Rabdomiossarcoma de ovário em paciente jovem: Relato de caso / Ovarian rhabdomyosarcoma in a young patient: report of case

O sarcoma de partes moles mais comum na infância é o rabdomiossarcoma. Entretanto a localização ovariana é extremamente rara. Acredita-se que este tumor se origina de células imaturas destinadas a compor o músculo esquelético, porém pode surgir em locais onde tipicamente não há músculo esquelético. O diagnóstico do Rabdomiossarcoma primário de ovário pode causar um dilema entre os clínicos, cirurgiões e patologistas, por se tratar de um tumor muito raro. Após o diagnóstico, é necessária a investigação de possíveis metástases. Este caso trata de uma paciente de 17 anos, submetida a parto cesáreo e, no intraoperatório, foi observado aumento de volume, inespecífico, de ovário direito sendo optado por não abordar naquele momento. De antecedentes pessoais, apresentava ooforectomia esquerda aos 13 anos, por Tumor de células da granulosa juvenil e lobectomia inferior esquerda por malformação adenomatosa cística aos 7 anos. Deu entrada no Pronto Socorro 17 dias após dar à luz com queixa de febre, vômitos e dor abdominal. Foi realizada ultrassonografia de urgência, onde foi visualizada massa sólida em fossa ilíaca direita medindo 14,0 x 11,2 x 10,8 cm. Realizada laparotomia exploradora com anexectomia direita e cito-redução subótima do tumor. O resultado anátomo-patológico demonstrou neoplasia maligna fusocelular com áreas de necrose em ovário. A complementação com o estudo imunohistoquímico concluiu rabdomiossarcoma embrionário. Ela voltou a procurar atendimento no Pronto Socorro dois meses após a abordagem com queixa de vômitos biliosos e epigastralgia. Realizou tomografia computadorizada que identificou recidiva do tumor. Durante a internação, evoluiu com quadro de tromboembolismo pulmonar agudo. Diante disso, foi iniciada terapia com enoxaparina em dose plena e quimioterapia com esquema VAC (Vincristina, Doxorrubicina e Ciclofosfamida). Entretanto, ela apresentou insuficiência de múltiplos órgãos, que culminou com o óbito da paciente. O curso clínico desse caso mostra a rápida progressão e letalidade dessa neoplasia. Além da histopatologia, a idade, o tamanho do tumor, a ressecabilidade, o subtipo histopatológico, a presença de metástase no momento do diagnóstico e a invasão linfonodal influenciam no curso clínico da doença. Palavras-chave: Neoplasias ovarianas. Rabdomiossarcoma. Ovário.

Carfilzomibe no tratamento de pacientes com mieloma múltiplo recidivado ou refratário, que receberam terapia prévia / Carfilzomib in the treatment of patients with relapsed or refractory multiple myeloma who have received prior therapy

