Satisfação com os cuidados de enfermagem de pacientes oncológicos em uso de antineoplásicos ambulatorial / Satisfaction with nursing care of oncology patients on outpatient antineoplastic drugs / Satisfacción con los cuidados de enfermería en pacientes oncológicos que utilizan fármacos antineoplásicos en régimen ambulatorio

RESUMO Objetivo: avaliar a satisfação do usuário oncológico ambulatorial em uso de antineoplásicos sobre os cuidados de enfermagem. Métodos: estudo transversal com abordagem quantitativa, realizado no Serviço de Quimioterapia de um hospital universitário localizado em Belém-PA - Brasil, com 200 usuários no período de junho de 2019 a junho de 2022, através de entrevista e uso do Instrumento de Satisfação do Paciente. Aplicou-se análise de qui-quadrado de Pearson e considerou-se p-valor ≤0,05. Resultados: os usuários relataram bom índice de satisfação na média geral dos domínios (>90%), destacando o domínio técnico-profissional, seguido do educacional e confiança. As variáveis de esclarecimento sobre as orientações médicas, dar bons conselhos, tomar iniciativa após as respostas dos pacientes foram associadas à satisfação do usuário conforme a topografia do câncer e a disponibilidade da equipe àqueles com diferentes graus de estadiamento. Conclusão: este estudo auxilia gestores na identificação e planejamento de melhorias nas áreas e serviços.

ABSTRACT Objective: Evaluate the satisfaction of outpatient oncology users taking antineoplastic drugs about nursing care. Methods: Exsectional study with a quantitative approach, carried out at the Chemotherapy Service of a university hospital located in Belém-PA - Brazil, with 200 users, from June 2019 to June 2022, through interviews and use of the Patient Satisfaction Instrument. Chi-square analysis, Pearson p-value, and chi-square analysis were applied, and the p-value ≤ 0.05 was considered. Results: Users reported good satisfaction in the overall average of the domains (>90%), highlighting the technical-professional domain, followed by the educational and confidence domains. The variables of clarification of medical guidelines, giving good advice, and taking the initiative after patient responses were associated with user satisfaction according to cancer topography and staff availability to those with different degrees of staging. Conclusion: This study assists managers in identifying and planning improvements in areas and services.

RESUMEN Objetivo: evaluar la satisfacción de los usuarios de oncología ambulatoria que utilizan fármacos antineoplásicos sobre los cuidados de enfermería. Métodos: estudio seccional con enfoque cuantitativo, realizado en el Servicio de Quimioterapia de un hospital universitario situado en Belém-PA - Brasilcon 200 usuarios en el período de junio de 2019 a junio de 2022, mediante entrevista y utilización del Instrumento de Satisfacción del Paciente. Se aplicó el análisis chi-cuadrado de Pearson y el valor p ≤0,05. Resultados: los usuarios declararon una buena satisfacción en la media global de los dominios (>90%), destacando el dominio técnico-profesional, seguido de los dominios educativo y de confianza. Las variables de aclaración sobre las directrices médicas, dar buenos consejos, tomar la iniciativa tras las respuestas de los pacientes se asociaron con la satisfacción de los usuarios según la topografía del cáncer y la disponibilidad del personal ante los distintos grados de estadificación. Conclusión: este estudio ayuda a los directivos a identificar y planificar mejoras en áreas y servicios.

Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Impact of quality of response on survival outcomes among multiple myeloma patients treated with novel agents - a retrospective analysis

Abstract BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Niš, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.

Boas Práticas na Administração do Rituximab: Revisão Integrativa da Literatura / Good practices in Rituximab Administration: Integrative Literature Review / Buenas Prácticas en la Administración de Rituximab: Revisión Integradora de la Literatura

Introdução: O rituximab é um anticorpo monoclonal quimérico camundongo/humano, amplamente utilizado no cenário terapêutico de vários diagnósticos. Por apresentar diferentes protocolos de administração, manejo e efeitos adversos, seu uso requer atenção da equipe de saúde. Objetivo: Descrever os protocolos infusionais do rituximab na primeira infusão, nas subsequentes e na dessensibilização, e caracterizar a sua segurança. Método: Revisão integrativa da literatura. A busca pelos periódicos foi realizada nas bases de dados e bibliotecas eletrônicas: LILACS, PubMed, MEDLINE, SciELO e BDEnf. Resultados: O cruzamento dos descritores proporcionou a identificação de 413 artigos. Destes, 113 foram lidos na íntegra e, ao final, 16 artigos foram aplicáveis ao desenho do estudo. Os artigos foram publicados entre os anos de 2016 e 2020, com predomínio da língua inglesa (87,5%). Quanto às principais formas de administração do medicamento, nove estudos abordaram a infusão por via intravenosa (em variadas modalidades de tempo) e sete por via subcutânea. Conclusão: De acordo com a literatura científica, todas as modalidades de infusão intravenosa e subcutânea demostram ser seguras e eficazes se os protocolos forem adequadamente indicados e corretamente aplicados

