Category: 3. Business

  • U.S. stock futures fall, gold hits record ahead of Fed meeting, Big Tech earnings

    U.S. stock futures fall, gold hits record ahead of Fed meeting, Big Tech earnings

    By Mike Murphy

    A worker shovels snow outside the New York Stock Exchange on Sunday.

    U.S. stock futures slumped and gold hit a record high Sunday as investors look ahead to a Fed interest-rate decision and Big Tech earnings this week.

    Dow Jones Industrial Average futures (YM00) fell more than 200 points, or 0.4%, late Sunday. S&P 500 futures (ES00) dropped 0.6 and Nasdaq-100 futures (NQ00) fell 0.8%, after Intel’s 17% plunge Friday.

    Gold futures (GC00) topped $5,000 an ounce for the first time, rising as high as $5,029 on Sunday. Gold is up 15% year to date, and has surged 79% over the past year. Silver futures (SI00), which last week hit $100 an ounce for the first time, continued to surge Sunday. Silver has rallied more than 45% in 2026, and is up more than 230% over the past year.

    Bitcoin (BTCUSD) slumped over the weekend, and was last trading around $86,400. West Texas crude (CL.1), the U.S. benchmark, dipped, and the ICE U.S. Dollar Index DXY, which compares the buck against a basket of rival currencies, declined 0.5% after the dollar lost 1.7% against the Japanese yen USDJPY on Friday

    Stocks mostly gained Friday, but ended the week lower. The S&P 500 SPX dipped 0.4% on the week, while the Dow DJIA declined 0.5% and the Nasdaq COMP slipped 0.1%. All three benchmarks suffered their second straight weekly declines, according to Dow Jones Market Data.

    The Federal Reserve’s interest-rate-setting committee meets Tuesday and Wednesday, with Fed Chair Jerome Powell expected to speak after its conclusion. Most economists and investors are expecting the Fed to keep rates unchanged, with perhaps no more rate cuts until summer – or even later. While inflation remains sticky and the job market is stagnant, Fed officials reportedly worry that more rate cuts could drive up inflation.

    Read more: The Fed is expected to stand pat this week. The big question is for how long?

    Wednesday will also bring quarterly earnings reports for three of the “Magnificent Seven” tech giants: Microsoft (MSFT), Facebook parent Meta (META) and Tesla (TSLA). Apple (AAPL) will report earnings Thursday.

    Big Tech weighs heavily on the S&P 500, and has helped drive strong gains for the overall market in recent years. But as AI infrastructure spending continues to rise sharply without showing big results – yet – investors are getting wary, and broadening their investments to non-tech sectors. That could be good news for the wider market, giving it more durability and making it less reliant on a handful of stocks.

    The upcoming “Magnificent Seven” companies’ earnings will show how those industry leaders are faring amid that cyclical trading, with eyes particularly on Apple and Google parent Alphabet, which reports Feb. 4.

    More: These 5 tech stocks could be big winners this earnings season

    Last week, markets were roiled by tariff threats – and their subsequent retraction – from President Donald Trump against eight of America’s European allies who oppose his desire to acquire Greenland.

    On Saturday, Trump again raised the specter of tariffs against a close ally, threatening Canada with new 100% levies if it goes ahead with a trade deal with China. “We can’t let Canada become an opening that the Chinese pour their cheap goods into the U.S,” U.S. Treasury Secretary Scott Bessent said Sunday during an interview on ABC’s “This Week.”

    But Canadian Prime Minister Mark Carney said Sunday his country has no plans for a free-trade agreement with China, and said a recent deal with China merely resolved some tariff-quota issues between the two countries.

    Furthermore, a little over a week ago, Trump said it was “OK” for Carney to sign a trade deal with China. “That’s what he should be doing. I mean, it’s a good thing for him to sign a trade deal. If you can get a deal with China, he should do that,” Trump told White House reporters on Jan. 15.

