Real-world outcomes of anti-EGFR therapy in advanced non-small cell lung cancer EGFR mutated in Peru.

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.

Comparative Profiling of Circulating Exosomal Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma.

Tuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis. It is estimated that one-third of the world's population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology.

Epidemiology of thymic epithelial tumors: 22-years experience from a single-institution.

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.

[Optimal cytoreduction in advanced ovarian cancer treated with dose-dense paclitaxel and carboplatin followed by interval surgery at the Peruvian National Institute of Neoplastic Diseases]. / Citorreducción óptima en cáncer de ovario avanzado tratado con paclitaxel a dosis densa y carboplatino seguido de cirugía de intervalo en el Instituto Nacional de Enfermedades Neoplásicas del Perú.

OBJECTIVES: To determine the rate of optimal cytoreduction in patients with advanced ovarian cancer who received neoadjuvant chemotherapy with dose-dense carboplatin and paclitaxel followed by interval debulking surgery (IDS). MATERIALS AND METHODS: A retrospective study of a series of cases of Peruvian women treated with neoadjuvant chemotherapy with carboplatin (6 AUC mg/mL/min) and paclitaxel (80 mg/m2 weekly) followed by IDS, at the National Institute of Neoplastic Diseases during the 2010-2014 period. RESULTS: The 41 patients who made it to the interval surgery had a median age of 59 years (range: 47-73 years). In 37 (90.2%) patients, high-grade serous adenocarcinoma histology was reported. Thirty-four (82.9%) achieved optimal cytoreduction and five (14.7%), a complete pathological response. Progression-free survival at one year and two years was 74.7% and 51.8%, respectively. Overall survival at one year and two years was 85.2% and 71.4%, respectively. The risk of progression and death was greater in patients without optimal cytoreduction and in patients with postsurgery levels of carcinoembryonic antigen 125 > 30 U/mL. CONCLUSIONS: Neoadjuvant therapy with dose-dense carboplatin and paclitaxel achieved an elevated frequency of optimal cytoreduction. The post-surgery levels of carcinoembryonic antigen 125 and optimal cytoreduction were independent factors of progression-free survival and overall survival.

OBJETIVOS: Determinar la tasa de citorreducción óptima en pacientes con cáncer de ovario avanzado que recibieron quimioterapia neoadyuvante con carboplatino y paclitaxel dosis densa seguido de cirugía de citorreducción de intervalo (CCI). MATERIALES Y MÉTODOS: Estudio de una serie de casos retrospectiva de mujeres peruanas tratadas con quimioterapia neoadyuvante con carboplatino (AUC 6 mg/ml/min) y paclitaxel (80 mg/m2 semanal) seguido de CCI, en el Instituto Nacional de Enfermedades Neoplásicas durante el período 2010-2014. RESULTADOS: Los 41 pacientes que alcanzaron cirugía de intervalo, tuvieron una mediana de edad de 59 años (rango: 47-73 años). En 37 (90,2%) pacientes se reportó histología de adenocarcinoma seroso de alto grado. Treinta y cuatro (82,9%) lograron citorreducción óptima y cinco (14,7%) respuesta patológica completa. La sobrevida libre de progresión al año y 2 años fueron 74,7% y 51,8%, respectivamente. La sobrevida global al año y 2 años fue 85,2% y 71,4%, respectivamente. El riesgo de progresión y muerte fue mayor en pacientes sin citorreducción óptima y pacientes con niveles de dosaje del antígeno carcinoembrionario 125 postoperatorio > 30 U/ml. CONCLUSIONES: La neoadyuvancia con carboplatino y paclitaxel dosis densa logró una frecuencia elevada de citorreducción óptima. Los niveles de antígeno carcinoembrionario 125 postoperatorios y citorreducción óptima resultaron factores independientes de sobrevida libre de progresión y sobrevida global.

[Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas]. / Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas.

