Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study.

Background: Induction chemotherapy (IC) followed by chemoradiation (CRT) is one treatment approach for patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV). This pilot study aimed to assess whether a circulating tumor (ct) DNA assay outperforms PET-CT in assessing treatment response in patients with HPV + OPSCC treated with induction chemotherapy (IC) followed by chemoradiation (CRT).

Materials And Methods: Patients treated with IC and definitive CRT for HPV + OPSCC were included. HPV ctDNA and PET-CT were performed pre-treatment, 2-3 weeks after IC and 3 months after CRT. CtDNA levels were correlated with tumor volumes. Post-IC and post- CRT ctDNA levels were correlated post-induction and post-treatment imaging responses.

Results: Seventeen patients were included. Baseline ctDNA levels correlated with volume of primary tumor (R2 = 0.33, p = 0.02), but did not correlate with nodal volumes (R2 = 0.01, p = 0.7) or total disease burden (R2 = 0.02, p = 0.6). After IC, 5.9 % (1/17) of patients had complete response by PET- CT, whereas 52.9 % (9/17) had complete molecular response by ctDNA testing. After completion of CRT, 76.5 % (13/17) patients had complete clinical response to treatment. Of patients who had ctDNA clearance after IC, 88.9 % (8/9) remained disease free after definitive CRT, whereas one had progressive disease diagnosed by both imaging and ctDNA. HPV ctDNA clearance after IC predicted disease control after CRT more strongly than PET-CT IC response (61.5 % (8/13) vs 7.7 % (1/13), p = 0.01).

Conclusions: HPV ctDNA clearance following IC outperforms standard imaging in assessing response and may help identify patients with favorable prognosis.