Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors / 医学前沿

The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors (ICIs) in China has not been quantified. This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology. A total of 11 ICIs were recommended for 17 cancer types. The estimated number of eligible patients annually was 1 290 156 (55.18%), which included 888 738 males (60.05%) and 400 468 females (46.67%). The estimated number of responders annually was 448 972 (19.20%), which included 309 023 males (20.88%) and 139 764 females (16.29%). Gastric cancer (n=291 000, 12.45%), non-small-cell lung cancer (n=289 629, 12.39%), and hepatocellular carcinoma (n=277 100, 11.85%) were the top three cancer types with the highest number of eligible patients. Non-small-cell lung cancer (n=180 022, 7.70%), hepatocellular carcinoma (n=75 648, 3.24%), and small-cell lung cancer (n=64 362, 2.75%) were the top three cancer types with the highest number of responders. In conclusion, ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.

Progress of Neoadjuvant Immunotherapy for Non-small Cell Lung Cancer / 中国肺癌杂志

Neoadjuvant immunotherapy, including neoadjuvant single- or dual-drug immunotherapy or combined immunotherapy with chemotherapy or radiotherapy, has witnessed a rapid development in non-small cell lung cancer. Clinical trials exhibited the encouraging pathological responses and certain clinical benefits in selected patients, with tolerable toxicity. Nivolumab with chemotherapy has been approved by Food and Drug Administration (FDA) as the first immunotherapy-based treatment for non-small cell lung cancer in the neoadjuvant treatment setting. There is the need for further evaluation of long-term efficacy, side effects or surgical issues for neoadjuvant immunotherapy in non-small cell lung cancer.
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Current Progress and Future Developments of Antibody Drug Conjugates in Lung Cancer / 中国肺癌杂志

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Chinese expert consensus of antibody-drug conjugate toxicity management for breast cancer / 中华肿瘤杂志

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.

Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Este documento é uma versão resumida do relatório técnico da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec e foi elaborado numa linguagem simples, de fácil compreensão, para estimular a participação da sociedade no processo de Avaliação de Tecnologias em Saúde (ATS) que antecede a incorporação, exclusão ou alteração de medicamentos, produtos e procedimentos utilizados no SUS. As recomendações da Comissão são submetidas à consulta pública pelo prazo de 20 dias. Após analisar as contribuições recebidas na consulta pública, a Conitec emite a recomendação final, que pode ser a favor ou contra a incorporação, exclusão ou alteração da tecnologia analisada. A recomendação final é, então, encaminhada ao Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde -SCTIE/MS, que decide sobre quais tecnologias em saúde serão disponibilizadas no SUS

Tratamiento preventivo en migraña: anticuerpos monoclonales contra la vía del péptido relacionado con el gen de la calcitonina / Migraine preventive treatment: monoclonal antibodies against calcitonine gene related peptide

Resumen La migraña es un trastorno muy prevalente que afecta a alrededor del 15% de los sujetos adultos. Es clasificada por la Organización Mundial de la Saludentre los primeros puestos como causa de discapacidad. Los tratamientos preventivos habituales hasta ahora derivan de otras indicaciones y por serendipia se utilizan en prevención de migraña: betabloqueantes, drogas antiepilépticas, antidepresivos tricíclicos, bloquean tes de canales de calcio, toxina botulínica. Todas ellas han mostrado eficacia similar al 50% en reducir el número de episodios migrañosos pese a efectos secundarios indeseados. Durante los últimos años, se ha evaluado la eficacia y seguridad de los anticuerpos monoclonales (AM) que actúan sobre la vía del péptido relacionado con el gen de la calcitonina (CGRP) en migraña. Dicho péptido es relevante en la activación del dolor en territorio meníngeoy es mediado por terminales nerviosas trigeminales una vez activado el proceso migrañoso. Su dosaje en crisis migrañosas ha sido elevado en diversos estudios y su neutralización/bloqueo, redunda en alivio del dolor. Los anticuerpos monoclonales erenumab, galcanezumab, fremanezumab, eptinezumab aprobados en el mercado EE.UU./Europa desde 2018 y tras varios trabajos de Fase III y abiertos de extensión, mostraron clara seguridad yeficacia y están presentes en nuestro medio desde mediados de 2019. Desarrollamos la racionalidad e indicaciones de uso de los mismos.

