Kelvin K. Chan

Nasopharyngeal carcinoma: The next challenges

Nasopharyngeal carcinoma (NPC) differs from other head and neck cancers in its aetiology, epidemiology and potential therapeutic options. Despite cure for the majority of the patients, challenges still exist in the prevention of disease relapse, treatment of patients with refractory or metastatic NPC and the management of long-term toxicities. This article discusses the specific challenges in pushing the boundaries of NPC treatments further, with an emphasis on prognostic/predictive markers, molecularly targeted therapies, immunotherapies and the areas of interest with regard to long-term toxicities arising from therapeutic interventions.

A preliminary investigation of worm infections in a bluetooth environment

Over the past year, there have been several reports of malicious code exploiting vulnerabilities in the Bluetooth protocol. While the research community has started to investigate a diverse set of Bluetooth security issues, little is known about the feasibility and the propagation dynamics of a worm in a Bluetooth environment. This paper is an initial attempt to remedy this situation.We start by showing that the Bluetooth protocol design and implementation is large and complex. We gather traces and we use controlled experiments to investigate whether a large-scale Bluetooth worm outbreak is viable today. Our data shows that starting a Bluetooth worm infection is easy, once a vulnerability is discovered. Finally, we use trace-drive simulations to examine the propagation dynamics of Bluetooth worms. We find that Bluetooth worms can infect a large population of vulnerable devices relatively quickly, in just a few days.

Hepatitis B Virus Screening Before Chemotherapy for Lymphoma: A Cost-Effectiveness Analysis

PURPOSE Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with antiviral prophylaxis. It remains unclear whether HBV screening is cost effective. METHODS A decision model was developed to compare the clinical outcomes, costs, and cost effectiveness of three HBV screening strategies for patients with lymphoma before R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy: screen all patients for hepatitis B surface antigen (HBsAg; Screen-All), screen patients identified as being at high risk for HBV infection (Screen-HR), and screen no one (Screen-None). Patients testing positive were administered antiviral therapy until 6 months after completion of chemotherapy. Those not screened were initiated on antiviral therapy only if HBV hepatitis occurred. Probabilities of HBV and lymphoma outcomes were derived from systematic literature review. A third-party payer perspective was adopted, costs were expressed in 2011 Canadian dollars, and a 1-year time horizon was used. RESULTS Screen-All was the dominant strategy. It was least costly at

A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck

32,589, compared with

Chemotherapy-Induced Cardiotoxicity: Detection, Prevention, and Management

32,598 for Screen-HR and

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials

32,657 for Screen-None. It was also associated with the highest 1-year survival rate at 84.99%, compared with 84.96% for Screen-HR and 84.86% for Screen-None. The analysis was sensitive to the prevalence of HBsAg positivity in the low-risk population, with Screen-HR becoming least costly when this value was ≤ 0.20%. CONCLUSION In patients receiving R-CHOP for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients.

Mesa: geo-replicated, near real-time, scalable data warehousing

BACKGROUND An open-label, multicenter, single-arm phase II trial was conducted to investigate the clinical activity of dacomitinib in recurrent/metastatic squamous-cell carcinoma of the head and neck (RM-SCCHN). PATIENTS AND METHODS Eligible patients were administered dacomitinib at 45 mg orally daily, in 21-day cycles. Primary end point was objective response rate. RESULTS Sixty-nine patients were enrolled with a median age of 62 years. Among response-evaluable patients, 8 [12.7%, 95% confidence interval (CI) 5.6% to 23.5%] achieved a partial response and 36 (57.1%) had stable disease, lasting ≥24 weeks in 9 patients (14.3%). The median progression-free survival (PFS) was 12.1 weeks and the median overall survival (OS) was 34.6 weeks. Most adverse events (AEs) were tolerable. The most common grade 3 or higher treatment-related AEs were diarrhea (15.9%), acneiform dermatitis (8.7%), and fatigue (8.7%). Treatment-related AEs led to at least one dose interruption in 28 (40.6%) patients and dose reductions in 26 (37.7%). Permanent treatment discontinuation occurred in 8 (11.6%) patients due to treatment-related AEs. CONCLUSIONS Dacomitinib demonstrated clinical activity in RM-SCCHN, and the primary end point of this study was met. The toxicity profile of this agent was generally manageable with dose interruptions and adjustments.

Cost-effectiveness of systemic therapies for metastatic pancreatic cancer

Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivors. It might manifest as arrhythmia, hypertension, myocardial ischemia, thromboembolism, heart failure, systolic dysfunction, or other adverse events. Anthracyclines and trastuzumab are the chemotherapeutic agents with the most documented cardiac side effects; however, the array of novel molecular targeting therapies available is concerning because their side effects are not yet well understood. Nevertheless, there are potential strategies to mitigate the risks of cardiac complications for cancer patients. In this article, the common systemic drugs with cardiotoxic potential and the monitoring and diagnostic tools, including the role of biomarkers for early detection, are reviewed. We will also review the use of cardioprotectant agents as pharmacological interventions in prophylactic and treatment settings. Our aim is to provide a concise and up-to-date summary of the detection, management, and prevention of chemotherapy-induced cardiotoxicity for the busy clinician.

Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement

PurposePalonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT3RAs in CINV prophylaxis.MethodsA literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT3RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT3RA-related adverse events.ResultsSixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT3RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.ConclusionsPalonosetron is safer and more efficacious than other 5-HT3RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

Postoperative intensity-modulated radiotherapy following surgery for oral cavity squamous cell carcinoma: patterns of failure.

Mesa is a highly scalable analytic data warehousing system that stores critical measurement data related to Googles Internet advertising business. Mesa is designed to satisfy a complex and challenging set of user and systems requirements, including near real-time data ingestion and queryability, as well as high availability, reliability, fault tolerance, and scalability for large data and query volumes. Specifically, Mesa handles petabytes of data, processes millions of row updates per second, and serves billions of queries that fetch trillions of rows per day. Mesa is geo-replicated across multiple datacenters and provides consistent and repeatable query answers at low latency, even when an entire datacenter fails. This paper presents the Mesa system and reports the performance and scale that it achieves.