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BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Qualidade de Vida , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Terapia de Salvação/métodosRESUMO
PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/radioterapia , Metástase Linfática/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Imagem MolecularRESUMO
There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.
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Neoplasias da Bexiga Urinária , Humanos , Terapia Combinada , Estadiamento de Neoplasias , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/radioterapia , Cistectomia , Terapia NeoadjuvanteRESUMO
PURPOSE: To conduct a systematic review to identify studies that assessed the association between CYP2C19 polymorphisms and clinical outcomes in peripheral artery disease (PAD) patients who took clopidogrel. METHODS: We systematically searched Ovid EMBASE, PubMed, and Web of Science from November 1997 (inception) to September 2020. We included observational studies evaluating how CYP2C19 polymorphism is associated with clopidogrel's effectiveness and safety among patients with PAD. We extracted relevant information details from eligible studies (e.g., study type, patient population, study outcomes). We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) Tool to assess the risk of bias for included observational studies. RESULTS: The outcomes of interest were the effectiveness and safety of clopidogrel. The effectiveness outcomes included clinical ineffectiveness (e.g., restenosis). The safety outcomes included bleeding and death related to the use of clopidogrel. We identified four observational studies with a sample size ranging from 50 to 278. Outcomes and comparison groups of the studies varied. Three studies (75%) had an overall low risk of bias. All included studies demonstrated that carrying CYP2C19 loss of function (LOF) alleles was significantly associated with reduced clinical effectiveness and safety of clopidogrel. CONCLUSIONS: Our systematic review showed an association between CYP2C19 LOF alleles and reduced functions of clopidogrel. The use of CYP2C19 testing in PAD patients prescribed clopidogrel may help improve the clinical outcomes. However, based on the limited evidence, there is a need for randomized clinical trials in PAD patients to test both the effectiveness and safety outcomes of clopidogrel.
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Clopidogrel , Citocromo P-450 CYP2C19 , Doença Arterial Periférica , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Genótipo , Humanos , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo Genético , Resultado do TratamentoRESUMO
Aim: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. The optimal treatment protocols are debated. Methodology: A systematic search and individual patient data analysis of published cases of SDC was performed. SPSS v21 was used for statistical analysis. Results: Data of 857 patients available. Median overall survival (OS) and progression-free survival (PFS) of the entire cohort 42 months and 24 months. Nodal involvement, males, primary size >5 cm, androgen receptor (AR) negativity significantly worse OS. Patients with surgery had a favorable median PFS (p = 0.000) and OS (p = 0.077). Patients with adjuvant radiation had better PFS (30 vs 18 months; p = 0.077). Conclusion: SDC has modest survival. Surgery and adjuvant radiation should be advocated for all patients. AR expression appears prognostic for survival.
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Although clopidogrel is a frequently used antiplatelet medication to treat and prevent atherothrombotic disease, clinicians must balance its clinical effectiveness with the potential side effect of bleeding. However, many previous studies have evaluated beneficial and adverse factors separately. The objective of our study was to perform a comprehensive meta-analysis of studies of clopidogrel's clinical effectiveness and/or risk of bleeding in order to identify and assess all reported risk factors, thus helping clinicians to balance patient safety with drug efficacy. We analyzed randomized controlled trials (RCTs) of maintenance use in four stages: search for relevant primary articles; abstract and full article screening; quality assessment and data extraction; and synthesis and data analysis. Screening of 7,109 articles yielded 52 RCTs that met the inclusion criteria. Twenty-seven risk factors were identified. "Definite risk factors" were defined as those with aggregated odds ratios (ORs) > 1 and confidence intervals (CIs) > 1 if analyzed in more than one study. Definite risk factors for major bleeding were concomitant aspirin use (OR 2.83, 95% CI 2.04-3.94) and long duration of clopidogrel therapy (> 6 months) (OR 1.74, 95% CI 1.21-2.50). Dual antiplatelet therapy, extended clopidogrel therapy, and high maintenance dose (150 mg/day) of clopidogrel were definite risk factors for any bleeding. Reduced renal function, both mild and severe, was the only definite risk factor for clinical ineffectiveness. These findings can help clinicians predict the risks and effectiveness of clopidogrel use for their patients and be used in clinical decision support tools.