BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment.

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.

Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities.

BACKGROUND: Soft tissue sarcomas (STS) comprise a diverse group of mesenchymal malignancies that require multidisciplinary care. Although surgery remains the primary form of treatment for those with localized disease, radiation therapy (RT) is often incorporated either in the neo- or adjuvant setting. Given the development of modern RT techniques and alternative dosing schedules, stereotactic ablative radiotherapy (SABR) has emerged as a promising technique. However, the current role of SABR in the treatment of STS of the extremities remains uncertain. METHODS AND MATERIALS: This was a single-center, prospective, single-arm phase II trial. Patients with localized STS who were candidates for limb-preservation surgery were included. Experimental treatment consisted of SABR with 40 Gy in 5 fractions, administered on alternate days, followed by surgery after a minimum interval of 4 weeks. The primary outcome was the rate of wound complication. Secondary outcomes included 2-year local control (LC), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) rates (and other toxicities). RESULTS: Twenty-five patients were enrolled between October 2015 and November 2019 and completed the treatment protocol. The median rate of histopathologic regression was 65% (range 0-100) and 20.8% of tumors presented pathologic complete response (pCR). Wound complications were observed in 7/25 patients (28%). Three patients underwent disarticulation by vascular occlusion after plastic reconstruction and one patient was amputated by grade 3 limb dysfunction. After a median follow up of 20.7 months, the 2-year estimated risk of local recurrence, distant metastasis and cause-specific death were 0%, 44.7% and 10.6% respectively. CONCLUSIONS: Neoadjuvant SABR appears to improve the pCR for patients with eSTS, with acceptable rate of wound complications. Nevertheless, this benefit should be weighed against the risk of late of vascular toxicity with SABR regimen since, even in a short median follow-up, a higher rate of amputation than expected was observed. A larger sample size with longer follow-up is necessary to conclude the overall safety of this strategy.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil.

BACKGROUND: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. OBJECTIVE: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. METHODS: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. RESULTS: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. CONCLUSION: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil / Abordando glioblastomas durante a pandemia pelo COVID-19: recomendações atuais e considerações no Brasil

ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

RESUMO Introdução: Pacientes com câncer, em geral, e particularmente pacientes com glioblastoma estão sob elevado risco de desenvolver síndrome respiratória aguda grave devido à infecção pelo SARS-CoV-2, e alcançar um equilíbrio entre risco de exposição à infecção e benefício clínico do tratamento seria o ideal. O comportamento agressivo desse grupo de tumores justifica a necessidade de equipe multidisciplinar para auxiliar nas decisões clínicas durante a pandemia vigente. O Brasil ocupa hoje o segundo lugar em número de casos e óbitos pela COVID-19, e as atuais disparidades no tratamento de pacientes neuro-oncológicos desafiarão as decisões clínicas e cirúrgicas dessa população, possivelmente afetando a sobrevida global. Objetivo: Guiar decisões clínicas e cirúrgicas relacionadas ao manejo de glioblastoma durante a pandemia pelo COVID-19 no Brasil por meio de pesquisa em literatura. Métodos: Busca sistemática no banco de dados eletrônico da PubMed por estudos ou consensos quanto à abordagem de glioblastoma durante a pandemia por COVID-19 até 18/07/2020. Resultado: Ao abordar o glioblastoma durante a pandemia pela COVID-19, parâmetros importantes que auxiliam no processo de tomada de decisão são idade, desempenho, perfil molecular tumoral e consentimento do paciente. Pacientes jovens devem seguir protocolo padrão após máxima ressecção cirúrgica, principalmente aqueles com metilação do promotor MGMT. Idosos e pacientes debilitados devem ser cuidadosamente avaliados, e monoterapia deve ser provavelmente considerada. Centros de saúde são orientados a utilizar-se da telemedicina e de meios para reduzir infecção local. Conclusão: A abordagem do glioblastoma durante a pandemia por COVID-19 será mundialmente desafiadora, mas particularmente no Brasil, onde ainda existe significativa inequidade no cuidado com a saúde.

Systemic dissemination of glioblastoma: literature review.

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

Systemic dissemination of glioblastoma: literature review

SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma.

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Qualidade de vida, depressão e câncer de mama: um estudo piloto da Faculdade de Medicina do ABC / Quality of life, depression and breast cancer: a pilot study of ABC School of Medicine

Muitas mulheres com diagnóstico de câncer de mama se deparam com conflitos pessoais. Há estudos na literatura que associam câncer de mama com pior qualidade de vida e depressão. Objetivo: Nosso objetivo neste trabalho foi avaliar qualidade de vida e depressão das pacientes com câncer de mama em quimioterapia (QT) e compará-las com um grupo de controle e com um grupo de pacientes em seguimento após terem completado a sua QT. Métodos: Aplicar questionário geral, questionário de qualidade de vida (QV), versão WHOQL-brief, e o questionário Beck para avaliação de depressão em pacientes: ao diagnóstico (grupo 1), antes do início da QT (D0), após uma semana do primeiro ciclo de QT (D1-7) e após uma semana do segundo ciclo de QT (D2-7); em pacientes em seguimento clínico (grupo 2); e no grupo de controle (grupo 3). Resultados: 1) Pacientes em QT apresentaram uma pontuação significativamente inferior apenas no domínio físico do questionário WHOQL quando comparadas ao grupo de controle (p<0,05), não apresentando alterados os domínios psicológico, social e ambiental, e pontuação total do questionário WHOQL; 2) não evidenciamos depressão quando analisamos diferenças de pontuação no questionário de Beck entre grupos 1 e 2 e entre os grupos 1 e 3. Conclusão: Não encontramos evidências de que a quimioterapia induza um nível significativo de depressão nas pacientes com câncer de mama a ela submetidas. À exceção de significativa mudança na pontuação do domínio físico, o início do tratamento quimioterápico parece não implicar em piora de qualidade de vida das mulheres com câncer de mama quando comparadas às mulheres em seguimento ou mulheres sem doença.

Many women after a diagnosis of breast cancer (BC) come across personal conflicts. Some studies have associated breast cancer with worsening quality of life (QOL) and depression. Aims: Evaluating the quality of life and depression of breast cancer patients treated with chemotherapy (CH) and comparing it with normal women and patients who already finished their chemotherapy. Methods: We employed a general questionare, a quality of life questionnaire WHOQL and the Beck depression questionnaire in the following groups of patients: group 1 - women with BC before chemotherapy (DO), one week after the first cycle (D1-7) and one week after the second cycle; group 2 - patients in the follow-up; and group 3 - control group of normal women. Results: 1) Group 1 reported poorer physical domain scores in the questionnaire WHOQL when compared with the contro group (p<0,05); 2) there was no evidence of significant differences in the Beck depression questionnaire scores between groups 1 and 2 or between groups 1 and 3. Conclusion: We believe that beginning chemotherapy does not produce a significant level of depression in BC patients who undergo this treatment acutely. Except for a significant decrease in the physical domain scores of the QOL questionnaire, beginning chemotherapy seems not to worsen overall QOL in women with BC when compared to women who already finished treatment or to normal healthy women.