Abstract Migraine is a very prevalent disorder that is estimated to affect about 10-15% of adult subjects. Ac cording to the World Health Organization migraine is one of the first causes of disability. Traditional preventive treatments discovered by serendipity include Beta blockers, antinconvulsants drugs, calcium channel blockers, tricyclic antidepressants and onabotulinum A and offer about 50% efficacy after controlled placebo trials and real life use. Because of lack of adherence and adverse events, there is a loss of beneficial sustain on these treat ments. Recently, the efficacy and safety of monoclonal antibodies (MA) that act on the peptide pathway related to the calcitonin gene (CGRP) has been evaluated in migraine, being the first specific tailored treatment on one of the multiple targets on migraine. This family of drugs: erenumab, galcanezumab, fremanezumab, eptinezumab, finished Fase III, extensions trials and many of them are in the market approved since 2018.Since 2019 are available in Argentina. We will describe the rationale for the prescription of this family of new drugs for migraine.

Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Relatório técnico com Leis que estabelece que a incorporação, a exclusão ou a alteração de novos medicamentos, produtos e procedimentos, bem como a constituição ou alteração de protocolo clínico ou de diretriz terapêutica são atribuições do Ministério da Saúde (MS). A estrutura de funcionamento da Conitec é composta por Plenário e Secretaria-Executiva. A gestão e a coordenação das atividades da Conitec, bem como a emissão do relatório de recomendação sobre as tecnologias analisadas são de responsabilidade da Secretaria-Executiva ­ exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE/MS).

Antibody-drug conjugates in HER2-positive breast cancer / 中华医学杂志(英文版)

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Peripheral Blood Inflammation Indicators as Predictive Indicators in Immunotherapy of Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death, of which non-small cell lung cancer (NSCLC) is the most common type. Immune checkpoint inhibitors (ICIs) have now become one of the main treatments for advanced NSCLC. This paper retrospectively investigated the effect of peripheral blood inflammatory indexes on the efficacy of immunotherapy and survival of patients with advanced non-small cell lung cancer, in order to find strategies to guide immunotherapy in NSCLC.@*METHODS@#Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. And were followed up until 10 December 2020, and the efficacy was evaluated according to RECIST1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were followed up for survival analysis. A clinical prediction model was constructed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR) based on NLR data at three different time points: before treatment, 6 weeks after treatment and 12 weeks after treatment (0w, 6w and 12w), and the accuracy of the model was verified.@*RESULTS@#173 patients were finally included, all of whom received the above treatment regimen, were followed up for a median of 19.7 months. The objective response rate (ORR) was 27.7% (48/173), the disease control rate (DCR) was 89.6% (155/173), the median PFS was 8.3 months (7.491-9.109) and the median OS was 15.5 months (14.087-16.913). The chi-square test and logistic multi-factor analysis showed that NLR6w was associated with ORR and NLR12w was associated with ORR and DCR. Further Cox regression analysis showed that NLR6w and NLR12w affected PFS and NLR0w, NLR6w and NLR12w were associated with OS.@*CONCLUSIONS@#In patients with advanced non-small cell lung cancer, NLR values at different time points are valid predictors of response to immunotherapy, and NLR <3 is often associated with a good prognosis.

Obtención de una versión IgG1 de ratón del rituximab para detectar la molécula CD20 humana / Obtaining a mouse IgG1 version of rituximab to detect the human CD20 molecule

