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BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Irinotecano , Leucovorina , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Pessoa de Meia-Idade , Masculino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Feminino , Idoso , Brasil , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Adulto , Quimiorradioterapia/métodos , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Conduta Expectante/estatística & dados numéricos , Resultado do Tratamento , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , SeguimentosRESUMO
OBJECTIVE: A comparative analysis of the association between sedentary behavior versus physical activity levels and tumor staging in women with breast cancer. METHODS: The present research adopted a cross-sectional study design to recruit a total of 55 adult and elderly women newly diagnosed with breast cancer for data collection and analysis. Inclusion criteria involved patients in procession of a formal approval for participation in the study by the treating physician and those not hitherto subjected to the first cycle of chemotherapy. RESULTS: Physical activity levels did not influence the pathological stage of breast cancer (p=0.26) or histological tumor grade (p=0.07) in the analyzed subjects. However, there was a significant association between physical activity levels and responsiveness to hormones (epidermal growth factor receptor (HER2), p<0.05) in the analyzed subjects. Significant difference was detected in the histological tumor grade in relation to the mean time spent sitting during the weekend (p<0.05). However, sedentary behavior had no influence on the tumor stage (p>0.05). CONCLUSION: Physical activity levels did not influence the tumor stage and histological tumor grade. Sedentary behavior had a significant influence on the histological tumor grade.
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Neoplasias da Mama , Adulto , Idoso , Humanos , Feminino , Comportamento Sedentário , Estudos Transversais , Brasil , PesquisadoresRESUMO
AIMS: Hepatocellular carcinoma (HCC) is a severe condition with poor prognosis that places a significant burden on patients, caregivers, and healthcare systems. Selective internal radiation therapy (SIRT) is a treatment available to patients with HCC which addresses some of the limitations of alternative treatment options. A cost-effectiveness analysis was undertaken into the use of SIRT using Y-90 resin microspheres for the treatment of unresectable intermediate- and late-stage HCC in Brazil. MATERIALS AND METHODS: A partitioned-survival model was developed, including a tunnel state for patients downstaged to receive treatments with curative intent. Sorafenib was the selected comparator, a common systemic treatment in Brazil and for which comparative evidence exists. Clinical data were extracted from published sources of pivotal trials, and effectiveness was measured in quality-adjusted life-years (QALYs) and life-years (LYs). The analysis was conducted from the Brazilian private payer perspective and a lifetime horizon was implemented. Comprehensive sensitivity analyses were conducted. RESULTS: LYs and QALYs were higher for SIRT with Y-90 resin microspheres versus sorafenib (0.27 and 0.20 incremental LYs and QALYs, respectively) and costs were slightly higher for SIRT (R$15,864). The base case incremental cost-effectiveness ratio (ICER) was R$77,602 per QALY. The ICER was mostly influenced by parameters defining the sorafenib overall survival curve and SIRT had a 73% probability of being cost-effective at a willingness-to-pay threshold of R$135,761 per QALY (3-times the per-capita gross domestic product in Brazil). Overall, sensitivity analyses confirmed the robustness of the results indicating that SIRT with Y-90 resin microspheres is cost-effective compared with sorafenib. LIMITATIONS: A rapidly evolving treatment landscape in Brazil and worldwide, and the lack of local data for some variables were the main limitations. CONCLUSIONS: SIRT with Y-90 resin microspheres is a cost-effective option compared with sorafenib in Brazil.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Sorafenibe/uso terapêutico , Análise Custo-Benefício , Radioisótopos de Ítrio , Brasil , Neoplasias Hepáticas/tratamento farmacológico , MicroesferasRESUMO
ABSTRACT Objective A comparative analysis of the association between sedentary behavior versus physical activity levels and tumor staging in women with breast cancer. Methods The present research adopted a cross-sectional study design to recruit a total of 55 adult and elderly women newly diagnosed with breast cancer for data collection and analysis. Inclusion criteria involved patients in procession of a formal approval for participation in the study by the treating physician and those not hitherto subjected to the first cycle of chemotherapy. Results Physical activity levels did not influence the pathological stage of breast cancer (p=0.26) or histological tumor grade (p=0.07) in the analyzed subjects. However, there was a significant association between physical activity levels and responsiveness to hormones (epidermal growth factor receptor (HER2), p<0.05) in the analyzed subjects. Significant difference was detected in the histological tumor grade in relation to the mean time spent sitting during the weekend (p<0.05). However, sedentary behavior had no influence on the tumor stage (p>0.05). Conclusion Physical activity levels did not influence the tumor stage and histological tumor grade. Sedentary behavior had a significant influence on the histological tumor grade.