INTRODUÇÃO: O mieloma múltiplo (MM) é uma neoplasia hematológica maligna caracterizada pela proliferação descontrolada de plasmócitos alterados na medula óssea, resultando na produção aumentada de imunoglobulinas não funcional (proteína monoclonal). O acúmulo destas imunoglobulinas e a interação dos plasmócitos com outras células da medula óssea resultam em anemia, lesões ósseas, infecções, hipercalcemia, injúria renal, fadiga e dor. A incidência mundial informada pelo Globocan é de 2,2 novos casos por 100.000 habitantes em homens e 1,5/100.000 em mulheres, com ocorrência, a nível mundial, de 176 mil novos casos e 117 mil mortes em 2020. Carfilzomibe é um agente antineoplásico, inibidor de proteassoma que se liga seletiva e irreversivelmente nos sítios ativos. Tem atividade antiproliferativa e pró-apoptóticas. PERGUNTA DE PESQUISA: Kyprolis® (carfilzomibe) em combinação com dexametasona é eficaz e seguro no tratamento de pacientes com mieloma múltiplo recidivado ou refratário que receberam uma terapia prévia quando em comparação a bortezomibe, ciclofosfamida, dexametasona, cisplatina, doxorrubicina, doxorrubicina lipossomal, etoposídeo, melfalana, vincristina ou talidomida? EVIDÊNCIAS CLÍNICAS: O demandante realizou as buscas na literatura utilizando as seguintes bases de dados: The Cochrane Library, Medline via PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Centre for Reviews and Dissemination (CRD), o que resultou na inclusão de 14 publicações. Na análise conduzida pela Secretaria Executiva foram consideradas 12 publicações referentes a um ensaio clínico randomizado e uma publicação de revisão sistemática. O estudo ENDEAVOR foi um ensaio clínico de fase III, multicêntrico, aberto, que incluiu 929 participantes randomizados para receber carfilzomibe+dexametasona ou bortezomibe+dexametasona. A mediana de SLP foi 18,7 meses (IC 95%, 15,6 a não estimável) no grupo que recebeu carfilzomibe comparado a 9,4 meses (IC 95%, 8,4 a 10,4) no grupo que recebeu bortezomibe, resultando em uma magnitude de benefício absoluto de 9,3 meses (HR 0,53 [IC95% 0,44 a 0,65]; p< 0,0001). A duração mediana de resposta foi 21,3 meses (IC95% 21,3 a não estimável) no grupo carfilzomibe e 10,4 meses (IC95% 9,3 a 13,8) no grupo bortezomibe. Em ambos os grupos, 98% dos participantes apresentaram eventos adversos (qualquer grau), sendo a anemia (43% versus 28%), diarreia (36,7% versus 40,6%) e febre (32,6% versus 15,4%) os eventos mais frequentes nos grupos carfilzomibe e bortezomibe, respectivamente. Os eventos adversos mais comuns grau 3 ou maior foram reportados em 81,9% dos participantes do grupo carfilzomibe (n=379) e 71,1% no grupo bortezomibe (n=324), sendo a anemia (17,3% no grupo carfilzomibe e 10,1% no grupo bortezomibe), hipertensão (14,9% versus 3,3%), trombocitopenia (12,5% versus 14,7%),os três eventos mais frequentes. Insuficiência cardíaca grau 3 ou superior, foi mais frequente no grupo carfilzomibe (6%) que no grupo bortezomibe (2%.). AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-efetividade. Na análise do cenário base, em um horizonte temporal de 30 anos, carfilzomibe acrescentou ganhos incrementais de 1,19 QALY, resultando em uma razão de custo utilidade incremental (RCEI) de R$ 195.310,00 por QALY. No cenário proposto pela Secretária-Executiva (horizonte temporal de 10 anos e valor de utilidade derivada do estudo ENDEAVOR), carfilzomibe gerou benefício de 0,63 QALY, com RCEI de R$ 365.830,00 por QALY. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Com o desconto apresentado pelo demandante, a incorporação de carfilzomibe ao SUS implica em custos adicionais ao sistema de saúde no montante de aproximadamente R$ 365 milhões em cinco anos. A principal limitação da análise foi a estimativa da população. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram identificadas 10 tecnologias potenciais para compor o esquema terapêutico de pacientes adultos com mieloma múltiplo recidivado ou refratário: Belantamabe mafodotin, Ciltacabtageno autoleucel, Elranatamab, Iberdomida, Idecabtagene vicleucel, Isatuximabe, nivolumabe, selinexor, teclistamab, venetoclax. Tais medicamentos são anticorpo monoclonal ligado a um antineoplásico, anticorpo biespecífico, anticorpo monoclonal, imumodulador, terapias baseadas em células T autólogas geneticamente modificadas (CAR-T), inibidor SINE, ou inibidor de Bcl-2. A maioria não possui registro na FDA, EMA ou Anvisa. CONSIDERAÇÕES FINAIS: Os resultados sugerem eficácia e segurança do carfilzomibe na população elegível, porém, no horizonte temporal de 10 anos, com QALY < 1, RCEI de R$ 365.830,00 por QALY e impacto orçamentário de aproximadamente R$ 17 milhões no primeiro ano de incorporação e R$ 131 milhões no 5º ano da incorporação, totalizando R$ 365 milhões em cinco anos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Plenário presentes na 109ª Reunião Ordinária da Conitec, realizada no dia 08 de junho de 2022, sem nenhuma declaração de conflito de interesse, deliberaram por unanimidade, encaminhar o tema para consulta pública com recomendação preliminar desfavorável à incorporação de carfilzomibe para o tratamento de mieloma múltiplo recidivado ou refratário no SUS. Os membros consideraram a evidência científica boa e favorável ao carfilzomibe, porém, a RCEI e o impacto orçamentário foram considerados muito altos para o tratamento de uma doença que já tem outras opções terapêuticas disponíveis no SUS. CONSULTA PÚBLICA: Entre os dias 08/07/2022 e 27/07/2022 foram recebidas 421 contribuições, sendo 152 pelo formulário para contribuições técnico-científicas e 269 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. A maioria foi a favor da incorporação de carfilzomibe no SUS (97% via formulário técnico-científico e 100%). O principal benefício apontado nas contribuições técnico-científicas foi sobre a eficácia, aumento da sobrevida e qualidade de vida, além da disponibilidade de mais uma opção terapêutica e promoção da igualdade no tratamento nos sistemas público e privado de saúde. A empresa detentora do registro do medicamento atualizou o preço do medicamento, e consequentemente os valores do impacto orçamentário e avaliação econômica. No impacto orçamentário o valor ficou em R$ 95,3 milhões em cinco anos. Nas contribuições de experiência e opinião, a totalidade dos respondentes discordou da recomendação preliminar da Conitec. No âmbito das opiniões e experiências positivas, foi mencionada a necessidade de garantir o acesso ao carfilzomibe, especialmente por representar uma alternativa para pacientes recidivados e refratários. Também foi citada a eficácia da tecnologia. Como dificuldades, destacou-se a falta de acesso pelo SUS. Em relação a outros medicamentos, foram mencionados benefícios, mas, também, a eficácia limitada no caso de pacientes recidivados. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário da Conitec, em sua 112ª Reunião Ordinária, realizada no dia 31 de agosto de 2022, deliberaram por maioria simples, recomendar a não incorporação no SUS de carfilzomibe para o tratamento de pacientes com mieloma múltiplo recidivado ou refratário, que receberam terapia prévia, no SUS. Não houve apresentação de dados clínicos adicionais. Com o preço do medicamento atualizado, ainda assim não se mostrou custo-efetivo. Foi assinado o Registro de Deliberação nº 765/2022. DECISÃO: Não incorporar, no âmbito do Sistema Único de Saúde - SUS, o carfilzomibe para o tratamento de pacientes com mieloma múltiplo recidivado ou refratário, conforme a Portaria nº 107, publicada no Diário Oficial da União nº 184, seção 1, página 75, em 27 de setembro de 2022.

