Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity.

Chemotherapeutic drugs and radiotherapy are fundamental treatments to combat cancer, but, often, the doses in these treatments are restricted by their non-selective toxicities, which affect healthy tissues surrounding tumors. On the other hand, drug resistance is recognized as the main cause of chemotherapeutic treatment failure. Rosmarinic acid (RA) is a polyphenol of the phenylpropanoid family that is widely distributed in plants and vegetables, including medicinal aromatic herbs, consumption of which has demonstrated beneficial activities as antioxidants and anti-inflammatories and reduced the risks of cancers. Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy, mainly due to its scavenger capacity. This review compiles information from 56 articles from Google Scholar, PubMed, and ClinicalTrials.gov aimed at addressing the role of RA as a complementary therapy in cancer treatment.

The role of resilience and coping strategies as predictors of well-being in breast cancer patients.

PURPOSE: This study investigated the role of resilience and coping strategies on breast cancer patients' well-being using a structural equation model. To achieve this objective, a model previously developed by Mayordomo's group was partially replicated using a longitudinal study design in an oncological sample. METHODS: The study was a longitudinal observational survey. Patients with breast cancer were recruited (N = 166). Resilience was measured with the Mexican Resilience Measurement Scale, coping strategies with the Forms of Coping and Dimensions Scale and perception of the psychological well-being with a short-form of Ryff's Scales of Psychological Well-Being at the start and end of adjuvant chemotherapy (T1 and T2 respectively). RESULTS: The results showed stability in the variables over time and revealed differences with respect to Mayordomo's model. The best predictor of well-being at T2 was well-being at T1. In addition, the model indicated that resilience had a direct impact on well-being through problem-focused coping. Indeed, resilience and problem-focused coping best explained well-being at T2. CONCLUSIONS: Both at the start and end of adjuvant chemotherapy for breast cancer, problem-focused coping positively predicted resilience, which in turn was a positive predictor of well-being. On the other hand, emotion-focused coping showed no association with resilience or well-being. As part of the multidisciplinary cancer team, oncology nurses have a key role to play in promoting resilience and problem-focused coping as an important goal of psychosocial interventions in breast cancer patients.

Impact of the SARS-CoV-2 on the journey of high-risk colon cancer patients within the scope of the Unified Health System in Brazil.

BACKGROUND: Colon cancer is an important cause of mortality related to cancer. During the COVID-19 pandemic, an important reallotment of assistance resources was necessary to tackle the crisis, directly impacting medical practice all over the globe. OBJECTIVE: To assess the impact of the Sars-Cov-2 pandemic on the time between diagnosis and the beginning of systemic treatment in patients diagnosed with high-risk colon neoplasia. METHODS: This is a retrospective study based on the analysis of medical records of patients diagnosed with colon neoplasia who required systemic treatment and were treated between March 2019 and March 2022, in a reference Oncology unit of the Brazilian Unified Health System. The study's population was divided into two groups: (I) Pre-COVID-19: diagnoses made between March 2019 and February 2020, (II) COVID-19: diagnoses made between March 2020 and March 2022. RESULTS: The sample consisted of 228 patients, 108 (47.97%) of whom were diagnosed during pre-COVID-19 and 118 (52.21%) diagnosed during the two years-period of COVID-19. Regarding the time between colonoscopy and surgery, the time between surgery and first consultation in clinical oncology, and the time between requesting and beginning of systemic treatment, a statistically significant reduction was observed during the COVID-19 period. CONCLUSION: A decrease in time between diagnosis and systemic treatment of patients with colorectal cancer during the COVID-19 pandemic was observed. Yet, even with this improvement, the time to begin treatment remains greater than the recommended by the current guidelines, regardless of the time of diagnosis (before or after the pandemic), which negatively impacts the disease outcome.

Identification and validation of a novel prognostic model based on platinum resistance-related genes in bladder cancer

ABSTRACT Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.

Identification and validation of a novel prognostic model based on platinum Resistance-related genes in bladder cancer.

BACKGROUND: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. MATERIALS AND METHODS: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. RESULTS: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. CONCLUSION: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.

Caracterización sobre los pacientes operados de cáncer colorrectal tratados con quimioterapia adyuvante en Camagüey

