Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia.

ABSTRACT: The introduction of all-trans retinoic acid combined with anthracyclines has significantly improved the outcomes for patients diagnosed with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries in which arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly because of high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the International Consortium on Acute Promyelocytic Leukemia study involving 806 patients with APL recruited from 2005 to 2020 in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has notably decreased to 14.6% compared with the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age of ≥40 years, Eastern Cooperative Oncology Group performance status score of 3, high-risk status based on the Programa Español de Tratamiento en Hematologia/Gruppo Italiano Malattie EMatologiche dell'Adulto classification, albumin level of ≤3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival rate is 81%, the 4-year disease-free survival rate is 80%, and the 4-year cumulative incidence of relapse rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.

Cyclophosphamide, Thalidomide, and Dexamethasone as Initial Therapy for Patients With Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up.

PURPOSE: Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS: Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION: Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.

Manejo de neoplasias oncohematológicas en el contexto de la pandemia de COVID-19: recomendación de expertos / Management of oncohematological neoplasms in the COVID-19 pandemic: experts recommendation

RESUMEN La pandemia por COVID-19 originado por el Coronavirus 2 causante de síndrome respiratorio agudo severo (SARS-CoV-2) es causante de una crisis de salud pública a nivel global. Muchos reportes indican resultados desalentadores en pacientes con cáncer respecto a la población general. Por ello, los expertos en el manejo de neoplasias oncohematológicas del Instituto Nacional de Enfermedades Neoplásicas, hospitales nacionales y una clínica privada de Lima Metropolitana han desarrollado recomendaciones obtenidas por consenso para continuar con el manejo de pacientes con neoplasias oncohematológicas en forma segura ante la coyuntura de pandemia.

ABSTRACT The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health crisis. Many reports indicate disappointing results in cancer patients compared to the general population. Therefore, experts in the management of oncohematological malignancies from the National Institute of Neoplastic Diseases, national hospitals and a private clinic in Metropolitan Lima have developed recommendations obtained by consensus to continue with the management of patients with oncohematological neoplasms safely in the face of the pandemic.

Comparative evaluation of the quality of Papanicolaou staining at different intervals of fixation times using 96% ethyl alcohol / Avaliação comparativa da qualidade da coloração de Papanicolaou em diferentes tempos de fixação em álcool etílico a 96%

ABSTRACT Introduction: Fixation of cytological smears consists of immediate immersion in appropriate fixative, in order to preserve cellular morphological characteristics, it is essential for the microscopic examination and diagnostic interpretation. Objective: To evaluate the influence of fixation times on the morphological and staining characteristics of samples fixed in ethanol and stained by the Papanicolaou method. Method: Experimental, quantitative and qualitative research was carried out on 99 samples of the jugal mucosa scrapings from 33 participants, fixed in 96% ethyl alcohol in three different times. Group A: 15 minutes; group B: 30 minutes; group C: seven days. The quality of staining was categorized in Optimal, Good, Regular and Poor, with subsequent recategorization at optimal and non-optimal. To verify the association among the groups and the categories, Fisher's exact test was performed, with significance level of 0.05. Results: From the 99 stained slides, 19 were discarded due to acellularity, remaining 80 slides. From these, 28 in group A, 26 in group B and 26 in group C were evaluated. In Group A, optimal quality was found in 60.7% (n = 17), good in 28.6% (n = 8), regular in 10.7% (n = 3) and poor in 0% (n = 0). In group B optimal was found in 61.5% (n = 16), good in 30.8% (n = 8), regular in 7.7% (n = 2) and poor in 0% (n = 0). In group C, optimal was found in 92.3% (n = 24), good in 7.7% (n = 2), regular in 0% (n = 0) and poor in 0% (n = 0). In the three groups, there was no representation of the Poor category. Conclusion: The results suggest that there is a significant difference in the staining quality (p-value = 0.01) according to the fixation time.