Tumor venéreo transmissível (TVT) nasal em cães / Nasal transmissible venereal tumor (TVT) in dogs

Background: Transmissible venereal tumors (TVT) are naturally occurring neoplasms that can be transmitted throughcopulation or cell transplantation. It is a disease that affects canines, has no preference for sex or breed, and generallynoticed in the external genital apparatus. Extragenital occurrence may eventually be seen; however, nasal involvementhas been described in only a few reports of studies conducted in Brazil. Therefore, the objective of this study is to report3 cases of nasal TVT in dogs who were treated in 2 municipalities in the mountainous region of Santa Catarina, Brazil.Cases: This case report includes 3 male mixed-breed canines of age 3-13. Only 1 of the animals was castrated. As per themedical history, some points, such as an enlarged nasal region, sneezing, nasal discharge, and hoarseness, reported by thedogs’ respective owners were similar among all the dogs. Likewise, nosebleed was observed on physical examination inall the cases. The result of cytological examination was inconclusive only in 1 case. Rhinoscopy, incisional biopsy, andhistopathological examination were then performed for achieving a definitive diagnosis. In the 2 cases wherein cytologygave conclusive results, the cytological smears showed changes suggestive of TVT, such as cells with eccentric nuclei andlittle cytoplasm, which had vacuoles inside them. In 2 cases, radiographic examinations of the skull were also performed.The images showed changes in bone radiopacity, conformation of trabeculae with areas of bone lysis and cell proliferation,and irregularity in the contour of the nasal bone. After TVT diagnosis was confirmed, chemotherapy was initiated usingvincristine at a dose of 0.75 mg/m2 for 2 cases and 0.025 mg/kg for the remaining case...