    -Mike Murphy

    This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal.

    (END) Dow Jones Newswires

    01-25-26 1837ET

    Copyright (c) 2026 Dow Jones & Company, Inc.

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  • Assessing Centerra Gold (TSX:CG) Valuation After High Conviction Upgrade And Key Project Milestones

    Assessing Centerra Gold (TSX:CG) Valuation After High Conviction Upgrade And Key Project Milestones

    Find winning stocks in any market cycle. Join 7 million investors using Simply Wall St’s investing ideas for FREE.

    Centerra Gold (TSX:CG) is back in focus after a leading brokerage moved the stock to its highest conviction rating, pointing to fresh permitting at Mount Milligan and updated economics at the Kemess copper gold project.

    See our latest analysis for Centerra Gold.

    Those permitting wins and the Kemess update have arrived alongside sharp market interest, with a 30 day share price return of 23.72% and a 90 day share price return of 66.27%, while the 1 year total shareholder return of 195.44% points to strong momentum that investors are now reassessing in light of Centerra Gold’s expanded project pipeline.

    If you are tracking how miners are repricing on new project news, it can help to widen the lens and see what else is moving among fast growing stocks with high insider ownership.

    With Centerra Gold shares up strongly over the past year and the stock now trading just under its CA$28.15 analyst price target and near its estimated intrinsic value, the key question is whether there is still a buying opportunity here or if the market is already pricing in future growth.

    Compared with the current CA$25.19 share price, the most followed narrative pegs Centerra Gold’s fair value at about CA$21.47, implying a premium that investors may want to unpack before leaning on recent momentum.

    The analyst price target for Centerra Gold has ticked higher by about C$0.25, with analysts pointing to updated fair value estimates, modest tweaks to discount and growth assumptions, as well as a lower projected future P/E multiple as key supports for the change.

    Read the complete narrative.

    Curious what supports that higher target even as the future earnings multiple comes down and margin assumptions shift? The most followed narrative blends projected revenue growth, profitability changes and a specific discount rate into one fair value line. If you want to see exactly which earnings and cash flow paths are doing the heavy lifting in that model, the full narrative walks through every step of the calculation.

    Result: Fair Value of CA$21.47 (OVERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, that fair value story can shift quickly if Mount Milligan’s grade uncertainty persists, or if higher all in sustaining costs squeeze margins at current gold prices.

    Find out about the key risks to this Centerra Gold narrative.

    While the most followed narrative sees Centerra Gold as 17% overvalued versus its CA$21.47 fair value line, the current P/E of 11x tells a different story. That multiple sits well below the Canadian Metals and Mining industry at 27.8x and peers at 35.2x, and also below a 14.9x fair ratio that the market could eventually lean toward. This raises the question of whether recent share price strength has fully closed that gap or not.

    See what the numbers say about this price — find out in our valuation breakdown.

    TSX:CG P/E Ratio as at Jan 2026

    If you look at this view and feel it misses something, or you simply prefer your own work, you can build a custom story in minutes with Do it your way.

    A great starting point for your Centerra Gold research is our analysis highlighting 4 key rewards and 2 important warning signs that could impact your investment decision.

    If you are serious about sharpening your watchlist, do not stop at one story. Use the Simply Wall St Screener to surface fresh, data driven stock ideas fast.

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include CG.TO.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • A Look At M/I Homes (MHO) Valuation As Shares Trade Below Popular Fair Value Estimates

    A Look At M/I Homes (MHO) Valuation As Shares Trade Below Popular Fair Value Estimates

    Find your next quality investment with Simply Wall St’s easy and powerful screener, trusted by over 7 million individual investors worldwide.

    M/I Homes (MHO) is back on investors’ radar after recent share price moves, with the stock closing at $133.45. You might be weighing how this homebuilder’s latest performance fits into your portfolio today.

    See our latest analysis for M/I Homes.

