Rebecca Arbuckle

Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial

BACKGROUND It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. METHODS Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. FINDINGS After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. INTERPRETATION Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Impact of Surveillance for Vancomycin-Resistant Enterococci on Controlling a Bloodstream Outbreak among Patients with Hematologic Malignancy

OBJECTIVE To determine the impact of stool surveillance cultures of critically ill patients on controlling vancomycin-resistant enterococci (VRE) outbreak bacteremia. DESIGN Stool surveillance cultures were performed on patients who had hematologic malignancy or were critically ill at the time of hospital admission to identify those colonized with VRE. Hence, contact isolation was initiated. SETTING A tertiary-care cancer center with a high prevalence of VRE. PARTICIPANTS All patients with hematologic malignancy who were admitted to the hospital as well as all of those admitted to the intensive care unit were eligible. RESULTS Active stool surveillance cultures performed between 1997 and 2001 decreased the incidence density of VRE bacteremias eightfold while vancomycin use remained constant. In fiscal year (FY) 1997 and FY 1998, there were five and three VRE outbreak bacteremias, respectively. The outbreak clones were responsible for infection in 69% of those patients with VRE bacteremia. However, the stool surveillance program resulted in the complete control of VRE bacteremia by FY 1999 until the end of the study. CONCLUSION Despite the steady use of vancomycin, the active surveillance program among high-risk patients with hematologic malignancy and those who were critically ill resulted in the complete control of VRE outbreak bacteremia at our institution.

Clinical-Use-Associated Decrease in Susceptibility of Vancomycin-Resistant Enterococcus faecium to Linezolid: a Comparison with Quinupristin-Dalfopristin

ABSTRACT The susceptibility of 135 vancomycin-resistant Enterococcus faecium bacteremic isolates to linezolid and quinupristin-dalfopristin was determined. All were susceptible to linezolid, while 88% were susceptible to quinupristin-dalfopristin prior to the clinical use of the drugs at our hospital. More than 6 months after their clinical use, a decrease in susceptibility was noted for only linezolid at 83%. This was related in part to a single G2576U gene mutation in domain V of the 23S rRNA gene.

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN Retrospective nonrandomized comparative trial. PATIENTS AND METHODS Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.

Prospective Study of Incidence and Severity of Epiphora and Canalicular Stenosis in Patients With Metastatic Breast Cancer Receiving Docetaxel

659 Background: To determine the incidence and severity of epiphora and canalicular stenosis in patients receiving weekly or every-3-weekly docetaxel. METHODS In this prospective trial, each patient underwent an ophthalmologic examination and probing and irrigation of the lacrimal drainage apparatus at baseline and at every 4-6 weeks after initiation of docetaxel. During each visit, epiphora and canalicular stenosis were graded. Patients with epiphora were treated with Tobradex drops. If epiphora worsened or findings on probing and irrigation suggested further canalicular narrowing, silicone intubation was offered. RESULTS 28 patients received weekly and 28 patients received every-3-weeks docetaxel. 18(64%) patients who received weekly docetaxel developed epiphora. Epiphora was mild in 7 patients, moderate in 5, and severe in 6. Nine patients had resolution of epiphora with Tobradex. Nine patients had worsened canalicular stenosis; 6 underwent surgery. The median cumulative docetaxel dose was 496.5 mg at onset of epiphora and 889.5 mg at surgery. 11 (39%) patients who received every-3-weeks docetaxel developed epiphora. The median cumulative docetaxel dose at the time of onset of epiphora in this group was 420 mg. Epiphora was mild in 9 patients, moderate in 1, and severe in 1. Nine patients had resolution of epiphora in response to Tobradex. Two patients underwent surgery. CONCLUSIONS Epiphora occurred in 64% of patients in the weekly group and 39% of patients in the every-three-weeks group. Moderate or severe canalicular stenosis was seen in about one-third of patients in the weekly group and none of the patients in the every-3-weeks group. [Table: see text].

Cost-effectiveness analysis of a randomized study comparing radiosurgery with radiosurgery and whole brain radiation therapy in patients with 1 to 3 brain metastases.

BackgroundIn this study, we compare 2 treatment options and determine cost-effectiveness and cost-utility. MethodsWe carried out a decision analysis populated with data from patients with brain metastasis in a concurrent trial randomized to either stereotactic radiosurgery (SRS) and observation or SRS and whole brain radiation therapy. Outcomes included actual life years saved (LYS), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs used were from the healthcare perspective and utilities were captured through a time-trade-off method, using 10-year, 5-year, and 1-year time horizons. One-way sensitivity analyses were carried out to determine robustness of the decision analysis model. ResultsCompared with SRS and whole brain radiation therapy, SRS and observation not only had a higher average cost (

Continued Challenges with the Use of Erythropoiesis‐Stimulating Agents in Patients with Cancer: Perspectives and Issues on Policy‐Guided Health Care

74,000 vs

Evaluation of medication compliance in patients on antidepressants at an outpatient tertiary cancer center setting

119,000, respectively) but also a higher average effectiveness (0.60 LYS vs 1.64 LYS, respectively) with an ICER of

Pharmacoeconomics in oncology

44,231/LYS or