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Colorectal cancer represents the third most diagnosed malignancy in the world. The liver is the main site of metastatic disease, affected in 30% of patients with newly diagnosed disease. Complete resection is considered the only potentially curative treatment for colorectal liver metastasis (CRLM), with a 5-year survival rate ranging from 35% to 58%. However, up to 80% of patients have initially unresectable disease, due to extrahepatic disease or bilobar multiple liver nodules. The availability of increasingly effective systemic chemotherapy has contributed to converting patients with initially unresectable liver metastases to resectable disease, improving long-term outcomes, and accessing tumor biology. In recent years, response to preoperative systemic chemotherapy before liver resection has been established as a major prognostic factor. Some studies have demonstrated that patients with regression of hepatic metastases while on chemotherapy have improved outcomes when compared to patients with stabilization or progression of the disease. Even if disease progression during chemotherapy represents an independent negative prognostic factor, some patients may still benefit from surgery, given the role of this modality as the main treatment with curative intent for patients with CRLM. In selected cases, based on size, the number of lesions, and tumor markers, surgery may be offered despite the less favorable prognosis and as an option for non-chemo responders.
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FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.
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Antineoplásicos Fitogênicos/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Humanos , Assistência PerioperatóriaRESUMO
PURPOSE: Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival. METHODS: The charts of all cases of metastatic colorectal cancer diagnosed between January 2005 and January 2016 in a tertiary hospital in Brazil were reviewed. Inclusion criteria were complete data on clinical staging, treatments received and all-RAS testing. Multivariate Cox proportional survival models were used to evaluate the impact of specific RAS variants on survival. RESULTS: There were 151 eligible patients and 61.6% had RAS alterations, the most common G12D (11.9%) and G12A (8.6%). Most patients received chemotherapy, including oxaliplatin (79%), irinotecan (53%) and bevacizumab (59%). Among RAS-wild type patients, 46% received anti-EGFR therapy. Median survival was 39.2 months for RAS-wildtype, 18.8 months for RAS G12A and 34.6 for other RASmutant patients (multivariate analysis for G12A vs RASwild type HR 1.94; 95% CI 0.83-5.51; p=0.12). CONCLUSION: Patients with metastatic colorectal cancer who have RAS mutations have shorter overall survival. Regarding the impact of specific KRAS alterations, G12A mutations have a worse prognosis.
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Adenocarcinoma/genética , Neoplasias Colorretais/genética , Genes ras , Proteínas ras/genética , Adenocarcinoma/patologia , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Mutação , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Breast reduction surgery is a common procedure and the rate of incidental findings in the removed specimens varies between 0% and 4.6%. There are no guidelines about pathological evaluation of breast reduction surgery. We reviewed all pathology reports of patients undergoing breast reduction surgery in a single tertiary institution in Brazil from January 2008 to August 2014. Exclusion criteria were a personal history of breast cancer, unclear reason for mastectomy and incomplete data on the pathology report. We considered "relevant findings" flat epithelial atypia, atypical hyperplasia, carcinomas in situ and invasive carcinoma. Of 1672 specimens from breast reduction surgery, 783 met inclusion criteria. Median patient age was 40 (8-77), 91% underwent bilateral mastectomy and 57% of the specimens weighted less than 200 g. In 55% of cases, 4 or more paraffin blocks were sampled. There were 40 (5.1%) relevant findings and the most common was atypical lobular hyperplasia (16-2%). There were 3 invasive carcinomas (0.38%). In multivariate analysis, the only variables associated with a higher odds of relevant pathological findings were patient age ≥ 40 (OR 4.73 CI95% 1.98-11.3 p < 0.001) and sampling of ≥4 paraffin blocks from each specimen (OR 6.69 95% CI 2.25-19.9 p < 0.001). The incidence of pre-malignant and malignant lesions in specimens from breast reduction surgery is around 5%, but this risk is significantly higher for patients older than 40 years-old. Sampling at least 4 paraffin blocks from each specimen significantly increases detection rates.