Introducción: El rituximab, anticuerpo quimérico que reconoce la molécula CD20 humana, se ha utilizado en el tratamiento de diversos trastornos linfoproliferativos de células B. Para la selección de los potenciales beneficiarios del tratamiento con rituximab se han desarrollado técnicas que, mediante el uso de anticuerpos monoclonales, detectan la presencia del CD20 en los linfocitos de estos pacientes. Objetivo: Obtener y caracterizar un anticuerpo recombinante IgG1 de ratón específico para la molécula CD20 humana, que contenga las regiones variables del anticuerpo rituximab. Métodos: Para la expresión estable del anticuerpo recombinante se empleó la transducción lentiviral de células de embrión de riñón humano (HEK293). La caracterización inmunoquímica del anticuerpo se realizó por la técnica de Western Blot y su capacidad de reconocimiento de la molécula CD20 humana se evaluó por citometría de flujo e inmunohistoquímica. Resultados: Se obtuvo el anticuerpo 1F5 que reconoce, por citometría de flujo, la molécula CD20 en líneas celulares humanas de origen linfoide, así como en células de sangre periférica de humanos sanos y pacientes con trstornos linfoproliferativos de células B. Sin embargo, la técnica de inmunohistoquímica solo permitió detectar con este anticuerpo la molécula CD20 en tejidos frescos, no así en los embebidos en parafina. Conclusiones: Este trabajo sugiere las potencialidades del uso del anticuerpo 1F5 para las mediciones de la expresión de CD20 por citometría de flujo en pacientes con leucemias B o linfomas B avanzados en fase de leucemización. Esto complementaría los estudios para la selección apropiada de pacientes para el tratamiento con el rituximab(AU)

Introduction: Rituximab, chimeric antibody specific for human CD20 molecule, has been widely used in the treatment of several B-cell linfoproliferative disorders. For the selection of patients with the greatest potential to benefit from the therapy with rituximab, a number of techniques using monoclonal antibodies have been developed to detect the CD20 molecule. Objective: To obtain and to characterize a mouse IgG1 recombinant antibody, specific for human CD20, that contains the variable regions of rituximab. Methods: The lentiviral transduction of human embryonic kidney cells (HEK293) was used for the stable expression of the recombinant antibody. The immunochemical characterization of the antibody was performed by Western Blot and the recognition of CD20 was evaluated by immunohistochemistry and flow cytometry. Results: We generated the antibody 1F5, able to recognize by flow cytometry the CD20 molecule expressed on lymphoid human cell lines, as well as peripheral blood mononuclear cells from healthy donors and patients with B-cell lymphoproliferative disorders. However, 1F5 antibody detected the CD20 molecule on fresh tissues, but not on formalin-fixed paraffin embedded tissues,by immunohistochemistry. Conclusions: This work suggests the potential use of 1F5 antibody for the measurement of CD20 expression by flow cytometry in patients with B-cell leukemias or B-cell lymphomas in phase of leukemization. This could complement the studies to ensure the appropriate selection of patients for the treatment with rituximab(AU)

Uso de rituximabe no tratamento de linfoma linfoplasmocítico durante terapia de substituição renal contínua / Rituximab use for lymphoplasmacytic lymphoma during continuous renal replacement therapy

RESUMO A segurança e a eficácia do rituximabe em pacientes com comprometimento renal não foram estabelecidas, e o mesmo ocorre com os efeitos da hemodiálise nos níveis séricos de rituximabe. Atualmente, apenas alguns relatos de caso avaliaram o nível sérico de rituximabe antes e após a diálise. Não foram até aqui publicados dados relativos ao uso de rituximabe em pacientes sob terapia de substituição renal contínua. Os autores apresentam um caso referente a uma mulher com 59 anos de idade atendida com quadro de tetraparesia paraneoplásica. Ela foi admitida no serviço de medicina intensiva devido a hemorragia alveolar com insuficiência respiratória e lesão renal aguda, que necessitou da utilização de terapia de substituição renal contínua. Após os procedimentos diagnósticos, estabeleceu-se o diagnóstico de linfoma linfoplasmocítico. Deu-se início ao tratamento com rituximabe e ciclofosfamida. Os níveis de rituximabe foram determinados no soro e no dialisato. Não se encontrou qualquer nível de rituximabe no dialisato. A paciente faleceu após 2 meses no serviço de medicina intensiva por pneumonia nosocomial causada por Pseudomonas aeruginosa resistente a múltiplos fármacos.