Tumor venéreo transmissível (TVT) nasal em cães / Nasal transmissible venereal tumor (TVT) in dogs

Background: Transmissible venereal tumors (TVT) are naturally occurring neoplasms that can be transmitted throughcopulation or cell transplantation. It is a disease that affects canines, has no preference for sex or breed, and generallynoticed in the external genital apparatus. Extragenital occurrence may eventually be seen; however, nasal involvementhas been described in only a few reports of studies conducted in Brazil. Therefore, the objective of this study is to report3 cases of nasal TVT in dogs who were treated in 2 municipalities in the mountainous region of Santa Catarina, Brazil.Cases: This case report includes 3 male mixed-breed canines of age 3-13. Only 1 of the animals was castrated. As per themedical history, some points, such as an enlarged nasal region, sneezing, nasal discharge, and hoarseness, reported by thedogs respective owners were similar among all the dogs. Likewise, nosebleed was observed on physical examination inall the cases. The result of cytological examination was inconclusive only in 1 case. Rhinoscopy, incisional biopsy, andhistopathological examination were then performed for achieving a definitive diagnosis. In the 2 cases wherein cytologygave conclusive results, the cytological smears showed changes suggestive of TVT, such as cells with eccentric nuclei andlittle cytoplasm, which had vacuoles inside them. In 2 cases, radiographic examinations of the skull were also performed.The images showed changes in bone radiopacity, conformation of trabeculae with areas of bone lysis and cell proliferation,and irregularity in the contour of the nasal bone. After TVT diagnosis was confirmed, chemotherapy was initiated usingvincristine at a dose of 0.75 mg/m2 for 2 cases and 0.025 mg/kg for the remaining case...(AU)

Angiogenesis' related genetic variants alter clinical features and prognosis of diffuse large B-cell lymphoma patients.

OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG's gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.

Combinação da auto-hemoterapia e sulfato de vincristina no tratamento de tumor venéreo transmissível em cadelas em Moçambique / Combination of autohemotherapy and vincristine sulfate in treatment of canine transmissible venereal tumor in bitches in Mozambique

Background: Canine transmissible venereal tumor (TVT) is a tumor of round cells. Vincristine sulfate is the most effective for TVT. Alternatively, hemotherapy is an alternative therapy that consists of the administration of autologous blood and the positive effects are associated with an immunomodulatory effect. Since chemotherapy has some collateral effects, it is necessary to study another treatment with minimal side effects. In this context, this report case aimed to describe the use of autohemotherapy associated with vincristine sulfate for treating a transmissible venereal tumor in the vulvar mucosa of 7 adult bitches, being the first case report in Mozambique, Africa. Case: Seven adult bitches, median size, were referred to the School Veterinary Hospital, School of Veterinary, Eduardo Mondlane University, Maputo, Mozambique, Africa, with a diagnosis of TVT in the vulvar mucosa. All bitches were treated weekly with autohemotherapy and vincristine sulfate for 21 days. The parameters assessed included clinical and TVT macroscopic examination, complete blood count, serum biochemical examination and urinalysis, and were evaluated 60-min before each treatment. No clinical side effects were identified during the treatments. Color, appearance and tumor size were changed during the treatment period, and all bitches showed complete remission of the tumor 21 days after the beginning of treatment or after the third therapeutic session. The values of the complete blood count, serum biochemical and urinalysis did not demonstrate significant variations throughout the evaluated time-points. The TVT cytopathological classification was lymphocytic (42.9 %), plasmacytic (28.6 %) and lymphoplasmacytic (28.6 %). Discussion: The aims of this report were to describe the combination of autohemotherapy and vincristine sulfate for treating the transmissible venereal tumor located in the vulvar mucosa of adult bitches, through clinical and laboratory evaluation, and was not...

Synchronous diagnosis of anaplastic large cell lymphoma and multiple myeloma in a patient: A case report.

RATIONALE: Synchronous development of both anaplastic large cell lymphoma (ALCL) and multiple myeloma (MM) in a patient is rare. To our knowledge, until now only one case has been reported. Treatment needs to cover both and is a challenge. Here we reported another case and discussed the diagnosis and treatment. PATIENT CONCERNS: This is a 63-year old woman who presented with a mass in upper abdominal skin. Positron emission tomography/computed tomography (PET/CT) showed the high metabolism in left abdominal skin and left axillary lymph nodes. Histopathologic and immunohistochemical evaluation identified the cutaneous mass as an ALK-negative ALCL. Bone marrow smear showed increased plasma cells which expressed CD38, CD138, and cLambda concomitantly. The increased monoclonal immunoglobulin IgD λ was detected by immunofixation electrophoresis. DIAGNOSES: Diagnosis of both ALCL and MM was confirmed. INTERVENTIONS: The patient successively received 6 cycles of B-CHOD regimen, one cycle of ID regimen, 2 cycles of DHAX regimen, one cycle of L-DA-EPOCH and autologous stem cell transplantation (ASCT). Then lenalidomide was performed as a maintenance therapy. OUTCOMES: Both ALCL and MM achieved complete remission. LESSONS: We reported a very rare case with synchronous development of ALCL and MM, in whom a good therapeutic response to chemotherapies followed by ASCT has been observed.

