Epidemiologia e os desfechos clínicos de pacientes com carcinoma de pequenas células do ovário, tipo hipercalcêmico (SCCOHT)

Objective: Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of patients with SCCOHT. Methods: We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. Results: Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo-oophorectomy performed in 26 patients (55%), and hysterectomy with bilateral salpingo-oophorectomy in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2 months with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. On multivariate analysis, factors associated with favorable prognosis included absence of large cell component (p = 0.0003, HR = 0.19, 95% CI 0.08 to 0.47) and early stage disease (p=0.0029, HR=0.28, 95% CI 0.12 to 0.64). Median overall survival (OS) for the 12 patients with a large cell component was 8.8 months compared with 19.4 months for the 35 patients without a large cell component. Median OS for patients with early stage disease was 35.3 months compared with 10.4 months for patients with advanced stage disease. A better prognosis was also associated with the use of radiotherapy (p = 0.0365, HR = 0.26, 95% CI 0.07 to 0.92). The multiagent chemotherapy regimen of vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin and etoposide (VPCBAE) was associated with a decreased rate of recurrence (p = 0.0394). Conclusion: These findings shows a predominant incidence in young adults, caucasian, with large. Frequent misinterpreted as other ovarian neoplasms. Surgery was part of the initial treatment of all patients followed by complementary platinum- based chemotherapy for most patients. High recurrence rates despite treatments. Favorable prognostic factors included absence of large cell component, early stage disease, use of radiotherapy and chemotherapy with VPCBAE regimen. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations.Objetivo: Carcinoma de pequenas células do ovário, tipo hipercalcêmico (SCCOHT) é doença rara de prognóstico pobre. Recentemente, demonstrou-se associação entre SCCOHT com mutações em genes SMARCA4, bem como, semelhanças moleculares e genéticas com tumor rabdoide maligno (TRM). O objetivo deste estudo é descrever as características clínicas, modalidades de tratamento e resultados oncológicos de série de pacientes com SCCOHT. Métodos: Foram analisados, retrospectivamente, dados de 47 pacientes com SCCOHT avaliados no MD Anderson Cancer Center, entre 1990 e 2014. Os prontuários médicos foram revisados para informações demográficas, achados patológicos, regimes de tratamento e desfechos oncológicos. Resultados: A idade média ao diagnóstico foi de 30 anos (variação 5-46). Todas as pacientes foram operadas, sendo salpingooforectomia unilateral (SOU) em 26 pacientes (55%), e histerectomia com salpingooforectomia bilateral (SOB) em 21 pacientes (45%). Dezesseis pacientes (34%) tinham doença em estádio I; seis (12,8%), estádio II; 23 (48,9%), estádio III; e dois pacientes (4,3%) tinham doença em estádio IV. Informações sobre o tratamento adjuvante estavam disponíveis de 43 pacientes: 83,3% receberam apenas quimioterapia; 9,5% quimioterapia seguida de radioterapia; 2,4% quimioterapia concomitante à radioterapia e 4,8% não receberam qualquer terapia adjuvante. O tempo de acompanhamento médio foi de 13,2 meses, com mediana de sobrevida global de 14,9 meses. Quimioterapia com multiagentes e radioterapia foram associadas a melhor prognóstico. Fatores associados ao prognóstico favorável em análise multivariada incluíram ausência de componente de grandes células (p= 0,0003, HR = 0,19, IC 95% 0,08 a 0,47) e doença em estádio inicial (p = 0,0029, HR = 0,28, IC 95% 0,12 a 0,64). A sobrevida global mediana (SG) para as 12 pacientes com um componente de grandes células foi de 8,8 meses, em comparação com os 19,4 meses das 35 pacientes sem um componente de grandes células. A SG mediana para pacientes com doença em estágio inicial foi de 35,3 meses, em comparação com 10,4 meses para pacientes com doença em estágio avançado. Um prognóstico melhor também foi associado ao uso de radioterapia (p = 0,0365, HR = 0,26, IC 95% 0,07 a 0,92). O regime quimioterápico multiagente de vinblastina, cisplatina, ciclofosfamida, bleomicina, doxorrubicina e etoposídeo (VPCBAE) foi associado à menor taxa de recorrência (p = 0,0394). Conclusão: Os resultados mostram incidência predominante em adultas jovens, caucasianas. Os tumores na primeira avaliação patológica foram frequentemente confundidos com outras neoplasias do ovário. Cirurgia fez parte do tratamento de todas as pacientes, seguido de quimioterapia complementar à base de platina para a maioria das pacientes. Houve altas taxas de recorrência apesar dos tratamentos. Fatores prognósticos favoráveis incluíram ausência de componente de grandes células, doença estádio inicial, uso de radioterapia e quimioterapia com regime VPCBAE. Mais estudos são necessários para confirmar os resultados encontrados, assim como, a adoção de tratamentos sistêmicos utilizados para TRM, bem como, o desenvolvimento de novos agentes com alvo nas mutações específicas.Dados abertos - Sucupira - Teses e dissertações (2020

A Potential Role for Complement in Immune Evasion by Mycobacterium leprae

Lepromatous leprosy is a model of immune evasion wherein pathogen-specific IL-10-secreting T cells and concomitant failure of Th-1 immunity permit uncontrolled proliferation of the intracellular pathogen, Mycobacterium leprae (M. leprae). The mechanism of this immune escape is unknown. Here, the authors report that phenolic glycolipid-1 (PGL-1), a major and distinguishing feature of the M. leprae cell wall, is expressed in the cell membrane of M. leprae-infected human dendritic cells, where it can activate complement in human serum. The authors demonstrate that PGL-1 and the C3 component of complement colocalize in lipid rafts in the dendritic cell membrane, and enter the immune synapse upon co-culture of M. leprae-infected DCs and T cells. Hence, activated C3 is strategically located to costimulate naive T cells via the complement regulatory protein, CD46, a process known to stimulate the differentiation of IL-10-secreting regulatory T cells. These observations suggest a potential novel mechanism of immune evasion, wherein M. leprae may subvert host natural immunity to provoke an adaptive response that favors bacillary survival.Dana FoundationHeiser Program for Research in Leprosy and TuberculosisUniversity of Miami Diabetes Research InstituteJuvenile Diabetes Research FoundationSylvester Comprehensive Cancer CenterUniv Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USAUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Miami, Miller Sch Med, Dept Dermatol, Miami, FL 33136 USAUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

Sustained Complete Response after Maintenance Therapy with Topotecan and Erlotinib for Recurrent Cervical Cancer with Distant Metastases

Introduction: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR) inhibitors may have a role in this setting. Case Description: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. Conclusion: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance

Radiotherapy for recurrent small cell carcinoma of the ovary: A case report and review of the literature

• Small cell carcinoma of the ovary is a rare and aggressive malignant tumor. • No effective treatment for recurrent disease has yet been described. • Patients with recurrent disease may respond to salvage surgery, chemotherapy, radiotherapy or a combination of these modalities