Tag: cancer

MRI Makes Prostate Screening More Precise

Posted on by Brian Casey

Prostate cancer screening isn’t a guideline-directed screening test yet, but this could change with the use of MRI and other tools. A series of papers published in several JAMA journals late last week indicates the progress that’s being made. 

As we’ve discussed in previous issues, prostate screening with PSA tests hasn’t met the threshold for clinical benefit achieved by other population-based screening exams.

  • PSA-based screening has been characterized by lower mortality benefits and relatively high rates of overdiagnosis and complications from follow-up procedures. 

But some researchers believe that PSA screening could be made more effective by using additional diagnostic tools like imaging and blood tests to focus on potentially high-risk disease for biopsy while active surveillance is used for less threatening prostate lesions. 

In the ProScreen trial in Finland, researchers tested the combination of PSA, a kallikrein four-panel blood test, and MRI in selecting patients for biopsy. 

  • Patients were sent to MRI if they had PSA scores of 3.0 ng/mL or higher and kallikrein scores of 7.5% or higher; those with abnormal MRI scans got targeted biopsy. 

The researchers tested the ProScreen protocol in a study of 61.2k men, with 15.3k invited to screening and 7.7k getting screened. Over a preliminary three-year follow-up period, researchers found …

  • 9.7% of men met the PSA threshold for a suspicious lesion; this fell to 6.8% after the kallikrein test and 2.7% after MRI, illustrating the protocol’s ability to reduce biopsies
  • Biopsy yield for high-grade cancer was 1.7%, which an editorial called a “remarkably high yield”
  • Overdetection of low-grade disease was 0.4%, compared to 3.2% in a comparable previous study

In a second study, this one in JAMA Oncology, researchers performed a meta-analysis of 80.1k men from 12 studies in which MRI was used to direct patients to prostate biopsy after PSA testing, finding that MRI-directed protocols had …

  • Higher odds of detecting clinically significant prostate cancer (OR=4.15) compared to PSA screening alone
  • Lower odds ratio for biopsy (OR=0.28)
  • Lower odds ratio for detecting clinically insignificant cancer (OR=0.34)

Finally, a secondary analysis in JAMA of a large UK trial illustrates the challenges of prostate screening without MRI guidance. Researchers reviewed 15-year outcomes of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), a study of 415k men,196k of whom were screened from 2002 to 2009 without the use of MRI, finding … 

  • PSA screening increased detection of low-grade cancer (2.2% vs. 1.6%) but not intermediate or high-grade disease
  • Screening reduced prostate cancer mortality by a small amount (0.69% vs. 0.78%)

The Takeaway

Taken together, new studies offer a roadmap toward making MRI an integral part of prostate screening, such that perhaps in years to come it can join other cancer tests as a population-based screening tool.

Lung Screening’s Long-Term Benefits

Posted on by Brian Casey

CT lung cancer screening produced lung cancer-specific survival over 80% in the most recent data from the landmark I-ELCAP study, a remarkable testament to the effectiveness of screening. 

The findings were published this week in Radiology from I-ELCAP, one of the first large-scale CT lung screening trials, and are the latest in a series of studies pointing to lung screening’s benefits. The findings were originally presented at RSNA 2022. 

The I-ELCAP study is ongoing and has enrolled 89k participants at over 80 sites worldwide from 1992-2022 who have been exposed to tobacco smoke and who received annual low-dose CT (≤ 3mGy) scans. Periodic I-ELCAP follow-up studies have documented the survival rates of those whose cancers were detected with LDCT, and the new numbers offer a 20-year follow-up, finding: 

  • Primary lung cancers were detected on LDCT in 1,257 individuals who had lung cancer-specific survival of 81%, matching the 10-year survival rate of 81%
  • 1,017 patients with clinical stage I lung cancer underwent surgical resection and saw a lung cancer-specific survival rate of 87%
  • The I-ELCAP survival rate is much higher than another landmark screening study, NLST, in which it was 73% for stage I cancer at 10 years
  • Lung cancer-specific survival hit a plateau after 10 years of follow-up, at a cure rate of about 80%

I-ELCAP is unique for a variety of reasons, one of which is that it continues to screen people beyond a baseline scan and 2-3 annual follow-up rounds – perhaps the reason for its higher survival rate relative to NLST. 

  • It also has included people who were exposed to tobacco smoke but who weren’t necessarily smokers – an important distinction in the debate over how broad to expand lung screening criteria.  