Introducción: El cáncer colorrectal es un problema de salud creciente en el mundo, el aumento en la expectativa de vida de las poblaciones, el continuo mejoramiento de las técnicas de tamizaje y la búsqueda activa de casos, son las razones por las cuales cada año se informa un aumento en el número global de casos diagnosticados con cáncer. Objetivo: Caracterizar a los pacientes operados de cáncer colorrectal tratados con quimioterapia. Métodos: Se realizó un estudio observacional, descriptivo de corte transversal, en pacientes atendidos en la consulta multidisciplinaria de cáncer colorrectal. El universo lo conformaron todos los pacientes que acudieron a consulta en ese período, la muestra a criterio de los autores la conformaron 55 pacientes tratados con quimioterapia adyuvantes por cáncer colorrectal. La fuente primaria de la investigación estuvo dada por la historia clínica. Resultados: En cuanto a la relación sexo y edad, se observó una mayor frecuencia del grupo de 70-79 años y en el sexo femenino. Según la localización topográfica existió predominio en colon sigmoides con 33 pacientes para un 60 % de la muestra estudiada. La variante histológica adenocarcinoma moderadamente diferenciado fue la de mayor presentación. Predominaron los pacientes en estadio IIIa de la enfermedad. El esquema de quimioterapia usado con mayor frecuencia fue el Folfox. Conclusiones: En la muestra, la mayoría de los pacientes estuvieron incluidos en el grupo etáreo entre 70-79 años de edad. La localización topográfica más frecuente fue el colon sigmoide y el tipo histológico, el adenocarcinoma moderadamente diferenciado. Predominaron los pacientes en el estadio IIIa y el tratamiento con quimioterapia adyuvante más utilizado fue el esquema de Folfox.

Introduction: Colorectal cancer is a growing health problem in the world, the increase in the life expectancy of populations, the continuous improvement of screening techniques and the active search for cases, are the reasons why an increase in the global number of cases diagnosed with cancer is reported each year. Objective: To characterize the patients operated on for colorectal cancer treated with adjuvant chemotherapy. Methods: An observational, descriptive, cross-sectional study was carried out in patients seen at the multidisciplinary colorectal cancer clinic. The universe was made up of all the patients who attended the consultation in that period, the sample at the authors' criteria was made up of 55 patients treated with adjuvant chemotherapy for colorectal cancer. The primary source of the investigation was given by the clinical history. Results: Regarding the relationship between sex and age, a higher frequency was observed in the group of 70-79 years and in the female sex. Regarding the topographic location, there was a predominance in the sigmoid colon with 33 patients for 60% of the sample studied. The moderately differentiated adenocarcinoma histological variant was the one with the highest presentation. Patients in stage IIIa of the disease were more frequent. The most frequently used chemotherapy regimen was Folfox. Conclusions: In the sample, most of the patients were included in the age group between 70-79 years of age. The most frequent topographic location was the sigmoid colon and the histological type was moderately differentiated adenocarcinoma. Patients in stage IIIa predominated and the most widely used adjuvant chemotherapy treatment was the Folfox regimen.

Effectiveness and safety of adjuvant chemotherapy compared to neoadjuvant chemotherapy in patients with penile cancer and positive lymph nodes regarding overall survival and free disease survival: a systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of adjuvant chemotherapy compared with neoadjuvant chemotherapy in patients with node-positive penile cancer in terms of overall and disease-free survival. METHODS: We conducted a search strategy in MEDLINE, Embase, and Central databases. We complemented the search with unpublished literature through manual search, conferences, thesis databases, Open Grey, Google Scholar, and Clinicaltrials.gov. There were no restrictions in language. We used the MINORS tool to assess the risk of bias. Furthermore, we performed a random-effects meta-analysis according to the expected heterogeneity. The outcomes were overall survival, progression-free survival, and adverse effects. The Effect measure was hazard ratio (HR) with a confidence interval of 95%. RESULTS: We included 1,197 patients. Seven articles reported overall survival; while 3 reported progression-free survival. The pooled overall survival HR was 1.41 (0.99-2.02), while the progression-free survival HR was 1.63 (1.09-2.44) for adjuvant vs neoadjuvant therapy. An analysis of adverse effects was not possible. CONCLUSIONS: There were no differences when comparing adjuvant vs. neoadjuvant chemotherapy or adjuvant vs. no intervention chemotherapy. We conclude that progression-free survival had a better response with adjuvant chemotherapy when compared with neoadjuvant therapy. We suggest more studies with adequate design to offer a stronger recommendation.

Resultados del tratamiento del hepatoblastoma en los Andes Ecuatorianos / Results of the treatment of hepatoblastoma in the Ecuadorian Andes