OBJECTIVE: To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. MATERIALS AND METHODS: Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. RESULTS: 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. CONCLUSIONS: Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

OBJETIVOS: Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. MATERIALES Y MÉTODOS: Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. RESULTADOS: 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. CONCLUSIONES: El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

Citorreducción óptima en cáncer de ovario avanzado tratado con paclitaxel a dosis densa y carboplatino seguido de cirugía de intervalo en el Instituto Nacional de Enfermedades Neoplásicas del Perú / Optimal cytoreduction in advanced ovarian cancer treated with dose-dense paclitaxel and carboplatin followed by interval surgery at the Peruvian National Institute of Neoplastic Diseases

RESUMEN Objetivos. Determinar la tasa de citorreducción óptima en pacientes con cáncer de ovario avanzado que recibieron quimioterapia neoadyuvante con carboplatino y paclitaxel dosis densa seguido de cirugía de citorreducción de intervalo (CCI). Materiales y métodos. Estudio de una serie de casos retrospectiva de mujeres peruanas tratadas con quimioterapia neoadyuvante con carboplatino (AUC 6 mg/ml/min) y paclitaxel (80 mg/m2 semanal) seguido de CCI, en el Instituto Nacional de Enfermedades Neoplásicas durante el período 2010-2014. Resultados . Los 41 pacientes que alcanzaron cirugía de intervalo, tuvieron una mediana de edad de 59 años (rango: 47-73 años). En 37 (90,2%) pacientes se reportó histología de adenocarcinoma seroso de alto grado. Treinta y cuatro (82,9%) lograron citorreducción óptima y cinco (14,7%) respuesta patológica completa. La sobrevida libre de progresión al año y 2 años fueron 74,7% y 51,8%, respectivamente. La sobrevida global al año y 2 años fue 85,2% y 71,4%, respectivamente. El riesgo de progresión y muerte fue mayor en pacientes sin citorreducción óptima y pacientes con niveles de dosaje del antígeno carcinoembrionario 125 postoperatorio > 30 U/ml. Conclusiones . La neoadyuvancia con carboplatino y paclitaxel dosis densa logró una frecuencia elevada de citorreducción óptima. Los niveles de antígeno carcinoembrionario 125 postoperatorios y citorreducción óptima resultaron factores independientes de sobrevida libre de progresión y sobrevida global.

ABSTRACT Objectives. To determine the rate of optimal cytoreduction in patients with advanced ovarian cancer who received neoadjuvant chemotherapy with dose-dense carboplatin and paclitaxel followed by interval debulking surgery (IDS). Materials and Methods. A retrospective study of a series of cases of Peruvian women treated with neoadjuvant chemotherapy with carboplatin (6 AUC mg/mL/min) and paclitaxel (80 mg/m2 weekly) followed by IDS, at the National Institute of Neoplastic Diseases during the 2010-2014 period. Results. The 41 patients who made it to the interval surgery had a median age of 59 years (range: 47-73 years). In 37 (90.2%) patients, high-grade serous adenocarcinoma histology was reported. Thirty-four (82.9%) achieved optimal cytoreduction and five (14.7%), a complete pathological response. Progression-free survival at one year and two years was 74.7% and 51.8%, respectively. Overall survival at one year and two years was 85.2% and 71.4%, respectively. The risk of progression and death was greater in patients without optimal cytoreduction and in patients with postsurgery levels of carcinoembryonic antigen 125 > 30 U/mL. Conclusions. Neoadjuvant therapy with dose-dense carboplatin and paclitaxel achieved an elevated frequency of optimal cytoreduction. The post-surgery levels of carcinoembryonic antigen 125 and optimal cytoreduction were independent factors of progression-free survival and overall survival.

Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas / Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas

RESUMEN Objetivos Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. Materiales y métodos Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. Resultados 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. Conclusiones El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

ABSTRACT Objective To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Materials and methods Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. Results 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Conclusions Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

Topoisomerase II-α as a predictive factor of response to therapy with anthracyclines in locally advanced breast cancer.

BACKGROUND: Topoisomerase II-α is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-α expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-α overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients. MATERIAL AND METHODS: Topoisomerase II-α, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-α status and dose intensity. RESULTS: Tumors from 40 patients (36%) showed topoisomerase II-α overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-α expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-α (P=0.010 and 0.027, respectively). Negative PR (P=0.041), positive HER2 (P=0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-α negative shown no significance (HR=0.92, IC 95% 0.39-2.15, P=0.839) while the multivariate analysis in topoisomerase II-α positive, dose intensity shown to be statistically significant (HR=2.725, IC 95% 1.07-6.95, P=0.036). CONCLUSIONS: Our data do not support a correlation between topoisomerase II-α expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-α may experience better clinical benefit with higher anthracycline dose intensity.