ABSTRACT Rituximab safety and efficacy in patients with renal impairment have not been established, nor have the effects of hemodialysis on serum rituximab level. There are only a few published case reports assessing serum rituximab level pre- and postdialysis. No data have been published regarding the usage of rituximab in patients with continuous renal replacement therapy. The authors present a case of a 59-year-old female patient who presented with paraneoplastic tetraparesis. She was admitted to the intensive care unit due to alveolar hemorrhage with respiratory failure and acute kidney injury requiring continuous renal replacement therapy. After a diagnostic workup, the diagnosis of lymphoplasmacytic lymphoma was established. Therapy with rituximab and cyclophosphamide was started. Rituximab levels were determined in serum and dialysate. No rituximab was found in the dialysate. The patient died after 2 months in the intensive care unit from nosocomial pneumonia due to multidrug-resistant Pseudomonas aeruginosa.

Macroglobulinemia de Waldenström: experiencia de 15 años en el Hospital del Salvador, Santiago, Chile / Waldenström macroglobulinemia: experience in 31 patients

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

Resultados de pacientes con linfoma del manto: impacto de terapias basadas en citarabina y trasplante hematopoyético / Cytarabine and hematopoietic cell transplantation for mantle cell lymphoma: analysis of 20 patients

Background: Mantle cell lymphoma (MCL) has high relapse and mortality rates. There is a survival benefit when treatment is intensified with cytarabine (AraC), hematopoietic cell transplantation (HCT) and maintenance with rituximab. Aim: To assess the outcomes of patients with MCL treated in a university hospital. Material and Methods: Review of an oncology center database and medical records identifying patients with MCL treated between 2006 and 2017. Death dates were obtained from the death certificate database of the National Identification Service. We analyzed the response rate, overall survival (OS) and progression-free survival (PFS). As a secondary objective, the survival impact of AraC, HCT and maintenance with rituximab, was also analyzed. Results: Information on 20 patients aged 62 ± 11 years, followed for a median of 45 months was retrieved. Eighty-five percent were diagnosed at an advanced stage. The most used first-line regime was R-CHOP in 11 patients, followed by R-HyperCVAD in five. Only 47% achieved complete response. 4-year PFS and OS were of 30 and 77% respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) significantly predicted PFS and OS. Maintenance with rituximab or HCT was associated with better PFS (48 vs 21 months, p < 0.01). The exposure to AraC or HCT, in refractory or relapsed disease, was associated with an increase in PFS from 9 to 28 months (p = 0,02) and 4-year OS from 40 to 100% (p = 0.05). OS increased even more, from 25 to 100% in those with high-risk MIPI (p = 0.04). Conclusions: The incorporation of AraC, HCT and maintenance with rituximab in the therapeutic backbone of MCL, especially for high-risk cases, was associated with improved survival.

Nimotuzumab y radioterapia en el tratamiento de tumores del tallo cerebral en niños y adolescentes / Nimotuzumab and radiotherapy in the treatment of brainstem tumors in children and adolescents

Introducción: Los tumores localizados en el tallo cerebral en los niños y adolescentes conllevan un mal pronóstico, especialmente aquellos infiltrantes y difusos. Con el tratamiento de radioterapia apenas llegan a más de 15 por ciento de supervivencia y no mejora la cifra con quimioterapia agregada. Objetivos: Estimar el efecto de la asociación del tratamiento radiante con el anticuerpo monoclonal Nimotuzumab en la supervivencia de niños y adolescentes con tumores del tallo cerebral. Método: Estudio clínico no aleatorizado, analítico, longitudinal y prospectivo. Se estudió una serie de 46 pacientes entre 2 y 18 años de edad que padecían de tumores del tallo cerebral, infiltrantes y difusos, desde enero de 2008 y en seguimiento hasta marzo de 2018. Todos se trataron con radioterapia, con dosis entre 54 y 59,8 cGrey, dosis diaria de 1,8 cGrey, y se irradiaban de lunes a viernes. Mientras duró el tratamiento radiante recibieron Nimotuzumab, en la dosis de 150 mg/m2 de superficie corporal, luego semanal con 8 dosis, y finalmente mensual durante uno o dos años. Resultados: Se alcanzó en la serie una supervivencia media de 18,4 meses, y una esperada de 42,9 por ciento a 2 años y 35,5 por ciento a 5 años, estabilizada hasta los 10 años. Conclusiones: La combinación de radioterapia y el anticuerpo monoclonal Nimotuzumab incrementa la supervivencia en niños y adolescentes con tumores del tallo cerebral y es bien tolerada, aun en periodos prolongados, e incluso en casos de recidiva(AU)

