AI Powers Two-for-One Screening

In our last issue, we described how effective coronary artery calcium scoring is in predicting future major adverse cardiovascular events. This week, we’re highlighting new research in AJR showing how – thanks to AI – CAC scoring can be performed on CT lung cancer screening exams, giving radiologists a two-for-one screening test.

Using data from one screening exam to also look for other diseases – known as opportunistic screening – has become a hot topic as a way to make screening even more clinically and economically effective. 

In the new study, South Korean researchers leveraged the country’s CT lung cancer screening program to also screen for CAC, a known marker for future cardiac events

  • They took two commercially available CAC scoring algorithms – Coreline Soft’s Aview CAC and Siemens Healthineers’ syngo Calcium Scoring – to analyze 1k low-dose CT chest images acquired from 2017-2023 as part of the national lung screening program. 

AI results were compared to radiologists’ interpretations of CAC presence and severity, finding … 

  • Substantial agreement between both the AI algorithms and the interpreting radiologists for CAC presence and severity (kappa=0.793 & 0.671)
  • The AI algorithms judged CAC to be more prevalent than radiologists (57-60% vs. 53%)
  • AI was more likely to judge CAC severity as mild (35-40% vs. 28%)
  • But less likely to grade it as severe (6.2%-7.3%  vs. 15%)
  • MACE incidence varied by CAC severity: no CAC (1.1-1.3%), mild (3-5%), moderate (2.9-7.9%), and severe (8.6-11%)

The researchers noted that, as with other studies, MACE incidence increased with CAC severity, underlining the importance of coronary calcium evaluation and supporting the use of CT lung screening for CAC detection. 

The Takeaway

Studies like this highlight the exciting role AI can play in making opportunistic screening a reality. With AI at their side, radiologists will be able to play an even more important role in catching disease early, when it can be treated most effectively.

CT Lung Screening’s Downstream Costs

The growing momentum of CT lung cancer screening was a major radiology news story in 2023. And while things are looking up as 2024 begins, there are still important issues to be sorted out for CT lung screening to achieve the same level of acceptance as other major cancer screening tests. 

A new study called PROSPR in Annals of Internal Medicine highlights some of these challenges

  • Researchers found a higher rate of invasive procedures and complications after CT screening compared to the National Lung Screening Trial, the landmark study that showed that low-dose CT screening reduces lung cancer mortality by 20%. 

The PROSPR researchers studied 9.3k individuals who got baseline LDCT lung screening scans from 2014 to 2018 across five US healthcare systems, finding: 

  • Abnormalities on baseline CT scans for 1.5k individuals (16%)
  • Of these, 9.5% were diagnosed with lung cancer within 12 months 
  • A 32% rate of downstream imaging of screened individuals 
  • A 2.8% rate of invasive procedures such as needle biopsy and bronchoscopy 
  • In those who got invasive procedures, rates were higher than NLST for all complications (31% vs. 18%) and for major complications (21% vs. 9.4%)

What gives with the higher complication rates? 

  • One explanation is that the PROSPR population was older and sicker than in NLST, with more individuals 65 and over (52% vs. 27%) and higher rates of current smoking (55% vs. 48%) and COPD (35% vs. 18%). 

Another reason could be that PROSPR’s population was more racially diverse, with fewer Whites than NLST (73% vs. 91%) and with a higher proportion of women (47% vs. 41%) – a sign of healthcare disparities. 

The PROSPR authors acknowledged that their findings could shift the debate over the benefits and harms of CT lung cancer screening in community practice – a debate that has raged in breast screening for decades.

The Takeaway

The PROSPR findings are something of a wake-up call amid the growing enthusiasm worldwide for CT lung cancer screening. It’s no surprise that real-world results will differ from the highly controlled environment of a clinical study like NLST, but lung screening proponents will need to be prepared with a plan for managing downstream findings and a response to screening skeptics who would use results like PROSPR to question whether lung screening should be performed at all.

Lung Screening’s Long-Term Benefits

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.

More Support for CT Lung Cancer Screening

Yet another study supporting CT lung cancer screening has been published, adding to a growing body of evidence that population-based CT screening programs will be effective in reducing lung cancer deaths. 

The new study comes from European Radiology, where researchers from Hungary describe findings from HUNCHEST-II, a population-based program that screened 4.2k high-risk people at 18 institutions. 

  • Screening criteria were largely similar to other studies: people between the ages of 50 and 75 who were current or former smokers with at least 25 pack-year histories. Former smokers had quit within the last 15 years. 

Recruitment for HUNCHEST-II took place from September 2019 to January 2022. Participants received a baseline low-dose CT (LDCT) scan, with the study protocol calling for annual follow-up scans (more on this later). Researchers found: 

  • The prevalence of baseline screening exams positive for lung cancer was 4.1%, comparable to the NELSON trial (2.3%) but much lower than the NLST (27%)
  • 1.8% of participants were diagnosed with lung cancer throughout screening rounds
  • 1.5% of participants had their cancer found with the baseline exam
  • Positive predictive value was 58%, at the high end of population-based lung screening programs
  • 79% of screen-detected cancers were early stage, making them well-suited for treatment
  • False-positive rate was 42%, a figure the authors said was “concerning”

Taking a deeper dive into the data produces interesting revelations. Overdiagnosis is a major concern with any screening test; it was a particular problem with NLST but was lower with HUNCHEST-II. 

