Mechanical Thrombectomy in Ischemic Strokes; the MR CLEAN trial

Berkhemer et al report in NEJM the results of a Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) that included patients with severe stroke and proximal-vessel occlusion.  The patients with acute ischemic stroke were randomly assigned to receive intra-arterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and could be treated within 6 hours after the onset of symptoms.

The primary outcome was evaluated based on the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death).

The study involved 500 stroke patients whose mean age was 65 years (23-96).  They were treated at 16 medical centers in the Netherlands with 233 assigned to intraarterial treatment while 267 to usual care alone.   Before the randomization 445 of (89.0%) were treated with intravenous alteplase, a tissue plasminogen activator. Retrievable stents were used to snare and remove the thrombus in 190 of the 233 patients (81.5%) assigned to intra-arterial treatment.  There was an absolute difference of 13.5 percentage points in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%) after three months. There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage about 19% in both groups at one month.

They concluded that in patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intra-arterial treatment administered with a mechanical device within 6 hours after stroke onset was effective and safe.

Incidence and Costs of Shorter Duration vs Conventional Irradiation After Breast Conserving Surgery

Bekelman et al in their study published in JAMA examined claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013.   

They classified patients with early-stage breast cancer treated with lumpectomy and whole breast irradiation (WBI) from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) that included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. Hypofractionated WBI (3-5 weeks of treatment) vs. conventional WBI (5-7 weeks of treatment).

Hypofractionated WBI increased from 10.6 in 2008 to 34.5% in 2013 in the hypofractionation-endorsed cohort and from 8.1% in 2008 to 21.2% in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1-year after diagnosis were $28747 for hypofractionated and $31641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; $1610-$4234; P < .001) and $64273 for hypofractionated and $72860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; $5316-$12 017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs. conventional WBI in either cohort.

They concluded that in spite the limitations of their study that they innumerate and discuss, hypofractionated WBI which is comparable in clinical efficacy, cosmesis, and toxicity after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013.  Mean total health care expenditures for patients receiving hypofractionated WBI were about 10% less than for patients receiving conventional WBI.

Benefits, Harms, and Costs of Screening with Digital Mammography

Stout et al in their article published by the JNCI, report on the economic impact digital mammography had as it has replaced film in the United States.

Their research compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs.

For every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and $0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to $5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective.

They concluded that transition to digital breast screening in the United States increased total costs for a small added health benefit.  While the value of digital mammography screening for breast cancer among women aged 40 to 49 years was cost effective the women should be cognizant of the high rate of false positives.

Increase in the cost of breast cancer screening results in no benefit for older women

Killelea et al in their paper published by the JNat Cancer Inst report that cost for breast cancer screening have increased dramatically since the introduction of newer imaging technologies such as digital mammography, computer aided detection, MRI and image guided biopsies, but the outcomes remain undefined, particularly among older women.

The authors used the Surveillance, Epidemiology, and End Results-Medicare linked database, and constructed two cohorts of women without a history of breast cancer, which they followed for 2 years. They compared the use and cost of screening mammography including digital mammography, CAD, and adjunct procedures such as CAD, breast ultrasound, MRI, and biopsies between the period of 2001 and 2002 and the period of 2008 and 2009.

There were 137150 women (mean age = 76.0 years) in the early cohort (2001-2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008-2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P < .001). CAD use increased from 3.2% to 33.1% (P < .001). Average screening-related cost per capita increased from $76 to $112 (P < .001), with annual national fee-for-service Medicare spending increasing from $666 million to $962 million. There was no statistically significant change in detection rates of early-stage tumors (2.45 vs 2.57 per 1000 person-years; P = .41).

The authors concluded that although breast cancer screening-related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed.

Accuracy depends on number of mammograms read

Suleiman et al report in the Journal of Medical Imaging, the effect the number of screening mammograms read per year has on the performance of expert radiologists from Australia and the United States in the detection of breast cancer.

Forty-one radiologists, 21 from Australia and 20 from the United States, reviewed 30 mammographic cases.  Twenty cases were abnormal while 10 cases were normal mammograms. Radiologists were asked to locate malignancies and assign a level of confidence. A jackknife free-response receiver operating characteristic, figure of merit (JAFROC, FOM), inferred receiver operating characteristic, area under curve (ROC, AUC), specificity, sensitivity, and location sensitivity were calculated using Ziltron software and JAFROC v4.1. A Mann-Whitney U test was used to compare the performance of Australian and U.S. radiologists.

The results showed that when radiologists’ experience and number of mammograms were reading per year were taken into account, the Australian radiologists sampled showed significantly higher sensitivity and location sensitivity while JAFROC (FOM) and inferred ROC (AUC) analyses showed no difference between the overall performance in the two countries. Receiver operating characteristic and location sensitivity were higher for the Australian radiologists who read the most cases per year.