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This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov).
Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG.
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BACKGROUND: Demonstrating safety and efficacy of new medical treatments requires clinical trials but clinical trials are costly and may not provide value proportionate to their costs. As most health systems have limited resources, it is therefore important to identify the trials with the highest value. Tools exist to assess elements of a clinical trial such as statistical validity but are not wholistic in their valuation of a clinical trial. This study aims to develop a measure of clinical trials value and provide an online tool for clinical trial prioritisation. METHODS: A search of the academic and grey literature and stakeholder consultation was undertaken to identify a set of criteria to aid clinical trial valuation using multi-criteria decision analysis. Swing weighting and ranking exercises were used to calculate appropriate weights of each of the included criteria and to estimate the partial-value function for each underlying metric. The set of criteria and their respective weights were applied to the results of six different clinical trials to calculate their value. RESULTS: Seven criteria were identified: 'unmet need', 'size of target population', 'eligible participants can access the trial', 'patient outcomes', 'total trial cost', 'academic impact' and 'use of trial results'. The survey had 80 complete sets of responses (51% response rate). A trial designed to address an 'Unmet Need' was most commonly ranked as the most important with a weight of 24.4%, followed by trials demonstrating improved 'Patient Outcomes' with a weight of 21.2%. The value calculated for each trial allowed for their clear delineation and thus a final value ranking for each of the six trials. CONCLUSION: We confirmed that the use of the decision tool for valuing clinical trials is feasible and that the results are face valid based on the evaluation of six trials. A proof-of-concept applying this tool to a larger set of trials with an external validation is currently underway.
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PURPOSE: High-grade disease accounts for ~ 70% of all glioma, and has a high mortality rate. Few modifiable exposures are known to be related to glioma risk or mortality. METHODS: We examined associations between lifetime physical activity and physical activity at different ages (15-18 years, 19-29 years, 30-39 years, last 10 years) with the risk of glioma diagnosis, using data from a hospital-based family case-control study (495 cases; 371 controls). We followed up cases over a median of 25 months to examine whether physical activity was associated with all-cause mortality. Physical activity and potential confounders were assessed by self-administered questionnaire. We examined associations between physical activity (metabolic equivalent [MET]-h/wk) and glioma risk using unconditional logistic regression and with all-cause mortality in cases using Cox regression. RESULTS: We noted a reduced risk of glioma for the highest (≥ 47 MET-h/wk) versus lowest (< 24 METh/wk) category of physical activity for lifetime activity (OR = 0.58, 95% CI: 0.38-0.89) and at 15-18 years (OR = 0.57, 95% CI: 0.39-0.83). We did not observe any association between physical activity and all-cause mortality (HR for lifetime physical activity = 0.91, 95% CI: 0.64-1.29). CONCLUSION: Our findings are consistent with previous research that suggested physical activity during adolescence might be protective against glioma. Engaging in physical activity during adolescence has many health benefits; this health behavior may also offer protection against glioma.
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Exercício Físico , Glioma , Adolescente , Estudos de Casos e Controles , Seguimentos , Glioma/epidemiologia , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities. METHODS: BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania. RESULTS: Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world's first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data. CONCLUSIONS: Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.
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Inteligência Artificial , Neoplasias Encefálicas , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Coleta de Dados , Humanos , Estudos Prospectivos , Sistema de Registros , VitóriaRESUMO
BACKGROUND: Management of preschool wheeze is based predominantly on symptom patterns. OBJECTIVE: To determine whether personalizing therapy using blood eosinophils or airway bacterial infection results in fewer attacks compared with standard care. METHODS: A proof-of-concept, randomized trial to investigate whether the prescription of inhaled corticosteroids (ICS) guided by blood eosinophils, or targeted antibiotics for airway bacterial infection, results in fewer unscheduled healthcare visits (UHCVs) compared with standard care. Children aged 1-5 years with ≥2 wheeze attacks in the previous year were categorized as episodic viral wheeze (EVW) or multiple trigger wheeze (MTW). The intervention group was prescribed ICS if blood eosinophils ≥3%, or targeted antibiotics if there is positive culture on induced sputum/cough swab. The control group received standard care. The primary outcome was UHCV at 4 months. RESULTS: 60 children, with a median age of 36.5 (range 14-61) months, were randomized. Median blood eosinophils were 5.2 (range 0-21)%, 27 of 60 (45%) children were atopic, and 8 of 60 (13%) had airway bacterial infection. There was no relationship between EVW, MTW and either blood eosinophils, atopic status or infection. 67% in each group were prescribed ICS. 15 of 30 control subjects and 16 of 30 patients in the intervention group had UHCV over 4 months (p = .8). The time to first UHCV was similar. 50% returned adherence monitors; in those, median ICS adherence was 67%. There were no differences in any parameter between those who did and did not have an UHCV. CONCLUSION: Clinical phenotype was unrelated to allergen sensitization or blood eosinophils. ICS treatment determined by blood eosinophils did not impact UHCV, but ICS adherence was poor.
