26 September 2023 Blog: On Whole Body MRI Scans

26 September 2023 Blog:  On Whole Body MRI Scans

 

A patient asked me my thoughts on a recent New York Times post on Prenuvo, a whole body MRI.  Here is the post:

For $2,499, Prenuvo will try to predict your future. The celebrity-endorsed company offers a roughly hour-long session of magnetic resonance imaging, or MRI, that scans your entire body, searching for early signs of cancer, aneurysms, liver diseases and even multiple sclerosis. It’s part of a crop of companies that claim they can revolutionize preventive health care with full-body scans — but experts warn this might not be the right approach.

In recent months, images of celebrities and influencers posing in branded scrubs in front of a glossy, cylindrical MRI machine have popped up on social media. Kim Kardashian wrote in the caption of a post she shared last month that Prenuvo “has really saved some of my friends’ lives.” In May, the television host Maria Menounos said that a Prenuvo scan had alerted her to a mass that turned out to be Stage 2 pancreatic cancer.

Many celebrities talk about their health on social media. But the ones that are documenting their body scans — complete with nearly identical photo ops — have taken the celebrity health endorsement to new heights in terms of cost. And considerable harm can come from screening, experts said.

What do experts say about the scans? Read more at the link in our bio.”

 

INTRODUCTION and GENERAL CONCEPTS of SCREENING

There is so much to unpack here that it is hard to know where to begin. But let’s start at the beginning “Prenuvo will try to predict your future.” It’s never a good sign when the first sentence is factually incorrect. What a whole body MRI is trying to do is illustrate your present. There have been no studies showing that whole body scanning can materially impact one’s health. In fact, MRI and CT scanning were developed for diagnostic purposes for patients with either known disease, serious complaints or trauma (the so-called ‘pan-scan’ is a mainstay of Emergency Medicine and Trauma Surgery). Only low-dose CT scans for lung cancer screening among at risk patients (i.e. prior or current smokers with at least 20 pack years of smoking – or 1 pack per day for 20 years) have undergone careful evaluation and study with two large randomized controlled trials showing that CT screening reduces lung cancer mortality rates in these at risk patients.

Moving along, the suggestion that the Prenuvo MRI will detect early signs of cancer, aneurysms, liver disease and even multiple sclerosis is a curious constellation of outcomes. Multiple sclerosis has typical clinical signs but is best confirmed using an MRI protocol both with and without contrast.  Prenuvo does not use contrast stating ‘we believe the combination of sequences that we take performs as well as contrast-enhanced MRI for tumor detection’ but no mention of MS detection. Similarly, aneurysms are best detected with magnetic resonance angiography (MRA) which is similar to an MRI but focuses on vessels, rather than organs. So oddly, 4 of the conditions they choose to highlight as detectable are not best identified using Prenuvo.

Pancreatic cancer (to which I would add ovarian cancer and kidney cancer) is really an outcome where Prenuvo could make a difference. Typically diagnosed at later stages, the annual incidence rate of pancreatic cancer is 12.9 cases per 100,000 person-years with a death rate of 11.0 per 100,000 person-years. Compare that to colon cancer which has an annual incidence rate of 36.6 cases per 100,000 person-years and a death rate of 13.1 per 100,000 person-years.  I did find it odd that they used the experience of “television host Maria Menounos” to highlight early detection at Stage 2 of disease. Diagnosing pancreatic cancer at Stage 2 only has a 5 year survival rate ranging from 13-39% as opposed to 84% for Stage 1A. A far better example would have been finding localized pancreatic cancer at Stage 1. Once again, an MRI is not the imaging modality of choice for pancreatic cancer detection in a high risk population – endoscopic ultrasound or a magnetic resonance cholangiopancreatography is preferred. 