Introduction: Rituximab is a mouse/human chimeric monoclonal antibody, widely used in the therapeutic setting of various diagnoses, due to its different administration, management and adverse effects protocols; its use requires attention by the healthcare team. Objective: Describe the infusion protocols for rituximab in the first, subsequent and desensitization infusions, and characterize their safety. Method: Integrative literature review. The search was performed in databases and electronic libraries: LILACS, PubMed, MEDLINE, SciELO and BDEnf. Results: In all, 413 articles were eligible after crossing the descriptors. Of these, 113 were read in full and eventually, 16 articles matched the study design. The articles were published from 2016 to 2020, predominantly in English (87.5%). Concerning the main routes of administration in the studies included, nine addressed the intravenous infusion (in different modalities of time) and seven, subcutaneously. Conclusion: According to the scientific literature, all intravenous and subcutaneous infusion modalities are shown to be safe and effective if the protocols are correctly selected and applied

Introducción: Rituximab es un anticuerpo monoclonal quimérico de ratón/humano, ampliamente utilizado em el ámbito terapéutico de diversos diagnósticos. Debido a sus diferentes protocolos de administración, manejo y efectos adversos, su uso requiere la atención del equipo de salud. Objetivo: Describirlos protocolos de infusión de rituximab em la primera, subsiguiente y desensibilización, y caracterizar su seguridad. Método: Es una revisión integradora de la literatura. La búsqueda de revistas se realizó en bases de datos y bibliotecas electrónicas: LILACS, PubMed, MEDLINE, SciELO y BDEnf. Resultados: Cruzar los descriptores proporciono la elegibilidad de 413 artículos. De estos, 113 fueron leí dos íntegramente y al final, 16 artículos fueron aplicables al diseño del estudio. Los artículos fueron publicados entre 2016 y 2020, con predominio del inglés (87,5%). En cuanto a las principales formas de administración del fármaco, entre los estudios incluidos, nueve abordaron la infusión intravenosa (en diferentes modalidades de tiempo) y siete la vía subcutánea. Conclusión: Según la literatura científica, todas las modalidades de infusión intravenosa y subcutánea se muestran seguras y efectivas si los protocolos están debidamente indicados y correctamente aplicados

Quimioterapia metronômica em tumores sólidos: dos conceitos à prática clínica - uma revisão narrativa / Metronomic chemotherapy in solid tumor: practice clinical and concepts ­ narrative review

O tratamento metronômico consiste na administração regular e contínua de quimioterápicos em baixa dose, preferivelmente via oral, sem pausas prolongadas, com objetivo de bloquear a proliferação tumoral. Este tratamento tem sido utilizado para uma série de tumores e nos últimos anos notou-se aumento da utilização em estudos clínicos, principalmente no cenário paliativo. Objetivo: Realizar uma revisão narrativa acerca do tema quimioterapia metronômica em tumores sólidos, nos seus aspectos de definição, racional biológico, indicação clínica, marcadores preditivos e prognósticos. Metodologia: Foi realizada uma pesquisa na base de dados PUBMED, maior base de dados de conteúdo médico, onde foram encontrados 575 artigos, dos quais 46 artigos se adequavam aos critérios de seleção (artigos em inglês publicados no período compreendido entre 2015 a 2020), dentre eles 32 artigos de revisão, 1 metanálise, 2 retrospectivos, 9 prospectivos e 2 descritivos. E, após análise pormenorizada, 529 artigos foram excluídos devido aos critérios de exclusão: artigos em outras línguas que não inglês e a utilização apenas de anticorpo, imunoterapia ou terapia alvo molecular sem quimioterapia associados. Resultados: A partir da análise dos 46 artigos, foram encontrados descrições acerca dos aspectos conceituais, teorias metronômicas, efeito angiogênico, imunológico e quiescência tumoral, efeito 4 "D" e indicação clínica, avaliação de eficácia, segurança, marcadores, precisão e custo efetividade. Conclusão: Verificou-se que evidências clínicas e pré-clínicas suportam o uso de quimioterapia metronômica como uma alternativa ao tratamento oncológico padrão em cenário de acesso restrito a novas drogas, tais como: terapia alvo ou imunoterapia, sendo a principal característica sua baixa toxicidade, acessibilidade, disponibilidade de drogas para administração oral e alta atividade anti-angiogênica, além de outros efeitos diretos e indiretos, os quais se traduzem em benefício clínico