    That latest move to $133.45 comes after a mixed short term stretch, with a 1 day share price return of 1.69% decline and a 7 day share price return of 2.70% decline, set against a 3 year total shareholder return of 126.53% and 5 year total shareholder return of 170.31%. This combination points to strong longer term momentum despite recent softness.

    If M/I Homes has you rethinking where housing fits in your portfolio, this could be a useful moment to compare it with other fast growing stocks with high insider ownership that are catching attention right now.

    With annual revenue and net income both showing recent declines, yet the share price sitting below the average analyst target of $157, you have to ask yourself: is M/I Homes undervalued, or is the market already pricing in future growth?

    With M/I Homes closing at $133.45 against a most-followed fair value estimate of $157, the current price sits well below that narrative benchmark.

    Strong balance sheet fundamentals (record-high equity, substantial cash reserves, low net debt, and aggressive share repurchases) not only provide downside protection but also amplify future earnings per share (EPS) and return on equity as demand and deliveries ramp up.

    Read the complete narrative.

    Analysts are tying this fair value to a detailed mix of revenue expectations, margin assumptions, and future P/E levels. Curious which input carries the most weight here, and how buybacks factor into the earnings path behind that $157 figure.

    Result: Fair Value of $157 (UNDERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, you still need to factor in the risk that softer new contracts and rising inventory exposure could pressure margins and weaken the case for upside.

    Find out about the key risks to this M/I Homes narrative.

    While the fair value narrative of $157 suggests upside, the Simply Wall St DCF model lands in a very different place, with an estimate of $38.03 per share. This would make the current $133.45 price look expensive rather than cheap. As an investor, which story do you trust more, the earnings path or the cash flows?

    Look into how the SWS DCF model arrives at its fair value.

    MHO Discounted Cash Flow as at Jan 2026

    Simply Wall St performs a discounted cash flow (DCF) on every stock in the world every day (check out M/I Homes for example). We show the entire calculation in full. You can track the result in your watchlist or portfolio and be alerted when this changes, or use our stock screener to discover 871 undervalued stocks based on their cash flows. If you save a screener we even alert you when new companies match – so you never miss a potential opportunity.

    If you are not fully aligned with these narratives or prefer to lean on your own work, you can test the numbers yourself in just a few minutes, then Do it your way.

    A great starting point for your M/I Homes research is our analysis highlighting 2 key rewards and 1 important warning sign that could impact your investment decision.

    If M/I Homes has sharpened your focus, do not stop here. The next step is to line up a few fresh watchlist candidates using focused screeners.

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include MHO.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • Merck no longer in talks to buy Revolution Medicines, WSJ reports – Reuters

    1. Merck no longer in talks to buy Revolution Medicines, WSJ reports  Reuters
    2. Exclusive | Merck No Longer in Talks to Buy Revolution Medicines  The Wall Street Journal
    3. Merck (MRK) Ends Acquisition Talks with Revolution Medicines Valued at $30 Billion  Intellectia AI
    4. Merck no longer in talks to acquire Revolution Medicines, WSJ reports  TipRanks
    5. Merck Ends Talks to Acquire Revolution Medicines, WSJ Reports  Bloomberg

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  • Amsterdam prepares to ‘ban the fatbikes’ amid rise in serious accidents | Netherlands

    Amsterdam prepares to ‘ban the fatbikes’ amid rise in serious accidents | Netherlands

    On a busy lunchtime, thick-tyred electric bikes zoom through the leafy lanes of the Vondelpark in Amsterdam. But after a marked rise in accidents – particularly involving children – these vehicles the Dutch call “fatbikes” are to be banned in some parts of the Netherlands.

    “It’s nonsense!” said Henk Hendrik Wolthers, 69, from the saddle of his wide-tyred, electric Mate bike. “I drive a car, I ride a motorbike, I’ve had a moped and now I ride a fatbike. This is the quickest means of transport in the city and you should be able to use it.”