Association of three factors (ABCB1 gene expression, steroid response, early response at day + 8) on the response to induction in patients with acute lymphoblastic leukemia.

Treatment of acute lymphoblastic leukemia (ALL) requires the combination of multiple drugs to integrate a complete remission. The different prognostic factors (age, leukocytes, risk, cytogenetic alterations) allow identifying those patients with a high risk of relapse, but there are few described factors that impact the induction response. The objective was to identify the utility of different risk factors (overexpression of the ABCB1 drug resistance gene, favorable response to steroids (FRS) and early response at day + 8 of treatment) on the percentage of complete remissions and overall survival. This is a prospective, observational study in adult patients with B-ALL without specific cytogenetic alterations, who started induction treatment based on a pretreatment with prednisone and subsequently vincristine (1.6 mg/m2 subcutaneous) plus daunorubicin (45 mg/m2 subcutaneously) on days + 1, + 8, + 15. The ABCB1 resistance gene was evaluated at diagnosis, the FRS at the end of the pretreatment and the early response during day + 8. A total of 53 adult patients diagnosed with ALL Philadelphia negative chromosome (Ph-), with immunophenotype B, with a normal karyotype, were studied. Cases with genetic abnormalities with a poor prognosis were excluded in order to reduce bias. The mean age was 48 years (range 17-68 years). 62.3% of patients were at high risk of relapse. When analyzing the risk factors, 30.2% showed high levels of the ABCB1 resistance gene, without showing an impact on the induction response (OR: 1.218, p = 0.743), but its overexpression was associated with a poor response to steroids as in the absence of early response. Individually, both the FRS (OR: 5.7, p = 0.004) and the absence of early response to day + 8 (OR: 6.42, p = 0.002) showed significance. By combining the different factors, having more than 2 was directly related to a failure (OR: 9.514, p = 0.000). The identification of factors such as FRS such as the persistence of blasts at the end of the first week of treatment is useful to identify patients at risk of failure in induction.

Vincristine and ivermectin combination chemotherapy in dogs with natural transmissible venereal tumor of different cyto-morphological patterns: A prospective outcome evaluation.

Vincristine is the first-line drug for the chemotherapy of canine transmissible venereal tumor (CTVT). Drug resistance is related to tumor cyto-morphological patterns of CTVT. There are anti-cancer properties of ivermectin, thus, a combination of ivermectin and vincristine could be an effective chemo-therapeutic treatment regimen for CTVT. Study aims, therefore, were to (1) assess the frequency of CTVT cyto-morphologies, and (2) evaluate treatment efficacy and possible adverse reactions to vincristine compared with a combination vincristine and ivermectin. Dogs (n = 41) with CTVT were characterized by tumor cyto-morphology and disease severity and of those, 20 were randomly allocated into two groups. There was a control group (G-Vin; n = 10) in which there was treatment with vincristine; and an experimental group (G-Iv/Vin; n = 10) in which there was treatment with the ivermectin/vincristine combination. Although dogs in the G-Iv/Vin group had more severe disease at the beginning of the study (P = 0.0031), the number of weeks and chemotherapy sessions until tumor remission were similar among dogs of the two groups, indicating both treatments were effective. There was a decrease in the leukocyte counts (P = 0.0020), related to neutropenia (P = 0.0371) in the G-Vin but not the G-Iv/Vin treatment group. There was no tumor resistance that developed during the study regardless of the treatment regimen used or tumor cytomorphology. In summary, the use of the vincristine/ivermectin combination was well tolerated and efficacious for CTVT treatment.

Reduced-dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study.

Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and < 10 years), white blood cell count of <50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of <0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.

Delayed Enucleation With Neoadjuvant Chemotherapy in Advanced Intraocular Unilateral Retinoblastoma: AHOPCA II, a Prospective, Multi-Institutional Protocol in Central America.

