Innovative blood test boosts accuracy of lung cancer screening

Published

5 months ago

June 11, 2024

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By Pooja Toshniwal Paharia Jun 11 2024 Reviewed by Lily Ramsey, LLM

In a recent study published in Cancer Discovery, researchers developed and validated a blood-based, cell-free deoxyribonucleic acid (cfDNA) fragmentome assay for lung cancer detection, which, if the results were positive, would be followed by low-dose computed tomography (LDCT).

Study: Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection . Image Credit: MMD Creative/Shutterstock.com Introduction

Lung cancer is a major death cause, and yearly screening is crucial. However, chest LDCT has low adoption due to patient barriers like inadequate awareness, radiation concerns, and limited availability.

Other challenges include poor smoking history recording, a lack of defined practices, and specialist follow-up.

A blood-based lung malignancy screening test, like the fragmentome technique, could increase screening rates by analyzing specific chromatin configurations in peripheral blood. About the study

In the present DELFI-L101 study, researchers developed a hematological test using machine learning to analyze DNA fragmentomes and identify individuals at risk of lung cancer. Individuals testing positive would undergo LDCT.

Beginning March 2021, the researchers enrolled 958 individuals aged 50–80 with ≥20 pack-years of smoking across 47 United States (US) facilities. Eligibility features resembled the LDCT screening criteria of the 2015 National Health Interview Survey (NHIS).

They excluded individuals with cancer therapy within one year, a history of hematologic malignancy or myelodysplasia, organ tissue transplantation, blood product transfusion within 120 days of enrollment, pregnancy, and participation in other trials.

The team divided the study participants into three groups: A (lung cancer), B (non-cancer controls), and C (cancer other than lung cancer). Related StoriesResearch reveals new pathways for treating never-smoker lung cancerCanada's plan to eliminate cervical cancer by 2040: HPV-based screening and vaccination keyLung cancer screening yields early diagnoses and increased cure rates in veterans

The American Joint Committee on Cancer's Cancer Staging Manual (AJCC) criteria ascertained the disease stage. Changes in cfDNA fragmentation patterns (fragmentomes) in blood revealed genomic and chromatin features of lung cancer.

The researchers trained the classifier on 576 cases and controls before validating it on another 382 cases and controls.

They used whole genome sequences from the training dataset to assess fragmentations in 504 non-overlapping-type 5.0 MB sections with strong mappability. Each region included 80,000 pieces and covered a genome size of 2.50 GB.

The team examined genome-wide alterations to Hi-C open-type (A compartment) and closed-type (B compartment) chromatin.

They created the classifier using principal component analysis (PCA) and logistic regressions, incorporating chromosomal arm-level changes, cfDNA fractions derived from the mitochondrial genome, and cfDNA fragment length distributions.

The researchers performed Monte Carlo simulations on 15 million individuals under three scenarios: Base Scenario: Current practices without hematological screening. Low Scenario: 10% uptake of hematological screening for individuals eligible for pulmonary cancer screening but not subjected to low-dose CT in the first year, increasing to 25% in five years. High Scenario: 20% uptake of hematological screening for the same group in the first year, increasing to 50% in five years. Results

The researchers observed 58% test specificity, 84% sensitivity, and 99.8% negative predictive value (NPV). Applying the rest to the screening-eligible group with 0.7% lung cancer prevalence, the number needed to screen (NNS) was 143.

Study validations showed negative and positive results related to NNS with LDCT imaging to detect 414 and 76 cases, respectively, yielding a 5.5 relative risk value. The positive predictive value (PPV) was almost double that of the LDCT qualifying requirements alone.

The cfDNA fragmentomes of lung squamous cell carcinoma (LUSC) patients comprised a component resembling cfDNA profiles from non-cancer individuals and another resembling A/B-type compartments noted in LUSC tissues.

Non-cancer individuals showed cfDNA patterns approximating lymphoblastoid Hi-C findings. Within common locations, fragmentations among samples provided by individuals with cancer presence and absence were similar.

