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

Exploration and thoughts on perioperative treatment of advanced gastric cancer / 中华胃肠外科杂志

Perioperative treatment is critical to improve the outcomes of patients with advanced gastric cancer. There are three therapeutic modes of perioperative treatment for resectable gastric cancer: neoadjuvant chemotherapy+ D1/D2 surgery+ adjuvant chemotherapy, D0/D1 surgery+ adjuvant radiochemotherapy, and D2 surgery+ adjuvant chemotherapy. Over the decades, a large number of clinical studies had been conducted to optimize the perioperative treatment mode of gastric cancer, including the postoperative radiotherapy and chemotherapy, and perioperative chemotherapy, and to explore the feasibility of preoperative radiochemotherapy, targeted therapy, and immunotherapy in advanced gastric cancer. After nearly 20 years of development and exploration, although the perioperative treatment mode for advanced gastric cancer has become standardized, there are still some core issues that need to be solved urgently, including the selection of population for perioperative treatment, the limitation of efficaly evaluation criteria, insufficient emphasis on laparoscopic exploration before neoadjuvant treatment, and lack of exploration in esophagogastric junction cancer. We should fully integrate the current clinical research data into clinical practice, adopt a multidisciplinary diagnosis and treatment mode, and follow the principles of standardized diagnosis and treatment based on a multi-dimensional analysis of patient characteristics, and formulate the most reasonable treatment strategy to ultimately benefit patients.

Linfomas cutáneos: serie de casos en México / A case series of cutaneous lymphomas in Mexico

Resumen Introducción: Los linfomas cutáneos primarios son un grupo heterogéneo de neoplasias de células T y B que se presentan en la piel, sin ninguna evidencia de enfermedad extracutánea en el momento del diagnóstico, y muestran diferencias considerables en histologia, fenotipo y pronóstico. Se consideran neoplasias poco frecuentes. Casos clínicos: Se presentan cinco casos de linfomas cutáneos diagnosticados en el Hospital Infantil de México Federico Gómez durante el periodo de 2010 a 2018. Las presentaciones clínicas más frecuentes en estos pacientes fueron dermatitis, costras hemáticas y úlceras necróticas. El inmunofenotipo más común fue el linfoma cutáneo no Hodgkin T/NK extranodal nasal primario. El esquema de tratamiento que se utilizó en la mayoría de los pacientes fue SMILE. El promedio de tiempo al diagnóstico fue de 7 meses. Conclusiones: El pronóstico depende del estadio de la enfermedad al diagnóstico, grado de afectación de la piel y presencia o ausencia de enfermedad extracutánea. Los linfomas cutáneos primarios son neoplasias poco frecuentes. Debido al diagnóstico tardío, el estadio de la enfermedad suele ser avanzado, por lo que, generalmente, el comportamiento es agresivo.

Abstract Background: Primary cutaneous lymphomas are a rare heterogeneous group of T and B cell skin neoplasms without any evidence of extracutaneous disease at the time of diagnosis, which show considerable differences in histology, phenotype and prognosis. Case reports: Five cases of cutaneous lymphomas treated at the Hospital Infantil de México Federico Gómez from 2010 to 2018 are described. The most frequent clinical presentations in these patients were dermatitis, blood scabs, and necrotic ulcers. The most common immunophenotype was non-Hodgkin T/NK primary nasal extranodal cutaneous lymphomas. The treatment scheme used in most patients was SMILE. The average time to diagnosis was 7 months. Conclusions: The prognosis depends on the stage of the disease at diagnosis, the degree of skin involvement, and the presence of extracutaneous disease. As primary cutaneous lymphomas are infrequent neoplasms, the stage of the disease is usually advanced and generally shows an aggressive behavior due to a late diagnosis.