PURPOSE: Treatment abandonment because of enucleation refusal is a limitation of improving outcomes for children with retinoblastoma in countries with limited resources. Furthermore, many children present with buphthalmos and a high risk of globe rupture during enucleation. To address these unique circumstances, the AHOPCA II protocol introduced neoadjuvant chemotherapy with delayed enucleation. PATIENTS AND METHODS: Patients with advanced unilateral intraocular disease (International Retinoblastoma Staging System [IRSS] stage I) were considered for upfront enucleation. Those with diffuse invasion of the choroid, postlaminar optic nerve, and/or anterior chamber invasion received six cycles of adjuvant chemotherapy (vincristine, carboplatin, and etoposide). Patients with buphthalmos and those with a perceived risk for enucleation refusal and/or abandonment were given two to three cycles of chemotherapy before scheduled enucleation followed by adjuvant chemotherapy to complete six cycles, regardless of pathology. RESULTS: A total of 161 patients had unilateral IRSS stage I disease; 102 underwent upfront enucleation, and 59 had delayed enucleation. The estimated 5-year abandonment-sensitive event-free and overall survival rates for the group were 0.81 ± 0.03 and 0.86 ± 0.03, respectively. The 5-year estimated abandonment-sensitive event-free survival rates for patients undergoing upfront and delayed enucleation were 0.89 ± 0.03 and 0.68 ± 0.06, respectively (P = .001). Compared with AHOPCA I, abandonment for patients with IRSS stage I retinoblastoma decreased from 16% to 4%. CONCLUSION: AHOPCA describes the results of advanced intraocular retinoblastoma treated with neoadjuvant chemotherapy. In eyes with buphthalmos and patients with risk of abandonment, neoadjuvant chemotherapy can be effective when followed by enucleation and adjuvant chemotherapy. Our study suggests that this approach can save patients with buphthalmos from ocular rupture and might reduce refusal of enucleation and abandonment.

Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study.

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.

Tumor venéreo transmissível em região perianal em canino: relato de caso / Transmissible venereal tumor in perianal region in canine: case report / Tumor venéreo transmisible en região perianal en perro: reporte de caso

o tumor venéreo transmissível ou Tumor de Sticker, trata se de uma neoplasia de ocorrência espontânea comum nos órgãos genitais, sem envolvimento de qualquer agente infeccioso em sua etiologia, quando células tumorais ou neoplásicas são implantadas mecanicamente, através de montas naturais e também por lambedura excessiva da área genital, ocasionando lesões em nariz, boca, cavidade oral e até mesmo na pele, porém tem sido descrito em várias localizações extragenitais, como ânus, globo ocular, tecido subcutâneo e pele. Foi atendido numa Clínica Veterinária em Maceió - AL, um cão, macho, raça Poodle, 7 anos, domiciliado, apresentando aumento de volume na região perianal, uma massa com aspecto vegetante irregular e friável há 2 semanas, com presença de secreção serossanguinolenta ininterrupta, foram realizados exames citológicos através de decalque da lesão, onde foi possível observar a presença de células redondas, excêntricas, com nucléolo único proeminente e com múltiplos vacúolos claros individualmente com limites citoplasmáticos bem definidos. Foi instituído tratamento com quimioterápico, através do sulfato de vincristina na dose de 0,1 mg/kg, administrado por via intravenosa com fluidoterapia, uma vez por semana, durante quatro semanas. O animal recebeu alta com remissão completa das lesões.(AU)

Transmissible venereal tumor or Sticker tumor is a neoplasm of spontaneous occurrence common in the genital organs, without involvement of any infectious agent in its etiology, when tumor or neoplastic cells are implanted mechanically, through natural mounts and also by excessive licking of the genital area, causing lesions in the nose, mouth, oral cavity and even in the skin, but has been described in several extragenital locations, such as anus, eyeball, subcutaneous tissue and skin. It was attended at a Veterinary Clinic in Maceió - Al, a dog, male, Poodle breed, 7 years old, domiciled with increased volume in the perianal region, a mass with irregular and friable vegetative appearance for 2 weeks, with uninterrupted serosanguinolenta secretion, cytological exams were performed through a lesion decal, where it was possible to observe the presence of round, eccentric cells with prominent single nucleolus and with multiple clear vacuoles individually with well defined cytoplasmic limits. Treatment with chemotherapy with vincristine sulfate at a dose of 0.1 mg/kg was given intravenously with fluid therapy once a week for four weeks. The animal was discharged with complete remission of the lesions.(AU)