Lung cancer patients had increased cell-free DNA representations fpr 1q, 3q, 5p, 8q, and 12p, as well as lower 1p, 3p, 4q, 5q, 10q, and 17p levels. Their cfDNA fragmentations differed from controls, revealing more closely packed chromatin in cfDNA of closed LUSC spaces, while lymphoblastoid reference regions showed the reverse impact.

At the cut-off of 0.2, ten-fold cross-validation with ten repeats within the training population yielded 50% overall specificity and sensitivities of 75%, 90%, 96%, and 97% for stages I, II, III, and IV, respectively. Sensitivity was constant across ages, with younger people having higher specificity. Using the 2015 NHIS data yielded 80% sensitivity and 58% specificity.

From the ‘base’ scenario (24,489 cases), lung cancer cases identified by screening increased to 63,523 (the ‘low’ scenario) and 100,346 (the ‘high’ scenario). In contrast, stage I cases increased by 4.80% and 9.70%, while stage IV diagnoses decreased by 4.20% and 8.70%, respectively.

In total, 4,720 deaths from lung malignancies could be averted in the ‘base’ scenario, 7,652 in the ‘low’ scenario, and 14,264 deaths in the ‘high’ scenario. LDCT use in screening could reduce the number of tests required to identify lung cancers from 202 (‘base’ scenario) to 150 (‘low’ scenario) and 139 (‘high’ scenario). Conclusion

Based on the study findings, the DNA fragmentome assay provides a novel, accurate, affordable, blood-based tool for initial lung cancer evaluation with LDCT follow-ups.

The assay could contribute to preventing lung cancer-related deaths, with moderate adoption rates possibly lowering late-stage diagnoses and fatalities. Journal reference:

Peter Mazzone et al., (2024) Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection, Cancer Discov (2024), doi: https://doi.org/10.1158/2159-8290.CD-24-0519.https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-24-0519/745696/Clinical-validation-of-a-cell-free-DNA-fragmentome?searchresult=1

Entertainment

Glastonbury Festival tickets sell out in 35 minutes

Published

2 hours ago

November 17, 2024

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Glastonbury Festival tickets sell out in 35 minutes

Standard Glastonbury Festival tickets for 2025 sold out in less than 40 minutes after organisers adopted a new booking system.

The new system saw Glastonbury hopefuls get “randomly assigned a place in a queue” instead of having to refresh the holding page once they went live.

Organisers said: “Thanks to everyone who bought one and sorry to those who missed out, on a morning when demand was much higher than supply. There will be a resale of any cancelled or returned tickets in spring 2025.”

Earlier in the week coach tickets sold out within half an hour for the famous festival in Somerset, which is set to take place between 25 and 29 June next year.

Tickets for the annual event at Worthy Farm sold quicker this year than last year when it took around an hour for all of them to go.

They cost £373.50 plus a £5 booking fee this year, up £18.50 from the price last year, and were sold exclusively through the See Tickets website.

Ticket sale methods and prices for events have been a controversial topic this year, particularly due to Oasis fans’ experience trying to get tickets to their reunion shows in August.

Fans were left outraged after spending hours queueing for tickets only to find some had more than doubled in price from around £148 to £355.

The band’s long-awaited reunion has led to much speculation that Noel and Liam Gallagher will headline Glastonbury, but they denied this while their tickets were up for sale.

“Despite media speculation, Oasis will not be playing Glastonbury 2025 or any other festivals next year,” they said in a statement. “The only way to see the band perform will be on their Oasis Live ’25 World Tour.”

The headliners this summer on the iconic Pyramid Stage were Dua Lipa, SZA and Coldplay, who made history as the first act to headline the festival five times.

2026 is likely to be a year off for Glastonbury, with the festival traditionally taking place four out of every five years, and the fifth year reserved for rehabilitation of the land.

US

Trump is unlikely to take Biden’s advice on China – and it could change the world

Published

2 hours ago

November 17, 2024

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Trump is unlikely to take Biden's advice on China - and it could change the world

As the two most powerful countries in the world, the relationship between the United States and China is the most consequential of all bilateral ties.