RESUMEN: El hepatoblastoma (HB), es una neoplasia maligna, que se origina en el hígado. La supervivencia (SV) depende de la extensión de avance de la enfermedad. El objetivo de este estudio fue determinar diferencias en la SV actuarial global (SVAG) y libre de enfermedad (SVLE) en pacientes con HB, según la extensión de su enfermedad. Serie de casos con seguimiento. Se incluyeron pacientes de entre 4 y 160 meses de edad tratados en un centro oncológico de Los Andes ecuatorianos (2000-2019). Las variables resultado fueron: lóbulo afectado, metástasis pulmonar, infiltración vascular, estadio PRETEXT, riesgo, histología, niveles de alfafetoproteína (AFP), remisión completa (RC), SVAG y SVLE. Se utilizó estadística descriptiva y analítica (Chi2, exacto de Fisher y corrección por continuidad). Se realizaron análisis de SV con curvas de Kaplan Meier y log-rank. Fueron estudiados 28 pacientes (53,6 % hombres), con una mediana de edad de 40 meses. Se verificaron metástasis pulmonares e infiltración vascular en el 25,0 % y 35,7 % de los casos respectivamente. La histología, estadio clínico y riesgo alto fueron mayoritariamente tipo epitelial (42,8 %), PRETEXT II (50,0 %) y riesgo alto (67,8 %) respectivamente. La media de AFP al diagnóstico fue 1055712ng/ml y 9 pacientes alcanzaron RC. La SVAG y SVLE general a 19 años fue 33,1 % y 26,0 % respectivamente. Según su extensión, la SVAG y la SVLE para los pacientes de riesgo estándar y alto fueron 50,0 % y 25,4 % (p=0,148); y 50,0 % y 14,7 % (p=0,037) respectivamente. La SVAG y SVLE verificadas son menores a las reportadas en otros estudios. La SVLE según su extensión, presentó diferencia significativa, sin embargo, este resultado debe ser tomado con cautela debido al número pequeño de pacientes.

SUMMARY: Hepatoblastoma (HB), is a malignant neoplasm, which originates in the liver. Survival (SV) depends on the extent of disease progression. The objective of this study was to determine differences in overall SV (OS) and disease-free (DFS) in patients with HB, according to the extent of their disease. Case series with follow-up. Patients between 4 and 160 months of age treated at an oncology center in the Ecuadorian Andes (2000-2019) were included. The result variables were affected lobe, lung metastasis, vascular infiltration, PRETEXT stage, risk, histology, alpha-fetoprotein levels (AFP), complete remission (RC), OS and DFS. Descriptive and analytical statistics (Chi2, Fisher's exact and continuity correction) were used. SV analyzes were performed with Kaplan Meier and log-rank curves. In this analysis 28 patients (53.6 % men), with a median age of 40 months, were studied. Lung metastases and vascular infiltration were verified in 25.0 % and 35.7 % of the cases, respectively. Histology, clinical stage, and high risk were mainly epithelial type (42.8 %), PRETEXT II (50.0 %), and high risk (67.8 %), respectively. The mean AFP at diagnosis was 1055712 ng / ml and 9 patients achieved CR. OS and DFS at 19 years were 33.1 % and 26.0 % respectively. According to their extension, the OS and DFS for standard and high risk patients were 50.0 % and 25.4 % (p = 0.148); and 50.0 % and 14.7 % (p = 0.037) respectively. The verified OS and DFS are lower than those reported in other studies. DFS according to its extension, presented a significant difference, however, this result should be considered with caution due to the small number of patients.

Impact of the 21-Gene Recurrence Score (Oncotype DX®) on adjuvant therapy decision-making: a collaborative multicenter cohort study from Argentina

Introduction: At present, more than half of patients diagnosed with early-stage breast cancer (BC) and express hormonal receptors will receive some adjuvant chemotherapy scheme, but only a few of them would benefit in terms of survival. Genomic platforms allow a better understanding of the heterogeneity of different types of hormonal receptor-positive and HER2-negative BC. They have proven their validity as tools to identify those patients who will obtain a clear benefit with the indication of chemotherapy treatment. The aim of this study is to analyze the use of the genomic platform, namely, Oncotype Dx® and its impact on the indication of adjuvant treatment, evaluated mainly as the change in treatment indication. Methods: Multicenter observational cohort study was performed in different Mastology units in Argentina. Patients underwent the Oncotype Dx to clarify the adjuvant treatment. Treatment decisions were settled before and after performing Oncotype Dx. Results: From January 2013 to December 2018, 211 patients with luminal A or B and HER2-negative breast carcinomas, who underwent the Oncotype Dx, were included. Based on our records, 40% of the patients change the indication of adjuvant treatment after the performance of the Oncotype Dx. Of these, 24% of patients who underwent initial endocrine therapy only adjusted their treatment with the addition of chemotherapy. Among patients with an initial CTH recommendation, 49% were able to receive endocrine therapy only when, due to traditional prognostic factors, they would have received chemotherapy. Conclusions: In our population, the use of the Recurrence Score was clinically significant in relation to the change of the established treatments. Consequently, it is a very important tool and a decisive factor in the adjuvant indication in patients with positive hormonal receptors and HER2neu-negative early BC.