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Asma , Eosinófilos , Administração por Inalação , Corticosteroides/uso terapêutico , Asma/diagnóstico , Pré-Escolar , Humanos , Fenótipo , Sons Respiratórios/diagnósticoRESUMO
In children with very severe cerebral palsy, an adversarial legal process for medical negligence, when liability is admitted, requires an estimate of life expectancy. Medical experts using the same cohort data and the same clinical facts can produce quite different life expectancies, leading to arguments in legal conferences and courts. The issues that commonly arise include between-country comparisons, projected and therapy-induced advanced life expectancies, and the contribution of epilepsy, scoliosis, and especially cognition to life expectancy. In this review, these factors are discussed from an arithmetic, statistical, and medical viewpoint to initiate debate on the issue, including whether median survival should be advocated.
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Paralisia Cerebral , Epilepsia , Escoliose , Paralisia Cerebral/complicações , Criança , Estudos de Coortes , Humanos , Expectativa de VidaRESUMO
OBJECTIVE: This pilot study tested the efficacy of two brief, phone-administered, behavioral interventions derived from behavioral activation in reducing burnout among doctoral students. METHODS: Sixty-six doctoral students demonstrating current high burnout were randomly assigned to one of three intervention conditions: (1) Reward: increasing pleasant, rewarding behaviors, (2) Approach: approaching important goals that they have been avoiding, or (3) Control: monitoring only. RESULTS: Results indicated that doctoral students treated with the approach intervention reported significantly lower burnout compared to participants in the control condition immediately after the intervention and at a 1-week follow-up. Results also suggested that students in the approach intervention also reported higher well-being compared to students in the control condition. CONCLUSION: These findings suggest that this approach intervention is an effective treatment for school burnout for doctoral students that can be delivered remotely through phone and web technology.
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Esgotamento Profissional , Esgotamento Psicológico , Terapia Comportamental , Esgotamento Profissional/terapia , Humanos , Projetos Piloto , EstudantesRESUMO
BACKGROUND: Glomerular filtration rate (GFR) measured by Chromium-51-EDTA excretion (51Cr-GFR) is considered the gold standard of renal function assessment, but serum creatinine in the Cockcroft-Gault (CG) formula is routinely used to estimate GFR for carboplatin dosing. Serum creatinine measured by isotope-dilution-mass-spectrometry (IDMS) can generate spuriously high GFR estimates when used in the CG formula. We hypothesized that GFR calculated using IDMS-creatinine in the CG formula (CG-GFR) exposes patients to inaccurate carboplatin dosing. METHODS: This is a multicenter retrospective study of patients who had a 51Cr-GFR assessment for malignant or non-malignant indications, with a matched CG-GFR. Carboplatin dose based on 51Cr-GFR at AUC5 was used as the reference. RESULTS: 550 patients were analyzed, median age 62 (19-90), 64% female. Indication for GFR evaluation: malignancy (85%), assessment for live kidney donation (12%), other (3%). Median ratio of CG-GFR: 51Cr-GFR 1.04 (0.43-3.38); <0.8 in 72 patients (13%), >1.2 in 180 patients (33%). Despite capping of CG-GFR at 125 mL/min, dosing according to AUC6 would have resulted in 18% of patients being underdosed and 23% overdosed by >100 mg compared to 51Cr-GFR. Subgroup analysis identified BMI (>35, MPE 39%), gender (female MPE 15%), GFR indication (malignancy MPE 11%) as risk factors for overestimate of CG-GFR, and BMI < 20 for underestimate (MPE -3.5%). CONCLUSIONS: The convention of considering AUC5 carboplatin based on 51Cr-GFR, and AUC6 carboplatin based on CG-GFR as equivalent is invalid and should be abandoned. When 51Cr-GFR is unavailable, capping CG-GFR at 125 mL/min is recommended.