  • Researchers said they used a volume-based nodule evaluation protocol, which reduced the false-positive rate compared to the nodule diameter-based approach in NLST.

Also, a high attrition rate occurred between the baseline scan and annual screening rounds, with only 12% of individuals with negative baseline LDCT results going on to follow-up screening (although the COVID-19 pandemic may have affected these results). 

The Takeaway

The HUNCHEST-II results add to the growing momentum in favor of national population-based CT lung screening programs. Germany is planning to implement a program in early 2024, and Taiwan is moving in the same direction. The question is, does the US need to step up its game as screening compliance rates remain low?

CT Lung Screening Saves Women

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.

CT Detects Early Lung Cancer

A massive CT lung cancer screening program launched in Taiwan has been effective in detecting early lung cancer. Research presented at this week’s World Conference on Lung Cancer (WCLC) in Singapore offers more support for lung screening, which has seen the lowest uptake of the major population-based screening programs. 

Previous randomized clinical trials like the National Lung Screening Trial and the NELSON study have shown that LDCT lung cancer screening can reduce lung cancer mortality by at least 20%. But screening adherence rates remain low, ranging from the upper single digits to as high as 21% in a recent US study. 

Meanwhile, lung cancer remains the leading cause of cancer death worldwide. To reduce this burden, Taiwan in July 2022 launched the Lung Cancer Early Detection Program, which offers biennial screening nationwide to people at high risk of lung cancer.

The Taiwan program differs from screening programs in the US and South Korea by including family history of lung cancer in the eligibility criteria, rather than just focusing on people who smoke. 

Researchers at WCLC 2023 presented the first preliminary results from the program, covering almost 50k individuals screened from July 2022 to June 2023; 29k had a family history of lung cancer and 19k were people who smoked heavily. Researchers found …

  • 4.4k individuals receive a positive screening result for a positive rate of 9.2%
  • 531 people were diagnosed with lung cancer for a detection rate of 1.1%
  • 85% of cancers were diagnosed at an early stage, either stage 0 or stage 1

This last finding is perhaps the most significant, as part of the reason for lung cancer’s high mortality rate is that it’s often discovered at a late stage, when it’s far more difficult to treat. As such, lung cancer’s five-year survival rate is about 25% – far lower than breast cancer at 91%.

The Takeaway

Taiwan is setting an example to other countries for how to conduct a nationwide LDCT lung cancer screening program, even as some critics take aim at population-based screening. Taiwan’s approach is broader and more proactive than that of the US, for example, which has erected screening barriers like shared decision-making.

Although it’s still early days for the Taiwan program, future results will be examined closely to determine screening’s impact on lung cancer mortality – and respond to screening’s critics.

RadNet’s UK Lung Cancer Screening Acquisition

RadNet advanced its AI-led cancer screening strategy, acquiring a 75% stake in Heart & Lung Health, a UK-based teleradiology network with a direct connection to the NHS’ lung cancer screening program.

Heart & Lung Health (HLH) has a network of over 70 cardiothoracic radiologists, and provides teleradiology reporting services for the NHS and a variety of UK hospitals and academic institutions.

Acquiring a UK telerad company might seem out of character for RadNet, which has historically focused its M&A on US-based imaging centers (and more recently global AI developers), only mentioned Europe once in its 2021 annual report, and exited the teleradiology business in 2020. However…

  • HLH is the leading reporting provider for NHS England Targeted Lung Health Check (TLHC), an AI-enabled lung cancer screening pilot program that might pave the way for a UK-wide program. 
  • TLHC requires all radiologists to use AI with their LDCT screening interpretations, suggesting that AI might also be required in a future UK-wide program.
  • HLH uses RadNet’s Aidence subsidiary’s lung cancer AI tools, and HLH will work with Aidence to further develop its solutions.

The Takeaway

RadNet started 2022 by acquiring two major cancer screening AI companies (Aidence and Quantib), which combined with its DeepHealth breast cancer AI business to support its ambitious new strategy to become a population-scale cancer screening leader. 

That goal might have seemed like a longshot to some, given AI’s uncertain path forward and RadNet’s geographic concentration in just seven US states. However, last week’s HLH acquisition showed that RadNet remains very committed to AI-driven cancer screening leadership, and its strategy might not be as geographically-challenged as some initially thought.

RevealDx & contextflow’s Lung CT Alliance

RevealDx and contextflow announced a new alliance that should advance the companies’ product and distribution strategies, and appears to highlight an interesting trend towards more comprehensive AI solutions.