Metronomic treatment consists of regular and continuous administration of low-dose chemotherapy, preferably orally, without prolonged pauses, with the aim of blocking tumor proliferation. This treatment has been used for a number of tumors and, in recent years, there has been an increase in its use in clinical studies, especially in the palliative setting. Objective: To carry out a narrative review on the topic metronomic chemotherapy in solid tumors, in its aspects of definition, biological rationale, clinical indication, predictive and prognostic markers. Methodology: A search was carried out in the PUBMED database, the largest database of medical content, where 575 articles were found, of which 46 articles fit the selection criteria (articles in English published between 2015 and 2020), among them 32 review articles, 1 meta-analysis, 2 retrospective, 9 prospective and 2 descriptive. And, after a detailed analysis, 529 articles were excluded, due to the exclusion criteria: articles in languages other than English and the use of antibody alone, immunotherapy or molecular targeted therapy without associated chemotherapy. Results: From the analysis of the 46 articles, descriptions were found about the conceptual aspects, metronomic theories, angiogenic, immunological and tumor quiescence effects, 4 "D" effect and clinical indication, evaluation of efficacy, safety, markers, precision and cost effectiveness . Conclusion: It was found that clinical and preclinical evidence support the use of metronomic chemotherapy as an alternative to standard cancer treatment in a scenario of restricted access to new drugs, such as targeted therapy or immunotherapy, the main feature being its low toxicity, accessibility, availability of drugs for oral administration and high anti-angiogenic activity, in addition to other direct and indirect effects, which translate into clinical benefit

A phase 2 trial of short-course Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) at interval cytoreductive surgery (iCRS) for advanced ovarian cancer / Quimioterapia Intraperitoneal Hipertérmica (HIPEC) de curta duração ao tempo da cirurgia citorredutora de intervalo (iCRS) para câncer de ovário avançado: ensaio clínico de fase 2

ABSTRACT Objective: to report the final analysis of a phase 2 trial assessing the efficacy and safety of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with advanced epithelial ovarian cancer (EOC). Methods: this was an open-label, multicenter, single-arm trial of HIPEC in patients with advanced EOC who underwent interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy (NACT). HIPEC was performed as a concentration-based regimen of platinum-based chemotherapy for 30 minutes. Primary endpoint was the rate of disease progression occurring at nine months following iCRS plus HIPEC (PD9). Secondary endpoints were postoperative complications, time to start adjuvant chemotherapy, length of hospital and ICU stay, quality of life (QoL) over treatment, and ultimately 2-year progression-free survival (PFS) and overall survival (OS). Analysis was by intention-to-treat with final database lock for survival outcomes on February 23, 2021. Results: fifteen patients with stage III EOC were enrolled between February 2015 and July 2019, in four centers. The intention to treat PD9 was 6.7%. With a median follow-up of 33 months (IQR, 24.3-46.5), the median PFS was 18.1 months and corresponding 2-year rates of PFS and OS was 33.3% and 93.3%, respectively. Three patients (20%) experienced graded III complications. Median length of hospital and ICU stay was 5 (IQR, 4-6.5) and 1 (IQR, 1-1) days, respectively. Time to restart systemic chemotherapy was 39 (IQR, 35-49.3) days and no significant difference over time in QoL was observed. Conclusions: we demonstrate preliminary efficacy and safety of short-course HIPEC in patient with advanced EOC.

RESUMO Objetivo: apresentar a análise final de ensaio clínico de fase 2 que avaliou a eficácia e a segurança da quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração em pacientes com câncer epitelial de ovário avançado (EOC). Métodos: estudo aberto, multicêntrico, de braço único avaliando a HIPEC em pacientes com EOC avançado submetidos a cirurgia citorredutora de intervalo (iCRS) após quimioterapia neoadjuvante (NACT). A HIPEC foi realizada como regime baseado na concentração de cisplatina, perfundida por 30 minutos. O desfecho primário foi a taxa de progressão da doença 9 meses após a iCRS com HIPEC (PD9). Os desfechos secundários foram complicações pós-operatórias, tempo para iniciar a quimioterapia adjuvante, tempo de internação e permanência em UTI, qualidade de vida (QoL) ao longo do tratamento e, finalmente, sobrevida cumulativa livre de progressão (PSF) e global (OS) em 2 anos. As análises foram em intenção de tratar (ITT) com fechamento dos dados para análise da sobrevida em 23 de fevereiro de 2021. Resultados: quinze pacientes com EOC em estágio III foram incluídos no estudo entre fevereiro de 2015 e julho de 2019 em quatro centros recrutadores. A PD9 por ITT foi de 6,7%. Com acompanhamento mediano de 33 meses (IQR, 24,3-46,5), a PFS mediana foi de 18,1 meses e as taxas correspondentes de PFS e OS em 2 anos foram 33,3% e 93,3%, respectivamente. Três pacientes (20%) apresentaram complicações grau III. O tempo mediano de internamento hospitalar e em UTI foi de 5 (IQR, 4-6,5) e 1 (IQR, 1-1) dias, respectivamente. O tempo para reinício da quimioterapia sistêmica foi de 39 dias (IQR, 35-49,3) e não foi observada diferença significativa na QoL ao longo do tratamento. Conclusões: demonstrou-se eficácia e segurança preliminares da HIPEC de curta duração em pacientes com EOC avançado.