Paniculitis secundaria a terapia target en paciente con melanoma, lo que el dermatólogo debe saber: reporte de un caso / Panniculitis in association with target therapy in melanoma patient, what the dermatologist should know: a case report

Las terapias target constituyen hoy en día una alternativa terapéutica cada vez más utilizada para el manejo de pacientes con melanoma metastásico. Sin embargo, se han descrito múltiples efectos farmacológicos adversos asociados a su uso, siendo los cutáneos los de mayor prevalencia. Se presenta el caso de un hombre de 55 años con diagnóstico de melanoma cutáneo metastásico etapa IV, BRAFV600E mutado, en tratamiento con dabrafenib/trametinib que consultó por desarrollo de lesiones nodulares eritematosas sensibles en extremidades superiores e inferiores, asociadas a sensación febril durante el curso del tratamiento. Se descartó alguna infección sobreagregada. Se realizó una biopsia de las lesiones cutáneas, con confirmación diagnóstica histopatológica de una paniculitis mixta de predominio septal, granulomatosa y con vasculitis leucocitoclástica. La paniculitis asociada a esta terapia ha sido descrita en la literatura y se ha considerado un efecto farmacológico inmunomediado adverso, relacionándose a un mejor pronóstico para el melanoma metastásico en tratamiento. Por lo tanto, así como en el caso presentado, se evita la suspensión del fármaco y se asocia terapia sintomática en caso de mayores molestias del paciente. Es de alta relevancia para el dermatólogo conocer e interpretar adecuadamente este efecto adverso farmacológico, y así indicar el manejo más adecuado para el paciente.

Target therapies are currently a therapeutic option increasingly used for the management of patients with metastatic melanoma. However, there are multiple adverse pharmacological effects associated with their use that have been described. Cutaneous adverse reactions are the most frequent. We report the case of a 55-year-old man with a diagnosis of stage IV BRAFV600E-mutated metastatic cutaneous melanoma undergoing treatment with dabrafenib/trametinib, who consulted due to the development of erythematous nodular lesions in the upper and lower limbs associated with febrile sensation during the course of treatment. Infection was ruled out and a biopsy of the skin lesions was done, which provided the histopathological confirmation of a predominantly septal, granulomatous with leukocytoclastic vasculitis, mixed panniculitis. Panniculitis associated with this therapy has been described in the literature and has been considered an immune-mediated pharmacological adverse effect. It is considered to be related to a better prognosis in the treatment of metastatic melanoma. Consequently, as shown in this case report, target therapy should not be discontinued and symptomatic medication should be given to alleviate patient discomfort. The dermatologist should know and properly interpret this adverse effect and prescribe the most appropriate management for the patient.

Leucemia agresiva de células natural killer en un paciente pediátrico / Agressive NK-cell leukemia in a pediatric patient

Resumen Introducción: Las neoplasias de células natural killer (NK) son poco frecuentes y representan <5% de todas las neoplasias linfoides. Comprometen diferentes entidades clínicas, como la leucemia de células NK, que es una neoplasia hematológica altamente agresiva con un pronóstico precario, que se presenta en hombres jóvenes y se observa con mayor frecuencia en ascendencia asiática. El virus de Epstein-Barr (VEB) parece estar relacionado con la patogenia de esta leucemia. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 1 año y 7 meses de edad, quien inició su padecimiento con síndrome anémico, febril, infiltrativo e hiperleucocitosis. En el aspirado de médula ósea se detectaron blastos de morfología L2 (96%), inmunofenotipo CD56 (80.87%) y desoxinucleotidil transferasa terminal (84.11%). En la biopsia de médula ósea se identificó CD2+ membranoso, CD3+ citoplásmico y CD56+ membranoso; la serología para VEB fue positiva. El paciente recibió dos esquemas diferentes de quimioterapia basados en metotrexato, ifosfamida, etopósido, dexametasona y L-asparaginasa, y se documentó remisión parcial. Actualmente, se encuentra vivo con la enfermedad. Conclusiones: La leucemia de células NK es rara en adultos jóvenes, pero aún más en pacientes en edad pediátrica. Además, es de muy difícil tratamiento, ya que solo se cuenta con algunos reportes de casos, la sobrevida es de semanas a meses y las oportunidades de tratamiento se limitan. Recientemente, se ha evidenciado la utilidad del trasplante de médula ósea alogénico o células de cordón umbilical, y se ha logrado una sobrevida a 2 años. Las posibilidades terapéuticas en estos pacientes se encuentran en estudio. Se espera lograr en un futuro cercano la remisión completa y sobrevida a 5 años.