Enterocolite Neutropênica em Paciente com Câncer de Mama em Uso de Quimioterapia Adjuvante: Relato de Caso / Neutropenic Enterocolitis in a Breast Cancer Patient using Adjuvant Chemotherapy: Case Report / Enterocolitis Neutropénica en Paciente con Cáncer de Mama que Usa Quimioterapia Adyuvante: Reporte de Caso

Introdução: A enterocolite neutropênica (EN) consiste em ulceração ou necrose da mucosa do ceco, íleo terminal e cólon ascendente, sendo uma condição clínica ocasionada como evento adverso de medicamentos, principalmente em esquemas quimioterápicos. Por ser uma condição com alto índice de mortalidade, o presente relato tem como objetivo contribuir significativamente para discussões que envolvem a EN e a participação da equipe multiprofissional no desfecho clínico. Relato do caso: Paciente do sexo masculino, 75 anos, com diagnóstico de câncer de mama, evoluindo com EN após tratamento com quimioterapia adjuvante. A presença de comorbidades e a idade foram os principais fatores complicadores do quadro de tiflite. Por ser uma toxicidade importante e que pode levar à piora do quadro clínico do paciente com câncer, abordar esse tema é fundamental para um diagnóstico mais rápido, com possibilidade de medidas preventivas. Conclusão: Sendo assim, em virtude do notório aumento dos casos de EN, aponta-se como perspectiva a qualificação da equipe de saúde para a inserção de profissionais ainda mais especializados, capazes de contribuir e identificar os sinais e sintomas relacionados com toxicidades hematológicas, resultado de tratamentos quimioterápicos.

Introduction: Neutropenic enterocolitis (NE) consists of ulceration or necrosis of the mucosa of the cecum, terminal ileum, and ascending colon, being a clinical condition caused by an adverse drug event, mainly in chemotherapy regimens. As it is a high mortality rate condition, this report aims to contribute significantly to discussions involving NE and the participation of the multidisciplinary team in the clinical outcome. Case report: This is a 75-year-old male patient diagnosed with Breast Cancer, who developed EN after treatment with adjuvant chemotherapy. The presence of comorbidities and age were the main complicating factors in typhlitis. As it is an important toxicity and can lead to a worsening of the clinical condition of cancer patients, addressing this issue is essential for a faster diagnosis with the possibility of preventive measures. Conclusion: Therefore, in view of the notorious increase of cases of NE, the perspective of the qualification of the health team is pointed out, for the inclusion of even more specialized professionals capable of contributing and identifying the signs and symptoms related to hematological toxicities, result of chemotherapy treatments.

Introducción: La enterocolitis neutropénica (EN) consiste en la ulceración o necrosis de la mucosa del ciego, íleon terminal y colon ascendente, siendo una condición clínica causada por un evento adverso farmacológico, principalmente en regímenes de quimioterapia. Al tratarse de una afección con una alta tasa de mortalidad, este informe tiene como objetivo contribuir de manera significativa a las discusiones que involucran al EN y la participación del equipo multidisciplinario en el resultado clínico. Relato del caso: Paciente masculino, 75 años, diagnosticado de cáncer de mama, que desarrolló EN después del tratamiento con quimioterapia adyuvante. La presencia de comorbilidades y la edad fueron los principales factores de complicación en Tiflite. Como se trata de una toxicidad importante y puede conducir a un empeoramiento de la condición clínica de los pacientes con cáncer, abordar esta cuestión es fundamental para un diagnóstico más rápido con la posibilidad de medidas preventivas. Conclusión: Por tanto, ante el notable incremento de casos de EN, se apunta la perspectiva de la calificación del equipo de salud, para la inclusión de profesionales aún más especializados capaces de aportar e identificar los signos y síntomas relacionados con las toxicidades hematológicas, un resultado de los tratamientos de quimioterapia.

Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer / Eficácia e toxicidade da quimioterapia adjuvante em pacientes com câncer de pulmão de células não pequenas

ABSTRACT Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

RESUMO Objetivo: A quimioterapia adjuvante melhora a sobrevida de pacientes com câncer pulmonar de células não pequenas (CPCNP) ressecado. No entanto, o esquema cisplatina-vinorelbina está relacionado com risco significativo de toxicidade clinicamente relevante. Nosso objetivo foi avaliar a eficácia, segurança e viabilidade da quimioterapia adjuvante para pacientes com CPCNP em um cenário de mundo real. Métodos: Estudo retrospectivo de coorte realizado em um único centro com pacientes com CPCNP em estágio I-III submetidos a cirurgia com intuito curativo entre 2009 e 2018. A quimioterapia adjuvante foi administrada a critério dos médicos. Os pacientes foram divididos em dois grupos: quimioterapia adjuvante e sem quimioterapia adjuvante (grupo controle). Os desfechos estudados foram sobrevida global (SG) e sobrevida livre de recidiva (SLR), bem como o perfil de segurança e viabilidade do esquema cisplatina-vinorelbina em um cenário de mundo real. Resultados: O estudo envolveu 231 pacientes, 80 dos quais receberam quimioterapia adjuvante. Destes, 55 receberam o esquema cisplatina-vinorelbina. As análises de sobrevida estratificadas pelo estágio do tumor mostraram que os pacientes com CPCNP em estágio II que receberam quimioterapia adjuvante apresentaram melhor SLR (p = 0,036) e SG (p = 0,017) do que os do grupo controle. Entre os pacientes com CPCNP em estágio III que receberam quimioterapia adjuvante, a SLR foi melhor (p < 0,001) e houve uma tendência a melhor SG do que no grupo controle (p = 0,060). Dos que receberam o esquema cisplatina-vinorelbina, 29% apresentaram neutropenia febril de grau 3-4, e 9% morreram em virtude de toxicidade. Conclusões: Os resultados confirmam o efeito benéfico da quimioterapia adjuvante em pacientes com CPCNP em um contexto real. No entanto, o esquema cisplatina-vinorelbina relacionou-se com taxas alarmantes de toxicidade e alternativas mais eficazes e menos tóxicas devem ser investigadas.