Any change in interactions and behaviour by either side does not just impact security, economic activity and trade in Washington and Beijing, but also affects the rest of the planet.

President Xi Jinping chose to make this point publicly as he said hello – and presumably goodbye – to Joe Biden when the two men met on the sidelines of an economic forum in Peru in what was likely their last face-to-face sit down before the US leader hands the keys to the White House over to Donald Trump.

“As two major countries, China and the United States should bear in mind the interest of the whole world and inject more certainty and positive energy into the turbulent world,” Mr Xi said, speaking through a translator.

“It is my consistent belief that as the world’s most important bilateral relationship, a stable China-US relationship is critical not only to the interests of the Chinese and American peoples but also to the future and destiny of the entire humanity.”

Mr Biden, whose relationship with his opposite number does not just span his four years as president but also when he previously served as vice president under Barack Obama, also focused on the importance of dialogue.

“We haven’t always agreed, but our conversations have always been candid and always been frank,” he said, sitting at a long table, surrounded by aides, with Mr Xi opposite him.

“I think that’s vital. These conversations prevent miscalculations, and they ensure the competition between our two countries will not veer into conflict. Be competition, not conflict.”

While clearly directed at him, it is doubtful that Mr Trump will heed the advice.

He has consistently criticised the Biden administration for being too soft on Beijing and has vowed to be much tougher – even saying he would impose 60% tariffs on Chinese imports.

The president-elect’s picks for top jobs in the White House, such as with China hawks Senator Marco Rubio as his desired secretary of state, and Representative Mike Walz as national security adviser, also point to a hardening in the US’ position on Beijing – which is on a trajectory to overtake Washington as the world’s number one superpower.

This moment of re-ordering in global dominance – something the UK was once forced to absorb when the sun set on the British Empire – is on course to happen regardless of who is in the White House.

But a more hostile and combative commander-in-chief in the White House makes it an increasingly perilous time for everyone.

It is perhaps why the current leaders in Beijing and Washington are so keen to stress that while their feelings towards one another go up and down, the ability to keep talking is critical.

Science

NASA and Microsoft Launch AI Tool to Make Earth Data Accessible

Published

4 hours ago

November 17, 2024

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NASA and Microsoft Launch AI Tool to Make Earth Data Accessible

A new artificial intelligence (AI) tool, Earth Copilot, has been introduced by NASA in collaboration with Microsoft to make Earth-related scientific data more accessible. Designed to summarise NASA’s extensive geospatial information, the AI-powered chatbot aims to simplify complex datasets and answer user queries with ease. By addressing questions like the environmental impact of events or changes in air quality, the tool seeks to bridge the gap between NASA’s vast database and users who may lack technical expertise.

Democratising Earth Science Data

The initiative is part of NASA’s effort to expand access to its data. According to Tyler Bryson, Corporate Vice President for Health and Public Sector Industries at Microsoft, many users struggle to utilise NASA’s database due to its technical nature. Extracting insights often requires specialised knowledge of geospatial analysis and data formats. By integrating AI into NASA’s data repository, Earth Copilot reduces the time needed to derive insights from scientific information, making the data more accessible in seconds.

Testing and Integration

Currently, Earth Copilot is in a testing phase, with NASA scientists and researchers evaluating its performance. Following this assessment, NASA plans to integrate the tool into its Visualisation, Exploration, and Data Analysis (VEDA) platform. VEDA already offers public access to some of NASA’s datasets, and Earth Copilot could enhance its usability for non-specialist users.

Potential Benefits

Earth Copilot is expected to transform how users interact with Earth science data by simplifying the process of analysis. The tool has been designed to answer complex questions, such as the effects of natural disasters or global events, using NASA’s comprehensive database. Its development aligns with the agency’s goal of enhancing public understanding of Earth’s systems and providing timely, accurate insights for decision-making.

While still limited to internal testing, Earth Copilot represents a promising step towards making Earth science data universally accessible.