Terapias sistémicas en carcinoma hepatocelular: secuencia de tratamientos / Systemic therapies in hepatocellular carcinoma: sequencing of treatment

El carcinoma hepatocelular (CHC) es una de las principales causas de morbilidad y mortalidad relacionada con el cáncer en todo el mundo. La mayoría de los casos ocurren en un contexto de cirrosis o hepatitis crónica. Los pacientes con CHC avanzado no disponían de terapias efectivas hasta el 2008, cuando el sorafenib, un inhibidor de la tirosina quinasa multi-target, demostró un beneficio en comparación con el placebo, en términos de supervivencia y tiempo a progresión de la enfermedad. Desde el 2016, diferentes tratamientos de primera y segunda línea con mecanismos de acción similares (lenvatinib, regorafenib, cabozantinib, ramucirumab) demostraron eficacia. Sin embargo, la investigación de fármacos que inhiben otras vías tumorales seguía siendo de máxima prioridad y los inhibidores de puntos de control inmunitario (ICI) mostraron resultados prometedores en el ámbito clínico para el tratamiento del CHC, revolucionando el manejo en estos pacientes. Recientemente, el anticuerpo contra la proteína de muerte programada-1 (PD-1), atezolizumab combinado con bevacizumab, demostró superioridad sobre el sorafenib en un ensayo clínico aleatorizado de fase III, convirtiéndose en la terapia de elección en primera línea. Actualmente están emergiendo resultados de múltiples estudios de fase III, que continuarán modificando el tratamiento del CHC. En este artículo se revisa la evolución y los cambios recientes de las terapias sistémicas para CHC, mostrando la secuencia actual de estos tratamientos, una vez iniciados.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Most cases occur in the context of cirrhosis or chronic liver inflammation. Patients with advanced HCC had no effective therapies until 2008, when sorafenib, a multi-target tyrosine kinase inhibitor, showed beneficial results when compared to placebo in terms of survival and time to progression. Since 2016, different first and second line treatments with similar mechanisms of action (lenvatinib, regorafenib, cabozantinib, ramucirumab) have shown efficacy. However, researchstudies with drugs that inhibit other tumor pathways remained a top priority, and immune checkpoint inhibitors (ICIs) showed promising results in the clinical setting of HCC management. Recently, antibodies against the programmed death protein-1 (PD-1), atezolizumab combined with bevacizumab, have shown superiority over sorafenib in a randomized phase III clinical trial, becoming the first-line therapy of choice. Results from multiple phase III studies are currently emerging, which will continue to modify HCC treatment. This article reviews recent developments and changes in systemic therapies for HCC, showing the current sequencing of these treatments once they begin.

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) en el tratamiento de la carcinomatosis peritoneal: primeros casos en Chile / PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) in the treatment of peritoneal carcinomatosis: first cases in Chile

Resumen Introducción: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) Es una técnica que, vía laparoscopía, permite administrar quimioterapia en aerosol intraperitoneal, para el tratamiento de la carcinomatosis, ya sea para disminuir masa tumoral y aumentar la resecabilidad, o como paliación sintomática. Objetivo: Presentar los dos primeros casos de PIPAC en Chile, las consideraciones técnicas y revisión de la literatura. Pacientes y Método: Se describe la forma en que un programa PIPAC fue implementado en Clínica Las Condes. Se describe la técnica. Este procedimiento se realizó en dos pacientes, ambas portadoras de carcinomatosis con ascitis refractaria. Resultados: No hubo complicaciones. Alta a las 24 h. Ambas pacientes presentaron disminución de la ascitis, la que se ha mantenido a los seis meses de seguimiento. Discusión: PIPAC es una técnica emergente, que ha demostrado ser segura, con escasas complicaciones, cuya indicación incluye carcinomatosis por cáncer de colon y ovario y que se está extendiendo a páncreas, vía biliar y estómago. Su rol exacto está por definirse. Conclusiones: PIPAC es una técnica factible de realizar en nuestro país; sus resultados preliminares son alentadores y exentos de complicaciones.

Introduction: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy is a technique that allows laparoscopic administration of aerosol chemotherapy in the peritoneum. This procedure is utilized for treatment of carcinomatosis, for debulk abdominal tumors, increasing resectability, or for palliation of abdominal symptoms. Aim: To present the first two cases of PIPAC performed in Chile, technical considerations and review of the literature. Patients and Method: The way this program was started at Clínica Las Condes is presented. The technique is described. This procedure was performed in two females, both with refractory ascites due to carcinomatosis. Results: The procedure was uneventfully and patients were discharged 24 hours later. Both patients showed important reduction of ascites, maintained at 6 months of followup. Discussion: PIPAC is a safe emerging technique, with low complication rate. It is indicated in carcinomatosis of colonic and ovarían origin and in selected cases of pancreatic, bile duct and gastric carcinomatosis. More prospective, randomized studies should be done to stablish its exact role. Conclusions: PIPAC is a feasible technique to perform in our country. Preliminary results are encouraging and no complications were observed.

Optimizing the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma / Otimização da dose efetiva da mitomicina C, do 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular

ABSTRACT Purpose: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. Methods: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. Results: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. Conclusion: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma.

