Connect with us

Published

on

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

Continue Reading

Entertainment

Justin Timberlake addresses ‘tough week’ at first concert since drink-driving arrest

Published

on

By

Justin Timberlake addresses 'tough week' at first concert since drink-driving arrest

Justin Timberlake has performed his first gig since his arrest for alleged drink-driving, telling the crowd it had been a “tough week”. 

The US star is currently on his The Forget Tomorrow World Tour and performed in Chicago on Friday night after being arrested earlier this week.

He told the screaming crowd: “We’ve been together through ups and downs, lefts and rights.

“It’s been a tough week, but you’re here and I’m here, and nothing can change this moment right now.”

The singer appeared emotional as he added: “I know sometimes I’m hard to love but you keep on loving me and I love you right back.”

Timberlake was in Long Island in New York state – having reportedly had dinner with friends – when he was pulled over by police in the early hours of Tuesday.

Officers said the 43-year-old had failed to pause at a stop sign and was seen not being able to stay in his lane.

Please use Chrome browser for a more accessible video player

Timberlake’s car caught on CCTV

Timberlake was held overnight and formally charged with a DWI (driving while intoxicated) misdemeanour at Sag Harbor Village Justice Court on Tuesday morning before being released.

According to a source talking to Page Six, the officer who pulled Timberlake over “was so young that he didn’t even know” who the star was.

A second source told the celebrity news outlet that during the arrest, Timberlake said: “This is going to ruin the tour.”

Justin Timberlake.
Pic: Sag Harbor/Reuters
Image:
Timberlake’s mugshot after his arrest. Pic: Sag Harbor/Reuters

Timberlake, who rose to fame with boyband NSYNC before finding huge success as a solo artist with hits including Like I Love You, Cry Me A River, SexyBack and Mirrors, is due to perform in Chicago again on Saturday night.

Further shows are scheduled across the US, Canada and Europe between June and December.

Follow Sky News on WhatsApp
Follow Sky News on WhatsApp

Keep up with all the latest news from the UK and around the world by following Sky News

Tap here

According to court documents filed about the star’s arrest, there was “a strong odour of an alcoholic beverage… emanating from his breath, he was unable to divide attention, he had slowed speech, he was unsteady afoot and he performed poorly on all standardised field sobriety tests”.

Timberlake also told officers he had one martini and was following some friends home, and refused to take a breath test.

His lawyer has said he is “looking forward to vigorously defending” the singer.

Timberlake’s next court date is scheduled for 26 July.

Continue Reading

US

Justin Timberlake addresses ‘tough week’ at first concert since drink-driving arrest

Published

on

By

Justin Timberlake addresses 'tough week' at first concert since drink-driving arrest

Justin Timberlake has performed his first gig since his arrest for alleged drink-driving, telling the crowd it had been a “tough week”. 

The US star is currently on his The Forget Tomorrow World Tour and performed in Chicago on Friday night after being arrested earlier this week.

He told the screaming crowd: “We’ve been together through ups and downs, lefts and rights.

“It’s been a tough week, but you’re here and I’m here, and nothing can change this moment right now.”

The singer appeared emotional as he added: “I know sometimes I’m hard to love but you keep on loving me and I love you right back.”

Timberlake was in Long Island in New York state – having reportedly had dinner with friends – when he was pulled over by police in the early hours of Tuesday.

Officers said the 43-year-old had failed to pause at a stop sign and was seen not being able to stay in his lane.

Please use Chrome browser for a more accessible video player

Timberlake’s car caught on CCTV

Timberlake was held overnight and formally charged with a DWI (driving while intoxicated) misdemeanour at Sag Harbor Village Justice Court on Tuesday morning before being released.

According to a source talking to Page Six, the officer who pulled Timberlake over “was so young that he didn’t even know” who the star was.

A second source told the celebrity news outlet that during the arrest, Timberlake said: “This is going to ruin the tour.”

