Research Spotlight

Posted May 5th 2017

Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy M.D.

Twelves, C., J. Cortes, J. O’Shaughnessy, A. Awada, E. A. Perez, S. A. Im, P. Gomez-Pardo, L. S. Schwartzberg, V. Dieras, D. A. Yardley, D. A. Potter, A. Mailliez, A. Moreno-Aspitia, J. S. Ahn, C. Zhao, U. Hoch, M. Tagliaferri, A. L. Hannah and H. S. Rugo (2017). “Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase iii beacon trial.” Eur J Cancer 76: 205-215.

Full text of this article.

BACKGROUND: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or >/= 2 sites of metastatic disease compared to treatment of physician’s choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. PATIENTS AND METHODS: HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (>/=5 points) in HRQoL scores were compared. RESULTS: Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P < 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of -9.4 and -10.8 points, respectively. CONCLUSION: There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression.


Posted May 5th 2017

Trouble on Both Sides: Pulmonary Embolism with Pneumothorax.

Carlos E. Velasco M.D.

Carlos E. Velasco M.D.

Velasco, C. E. and C. Howard (2017). “Trouble on both sides: Pulmonary embolism with pneumothorax.” Am J Med 130(5): 530-533.

Full text of this article.

Potential causes of syncope range from fairly trifling to life threatening. For a 49-year-old, previously healthy, African American man, the trigger proved dangerous. While unloading cargo from a truck, he fainted and fell approximately 3 feet to the ground. When emergency medical services arrived, his manager reported that the patient lost consciousness but was unable to quantify the period of time. The patient, upon awakening, experienced shortness of breath with severe right-sided chest and back pain. He attributed his accident to fatigue, stating that he had worked as a security guard the previous night, was tired, and simply fell asleep while emptying the vehicle. He denied seizure-like activity, prodrome, drug use, a family history of syncope, and loss of bowel or bladder function.


Posted May 5th 2017

Significance of Measured Intraoperative Portal Vein Flows After Thrombendvenectomy in Deceased Donor Liver Transplants with Portal Vein Thrombosis.

Peter T. Kim M.D.

Peter T. Kim M.D.

Draoua, M., N. Titze, A. Gupta, H. T. Fernandez, M. Ramsay, G. Saracino, G. McKenna, T. Giuliano, G. B. Klintmalm and P. T. W. Kim (2017). “Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplants with portal vein thrombosis.” Liver Transpl: Apr [Epub ahead of print].

Full text of this article.

BACKGROUND: Adequate portal vein (PV) flow in liver transplantation is essential for a good outcome, and it may be compromised in patients with portal vein thrombosis (PVT). This study evaluated the impact of intraoperatively measured PV flow after PV thrombendvenectomy on outcomes after deceased donor liver transplantation. STUDY DESIGN: The study included 77 patients over a 16-year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into two groups: high PV flow (>1300 mL/min, N = 55) and low PV flow (60 years (hazard ratio 3.04, confidence interval 1.36-6.82; P = 0.007) and low portal flow (HR 2.31 (1.15-4.65, P=0.02) were associated with worse survival. CONCLUSION: PV flow <1300 mL/min after PV thrombendvenectomy for PVT during deceased donor liver transplantation was associated with higher rates of biliary strictures and worse graft survival. Consideration should be given to identifying reasons for low flow and performing maneuvers to increase PV flow when intraoperative PV flows are <1300 mL/min.


Posted May 5th 2017

Tick tock. Tick tock. Tic-tic-tic-tic: If you watch the pot long enough, it boils.

James R. Edgerton M.D.

James R. Edgerton M.D.

Edgerton, J. R. (2017). “Tick tock. Tick tock. Tic-tic-tic-tic: If you watch the pot long enough, it boils.” J Thorac Cardiovasc Surg 153(5): 1095-1096.

Full text of this article.

In this issue of the Journal, Damiano and colleagues1 provide 5-year results of surgical ablation (SA) concomitant to coronary artery bypass grafting (CABG). Given the problems associated with following referral patients over 5 years, this is a laudable effort. In surgical and catheter ablation literature filled with glowing 1-year results, this type of long-term follow-up, reported according to the 2012 Consensus Statement,2 is sorely needed. And the results are sobering: 70% of patients were free of atrial tachyarrhythmias and off antiarrhythmic drugs at 5 years. These results are similar to a previously reported larger group of 512 patients who had a 66% similar outcome.3 These papers, in the modern reporting era of continuous rhythm monitoring, contrast with their 2003 report of 98% freedom from AF at 5 years in patients undergoing CABG/maze.4…Despite these things, we need to be aggressively treating our operative patients who have AF.


Posted May 5th 2017

Where Are We Now? A Clinicians’ Guide to the Use of Follow-On Insulin for Patients with Diabetes.

Priscilla A. Hollander M.D.

Priscilla A. Hollander M.D.

Edelman, S. V., P. A. Hollander and E. E. Wright, Jr. (2017). “Where are we now? A clinicians’ guide to the use of follow-on insulin for patients with diabetes.” Am J Med 130(5): 614.

Full text of this article.

Insulin has been used as a standard treatment for patients with diabetes for almost 100 years. Over time, advances in insulin development have improved its pharmacologic properties. (Online access: http://courses.elseviercme.com/t2dm/666). Most recently, the US Food and Drug Administration approved a novel, follow-on basal insulin agent, with more expected to be commercially available in the near future. With the imminent availability of follow-on basal insulin agents, clinicians need to be aware of the potential benefits and concerns in order to facilitate informed decision making and to provide the best possible advice and guidance to their patients with diabetes. This program will review how follow-on insulin products are developed, manufactured, and receive regulatory approval; evaluate clinical trial data for new and emerging follow-on basal insulin agents; and provide practical information and guidance on how they may be incorporated into clinical practice. While it is unknown how follow-on basal insulins will affect patient outcomes, they have the potential to increase access to treatment among patients with diabetes and reduce healthcare costs. http://courses.elseviercme.com/alzheimer/593e.