RESUMEN Introducción: La fijación de extensiones citológicas consiste en la inmersión inmediata en fijador adecuado para preservar la morfología celular, siendo esencial para el análisis microscópico y la interpretación diagnóstica. Objetivo: Evaluar la influencia de los tiempos de fijación en las características morfológicasy de tinción de muestras fijadas con metanoly tenidas con el método de Papanicolaou. Método: Se realizó una investigación experimental, cuantitativa y cualitativa de 99 muestras de raspado de la mucosa yugal de 33 participantes, fijadas con etanol al 96% en tres tiempos distintos. Grupo A: 15 minutos; grupo B: 30 minutos; grupo C: 7 días. La calidad de la tinción fue categorizada en óptima, buena, regular y mala, con posterior reclasificación en óptima y no óptima. Para determinar la asociación entre los grupos y las categorias, se realizó la prueba exacta de Fisher, con un nivel de significación del 0,05. Resultado: De las 99 muestras tenidas, 19 fueron desechadas por acelularidad, quedando 80 para ser analizadas. De estas muestras, 28 fueron evaluadas en el grupo A, 26 en el grupo B y 26 en el grupo C. En el grupo A, hemos encontrado calidad óptima - 60,7% (n =17); buena - 28,6% (n = 8); regular -10,7% (n = 3) y mala - 0% (n = 0). En el grupo B, óptima - 61,5% (n = 16); buena - 30,8% (n = 8); regular - 7,7% (n = 2); y mala - 0% (n = 0). En el grupo C, óptima - 92,3% (n = 24); buena - 7,7% (n = 2); regular - 0% (n = 0) y mala - 0% (n = 0). En los tres grupos no hubo representación en la categoria mala. Conclusión: Los resultados sugieren que hay diferencia significativa en la calidad de la tinción (p = 0,01) de acuerdo con el tiempo de fijación.

RESUMO Introdução: A fixação dos esfregaços citológicos consiste na imersão imediata em fixador adequado para preservar as características morfológicas celulares, sendo essencial para a análise microscópica e a interpretação diagnóstica. Objetivo: Avaliar a influência dos tempos de fixação nas características morfológicas e tintoriais de amostras fixadas em álcool etílico e coradas pelo método de Papanicolaou. Método: Realizou-se pesquisa experimental, quantitativa e qualitativa de 99 amostras de raspado da mucosa jugal de 33participantes, fixadas em álcool etílico 96% em três tempos diferentes. Grupo A: 15 minutos; grupo B: 30 minutos; grupo C: sete dias. A qualidade da coloração foi categorizada em ótima, boa, regular e ruim, com posterior recategorização em ótimo e não ótimo. Para verificar a associação entre os grupos e as categorias, realizou-se teste exato de Fisher, com nível de significância de 0,05. Resultado: Das 99 lâminas coradas, 19 foram desprezadas por acelularidade, restando 80 lâminas para serem analisadas. Destas, foram avaliadas 28 no grupo A, 26 no grupo B e 26 no grupo C. No grupo A, foi encontrada qualidade ótima - 60,7% (n = 17); boa - 28,6% (n = 8); regular - 10,7% (n = 3) e ruim - 0% (n = 0). No grupo B, ótima - 61,5% (n = 16); boa - 30,8% (n = 8); regular - 7,7% (n = 2); e ruim - 0% (n = 0). E no Grupo C, ótima - 92,3% (n = 24); boa - 7,7% (n = 2); regular - 0% (n = 0); e ruim - 0% (n = 0). Nos três grupos não houve representação na categoria ruim. Conclusão: Os resultados sugerem que há diferença significativa na qualidade da coloração (p = 0,01) de acordo com o tempo de fixação.

