Results From ASCO GI
At ASCO GI 2023, Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia, presented patient cases and reviewed data from studies of ctDNA in colon or colorectal cancer.2 Dr Tie noted that 3 recent studies showed post-operative ctDNA to be “highly prognostic.”1,4,5
She also highlighted data from the DYNAMIC trial, which included 455 patients with stage II colon cancer who were randomly assigned to standard risk factor-guided management or ctDNA-guided management.6 In the ctDNA-guided group, patients with detectable post-operative ctDNA received adjuvant chemotherapy, and ctDNA-negative patients did not.
Ultimately, adjuvant chemotherapy was administered to 15% of patients in the ctDNA-guided group and to 28% in the standard-management group.
Despite the receipt of adjuvant chemotherapy in approximately half as many patients, the 2-year recurrence-free survival (RFS) rate was 93.5% in the ctDNA-guided group and 92.4% in the standard-management group.
The 3-year RFS rate was 92.5% among ctDNA-negative patients who did not receive adjuvant chemotherapy and 86.4% among ctDNA-positive patients who received adjuvant chemotherapy (HR, 1.83; 95% CI, 0.79-4.27).
Dr Tie noted that the DYNAMIC trial results were consistent with the GALAXY results,1 but observational studies and cross-trial comparisons have limitations, and ongoing trials will provide more definitive evidence.
Also at ASCO GI 2023, Claus L. Andersen, PhD, of Aarhus University Hospital in Denmark, discussed the role of ctDNA monitoring in patients with curative-intent liver resection for oligometastatic colorectal cancer — a setting in which postoperative adjuvant chemotherapy is standard practice, but recurrences are common.3
Dr Andersen and colleagues previously reported that ctDNA detection was a strong predictor of RFS in that setting (HR, 4.5; 95% CI, 2.1-9.5; P <.0001).7
Dr Andersen analyzed data from 7 published studies including a total of 461 patients and found that ctDNA had a mean positive predictive value of 0.90 and a mean negative predictive value of 0.53.7-13
Dr Andersen cautioned, however, that the site of recurrence seems to matter. ctDNA detects liver metastases more reliably than lung metastases or other sites of recurrence.
Dr Andersen concluded that ctDNA could enable patients with oligometastatic disease to be stratified into high- and low-risk groups, guide the choice of imaging modality, and guide therapeutic choice and surveillance during and after therapy. However, more studies are needed to document clinical utility.
Remaining Areas of Uncertainty
Although studies have suggested that ctDNA testing can identify colorectal cancer patients with a high risk of recurrence who may benefit from adjuvant chemotherapy, some basic information that informs the use of ctDNA testing is unclear.
For example, it isn’t clear when the first post-treatment ctDNA test should be done. A retrospective study suggested that ctDNA may be detected as early as 2 weeks after surgery.14 Another study suggested that postoperative surges in non-tumor derived DNA can interfere with ctDNA detection, so additional samples should be collected after week 4.15
Dr Tie noted that the turnaround from the time a blood specimen is obtained to the time a ctDNA result is available is approximately 2 weeks. She recommended that, for future studies, researchers consider analyzing blood specimens at week 4 and week 7 after surgery (or later), sequentially instead of concurrently.6
Another unknown is which technique is best for assessing the presence of ctDNA. The GALAXY and DYNAMIC trials used a tumor-informed ctDNA test, but a tumor-agnostic, panel-based ctDNA test may have advantages, according to researchers.16
There is “a lot of exciting new evidence emerging about ctDNA,” said George Chang, MD, of the University of Texas MD Anderson Cancer Center in Houston, who co-chaired the ASCO GI session in which Dr Andersen and Dr Tie made their presentations.17
Dr Chang added, however, that more information is needed before ctDNA can be used in clinical practice.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.
1. Kotani D, Oki E, Nakamura Y, et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med. 2023;29:127-134. doi:10.1038/s41591-022-02115-4
2. Tie J. Case discussion: Adjuvant therapy in colon cancer. ASCO GI 2023. January 19-21, 2023.
3. Andersen, CL. Locoregional therapy for oligometastatic disease. ASCO GI 2023. January 19-21, 2023.
4. Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. doi:10.1126/scitranslmed.aaf6219.
5. Tie J, Cohen J, Lahouel K, et al. Circulating tumour DNA (ctDNA) dynamics, CEA and sites of recurrence for the randomised DYNAMIC study: Adjuvant chemotherapy (ACT) guided by ctDNA analysis in stage II colon cancer (CC). ESMO 2022. Abstract 318M0.
6. Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386:2261-2272. doi:10.1056/NEJMoa2200075
7. Øgaard N, Reinert T, Henriksen TV, et al. Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study. Eur J Cancer. 2022;163:163-176. doi:10.1016/j.ejca.2021.12.026
8. Tie J, Wang Y, Cohen J, et al. Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study. PLoS Med. 2021;18(5):e1003620. doi: 10.1371/journal.pmed.1003620
9. Wang D-S, Yang H, Liu X-Y, et al. Dynamic monitoring of circulating tumor DNA to predict prognosis and efficacy of adjuvant chemotherapy after resection of colorectal liver metastases. Theranostics. 2021;11(14):7018-7028. doi:10.7150/thno.59644
10. Reinert T, Skindhøj Petersen LM, Henriksen TV, et al. Circulating tumor DNA for prognosis assessment and postoperative management after curative-intent resection of colorectal liver metastases. Int J Cancer. 2022;150(9):1537-1548. doi:10.1002/ijc.33924
11. Nishioka Y, Chun YS, Overman MJ, et al. Effect of co-mutation of RAS and TP53 on postoperative ctDNA detection and early recurrence after hepatectomy for colorectal liver metastases. J Am Coll Surg. 2022;234(4):474-483. doi:10.1097/XCS.0000000000000093.
12. Marmorino F, Prisciandaro M, Giordano M, et al. Circulating tumor DNA as a marker of minimal residual disease after radical resection of colorectal liver metastases. JCO Precis Oncol. 2022;6:e2200244. doi:10.1200/PO.22.00244
13. Newhook TE, Overman MJ, Chund YS, et al. Prospective study of perioperative circulating tumor dna dynamics in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2022 Jul 6;10.1097/SLA.0000000000005461. doi:10.1097/SLA.0000000000005461.
14. Cohen SA, Kasi PM, Aushev VN, et al. Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I-III colorectal cancer. ASCO GI 2023. January 19-21, 2023. Abstract 5.
15. Henriksen TV, Reinert T, Christensen E, et al. The effect of surgical trauma on circulating free DNA levels in cancer patients- implications for studies of circulating tumor DNA. Mol Oncol. 2020;14(8):1670-1679. doi:10.1002/1878-0261.12729
16. Montagut C and Vidal J. Liquid biopsy for precision adjuvant chemotherapy in colon cancer. N Engl J Med. 2022;386:2330-2331. doi:10.1056/NEJMe2204625
17. Circulating tumor DNA: Prime time or jumping too soon? ASCO GI 2023. January 19-21, 2023.