Tratamiento Neoadyuvante en cáncer de mama HER2 positivo. La era de la terapia dirigida / Neoadjuvant treatment in HER2 positive breast cancer. The Age of Targeted Therapy

Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina

Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine

Câncer de Mama Multifocal: Relato de Caso / Multifocal Breast Cancer: Case Report / Cáncer de Mama Multifocal: Relato de caso

Introdução: O câncer de mama é a neoplasia que mais acomete o sexo feminino, sendo a primeira causa de morte por câncer em mulheres.O carcinoma mamário representa um grupo heterogêneo de doenças. Casos individuais diferem uns dos outros na morfologia, fenótipo e prognóstico. As patologias malignas das mamas podem se manifestar como tumores unifocais, multifocais e/ou multicêntricos. A incidência de tumores multifocais e multicêntricos no câncer de mama varia de 13% a 70%. Relato do caso: Paciente L.C., sexo feminino, 65 anos, com relato de nódulo palpável em mama direita em setembro de 2015. O estudo anatomopatológicodo nódulo mostrou carcinoma intraductal. Realizada quadrantectomia, com anatomopatológico que identificou carcinoma papilífero bem diferenciado intracístico e invasivo damama, associado a componente intraductal cribriforme e papilar, com margens e linfonodo sentinela livres e imuno-histoquímica compatível com perfil triplo-negativo. Em fevereiro de 2019, apresentou duas novas lesões em mama contralateral, identificadas como carcinoma ductal invasivo multifocal com papiloma intraductal associado, e carcinoma ductal invasivo associado a componente intraductal in situ dos tipos papilar, sólido e cribriforme, com imuno-histoquímica com perfis moleculares distintos entre si, sendo uma lesão do tipo luminal A e a outra, luminal híbrido. Conclusão: Este estudo relata um caso de uma paciente que apresentou lesões neoplásicas em ambas as mamas, em tempos distintos e com perfis histológicos e imuno-histoquímicos diferentes. Dessa forma, destacam-se a raridade do caso e a relevância da terapia dirigida a alvos específicos, uma vez que a paciente apresentava lesões com perfis moleculares distintos.

Introduction: Breast cancer is the neoplasm that most affects females, being the first cause of death by cancer in women. Breast carcinoma is a heterogeneous group of diseases. Individual cases differ from each other in morphology, phenotype and prognosis. Malignant breast pathologies can manifest as single, multifocal and/or multicentric tumors. The incidence of multifocal and multicentric tumors in breast cancer varies from 13% to 70%. Case report: Patient L.C., female, 65 years old, with a palpable nodule in the right breast in September 2015. The anatomopathological study of the nodule showed intraductal carcinoma. She underwent quadrantectomy, with anatomopathological examination that identified well-differentiated intracystic and invasive papillary carcinoma of the breast, associated with a cribriform and papillary intraductal component, with free sentinel lymph node and margins and immunohistochemistry compatible with triple negative profile. In February 2019, she presented two new lesions in contralateral breast, identified as invasive multifocal ductal carcinoma, with associated intraductal papilloma, and invasive ductal carcinoma, associated with an in situ intraductal component of the papillary, solid and cribriform types, with immunohistochemistry with different molecular profiles, being one lesion classified as luminal A and the other, hybrid luminal. Conclusion: This study reports a case of a patient who had neoplastic lesions in both breasts, at different times and with distinctive histological and immunohistochemical profiles. Thus, the rarity of the case and the relevance of the therapy aimed at specific targets are highlighted, since the patient presented lesions with different molecular profiles.