The companies will integrate RevealDx’s RevealAI-Lung solution (lung nodule characterization) with contextflow’s SEARCH Lung CT software (lung nodule detection and quantification), creating a uniquely comprehensive lung cancer screening offering. 

contextflow will also become RevealDx’s exclusive distributor in Europe, adding to RevealDx’s global channel that includes a distribution alliance with Volpara (exclusive in Australia/NZ, non-exclusive in US) and a platform integration deal with Sirona

The alliance highlights contextflow’s new partner-driven strategy to expand SEARCH Lung CT beyond its image-based retrieval roots, coming just a few weeks after announcing an integration with Oxipit’s ChestEye Quality AI solution to identify missed lung nodules.

In fact, contextflow’s AI expansion efforts appear to be part of an emerging trend, as AI vendors work to support multiple steps within a given clinical activity (e.g. lung cancer assessments) or spot a wider range of pathologies in a given exam (e.g. CXRs):

  • Volpara has amassed a range of complementary breast cancer screening solutions, and has started to build out a similar suite of lung cancer screening solutions (including RevealDx & Riverain).
  • A growing field of chest X-ray AI vendors (Annalise.ai, Lunit, Qure.ai, Oxipit, Vuno) lead with their ability to detect multiple findings from a single CXR scan and AI workflow. 
  • Siemens Healthineers’ AI-RAD Companion Chest CT solution combines these two approaches, automating multiple diagnostic tasks (analysis, quantification, visualization, results generation) across a range of different chest CT exams and organs.

The Takeaway

contextflow and RevealDx’s European alliance seems to make a lot of sense, allowing contextflow to enhance its lung nodule detection/quantification findings with characterization details, while giving RevealDx the channel and lung nodule detection starting points that it likely needs.

The partnership also appears to represent another step towards more comprehensive and potentially more clinically valuable AI solutions, and away from the narrow applications that have dominated AI portfolios (and AI critiques) before now.

MD Anderson’s Lung Cancer Blood Test

MD Anderson researchers developed a blood and risk-based test that could improve how we identify lung cancer screening candidates, potentially bringing more high-risk patients into screening while keeping more low-risk patients out.

The Blood + Risk Test – The test combines MD Anderson’s blood-based protein biomarker test with a lung cancer risk model that analyzes patient smoking history (the PLCOm2012 model). This combined test would be used to identify patients who should enroll in LD-CT screening programs.

The Study – MD Anderson researchers used the test to analyze 10k blood samples from 2,745 people with a +10 pack-year smoking history (including 1,299 samples from 552 people who developed cancer), finding that the blood + risk test:

  • Identified 105 of the 119 people diagnosed with cancer within one year
  • Beat the USPSTF 2021 criteria’s sensitivity (88.4% vs. 78.5%) and specificity (56.2% vs. 49.3%)
  • Identified 9.2% more lung cancer cases than the USPSTF criteria
  • Referred 13.7% fewer unnecessary screening patients than the USPSTF criteria

Blood-Based Momentum – Blood-based tests appear to be gaining momentum as a first-line cancer screening method, as the last 6 months brought a promising new MGH lung cancer test and a key validation milestone for the multi-cancer early detection blood test (MCED; detects 50 types of cancer).

The Takeaway – Although there’s still more research to be done, blood-based tests could bring more high-risk patients into LD-CT lung cancer screening programs, while reducing screening participation among patients who don’t actually need it. In other words, blood tests like these could address lung cancer screening’s two biggest challenges.

Volpara’s Lung Cancer Push

Breast imaging AI leader Volpara Health took a big step into the lung cancer AI segment last week, launching partnerships with Riverain Technologies and RevealDx. Here are some details.

Volpara & Riverain – Volpara and Riverain announced plans to integrate Riverain ClearRead CT (AI-based lung nodule detection) and the Volpara Lung platform (lung cancer screening reporting, tracking, and risk assessment), giving Volpara a market-leading detection partner and extending the clinical value of both tools.

Volpara & RevealDx – Within days, Volpara announced a $250k strategic investment in AI-based lung nodule diagnosis startup RevealDx, that will allow Volpara to sell RevealDx’s RevealAI-Lung tool (CE-marked, FDA pending) in the US and make Volpara its exclusive distributor in Australia / New Zealand. 

Not That Surprising – Volpara’s lung cancer screening expansion isn’t as surprising as some might think. Volpara first entered the lung cancer screening segment through its 2019 acquisition of MRS Systems, which likely targeted MRS’ breast cancer screening management software but also included its lung cancer screening platform (used w/ 8% of US LC screenings). Volpara also built its business around supporting population-scale cancer screening workflows and it has a long history of complementary partnerships within its breast imaging business.

The Takeaway – Lung cancer screening volumes are about to significantly increase in the US (and potentially globally), creating new bandwidth and workflow constraints, and driving demand for comprehensive solutions that support the entire screening and patient management pathway. With these alliances, Volpara, Riverain, and RevealDx are far better positioned to support that pathway.

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