Latest news with #ctDNA
Medscape
2 days ago
- Health
- Medscape
Can New Biomarker Help Identify High-Risk DLBCL Patients?
For patients with diffuse large B-cell lymphoma (DLBCL), the detection of circulating tumor DNA (ctDNA) following first-line treatment is independently predictive of disease recurrence and overall survival over 2 years, suggesting important prognostic value of the biomarker to improve upon standard assessment with PET-CT imaging. 'We demonstrated the prognostic value of ctDNA MRD [minimal residual disease] in first-line DLBCL cell patients [and that] ctDNA MRD provides independent evidence of residual disease beyond PET-CT,' said first author Steven Wang, MD, of Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands, in presenting the findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. 'These results support the integration of ctDNA MRD as a standard component of response evaluation in first-line DLBCL treatment,' he said. The prognosis for long-term outcomes in DLBCL currently relies on PET-CT; however, key challenges with the approach include sometimes suboptimal sensitivity and specificity, with the potential to miss microscopic residual disease. Liquid biopsy-based analysis of ctDNA, increasingly used in other cancers, meanwhile offers a radiation-free, non-invasive method for the assessment and monitoring of DLBCL. To further investigate the biomarker's prognostic benefits in DLBCL in a prospective context, Wang and colleagues evaluated data on 160 patients at more than 50 centers in the Netherlands and Belgium in the HOVON-902 trial. Of the patients, most (79%) had stage 3 or 4 disease. All patients had been treated with curative-intent first-line therapy, with either R-CHOP or DA-EPOCH-R chemotherapy regimens. In the assessment of ctDNA MRD, the investigators utilized the phased variant (PV) enrichment and detection sequencing (PhasED-Seq) assay, which targets unique 'phased variant' alterations, or multiple mutations on the same DNA molecule. The design boosts the assay's sensitivity compared with other tests, which can have limitations such as error profiles of single nucleotide variants (SNVs). Among the patients, most (90%) had DLBCL, with 9% having high-grade B-cell lymphoma and 1% with primary mediastinal large B-cell lymphoma. In terms of the distribution of International Prognostic Index (IPI) risk level, 22% were low-risk, 29% low-intermediate risk, 27% high-intermediate risk, and 22% at high-risk. Patients' median age was 67.5 years. With 31 months of median follow-up in the cohort overall, the 24-month rates of progression-free survival (PFS) and overall survival (OS) were 74% and 86%, respectively. The rates of PFS after 3 years were substantially higher for those who were MRD-negative at the end of treatment compared with those who were MRD-positive (85% vs 15%, respectively; hazard ratio [HR] 11.03; P < .0001), and 3-year rates of OS were also higher (92% vs 41%; HR, 7.38; P < .0001). The findings show that 'end-of-treatment ctDNA MRD is strongly prognostic for PFS and OS,' Wang said. Higher cancer stage and IPI risk were associated with MRD positivity (both P < .05), and ctDNA was the most strongly prognostic of PFS (HR, 11.03), compared with end-of-treatment PET-CT results (HR, 5.31) or IPI level of risk (HR, 1.61). Of patients who did not have a complete response based on PET results, MRD-positivity was likewise significantly prognostic for worse PFS at 3 years (PFS 4%) compared with those who were MRD-negative (PFS 64%), importantly suggesting the ability of MRD to adjudicate imaging results (HR for PFS, 6.78; P < .0001). 'End of treatment ctDNA MRD-positivity in patients without complete response have especially poor outcomes,' Wang noted. All of the patients who did not achieve a complete molecular response and remained MRD-positive experienced a relapse. The prognostic accuracy of ctDNA-MRD status was observed across subgroups, including based on the source of baseline sample (tumor vs plasma), best clinical response, IPI, sex, lactate dehydrogenase, stage, or extranodal disease. The researchers also examined how ctDNA MRD status at the end of treatment correlated with the timing of response, and they found that 80% of patients who relapsed within a year of treatment had positive ctDNA MRD at the end of treatment, while only 22% of patients who relapsed after the first 12 months of first-line therapy had positive MRD. 'This distinction is important as early relapsers might be eligible for CAR T-cell therapy, and this demonstrates that end of treatment ctDNA MRD can reliably predict early relapses; however, long late relapses might require longitudinal MRD monitoring,' Wang explained. 'These data demonstrate the robust prognostic value of ctDNA MRD by PhasED-Seq in first-line DLBCL patients,' Wang said. ctDNA Risk-Stratification Benefits Important Discussing the research at the meeting, Mark Roschewski, MD, of the National Cancer Institute, Bethesda, Maryland, agreed that results on the timing of events were notably important. 'Now we can have a better understanding of when these events get captured [on ctDNA testing] and what we saw is that mostly these are early events,' said Roschewski, who recently co-authored a review of ctDNA as measurable residual disease in aggressive B-cell lymphoma. Roschewski noted that the benefits of ctDNA are reflected in changes in National Comprehensive Cancer Network (NCCN) Guidelines, which indicate that ctDNA, using a sufficient test — such as PhasED Seq — does appear to be suitable as an alternative to invasive tissue biopsies for positive PET scans. However, the most important thing that the research shows — which validates other findings — is that 'these tests can actually risk-stratify patients who have positive as well as negative PET scans, improving upon our current definition of remission,' Roschewski added. Ultimately, the findings show that 'ultrasensitive ctDNA at the end of frontline therapy for large B-cell lymphoma is the most precise tool to define remission,' he said. Not Ready for Prime Time? However, for all of its promising benefits, a key concern expressed in the Q&A portion of the session was whether ctDNA could indeed be relied upon to replace a tissue biopsy in real-world practice. For instance, while a positive PET scan and positive ctDNA MRD result could likely give clinicians confidence in moving ahead with second-line therapy, the approach may be less clear if a patient is PET-negative but MRD-positive. 