Abstract Background: Natural killer (NK) cell neoplasms are rare and represent <5% of all lymphoid neoplasms. They involve different clinical entities, of which one is NK cell leukemia, a highly aggressive hematologic neoplasm with poor prognosis that presents in young men and is more frequently seen in Asian descent. Epstein-Barr virus (EBV) seems to be related to the pathogenesis. Case report: A male patient of 1 year and 7 months of age, who began his condition with anemic, febrile, infiltrative syndrome and hyperleukocytosis is described. Bone marrow aspirate showed L2 morphology blasts (96%), CD56 (80.87%) and terminal deoxynucleotidyl transferase (84.11%) immunophenotype. Bone marrow biopsy showed membranous CD2+, cytoplasmic CD3+ and membranous CD56+; serology positive to EBV. The patient received two different chemotherapy schemes based on methotrexate, ifosfamide, etoposide, dexamethasone and L-asparaginase, which resulted in partial remission. Currently, the patient lives with the disease. Conclusions: NK cells leukemia is rare in young adults, but even more in pediatric patients, for which it is very difficult to treat because only a few cases have been reported in the literature, the survival varies from weeks to months and the chances of treatment are limited. Recently, the usefulness of allogeneic bone marrow transplantation or umbilical cord cells has been demonstrated, achieving a 2-year survival. The therapeutic possibilities in these patients are under study. In the near future, we hope to achieve the complete remission of the disease and a 5-year survival.

El ácido valproico como agente sensibilizador al tratamiento anticáncer / Valproic acid as a sensitizing agent in anticancer treatment

Resumen El ácido valproico es un fármaco antiepiléptico con más de 50 años de uso clínico. En la década pasada se descubrieron sus efectos anticancerígenos. El análisis de grupos de pacientes que utilizaron este fármaco durante años ha mostrado que disminuye la frecuencia de cáncer de cabeza y cuello. Estudios recientes evidencian el efecto anticáncer al combinar el ácido valproico con la quimioterapia, terapia biológica e inhibidores de sistemas antioxidantes, con resultados excepcionales. En esta revisión se analiza el metabolismo del ácido valproico y su aplicación contra el cáncer.

Abstract Valproic acid is an antiepileptic drug with more than 50 years of clinical use. In the past decade, its anticancer effects were discovered. Analyses in groups of patients who used this drug for years have shown that it decreases the frequency of head and neck cancer. Recent studies show the anticancer effect of combining valproic acid with chemotherapy, biological therapy and antioxidant systems inhibitors, with exceptional results. In this review, we analyze the metabolism of valproic acid and its application against cancer.

Effect of FOLFOX6 chemotherapy on serum VEGF expression in advanced colorectal cancer patients

SUMMARY OBJECTIVE: To explore the effect of FOLFOX6 chemotherapy on serum vascular endothelial growth factor (VEGF) expression in advanced colorectal cancer patients. METHODS: A retrospective analysis of 81 patients with advanced colorectal cancer who visited our hospital from March 2014 to February 2016 was performed. All the patients were treated with FOLFOX6 chemotherapy. On day 1, patients received oxaliplatin 100 mg/m2 ivgtt (2h), calcium folinate 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus and 5 fluorouracil 2500 mg/m2 ivgtt (5h). The treatment course was 2 weeks, and 4 treatment courses were required. The changes in the levels of VEGF and CRP and quality of life before and after 4 courses of chemotherapy were observed and therapeutic effects and adverse reactions after chemotherapy were evaluated. RESULTS: After treatment, the total efficiency of chemotherapy was 82.72% (67/81) with 24 cases in complete remission, 25 cases in partial response, 18 cases in stable disease and 14 cases in progressive disease. The levels of CRP and VEGF after the treatment were significantly lower than those before treatment (5.69±0.77) mg/L vs. (7.99±1.36) mg/L; (443.26±21.55) pg/mL vs. (542.83±20.44) pg/mL] (P<0.05). The KPS grade after treatment was significantly higher than that before treatment (57.84±4.6) point vs. (50.99±3.73) point] (P<0.05). Among them, 3 cases developed a rash, 5 cases experienced hair loss, and 9 cases developed nausea and vomiting. CONCLUSION: FOLFOX6 chemotherapy can decrease serum VEGF expression in patients with advanced colorectal cancer and enhance the curative effect with high safety, which is good for the improvement of patients' survival.