 

LEAD TIME BIAS

Those who follow my posts know that I won’t let a chance to introduce an epidemiologic concept go to waste – and this blog post is no different. One critique of Prenuvo comes from  lead time bias. Lead time is the period of time between the detection of a medical condition by screening and when it ordinarily would have been diagnosed because a patient experiences symptoms and seeks medical care. A disease for which early treatment is no more effective than late treatment can make early detection look more ‘effective’, when in fact all the patient experiences is more disease time.  This is illustrated in the figure below:


Specific screening for breast (mammography), lung (low dose CT scan among appropriate risk patients, detailed above) and colorectal cancers (colonoscopy) are known to be effective because randomized controlled trials have shown that the mortality rates of those screened are lower than a comparable group of unscreened individuals.

 

LENGTH TIME BIAS

A second epidemiologic Achilles heel of Prenuvo comes from  length time bias. Screening works best when a medical condition develops slowly (this is part of the reason that colonoscopy is such a good screening tool and can be done once every 10 years for an average risk patient with no polyps).  Screening tests like Prenuvo are more likely to find slow-growing tumors because they are present for a longer period of time before they cause symptoms.  This is illustrated in the figure below:

Because screening tends to find tumors with an inherently better prognosis, mortality rates may appear to be better but this has nothing to do with the screening process itself. It simply reflects what the Prenuvo is good at detecting.

 

FALSE POSITIVE RATE

One of the critiques I have specifically left out (until now) are concerns about false positive results arising from the Prenuvo screening. This actually may be one aspect where Prenuvo performs fairly well as it is an expected cost of any screening test.  In short, a false-positive screening test results in an abnormal result in a person without disease. These can then lead to the inconvenience, expense and potential risks associated with obtaining follow-up procedures. About 10% of mammograms lead to a false positive result, and in a study of ovarian cancer screening (CA-125 lab testing and ultrasound) returned an 8.4% false positive rate and one third of those cases underwent surgery. In that study, five times more women without ovarian cancer underwent surgery than did women with ovarian cancer.

My assumption would be that the Prenuvo screening would have a similar false positive rate of between 8-10%. But where clinicians get into trouble with higher false positive rates is when multiple tests are run (the so-called ‘covering all the bases’ phenomenon) occur at once wherein among several dozen tests, it is not unusual to have one or more return as ‘abnormal.’ So having the Prenuvo testing by itself could be a reasonable approach to reduce a cumulative false positive rate.  It is important to note, however, that practice variation can contribute to the false-positive rate.  This is a phenomenon we see with mammography wherein similar large screening programs in the US returned false positive rates nearly twice as high as in the UK – but with similar cancer detection rates. I would not imagine that the true false positive rate of Prenuvo screening will ever be known or publicized but an 8-10% rate remains a fair assumption.

 

SUMMARY: IS IT WORTH IT?

I suppose that the real question is for $2499, is it worth it? I’m not really sure how to answer that, because there are no guidelines on how often the Prenuvo should be performed. Is it annual?  Every five years?  Every ten? But to provide some framework, we know that colonoscopies ($1500, done every 5 to 10 years), mammograms ($200 performed annually), and Low Dose CTs of the Lungs among smokers ($500, done annually) do reduce mortality rate. Prenuvo has placed itself strategically with newer detection technologies such a Galleri which is a blood-based test seeking to detect early stage cancers ($1000, recommended annually). A vigorous evaluation of its efficacy would be reasonable, but as a cash-pay service there is little likelihood that Prenuvo will invest in research when they can put those dollars into marketing and endorsements.

 

September 2023 Newsletter

Welcome to the September 2023 Newsletter for

Santa Monica Primary Care.

In this issue, we cover seasonal vaccines coming due this Fall  (Flu, COVID booster and RSV) with some detail on how they are formulated and deemed effective. We borrow heavily from analysis performed by the UK’s Joint Committee on Vaccination and Immunization (or “Immunisation”).

Flu Shots are “IN”: On Seasonal Influenza Vaccine

Doses of the 2023/2024 seasonal flu shot are stocked in our office and can be given any time as the best time to receive the vaccine is during the months of September and October.

