10 research outputs found
How should health systems prepare for the evolving COVID-19 pandemic? Reflections from the perspective of a Tertiary Cancer Center
INTRAPERITONEAL CHEMOTHERAPY FOR GASTRIC CANCER WITH PERITONEAL CARCINOMATOSIS: STUDY PROTOCOL OF A PHASE II TRIAL
ABSTRACT BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18–75 years; Peritoneal carcinomatosis with peritoneal cancer index<12; Eastern Cooperative Oncology Group 0/1; good clinical status; and lab exams within normal limits. The study protocol consists of four cycles of intraperitoneal chemotherapy with paclitaxel associated with systemic chemotherapy. After treatment, patients with peritoneal response assessed by staging laparoscopy undergo conversion gastrectomy. RESULTS: The primary outcome is the rate of complete peritoneal response. Progression-free and overall survivals are other outcomes evaluated. The study started in July 2022, and patients will be screened for inclusion until 30 are enrolled. CONCLUSIONS: Therapies for advanced gastric cancer patients have been evaluated in clinical trials but without success in patients with peritoneal metastasis. The treatment proposed in this trial can be promising, with easy catheter implantation and ambulatory intraperitoneal chemotherapy regime. Verifying the efficacy and safety of paclitaxel with systemic chemotherapy is an important progress that this study intends to investigate
Prospective study of biomarkers in squamous cell carcinoma of the anal canal and their influence on treatment outcomes
Introdução: O tumor de canal anal é raro, sendo a histologia epidermóide a mais frequente. A quimio-radioterapia é capaz de curar a maioria dos casos de câncer de canal anal localizado, entretanto, um grupo de pacientes apresenta resistência primária ao tratamento multimodal. Métodos: Estudo de coorte prospectivo desenhado para avaliar a influência de biomarcadores (HIV, Ki-67, PD-L1, HPV e mutações no DNA tumoral) na resposta do câncer de canal anal ao tratamento com quimio-radioterapia. Resposta completa aos 6 meses após tratamento foi o desfecho primário. O DNA tumoral foi avaliado por sequenciamento genético, através do painel TruSight Tumor 26®. HPV foi testado pelo teste PapilloCheck®. Ki-67 e PD-L1 foram avaliados por imunoistoquímica. Sorologia para HIV foi realizada em todos os pacientes antes do início do tratamento. Resultados: Os pacientes foram recrutados de outubro/2011 a dezembro/2015 e 75 foram avaliados para resposta após o tratamento. A idade mediana foi de 57 anos, a maioria dos pacientes apresentou estadio III ao diagnóstico 65% (n=49) e 12% (n=9) tinha sorologia positiva para HIV. Aos 6 meses após término da quimio-radioterapia 62,7% (n=47) dos pacientes apresentou resposta completa, 24% (n=18) resposta parcial e 13,3% (n=10) progressão de doença. HPV foi avaliado em 67 amostras e encontrado em 70,1%, sendo o HPV 16 o tipo mais frequente. A pesquisa de PD-L1 foi realizada em 61 amostras e 16,4% (n=10) apresentou expressão > 1%. Idade, estadio clínico, HIV, expressão de Ki-67, presença de HPV, expressão de PD-L1 e interrupção de tratamento foram avaliados como preditores de resposta, aos 6 meses após o término do tratamento, por meio de regressão logística multivariada. Pacientes com estadio II apresentaram 4,7 vezes mais chance de resposta completa que pacientes com estadio III (OR=4,70; IC95%=1,36-16,30; p=0,015). Quando considerada resposta completa e/ou parcial, a presença do vírus HIV foi associada a pior resposta: pacientes HIV negativo apresentaram 5,7 vezes mais chance de resposta completa e/ou parcial que pacientes HIV positivo (OR=5,72; IC95%=2,5-13,0; p < 0,001). Foi possível a realização de sequenciamento do DNA tumoral em 25 pacientes avaliáveis para resposta, sendo as mutações mais frequentes encontradas nos genes PIK3CA (n=6) e MET (n=6). Não houve diferença em resposta de acordo com presença dessas mutações. Conclusões: Aos 6 meses após término do tratamento com quimio-radioterapia a expressão de Ki-67, PD-L1, presença de HPV e mutações em PIK3CA e MET não foram associadas com resposta ao tratamento. Pacientes com estadio III e pacientes portadores do vírus HIV apresentaram pior resposta ao tratamentoBackground: While chemoradiation is the curative treatment for squamous cell carcinoma of the anal canal, some patients present primary resistance. As a rare tumor, predictors of response remain unknown. Patients and Methods: Prospective cohort study aimed at evaluating biomarkers (Ki-67, PD-L1, Human papillomavirus (HPV), tumor mutations and HIV) possibly associated with tumor response to chemoradiation. Complete response at 6 months was the primary endpoint. Tumor DNA was analyzed by next-generation sequencing (TruSight Tumor 26 ®). HPV was tested by PapilloCheck®. KI-67 and PD-L1 were evaluated by immunohistochemistry. Results: Seventyeight patients were recruited from October/2011 to December/2015, and 75 were evaluable for response. Median age was 57 years, 65% (n=49) were stage III, and 12% (n=9) were HIV positive (HIV+). At 6 months 62.7% (n=47) presented complete response, 24% (n=18) partial response and 13.3% (n=10) disease progression. HPV was evaluated in 67 and found in 70.1%, the majority being HPV 16. PD-L1 was tested in 61 being 16.4% (n=10) positive. Age, clinical stage, HIV status, KI-67, HPV, PD-L1 and treatment interruption were tested as predictive factors for complete response at 6 months by logistic regression. On multivariate analyses, stage II patients were 4.7 more likely to achieve complete response than stage III (OR=4.70; IC95%=1.36-16.30; p=0.015). When we considered patients with complete and partial response, HIV+ was associated with a worse response (OR=5.72; IC95%=2.5-13.0; p < 0.001). Twenty-five patients had samples proper for NGS and 17 had at least one mutation, with PIK3CA (n=6) and MET (n=6) being the most common mutated genes. There were no differences in response according to MET or PIK3CA status. Conclusions: At 6 months after chemoradiation Ki-67, PD-L1, HPV and mutations in PIK3CA and MET were not associated with response. Patients with stage III disease and patients HIV+ had a significantly poor respons
Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies
Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease
Renal medullary carcinoma response to chemotherapy: a referral center experience in Brazil
Renal medullary carcinoma (RMC) is rare, accounting for less than 1% of all renal neoplasms. Case reports suggest RMC is highly aggressive, poorly responsive to chemotherapy, often metastatic at diagnosis, affects young men with sickle cell trait, and median overall survival (mOS) is less than 12 months. We report the epidemiological characteristics, treatments performed, response rate to each treatment and mOS of five patients with RMC. All patients had sickle cell trait, four were male, three had metastatic disease at diagnosis and mean age at diagnosis was 25 years. Non-metastatic patients were submitted to nephrectomy. Two patients had partial response to first line chemotherapy including cisplatin and gemcitabine. There was no response to sunitinib or second line chemo - therapy; mOS was 6 months. Due to its rarity, case series are the only evidence available to discuss the treatment for RMC. In our experience, only cisplatin and gemcitabine based regimen offered response