RESUMO OBJETIVO: Explorar o efeito da quimioterapia Folfox6 na expressão do fator de crescimento endotelial vascular sérico (VEGF) em pacientes com câncer colorretal avançado. MÉTODOS: Uma análise retrospectiva de 81 pacientes com câncer colorretal avançado que visitaram nosso hospital de março de 2014 a fevereiro de 2016 foi realizada. Todos os pacientes foram tratados com quimioterapia Folfox6. No dia 1, os doentes receberam oxaliplatina 100 mg / m2 ivgtt (2h), folinato de cálcio 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus e 5 fluorouracil 2.500 mg/m2 ivgtt (5h). O curso de tratamento foi de duas semanas e foram necessários quatro cursos de tratamento. Foram observadas as alterações nos níveis de VEGF e CRP e qualidade de vida antes e após quatro cursos de quimioterapia e avaliados os efeitos terapêuticos e reações adversas após a quimioterapia. RESULTADOS: Após o tratamento, a eficácia total da quimioterapia foi de 82,72% (67/81), com 24 casos em remissão completa, 25 casos em resposta parcial, 18 casos em doença estável e 14 casos em doença progressiva. Os níveis de CRP e VEGF após o tratamento foram significativamente inferiores aos do tratamento (5,69 ± 0,77) mg / L vs. (7,99 ± 1,36) mg / L; (443,26 ± 21,55) pg / mL vs. (542,83 ± 20,44) pg / mL] (P < 0,05). O grau de KPS após o tratamento foi significativamente maior do que antes do tratamento (57,84 ± 4,6 pontos) vs. (50,99 ± 3,73 pontos)] (P < 0,05). Entre eles, três casos desenvolveram erupção cutânea, cinco casos sofreram perda de cabelo e nove casos desenvolveram náuseas e vômitos. CONCLUSÃO: A quimioterapia Folfox6 pode, obviamente, diminuir a expressão de VEGF no soro em pacientes com câncer colorretal avançado e melhorar o efeito curativo com alta segurança, o que é bom para a melhoria da sobrevivência dos pacientes.

First - line, non - cryopreserved autologous stem cell transplant for poor - risk germ - cell tumors: Experience in a developing country

ABSTRACT Purpose: The current first - line treatment for non - seminomatous germ cell tumor (NSGCT) consists of four cycles of cisplatin, etoposide, and bleomycin (BEP), which results in 5 - year overall survival < 60% in patients with poor - risk features. Autologous hematopoietic stem cell transplantation (auto - HSCT) as a method for overcoming high toxicity after high dose chemotherapy (HDC) has been explored in different solid tumors, but has remained standard practice only for NSGCT. Our objective was to describe outcomes of patients with poor - risk NSGCT who underwent first - line autologous HSCT in a tertiary center in Mexico. Patients and Methods: Twenty nine consecutive patients with NSGCT who received first - line, non - cryopreserved autologous HSCT at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, Mexico, from November 1998 to June 2016, were retrospectively analyzed. Results: The median age at transplantation was 23 (15 - 39) years. Most patients (n = 18, 62%) had testicular primary tumor, and 23 had metastases (79%). Complete response after auto - HSCT was observed in 45%. Non - relapse mortality was 0. Five - year relapse / progression free and overall survival were 67% and 69%, respectively. Conclusions: This small single limited - resource institution study demonstrated that patients with poor - risk NSGCT are curable by first - line HDC plus autologous HSCT and that this procedure is feasible and affordable to perform using non - cryopreserved hematopoietic stem cells.