The rationale for such timing is that annual local epidemics follow a fairly predictable
seasonal pattern with outbreaks in North America occurring between November and March. These begin abruptly, peaking in 3 weeks, and then end about 8 weeks later. Viral spread during winter months is presumed to be favored by improved virus survival in lower temperature environments and, indoor crowding due to cold weather. These annual epidemics can affect 10% to 30% of the world population.

Each year in January, a review of circulating influenza viruses is undertaken by the World Health Organization (WHO) and the most likely epidemic strains from two main categories – Influenza A and Influenza B – are selected. For Influenza A this year’s shot contains the ‘swine flu’ familiar H1N1 as well as H3N2 subtypes (H and N are specific surface proteins termed hemagglutinin and neuraminidase). The Influenza B lineages generally cause less severe disease and are called Yamagata and Victoria. So there are 4 components which is why you will hear the shot referred to as ‘quadrivalent’.

The decision on which strains to include in the vaccine formulation is based on global
surveillance data but, in the end, it is a prediction and not always correct. As such, the
effectiveness of the seasonal flu shot can vary from year to year. Even if the vaccine doesn’t completely prevent the flu, it can still reduce the severity and complications of the illness should you become infected.

Vaccination is associated with a reduced incidence of influenza from 2.3% among adults who were unvaccinated as compared to 0.9% among vaccinated. This effect is even stronger among those 65 years and older, wherein vaccination reduced the incidence from 6% to 2.4%.

Side effects to the flu vaccine are generally mild, most common being local injection site reaction (soreness), headache, muscle aches or low grade fever – all resolving within a day or so. About 15% of flu vaccine recipients experience a side effect.

COVID-19 Boosters Will Be “IN”: On the 2023 Booster

For the first time ever, our office will be stocking a COVID vaccine, in this case the 2023
booster. We have been able to bypass the LA County Health Department who had been unwilling to supply us with vaccines and instead are receiving them directly frow the manufacturers. Unlike the influenza vaccine which has population-wide applicability, I am favoring a narrow scope of vaccine efforts for COVID-19. Some of this recommendation is based on bivalent booster experience of 2022 wherein only 17% of the total US population ever received a booster dose. That percentage was a bit better for those over the age of 65 years at 43.3%.

Similar to influenza, COVID historically (until 2023 that is) has had a strong Winter surge beginning right after Thanksgiving (not a big surprise why an airborne virus would spike after such). The Fall 2023 COVID booster, which should gained FDA approval this week, targets the XBB.1.5 a coronavirus subvariant that emerged in late 2022. While XBB.1.5 only makes up 3.1% of the currently circulating variants in the US, basic science data has indicated that its offshoots (EG.5, FL.1.5.1, KBB.1.16.1 and KBB.1.16) share a close relationship with KBB.1.5. As such, it is expected that the updated booster will provide protection against these related variants

The UK’s Joint Commission on Vaccination and Immunization (JCVI) has offered some of the most coherent advice on boosters, recommending them for those at high risk of serious disease and therefore most likely to benefit from vaccination. These include:

Similarly, we will advise patients over 65 and those in higher risk groups to strongly consider having the booster by the end of October in time for an expected late November to January surge in cases (this differs from the UK recommendation to have the booster by the end of December). The crux of the JCVI’s advice is based on a coherent analysis of the number needed to vaccinate to prevent a hospitalization or death due to COVID-19. Based on the 2022 booster experience, it would require giving a booster to 240 high risk >90 year olds to prevent one COVID death but over 2 million booster doses to prevent one death amongst healthy 15-19 year olds.

Vaccine efficacy of the 2022 booster dropped rapidly from 53% 2-4 weeks after vaccination to 28% at greater than 15 weeks. Protection against hospitalization after an mRNA booster increases in the two weeks after vaccination and then declines towards a stable plateau of around 50-60% by six months.

