January 25, 2024
2 minute read
Important points:
- Patients who are ctDNA positive during the MRD window have significantly worse DFS.
- Both ctDNA-based detection of MRD and ctDNA dynamics in response to adjuvant therapy prognosticate patient outcome.
Detection of molecular residual disease based on circulating tumor DNA appears to be highly predictive of patient outcome, according to data presented at the ASCO Gastrointestinal Cancer Symposium.
Researchers also found that the dynamics of circulating tumor DNA (ctDNA) in response to adjuvant chemotherapy was also an important predictor of patient outcome.
“Our data demonstrate the prognostic value and predictive power of circulating tumor DNA detection in (approximately) 3,000 patients analyzed at 24 months.” Hiroki Onsen,medical doctor, members from Japan’s Osaka Medical and Pharmaceutical University said during a presentation. “The importance of circulating tumor DNA quantification [mean tumor molecules/mL] is also displayed. ”
Background and methodology
Previous data analysis from the observational GALAXY study showed that detection of postoperative molecular residual disease (MRD) is not only a prognostic indicator of patient outcome but also a significant risk factor for recurrence. Ta. BRAF V600E mutation status.
The researchers conducted an updated analysis and correlation of ctDNA dynamics with outcomes in patients with radically resected stage II to stage IV colorectal cancer in the same study.
They provide personalized, tumor-informed detection and quantification of ctDNA in serial plasma samples collected at 1, 3, 6, 9, 12, 18, and 24 months post-surgery until disease recurrence. A different assay was used. The researchers also performed CT scans of the chest, abdomen, and pelvis every six months.
Study participants were treated with adjuvant chemotherapy or followed-up after curative surgery.
DFS served as the primary endpoint of the study, defined as the time from the date of surgery to the date of detection of recurrence/death from any cause.
Of the 5,781 colorectal cancer patients enrolled in the GALAXY study, 2,998 met inclusion criteria for data analysis.
The researchers noted that the median follow-up was 16.14 months (range, 0.23-42.14).
result
Of the 2,860 patients in whom researchers performed ctDNA analysis during the postoperative MRD period, 275 (14.8%) had positive ctDNA results and 1,783 (85.2%) tested negative for ctDNA.
The researchers observed that stage II to stage II colorectal cancer patients who had a positive ctDNA test during the MRD period had a significantly inferior DFS compared to patients who tested negative for ctDNA (33.5 % vs. 89.3%, HR = 12.05, 95% CI, 9.46-15.34). )
Within the MRD-positive subgroup, landmark analysis of ctDNA dynamics from initial MRD detection to 3 months showed that patients who remained ctDNA positive experienced disease recurrence compared to those who showed ctDNA clearance. It was shown to be more than 5 times more likely. (HR = 5.4; 95% CI, 3.58-7.67).
Of the 309 MRD-positive patients, 181 received adjuvant therapy, of which 132 (72.9%) subsequently underwent ctDNA clearance.
The researchers noted that patients with sustained clearance had better outcomes compared to those with transient ctDNA clearance (HR = 32.57; 95% CI, 9.94-106.76).
We also reported that patients who were MRD positive, received adjuvant therapy, and had a >50% reduction in ctDNA levels after 6 months had a significantly longer DFS than those with <50% reduction (HR = 2.41; 95 % CI, 1.42-4.09).
next step
According to the researchers, the results provide several markers for oncologists to focus on when treating this patient population.
“Patients with stage I to IV disease in whom ctDNA was detected after surgery have significantly lower DFS at 24 months than patients with negative ctDNA,” Dr. Yugami said, adding that “ctDNA status during surveillance is associated with significantly lower DFS. It’s very relevant,” he added.
Yugami said the results also suggest that a decrease in ctDNA concentration after six months is a useful predictor of treatment outcome.
“ctDNA-based adjuvant strategies will be further established by the ongoing randomized interventional VEGA and ALTAIR clinical trials that are part of CIRCULATE-Japan,” Yugami said.
perspective
Dr. Brett L. Ecker
Surgical resection may have curative effects in the management of colorectal cancer (CRC). However, recurrence rates after surgery reach 30% in patients with American Joint Committee on Cancer (AJCC) pathological stage II to stage III CRC and as high as 80% in patients with resected AJCC stage IV CRC. There is a possibility. The benefits of adjuvant chemotherapy for selected populations of patients with colorectal cancer are well established, with demonstrated efficacy in improving recurrence and survival rates. Traditionally, we have used clinical and pathological features to select patients most likely to relapse and used cytotoxic chemotherapy for these patients, but only effective It was only partially.
Latest data from CIRCULATE-JAPAN, the largest prospective study of ctDNA in patients with resected colorectal cancer, improves our understanding of recurrence and the use of adjuvant chemotherapy to minimize cancer recurrence. We keep it up to date. Originally published last year, natural medicine, the authors shared mature data at ASCO GI. These data confirmed that patients with ctDNA-negative colorectal cancer have a very low risk of recurrence. The 2-year DFS rate for the MRD-positive subset is 30% versus 92% at 2 years. Beyond prognosis, ctDNA status was predictive of adjuvant chemotherapy efficacy. ctDNA-negative patients had an excellent prognosis regardless of the use of adjuvant chemotherapy. In contrast, chemotherapy was selectively associated with improved recurrence-free survival in ctDNA-positive patients. Finally, the researchers shared new data from a surveillance cohort of patients who underwent sequential ctDNA testing. Not surprisingly, patients with transient ctDNA clearance suffered from late relapse. No recurrence was observed in patients with sustained ctDNA clearance.
Taken together, these data support a relapse model in which micrometastatic cells actively replicating and releasing DNA lead to clinical relapse and serve as reliable biomarkers to accurately identify this preclinical relapse state. The Signatera ctDNA platform is established. Ongoing randomized studies in this population (i.e., the VEGA and ALTAIR clinical trials) are investigating whether chemotherapy for patients with ctDNA-positive-only disease can “jump-start” treatment to even prevent clinical relapse from occurring. I’ll make it clear what’s going on.
Dr. Brett L. Ecker
Rutgers Cancer Institute, New Jersey
Rutgers Robert Wood Johnson Medical School
Disclosure:
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Hiroshi Yugami et al. Abstract 6. Presentation location: ASCO Gastrointestinal Cancer Symposium. January 18-20, 2024. San Francisco.
Disclosure: Mr. Yugami has not reported any relevant financial disclosures. Please refer to this study for relevant financial disclosures of all other authors.