CT Screenings Can Reduce Lung Cancer Mortality

A study published in the New England Journal of Medicine, focused on data from 13,195 men and 2,594 women aged 50 to 74 years old who were heavy smokers, found that participants had a lower mortality if they were screened with computed tomography (CT).

All individuals were followed for a minimum of 10 years and each was randomly assigned to get either low-dose CT scans at baseline, a year, three years and 5.5 years, or no screenings at all. Participants who were screened had lower death rates than the control group: 24% lower for men and 33% lower for women.  The overall referral rate for suspicious nodules was 2.1%.

A U.S. trial of nearly 54,000 heavy smokers in 2011 also found a 20% drop in lung cancer deaths via screenings with CT in comparison to chest X-rays. 

Following the U.S. study, the U.S. Preventive Services Task Force recommended low-dose CT screening for people aged 55 to 80 who had a history of smoking equal to a pack a day for 30 years and were either still smoking or had quit within the past 15 years. 

The American Cancer Society states that lung cancer is responsible for 25% of all cancer deaths and estimates that 72,500 men and 63,220 women in the U.S. are expected to die of lung cancer in 2020

How effective is screening mammography?

A study by Welch et al published in New Engl J Med added to the growing evidence that for every woman who was helped by screening mammography many have been harmed.

The authors used data from the SEER program from 1975 through 2012. They calculated the size-specific cancer case fatality rate in women 40 year old and older for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing 10 years (2000 through 2002).

Screening did result in more cancers being detected, with invasive tumors measuring <2 cm or in situ carcinomas increased from 36% to 68%; and the detected tumors that were large, which were invasive cancers and measuring ≥2 cm decreased from 64% to 32%.  Surprisingly though the data suggest that only about 30 of the 162 additional small tumors per 100,000 women that screening mammograms found would ever have progressed to a dangerous stage. That means that 132, or 81 percent, of the 162 extra tumors detected represented overdiagnosis, that resulted to treatment of tumors that were never destined to harm.

Most importantly, the incidence of metastatic cancer, which is the type that causes most deaths, was flat. 

In conclusion the findings from this study indicate that screening mammography finds many small cancers the dogma that all will grow, metastasize resulting in fatality is questionable. The authors also suggest that although screening may decrease cancer mortality as reflected by the declining incidence of larger tumors, they believe that the two thirds reduction in breast cancer mortality is due to recent advances in treatment. 

N Engl J Med 2016; 375:1438-1447

Stent versus surgery in carotid stenosis

In a study published in NEJM Rosenfield et al report the findings of a trial that compared carotid artery stenting with “embolic protection” to carotid endarterectomy.

In this trial, the authors compared carotid-artery stenting with “embolic protection” and carotid endarterectomy in 1453 patients who were 79 years of age or younger who had severe carotid stenosis and were asymptomatic.  Patients were followed for up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a non-inferiority margin of 3 percentage points.

The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group (P=0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group (P=0.51), and the overall survival rates were 87.1% and 89.4%, respectively (P=0.21). The cumulative 5-year rate of stroke-free survival was 93.1% in the stenting group and 94.7% in the endarterectomy group (P=0.44).

The authors concluded that stenting was not inferior to endarterectomy with regard to the rate of the primary composite end point at 1 year. In analyses that included up to 5 years of follow-up, there were no significant differences between the study groups in the rates of non–procedure-related stroke, all stroke, and survival.

N Engl J Med 2016; 374:1011-1020

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.

Malpractice Reform does not Affect ED Utilization

Waxman et al report in NEJM their findings regarding the effect legal reform had in the practice of medicine, in three states, Texas, Georgia, and South Carolina, which between 2003 and 2005, enacted legislation that changed the malpractice standard for emergency care to gross negligence.  

Using a 5% random sample of Medicare fee-for-service beneficiaries, they identified all emergency department visits to hospitals in the three reform states and in neighboring (control) states from 1997 through 2011. They compared patient-level outcomes, before and after legislation, in reform states and control states. Outcomes were policy-attributable changes in the use of computed tomography (CT) or magnetic resonance imaging (MRI), per-visit emergency department charges, and the rate of hospital admissions.

For eight of the nine states–outcome combinations tested, they found no reduction in the rates of CT or MRI utilization or hospital admission in any of the three reform states and no reduction in charges in Texas or South Carolina. In Georgia, reform was associated with a 3.6% reduction in per-visit emergency department charges.

They conclude that legislation that substantially changed the malpractice standard for emergency physicians in three states had little effect on the intensity of practice, as measured by imaging rates, average charges, or hospital admission rates.

A Controlled Trial of Renal Denervation in Patients with Resistant Hypertension

Bhatt et al published in the NEJM the findings of multicenter prospective trial of patients with severe resistant hypertension who were randomly assigned to undergo renal denervation or a sham procedure.

Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure.

A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was −14.13±23.93 mm Hg in the denervation group as compared with −11.74±25.94 mm Hg in the sham-procedure group for a difference of −2.39 mm Hg.  The change in 24-hour ambulatory systolic blood pressure was −6.75±15.11 mm Hg in the denervation group and −4.79±17.25 mm Hg in the sham-procedure group, for a difference of −1.96 mm Hg.

This blinded trial did not show a significant reduction of systolic blood pressure or difference in safety in the two groups of patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. 

The results of this landmark study that was designed to reduce clinical bias negate findings from prior reports that did not include sham treatment and reported that catheter renal artery denervation reduces blood pressure in patients with resistant hypertension.  The study reminds us of the importance of conducting blinded trials with sham controls before new treatments or devices are adopted.

Bhatt DL, Kandzari,DE, O'Neill WW et al:  A Controlled Trial of Renal Denervation for Resistant Hypertension.  N Engl J Med. 2014 Mar 29. [Epub ahead of print]

http://www.nejm.org/doi/full/10.1056/NEJMoa1402670?query=featured_home#t=article

DOI: 10.1056/NEJMoa1402670