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Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Achados Incidentais , Mamoplastia , Lesões Pré-Cancerosas/patologia , Adolescente , Adulto , Idoso , Neoplasias da Mama/cirurgia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Criança , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Lesões Pré-Cancerosas/cirurgia , Prognóstico , Adulto JovemRESUMO
INTRODUCTION: Levels of carbohydrate antigen 19-9 (CA19-9) in metastatic pancreatic cancer are used in daily practice as a marker of response to chemotherapy. The association between CA19-9 levels and mortality remains uncertain. This study sought to determine the most accurate level of CA19-9 associated with early mortality, both at diagnosis and during the course of metastatic disease. METHODS: This research is a retrospective analysis of 64 patients with metastatic adenocarcinoma of the pancreas evaluated from January 2010 to December 2015. A receiver-operating characteristic (ROC) curve analysis was performed to evaluate the CA19-9 value and the association with early death (death within 2 months after diagnosis of advanced disease). The survival analysis was estimated by the Kaplan-Meier method, and variables of interest were assessed by proportional hazards regression Cox models. RESULTS: The mortality rate was 92.2%, and the estimated median survival was 11.0 months. For the ROC curve analysis of initial CA19-9, an area under the curve of 0.868 (95% confidence interval 0.782 to 0.954) was obtained; the cutoff of 2504 U/ml had a sensitivity of 100% and specificity of 82.8% for early death. The effect of initial CA19-9 and chemotherapy contributed independently to the survival time, and every increase of 1000 CA19-9 units increased the risk of death by 9% (p = 0.0003). CONCLUSION: CA19-9 levels in advanced pancreatic adenocarcinoma are associated independently with worse prognosis and early death. CA19-9 levels could be considered as a stratification factor for future clinical trials.
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Antineoplásicos/uso terapêutico , Antígeno CA-19-9/sangue , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias PancreáticasRESUMO
Purpose: Evaluate the association between the use of phase I expansion cohorts (ECs) and drug performance in phase II as well as time to approval by the FDA.Experimental Design: We performed a systematic search of MEDLINE for single-agent dose-finding adult oncology phase I trials published in 2006 to 2011 and subsequent phase II trials. Successful phase II trials were those that met their primary endpoints. Dates of approval were obtained from the Drugs@FDA website in April 2014. A logistic regression model was used to determine the associations between variables and success in phase II.Results: We identified 533 phase I trials evaluating 381 drugs; 112 drugs had at least one phase I trial with an expansion cohort. Phase I trials with expansion cohorts of two to 20 patients were associated with a higher rate of successful phase II trials than those with no expansion cohort [48% vs. 27%; OR, 2.1; 95% confidence interval (CI), 1.1-4.0; P = 0.037]. Phase II success rates were the same for expansion cohort with two to 20 and more than 20 patients (48% vs. 52%). Other positive associations were disease-specific trials (OR, 1.7; 95% CI, 1.0-2.9; P = 0.037), industry sponsorship (OR, 2.9; 95% CI, 1.5-5.7; P = 0.0024), and response rate of 6% to 20% (OR, 2.89; 95% CI, 1.6-5.2; P = 0.0007). Drugs tested in phase I trials with expansion cohorts had a higher rate of 5-year approval (19% vs. 5%; HR, 4.4; 95% CI, 2.2-8.8; P < 0.001).Conclusions: The use of expansion cohorts in phase I trials was associated with success of subsequent phase II trials. However, confounders may play a role in this association. Clin Cancer Res; 23(15); 4020-6. ©2017 AACR.