    An increasing number of road safety experts, doctors and politicians in the Netherlands disagree. Although motor assistance on e-bikes is limited to just over 15mph, many fatbike riders modify the factory settings to reach speeds of 25mph in this busy park.

    The safety organisation VeiligheidNL estimates that 5,000 fatbike riders are treated in A&E departments each year, on the basis of a recent sample of hospitals. “And we also see that especially these young people aged from 12 to 15 have the most accidents,” said the spokesperson Tom de Beus.

    The Vondelpark will become a fatbike-free area of the city once the new measures are brought in. Photograph: Piroschka Van De Wouw/Reuters

    Now Amsterdam’s head of transport, Melanie van der Horst, has said “unorthodox measures” are needed and has announced that she will ban these heavy electric bikes from city parks, starting in the Vondelpark. Like the city of Enschede, which is also drawing up a city centre ban, she is acting on a stream of requests “begging me to ban the fatbikes”.

    In the park, her plans stirred mixed reactions. While four in five fatbike riders who whizzed past said they were “too busy” to talk, 31-year-old Joost was sceptical. “It will be senseless,” he said. “Normal bicycles use the park, city vehicles use it. It’s all about having the appropriate speed.”

    But Muriel Winkel, 33, running with her dog, Joop, was enthusiastic. “They are all souped-up, which people don’t do with evil intentions, but they often ride carelessly, without watching out,” she said. “Sometimes, my dog really gets a fright.”

    Some point out that the tensions around electric bikes will soon reach other countries, especially with more political interest in stimulating active mobility.

    In this land of early adopters, 48% of bicycles sold in 2024 were electric and another 13% were fatbikes, according to figures from RAI Vereniging and BOVAG motoring associations. In Amsterdam, a third of journeys are made by cycling.

    The roadside assistance organisation ANWB said that the problem was not necessarily with the wide-tyred bike model – but the ease with which people could speed it up to use like a moped, “combined with risky behaviour”.

    Florrie de Pater, the chair of the Fietsersbond Amsterdam cycling association, said that the rise of illegal bikes, plus a lack of enforcement, was scaring old people and children off the roads. “Because of the dangers of those who are cycling fast, especially older people over 55 or 60 simply leave their bikes at home,” she said. “We also hear that parents no longer dare to let their children cycle to school.”

    The brain injury specialist Marcel Aries, a consultant at Maastricht University Medical Center, said more authorities needed to consider controversial bans, alongside the helmet requirement for children on electric bikes from 2027. “It is reasonable for governments and municipalities to consider measures that may be unpopular,” he said. “They are public health responses to increasingly congested streets and widening speed gaps between cars, cyclists and pedestrians.”

    His view is shared by Marlies Schijven, a professor of surgery at the Amsterdam University Medical Center, whose frustrated LinkedIn post on dangerous riders in 2024 has been viewed 2.9m times. “It is a good step, but a baby step, only in one Amsterdam park,” she said. “The problem is much larger. We still see pain, misery and death every day at our morning meeting in the hospital.”

    Wolthers, the fatbike owner, agreed that the problem was in letting children ride these powerful vehicles. “Children go through red, they don’t signal and they also can’t assess the traffic,” he said. “Hospitals have a chilling term for them: potential donors.”

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  • Pregnancy-Triggered Vaso-Occlusive Crises in Hemoglobin SE Disease Complicated by Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report

    Pregnancy-Triggered Vaso-Occlusive Crises in Hemoglobin SE Disease Complicated by Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report

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  • The looming risk of food shortages and anarchy in the UK | Farming

    The looming risk of food shortages and anarchy in the UK | Farming

    Your case for the accumulation of public food reserves in the UK, to ensure that we can feed the nation in the event of war, trade disagreements or world shortages, is well made (Editorial, 20 January). We are rapidly moving into times where the risks of such scenarios are high. Without food for its population, the UK would face economic and political breakdown and anarchy.