Análisis retrospectivo de pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina / Retrospective analysis of patients with locally advanced or metastatic gastric cancer in Argentina

OBJETIVO Describir las características clínicas, los patrones de tratamiento y los costos asociados en pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina, en los sectores público y privado. MÉTODOS Una cohorte histórica de pacientes que recibieron tratamiento de quimioterapia de primera línea (análogo de platino y/o una fluoropirimidina) y fueron seguidos durante al menos tres meses después de la última administración de un agente citotóxico de primera línea fueron elegibles. Se extrajeron los datos a través de un cuestionario estructurado a partir de los registros médicos de cuatro hospitales argentinos. Las estimaciones de los costos de tratamiento también se calcularon utilizando los costos unitarios de los hospitales participantes. RESULTADOS Entre los 101 pacientes, más de tres cuartas partes (79,2%) eran hombres, 41,6% fueron diagnosticados con enfermedad metastásica en estadio IV, la edad media fue de 57,7 años y el 27,7% tenían antecedentes de tabaquismo. Antes del diagnóstico de cáncer gástrico metastásico, el 42,4% de los pacientes habían recibido gastrectomía total. El 97% de los pacientes recibió una terapia doble o triplete, de los cuales el tratamiento más frecuente fue la epirubicina en combinación con oxaliplatino y capecitabina (38%), seguida de capecitabina + oxaliplatino (29%). Alrededor del 36% de los pacientes respondieron al tratamiento de primera línea (respuesta completa y parcial). Del 76,2% de los pacientes que siguieron un tratamiento de segunda línea, al 37,7% todavía se les administró un análogo de platino y/o fluoropirimidina. Durante el período de seguimiento, el 50% de los pacientes progresó y el 32,8% tenía enfermedad estable. La terapia de apoyo consistió principalmente en visitas ambulatorias después de la última línea de quimioterapia (16,8%), radioterapia paliativa (16,8%) y cirugía (30,7%). Se observaron diferencias significativas entre los costos de los hospitales públicos y privado. CONCLUSIONES Comprender los patrones de tratamiento en pacientes con cáncer gástrico localmente avanzado o metastásico puede ayudar a abordar las necesidades médicas no satisfechas para un mejor manejo del paciente y la mejora de sus resultados clínicos en Argentina.

AIM To assess patient and disease characteristics, treatment patterns and associated costs in patients with locally advanced or metastatic gastric cancer in Argentina, in the public and private sectors. METHODS A historic cohort of patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed-up for at least three months after the last administration of a first-line cytotoxic agent were eligible. Case-report forms were prepared based on medical records from four Argentinian hospitals. Estimates of treatment costs were also calculated using the unit costs of the participating hospitals. RESULTS Of 101 patients, more than three quarters (79.2%) were male, 41.6% were diagnosed with metastatic stage IV disease (mean age, 57.7years), and 27.7 % had a smoking history. Before locally advanced or metastatic gastric cancer diagnosis, 42.4% of the patients had received total gastrectomy. Ninety-seven percent of the patients received a doublet or triplet therapy, of which epirubicin in combination with oxaliplatin and capecitabine was the most common treatment (38%), followed by capecitabine plus oxaliplatin (29%). Around 36% of the patients responded to first-line treatment (complete and partial response). Out of the 76.2% of the patients who followed a second-line treatment, 37.7% were still administered a platinum analog and/or fluoropyrimidine. During the reported follow-up period, 50% of the patients progressed, and 32.8% had stable disease. The best supportive care consisted mostly of outpatient visits after last-line therapy (16.8%), palliative radiotherapy (16.8%), and surgery (30.7%). We observed significant differences between public and private hospital costs. CONCLUSIONS Understanding treatment patterns in patients with locally advanced or metastatic gastric cancer may help address unmet medical needs for better patient management and improvement of their clinical outcome in Argentina.

Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

Análisis costo-efectividad de lenalidomida en combinación con dexametasona frente a bortezomib combinado con dexametasona en el tratamiento en segunda línea del mieloma múltiple en Chile / Cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone for the second-line treatment of multiple myeloma in Chile

CONTEXTO: El mieloma múltiple es una neoplasia de las células plasmáticas de la medula ósea. Las terapias disponibles no son curativas y la mayoría de los pacientes se vuelve refractario al tratamiento. Agentes como lenalidomida y bortezomib han demostrado su eficacia en el tratamien-to en segunda línea de estos pacientes. OBJETIVO: Evaluar el costo-efectividad de la combinación lenalidomida/dexametasona frente a bortezomib/dexametasona en pacientes con mieloma múltiple, no candidatos a trasplante, previamente tratados con bortezomib, desde la perspectiva del sistema nacional de salud chileno. METODOLOGÍA: Se empleó un modelo de Markov que simula la evolución de una cohorte de pacientes a través de cuatro estados de salud (preprogresión en tratamiento, preprogresión sin tratamiento, progresión o muerte) en un horizonte temporal de 25 años. Los datos de eficacia, uso de recursos y frecuencia de efectos adversos fueron extraídos de los ensayos sobre mieloma múltiple MM-009 y MM-010 y de un estudio retrospectivo de retratamiento con bortezomib. Todos los parámetros fueron validados por expertos. Se aplicó una tasa de descuento en costos y beneficios de 3%. La robustez de los resultados fue evaluada mediante un análisis de sensibilidad univariante y probabilístico. RESULTADOS: El tratamiento con lenalidomida/dexametasona proporciona 1,41 años de vida y 0,83 años de vida ajustados por calidad incrementales respecto a bortezomib/dexametasona, con un costo incremental de 11 864 597,86 pesos chilenos (19 589,86 dólares). La ratio de cos-to-efectividad y costo-utilidad incremental se cifró en 8 410 266,92 pesos chilenos (13 886,35 dólares) por año de vida ganado y 14 271 896,16 pesos chilenos (23 564,59 dólares) por año de vida ajustado por calidad respectivamente. CONCLUSIÓN: La lenalidomida/dexametasona representa una alternativa potencialmente costo-efectiva, desde la perspectiva del sistema nacional de salud chileno, para el tratamiento en segunda línea de pacientes con mieloma múltiple no candidatos a trasplante.

BACKGROUND: Multiple myeloma is a hematologic malignancy affecting bone marrow derived plasma cells. Current therapies are not able to eradicate the disease and most patients become refractory to the treatment. Lenalidomide and bortezomib have proved effective in the second-line treatment of these patients. OBJECTIVE: To evaluate the cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone in patients with multiple myeloma previously treated with bortezomib, from the perspective of the Chilean National Health Service. METHODOLOGY: A four-state Markov model (preprogression on treatment; preprogression off treatment, progression and death) was used to simulate the evolution of a cohort of multiple myeloma patients over a 25-year time horizon. Efficacy data, resource use and frequency of adverse events were extracted from MM009/010 studies and a retrospective analysis of retreatment with bortezomib. All inputs were validated by experts. A 3% annual discount rate was used for costs and health outcomes. The robustness of the results was evaluated through univariate and probabilistic sensitivity analyses. RESULTS: Lenalidomide in combination with dexamethasone treatment provided 1.41 incremental life years and 0.83 incremental quality-adjusted life years in comparison with bortezomib in combination with dexamethasone, with an incremental cost of 11 864 597.86 CLP (19 589.86 US$). The incremental cost-effectiveness and cost-utility ratio were estimated at 8 410 266.92 CLP (13 886,35 US$) / incremental life year and 14 271 896.16 CLP (23 564,59 US$)/incremental quality-adjusted life years, respectively. CONCLUSIONS: Lenalidomide in combination with dexamethasone represents a potentially cost-effective alternative for the second-line treatment of patients with multiple myeloma who are not eligible for transplantation, from the perspective of the Chilean National Health Service.