Introducción: El cáncer de mama es la neoplasia que más afecta a las mujeres, siendo la primera causa de muerte por cáncer en las mujeres. El carcinoma de mama representa un grupo heterogéneo de enfermedades. Los casos individuales difieren entre sí en morfología, fenotipo y pronóstico. Las patologías mamarias malignas pueden manifestarse como tumores únicos, multifocales y/o multicéntricos. La incidencia de tumores multifocales y multicéntricos en el cáncer de mama varía del 13% al 70%. Relato del caso: Paciente L.C., mujer, 65 años, con un nódulo palpable en el seno derecho en septiembre de 2015. El estudio anatomopatológico de la lesión mostró carcinoma intraductal. La paciente se sometió a una cuadrantectomía, con un examen anatomopatológico que identificó un carcinoma papilar invasivo e intraquístico bien diferenciado de mama, asociado con un componente intraductal cribiforme y papilar, con ganglio linfático y márgens libres y inmunohistoquímica compatible con perfil triple negativo. En febrero de 2019, presentó dos nuevas lesiones en el seno contralateral, identificadas como carcinoma ductal multifocal invasivo, con papiloma intraductal asociado y carcinoma ductal invasivo, asociado con un componente intraductal in situ de los tipos papilar, sólido y cribiforme, con inmunohistoquímica con diferentes perfiles moleculares, siendo una lesión del tipo luminal A y la otra, luminal híbrida. Conclusión: Este estudio reporta un caso de una paciente que tenía lesiones neoplásicas en ambos senos, en diferentes momentos y con diferentes perfiles histológicos e inmunohistoquímicos. Por lo tanto, se destaca la rareza del caso y la relevancia de la terapia dirigida a objetivos específicos, una vez que la paciente presentó lesiones con diferentes perfiles moleculares.

Cáncer colorrectal metastásico: supervivencia global con diferentes alternativas de tratamiento en Lima Metropolitana / Metastatic colorrectal cancer: overall survival rates with different therapy approaches in Lima

Objetivos: Evaluar la supervivencia global del cáncer colorrectal metastásico en Lima Metropolitana de acuerdo a la terapia empleada (independientemente del estado mutacional del gen K-ras) y comparar los resultados con los obtenidos en otros estudios similares en el mundo. Materiales y métodos: Estudio multicéntrico retrospectivo. Se analizaron las historias clínicas de pacientes con cáncer colorrectal metastásico, entre enero del 2010 y diciembre del 2014, en pacientes que fueron tratados en hospitales especializados de Lima Metropolitana. De los 419 casos con diagnóstico de cáncer colorrectal metastásico, 320 cumplieron con los criterios de inclusión correspondientes (76,4%), por lo cual fueron considerados en este estudio. Resultados: La mediana de la edad del total de participantes fue 63 años (rango: 15 a 90 años). El porcentaje de supervivencia a 2 y 5 años fue: 87,3% y 12,9% para aquellos que fueron sometidos a resección de metástasis y fue de 39,6% y 9,1% para aquellos pacientes con tratamiento quimioterápico (con o sin terapia biológica), la diferencia en estos dos grupos fue estadísticamente significativa en favor de la resección de las metástasis (p<0,001). La mediana de supervivencia global fue de 18,1 meses (IC 95%: 16,5-19,7) para el grupo que recibió quimioterapia versus 24,2 meses (IC 95%: 18,1-30,3) para los pacientes que recibieron anticuerpos monoclonales más quimioterapia; aunque, no hubo diferencias significativas. Conclusiones: La supervivencia evaluada en los diferentes grupos del estudio, independientemente del estado mutacional del exón 2 del gen K-ras, estuvo encuadrada dentro de lo que usualmente se puede encontrar reportado en la literatura médica actual.

Objectives: To assess overall survival rates of metastatic colorectal cancer in Lima, according to the therapy schedule used (independently of the K-ras gene mutational status), and to compare these results with those obtained in other similar studies elsewhere. Materials and Methods: This is a retrospective multicenter study. Clinical records of patients with metastatic colorectal cancer treated in specialized Lima hospitals within a time frame between January 2010 and December 2014 were analyzed. Out of 419 cases with a diagnosis of metastatic colorectal cancer, 320 (76.4%) complied with inclusion criteria and were considered for this study. Results: Mean age for participants was 63 years (range: 15 to 90 years). Survival 2-year and 5-year rates were 87.3% and 12.9% for those who underwent metastatic disease resection, and 39.6% and 9.1% for those patients who received chemotherapy (with or without biologics). Differences were statistically significant, favoring metastatic disease resection (p<0.001). Median overall survival rates were 18.1 months (95% CI: 16.5-19.7) for patients treated with chemotherapy and 24.2 months (95% CI: 18.1-30.3) for those who received monoclonal antibodies plus chemotherapy, but there were no significant differences between these groups. Conclusions: Survival rates found in the different groups included in this study, independently of the mutational status of the exon 2 of the K-ras gene, were well within the ranges that have been usually reported in the literature.

Extension of surgical treatment and adjuvant chemotherapy in patients with incidental gallbladder cancer.