While you can have both the flu vaccine and COVID booster at the same time, it may be more prudent to separate the two. That way in the case of an unlikely, but possible, vaccine reaction -the cause will be apparent. A recent study from Sheba Medical Center in Israel showed that systemic reactions among those who received a flu+COVID co-administration was 27.6% as compared to 27.4% for COVID only and 12.7% in flu only. However, COVID spike protein antibody levels were 19% higher amongst those who received the COVID booster separately as compared to those who received COVID and flu vaccines together (link:https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809119

RSV Vaccine is OUT there: On the New RSV Vaccine

This Fall will be the first time that an RSV (Respiratory Syncytial Virus) vaccine becomes available but is not a vaccine we will stock in the office. It will be available, however, at local pharmacies. Approved in May 2023, two RSV vaccines are available in the prevention of respiratory tract disease – Arevxy (82% effective) and Abrysvo (67% effective)

RSV is a common respiratory illness that infects up to 90% of children in their first two years of life and frequently reinfects both older children and adults. In most cases, RSV infection is mild and may even go unnoticed – with infants under the age of one year and the elderly at greatest risk. For infants, RSV can cause such severe inflammation of the small airways in the lungs that significant breathing difficulties can occur. There is no pharmacotherapy other than supportive care with fluid and respiratory support. RSV is a leading cause of infant mortality globally and, in
some developing countries, is second only to malaria as a cause of death among infants.

The burden of RSV disease in adults is less well understood but undoubtedly
underestimated given that it is most typically (and correctly) associated with respiratory illness in infancy. The same JCVI grappled with a population-wide rollout of RSV vaccine in the UK where the annual number of deaths was estimated to be somewhere between 741 and 6472. The US has about 5 times the population of the UK so that would translate to between 3700 and 32000 deaths here. They also considered the burden of RSV on the health system in general and concluded that a programme for those 75 years and older would be the most ‘efficient’ but one directed at 65 years and older would provide the most benefit. Note: they only considered the Arevxy, noting that these data provided the most ‘comprehensive read out’ and is also more effective. The committee was hopeful that Arevxy would provide multi-year protection, as RSV does not have the same mutation frequency as COVID-19 and influenza. At $336 a dose, one would certainly hope for longer lasting protection.

Side effects seem to be generally mild but common. 34% of recipients reported fatigue, 29% muscle aches and 27% a headache. These typically resolved in 24 to 48 hours.The current RSV vaccine is recommended only as a single dose for individuals 60 years and older in the United States. I would revise that upwards to 65 years of age. Those most likely to benefit would be those with pulmonary disease (such as COPD or asthma), cardiovascular disease, moderate to severe immune compromise, and diabetes. The CDC does not recommend against co-administration with seasonal flu shot or other vaccines although antibody titers for both influenza and RSV were lower when given together. So my recommendation would be to separate RSV vaccination out from other shots by two weeks.

 

Vaccine Recap

Seasonal Flu: An unqualified, yes
COVID Booster: Everybody 65 and older, patients with an immunosuppressed household member, those under age 64 with a risk factor for severe disease
RSV Vaccine: Everybody over the age of 65, those 60-64 with asthma, COPD, diabetes or immune compromise

.

What’s Happening with COVID?

In August, the Los Angeles County Health Department reported a “concerning increase” in reported COVID-19 cases and indeed cases in our clinic showed a notable uptick as compared to much of the Spring of 2023. We had a total of 13 cases, of which 10 were first time infections (Figure 1 below).

Total COVID-19 Cases(Blue) and Repeat Infections (Red) by Month in 2022/2023: Santa Monica Primary Care

Smoothed Daily incident Case Rate (per 100,000 population) of SARS-CoV2: Los Angeles Country, California

While this did represent a significant increase, it is important to contextualize the magnitude of such against the historic low rates of this Spring. Historically, a mid to late summer surge has been seen in every year since the pandemic began, but rates this summer (Green Line in Figure 3 below) were the lowest we have ever seen, including the Summer of 2020 (Blue Line). We were all under shelter-in-place orders during the Summer of 2020 as well.

Smoothed Daily incident Case Rate (per 100,000 population) of SARS-CoV2: Los Angeles Country, California for 2020(Blue), 2021(Red), 2022(Yellow), and 2023 (Green)

Follow us on social media accounts for timely updates

 

Visit Our Website And follow Our Blog Posts