Introduction: Tumors localized in the brainstem of children and adolescents entail a bad prognosis, especially those that are intrinsic and diffuse. With radiotherapy treatment, patients barely get a 15 percent of survival, and the numbers don't improve with added chemotherapy. Objectives: To estimate the effect of the association of radiotherapy treatment with Nimotuzumab monoclonal antibody in the survival of children and adolescents with brainstem tumors. . Method: Non randomized, analytical, longitudinal and prospective clinical study that was authorized by the National Regulatory Authority. There was studied a group of 46 patients aged from 2 to 18 years that suffered from intrinsic and diffuse brainstem tumors, from January 2008 (and in follow up) to March 2018. All the patients were treated with radiotherapy, with doses among 54 and 59,8 Grey, daily doses of 1,8 Grey, and from Monday to Friday. While they were under radiotherapy treatment, they get Nimotuzumab, in doses of 150 mg/m2 of corporal surface; then weekly doses of 8 shots; and finally, monthly doses during one or two years. Results: In this group there was a survival mean of 18, 4 months, and an expected survival of 42, 9 percent for 2 years and 35, 5 percent for 5 years that can be stabilized to 10 years. Conclusions: Combination of radiotherapy and Nimotuzumab monoclal antibody can increase the survival from brainstem tumors in children and adolescents(AU)

Miocardiopatia não compactada em gestante com linfoma não Hodgkin. Relato de caso / Non-compaction cardiomyopathy in pregnant women with non-Hodgkin lymphoma: a case report

A miocardiopatia não compactada é uma doença congênita rara, que pode ocorrer isoladamente ou associada a outros defeitos, por falha no processo de compactação das fibras miocárdicas, resultando na persistência de trabeculações e recessos profundos. A associação entre a miocardiopatia não compactada e gestação é incomum na literatura, assim como a relação com macroglobulinemia de Waldenstrom, um tipo de linfoma não Hodgkin. Descrevemos aqui a rara associação destas três patologias. Trata-se de paciente do sexo feminino, sem antecedentes hematológicos, neoplasias ou cardiopatias, que procurou o serviço com queixa de astenia progressiva, dores no corpo, perda ponderal importante e anemia. Na investigação diagnóstica, a imunoeletroforese de proteína constatou pico monoclonal em IgM Kappa, com inventário medular por imunofenotipagem e biópsia de medula óssea com Kappa+, CD19+, CD20+, CD38 e CD79b, confirmando diagnóstico de neoplasia de linfócitos B maduros. Na terapêutica, optou-se pelo esquema de primeira linha com dexametasona, rituximabe e ciclofosfamida (DRC) − este último considerado agente alquilante cardiotóxico. Em triagem pré-quimioterápica, o eletrocardiograma mostrou alteração da repolarização ventricular anterosseptal. O ecocardiograma transtorácico evidenciou trabeculações excessivas no ápice do ventrículo esquerdo, sugerindo não compactação do miocárdio. A ressonância magnética confirmou o diagnóstico. Foi iniciada terapia com metoprolol e ácido acetilsalisílico. Todavia, após o último ciclo de terapia quimioterápica, paciente descobriu gravidez (G1P1A0). O período gestacional e o puerpério evoluíram sem manifestações clínicas de insuficiência cardíaca, em classe funcional I (New York Heart Association), mesmo com redução da fração de ejeção do ventrículo esquerdo ao ecocardiograma transtorácico. (AU)