Quality in cytopathology: an analysis of the internal quality monitoring indicators of the Instituto Nacional de Câncer / Qualidade em citopatologia: análise de indicadores de monitoramento interno de qualidade do Instituto Nacional de Câncer

Introduction: Quality control programs are required to ensure the effectiveness of Pap smear, which still remain a key strategy for control of cervical cancer worldwide. Objective: This study was based on the retrospective and quantitative analysis of the post-analytical phase indicators from the internal quality monitoring (IQM) program for cytopathology laboratories, such as: positivity rate, atypical squamous cell (ASC)/satisfactory exams ratio, ASC/abnormal test results ratio, ASC/squamous intraepithelial lesions (SIL) ratio, percentage of tests compatible with high-grade squamous intraepithelial lesion (HSIL), and total of false negative. Materials and methods: The information was extracted from the computerized system of the Section for Integrated Technology in Cytopathology (Seção Integrada de Tecnologia em Citopatologia [SITEC]), a reference institution for cancer cytopathology, from July 2013 to June 2014. From a total of 156,888 Pap smears, 157,454 were considered satisfactory for indicator analysis and 566 were excluded because they were considered unsatisfactory and/or rejected for analysis. The data was organized in tables using Microsoft Excel 2010 software, and categorized as indicators. Results: The averages for the indicators were: 7.2% for positivity rate, 56.9 for ASC/abnormal test ratio, 4.1 for ASC/satisfactory tests ratio, 1.4 for ASC/SIL ratio, 0.6% percentage for tests compatible with HSIL, and 2.1% for false-negative rate. Conclusion: The results show that an Internal Quality Monitoring Program is essencial to ensure quality for cytopathology laboratories, and a randomized review of at least 10% of the negative exams, as recommended by the Brazilian Ministry of Health/Instituto Nacional de Câncer (INCA), since is an effective method, especially for large laboratories. .

Introdução: A estruturação de um sistema de controle de qualidade é necessária para garantir a efetividade do exame preventivo ginecológico, que permanece como principal estratégia para controle do câncer do colo do útero no mundo. Objetivos: Análise retrospectiva e quantitativa dos indicadores da fase pós-analítica do monitoramento interno de qualidade (MIQ) para laboratórios de citopatologia, como: índice de positividade, razão atipias escamosas de significado indeterminado (ASC)/exames satisfatórios, razão ASC/exames alterados, razão entre ASC/lesões intraepiteliais escamosas (SIL), percentual de exames compatíveis com lesão intraepitelial escamosa de alto grau (HSIL), além do total de falso negativos. Materiais e métodos: As informações foram extraídas do sistema informatizado da Seção Integrada de Tecnologia em Citopatologia (SITEC), instituição de referência em citopatologia oncológica, no período de julho de 2013 até junho de 2014. De um total de 157.454 exames citopatológicos no período, 156.888 foram considerados satisfatórios para análise dos indicadores e 566 foram excluídos por serem classificados como insatisfatórios e/ou rejeitados. Todos os dados obtidos para análise foram organizados em tabelas utilizando-se o programa Microsoft Excel 2010, nas quais foram categorizados em indicadores. Resultados: A média obtida dos indicadores foi de 7,2% para o índice de positividade, 56,9 para a razão de ASC/exames alterados, 4,1 para a razão ASC/exames satisfatórios, 1,4 para ASC/SIL, 0,6% para exames compatíveis com HSIL e 2,1% de exames falso negativos. Conclusão: Os resultados demonstram que o MIQ é fundamental para manter a qualidade dos laboratórios de citopatologia, e a revisão aleatória de pelo menos 10% dos exames considerados negativos, conforme orientação do Ministério da Saúde/Instituto Nacional de Câncer (INCA), é um método eficaz principalmente em laboratórios de grande porte. .

[Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients with gastric cancer in the National Institute of Cancer, Lima, Peru]. / Tratamiento adyuvante con quimioterapia y radioterapia luego de gastrectomía y disección ganglionar D2 en pacientes con cáncer gástrico en el Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú

INTRODUCTION: Adjuvant chemo radiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT0116 pivotal trial established adjuvant chemo radiation as the standard care for resected high risk adenocarcinoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standard surgery for gastric cancer. OBJECTIVE: To prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in patients' with gastric cancer is effective. MATERIAL AND METHODS: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima-Peru between 2001 and 2006. Standard treatment at institution is D2 lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant therapy. Survivalcurves were calculated according to Kaplan-Meier method and compared with log-rank test. RESULTS: 84 patients were included 60.7% male and 39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2 (15.5%), T3- T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survival was 23.9%. However when we analyzed by subgroups the overall survival, was in group N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups were N1 (100%), N2 (51.9%) and N3 (16.3%). CONCLUSIONS: Adjuvant chemo radiotherapy decreased risk of death and relapse to three years mainly in patients with node positive N1-N2, who underwent curative resection with D2 lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is necessary improve the chemotherapy in this group of patients for decrease the rate of relapse.

