Rectal Adenocarcinoma

The preliminary results from a whole genome minimal residual disease (MRD) test were evaluated in 31 patients with locally advanced rectal cancer (LARC). C2i Genomics and Memorial Sloan Kettering performed a collaborative study as part of the Organ Preservation for Rectal Adenocarcinoma (OPRA) trial. The test was evaluated for the ability to serve as a prognostic biomarker to guide the course of treatment toward either an organ-sparing watch-and-wait protocol or surgical resection. Called the C2inform test, it utilizes whole genome sequencing (WGS) to characterize the complete set of cancer alterations and then applies artificial intelligence (AI)-driven pattern recognition to detect traces of cancer in patient plasma samples. Most people with rectal cancer have a mesorectal excision (TME) as part of their surgery. This is when surgeons remove some of the fatty tissue around the rectum (mesorectum). They do this because the tissue contains lymph nodes and blood vessels and means all the lymph nodes near the tumour can be removed reducing the risk of cancer returning. When possible the surgeon will join the colon to the top of the anus. The OPRA trial demonstrated that total TME can be deferred—with equivalent survival outcomes—for the nearly 50% of LARC patients that obtain a complete response following neoadjuvant therapy, the administration of therapeutic agents, before main treatment or surgery. This organ-sparing protocol provides a path for patients to avoid significant morbidities and associated impairment to quality of life resulting from surgery. A high proportion of patients develop tumor regrowth and earlier detection can expedite this surgical intervention. googletag.cmd.push(function () { googletag.display('text-ad1'); }); The present study represents a breakthrough in locally advanced rectal cancer treatment, highlighting the efficacy of circulating tumor DNA (ctDNA) for non-invasive monitoring of MRD and response to neoadjuvant therapy. The C2inform test identified ctDNA with 96% sensitivity in patient plasma samples taken at baseline, before neoadjuvant therapy. The tumor fraction (TF) levels detected at baseline separated responders from non-responders. Tumor detection at follow-up was associated with a higher rate of recurrence and tumor was detected at follow-up for five out of five patients who developed recurrence. Overall TF dynamics showed clearance of ctDNA down to the non-detection level throughout treatment in patients with a complete response, while non-responders exhibited non-decreasing and often increasing estimates of ctDNA burden. Detection of ctDNA at follow-up for all patients who recurred is indicative of potential clinical utility for treatment de-escalation in the context of organ preservation. Asaf Zviran, CEO and co-founder of C2i Genomics said: “We recognize the urgent need for more effective cancer treatment options. “Surgery is still considered the mainstay of treatment for LARC. However, we hope with this advanced MRD monitoring and the introduction of immuno-oncology (IO) neoadjuvant treatments, invasive surgeries can be avoided, allowing us to tailor treatment plans based on a patient's unique clinical measurements.” Expanding on these results, C2i has also partnered with the Spier Family Foundation and Massachusetts General Hospital (MGH) to evaluate ctDNA monitoring in the context of rectal cancer organ preservation in a prospective observational study. This study aims to determine whether the presence of ctDNA in blood specimens can detect rectal cancer response and risk of recurrence earlier.