prediction of residual disease by circulating dna detection after potentiated radiotherapy for locally advanced head and neck cancer

Conditions: Locally Advanced Head and Neck Carcinoma

Summary: sixty percent of newly diagnosed head and neck squamous cell carcinomas (hnsccs) are at a locally advanced (la) stage. depending on tumor site, stage, and resectability, locoregional failure rates can range from 35% to 65%. the persistence of residual disease at the end of treatment is a major prognostic element but is not always reliably assessed by current imaging techniques. up to 40-50% of patients have residual adenomegaly and only 30% have viable disease when further adenectomy is performed. sensitive and reproducible detection of residual disease after treatment is a major challenge in this patient category. 18f-fluorodeoxyglucose (18f-fdg) positron emission tomography-computed tomography (pet/ct) guided surveillance, with a negative predictive value of 95-97%, has proven to be non-inferior to cervical curage in hnsccs with residual adenomegaly. cervical curage is now indicated only if the response assessed by pet-ct is incomplete. nevertheless, the ability of pet-ct to predict treatment failure is unsatisfactory due to a high frequency of false positives, because of inflammatory changes, with a positive predictive value of about 20-50%. circulating tumor dna (ctdna) may provide a more reliable assessment of response to potentiated radiotherapy. liquid biopsy monitoring of response in patients treated with potentiated radiation therapy for locally advanced hnsccs a has been shown to be feasible. in 85% of patients, ctdna is detectable and correlates significantly with tumor volume and response to treatment. in addition, one study showed that post-radiotherapy analysis of circulating hpv16 viral dna (cvdna) in patients with hpv16-related hnsccs complemented pet-ct and helped guide management decisions. hpv16 cvdna and pet-ct have similar negative predictive values, whereas the positive predictive value is higher for hpv16 cvdna (100% versus 50%). nevertheless, current data are insufficient to allow routine use of this marker. this is a multicenter, single arm, open study for patients with a locally advanced head and neck cancer for which a potentiated radiotherapy is indicated.


Eligibility criteria:
inclusion criteria: * age ≥ 18 years and ≤ 80 years * histologically confirmed, never treated squamous cell carcinoma with lymph node involvement * squamous cell carcinoma p16+or p16-, stage iii, iva or ivb, n1 minimum, resectable but not operated or unresectable, with indication for potentiated radiotherapy * oral cavity, oropharynx, hypopharynx or larynx, cervical adenopathies without primary * availability of ffpe samples prior to treatment initiation * detection of circulating dna in the initial blood sample * obtaining informed consent from the patient * affiliation to the french social security system exclusion criteria: * tumor of the nasopharynx, sinuses, nasal cavity, salivary glands or thyroid cancer * treatment by exclusive radiotherapy * contraindication to cervical lymph node dissection * metastatic disease (stage ivc) * previous treatment for head and neck cancer * history of other cancer in the last 3 years (except carcinoma in situ, basal cell skin carcinoma, localized prostate cancer gleason 6) * pregnant or breastfeeding woman * patient under guardianship or curators * psychological disorder (cognitive disorders, vigilance disorders, etc.) or social reasons (deprivation of liberty by judicial or administrative decision) or geographical reasons that could compromise the medical follow-up of the trial or compliance with the treatment