El tumor venéreo transmisible o Tumor de Sticker, se trata de una neoplasia de ocurrencia espontánea común en los órganos genitales, sin implicación de ningún agente infeccioso en sue tiología, cuando células tumorales o neoplásicas son implantadas mecánicamente, a través de montas naturales y también por lamedura excesiva de la zona genital, ocasionando lesiones en nariz, boca, cavidad oral e incluso en la piel, pero ha sido descrito en varias localizaciones extragenitales, como ano, globo ocular, tejido subcutáneo y piel. En el caso de la vacunación, se observó un aumento del volumen en la región perianal, una masa con aspecto vegetativo irregular y friable hace 2 semanas, con presencia de secreción serosanguinolenta ininterrumpida, se realizaron exámenes citológicos a través de la caldera de la lesión, donde fue posible observar la presencia de células redondas, excéntricas, con nucléolo único prominente y con múltiples vacuolos claros individualmente con límites citoplasmáticos bien definidos. Se estableció tratamiento con quimioterápico a través del sulfato de vincristina a una dosis de 0,1 mg/kg, administrada por vía intravenosa con fluidoterapia una vez a la semana durante cuatro semanas. El animal recibió alta con remisión completa de las lesiones.(AU)

Tumor venéreo transmissível em região perianal em canino: relato de caso / Transmissible venereal tumor in perianal region in canine: case report / Tumor venéreo transmisible en região perianal en perro: reporte de caso

o tumor venéreo transmissível ou Tumor de Sticker, trata se de uma neoplasia de ocorrência espontânea comum nos órgãos genitais, sem envolvimento de qualquer agente infeccioso em sua etiologia, quando células tumorais ou neoplásicas são implantadas mecanicamente, através de montas naturais e também por lambedura excessiva da área genital, ocasionando lesões em nariz, boca, cavidade oral e até mesmo na pele, porém tem sido descrito em várias localizações extragenitais, como ânus, globo ocular, tecido subcutâneo e pele. Foi atendido numa Clínica Veterinária em Maceió - AL, um cão, macho, raça Poodle, 7 anos, domiciliado, apresentando aumento de volume na região perianal, uma massa com aspecto vegetante irregular e friável há 2 semanas, com presença de secreção serossanguinolenta ininterrupta, foram realizados exames citológicos através de decalque da lesão, onde foi possível observar a presença de células redondas, excêntricas, com nucléolo único proeminente e com múltiplos vacúolos claros individualmente com limites citoplasmáticos bem definidos. Foi instituído tratamento com quimioterápico, através do sulfato de vincristina na dose de 0,1 mg/kg, administrado por via intravenosa com fluidoterapia, uma vez por semana, durante quatro semanas. O animal recebeu alta com remissão completa das lesões.

Transmissible venereal tumor or Sticker tumor is a neoplasm of spontaneous occurrence common in the genital organs, without involvement of any infectious agent in its etiology, when tumor or neoplastic cells are implanted mechanically, through natural mounts and also by excessive licking of the genital area, causing lesions in the nose, mouth, oral cavity and even in the skin, but has been described in several extragenital locations, such as anus, eyeball, subcutaneous tissue and skin. It was attended at a Veterinary Clinic in Maceió - Al, a dog, male, Poodle breed, 7 years old, domiciled with increased volume in the perianal region, a mass with irregular and friable vegetative appearance for 2 weeks, with uninterrupted serosanguinolenta secretion, cytological exams were performed through a lesion decal, where it was possible to observe the presence of round, eccentric cells with prominent single nucleolus and with multiple clear vacuoles individually with well defined cytoplasmic limits. Treatment with chemotherapy with vincristine sulfate at a dose of 0.1 mg/kg was given intravenously with fluid therapy once a week for four weeks. The animal was discharged with complete remission of the lesions.

El tumor venéreo transmisible o Tumor de Sticker, se trata de una neoplasia de ocurrencia espontánea común en los órganos genitales, sin implicación de ningún agente infeccioso en sue tiología, cuando células tumorales o neoplásicas son implantadas mecánicamente, a través de montas naturales y también por lamedura excesiva de la zona genital, ocasionando lesiones en nariz, boca, cavidad oral e incluso en la piel, pero ha sido descrito en varias localizaciones extragenitales, como ano, globo ocular, tejido subcutáneo y piel. En el caso de la vacunación, se observó un aumento del volumen en la región perianal, una masa con aspecto vegetativo irregular y friable hace 2 semanas, con presencia de secreción serosanguinolenta ininterrumpida, se realizaron exámenes citológicos a través de la caldera de la lesión, donde fue posible observar la presencia de células redondas, excéntricas, con nucléolo único prominente y con múltiples vacuolos claros individualmente con límites citoplasmáticos bien definidos. Se estableció tratamiento con quimioterápico a través del sulfato de vincristina a una dosis de 0,1 mg/kg, administrada por vía intravenosa con fluidoterapia una vez a la semana durante cuatro semanas. El animal recibió alta con remisión completa de las lesiones.

