Protocolo Latino-Americano de Sarcoma de Ewing : um estudo sobre as características clínicas e patológicas dos pacientes

Introdução: O Sarcoma de Ewing (SE) e o Tumor Neuroectodérmico Periférico (PNET) são tumores pequenos, redondos, de células azuis da infância e adolescência, que apresentam translocação cromossômica EWS em 85% dos casos, e imuno-histoquímica com expressão de superfície glicoproteína CD99. O diagnóstico pode ser desafiador e requer um patologista experiente em tumores ósseos e malignidades pediátricas. Métodos: O estudo atual do Grupo Cooperativo Latino-Americano de Sarcoma foi projetado para determinar a eficácia e segurança de um regime de quimioterapia com intervalo comprimido e a incorporação de quimioterapia metronômica para pacientes com SE recém-diagnosticada. Os relatórios de patologia de todos os centros com painel de imuno-histoquímica e translocações EWS foram recuperados dos prontuários médicos retrospectivamente e são descritos juntamente com dados demográficos e dados prognósticos e de sobrevida. Resultados: Foram analisados 400 pacientes em 31 centros com laudos completos de patologia. A translocação EWS foi feita em 20% dos pacientes (87/400). A Argentina realizou confirmação genética em pelo menos 40% dos pacientes, enquanto centros no Brasil, Chile e Uruguai somente solicitam quando o diagnóstico diferencial é necessário. NKX2-2 foi realizado em 61 pacientes (15,25%) e foi positivo em 95% dos casos. 7,5% dos pacientes foram diagnosticados com PNET. Os marcadores de diferenciação muscular mais frequentes foram a desmina e a miogenina. A sinaptofisina parece ser o marcador neural mais frequente, juntamente com LCA/CD45 e TdT como marcadores linfóides. Marcadores diferenciais epiteliais não foram comumente solicitados, mas foram positivos em cerca de 10% dos casos. O KI67 foi analisado em menos de 20% dos pacientes e a maioria apresentou índice alto (>30%). A idade mediana ao diagnóstico foi de 10,72 anos (variação de 0,02 a 32,85 anos). Os membros inferiores foram o local de tumor primário mais frequente (28,3%), seguido de tórax (21,9%), pelve (16,8%). A taxa de resposta geral foi de 82,5% (RC 18,8%, PR 63,6%), enquanto 10 pacientes (3,3%) apresentaram doença progressiva (DP). A ressecção cirúrgica do tumor foi realizada em 160 (50,8%) pacientes, cirurgia em combinação com radioterapia em 71 (28%) pacientes e radioterapia isolada em 51 (21%) pacientes. A análise da resposta histológica à quimioterapia pré-operatória de acordo com os critérios do Índice de Necrose (NI) foi determinada em 123 pacientes, e a distribuição mostrou que 54,5% e 45,5% tinham NI 30%). The median age at diagnosis was 10.72 years (range 0.02 to 32.85 years). Lower limbs were the most frequent primary tumor site (28.3%), followed by chest (21.9%), pelvis (16.8%). Overall response rate was 82.5% (CR 18.8%, PR 63.6%), while 10 patients (3.3%) had progressive disease (PD). Surgical tumor resection was performed in 160 (50.8%) patients, surgery in combination with radiation in 71 (28%) patients, and radiation alone in 51 (21%) patients. Analysis of histological response to preoperative chemotherapy according to Necrosis Index (NI) criteria was determined in 123 patients, and the distribution showed that 54.5% and 45.5% had NI <99% and 100%, respectively.Conclusion: Implementation of a multi-institutional protocol was feasible and resulted in outcomes that are comparable to those of groups in high-income countries. Only a minority of patients perform molecular testing and broad panel immunohistochemistry due to limited resources. Further collaboration is underway to standardize pathological diagnosis and molecular testing

Neurokinin-1 Receptor Antagonists for Chemotherapy-Induced Nausea and Vomiting: A Systematic Review

The addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention. We systematically searched the MEDLINE, EMBASE, and CENTRAL databases, and meeting proceedings for randomized controlled trials (RCTs) that evaluated NK1R antagonists plus standard antiemetic therapy for CINV prevention. Complete response (CR) to therapy was defined as the absence of emesis and the absence of rescue therapy. The endpoints were defined as CR in the overall phase (during the first 120 hours of chemotherapy), CR in the acute phase (first 24 hours), and the delayed phase (24120 hours) after chemotherapy, nausea, and toxicity. Subgroup analyses evaluated the type of NK1R antagonist used, the emetogenic potential of the chemotherapy regimen, and prolonged use of 5-HT3 (serotonin) receptor antagonists, a class of standard antiemetic agents. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates and publication bias were two-sided. Seventeen trials (8740 patients) were included in this analysis. NK1R antagonists increased the CR rate in the overall phase from 54% to 72% (OR = 0.51, 95% CI = 0.46 to 0.57, P < .001). CR and nausea were improved in all phases and subgroups. The expected side effects from NK1R antagonists did not statistically significantly differ from previous reports; however, this analysis suggests that the incidence of severe infection increased from 2% to 6% in the NK1R antagonist group (three RCTs with a total of 1480 patients; OR = 3.10; 95% CI = 1.69 to 5.67, P < .001). NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.104171280129

Risk factors associated with the development of oral mucositis in pediatric oncology patients : systematic review and meta-analysis

Objectives: Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the devel-opment of OM in pediatric cancer patients.Methods: A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients.Results: Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta- analysis showed that groups submitted to high- risk chemotherapy for OM had a 2.79- fold increased risk of OM.Conclusions: Identifying risk factors for OM is essential in order to allow individual-ized and early prevention treatment