RESUMO Objetivo: Otimizar a dose efetiva de mitomicina C, 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular (CBC). Métodos: Culturas de células de células de carcinoma basocelular e de fibroblastos foram tratadas com diferentes concentrações de mitomicina C, 5fluorouracil e combinação de ambos. Além disto, foram investigados a viabilidade celular, o ciclo celular, a apoptose e a expressão dos genes TP53, CDKN1A e CDK6. O medicamento mais eficaz, em sua dosagem otimizada, foi administrado em últiplas injeções intralesionais em uma mulher de 65 anos com carcinoma basocelular nódulo-ulcerativo periorbital avançado. Resultados: A concentração de 0,00312 mg/mL de mitomicina C e a de 0,312 mg/mL de 5fluorouracil foram consideradas as ideias. A viabilidade média das células de carcinoma basocelular tratadas com mitomicina C isoladamente e em combinação foi significativamente menor que nas células de controle (respectivamente, p=0,002 e p=0,04). Todos os grupos de carcinoma basocelular tratados demonstraram interrupção do ciclo celular na fase S. As células de carcinoma basocelular tratadas com mitomicina C mostraram maiores taxas de apoptose (p=0,002) e significativa regulação positiva do gene TP53 (p=0,0001). Além disso, o gene CDKN1A foi positivamente regulado e o gene CDK6 foi negativamente regulado em células de carcinoma basocelular tratadas com 5fluorouracil (respectivamente, p=0,0001 e p=0,01) ou com a combinação de medicamentos (respectivamente, p=0,007 e p=0,001). Injeções posteriores de mitomicina C na paciente em questão levaram à melhora significativa da lesão do carcinoma basocelular. Conclusão: Nossos resultados in vitro otimizaram as doses efetivas de mitomicina C e 5fluorouracil na cultura de células de carcinoma basocelular e mostraram que a mitomicina C tem mais eficácia na apoptose de células de carcinoma basocelular do que o 5fluorouracil e a combinação de ambos. Injeções intralesionais de doses otimizadas de mitomicina C podem ser propostas para o tratamento não cirúrgico do células de carcinoma basocelular avançado de pálpebra.

Supervivencia relacionada con la respuesta patológica, luego de quimioterapia neoadyuvante en cáncer de mama / Survival related to pathological response, after Neoadjuvant Chemotherapy in breast cancer

Quimioterapia neoadyuvante (NAC) en cáncer de mama permite conocer la sensibilidad del tumor al tratamiento, alcanzar respuesta patológica completa (pRC), está asociada a mejor supervivencia en cáncer de mama localmente avanzado. El objetivo de este estudio fue conocer el impacto de la pRC en la supervivencia en una cohorte de pacientes tratadas con NAC y cirugía. Se realizo un estudio de diseño observacional de tipo retrospectivo, correlacional, con un seguimiento promedio de 90 meses, de una cohorte de pacientes tratadas con NAC y cirugía desde enero del 2009 a diciembre del 2011. El análisis de datos se realizó mediante el software estadístico SPSS v22.0, para el análisis de supervivencia se utilizó el método de Kaplan Meier, para comparar supervivencias se consideró significativa una p<0,05. Entre las características principales de 199 pacientes, se destacan: edad joven a la presentación, elevado índice de proliferación y alta frecuencia del tipo inflamatorio. pRC ocurrió en el 14,1% de pacientes y la supervivencia global (SG) de acuerdo con la respuesta patológica se comparó entre aquellas pacientes que obtuvieron pRC, con las que tuvieron enfermedad residual, con una SG del 71,4% vs 45% respectivamente, con una diferencia significativa (p:0.009). En esta cohorte de pacientes la pRC impactó en la supervivencia en todos los subtipos clínico-patológicos, sobre todo en el subtipo triple negativo. Evaluar los datos en el entorno real es importante para definir estrategias y mejorar los resultados.

Neoadjuvant chemotherapy (NAC) in breast cancer allows knowing the sensitivity of the tumor to treatment, achieving pathological response complete (pRC), and is associated with better survival in locally advanced breast cancer. The objective of this study was to determine the impact of pRC on survival in a cohort of patients treated with NAC and surgery. A retrospective, correlational observational design study was carried out, with an average follow-up of 90 months, of a cohort of patients treated with NAC and surgery from January 2009 to December 2011. Data analysis was performed using the software SPSS v22.0 statistic, for the survival analysis the Kaplan Meier method was used, to compare survivals a p <0.05 was considered significant. Among the main characteristics of 199 patients, the following stand out: young age at presentation, high proliferation index and high frequency of the inflammatory type. pRC occurred in 14.1% of patients and overall survival (OS) according to the pathological response was compared between those patients who obtained pRC, with those who had residual disease, with an OS of 71.4% vs 45% respectively, with a significant difference (p: 0.009). In this cohort of patients, pRC impacted on survival in all clinicopathological subtypes, especially in the triple negative subtype. Evaluating data in the real environment is important to define strategies and improve results.