Justin Timberlake.
Pic: Sag Harbor/Reuters
Image:
Timberlake’s mugshot after his arrest. Pic: Sag Harbor/Reuters

Timberlake, who rose to fame with boyband NSYNC before finding huge success as a solo artist with hits including Like I Love You, Cry Me A River, SexyBack and Mirrors, is due to perform in Chicago again on Saturday night.

Further shows are scheduled across the US, Canada and Europe between June and December.

Follow Sky News on WhatsApp
Follow Sky News on WhatsApp

Keep up with all the latest news from the UK and around the world by following Sky News

Tap here

According to court documents filed about the star’s arrest, there was “a strong odour of an alcoholic beverage… emanating from his breath, he was unable to divide attention, he had slowed speech, he was unsteady afoot and he performed poorly on all standardised field sobriety tests”.

Timberlake also told officers he had one martini and was following some friends home, and refused to take a breath test.

His lawyer has said he is “looking forward to vigorously defending” the singer.

Timberlake’s next court date is scheduled for 26 July.

Continue Reading

US

Arkansas supermarket shooting leaves three dead and 10 wounded as gunman arrested

Published

on

By

Arkansas supermarket shooting leaves three dead and 10 wounded as gunman arrested

A supermarket shooting in Arkansas, US, has left three people dead and 10 others wounded.

Parked cars and shop windows were left riddled with bullet holes after a gunman opened fire on Friday, forcing bystanders to dive for cover.

Among the injured were two police officers who shot back at the gunman – before he was arrested.

The incident took place around 11.30am local time at the Mad Butcher supermarket in Fordyce – a city of just over 3,000 people located 65 miles south of Little Rock.

Colonel Mike Hagar, director of Arkansas State Police, told reporters: “It’s tragic, our hearts are broken”.

The gunman was identified by police as 44-year-old Travis Eugene Posey.

Posey was taken to jail and charged with three counts of murder.

Other charges are still pending and no court date has been set, according to the inmate roster.

Pic: AP
Image:
Police on the scene of the attack in the aftermath of the shooting. Pic: AP

Neither Posey’s, nor the officers’ injuries were life threatening, but among the others the injuries ranged from “not life-threatening to extremely critical”, Col Hagar said.

It wasn’t immediately clear what the motive for the shooting was, nor if it took place predominantly inside or outside the shop.

Roderick Rogers, a member of the city council, witnessed the attack.

He said he saw people fleeing for cover in all directions and added: “People were just jumping into cars to get to safety.”

Law enforcement officers work the scene of the shooting. Pic: AP
Image:
Law enforcement officers work the scene of the shooting. Pic: AP

Amiya Doherty said she was in her mum’s car in the car park of the shop when she heard what she thought were fireworks.

But she then saw a man holding a gun and firing and said she ducked out of view.

“I held my sister’s hand and I told her I love her,” Ms Doherty told Little Rock television station KATV.

Images from the scene showed a slew of bullet holes in the grocery store’s window, and spent shell casings strewn throughout the parking lot.

The shooting took place at the Mad Butcher grocery store in Fordyce, Arkansas. Pic: AP
Image:
The shooting took place at the Mad Butcher grocery store in Fordyce, Arkansas. Pic: AP

Arkansas governor Sarah Huckabee Sanders said she had been briefed on the shooting.

In a post on social media she added: “I am thankful to law enforcement and first responders for their quick and heroic action to save lives.

“My prayers are with the victims and all those impacted by this.”

Follow Sky News on WhatsApp
Follow Sky News on WhatsApp

Keep up with all the latest news from the UK and around the world by following Sky News

Tap here

Read more from Sky News:
Hollywood legend Donald Sutherland has died
Shocking moment drunk driver ploughs into cyclists
Republican ‘sorry’ for repeatedly pouring water in colleague’s bag

The White House said President Joe Biden has been briefed on the shooting and his team will continue to keep him updated.

David Rodriguez, 58, had stopped at his local petrol station in the town when he heard what he thought were fireworks.

But he too saw people fleeing from the shop and one person lying on the ground.

“The police started to show up, and then there was massive gunfire and ambulances pulling up,” he said.

“The bullets were just flying.”

Continue Reading

Trending