Oropharyngeal cancer (OPC) is the most common type of head and neck cancer. The current standard treatment for this cancer is radiotherapy (RT) of the tumour and lymph nodes of both sides of the neck, combined with concurrent chemotherapy for advanced stages. Even though a small proportion of patients with this cancer have involvement of the lymph nodes of the neck on the opposite side of the tumour (contralateral involvement) or involvement of the lymph nodes on both sides of the neck (bilateral involvement), bilateral radiotherapy is performed due to the risk of contralateral microscopic involvement, which is invisible on imaging and clinical examination. Bilateral radiotherapy causes more adverse events, leading to a decrease in quality of life. Lymphatic mapping using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging is a technique that visualises the lymphatic drainage of the tumour and thus determines whether radiotherapy should be delivered unilaterally or bilaterally to the lymph nodes. This technique would therefore reduce adverse events and improve quality of life, while maintaining the efficacy of radiotherapy. The goal of the clinical trial SELECT-FR is to investigate if the efficacy of a lymphatic drainage mapping with a SPECT-CT-guided approach is acceptable in terms of two-year Disease Free Survival (DFS) rate in patients with lateralized OPC.
SELECT-FR is a national, randomized, phase II, non-comparative trial. Patients aged 18 or over, with lateralized oropharyngeal squamous cell carcinoma (tonsil, soft palate, pharyngeal wall or tongue base) not involving or crossing midline, Human Papilloma Virus (HPV) positive or negative, T1-T3 with no contralateral nodes or nodes \> 6 cm on Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography-Computed Tomography (PET-CT). Eligible subjects will be randomized at a 1:1 ratio into the experimental and control arms. * Experimental arm: Patients will receive definitive RT to the primary tumour and ipsilateral neck nodes, while contralateral neck RT treatment will be guided by lymphatic mapping with SPECT-CT. * Control arm: Patients will receive definitive RT to the primary tumour and bilateral neck nodes (Note: candidates for standard unilateral neck RT are not eligible). Randomization will be stratified by the following factors: * Anatomical location of primary tumour: lateral vs. intermediate vs. medial. * HPV status (p16 immunohistochemistry) and smoking status: p16 positive ≤ 10 pack year vs. p16 positive \> 10 pack year vs. p16 negative any. * Extent of disease: limited vs. other: * p16 positive: limited \[T1-T2, N0-N1 (single node \< 3cm without radiologic extranodal extension)\] vs. other. * p16 negative: limited \[T1-T2, N0-N1 (without radiologic extranodal extension)\] vs. other. * Use of concurrent systemic therapy: yes vs. no. In both arms, time from randomization to initiation of RT will be no longer than 6 weeks. Patients will receive RT with or without standard concurrent chemotherapy in either standard fractionation (7 weeks) or altered fractionation (6 weeks). In both arms, all patients will be followed by local investigator as follow: * Treatment period: every week. * Follow-up period: every 3 months until 24 months after treatment and then every 6 months until 36 months after treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
128
Lymphatic mapping with SPECT-CT
Patients will receive definitive radiotherapy to the primary tumour and bilateral neck nodes.
Patients will receive definitive radiotherapy to the primary tumour and ipsilateral neck nodes while radiotherapy to the contralateral neck nodes will be guided by lymphatic mapping with SPECT-CT.
CHU Brest
Brest, France
Centre François Baclesse
Caen, France
CHU Caen
Caen, France
Centre Georges François Leclerc
Dijon, France
Centre de Radiothérapie Guillaume Le Conquérant
Le Havre, France
Centre Oscar Lambret
Lille, France
Institut Régional du Cancer de Montpellier
Montpellier, France
Hôpital Tenon
Paris, France
Centre Henri Becquerel
Rouen, France
Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
Strasbourg, France
...and 2 more locations
Two-years Disease Free Survival (DFS) rate
The primary endpoint is 2 year-Disease-Free Survival rate (2y-DFS) defined as patients free of disease at two years. Patients without any event before 2 years will be considered as success, patients lost to follow-up before 2 years will be considered as failure.
Time frame: At 2 years after treatment
Disease free survival
Disease-free survival (DFS) is defined as time from randomization to the date of first record of any of the following events including local, regional, or distant recurrence or death from any cause. DFS will be censored on the date of last visit with disease assessment.
Time frame: From randomization to any of the following events: local, regional, or distant recurrence or death from any cause, up to 3 years after treatment.
Overall survival (OS)
Overall survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The follow-up of subjects still alive will be censored at the date of last visit/contact.
Time frame: From randomization to the date of death from any cause, up to 3 years after treatment.
Isolated Contralateral Neck Failure (iCNF)
Isolated Contralateral Neck Failure (iCNF) is defined as the time from the date of randomization to the date of iCNF. Local ipsilateral neck failure, or distant failure diagnosed concurrently with iCNF or before are not considered events of interest but as competing risks events in the analysis of this endpoint. Subjects without any of the listed events (i.e. events of interest or competing risks events) are censored at the date of the most recent follow-up examination.
Time frame: From randomization to the date of iCNF, up to 3 years after treatment.
Local-regional failure (LRF)
Local-regional failure (LRF) is defined as the time from the date of randomization to the date of any local or regional failure. Distant recurrence/progression diagnosed before local or regional failure are not considered events of interest, but as competing risks events in the analysis of this endpoint. Subjects without any of the listed events (i.e. events of interest or competing risks events) are censored at the date of the most recent follow-up examination.
Time frame: From randomization to the date of any local or regional failure, up to 3 years after treatment.
Distant metastases (DM)
Distant metastases (DM) are defined as clear evidence of distant metastases in the lung, bone, brain, liver or other distant sites. Biopsy is recommended where possible according to local practices. Distant sites can be evaluated by CT scans or PET-CT. Distant metastasis free survival is defined as the time from the date of randomization to the date of distant metastases. All other events are not considered events of interest, but as competing risks events in the analysis of this endpoint.
Time frame: From randomization until clear evidence of distant metastasis, up to 3 years after treatment.
Incidence and Severity of Treatment-Related Adverse Events
Toxicities will be measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0). The NCI-CTCAE is a descriptive terminology which can be used for Adverse Event (AE) reporting and it is widely accepted in the community of oncology research as the leading rating scale for adverse events. A grading (severity) scale is provided for each AE term. This scale is divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death"). Toxicities will be measured by the investigator weekly during Radiotherapy (RT), at 1 month and 3 months after completion of RT to assess acute toxicities and then at each follow up visit following completion of RT to assess late toxicities until 36 months post RT.
Time frame: Throughout study completion, up to 3 years after treatment.
Incidence and Severity of Treatment-Related Adverse Events reported by patients (using items of PRO-CTCAE)
Patient reported toxicities will be evaluated using selected items of the validated Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). It is recognized that clinician-reported adverse events (AEs) may substantially under-report the incidence and severity of symptoms occurring as a consequence of treatment. In response to this awareness, the NCI has developed a set of patient-reported items (called PRO-CTCAE) that complement the CTCAE and capture the patient's perspective on the subjective aspects of adverse events. PRO-CTCAE H\&N information will complement the clinician CTCAE reporting. A collection of 15 specific PRO-CTCAE Head \& Neck (H\&N) items is proposed. Patient reported toxicities will be evaluated at baseline, end of treatment, 12, and 24 months after the end of treatment.
Time frame: Throughout study completion, up to 2 years after treatment.
Gastrostomy tube usage
Gastrostomy tube usage will be assessed for the presence of a gastrostomy tube as well as usage of the gastrostomy tube at each visit until tube removal.
Time frame: Throughout study completion, up to 3 years after treatment.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.