Squamous cell carcinomas of the upper aero-digestive tract (SCC-UADT) represent the seventh cause of cancer and affect approximately 600,000 patients per year worldwide. The majority of UADT cancers are diagnosed at an advanced stage (70.3% at stage III and IV) and less than 60% of these patients are free of the disease at 3 years, despite aggressive multimodal local treatment by surgery and /or radiochemotherapy. The average progression-free survival (PFS) at 2 years varies between 45 and 60% depending on the studies. Tumor recurrence is most often incurable. To our knowledge, no study has demonstrated the benefit of early evaluation of the rate of decrease in ctDNA at 1 month after the end of radiotherapy alone or associated with concomitant treatment, as a predictive factor of PFS in UADT squamous cell carcinomas regardless of their HPV status. The main objective of this study is to evaluate the value of measuring the quantity of circulating tumor DNA (ctDNA) at 1 month post-treatment as a predictive factor for PFS at 24 months.

This is a prospective, multicenter cohort study carried out on a total of 188 patients suffering from non-metastatic stage III and IV SCC-UADT (oral cavity, larynx, oropharynx, hypopharynx, maxillary sinus), naïve to any treatment during a consultation or day hospitalization during the radiotherapy consultation.

The objective of the study is to evaluate the value of measuring the quantity of circulating tumor DNA (ctDNA) at 1 month post-treatment as a predictive factor for PFS at 24 months. This objective will be achieved by quantitatively measuring the number of copies of methylated ctDNA of genes of interest per mL of plasma; This measurement of ctDNA will be evaluated by the rate of decrease in ctDNA between the centering scanner sample and 1 month post-treatment. Two groups will be then considered: patients with a reduction ≥ 85% and those with a reduction < 85%.

In addition, the interest of measuring the quantity of ctDNA at 1 month post-treatment as a predictive factor of overall survival (OS) and specific survival (SS) at 24 months, the kinetics of the evolution of the quantities of ctDNA during the treatment and during follow-up up to 24 months and the evolution of ctDNA quantities during treatment and follow-up as a predictive factor for PFS and OS at 24 months will also be evaluated during this study. . The analyzes will be carried out in subgroups of populations according to their p16 status (HPV viral protein) and according to the presence or absence of concomitant treatment (Cisplatin or Cetuximab).

Inclusion Criteria

• OMS 0 to 2;
• Patient suffering from UADT squamous cell carcinoma, newly diagnosed and histologically proven, regardless of the p16 protein status, naïve to any treatment for this cancer;
• Non-metastatic cancer of stages III (N1), IVa (N1 minimum) or IVb;
• Cancer localized in the oral cavity, larynx, oropharynx, hypopharynx and maxillary sinus;
• Patient for whom treatment with curative radiotherapy associated or not with concomitant treatment (Cisplatin or Cetuximab) has been validated in a multidisciplinary consultation meeting (RCP);
• Patient capable and willing to follow all study procedures in accordance with the protocol;
• Patient having understood, signed and dated the consent form communicated on the day of inclusion;
• Patient affiliated to the social security system.

Exclusion Criteria:

• Minor patient;
• Cancer located in the cavum, ethmoidal sinus, salivary glands and skin (cutaneous squamous cell carcinoma);
• Patient already treated for UADT tumor;
• Patient treated with immunotherapy;
• Patient who has already had cancer within 5 years (cancer other than in the UADT sphere);
• OMS > 2;
• Contraindication to radiotherapy treatment associated or not with concomitant treatment;
• Patient already included in another therapeutic trial;
• Metastatic disease (stage IVc);
• Pregnant woman, who may be pregnant, or currently breastfeeding;
• Persons deprived of liberty or under guardianship (including curatorship).

The investigator centers responded to a feasibility questionnaire. After their agreement, they have access to the protocol, the synopsis and all the study documents as well as the eCRF for data entry.