Análise de expressão imunohistoquímica de PD-1, PD-L1 e CTLA-4 no tecido metastático e avaliação de seu papel prognóstico em carcinoma renal de células claras metastático / Analysis of immunohistochemical expression of PD-1, PD-L1 and CTLA-4 in metastatic tissue and assessment of their prognostic role in metastatic clear cell renal carcinoma

Introdução: Apesar dos grandes avanços no tratamento sistêmico com as terapias anti-VGFR e os CPIs, os pacientes com CCRm ainda são tratados da mesma forma. Há apenas fatores clínicos e laboratoriais prognósticos, mas não preditivos de resposta, como já existem em outros tumores. A busca de biomarcadores falhou em todos os estudos de fase III que ditam as terapias atuais, representando uma área de grande desafio no tratamento dos CCRm. O entendimento da heterogeneidade, não somente intratumoral no tumor primário, como também nas metástases, torna este desafio ainda maior. Onde poucos estudos analisaram biomarcadores nas metástases. Materiais e Métodos: Foram analisados dados de 60 pacientes com CCRccm tratados no A.C.Camargo Cancer Center. O propósito desta análise foi estudar a expressão imunohistoquímica de PD-1, PD-L1 e CTLA-4 em tecido de metástase de carcinoma de células claras renal e sua eventual associação com desfechos clínicos e prognóstico na doença. Resultados: Para a análise de sobrevida global, a ausência de nefrectomia, existência de metástase óssea e metástase em tecido mole conferiram um prognóstico ruim aos pacientes analisados. Com relação a análise de sobrevida livre de progressão as variáveis grau ISUP e metástase em tecido mole conferiram um pior prognóstico aos pacientes analisados. Com relação as variáveis clínicas, para a análise de sobrevida global, os pacientes que apresentaram KPS < 80 apresentaram prognóstico pior. Com relação a análise de sobrevida livre de progressão, os pacientes que apresentaram as variáveis de KPS < 80 e hipercalcemia apresentaram um pior prognóstico. Foi observado significância estatística para o marcador molecular PD-1 para a análise de sobrevida global, as amostras sem a expressão a expressão de PD-1 apresentaram mediana de 73,9 meses, enquanto os pacientes que apresentaram expressão deste biomarcador não atingiram a mediana (p=0,044). Conclusão: Quando avaliadas na metástase de carcinoma de células claras renal a expressão imuno-histoquímica de PD-1 tem papel prognóstico para sobrevida global, porém o marcador não se mostrou ser uma variável de importância prognóstica independente das outras variáveis. A expressão de IHQ de PD-L1 e CLTA-4 em CCRccm não demonstrou ter um papel prognóstico.

Introduction: Despite major advances in systemic treatment with anti-VGFR therapies and checkpoint inhibitors (CPIs), patients with metastatic renal cell carcinoma (mRCC) are still treated in the same way. There are only prognostic clinical and laboratory factors, but not predictive or selector of therapies, as they already exist in other tumors. The search for biomarkers has failed in all phase III studies that dictate current therapies, representing an area of great challenge in the treatment of mRCC. The understanding of heterogeneity, not only intratumoral in the primary tumor, but also in metastases, makes this challenge even greater. Few studies have analyzed biomarkers in metastasis. Materials and Methods: Data from 60 patients with mCRC treated at the A.C.Camargo Cancer Center were analyzed. The purpose of this analysis was to study the IHQ expression of PD-1, PD-L1 and CTLA-4 in renal clear cell carcinoma metastasis tissue and their eventual association with clinical outcomes and prognosis in the disease. Results: For the analysis of overall survival, the absence of nephrectomy, presence of bone metastasis and metastasis in soft tissue conferred a poor prognosis to the patients analyzed. Regarding the analysis of progression-free survival, the variables ISUP grade and soft tissue metastasis conferred a worse prognosis to the patients analyzed. Regarding clinical variables, for the analysis of overall survival, patients who had KPS < 80 had a worse prognosis. Regarding the analysis of progression-free survival, patients who presented the variables of KPS < 80 and hypercalcemia had a worse prognosis. Statistical significance was observed for the molecular marker PD-1 for the analysis of overall survival, patients who lost PD-1 expression had a median of 73.9 months, while patients who showed expression of this biomarker did not reach the median (p =0.044). Conclusion: When evaluated in renal clear cell carcinoma metastasis, the immunohistochemical expression of PD-1 has a prognostic role for overall survival, but the biomarker was not shown to be a variable of prognostic importance independent of the other variables. IHQ expression of PD-L1 and CLTA-4 in CCRccm has not been shown to have a prognostic role

Treatment Patterns Among Patients With Advanced Prostate Cancer in Brazil: An Analysis of a Private Healthcare System Database.

Background: With the ongoing expansion of life-prolonging therapies approved to treat advanced prostate cancer, there is currently an unmet need to better understand real-world treatment patterns and identify optimal treatment sequencing for men with metastatic castration-resistant prostate cancer (mCRPC). Methods: In this retrospective, observational cohort analysis, patients with confirmed mCRPC were identified in the Auditron claims database and used to describe mCRPC treatment patterns and trends in the Brazilian private healthcare system from 2014 to 2019. Demographics and clinical characteristics, prostate cancer stage at diagnosis, and type and number of treatment lines were evaluated. The primary endpoint was identification of the drugs used in first-line therapies in mCRPC, and the secondary endpoint included a description of sequential lines of therapy (second and third lines) in mCRPC. Results: A total of 168 electronic patient records were reviewed. Docetaxel was the most frequently used first-line treatment (35.7%), followed by abiraterone (33.3%) and enzalutamide (13.1%). Docetaxel, abiraterone, and enzalutamide also accounted for 34.6%, 28.0%, and 15.0%, respectively, of second-line therapies. In third-line therapies, cabazitaxel (26.1%), enzalutamide (23.9%), docetaxel (15.2%), and abiraterone (15.2%) were most commonly prescribed. Irrespective of stage at diagnosis, treatment patterns were similar once the disease progressed to the metastatic castration-resistance stage. Conclusions: Docetaxel was the most frequently utilized therapy for mCRPC treatment, followed by abiraterone and enzalutamide. Although the current analyses provide real-world insights into treatment patterns for patients with mCRPC in Brazil, additional real-world data are needed to further validate and expand on these findings.

Development and validation of a HPLC method for standardization of herbal and commercial extracts of Myrcia uniflora

Myrcia uniflora Barb. Rodr., Myrtaceae, popularly known as "pedra-hume-caá" in Brazil, is sold as dry extracts in capsules or as tinctures for the treatment of diabetes mellitus. Previous phytochemical studies on this species described the occurrence of the flavonoids mearnsitrin and myricitrin. In the present study, the chromatographic profiles of M. uniflora leaves and commercial extracts were determined using HPLC-PAD. Myricitrin was used as an external standard in the development and validation of the HPLC method. The proposed method is simple, rapid and reliable and can be successfully applied in industry for standardization of herbs and phytomedicines commercialised in Brazil as "pedra-hume-caá".