Central nervous system international prognostic index impacts overall survival in diffuse large b-cell lymphoma treated with r-chop in a third level cancer center from Mexico: a survey of 642 patients

Background: Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. Objective: The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). Methods: In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. Results: Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. Conclusions: CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Factors affecting pathological complete response after neoadjuvant chemotherapy in breast cancer: a single-center experience

SUMMARY OBJECTIVE: The aim of this study was to examine the characteristics of patients admitted to our hospital with a diagnosis of breast cancer who reached pathological complete response after being operated following eight cycles of neoadjuvant chemotherapy. METHODS: Between 2015-2020, patients with pathological complete response who were operated on after neoadjuvant chemotherapy and sent to our clinic for radiotherapy were evaluated. RESULTS: The median age of the patients was 51 years. The most common histological type was invasive ductal cancer. The number of pathological complete response patients was 74 (28%), and the number of non-pathological complete response patients was 188 (72%). Patients with pathological complete response had a smaller tumor diameter than the non-pathological complete response group (p=0.001). For pathological complete response, T1 stage, N1 stage, NG 3, Ki-67 >20%, negative estrogen receptor, negative progesterone receptor, positive Cerb-B2, and adding trastuzumab to chemotherapy were statistically significant (p<0.05). Before neoadjuvant chemotherapy, stage T1-T2 (p=0.036), LN0-1 (p=0.026), Cerb-B2 positivity (p=0.025), and an initial nuclear grade of three (p=0.001) were found to be the factors affecting pathological complete response. CONCLUSIONS: With neoadjuvant chemotherapy, the size of locally advanced tumors decreases, allowing breast conserving surgery. The neoadjuvant chemotherapy response can be used as an early indicator of the prognosis of patients with breast cancer. Today, neoadjuvant chemotherapy is also used for patients with early-stage, operable breast cancer because it has been shown in many studies that reaching pathological complete response is associated with positive long-term results. If we can identify patients who have reached pathological complete response before neoadjuvant chemotherapy, we think we can also determine a patient-specific treatment plan at the beginning of treatment.

Uterine rescue in high-risk gestational trophoblastic neoplasia treated with ema-co by uterine arteries embolization due to arteriovenous malformations / Resgate uterino em neoplasia trofoblástica gestacional de alto risco tratada com EMA-CO por embolização de artérias uterinas devido a malformações arteriovenosas

Abstract Complete hydatidiform mole (CHM) is a rare type of pregnancy, in which 15 to 20% of the cases may develop into gestational trophoblastic neoplasia (GTN). The diagnostic of GTN must be done as early as possible through weekly surveillance of serum hCG after uterine evacuation.We report the case of 23-year-old primigravida, with CHM but without surveillance of hCG after uterine evacuation. Two months later, the patient presented to the emergency with vaginal bleeding and was referred to the Centro de Doenças Trofoblásticas do Hospital São Paulo. She was diagnosed with high risk GTN stage/score III:7 as per The International Federation of Gynecology and Obstetrics/World Health Organization (FIGO/WHO). The sonographic examination revealed enlarged uterus with a heterogeneous mass constituted of multiple large vessels invading and causing disarrangement of the myometrium. The patient evolved with progressive worsening of vaginal bleeding after chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) regimen. She underwent blood transfusion and embolization of uterine arteries due to severe vaginal hemorrhage episodes, with complete control of bleeding. The hCG reached a negative value after the third cycle, and there was a complete regression of the anomalous vascularization of the uterus as well as full recovery of the uterine anatomy. The treatment in a reference center was essential for the appropriate management, especially regarding the uterine arteries embolization trough percutaneous femoral

Resumo Mola hidatiforme completa (MHC) é um tipo raro de gravidez, na qual 15 a 20% dos casos podem desenvolver neoplasia trofoblástica gestacional (NTG). O diagnóstico de NTG deve ser feito o mais cedo possível, pelo monitoramento semanal do hCG sérico após esvaziamento uterino. Relatamos o caso de uma paciente primigesta, de 23 anos de idade, com MHC, sem vigilância de hCG após esvaziamento uterino. Dois meses depois, a paciente compareceu na emergência com sangramento vaginal, sendo encaminhada ao Centro de Doenças Trofoblásticas do Hospital São Paulo, onde foi diagnosticada com NTG de alto risco, estádio e score de risco III:7 de acordo com a The International Federation of Gynecology and Obstetrics/Organização Mundial de Saúde (FIGO/OMS). O exame ultrassonográfico revelou útero aumentado com uma massa heterogênea constituída pormúltiplos vasos volumosos invadindo e desestruturando o miométrio. A paciente evoluiu com piora progressiva do sangramento vaginal após quimioterapia com o regime etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Ela foi submetida a transfusão de sangue e embolização das artérias uterinas devido aos episódios graves de hemorragia vaginal, com completo controle do sangramento. O hCG atingiu valor negativo após o terceiro ciclo, havendo regressão completa da vascularização uterina anômala, assim como recuperação da anatomia uterina. O tratamento em um centro de referência permitiu o manejo adequado, principalmente no que se refere à embolização das artérias uterinas através da punção percutânea da artéria femoral, que foi crucial para evitar a histerectomia, permitindo a cura da NTG e a manutenção da vida reprodutiva.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Endoscopic characteristics of patients with complete pathological response after neoadjuvant chemotherapy for gastric and esophagogastric junction adenocarcinomas / Características endoscópicas de pacientes com resposta patológica completa após quimioterapia neoadjuvante para adenocarcinomas gástricos e de junção esofagogástrica

