ABSTRACT
OBJECTIVES: NSCLC patients harboring EGFR mutation invariably developed resistance to EGFR TKI. We postulated that oligoresidual disease (ORD) after initial TKI might harbor resistant clones. This study aimed to test if preemptive local ablative therapy (LAT) can improve progression free survival (PFS) or not compared to historic data. MATERIALS AND METHODS: Patients indicated for EGFR TKI who possessed ORD (≤ 4 PET-avid lesions) after an initial 3-month TKI therapy were enrolled. After screening PET-CT, eligible patients with PET-avid ORDs were treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians' discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was repeated on the 3rd and 12th month post-LAT (or at progression) apart from regular imaging. Further LAT was allowed in oligoprogressive disease. Primary endpoint was PFS rate at one-year from enrollment. Overall survival (OS), PFS and treatment safety were secondary endpoints. A post hoc comparison with screen failure cohort was performed. RESULTS: Eighteen patients were enrolled from 2014-17. Recruitment was stopped before the planned number (34) due to slow accrual. Two were excluded due to consent withdrawal and significant protocol violation. Median follow up was 39.1 months. Among the 16 analyzed patients, the one-year PFS rate (i.e. 15 month post TKI) was 68.8 %. Median OS was 43.3 months. All LAT were done by SABR, and none experienced ≥ grade 3 SABR related toxicities. Compared with screen failure cohort (n = 48), pre-emptive LAT effectively reduced risk of progression (HR 0.41, p = 0.0097). CONCLUSION: Preemptive LAT in ORD appeared to be safe and feasible. The 1-year PFS rate was encouraging. However, potential biases and the limitations of the study should not be overlooked. Further randomized studies are warranted.
Subject(s)
Adenocarcinoma of Lung/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Radiosurgery/methods , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/secondary , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Male , Middle Aged , Mutation , Prognosis , Prospective Studies , Protein Kinase Inhibitors/therapeutic use , Survival RateABSTRACT
Patients with severe aortic stenosis are commonly elderly and with significant comorbidity. Surgical intervention can improve symptoms and survival in severe aortic stenosis. However, a large proportion of patients do not undergo surgical intervention because they are deemed to be inoperable or too high risk. Over the last decade, transcatheter aortic valve replacement (TAVR) has been developed, providing an effective, less-invasive alternative to open cardiac surgery for inoperable or high-risk patients. The purpose of this review is to provide an overview of risk assessment in TAVR. Specifically, this article reviews the epidemiology of aortic stenosis, describes the risks and benefits of TAVR across multiple outcome measures, explores frailty and other elderly risk factors as metrics for improved risk assessment and discusses the application of improved risk assessment in TAVR decisions.
Subject(s)
Aortic Valve Stenosis/surgery , Cardiac Catheterization/methods , Heart Valve Prosthesis Implantation/methods , Aged , Aortic Valve Stenosis/epidemiology , Aortic Valve Stenosis/pathology , Decision Making , Frail Elderly , Heart Valve Prosthesis Implantation/adverse effects , Humans , Outcome Assessment, Health Care , Risk Assessment , Risk Factors , Severity of Illness IndexABSTRACT
BACKGROUND: Comorbidity, disability, and polypharmacy commonly complicate the care of patients with heart failure. These factors can change biological response to therapy, reduce patient ability to adhere to recommendations, and alter patient preference for treatment and outcome. Yet, a comprehensive understanding of the complexity of patients with heart failure is lacking. Our objective was to assess trends in demographics, comorbidity, physical function, and medication use in a nationally representative, community-based heart failure population. METHODS: Using data from the National Health and Nutrition Examination Survey, we analyzed trends across 3 survey periods (1988-1994, 1999-2002, 2003-2008). RESULTS: We identified 1395 participants with self-reported heart failure (n=581 in 1988-1994, n=280 in 1999-2002, n=534 in 2003-2008). The proportion of patients with heart failure who were ≥80 years old increased from 13.3% in 1988-1994 to 22.4% in 2003-2008 (P <.01). The proportion of patients with heart failure who had 5 or more comorbid chronic conditions increased from 42.1% to 58.0% (P <.01). The mean number of prescription medications increased from 4.1 to 6.4 prescriptions (P <.01). The prevalence of disability did not increase but was substantial across all years. CONCLUSION: The phenotype of patients with heart failure changed substantially over the last 2 decades. Most notably, more recent patients have a higher percentage of very old individuals, and the number of comorbidities and medications increased markedly. Functional disability is prevalent, although it has not changed. These changes suggest a need for new research and practice strategies that accommodate the increasing complexity of this population.