Successful Use of EPOCH-R in 2 Young Adult Patients With Burkitt Lymphoma and Acute Kidney Injury: A Case Report.

Pediatric Burkitt lymphoma has historically been treated with intensive methotrexate-based chemotherapy, which improves patient survival while causing severe toxicities. Young patients typically have better outcomes with intensive therapies, while adults and immunocompromised patients have higher toxicities and worse outcomes. Newer treatment regimens, including etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab (EPOCH-R), show promise for these patients. However, few studies exist to demonstrate efficacy and improved toxicity profile with EPOCH-R. We present 2 cases: a 25-year-old male with Down syndrome and an 18-year-old male with Burkitt lymphoma and significant renal injury who were successfully treated with EPOCH-R with minimal toxicities.

Primary gastric diffuse large B-cell lymphoma: The role of dose-dense chemotherapy.

OBJECTIVE: To assess if the use of a dose-dense regimen of chemotherapy can improve the prognosis in patients with primary gastric diffuse large B-cell lymphoma in early stages (I-II) but associated with worse prognostic factors. METHODS: One hundred and eight consecutive patients with primary gastric diffuse large B-cell lymphoma in early stages (I-II) with high serum levels of lactic dehydrogenase and beta 2 microglobulin (more than >2 of normal levels), which were associated with a worse prognostic outcome, were treated with a dose-dense chemotherapy: CHOP with increased doses of cyclophosphamide and doxorubicin, was administered every 14 days (instead of 21 days). The end points of this study were to improve outcome measured from progression-free survival and overall survival and to evaluate acute toxicities. RESULTS: Complete response was achieved in 85 patients (78%). Actuarial curves at five years show that progression-free survival was 82% and overall survival was 85%. Hematological toxicities were severe, but no death-related treatment was observed. CONCLUSIONS: We considered that in this setting of patients, the use of a dose-dense regimen could be of benefit because it improves outcome and toxicities were well controlled.

Treatment of Nonmetastatic Unilateral Retinoblastoma in Children.

Importance: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. Objective: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. Design, Setting, and Participants: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. Interventions: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. Main Outcomes and Measures: Probability of event-free survival (extraocular relapse and death from any cause were considered events). Results: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). Conclusions and Relevance: Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab.

BACKGROUND: The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases. AIM: We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL). METHODS: Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment. RESULTS: Seven patients were followed and median age was 56.0 ± 5.0 years (range, 41.9-71.6 years). At baseline, the mean level of IgG was 333.7 ± 40.8 and IgM 40.9 ± 11.3 mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%). CONCLUSION: Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.

Vincristine-loaded hydroxyapatite nanoparticles as a potential delivery system for bone cancer therapy.

Despite advances in the development of new therapeutic agents and diagnostic imaging techniques, the 5-year survival of osteosarcoma, the most common type of bone cancer, remains practically unaltered for the last three decades at around 60%. Nanoparticle-based carriers have emerged as new class of drug delivery systems that could potentially overcome conventional chemotherapy limitations, by promoting a better drug biodistribution profile by allowing a preferential accumulation of the drug in the desired tissue, while minimising non-targeted tissue toxicity, thus resulting in an improved overall therapeutic effectiveness. Hydroxyapatite nanoparticles (HANP) are known to be biocompatible and non-immunogenic and have shown to be preferentially accumulated in bone tissues being considered a promising carrier to bone tissues. Herein, we successfully synthesised mesoporous hydroxyapatite nanoparticles with mean size of 285.32 ± 10.29 nm and superficial area of 103.5 m2/g, containing significant quantities of chemotherapeutic drug vincristine. A spectrophotometric method was developed and validated aiming to quantify the vincristine (VCR)-loaded in nanoparticles. Chorioallantoic membrane assay revealed relevant anti-angiogenic activity of system, leading to accentuated reduction in the number of blood vessels in fertilised eggs. Findings presented in this paper suggested that VCR-loaded HANP has a promising future as a nanocarrier for bone cancer treatment.