The findings come as CT lung cancer screening is generating growing momentum. Studies this year from Germany, Taiwan, and Hungary have demonstrated screening’s value, and several countries are ramping up national population-based screening programs. 

The Takeaway

The 20-year I-ELCAP data show that CT lung cancer screening works if you can get people to do it. But achieving survival rates over 80% also requires work on the part of healthcare providers, in terms of defined protocols for working up findings, data management for screening programs, and patient outreach to ensure adherence to annual screening. Fortunately, I-ELCAP offers a model for how it’s done.

Making Screening Better

Posted on by Brian Casey

While population-based cancer screening has demonstrated its value, there’s no question that screening could use improvement. Two new studies this week show how to improve on one of screening’s biggest challenges: getting patients to attend their follow-up exams.

In the first study in JACR, researchers from the University of Rochester wanted to see if notifying people about actionable findings shortly after screening exams had an impact on follow-up rates. Patients were notified within one to three weeks after the radiology report was completed. 

They also examined different methods for patient communication, including snail-mail letters, notifications from Epic’s MyChart electronic patient portal, and phone calls. In approximately 2.5k patients within one month of due date, they found that follow-up adherence rates varied for each outreach method as follows:

  • Phone calls – 60%
  • Letters – 57%
  • Controls – 53%
  • MyChart notifications – 36%

(The researchers noted that the COVID-19 pandemic may have disproportionately affected those in the MyChart group.) 

Fortunately, the university uses natural language processing-based software called Backstop to make sure no follow-up recommendations fall through the cracks. 

  • Backstop includes Nuance’s mPower technology to identify actionable findings from unstructured radiology reports; it triggers notifications to both primary care providers and patients about the need to complete follow-up.

Once the full round of Backstop notifications had taken place, compliance rates rose and there was no statistically significant difference between how patients got the early notification: letter (89%), phone (91%), MyChart (90%), and control (88%). 

In the second study, researchers in JAMA described how they used automated algorithms to analyze EHR data from 12k patients to identify those eligible for follow-up for cancer screening exams.

  • They then tested three levels of intervention to get people to their exams, ranging from EHR reminders to outreach to patient navigation to all three. 

Patients who got EHR reminders, outreach, and navigation or EHR reminders and outreach had the highest follow-up completion rates at 120 days compared to usual care (31% for both vs. 23%). Rates were similar to usual care for those who only got EHR reminders (23%).

The Takeaway

This week’s studies indicate that while health technology is great, it’s how you use it that matters. While IT tools can identify the people who need follow-up, it’s up to healthcare personnel to make sure patients get the care they need.

CT Lung Screening Saves Women

Posted on by Brian Casey

October may be Breast Cancer Awareness Month, but a new study has great news for women when it comes to another life-threatening disease: lung cancer. 

Italian researchers in Lung Cancer found that CT lung cancer screening delivered survival benefits that were particularly dramatic for women – and could address cardiovascular disease as well. 

  • They found that in addition to much higher survival rates, women who got CT lung screening after 12 years of follow-up had lower all-cause mortality than men. 

Of all the cancer screening tests, lung screening is the new kid on the block.

  • Although randomized clinical trials have shown it to deliver lung cancer mortality benefits of 20% and higher, uptake of lung screening has been relatively slow compared to other tests.

In the current study, researchers from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan analyzed data from 6.5k heavy smokers in the MILD and BioMILD trials who got low-dose CT screening from 2005 to 2016. 

In addition to cancer incidence and mortality, they also used Coreline Soft’s AVIEW software to calculate coronary artery calcium (CAC) scores acquired with the screening exams to see if they predicted lung cancer mortality. Researchers found that after 12 years of follow-up …

  • There was no statistically significant difference in lung cancer incidence between women and men (4.4% vs. 4.7%)
  • But women had lower lung cancer mortality than men (1% vs. 1.9%) as well as lower all-cause mortality (4.1% vs. 7.7%), both statistically significant
  • Women had higher lung cancer survival than men (72% vs. 52%)
  • 15% of participants had CAC scores between 101-400, and all-cause mortality increased with higher scores
  • Women had lower CAC scores, which could play a role in lower all-cause mortality due to less cardiovascular disease

The Takeaway

This is a fascinating study on several levels. First, it shows that lung cancer screening produces a statistically significant decline in all-cause mortality for women compared to men.

Second, it shows that CT lung cancer screening can also serve as a screening test for cardiovascular disease, helping direct those with high CAC scores to treatment such as statin therapy. This type of opportunistic screening could change the cost-benefit dynamic when it comes to analyzing lung screening’s value – especially for women.