Tratamiento adyuvante con quimioterapia y radioterapia luego de gastrectomía y disección ganglionar D2 en pacientes con cáncer gástrico en el Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú / Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients with gastric cancer in the National Institute of Cancer, Lima, Peru

Introducción: La quimio radioterapia adyuvante es una alternativa de tratamiento especialmente para pacientes con cirugías inferiores a D2. El estudio INT016 estableció la quimio radioterapia adyuvante como el cuidado estándar para adenocarcinoma resecado de alto riesgo del estómago en Estados Unidos, sin embargo, se vio obstaculizado por la cirugía sub óptima. Existe controversia acerca de la eficacia de esta terapia adyuvante en pacientes sometidos a linfandenectomía D2. En nuestra institución la linfandenectomía D2 es la cirugía estándar para cáncer gástrico. Objetivo: Demostrar que la terapia adyuvante de quimio y radioterapia en pacientes con cáncer gástrico sometidos a gastrectomía y disección ganglionar D2 es efectiva. Materiales y métodos: Estudio retrospectivo de pacientes con adenocarcinoma gástrico estadío II a IV M0 quienes se sometieron a resección curativa en el Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú en el periodo 2001 a 2006. El tratamiento estándar en la Institución es la linfandenectomía D2 y quimio radioterapia adyuvante de acuerdo al INT016. Las curvas de sobrevida fueron estimadas con el método Kaplan-Meier y comparadas con la prueba logrank. Resultados: 84 pacientes fueron incluidos 60,7% hombres y 39,3% mujeres. La edad media fue 49,5 años. Los estadios patológicos fueron T1-T2 (15,5%), T3-T4 (84,5%), N0-N1 (10,7%), N2-N3 (89,3%). Linfandenectomía D2 fue desarrollada en todos los pacientes. Encontramos una sobrevida libre de enfermedad a 3 años de 17% y una sobrevida global de 23,9%. Cuando se analiza por subgrupos, la sobrevida global en los grupos N1, N2 y N3 fueron 66,7%, 58,9% y 18,3%, respectivamente y la sobrevida libre de enfermedad fue 100%, 51,9% y 16,3%, respectivamente. Conclusiones: La quimio radioterapia adyuvante podría ser una alternativa para disminuir el riesgo de muerte y recaída a tres años principalmente en pacientes con ganglios positivos N1-N2, quienes se sometieron a resección curativa con linfandenectomía D2, pero la recurrencia fue más frecuente en ganglios positivos N3, la quimioterapia en este grupo de pacientes podría ser una alternativa para disminuir la tasa de recaída.

Introduction: Adjuvant chemo radiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT0116 pivotal trial established adjuvant chemo radiation as the standard care for resected high risk adenocarcinoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standard surgery for gastric cancer. Objective: To prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in patients’ with gastric cancer is effective. Material and methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima-Peru between 2001 and 2006. Standard treatment at institution is D2 lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant therapy. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test. Results: 84 patients were included 60.7% male and 39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2 (15.5%), T3-T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survival was 23.9%. However when we analyzed by subgroups the overall survival, was in group N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups were N1 (100%), N2 (51.9%) and N3 (16.3%). Conclusions: Adjuvant chemo radiotherapy decreased risk of death and relapse to three years mainly in patients with node positive N1-N2, who underwent curative resection with D2 lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is necessary improve the chemotherapy in this group of patients for decrease the rate of relapse.