    You mention the urgent need to accumulate national stocks of food supplies, probably mostly imported, but say nothing about the UK’s own capacity to produce its own food supply from the agricultural and horticultural industries. In a lengthy period of worldwide food shortage, this would be the only way of avoiding food shortages.

    Following the food shortages of the second world war, we did reach a level of 78% self-sufficiency in 1984, but this has gradually fallen to 62%. This level of home production is about to decline rapidly as the demand for land from a range of other more lucrative uses continues to grow. House- and road-building, the use of agricultural land for woodland and other carbon-saving purposes, solar farms, the creation of new wildlife habitats, recreational use and the general unprofitability of farming will see our self-sufficiency fall again over the next decade. The government’s own land use framework predicts a 10% reduction in farmland by 2050, but this is likely far short of reality.

    These alternative uses of land are all beneficial and desirable, but are they ultimately more important than feeding the population? Most other countries do not think so.
    Richard Harvey
    Owston, Leicestershire

    Have an opinion on anything you’ve read in the Guardian today? Please email us your letter and it will be considered for publication in our letters section.

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  • How FX derivatives trading really moves exchange rates

    How FX derivatives trading really moves exchange rates

    London Business School’s Hélène Rey and Vania Stavrakeva, Vice President and Economist at the Boston Fed, Jenny Tang, LBS Economics PhD programme participant, Adrien Rousset Planat, together with Sinem Hacioglu Hoke of the Federal Reserve Board of Governors, and Daniel A. Ostry of the Bank of England, present the clearest picture yet of how the global foreign exchange (FX) derivatives market actually works, and how it shapes exchange rates, in a new National Bureau of Economic Research working paper, Topography of the FX Derivatives Market: A View from London.

    Using an unprecedented dataset covering 100m FX derivatives transactions in London, the world’s largest FX trading centre, the researchers map how different players interact day by day. Their findings show that exchange rates are influenced not just by macroeconomic news, but by who is trading and why.

    The research finds that pension funds, investment funds, insurers and non-financial companies mainly use FX derivatives to hedge currency risk, especially exposure to the US dollar. Dealer banks sit at the centre of this activity, absorbing these hedging positions and providing liquidity to the market.

    By contrast, hedge funds use FX derivatives primarily to speculate, frequently changing positions in response to interest rates, economic news and momentum strategies. These speculative trades play a key role in transmitting monetary policy shocks into exchange rate movements.

    The study also uncovers an important but less visible group: non-bank market makers, who often end up holding the residual currency risk created by speculative trading, even though they keep little long-term exposure overall.

    Crucially, the researchers show that FX derivatives trading is not just a sideshow to spot markets. Speculative flows by hedge funds help drive currency appreciation after interest-rate surprises, while the unwinding of hedges by investment funds can fuel dollar strength during periods of rising financial stress.

    The findings challenge standard models of exchange rates and highlight why understanding the structure and composition of FX derivatives markets is essential for policymakers, central banks and investors alike.

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  • Assessing Bancorp (TBBK) Valuation As Bearish Earnings Expectations Raise Volatility Risk

    Assessing Bancorp (TBBK) Valuation As Bearish Earnings Expectations Raise Volatility Risk

    Track your investments for FREE with Simply Wall St, the portfolio command center trusted by over 7 million individual investors worldwide.

    Bancorp (TBBK) is drawing attention ahead of its quarterly earnings report, with analysts flagging the event as a possible source of stock price swings and turning more cautious on near term earnings expectations.

    See our latest analysis for Bancorp.

    Those earnings expectations come after a sharp 14.73% 90 day share price decline and a 5.75% one day drop to US$67.19. However, the 1 year total shareholder return of 20.93% and 5 year total shareholder return of about 4x suggest longer term momentum has still been positive even as shorter term sentiment cools.