Respuesta histológica completa a la neoadyuvancia en carcinoma gástrico avanzado: A propósito de un caso y revisión de la literatura / Histological complete response to neoadjuvant therapy in advanced gastric carcinoma: A case report and review of literature

La presente comunicación, describe el primer caso en el Instituto Regional de Enfermedades Neoplásicas "Luis Pinillos Ganoza" IREN Norte en la que una paciente con carcinoma gástrico avanzado ha mostrado respuesta histopatológica completa a neoadyuvancia. Se presenta una paciente mujer de 70 años con diagnóstico histopatológico de adenocarcinoma gástrico tubular moderadamente diferenciado, localmente avanzado con imágenes de adenopatías perigástricas asociadas y pérdida de la interfase entre tumoración gástrica, hilio hepático y vesícula biliar. Luego de 6 cursos de quimioterapia neoadyuvante con esquema FOLFOX - 4 al 80%, se obtiene una respuesta casi completa desde el punto de vista tomográfico; por ello a la paciente se le realiza gastrectomía subtotal distal más linfadenectomía D2 más gastroyeyunoanastomosis Billroth II término lateral tipo Hofmeister Finsterer, verificándose, al examen microscópico de la pieza operatoria, sólo gastritis crónica y aguda con áreas mucosas y cambios reactivos. No se observa neoplasia maligna viable. Ganglios linfáticos: 0/33. Paciente evoluciona favorablemente. A propósito del caso se hace una revisión de la literatura médica relevante actualizada

This communication describes the first case in the Regional Institute of Neoplastic Diseases "Luis Pinillos Ganoza" IREN North in which a patient with advanced gastric carcinoma showed complete response to neoadjuvant histopathologic. We describe the case of a patient woman of 70 years old with histopathologic diagnosis of moderately differentiated tubular gastric adenocarcinoma, locally advanced associated with images of perigastric lymphadenopathy and loss of the interface between gastric tumor, hepatic hilum and gallbladder. After 6 courses of neoadjuvant chemotherapy with FOLFOX scheme - 4 to 80%, an almost complete response from the point of tomographic view is obtained, so the patient is underwent to distal subtotal gastrectomy lymphadenectomy D2 more gastrojejunoanastomosis Billroth II termino lateral type Hofmeister Finsterer verifying on microscopic examination of surgical specimen only acute and chronic gastritis with mucous areas and reactive changes. No feasible malignancy is observed. Lymph nodes: 0/33. Commenting on the case, a review of recent relevant literature is realized

Excelente respuesta a tratamiento con ABVD en pacientes con linfoma de Hodgkin localizado / Response to ABVD chemotherapeutic protocol in patients with early stage Hodgkin’s lymphoma

Background: Recent trials show that > 90% of patients with early stage Hodgkin`s Lymphoma (ESHL) can be cured, especially when using the ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapeutic (CT) protocol. The use of radiotherapy (RT) is variable and can be selected according to the presence of specific risk factors, including PET-CT, as recently reported. Aim: To report the experience in the treatment of ESHL. Material and Methods: Retrospective and descriptive analysis of patients with ESHL treated at the Red de Salud UC-Christus between 2011-2015. Results: Twenty-two patients were treated. In 73%, the tumor was of nodular sclerosis histologic type. Most patients (95%) were in stage II, and 78% had a favorable prognosis according to the Deutsche Hodgkin Studiengruppe (GHSG) criteria. All patients were stratified using PET-CT and treated using the ABVD CT protocol, for 4-6 cycles. Only 5 patients received RT. There was no change of conduct after interim-PET-CT results. Ninety one percent of patients achieved complete response and there were two cases of refractory disease. Both cases underwent hematopoietic stem cell transplantation. After 17 months of median follow-up, 91% of patients are relapse-free, and only one patient died (5%). Conclusions: ABVD offers excellent results for ESHL patients. The benefit of PET-CT should be evaluated with prospective protocols, aiming to select patients needing RT or to reduce the number of CT cycles.

Beneficio de la quimioterapia adyuvante en pacientes con cáncer de colon: cohorte retrospectiva de un hospital clínico universitario / Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study

Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94).Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.

