallis test. The results were correlated with measurement of post-surgical global frontal symmetry using Spearman's correlation. RESULTS: High satisfaction levels were obtained in reconstructed patients in the evaluated scales, with medians above 95 points. Scores were significantly higher in patients aged between 35 and 54 years (p < 0.05). Satisfaction with breast appearance correlated positively and significantly with post-surgical frontal symmetry. CONCLUSIONS: The high satisfaction levels achieved suggest a high effectiveness of the reconstructive surgical techniques used, especially with latissimus dorsi plus implant technique; this statement is verified by the positive correlation between satisfaction with the appearance of the breasts and the overall post-surgical symmetry

Nueva metodología para medir simetría frontal en pacientes reconstruidas por cáncer de mama / A new method to measure frontal symmetry in patients undergoing breast reconstruction due to breast cancer

INTRODUCCIÓN: El resultado estético de la reconstrucción mamaria depende de varios factores difíciles de evaluar, y lleva por tanto a una variabilidad muy significativa en los resultados obtenidos. La valoración habitual es subjetiva. De ahí la inquietud por disponer de una herramienta de valoración objetiva. OBJETIVO: Crear una metodología para medir resultados estéticos de la simetría frontal en la reconstrucción mamaria mediante el uso de un software. MÉTODO: En el Instituto Nacional de Oncología de Cuba, en el período entre diciembre de 2011 y diciembre de 2017, se aplicó una nueva metodología para medir la simetría mamaria. El software fue desarrollado íntegramente por los autores. Toma como entrada una imagen frontal. En cada medición se evaluaron las medidas aportadas por el software. Se aplicó a un grupo control de 74mujeres, de una población sana, a un grupo de 56pacientes tributarias de reconstrucción mamaria inmediata y a un grupo de 45pacientes con reconstrucción mamaria diferida. Se analizaron variables sociodemográficas y oncorreconstructivas. En el análisis estadístico se usó la mediana. RESULTADOS: La mayoría de las pacientes estaban en percentiles mayores del 75, por lo que los resultados estéticos fueron muy satisfactorios, con mejores resultados en los casos en que se practicó cirugía inmediata. CONCLUSIONES: Se desarrolló un nuevo método cuantitativo para medir simetría frontal en pacientes reconstruidas por cáncer de mama. Los mejores resultados fueron en las pacientes reconstruidas de forma inmediata. El método es de fácil aplicación y económico

INTRODUCTION: The aesthetic result of breast reconstruction depends on several factors that are difficult to evaluate, leading to highly significant variability in the results. Evaluation is usually subjective and consequently there is strong interest in a tool that could provide objective valuation. OBJECTIVE: To create a method to measure the aesthetic results of frontal symmetry in breast reconstruction, by means of software. METHOD: A new method was applied to measure breast symmetry in the National Institute of Oncology of Cuba between December 2011 and December 2017. The software was developed entirely by the authors. First, a frontal image was taken. Each subsequent measurement provided by the software was evaluated. The method was applied in a control group of 74women from a healthy population, a group of 56patients suitable for immediate breast reconstruction, and a group of 45patients with delayed breast reconstruction. Sociodemographic variables and the technique surgical were analysed. In the statistical analysis, the median was used. RESULTS: Most of the patients were in percentiles higher than the 75th percentile, indicating highly satisfactory aesthetic results. Better results were obtained in patients undergoing immediate reconstruction. CONCLUSIONS: A quantitative new method was developed to measure frontal symmetry in patients undergoing reconstruction due to breast cancer. The best results were obtained in patients undergoing immediate reconstruction. The method is easy to apply and inexpensive