Prediction of Residual Disease by Circulating DNA Detection After Potentiated Radiotherapy for Locally Advanced Head and Neck Cancer (NeckTAR)

Centre Jean Perrin

Status

Enrolling

Conditions

Locally Advanced Head and Neck Carcinoma

Treatments

Biological: Blood sample

Study type

Interventional

Funder types

Other

Identifiers

NCT05710679

2022-A01668-35

Details and patient eligibility

About

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.

Enrollment

63 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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 (N1), IVa or IVb (UICC classification 8th edition), N1 minimum, and oropharyngeal sqamous cell carcinomas p16+ stage I or II, N1 minimum, resectable but not operated or unresectable, with indication for concomitant or sequential radiochemotherapy with induction chemotherapy using Docetaxel, Platinum, 5-Fluorouracil (TPF or modified TPF according to the practices of the investigating centers)
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