Resultados en el tratamiento de pacientes con leucemia mieloide aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica entre los años 2010-2014 / Results of acute myeloid leukemia treatment. Analysis of 63 patients between 2010-2014

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, emphasizing its high recurrence rate despite hematopoietic cell transplantation (HCT). Aim: To report the results of AML treatment at the Catholic University of Chile Clinical Hospital. Patients and Methods: Review of medical records of patients with AML. Results: 63 patients, median age 55.4 years (range:16-89), treated between 2010 and 2014. Admission laboratory values showed (median values): leukocytes 45.989/mm³, hemoglobin 9.1 g/dl, platelets 75.548/mm³, peripheral blood blasts 38% and bone marrow blasts 74%. According to cytogenetic risk classification we observed the following groups: favorable 8% (n = 5), intermediate 51% (n = 32), unfavorable 13% (n = 8) and unknown 28% (n = 17). Seventy five percent of patients received induction chemotherapy and 25% palliative care. Median survival of treated and palliative care patients was 27.3 and 1 month respectively. Induction chemotherapy (IC) mortality (ICM) was 4.2%. Seventy percent (n = 33) of patients who received IC had complete response (CR) with a 3-year relapse free survival (RFS) of 25% and overall survival (OS) of 31%. Multivariate analysis demonstrated that achievement of CR, cytogenetic risk group and receiving consolidation chemotherapy were significantly associated with better RFS and OS. Conclusions: AML treatment with standard chemotherapy in our center achieves similar results to what has been described in international series regarding induction rates and ICM, however RFS and OS are still very low, especially in intermediate and high cytogenetic risk groups.

Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease / Avaliação da Função Autonômica na Doença de Chagas Através da Análise de Histogramas de Intervalos RR com Retificação de Fase

Background: In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. Objective: This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. Methods: Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05). Results: Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. Conclusion: HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. .

Fundamento: Na doença de Chagas (DCh) crônica, a função autonômica cardíaca está frequentemente comprometida e traz implicações quanto ao prognóstico. A retificação de fase da série de intervalos RR isola as influências simpática (fase de aceleração – AC) e parassimpática (fase de desaceleração – DC) na modulação autonômica cardíaca. Objetivo: Este estudo investigou a variabilidade da frequência cardíaca (VRR) como função dos intervalos RR, para avaliar a função autonômica em indivíduos saudáveis e com DCh. Métodos: Os grupos controle (n = 20) e com DCh (n = 20) foram estudados. Todos fizeram o teste de inclinação ortostática de 60 minutos, com o registro do ECG. O histograma da série de intervalos RR dividido em classes de 100 ms, variando de 600 a 1100 ms foi calculado. Para cada classe, foram calculados os intervalos RR médios (MNN) e a diferença média quadrática (RMS) entre os intervalos RR normais que se encaixavam naquela classe. A média de todos os valores de RMS foi analisada como uma função dos MNN na série inteira (RMST) e nas fases de aceleração (RMSAC) e desaceleração (RMSDC). A inclinação das linhas de regressão linear foi comparada entre grupos através do teste t de Student. Os coeficientes de correlação foram testados antes das comparações. A RMS sofreu transformação logarítmica (α < 0,05). Resultados: O coeficiente de correlação foi significativo em todas as regressões (p < 0,05). No grupo controle, a RMST, a RMSAC e a RMSDC aumentaram de forma significativa proporcionalmente ao MNN (p < 0,05). No grupo com DCh, apenas a RMSAC mostrou um aumento significativo como função do MNN, enquanto a RMST e a RMSDC não aumentaram significativamente. Conclusão: A VRR aumenta proporcionalmente ao intervalo RR em indivíduos saudáveis. Este comportamento é perdido na DCh, especialmente na DC, indicando incompetência vagal cardíaca. .

Hyperthermic intraperitoneal chemotherapy for ovarian cancer: is there a role? / 부인종양

No abstract available.

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study / 부인종양

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51+/-9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73+/-5.51 days and the mean hospitalization time was 24.0+/-10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.