RESUMO
PURPOSE: To investigate responses in the primary tumour to different systemic treatment regimens in patients with metastatic renal cell carcinoma (mRCC). METHODS: A single-centre retrospective analysis of treatment-naive mRCC patients without prior nephrectomy receiving VEGF tyrosine kinase inhibitors (VEGF only), immune checkpoint inhibitors (IO only), or combinations thereof (IO + VEGF). The primary outcome was the rate of partial response in the primary tumour (primary tumour PR, ≥ 30% diameter reduction). Secondary outcomes were time to best primary tumour diameter change, overall survival (OS) and progression-free survival (PFS) by Kaplan-Meier analysis. Predictors of survival outcomes were explored by Cox proportional hazards regression analysis. RESULTS: The rate of primary tumour PR was 14% for VEGF only (4/28 patients), 22% for IO only (5/23) and 50% for IO + VEGF (7/14), with median best primary tumour diameter change of - 8.0%, + 5.1%, and - 31.1% respectively, and median time to best primary tumour diameter change of 3.2, 3.0 and 6.9 months respectively. Median OS was significantly greater with IO + VEGF compared to VEGF only (HR 0.45, p = 0.04) and non-significantly greater compared to IO only (HR 0.46, p = 0.06). In multivariable analysis, primary tumour PR was the only response variable significantly associated with both OS (adjusted HR 0.32, p = 0.01) and PFS (adjusted HR 0.29, p < 0.01). CONCLUSION: mRCC patients without prior nephrectomy receiving first-line IO + VEGF regimens showed the greatest primary tumour responses, suggesting further prospective evaluation of this combination in the neoadjuvant and deferred cytoreductive nephrectomy settings.
Assuntos
Inibidores da Angiogênese , Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Idoso , Resultado do Tratamento , Taxa de Sobrevida , AdultoRESUMO
The standard-of-care for muscle-invasive bladder cancer is radical surgery with neoadjuvant cisplatin-based chemotherapy. Despite curative intent from these interventions, relapse rates post-surgery remain high, with approximately 50% of patients developing local or distant recurrence within 2 years of surgery and a 5-year survival of only 50-60%. Identifying patients who are high risk for relapse post-surgery is a priority. Monitoring patients for circulating tumor DNA (ctDNA) is a minimally invasive approach that appears attractive for selecting patients potentially suitable for adjuvant treatment with checkpoint inhibitors. IMvigor011 (NCT04660344) is a global, double-blind, randomized phase III study assessing the efficacy of atezolizumab (anti-PD-L1) versus placebo in patients with high-risk muscle-invasive bladder cancer who are ctDNA positive post-cystectomy. The primary end point is disease-free survival in participants who are ctDNA positive within 20 weeks of cystectomy.
Imvigor011 is a clinical trial looking at whether selecting patients who have signs of residual cancer molecules in their blood after having an operation for bladder cancer is better than the standard-of-care surveillance CT scans. This may be useful in picking up cancer that has come back after surgery, before it would be visible on CT scans. Patients who have had surgery for bladder cancer will have regular blood tests for 1 year after their surgery. If this cancer molecule is detected in their blood, it may indicate that the cancer has come back. These patients are then allocated by chance into one of two groups: receiving either an anticancer treatment or a placebo. Previous studies have suggested that giving anticancer treatment to patients who have this residual cancer molecule in their blood will improve how well they do after surgery. Clinical Trial Registration: NCT04660344 (ClinicalTrials.gov).
Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/cirurgia , Cisplatino , Anticorpos Monoclonais Humanizados/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Cistectomia , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
BACKGROUND: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. METHODS: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. RESULTS: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. CONCLUSIONS: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.
RESUMO
BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Junior doctors describe a need for greater support and training in end of life care (EoLC) communication skills. The Second Conversation project was designed by a multi-professional steering group as a workplace based training intervention for junior doctors to improve their skills and confidence in undertaking EoLC conversations. Qualitative interviews were carried out with 11 junior doctors and five senior doctors across two sites who took part in, or facilitated, a 'second conversation'. This is a three-step training intervention that involves 1) observation - the junior doctor observes an EoLC conversation between a senior doctor and patient/caregiver; 2) direct experience - the junior doctor undertakes a follow-up second conversation with the patient/caregiver; and 3) reflection - the junior doctor discusses and reflects on the experience with a senior colleague. Interviews were analysed using framework analysis and findings informed iterative changes to the intervention and its implementation using 'Plan, Do, Study, Act' cycles. Benefits that were identified included the flexibility of the intervention and its positive impact on the confidence and skills of junior doctors. The Second Conversation was felt to be of most value to newly qualified doctors and worked well on wards where length of stay was longer and EoLC conversations frequently happen. Further evaluation and exploration of patient and caregiver experiences is required.
RESUMO
BACKGROUND: Over recent years there has been a trend towards developing high-quality assessments to assess a doctor's performance in the workplace. Case-based discussion (CbD) is a form of workplace-based assessment that has the potential to provide feedback to trainees on their performance or management of a specific case. The aim of this study was to explore how CbDs are perceived and implemented in practice amongst a UK cohort of medical trainees. METHODS: This study involved 78 medical trainees at a UK hospital completing a questionnaire rating their last CbD experience, including the duration spent receiving feedback, whether it was pre-planned or ad hoc and how they responded to the feedback received. Focus groups were conducted involving 12 trainees to discuss common themes on feedback arising from the questionnaire, and thematic analysis was carried out following these discussions. RESULTS: Only 19 per cent of assessments were pre-planned and the average duration of assessments was 6-10 minutes, with feedback lasting less than 5 minutes. A total of 76 per cent of trainees responded to the feedback they received by completing self-directed learning or by addressing the specific action points arising from the feedback. The focus groups highlighted the barriers to incorporating these assessments into everyday practice, including appreciating the time constraints and the importance of trainer engagement in the assessment process. The aim of this study was to explore how CbDs are perceived and implemented in practice CONCLUSION: This study demonstrates that most trainees appreciate the educational value of CbDs, but more emphasis and training is required in planning these assessments and in providing feedback that is both specific and actionable.
Assuntos
Atitude do Pessoal de Saúde , Competência Clínica , Retroalimentação , Assistência ao Paciente , Grupos Focais , Humanos , Médicos , Inquéritos e Questionários , Reino Unido , Local de TrabalhoAssuntos
Corticosteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Aleitamento Materno , Complicações na Gravidez/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Esquema de Medicação , Prescrições de Medicamentos/normas , Medicina Baseada em Evidências/métodos , Feminino , Humanos , Troca Materno-Fetal , GravidezAssuntos
Analgésicos/uso terapêutico , Aleitamento Materno , Complicações na Gravidez/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Esquema de Medicação , Prescrições de Medicamentos/normas , Medicina Baseada em Evidências/métodos , Feminino , Humanos , Troca Materno-Fetal , GravidezRESUMO
The demand for endoscopic procedures continues to increase and is likely to continue to do so for the foreseeable future. Alongside elective diagnostic procedures, the number of complex and therapeutic procedures is increasing. It is therefore vital that the consent process is comprehensive, and high standards in consenting patients are maintained. Consent is defined as a patient's agreement to treatment or an intervention proposed by a health professional. Careful patient selection is required when proposing endoscopic procedures with an appreciation of the risks and complications that are involved. This paper addresses the various components of gaining informed consent and the legal issues surrounding this process. Additionally, this article reviews legislation and focuses upon specific instances where further considerations have to be made; in a patient who lacks capacity, in children, in percutaneous endoscopic gastrostomy and in the patient who is a Jehovah's Witness.