POCUS Cuts DVT Stays

Posted on by Brian Casey

Using POCUS in the emergency department (ED) to scan patients with suspected deep vein thrombosis (DVT) cut their length of stay in the ED in half. 

Reducing hospital length of stay is one of the holy grails of healthcare quality improvement. 

  • It’s not only more expensive to keep patients in the hospital longer, but it can expose them to morbidities like hospital-acquired infections.

Patients admitted with suspected DVT often receive ultrasound scans performed by radiologists or sonographers to determine whether the blood clot is at risk of breaking off – a possibly fatal result. 

  • But this requires a referral to the radiology department. What if emergency physicians performed the scans themselves with POCUS?

To answer this question, researchers at this week’s European Emergency Medicine Conference presented results from a study of 93 patients at two hospitals in Finland.

  • From October 2017 to October 2019, patients presenting at the ED received POCUS scans from emergency doctors trained on the devices. 

Results were compared to 135 control patients who got usual care and were sent directly to radiology departments for ultrasound. 

  • Researchers found that POCUS reduced ED length of stay from 4.5 hours to 2.3 hours, a drop of 52%.

Researchers described the findings as “convincing,” especially as they occurred at two different facilities. The results also answer a recent study that found POCUS only affected length of stay when performed on the night shift. 

The Takeaway
Radiology might not be so happy to see patient referrals diverted from their department, but the results are yet another feather in the cap for POCUS, which continues to show that – when in the right hands – it can have a big impact on healthcare quality.

Screening Foes Strike Back

Posted on by Brian Casey

Opponents of population-based cancer screening aren’t going away anytime soon. Just weeks after publication of a landmark study claiming that cancer screening has saved $7T over 25 years, screening foes published a counterattack in JAMA Internal Medicine casting doubt on whether screening has any value at all. 

Population-based cancer screening has been controversial since the first programs were launched decades ago. 

  • A vocal minority of skeptics continues to raise concerns about screening, despite the fact that mortality rates have dropped and survival rates have increased for the four cancers targeted by population screening.

This week’s JAMA Internal Medicine featured a series of articles that cast doubt on screening. In the main study, researchers performed a meta-analysis of 18 randomized clinical trials (RCTs) covering 2.1M people for six major screening tests, including mammography, CT lung cancer screening, and colon and PSA tests. 

  • The authors, led by Norwegian gastroenterologist Michael Bretthauer, MD, PhD, concluded that only flexible sigmoidoscopy for colon cancer produced a gain in lifetimes. They conclude that RCTs to date haven’t included enough patients who were followed over enough years to show screening has an effect on all-cause mortality.

But a deeper dive into the study produces interesting revelations. For CT lung cancer screening, Bretthauer et al didn’t include the landmark National Lung Screening Trial, an RCT that showed a 20% mortality reduction from screening.

  • With respect to breast imaging, the researchers only included three studies, even though there have been eight major mammography RCTs performed. And one of the three included was the controversial Canadian National Breast Screening Study, originally conducted in the 1980s.

When it comes to colon screening, Bretthauer included his own controversial 2022 NordICC study in his meta-analysis. 

  • The NordICC study found that if a person is invited to colon screening but doesn’t follow through, they don’t experience a mortality benefit. But those who actually got colon screening saw a 50% mortality reduction.  

Other articles in this week’s JAMA Internal Medicine series were penned by researchers well known for their opposition to population-based screening, including Gilbert Welch, MD, and Rita Redberg, MD.

The Takeaway

There’s an old saying in statistics: “If you torture the data long enough, it will confess to anything.” Among major academic journals, JAMA Internal Medicine – which Redberg guided for 14 years as editor until she stepped down in June – has consistently been the most hostile toward screening and new medical technology.

In the end, the arguments being made by screening’s foes would carry more weight if they were coming from researchers and journals that haven’t already demonstrated a longstanding, ingrained bias against population-based cancer screening.

Value of Cancer Screening

Posted on by Brian Casey

A new study claims that medical screening for diseases like breast and cervical cancer has saved lives and generated value of at least $7.5T (yes, trillion) over the last 25 years. The findings, published in BMC Health Services Research, are a stunning rebuke to critics of screening exams.

While the vast majority of doctors and public health officials support evidence-based screening, a vocal minority of skeptics continues to raise questions about screening’s efficacy. These critics emphasize the “harms” of screening, such as overdiagnosis and patient anxiety – an accusation often levied against breast screening. 

