866P - Prognostic performance of a genome-wide methylome enrichment platform in head and neck cancer

Background

The utilization of plasma-based tests to quantify circulating tumor DNA (ctDNA) is emerging as a promising new approach to cancer management. ctDNA quantification can be used to assess prognosis and to detect minimal residual disease following initial treatment. Here we demonstrate the feasibility of using a tumor-uninformed genome-wide methylome enrichment platform for ctDNA quantification and prognostic prediction in head and neck cancer.

Methods

Biobanked pre-treatment samples from individuals with newly diagnosed stage I-IV head and neck cancer (University Health Network) were analyzed with a bisulfite-free, non-degradative genome-wide DNA methylation enrichment platform using 5-10 ng of cell-free DNA isolated from plasma. ctDNA was quantified from average normalized counts across informative regions. Events were defined as recurrence or progression. A ctDNA quantity threshold was set such that 95% of samples without an event fell below the threshold (i.e. 95% specificity). Time to recurrence or progression event was compared for samples with ctDNA quantities above the threshold to those below the threshold.

Results

Among 93 samples included (7 stage I, 17 stage II, 23 stage III, 46 stage IV), the median follow-up time was 50.6 months, with 25 events. The likelihood of recurrence or progression was significantly higher in samples with ctDNA above the threshold [hazard ratio (HR) 3.18 (95% CI 1.09, 9.28), log-rank P=0.026]. In multivariate analysis accounting for cancer stage and clinical characteristics (sex, age, smoking history, BMI), ctDNA quantification above the threshold showed a similar association [HR 3.51 (95% CI 1.1, 11.19), P=0.034].

Conclusions

This analysis demonstrates the feasibility of using a blood-based, tumor-uninformed genome-wide methylome enrichment platform for ctDNA quantification and prognostic prediction in head and neck cancer, using treatment-naïve plasma samples. Future studies in post-treatment and longitudinal samples will be required to evaluate the utility of this genome-wide methylome enrichment platform for cancer management applications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Adela, Inc.

Funding

Adela, Inc.

Disclosure

G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Novartis, Lilly, Pfizer, Merck, EMD Serono, Jazz, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Takeda, AstraZeneca, EMD Serono. J. Zhang: Financial Interests, Personal, Full or part-time Employment: Adela, GRAIL; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Illumina. O. Hall: Financial Interests, Personal, Full or part-time Employment: Adela, RAND Corporation, Standard of Proof; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: GSK, Haleon PLC ADR, Merck, Organon and Co, Williams Company. J. Bergener: Financial Interests, Personal, Full or part-time Employment: Adela; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Institutional, Other, Patents associated with cfMeDIP-seq technology: Adela. Y. Wang: Financial Interests, Personal, Full or part-time Employment: Adela; Financial Interests, Personal, Stocks/Shares: Adela. B. Brown: Financial Interests, Personal, Other, Consultant: Pattern Biosciences, NAMSA; Financial Interests, Personal, Full or part-time Employment: Adela Bio, Natera, Talis Biomedical; Financial Interests, Personal, Stocks/Shares: Adela Bio. J. Min: Financial Interests, Personal, Full or part-time Employment: Adela, Guardant Health; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Guardant Health. S.Y. Shen: Financial Interests, Personal, Full or part-time Employment: Adela; Financial Interests, Personal, Stocks/Shares: Adela; Financial Interests, Institutional, Other, Patents associated with cfMeDIP-seq technology: Adela. A. Polio: Financial Interests, Personal, Full or part-time Employment: Adela; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Oyster Point Pharma . E. Sosa: Financial Interests, Personal, Full or part-time Employment: Adela, GRAIL; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Illumina. S. Bratman: Financial Interests, Personal, Full or part-time Employment: Adela; Non-Financial Interests, Personal, Officer: Adela; Non-Financial Interests, Personal, Member of Board of Directors: Adela; Financial Interests, Personal, Ownership Interest: Adela; Financial Interests, Personal, Royalties: Roche. B. Allen: Financial Interests, Personal, Full or part-time Employment: Adela, GRAIL; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Illumina. K. Brown: Financial Interests, Personal, Full or part-time Employment: Adela, Inc., Myriad Genetics; Financial Interests, Personal, Stocks/Shares: Myriad Genetics; Financial Interests, Personal, Other, Stock Options: Adela, Inc.. A. Licon: Financial Interests, Personal, Full or part-time Employment: Adela, Invitae; Financial Interests, Personal, Stocks/Shares, Stock Options: Adela; Financial Interests, Personal, Stocks/Shares: Invitae. A. Hartman: Financial Interests, Personal, Full or part-time Employment: Adela; Non-Financial Interests, Personal, Officer: Adela; Financial Interests, Personal, Ownership Interest: Adela; Financial Interests, Personal, Stocks/Shares: Delfi, Mirvie. D.D. De Carvalho: Financial Interests, Personal, Full or part-time Employment: Adela; Non-Financial Interests, Personal, Officer: Adela; Financial Interests, Personal, Ownership Interest: Adela; Non-Financial Interests, Institutional, Other, Patents associated with cfMeDIP-seq technology: Adela. B. Ho Park: Financial Interests, Personal, Royalties: Horizon Discovery LTD; Financial Interests, Personal, Advisory Board: Jansen, Guardant Health, Jackson Laboratories, Hologics, Caris; Financial Interests, Personal, Ownership Interest: Celcuity; Non-Financial Interests, Personal and Institutional, Advisory Board: Tempus; Financial Interests, Institutional, Sponsor/Funding: GE Healthcare, Lilly, Pfizer. All other authors have declared no conflicts of interest.