OBJECTIVE: To describe the results of the extension of surgical treatment and adjuvant chemotherapy (ACT) in incidental gallbladder cancer (CVB), in terms of postoperative morbidity (POM) and 5-year overall survival rate. METHOD: Case series of patients operated on for incidental GBC in Clínica Mayor, Temuco, Chile (2001-2016). All cases were treated by partial hepatectomy (segments IVb and V), and regional lymphadenectomy. The minimum follow-up time was 12 months. Outcome variables were MPO and 5-year overall survival rate. Other variables of interest were: infiltration depth in vesicular wall, lymph nodes and resected liver; surgical time, need for reoperation, hospital stay, follow-up and mortality. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact and t-test and non-parametrical tests for continuous variables and Kaplan Meier curves. RESULTS: The series was composed of 50 patients, whose average age was 58.6 ± 9.6 years; 68.0% of which were women. The mean surgical time and hospital stay were 224 ± 93 min (90 to 480) and 6.9 ± 2.9 days (4 to 20), respectively. POM was 28.0%. 5-year overall survival rate was 47%. There were no reoperations or mortality. CONCLUSIONS: The results verified in terms of POM and 5-year overall survival rate are similar to previously reported series.

OBJETIVO: Describir los resultados de la extensión del tratamiento quirúrgico y la quimioterapia adyuvante en el cáncer de vesícula biliar (CVB) incidental, en términos de morbilidad posoperatoria (MPO) y de supervivencia global (SVG) a 5 años. MÉTODO: Serie de casos de pacientes intervenidos por CVB incidental en Clínica Mayor, Temuco, Chile (2001-2016). Todos los casos fueron tratados mediante hepatectomía parcial de segmentos IVb y V, y linfadenectomía regional. El tiempo mínimo de seguimiento fue de 12 meses. La variables resultado fueron: MPO y la SVG a 5 años. Otras variables de interés fueron: profundidad de infiltración en la pared vesicular, de linfonodos y del hígado resecado, tiempo quirúrgico, necesidad de reintervención, estancia hospitalaria, seguimiento y mortalidad. Se aplicó estadística descriptiva, y análisis bivariados, aplicando prueba exacta de Fisher y t-test; o pruebas no paramétricas para variables continuas; y curvas de Kaplan-Meier. RESULTADOS: La serie está compuesta por 50 pacientes, con edad media de 58.6 ± 9.6 años; 68.0% de los cuales eran mujeres. La media del tiempo quirúrgico y de estancia hospitalaria fueron 224±93 minutos (90 a 480) y 6.9±2.9 días (4 a 20) respectivamente. La MPO fue 28.0%. La SVG a 5 años fue 47%. No hubo reintervenciones ni mortalidad. CONCLUSIONES: Los resultados verificados en términos de MPO y SVG a 5 años, son similares a los reportados anteriormente.

Fulvestrant-induced toxic epidermal necrolysis

Abstract Toxic epidermal necrolysis is a condition with massive keratinocyte apoptosis, and it is associated with high mortality rates. Fulvestrant, an estrogen receptor antagonist, is indicated in the treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women. To our knowledge, this is the first described case of toxic epidermal necrolysis due to fulvestrant. A 56-year-old woman received 500 mg of intramuscular fulvestrant monthly for metastatic ductal carcinoma of the breast. Five days after the first dose, the patient presented with a maculopapular rash that evolved to blisters, and a detachment of the epidermis in over 30% of the total body surface area. Histological analysis was compatible with toxic epidermal necrolysis. Fulvestrant was discontinued, topical management and supportive care were initiated.

Gene signatures for breast cancer, clinical utility and therapeutic applications / Firmas genéticas para cáncer de mama, utilidad clínica y aplicaciones terapéuticas

Gene signatures quantify hormone receptors and proliferation genes, combining multivariate prediction models. Hormone-negative tumors have greater proliferation and the prognostic value is limited. The first generation of prognostic signatures (Oncotype DX, MammaPrint, Genomic Degree Index) predict recurrence at 5 years. Subsequent tests (Prosigna, EndoPredict, Breast Cancer Index) have better prognostic value for recurrence and are predictive of early relapse. There are no useful prognostic genetic tests for hormone-negative tumors, or predictors of response to treatment. The recent expansion of high-performance technology platforms including the low-cost sequencing of tumor-derived DNA and circulating RNA and the reliable rapid quantification of microRNAs offer new opportunities to build prediction models.

Las firmas genéticas cuantifican receptores hormonales y genes de proliferación, combinando modelos de predicción multivariados. Tumores hormono-negativos tienen mayor proliferación y el valor pronóstico es limitado. La primera generación de firmas de pronóstico (Oncotype DX, MammaPrint, Índice de grado genómico) predicen recurrencia a 5 años. Las pruebas subsecuentes (Prosigna, EndoPredict, Índice de Cáncer de Mama) poseen mejor valor pronóstico para recurrencia y son predictivas de recaída temprana. No existen pruebas genéticas pronósticas útiles para tumores hormono-negativos, ni predictores de respuesta al tratamiento. La reciente expansión de las plataformas tecnológicas de alto rendimiento incluyendo la secuenciación de bajo costo de DNA derivado del tumor y RNA circulante y la cuantificación rápida fiable de microARN ofrecen nuevas oportunidades para construir modelos de predicción.