    If this sort of pre earnings tension has you looking wider, it could be a good moment to broaden your watchlist and check out fast growing stocks with high insider ownership.

    With Bancorp trading below analyst price targets and sitting on a 45% intrinsic discount, the key question is whether recent weakness has left the shares undervalued or if the market already reflects its future growth.

    The most followed narrative currently points to a fair value of $76.50 for Bancorp versus the last close at $67.19, so the market is sitting below that anchor while analysts and narrative authors keep their long term assumptions steady.

    The Bancorp is experiencing substantial growth in Fintech Solutions, driven by increasing volumes and expanded partnerships. This growth is expected to continue with credit sponsorship and higher fees from ACH, card, and payment processing. These initiatives are likely to boost revenue significantly in the coming years.

    Read the complete narrative.

    Want to see what sits behind that fintech story and a fair value above today’s price? The narrative leans on richer margins, higher earnings power and a lower future earnings multiple than many investors might assume. Curious which set of conservative sounding inputs still supports that valuation gap?

    Result: Fair Value of $76.50 (UNDERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, the story could change quickly if fintech partners pull back or if REBL loans and leasing experience additional credit issues that pressure margins and earnings guidance.

    Find out about the key risks to this Bancorp narrative.

    The earlier fair value of $76.50 paints Bancorp as undervalued by about 12%. On earnings multiples, the picture is more mixed. The shares trade on a P/E of 13x, which is higher than the US Banks industry at 11.8x, but below peers at 15x and below a fair ratio of 15.4x.

    In plain terms, the stock is priced richer than the sector overall but cheaper than similar names and the fair ratio the market could move towards. This leaves you weighing whether that gap looks like a cushion or a warning sign.

    See what the numbers say about this price — find out in our valuation breakdown.

    NasdaqGS:TBBK P/E Ratio as at Jan 2026

    If you see the numbers differently or prefer to test your own assumptions, you can build a custom Bancorp view in just a few minutes with Do it your way.

    A great starting point for your Bancorp research is our analysis highlighting 3 key rewards and 1 important warning sign that could impact your investment decision.

    If Bancorp has caught your eye, do not stop there. Broaden your opportunity set now so you are not relying on a single story.

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include TBBK.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • ctDNA Positivity Associated With Worse Survival, Higher Recurrence Risk in Patients With NSCLC

    ctDNA Positivity Associated With Worse Survival, Higher Recurrence Risk in Patients With NSCLC

    Circular tumor DNA (ctDNA) positivity is associated with poorer survival and higher recurrence rates among patients with non–small cell lung cancer (NSCLC), but early detection may allow for timely intervention and improved outcomes, according to a study published in Translational Lung Cancer Research.1

    Evidence Gaps on the Prognostic Utility of ctDNA in NSCLC

    Despite treatment advances, many patients with stage I to III NCSLC still experience disease progression, resulting in poor prognosis and low 5-year survival rates. Imaging is commonly used to assess treatment response and monitor postoperative recurrence. The results, however, do not always align with pathological findings from invasive procedures such as surgical resection or biopsy. This highlights the need for accurate, non-invasive biomarkers that can predict prognosis, guide timely treatment decisions, and reduce recurrence risk.

    In recent years, ctDNA sequencing has emerged as a promising non-invasive method for detecting minimal residual disease. These DNA fragments originate from tumor cells and carry tumor-specific genetic information, with the potential to be used in early diagnosis, prognostic stratification, disease monitoring, and treatment response assessment across cancer types.2

    The researchers noted that ctDNA testing is highly sensitive, less repetitive, and more cost-effective than traditional approaches.1 Despite this, prior studies evaluating the early detection and prognostic utility of ctDNA in NSCLC often focused on specific disease stages or individual outcomes. To better understand the broader role of ctDNA in NSCLC treatment, the investigators conducted a comprehensive systematic review and meta-analysis of global research examining ctDNA detection at multiple time points and its association with various prognostic outcomes.

