Locally Advanced Head and Neck Carcinoma
Conditions
Brief 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.
Interventions
BIOLOGICALBlood sample
The 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)
Sponsors
Centre Jean Perrin
GIRCI Auvergne Rhone-Alpes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Biological samples of patients included in the study (i.e., patients treated with radiochemotherapy for a locally advanced head and neck cancer) will be analysed (Next generation sequencing (NGS)): * At inclusion : a FFPE block + a blood sample to identify tumor specific variants (tcDNA and cvDNA) * 3 months after radiotherapy in case of incomplete response (PET-CT) : a blood sample to search if the tumor specific variants identified before the treatment are found Patients with incomplete response after 3 months radiochemotherapy will undergone a salvage adenectomy. The main objective is to assess the ability of circulating DNA to predict residual disease during salvage adenectomy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients with incomplete cervical lymph node response on PET-CT after radiochemotherapy having circulating DNA (cDNA) | 3 months after potentiated radiotherapy | Presence/absence of circulating DNA after treatment versus presence/absence of residual disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cDNA detection rate among patients with residual adenomegaly after treatment | at three-months after potentiated radiotherapy. | 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 | at three-months after potentiated radiotherapy. | Evaluated by overall and progression-free survival |
| Assessment of the prognosis value of the presence of residual adenomegaly | At month 27 | 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 | Inclusion | evaluated the mutational profiles from FFPE block and the inclusion blood sample |
| Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor | Inclusion | — |
| Test of the concordance between real-time polymerase chain reaction (PCR) and NGS on formalin-fixed paraffin-embedded (FFPE) for simultaneous detection and genotyping of HPV-HR at diagnosis | Inclusion | — |
| Number of patients with ctDNA and cvDNA detection at diagnosis and the clinical, paraclinical and pathological features of the cancer | Through study completion, an average of 66 months | — |
| Evaluation of interobserver reproducibility of the interpretation of SUVmax measurements of residual cervical adenomegaly. | 3 months after potentiated radiotherapy | A centralized review of the PET-CT will be done by the sponsor to evaluate the reproducibility of the interpretation of SUVmax measurements of residual cervixal adenomegaly (pathological/benign/equivocal) |
Countries
France
Contacts
CONTACTAngeline GINZAC COUVÉ, PhD
PRINCIPAL_INVESTIGATORMaureen BERNADACH, MD
Centre Jean Perrin
Outcome results
None listed