On thin ice: barriers to adoption of surveillance for patients with stage I testicular seminoma. Survey of US radiation oncologists.

PURPOSE: Most men with stage I testicular seminoma are cured with surgery alone, which is a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (ROs) is unknown. MATERIALS AND METHODS: We surveyed practicing US ROs via an online questionnaire. Respondent's characteristics, self-rated knowledge, perceived patient compliance rates with observation were analyzed for association with treatment recommendations. RESULTS: We received 353 responses from ROs, of whom 23% considered themselves experts. A vast majority (84%) recommend observation as a default strategy, however this rate drops to 3% if the patient is believed to be noncompliant. 33% of respondents believe that survival is jeopardized in case of disease recurrence, and among these respondents only 5% support observation. 22% of respondents over-estimate the likelihood of noncompliance with observation to be in the 50-80% range. Responders with a higher perceived noncompliance rate are more likely to recommend adjuvant therapy (Fisher's exact p<0.01). Only 7% of respondents recommend observation for stage IS seminoma and 45% administer adjuvant RT in patients with elevated pre-orchiectomy alpha-fetal protein levels. CONCLUSIONS: Many US ROs over-estimate the likelihood that stage I testicular seminoma patients will be noncompliant with surveillance and incorrectly believe that overall survival is jeopardized if disease recurs on surveillance. Observation is quickly dismissed for patients who are not deemed to be compliant with observation, and is generally not accepted for patients with stage IS disease. There is clearly an opportunity for improved physician education on evidence-based management of stage I testicular seminoma.

Fatores associados a não reconstrução do trânsito intestinal em pacientes com câncer retal submetidos à ressecção anterior do reto e ileostomia de proteção / Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy

RESUMO Objetivo: avaliar os fatores associados ao não fechamento de ileostomia protetora após ressecção anterior do reto com excisão total do mesorreto por câncer retal, a morbidade associada ao fechamento destas ileostomias e a taxa de estomia permanente em pacientes com adenocarcinoma retal. Métodos: estudo retrospectivo de 174 pacientes consecutivos com diagnóstico de tumores retais, dos quais 92 foram submetidos à ressecção anterior do reto com intenção curativa, anastomose coloanal ou colorretal e ileostomia de proteção. Foi realizada análise multivariada visando a determinar os fatores associados à permanência definitiva da estomia, assim como o estudo da morbidade nos que se submeteram à reconstrução do trânsito. Resultados: no período de seguimento de 84 meses, 54 dos 92 pacientes avaliados (58,7%) tiveram a ileostomia fechada e 38 (41,3%) permaneceram com a estomia. Entre os 62 pacientes que tiveram a ileostomia fechada, 11 (17,7%) apresentaram algum tipo de complicação pós-operatória: três com deiscência de anastomose ileal, cinco com obstrução intestinal, dois com infecção de ferida operatória e um com pneumonia. Oito destes pacientes necessitaram de um novo estoma. Conclusão: de acordo com a análise multivariada, os fatores associados à permanência da estomia foram fístula de anastomose, presença de metástases e fechamento da ileostomia durante quimioterapia.

ABSTRACT Objective: to evaluate the factors associated with non-closure of protective ileostomy after anterior resection of the rectum with total mesorectum excision for rectal cancer, the morbidity associated with the closure of ileostomies and the rate of permanent ileostomy in patients with rectal adenocarcinoma. Methods: we conducted a retrospective study with 174 consecutive patients diagnosed with rectal tumors, of whom 92 underwent anterior resection of the rectum with coloanal or colorectal anastomosis and protective ileostomy, with curative intent. We carried out a multivariate analysis to determine the factors associated with definite permanence of the stoma, as well as studied the morbidity of patients who underwent bowel continuity restoration. Results: In the 84-month follow-up period, 54 of the 92 patients evaluated (58.7%) had the ileostomy closed and 38 (41.3%) remained with the stoma. Among the 62 patients who had the ileostomy closed, 11 (17.7%) presented some type of postoperative complication: three had ileal anastomosis dehiscence, five had intestinal obstruction, two had surgical wound infection, and one, pneumonia. Eight of these patients required a new stoma. Conclusion: according to the multivariate analysis, the factors associated with stoma permanence were anastomotic fistula, presence of metastases and closure of the ileostomy during chemotherapy.

Efeitos da sinvastatina na mucosite gastrointestinal induzida por 5-fluorouracil em ratos / Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats

RESUMO Objetivo: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. Métodos: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. Resultados: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. Conclusão: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

ABSTRACT Objective: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. Methods: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. Results: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. Conclusion: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.