    Specifically, they searched multiple databases for studies published between January 2016 and May 2022, with updates monitored through June 2024. Eligible studies compared patients with ctDNA positivity vs negativity and reported associated survival outcomes. The researchers then pooled HRs or risk ratios (RRs) for relapse-free survival (RFS), overall survival (OS), and recurrence risk using random-effects models.

    CtDNA Positivity Predicts Worse Survival, Higher Recurrence Risk in NSCLC

    The literature search identified 52 eligible studies, including 50 original research articles, 1 conference abstract, and 1 research letter. The studies were published between 2016 and 2024 and were conducted across several countries, most commonly China and the US. Most focused on stage II and III NSCLC, with sample sizes ranging from 12 to 330 patients. Across studies, ctDNA was collected at multiple time points, including baseline, post-surgery, post-treatment, and during surveillance, using varied definitions of positivity.

    Baseline ctDNA was associated with poorer RFS in the overall NSCLC population (HR, 2.23; 95% CI, 1.82-2.75; I2 = 49%). Among patients with resectable NSCLC, positive ctDNA detected immediately after surgery was strongly linked to worse RFS (HR, 5.64; 95% CI, 3.88-8.19; I2 = 36%). Following treatment completion, patients with positive ctDNA were at a significantly higher risk of recurrence in both resectable (HR, 5.82; 95% CI, 3.12-10.87; I2 = 53%) and unresectable (HR, 2.72; 95% CI, 1.99-3.72; I2 = 39%) NSCLC, with elevated risk persisting during long-term surveillance.

    CtDNA positivity was also consistently associated with poorer OS throughout the course of treatment. At baseline, positive ctDNA predicted worse OS in both resectable (HR, 4.15; 95% CI, 2.45-7.02) and unresectable (HR, 1.74; 95% CI, 1.49-2.03) NSCLC. This persisted post-treatment, as patients with positive ctDNA and resectable disease had significantly worse OS following surgery (HR, 4.17; 95% CI, 2.22-7.84; I2 = 12%), while those with positive ctDNA and unresectable disease experienced poorer OS after completing treatment (HR, 3.38; 95% CI, 1.97-5.80; I2 = 57%). Studies also reported that this association remained statistically significant during the surveillance period.

    Lastly, ctDNA positivity was associated with an increased risk of recurrence across NSCLC subtypes. Patients with positive ctDNA had a higher recurrence risk at baseline (RR, 1.67; 95% CI, 1.27-2.20; I2 = 64%), after treatment completion (RR, 3.13; 95% CI, 2.09-4.67; I2 = 52%), and during long-term surveillance (RR, 5.42; 95% CI, 3.20-9.18; I2 = 81%). Among studies enrolling at least 10 patients, the median interval between ctDNA detection and radiographic or clinical recurrence was 2.93 months (range, 1.70-12.60).

    Realizing ctDNA’s Potential Through Further Research

    The researchers acknowledged several limitations, including significant heterogeneity across studies. Many included studies were also small and retrospective, which may limit the robustness of these findings. Still, they expressed confidence in their research and used it to identify areas for future investigation.

    “These findings underscore the potential of ctDNA-based liquid biopsy to refine risk stratification, guide individualized treatment decisions, and ultimately improve clinical outcomes in NSCLC,” the authors concluded. “Prospective trials with standardized methodologies are warranted to further substantiate these clinical benefits.”

    References

    1. Chen X, Zhang M, Zhou Q, et al. Circulating tumor DNA as prognostic markers of non-small cell lung cancer (NSCLC): a systematic review and meta-analysis. Transl Lung Cancer Res. 2025;14(12):5491-5508. doi:10.21037/tlcr-2025-900
    2. Schmid S, Jochum W, Padberg B, et al. How to read a next-generation sequencing report-what oncologists need to know. ESMO Open. 2022;7(5):100570. doi:10.1016/j.esmoop.2022.100570

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