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.
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
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)
Single group
Blood sample
Biological/VaccineThe intervention consist in a blood sample that will be taken twice : * at the inclusion (before treatment) * 3 months after the radiochemotherapy in case of incomplete response (PET-CT)
Rate of patients with incomplete cervical lymph node response on PET-CT after radiochemotherapy having circulating DNA (cDNA)
Presence/absence of circulating DNA after treatment versus presence/absence of residual disease
cDNA detection rate among patients with residual adenomegaly after treatment
The detection of cDNA and response on CT-Scan will be compared
Assessment of the prognostic value of cDNA detection 3 months after the end of radiochemotherapy for patients with residual adenomegaly
Evaluated by overall and progression-free survival
Assessment of the prognosis value of the presence of residual adenomegaly
Evaluated by overall and progression-free survival
Rate of concordance of mutational profiles and Human papillomavirus-high risk (HPV-HR) genotypes between the primary tumor and cDNAs at diagnosis
evaluated the mutational profiles from FFPE block and the inclusion blood sample
Click on the lead sponsor to view all of their trials.
Centre Jean Perrin
Lead sponsor
GIRCI Auvergne Rhone-Alpes
Collaborator
