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A primary-tumor-informed whole genome sequencing assay was used to detect circulating tumor DNA (ctDNA) and estimate tumor fraction before, during, and after neoadjuvant therapy. ctDNA was detected in 95% of baseline samples, and tumor fraction predicted sustained clinical complete response. High tumor fraction during or after therapy reduced sustained response and increased relapse risk, while very low tumor fraction during surveillance persisted in many patients without recurrence, supporting high sensitivity while specificity needs further study.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ultrasensitive-ctdna-monitoring-for-organ-preservation-in-patients-with-locally-advanced-rectal-cancer-article/455557/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ultrasensitive-ctdna-monitoring-for-organ-preservation-in-patients-with-locally-advanced-rectal-cancer-article/455557.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How was ctDNA measured in this study?","Question",{"text":112,"@type":113},"The study used a primary-tumor-informed whole genome sequencing (WGS) assay to detect circulating tumor DNA (ctDNA) and estimate tumor fraction before, during, and after neoadjuvant therapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What did tumor fraction predict for clinical outcomes?",{"text":117,"@type":113},"Tumor fraction was a significant baseline predictor of sustained clinical complete response (scCR). High tumor fraction during or after neoadjuvant therapy was linked to lower likelihood of scCR and higher relapse risk.",{"name":119,"@type":110,"acceptedAnswer":120},"What does very low ctDNA during surveillance indicate?",{"text":121,"@type":113},"Very low tumor fraction during surveillance was found in many patients who did not experience recurrence, suggesting persisting low amounts of ctDNA and highlighting the need to balance sensitivity with specificity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},455557,1791322747,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","npj | precision oncology Article  \n\n| Published in partnership with The Hormel Institute, University of Minnesota |  | |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41698-025-01208-w](https://doi.org/10.1038/s41698-025-01208-w) |  |  |\n| Ultrasensitive ctDNA monitoring for organ preservation in patients with locally advanced rectal cancer\u003Cbr> Check for updates |  |  |\n| Paolo Manca1,2, Chin-Tung Chen3, Farheen Shah4, Christina Lee3, Dylan Domenico4, Dana Omer3, Santiago Gonzalez5, Ino De Bruijn4, Samuel Ahuno4, Walid K. Chatila4, Madison Darmofal4, ImanTavassoly5, Adam J. Widman1, Michael F. Berger6, Brian Loomis6, Elli Papaemmanuil4, RonaYaeger1, Asaf Zviran5, Julio Garcia-Aguilar3  & Francisco Sanchez-Vega4  |  |  |\n| Optimal selection of patients with locally advanced rectal cancer for watch and wait (WW) and optimal management during follow-up remain challenging. We employed a primary-tumor-informed whole genome sequencing (WGS) assay to detect circulating tumor DNA (ctDNA) and estimate tumor fraction (TF) before, during and after neoadjuvant therapy. ctDNA was detected in 95% of baseline samples, and TF was a significant baseline predictor of sustained clinical complete response (scCR) . High TF during or after neoadjuvant therapy was associated with lower likelihood of scCR and higher risk of relapse. Very low TF during surveillance was detected in a large proportion of patients who did not experience a recurrence, suggesting the existence of persisting low amounts of ctDNA. WGSbased ctDNA assessment thus provides high sensitivity, which is crucial for treatment de-escalation, but additional research is needed to also ensure good specificity (the trial is registered in ClinicalTrials.gov with the identifier NCT02008656) . |  |  |\n| Management of locally advanced rectal cancer (LARC) has shifted from the one-size-fits-all paradigm of long-course neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME)and adjuvant systemic chemotherapy to a plethora of new strategies aimed at anticipating, intensifying, deintensifying or omitting one or more of the three treatment modalities1–5.\u003Cbr>Organ preservation is supported by an increasingly solid amount of evidence accumulated from retrospective case series over the years6–10, and recently also from prospective clinical trials. As an example, the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial11 was a randomized phase II trial in which patients underwent total neoadjuvant therapy (TNT) in the form of induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and were subsequently offered, in case of complete or near-complete clinical response (cCR or ncCR), strict observation without rectum resection. At its most recent update, the rates of organ preservation at 5 years were 39% and 54% in the INCT-CRT and the CRTCNCT cohorts, respectively12. | Watch and wait (WW) is now a standard option offered to rectal cancer patients with a cCR or ncCR to neoadjuvant therapy (NAT) in the United States13. Nevertheless, both patientselection and follow-up strategies are active areas ofinvestigation for this approach. Assessment ofcCR can be challenging14 and a substantial fraction of patients with an apparent clinical response after NAT experience regrowth during surveillance6, 12. This happens more often inpatientswith ncCRand limits the organ preservation rate of this strategy. Moreover, while WW has been carried out at high-volume centers with high rectal cancer expertise and excellent resources for thorough and complete multimodal follow-up, doubts have been raised regarding broad implementation of a rectum-preserving approach, which requires important safeguards to ensure patient safety15. In this context, objective and precise noninvasive tools to improve patient selection based on radiological, endoscopic and clinical evaluation are urgently needed.\u003Cbr>In parallel with the efforts to impr","cbCaiizZgtjJw4Fy","https://ap.wps.com/l/cbCaiizZgtjJw4Fy","pdf",5781912,11,"English","# Optimal monitoring with ctDNA in watch-and-wait\n## Study approach using primary-tumor-informed WGS\n## Predictive value of tumor fraction for sustained clinical complete response\n## Surveillance findings and relapse risk","[{\"question\":\"How was ctDNA measured in this study?\",\"answer\":\"The study used a primary-tumor-informed whole genome sequencing (WGS) assay to detect circulating tumor DNA (ctDNA) and estimate tumor fraction before, during, and after neoadjuvant therapy.\"},{\"question\":\"What did tumor fraction predict for clinical outcomes?\",\"answer\":\"Tumor fraction was a significant baseline predictor of sustained clinical complete response (scCR). High tumor fraction during or after neoadjuvant therapy was linked to lower likelihood of scCR and higher relapse risk.\"},{\"question\":\"What does very low ctDNA during surveillance indicate?\",\"answer\":\"Very low tumor fraction during surveillance was found in many patients who did not experience recurrence, suggesting persisting low amounts of ctDNA and highlighting the need to balance sensitivity with specificity.\"}]","Ultrasensitive ctDNA monitoring for organ preservation in patients with locally advanced rectal cancer - Article | PDF",1790743415,28]