ABSTRACT Background: Gastric and esophagogastric junction adenocarcinoma are responsible for approximately 13.5% of cancer-related deaths. Given the fact that these tumors are not typically detected until they are already in the advanced stages, neoadjuvancy plays a fundamental role in improving long-term survival. Identification of those with complete pathological response (pCR) after neoadjuvant chemotherapy (NAC) is a major challenge, with effects on organ preservation, extent of resection, and additional surgery. There is little or no information in the literature about which endoscopic signs should be evaluated after NAC, or even when such re-evaluation should occur. Aim: To describe the endoscopic aspects of patients with gastric and esophagogastric junction adenocarcinomas who underwent NAC and achieved pCR, and to determine the accuracy of esophagogastroduodenoscopy (EGD) in predicting the pCR. Methods: A survey was conducted of the medical records of patients with these tumors who were submitted to gastrectomy after NAC, with anatomopathological result of pCR. Results: Twenty-nine patients were identified who achieved pCR after NAC within the study period. Endoscopic responses were used to classify patients into two groups: G1-endoscopic findings consistent with pCR and G2-endoscopic findings not consistent with pCR. Endoscopic evaluation in G1 was present in an equal percentage (47.4%; p=0.28) in Borrmann classification II and III. In this group, the predominance was in the gastric body (57.9%; p=0.14), intestinal subtype with 42.1% (p=0.75), undifferentiated degree, 62.5% (p=0.78), Herb+ in 73.3% (p=0.68). The most significant finding, however, was that the time interval between NAC and EGD was longer for G1 than G2 (24.4 vs. 10.2 days, p=0.008). Conclusion: EGD after NAC seems to be a useful tool for predicting pCR, and it may be possible to use it to create a reliable response classification. In addition, the time interval between NAC and EGD appears to significantly influence the predictive power of endoscopy for pCR.

RESUMO Racional: O adenocarcinoma gástrico e da junção esofagogástrica é responsável por aproximadamente 13,5% das mortes relacionadas ao câncer. Dado que esses tumores não são normalmente detectados até que já estejam em estágios avançados, a neoadjuvância desempenha um papel fundamental na melhoria da sobrevida em longo prazo. A identificação daqueles com resposta patológica completa (pCR) após a quimioterapia neoadjuvante (NAC) é um grande desafio, com efeitos na preservação do órgão, extensão da ressecção e cirurgia adicional. Há pouca ou nenhuma informação na literatura sobre quais sinais endoscópicos devem ser avaliados após a NAC, ou mesmo quando essa reavaliação deve ocorrer. Objetivo: Descrever os aspectos endoscópicos de pacientes com adenocarcinoma gástrico e da junção esofagogástrica que foram submetidos à quimioterapia neoadjuvante e alcançaram pCR, e determinar a acurácia da esofagogastroduodenoscopia (EGD) em predizer a pCR. Métodos: Foram revisados os prontuários de pacientes submetidos à gastrectomia subtotal e total após NAC, com resultado anatomopatológico de pCR. Resultados: Vinte e nove pacientes que alcançaram pCR após NAC foram identificados no período estudado. As respostas endoscópicas foram usadas para classificar os pacientes em dois grupos: G1- achados endoscópicos consistentes com pCR, G2 - achados endoscópicos não consistentes com pCR. A avaliação endoscópica no G1 esteve presente em igual percentual (47,4%; p=0,28) na classificação de Borrmann II e III. Nesse grupo, a predominância foi no corpo gástrico (57,9%; p=0,14), subtipo intestinal com 42,1% (p=0,75), grau indiferenciado, 62,5% (p=0,78), Herb+ em 73,3% (p=0,68). O achado mais significativo, no entanto, foi que o intervalo de tempo entre NAC e EGD foi maior para G1 do que G2 (24,4 vs. 10,2 dias, p=0,008). Conclusão: A EGD após NAC, nessa pesquisa, sugeriu ser método útil para prever pCR, mediante uma classificação de resposta confiável. Além disso, o intervalo de tempo entre NAC e EGD parece influenciar significativamente a sua capacidade preditiva de diagnosticar a pCR.

Neoadjuvant chemoradiotherapy followed by transhital esophagectomy in locally advanced esophageal squamous cell carcinoma: impact of pathological complete response / Quimiorradioterapia neoadjuvante seguido de esofagectomia transhital no carcinoma espinocelular do esôfago avançado: impacto da resposta patológica completa

ABSTRACT Background Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. Aim: To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. Methods: Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. Results The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). Conclusions There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.