Screening’s critics also target the downstream costs of medical tests intended to confirm suspicious findings. They argue that a single screen-detected finding can lead to a cascade of additional healthcare spending that drives up medical costs.

But the new study offers a counter-argument, putting a dollar figure on how much screening exams have saved by detecting disease earlier, when it can be treated more effectively. 

The research focused on the four main cancer screening tests – breast, cervical, colon, and lung cancer – analyzing the impact of preventive screening on life-years saved and its economic impact from 1996 to 2020, finding …

  • Americans enjoyed at least 12M more years of life thanks to cancer screening
  • The economic value of these life-years added up to at least $7.5T
  • If everyone who qualified for screening exams got them, it would save at least another 3.3M life-years and $1.7T in economic impact
  • Cervical cancer screening had by far the biggest economic impact ($5.2T-$5.7T), followed by breast ($0.8T-$1.9T), colorectal ($0.4T-$1T), and finally lung ($40B). 

Lung cancer’s paltry value was due to a small eligible population and low screening adherence rates. This finding is underscored by a new article in STAT that ponders why CT lung cancer screening rates are so low, with one observer calling it the “redheaded stepchild” of screening tests.  

The Takeaway
Screening skeptics have been taking it on the chin lately (witness the USPSTF’s U-turn on mammography for younger women) and the new findings will be another blow. We may continue to see a dribble of papers on the “harms” of overdiagnosis, but the momentum is definitely shifting in screening’s favor – to the benefit of patients.

Radiation and Cancer Risk

Posted on by Brian Casey

New research on the cancer risk of low-dose ionizing radiation could have disturbing implications for those who are exposed to radiation on the job – including medical professionals. In a new study in BMJ, researchers found that nuclear workers exposed to occupational levels of radiation had a cancer mortality risk that was higher than previously estimated.

The link between low-dose radiation and cancer has long been controversial. Most studies on the radiation-cancer connection are based on Japanese atomic bomb survivors, many of whom were exposed to far higher levels of radiation than most people receive over their lifetimes – even those who work with ionizing radiation. 

The question is whether that data can be extrapolated to people exposed to much lower levels of radiation, such as nuclear workers, medical professionals, or even patients. To that end, researchers in the International Nuclear Workers Study (INWORKS) have been tracking low-dose radiation exposure and its connection to mortality in nearly 310k people in France, the UK, and the US who worked in the nuclear industry from 1944 to 2016.

INWORKS researchers previously published studies showing low-dose radiation exposure to be carcinogenic, but the new findings in BMJ offer an even stronger link. For the study, researchers tracked radiation exposure based on dosimetry badges worn by the workers and then rates of cancer mortality, and calculated rates of death from solid cancer based on their exposure levels, finding: 

  • Mortality risk was higher for solid cancers, at 52% per 1 Gy of exposure
  • Individuals who received the occupational radiation limit of 20 mSv per year would have a 5.2% increased solid cancer mortality rate over five years
  • There was a linear association between low-dose radiation exposure and cancer mortality, meaning that cancer mortality risk was also found at lower levels of exposure 
  • The dose-response association seen the study was even higher than in studies of atomic bomb survivors (52% vs. 32%)

The Takeaway

Even though the INWORKS study was conducted on nuclear workers rather than medical professionals, the findings could have implications for those who might be exposed to medical radiation, such as interventional radiologists and radiologic technologists. The study will undoubtedly be examined by radiation protection organizations and government regulators; the question is whether it leads to any changes in rules on occupational radiation exposure.

Theranostics Grabs SNMMI Spotlight

Posted on by Brian Casey

The emerging field of theranostics – in which two radiopharmaceuticals work in tandem for diagnostic and therapeutic purposes – is one of the most exciting new areas of medicine. Nowhere is this more evident than at this week’s SNMMI 2023 meeting in Chicago. 

Theranostics involves the use first of a highly targeted diagnostic radiotracer to detect pathology with a technology like PET, then sending in another tracer to deliver a stronger radioactive payload to the site of disease – almost the definition of precision medicine. Some estimates are that theranostics could soon develop into a market worth $30B.