'What I worry about is that [ctDNA] is prognostic, but not predictive, and with a relatively small dataset in this study, what are the implications in terms of overtreatment in that kind of situation?' one audience member noted. 'This is an important point,' responded Roschewski. 'However, we should recognize that with the way things are done now, our PET scans have a positive predictive value of about 50%,' he said. 'One of the concerns, and we see it in the data, is that these patients with a positive PET scan are getting second-line therapy when they don't even have any active disease.' 'So, this is something that is already happening,' he explained. Guidelines in such situations suggest either repeating the PET scan or the biopsy, hence delaying therapy. 'So, a negative ctDNA test could help you get information sooner,' Roschewski said. 'But would it improve patient outcomes?' the audience member pressed, getting to the issue of clinical utility. 'That's something we don't have data on yet,' Roschewski conceded. 'I completely agree that this may not be ready for general clinical care without that data, but it may be fine in the context of a clinical trial for now.' Roschewski noted that the good news is that 'at least three clinical trials' are currently being planned to address the issues. He noted that 'we are able to [use this] in other hemolytic malignancies, but we have not gotten there yet [with DLBCL] and we need prospective trials to tell us what to do.' The encouraging news, however, is 'if we see success here, there is no reason to stop at large cell lymphoma. There are other curable lymphomas that we would like to test this in, and I think this could be a domino effect in which we start thinking about this all across therapies for a bunch of different lymphomas,' Roschewski said. ctDNA Benefits in Early Disease Assessment Anticipated Jane N. Winter, MD, professor of medicine, Division of Hematology/Oncology, Northwestern University, Chicago, Illinois, agreed that, with the data showing that ct-DNA is a powerful predictor of clinical outcome and can identify patients at high risk of relapse, 'the big question is how we should use this information.' For instance, 'how important is it to identify refractory disease immediately at the end-of-treatment?' she said in an interview. 'I'm hopeful that ctDNA kinetics early in the course of therapy can help us identify patients for escalation of therapy,' said Winter, a past president of the American Society of Hematology. 'Similarly, we might be able to use ctDNA to deescalate or abbreviate therapy.' Ultimately, the results underscore that 'ctDNA at the end of treatment is a powerful predictor of progression/relapse,' Winter said. 'I'm very interested in using ctDNA as part of an early disease assessment.'
Yahoo
3 days ago
- Business
- Yahoo
In Largest Molecular Residual Disease (MRD) Study in Colon Cancer, Guardant Reveal Testing Prior to Chemotherapy Provides Robust Stratification for Risk of Disease Recurrence and Survival to Enable Timely Treatment Decisions
Data support routine use of circulating tumor DNA testing in management of stage III colon cancer patients Tumor fraction analysis provides further insights for patient management in patients with ctDNA detected PALO ALTO, Calif., May 31, 2025--(BUSINESS WIRE)--Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, and its research collaborators today presented results of the largest study to date evaluating circulating tumor DNA (ctDNA) in colon cancer prior to chemotherapy, demonstrating the ability of the Guardant Reveal™ test to stratify the risk of disease recurrence and overall survival, and thus inform treatment decisions after surgery. Data from the phase III trial of FOLFOX-based adjuvant chemotherapy (NCCTG N0147) involving over 2,000 patients with stage III colon cancer with median follow-up of 6.1 years were presented at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting. Results demonstrated that circulating tumor DNA detected in the bloodstream after cancer surgery and prior to the start of adjuvant therapy, using the Guardant Reveal test, is a strong predictor of the risk of disease recurrence and poorer survival, and suggest the potential for ctDNA testing to improve decision-making at a critical time point for post-operative chemotherapy. Specifically: Among patients with post-surgical ctDNA detected, 62.6% had the cancer return within 3 years, despite having had adjuvant chemotherapy, while only 15.4% of patients with undetectable ctDNA recurred in the same period. The level of ctDNA, or tumor fraction, showed promise in identifying individuals who are less likely to clear residual disease with adjuvant treatment. "Thirty percent of patients with stage III colon cancer will relapse after surgery, despite having standard adjuvant chemotherapy," said Frank Sinicrope, MD, professor of oncology and medicine at Mayo Clinic and principal investigator for the study. "In this study, we demonstrate that analysis of postsurgical ctDNA can improve the prediction of disease recurrence over standard staging criteria, which may help guide patient management and follow-up. These data further support the routine use of ctDNA in management of stage III colon cancer patients." "With the Guardant Reveal test, a simple blood draw can be used to identify colorectal cancer patients who have molecular residual disease and are most likely to benefit from