RESUMO Racional: A terapia multimodal com quimioradioterapia neoadjuvantes, seguido de esofagectomia tem oferecido melhores resultados de sobrevida, em comparação à esofagectomia isolada, no câncer do esôfago avançado. Além disso, os doentes que apresentam resposta patológica completa ao tratamento neoadjuvante, têm evoluido com maior sobrevida global e maior sobrevida livre de doença em comparação aos que apresentam resposta incompleta. Objetivo: Comparar os resultados de sobrevida global e sobrevida livre de doença entre os doentes com resposta completa e incompleta, submetidos à quimioradioterapia neoadjuvante, com dois esquemas terapêuticos, seguidos de esofagectomia transhiatal. Métodos: Estudo retrospectivo, aprovado pelo Comitê de Ética em pesquisa, analisando os prontuários de 56 doentes, divididos em dois grupos de pacientes, submetidos a radioterapia (4400 a 5400 cGY) e quimioterapia (5-Fluorouracil+Cisplatina versus Paclitaxel+Carboplatina) neoadjuvantes e posteriormente a tratamento cirúrgico, no período de 2005 a 2012, portadores de carcinoma espinocelular do esôfago. Resultados: Os grupos não diferiram significativamente quanto ao gênero, raça, idade, complicações pós-operatórias, sobrevida livre de doença e sobrevida global. A sobrevida em 5 anos de doentes com resposta incompleta e completa foram, respectivamente, 18,92% e 42,10% (p>0,05). Entretanto, os doentes que receberam Paclitaxel+Carboplatina, tiveram melhores respostas patológicas completas à neoadjuvância, em comparação ao 5-Fluorouracil+Cisplatina (47,37% versus 21,62% - p=0,0473, p<0,05). Conclusões: Não houve diferença estatística na sobrevida global e na sobrevida livre de doença dos doentes que apresentaram resposta patológica completa à neoadjuvância. Os doentes submetidos ao esquema terapêutico com Paclitaxel e Carboplastina, mostraram diferença significativa com melhor resposta patológica completa e evolução da doença. Novos parâmetros são indicados para esclarecer o real valor na sobrevida, da resposta patológica completa à neoadjuvância, no câncer de esôfago.

Radiotherapy for early and advanced stages Follicular Lymphoma

OBJECTIVES To evaluate the results of radiotherapy (RT) for follicular lymphoma (FL) under different management scenarios. METHODS We retrospectively assessed consecutive patients with FL who had undergone irradiation between 2010 and 2018. All patients had biopsy-proven FL and were positron emission tomography-staged, although some (35.3%) were reassessed with computed tomography after treatment alone. Rituximab was only available to FL patients after 2016. RESULTS Thirty-four patients were selected, with a mean age at diagnosis of 61.6 years (34-89 years). The median follow-up duration was 49.4 months. Most patients were female (58.8%) and showed good performance on the Eastern Cooperative Oncology Group (ECOG) scale (ECOG 0-55.9%). The mean overall survival (OS) and progression-free survival were 48.7 and 33.6 months, respectively, with four deaths reported. OS rates at 2 and 3 years were 94.1% and 91.2%, respectively. Four patients showed transformation into aggressive lymphomas and underwent rituximab-based systemic treatment. Transformation-free survival was 47.8 months, and all patients with transformed disease were alive at assessment. Five patients had in-field relapse, all of them also relapsed elsewhere, and the mean relapse-free survival time was 40.3 months. No median end points were reached on assessment. CONCLUSION FL is an indolent disease. Our findings show good outcomes for patients treated with radiation, with a low transformation rate and excellent management of relapsed disease. RT is an important part of these results.

miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease

OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.

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.

Hemophagocytosis by blasts in a child with acute monocytic leukemia after chemotherapy / Hemofagocitose por células blásticas em paciente pediátrico com leucemia monocítica aguda após quimioterapia

ABSTRACT Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-year-old female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient's karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.

RESUMO Objetivo: Descrever um caso de um paciente pediátrico que apresentou linfo-histiocitose hemofagocítica (LHH) associada à leucemia monocítica aguda pós-quimioterapia, com hemofagocitose causada pelas próprias células leucêmicas. Descrição do caso: Em um hospital universitário do Sul do Brasil, uma menina de três anos foi diagnosticada com leucemia monocítica aguda com cariótipo normal. Após receber protocolo quimioterápico, atingiu remissão seis meses depois do início do tratamento, recaíndo quatro meses após com um cariótipo complexo envolvendo ambos os cromossomos, 8p e 16q. A medula óssea mostrava-se infiltrada por células blásticas vacuolizadas com aspecto monocítico, com evidências de hemofagocitose. A criança apresentou um declínio clínico progressivo e dois meses após a recaída foi a óbito. Comentários: A LHH é uma condição inflamatória rara e agressiva caracterizada por citopenias, hepatoesplenomegalia, febre e hemofagocitose na medula óssea, linfonodos, baço e fígado. A LHH associada a doenças malignas, embora seja uma condição rara, é potencialmente fatal. A paciente deste caso apresentou cinco dos oito critérios estabelecidos para o diagnóstico de LHH. A evolução do cariótipo do paciente, independentemente do perfil do diagnóstico, pareceu ser secundária ao tratamento da leucemia monocítica aguda, sendo que a instabilidade citogenética pode ter influenciado o comportamento atípico observado nas células leucêmicas. Este é um dos raros casos de LHH em uma criança com leucemia monocítica aguda.