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Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Creatinina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Carboplatina/farmacologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
Coinfecção , Fibrose Cística , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Estafilocócicas , Staphylococcus aureus , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Humanos , Infecções por Pseudomonas/complicações , Coinfecção/microbiologia , Infecções Estafilocócicas/complicações , Masculino , Feminino , Adulto , Doença Crônica , CriançaRESUMO
We report a 23 year old female with biallelic truncating variants in the ITCH (Itchy E3 Ubiquitin protein ligase, mouse homolog of; OMIM60649) gene associated with marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. The condition has only been reported once previously (Lohr et al., American Journal of Human Genetics, 2010, 86, 447-453) in 10 children from an Old Order Amish family found to have a homozygous frameshift truncating variant in association with failure to thrive, chronic lung disease, motor and cognitive delay, and variable autoimmune diseases including autoimmune hepatitis, enteropathy, hypothyroidism, and diabetes. The condition is listed in OMIM as Autoimmune disease, Multisystem with Facial Dysmorphism (OMIM613385). The clinical course as well as the dysmorphic facial and limb features overlap closely with our patient. We believe the triad of marked syndromic short stature, chronic lung disease, and dysmorphism (with or without cognitive impairment and wider autoimmune involvement) is distinctive.
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Alelos , Proteínas Repressoras/genética , Ubiquitina-Proteína Ligases/genética , Feminino , Mutação da Fase de Leitura , Homozigoto , Humanos , Fenótipo , Adulto JovemRESUMO
BACKGROUND: The impact of regulatory approvals of new therapies for castration-resistant prostate cancer (CRPC) in Australia is unclear. AIMS: To determine if changes in novel therapy access in Australia affected how clinicians initially managed men with newly diagnosed CRPC. METHODS: Data from patients diagnosed with CRPC from 2013 to 2016 across three Australian hospitals were retrospectively collected. Baseline clinicopathological factors and initial management decision at the time of CRPC development (early treatment (ET) vs deferred treatment (DT)) were recorded. Categorical variables between cohorts were compared by Chi-squared analysis. Cox regression analysis was performed to assess the impact of CRPC diagnosis year on time to commencing life-prolonging systemic treatment (TTT). RESULTS: Our study identified 137 CRPC patients, with 126 (92%) patients receiving life-prolonging systemic treatment. The median age was 73 years. The initial management decision was DT in 71 (52%) patients and ET in 66 (48%) patients. There was a significant shift from DT to ET during the study period (2013-2014: DT 61% vs ET 33%; 2015-2016: DT 39% vs ET 67%; P = 0.004), with a rise in novel androgen receptor signalling inhibitor use and simultaneous reduction in first-generation antiandrogen use at CRPC development. Each successive CRPC diagnosis year was associated with shorter TTT on univariate analysis (HR: 1.5, 95% CI: 1.3-1.7, P < 0.001). CONCLUSION: Over time, clinicians are favouring earlier introduction of life-prolonging systemic treatment at the development of CRPC. This trend is largely driven by substantial uptake of novel androgen receptor signalling inhibitors as the preferred initial treatment for CRPC patients.
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Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Progressão da Doença , Análise Fatorial , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. METHODS: Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. RESULTS: For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. CONCLUSIONS: In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society.
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Bevacizumab/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Austrália , Neoplasias Encefálicas/diagnóstico por imagem , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Detecção Precoce de Câncer , Feminino , Glioblastoma/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.
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Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/uso terapêutico , Glioblastoma/tratamento farmacológico , Angiografia por Ressonância Magnética , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioblastoma/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.
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Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/uso terapêutico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/radioterapia , Intervalo Livre de Doença , Feminino , Glioblastoma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Qualidade de VidaAssuntos
Fibrose Cística/complicações , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Glioblastoma is the most malignant and most common primary brain tumour and is treated with resection followed by post-operative radiotherapy and chemotherapy. However, a significant amount of patients are older than 80 years, and such an approach may not be appropriate. Data on patients aged 80 or older with glioblastoma from two hospitals was collected using the CNS Tumour Database on the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) system operated by BioGrid. Between 2008 and July 2011, 40 patients aged 80 years or older were diagnosed with glioblastoma. The median ECOG PS was 2 and the ASA score was 3. All 40 patients underwent surgery and 33% had a gross total resection. Only six patients (15%) had either post-operative radiotherapy or chemotherapy. The overall median survival was 4 months (range 0-18 months) and 28% of patients lived between 6 and 24 months. This is the largest reported cohort of very elderly patients with glioblastoma. Patients tolerated surgery but few went on to receive post-operative radiotherapy or chemotherapy. This patient population requires special attention and in particular would benefit from participation in suitable clinical trials to determine the best care regime.