Non-compaction cardiomyopathy is a rare congenital disease that can occur in isolation or associated with other defects, due to failure in compaction of myocardial fiber, resulting in persistence of myocardial trabeculations and deep recesses. The association between non-compaction cardiomyopathy and gestation, as well as the relationship with Waldenstrom's macrobulinemia, a type of Non-Hodgkin's Lymphoma (NHL), are not common in the literature. This study describes the rare association of these three pathologies. This is the case of a female patient with no history of hematological, neoplastic, or heart diseases, who sought the service with complaints of progressive weakness, body aches, important weight loss, and anemia. During the diagnostic investigation, protein immunoelectrophoresis showed a monoclonal peak in IgM Kappa monoclonal gammopathy, with a medullary inventory by immunophenotyping and bone marrow biopsy with Kappa+, CD19+, CD20+, CD38 and CD79b, confirming the diagnosis of mature B-cell lymphocyte neoplasm. The first line therapy chosen was dexamethasone, rituximab, and cyclophosphamide (CKD), with the latter being considered a cardiotoxic alkylating agent. At pre-chemotherapy screening, the electrocardiogram showed an alteration of the anteroseptal ventricular repolarization. Transthoracic echocardiography (ETT) showed excessive trabeculations at the apex of the left ventricle (LV), suggesting no compaction of the myocardium. The magnetic resonance imaging confirmed the diagnosis.Therapy with metoprolol and acetylsalicylic acid was started. However, after the last cycle of chemotherapy, the patient found she was pregnant (G1P1A0). The gestational and puerperium period progressed with no clinical manifestations of heart failure, in functional class I (New York Heart Association), albeit the reduction of the ejection fraction of the left ventricular shown in the transthoracic echocardiography. (AU)

Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy: Trends and perspectives

Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC.

El hepatocarcinoma (HCC) es la segunda causa de muerte relacionada con el cáncer en el mundo y es la principal causa de muerte en pacientes cirróticos. Desafortunadamente, la incidencia de HCC ha crecido significativamente en la última década. Los tratamientos curativos como la cirugía, el trasplante de hígado o la ablación solo pueden aplicarse en menos del 30% de los casos. El sorafenib es el tratamiento de primera línea para el HCC avanzado, mientras que el regorafenib se reserva como segunda línea. Sin embargo, todavía son necesarios nuevos enfoques terapéuticos potentes y más específicos para el HCC avanzado. El hígado constituye un microambiente inmunológico único, aunque la inmunidad antitumoral parece ser factible mediante el uso de inhibidores de punto de control como nivolumab. La eficacia puede aumentarse adicionalmente combinando inhibidores de puntos de control inmunitario o aplicando tratamientos loco-regionales. En este sentido, el éxito del uso de anticuerpos monoclonales, que bloquean el control inmunitario, ha renovado el interés en la inmunoterapia para el HCC.

Current approaches to immunotherapy in noncolorectal gastrointestinal malignancies

Noncolorectal gastrointestinal (GI) malignancies are among the most frequently diagnosed cancers. Despite the undeniable progress in systemic treatments in recent decades, further improvements using cytotoxic chemotherapy seem unlikely. In this setting, recent discoveries regarding the mechanism underlying immune evasion have prompted the study of molecules capable of inducing strong antitumor responses. Thus, according to early data, immunotherapy is a very promising tool for the treatment of patients with GI malignancies. Noncolorectal GI cancers are a major public health problem worldwide. Traditional treatment options, such as chemotherapy, surgery, radiation therapy, monoclonal antibodies and antiangiogenic agents, have been the backbone of treatment for various stages of GI cancers, but overall mortality remains a major problem. Thus, there is a substantial unmet need for new drugs and therapies to further improve the outcomes of treatment for noncolorectal GI malignancies. "Next-generation" immunotherapy is emerging as an effective and promising treatment option in several types of cancers. Therefore, encouraged by this recent success, many clinical trials evaluating the efficacy of immune checkpoint inhibitors and other strategies in treating noncolorectal GI malignancies are ongoing. This review will summarize the current clinical progress of modern immunotherapy in the field of noncolorectal GI tumors.

Cancer immunology and melanoma immunotherapy

Abstract: The stimulation of the immune system, in order to generate an attack against cancer cells, similarly to that which occurs in infectious disease, has long been matter of interest in oncology; however, only limited success has been achieved, with different treatment strategies tested in recent years. The development of new immune checkpoint inhibitors is currently changing this scenario, and immunotherapy is becoming a real choice among traditional cytotoxic treatments to fight cancer. Recent reports have shown efficacy and safety with the use of pembrolizumab, nivolumab, and ipilimumab for the treatment of different neoplasms, especially melanoma. In this article, we propose a review of the mechanisms of action involved in cancer immunology, the response evaluation of immunotherapies, and its toxicity profile, as well as a summary of the main clinical trials that led to the adoption of these new drugs for melanoma treatment.