864P - Serial cell-free tumor DNA in prognosing survival in patients with head and neck squamous cell carcinoma treated with upfront surgery

Background

Cell-free tumor DNA (ctDNA) is an emerging biomarker in head and neck squamous cell carcinoma (HNSCC) that noninvasively provides molecular information and may allow for more accurate disease staging, risk stratification and early relapse detection through minimal residual disease assessment. We investigated the prognostic value of serial ctDNA in patients with HNSCC treated with upfront surgery.

Methods

Forty-one HNSCC patients treated with curative-intent surgery from the SCANDARE cohort (NCT03017573) were evaluated for longitudinal ctDNA-based NGS. Personalized dedicated NGS panels (OncoFOLLOW) were designed to detect up to 60 somatic variants. Twenty-one/41 patients (51%) received adjuvant (chemo)radiotherapy, and 31/41 patients (76%) experienced recurrence. Serial plasma samples were collected from 41 patients at surgery, 36 patients within a median time of 3.3 weeks after surgery (range, 1-19 weeks), 20 patients at six months, and 22 patients at recurrence. Results of serial ctDNA analyses were correlated with progression-free survival (PFS) and overall survival (OS).

Results

ctDNA was detected at surgery (n = 21/41; 51%), within 1-19 weeks after surgery (n = 15/36; 42%), at six months (n = 6/20; 30%), and at recurrence (n = 15/22; 68%). Recurrence occurred in 15 cases (including four patients [27%] who did not receive adjuvant therapy) with detected ctDNA within 1-19 weeks after surgery. Detection of ctDNA within 1-19 weeks after surgery was associated with shorter PFS (HR = 3.5; 95% CI, 1.5-7.8; P = 0.003) and OS (HR = 3.0; 95% CI, 1.0-9.3; P = 0.05) in univariate but not in multivariate analysis. Detection of ctDNA at six months correlated with poorer PFS (but not OS) in univariate (HR = 8.9; 95% CI, 2.2-37.0; P = 0.003) and multivariate (HR = 30.7; 95% CI, 2.6-370.8; P = 0.007) analyses. In addition, we found that ctDNA positivity at surgery correlated with poorer OS (but not PFS) in univariate but not in multivariate analysis (HR = 3.4; 95% CI, 1.1-11.3; P = 0.04).

Conclusions

Serial ctDNA analyses at surgery and in the postoperative setting had a strong prognostic value. Early detection of ctDNA after surgery might be of interest to stratify HNSCC patients for adjuvant therapy when treated with upfront surgery.

Clinical trial identification

NCT03017573 SCANDARE.

Editorial acknowledgement

Legal entity responsible for the study

C. Le Tourneau.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.