In addition to talks on theranostics, SNMMI 2023 highlights so far have included presentations covering the following:

  • An ultra-high-resolution brain PET scanner that can visualize and quantify nuclei in the brainstem for the first time, opening up new inquiries into neurological disorders like Alzheimer’s disease
  • The discovery of the optimal tracer kinetic model for quantifying myocardial uptake of 18F-flutemetamol in patients with transthyretin (ATTR) cardiac amyloidosis, a buildup of amyloid plaque in the heart
  • A technique called augmented whole-body scanning via magnifying PET (AWSM-PET) that uses two high-resolution add-on detectors as an “outsert” to improve image resolution and reduce noise
  • Imaging of rheumatoid arthritis with 68Ga-FAPI PET/CT, which showed a greater number and degree of affected joints than FDG-PET/CT
  • A PET radiotracer called 18F-Cholestify has the potential to improve neuroimaging by visualizing metabolic cholesterol degradation in the brain.

The commercial side of SNMMI 2023 is active as well. Siemens Healthineers, GE HealthCare, and United Imaging Healthcare are launching new hybrid scanners, and other vendor news includes the following: 

  • Blue Earth Diagnostics is touting its recent shipments of Posluma, a PET radiotracer targeting PSMA in prostate cancer patients
  • GE HealthCare is migrating AIR technologies found on its MRI scanners to its new Signa PET/MRI AIR system (see below) 
  • Isotopia is discussing its plans for a US radioisotope manufacturing facility
  • Lantheus researchers are presenting talks on AI-enabled PSMA-PET reporting using its Pylarify AI software
  • Mediso received FDA clearance for its InterView Fusion and InterView XP multimodality image processing and reporting software
  • Siemens Healthineers has launched a new PET/CT scanner, Biograph Vision.X, sporting a 20% improvement in time of flight (see below)
  • Subtle Medical is demonstrating its SubtlePET solution, which uses AI to remove noise for low-count PET images, enabling up to 75% faster PET scans
  • Telix Pharmaceuticals is highlighting clinical results of several agents: the Illucix gallium-based prostate cancer imaging agent; ProstACT lutetium-based antibody-directed prostate cancer therapy; and TLX250-CDx, a zircon-89-based tracer for diagnosing clear cell renal cell carcinoma.
  • United Imaging Healthcare is launching uMI Panorama, a new wide-bore PET/CT scanner (see below).  

The Takeaway

This week’s proceedings in Chicago illustrate the new energy that theranostics is bringing to nuclear medicine and molecular imaging, one of radiology’s most venerable modalities. Stay tuned for the announcement of SNMMI’s Henry N. Wagner, Jr. Image of the Year award, always a conference highlight.  

Is There Hope for CT Lung Screening?

Posted on by Brian Casey

New data on CT lung cancer screening rates offer a good news/bad news story. The bad news is that only 21.2% of eligible individuals in four US states got screened, far lower than other exams like breast or colon screening.

The good news is that, as low as the rate was relative to other tests, 21.2% is still much higher than previous estimates. And the study itself found that the rate of CT lung screening has risen over 8 percentage points in 3 years. 

Compliance has lagged with CT lung screening ever since Medicare approved payments for the exam in 2015. A recent JACR study found that screening rates were low for eligible people for both Medicare and commercial insurance (3.4% and 1.8%).

Why is screening compliance so low? Explanations have ranged from fatalism among people who smoke to reimbursement requirements for “shared decision-making,” which unlike other screening exams require patients and providers to discuss CT lung screening before an exam can be ordered.

In this new study in JAMA Network Open, researchers examined screening rates in four states – Maine, Michigan, New Jersey, and Rhode Island – from January 2021 to January 2022. The study drew data from the National Health Interview Survey and weighted it to reflect the population of the US of individuals eligible for CT lung screening, based on the criteria of ages 55-79, 30-pack-year smoking history, and having smoked or quit within the past 15 years. Major findings included: 

  • The rate for CT lung cancer screening was 21.2%, up from 12.8% in 2019
  • People with a primary health professional (PHP) were nearly 6 times more likely to get screened (OR=5.62)
  • The age sweet spot for screening was 65-77, with lower odds for those 55-64 (OR=0.43) and 78-79 (OR=0.17)
  • Rates varied between states, with Rhode Island having the highest rate (30.3%) and New Jersey the lowest (17.5%).
  • Of those who got screened, 27.7% were in poor health and 4.5% had no health insurance

The Takeaway

The findings offer some hope for CT lung screening, as the compliance rate is among the highest we’ve seen among recent research studies. On the other hand, many of those screened were in such poor health they might not benefit from treatment. The high rate of compliance in people with PHPs indicates that promoting screening with these providers could pay off, especially given the requirement for shared decision-making. 

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