ctDNA points to colon cancer recurrence
medwireNews: Presence of circulating tumour DNA (ctDNA) in post-surgery plasma samples can identify stage II colon cancer patients with a high recurrence risk, indicates research.
Adjuvant treatment decisions in this particular population remain “one of the most challenging areas in colorectal oncology”, explain the study authors. Only a minority of patients defined as high-risk on the basis of clinicopathological factors experience recurrence and the evidence to support the selective treatment of these patients is lacking, they say.
In this study, the researchers used massively parallel sequencing-based assays to detect ctDNA with a tumour-specific mutation from blood samples obtained 4–10 weeks after curative section of stage II colon cancer in 230 patients.
Among 178 patients who did not receive adjuvant chemotherapy, 7.9% were positive for postoperative ctDNA while the remaining 92.1% were negative, report Jeanne Tie (Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia) and colleagues.
Radiological recurrence of disease was documented in 78.6% of the 14 ctDNA-positive patients, but in only 9.8% of the 164 participants without ctDNA in their postoperative plasma sample during a median follow-up of 27 months.
And recurrence-free survival (RFS) was significantly shorter in ctDNA-positive versus negative patients, with a hazard ratio (HR) of 18 for recurrence, and estimated 3-year RFS rates of 0% and 90%, respectively.
As shown by time-dependent receiver operating characteristic curve analysis, postoperative DNA predicted radiological recurrence at 12 months with a sensitivity of 43% and a specificity of 97%. At 36 months the corresponding values were 48% and 100%.
Furthermore, when the 52 participants given adjuvant chemotherapy at the physician’s discretion were considered, being ctDNA-positive immediately after completion of adjuvant chemotherapy was associated with poorer RFS, with a significant HR of 11.
“Whereas histopathologic or molecular characteristics of tumors that are associated with a higher recurrence risk indicate a propensity for metastasis, the presence of circulating DNA molecules containing somatic mutations found in an individual’s tumor is a direct indication that occult tumor cells remain after surgery”, say Tie et al.
And given that ctDNA positivity was associated with an “extremely high risk” of relapse while the lack of the marker signalled a low risk, ctDNA measurements could help to guide adjuvant chemotherapy decision, they conclude in Science Translational Medicine.
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