Using ctDNA to Predict Cancer Recurrence and Guide Therapy Selection

The ctDNA testing method demonstrated 93% sensitivity for relapse detection at variant allele frequencies of 0.1% and above, the authors reported, with no false positives in the control group. This meant that 2 or more SNVs were detected in 13 of the 14 patients with confirmed NSCLC relapse either before, or at the point of, clinical relapse. Significantly, the patient-specific technology identified 43% more early-stage lung cancer cases than a generic ctDNA assay panel,⁴ and identified recurrence up to approximately 11 months ahead of standard imaging.³

In addition to the longer lead times for predicting disease recurrence, the authors wrote, the personalized ctDNA assay could help practitioners better cater adjuvant therapy to the individual, and help drug makers create more effective treatments.

Adjuvant platinum-based chemotherapy only improves postsurgery cure rates by 5% and causes acute toxicities in 20% of patients, the authors stated.  Thus, they concluded:

“Bespoke ctDNA profiling can characterize the subclonal dynamics of relapsing NSCLC and identify adjuvant chemotherapy resistance. These findings indicate that drug development guided by ctDNA platforms to identify residual disease, define adjuvant treatment response, and target emerging subclones before clinical recurrence in NSCLC is now feasible.”⁴

Now that an increasing number of studies are finding similar results in an expanding range of cancers, researchers say they also foresee a time when ctDNA analysis could be used regularly to guide treatment decisions.

“Ultimately,” they remarked, “ctDNA analysis could be incorporated into routine follow-up for early detection of relapse and consequently potentially earlier initiation of alternate treatment such as immunotherapy.”²

References

1. Natera and Fox Chase Cancer Center to collaborate on kidney cancer study [press release]. http://investor.natera.com/phoenix.zhtml?c=254055&p=irol-newsArticle_print&ID=2363785. Published August 15, 2018. Accessed October 16, 2018.
2. Birkenkamp-Demtröder K, Christensen E, Sharma S, et al. Sequencing of plasma cfDNA from patients with locally advanced bladder cancer for surveillance and therapeutic efficacy monitoring. Poster presented at: the American Association for Cancer Research Annual Meeting; April 17, 2018: Chicago, IL. Abstract 3653.
3. Reinert T, Henriksen TV, Rasmussen MH, et al. Personalized circulating tumor DNA analysis to monitor colorectal cancer. Poster presented at: the American Association for Cancer Research Annual Meeting; April 17, 2018: Chicago, IL. Abstract 1590.
4. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446-451.