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Idoso de 80 Anos ou mais/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Glioblastoma/epidemiologia , Fatores Etários , Idoso , Austrália/epidemiologia , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Terapia Combinada , Bases de Dados Factuais , Feminino , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Análise de Sobrevida , Resultado do TratamentoRESUMO
A rare, yet serious, complication of mechanical heart valves is symptomatic obstructive prosthetic valve thrombosis. The risk of valve thrombosis is magnified in patients who are nonadherent to prescribed anticoagulation. In this case report, we describe a 48-year-old male patient with a history of mechanical aortic valve replacement surgery, who stopped taking prescribed warfarin therapy 2 years before presentation and subsequently developed acute decompensated heart failure secondary to valvular dysfunction. Low-dose alteplase therapy was administered successfully with no bleeding complications and a complete return of valvular function.
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Estenose da Valva Aórtica/terapia , Fibrinolíticos/uso terapêutico , Oclusão de Enxerto Vascular/tratamento farmacológico , Próteses Valvulares Cardíacas , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Anticoagulantes/uso terapêutico , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Trombose/etiologiaRESUMO
Anti-angiogenic therapy for glioblastoma has been in the spotlight for several years, as researchers and clinicians strive to find agents with meaningful efficacy against glioblastoma. Bevacizumab in particular, in the second half of the last decade, became the most significant breakthrough in anti-glioblastoma therapy since temozolomide. Optimism for bevacizumab has been somewhat challenged given recent clinical trials that have raised questions regarding its clinical effectiveness, the optimal timing of its use and the validity of endpoints, among other issues. In addition, uncertainty has recently arisen regarding the effects of bevacizumab on quality of life and neurocognitive function, two key clinical endpoints of unquestionable significance among glioblastoma patients. In this review, we highlight these controversies and other recent work related to bevacizumab for glioblastoma.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Bevacizumab , Ensaios Clínicos como Assunto , Humanos , Qualidade de VidaRESUMO
OBJECTIVE: To examine the patterns of care and outcomes for metastatic renal cell carcinoma (mRCC) in Australia, where there are limited reimbursed treatment options. In particular, we aim to explore prescribing patterns for first-line systemic treatment, the practice of an initial watchful-waiting approach, and the use of systemic treatments in elderly patients. SUBJECTS/PATIENTS AND METHODS: Patients with mRCC undergoing treatment between 2006 and 2012 were identified from four academic hospitals in Victoria and Australian Capital Territory. Demographic, clinicopathological, treatment, and survival data were recorded by chart review. Descriptive statistics were used to report findings. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test. The study was supported by a grant from Pfizer Australia. RESULTS: Our study identified 212 patients with mRCC for analysis. Patients were predominantly of clear cell histology (75%), Eastern Cooperative Oncology Group performance status <2 (67%) and with favourable/intermediate Memorial Sloan-Kettering Cancer Center risk (68%). The median age at diagnosis was 61 years. In all, 163 (77%) patients received first-line systemic therapy, while 49 (23%) received best supportive care (BSC). The most frequently used first-line treatment was sunitinib (125 patients, 77%). Patients who received sunitinib had a median overall survival (OS) of 27.6 months. In all, 43% of patients who received sunitinib underwent a watchful-waiting period of >90 days before initiating treatment; these patients had a median OS of 56.3 months. Elderly patients (50 patients aged ≥70 years) were more likely to receive BSC alone than younger patients (46% vs 16%, P < 0.001). Of those who received systemic therapy, elderly patients were also more likely to have upfront dose reductions (30% vs 8%, P = 0.03). CONCLUSION: Our study of patients with mRCC treated in Australian centres showed that sunitinib was the most commonly prescribed systemic treatment between 2006 and 2012, associated with survival outcomes similar to pivotal studies. We also found that an initial watchful-waiting approach is commonly adopted without apparent detriment to survival. And finally, we found that age has an impact on the prescribing of systemic therapy.
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Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Gerenciamento Clínico , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
We report a case of an 82-year-old man with renal cell carcinoma who developed a cardiac metastasis within the interventricular septum. He had been under watchful waiting for indolent metastatic renal cell carcinoma for many years before developing symptoms consistent with heart failure. At this time, a 44 mm interventricular septal mass, consistent with a cardiac metastasis, was identified as the cause of his symptoms. Pazopanib was initiated which led to both a clinical and radiological response.