adjuvant therapy," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "This large study confirms the test's ability to identify high risk of cancer returning and support oncologists in making more informed therapeutic decisions to help improve patient outcomes." The full abstract for the presentation can be found on the ASCO website. About Guardant Reveal Guardant Reveal, which runs on the Guardant Infinity™ smart liquid biopsy platform, is a blood test that uses epigenomic (methylation) analysis to detect circulating tumor DNA, a marker of minimal residual disease, to predict cancer recurrence, helping to guide clinical decisions after surgery or chemotherapy. The test is covered by Medicare for patients with colorectal cancer in the early post-surgical setting and for surveillance testing to monitor for disease recurrence after curative intent treatment. About Molecular Residual Disease Molecular residual disease refers to a subclinical measure of cancer burden that remains during and following treatment. A patient's MRD status is a reliable indicator of clinical outcome and response to therapy and can be used for risk stratification and to guide treatment options when used in conjunction with other clinical data. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer. For more information, visit and follow the company on LinkedIn, X (Twitter) and Facebook. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health's liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health's financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operation" and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2024, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health's views as of any date subsequent to the date of this press release. View source version on Contacts Investor Contact: Zarak Khurshidinvestors@ Media Contact: Michael Weistpress@ +1 317-371-0035
The Sun
5 days ago
- Health
- The Sun
‘Revolutionary test' that detects cancer up to a YEAR before it shows on scans to be rolled out on NHS in world first
SUPER sensitive cancer blood tests will be rolled out to NHS patients in a world first. People diagnosed with breast or lung cancers will be tested for circulating tumour DNA, known as ctDNA, to find fragments of disease in their blood. 1 Results will give doctors a quick read on their cancer type, speeding up access to specialised treatment with higher chances of success. Clinics typically have to wait for the results of scans and surgical biopsies to be sure what they are seeing. New 'liquid biopsies' could also one day be used to stop cancer spreading, predict the risk of it coming back and guide treatment changes. Professor Peter Johnson, NHS England's director for cancer, said: 'Liquid biopsies are leading us into a new era of personalised cancer care. 'We are now able to expand the use of this revolutionary test on the NHS to help tailor treatment for thousands of patients across the country. 'It has the potential to help us scan the body in a single blood test to see where and how cancer may be developing and target it with speed and precision to help save more lives. 'We hope to roll it out for patients with other forms of cancer in the near future.' ctDNA tests will be offered to patients with advanced breast cancer that is not responding to treatment, and people with suspected non-small cell lung cancer. Following successful pilots, England is the first country to begin a mass rollout and will test thousands of Brits every year. It is hoped many will be spared from unnecessary tests, surgery or chemotherapy. NHS rolls out bowel cancer screening to 50 and 52-year-olds after Dame Debs' campaigning Dr Isaac Garcia-Murillas, from The Institute of Cancer Research, London, said: 'The potential for patient benefit and cost savings to the NHS is incredible. 'The main point is it's non-invasive so there is no need for tumour biopsies, which can be painful. 'And often by the time you have tested a tumour by imaging it has already grown. 'If you pick it up earlier you can intervene earlier and smaller tumours might respond better to drugs. 'This test allows you to see cancer cells that are undetectable on others.' The NHS blood testing could see lung cancer patients get the best treatment weeks earlier, compared to waiting for scans and biopsy results. Women with hard-to-treat breast cancer will have tumour DNA analysed to work out the best targeted approach. Research by Dr Garcia-Murillas last year found the blood tests can detect signs of cancer growing back up to a year before it shows on a scan. Doctors hope the blood testing will become so accurate and simple that it can be used to monitor tumours in near real time. Dr Julie Gralow, president of the American Society of Clinical Oncology, said: 'This is a cool way of not having to stick needles into wherever the cancer is to test it, but just drawing blood. 'It's live monitoring at a level that is actually much more specific and early than waiting for it to show up on scans.' Cancer tests currently available in the UK In the UK, several cancer screening programs and diagnostic tests are available, including blood tests, imaging scans, and biopsies. Screening programs for breast, cervical, and bowel cancers are offered to specific age groups, while other tests, like those for lung cancer and prostate cancer, are available through a doctor's referral or self-referral. Breast screening Offered to women aged 50 to 70, with self-referral for women over 70, using mammograms to detect early signs of breast cancer. Bowel screening Home test kits are sent to individuals aged 50 to 74 every two years, with the option for those over 75 to self-refer. Cervical screening Offered to women, some transgender men, and some non-binary people aged 25 to 64, using Pap tests and HPV tests to detect changes in the cervix. Prostate cancer screening There is no national screening program for prostate cancer in the UK due to the unreliability of the PSA test.
