Head-and-neck Cancer
Conditions
Keywords
Proton radiotherapy, DAHANCA
Brief summary
Patients with squamous cell carcinoma of the pharynx or larynx and an anticipated benefit of proton radiotherapy in reducing the risk of late dysphagia or xerostomia are randomized to proton or photon radiotherapy (2:1)
Detailed description
DAHANCA 35 is two parallel conducted, but separate randomized studies, within the same trial (DAHANCA 35D and DAHANCA 35X) by the Danish Head-Neck Cancer Study Group (DAHANCA). In patients with squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy a proton and a photon doseplan is prepared. If proton radiotherapy reduces the anticipated absolute risk of dysphagia \>= grade 2 (DAHANCA scale, DAHANCA 35D) or severe xerostomia \>= grade 4 (EORTC Head-Neck 35, DAHANCA 35X) more than 5%, the patient is randomised to either proton therapy or photon therapy, 2:1. The anticipated risk of xerostomia and dysphagia is estimated using Normal-Tissue Complication Models (NTCP). Patient are analysed according to the primary endpoint (dysphagia and/or xerostomia) after which they were enrolled. DAHANCA 35D is expected to enroll 360 patients and DAHANCA 35X 240 patients (in total 600 patients).
Interventions
RADIATIONProton radiotherapy
Proton radiotherapy
RADIATIONPhoton radiotherapy
Photon radiotherapy
Sponsors
The Novo Nordic Foundation
Danish Head and Neck Cancer Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically proven squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy with curative intent * A predicted clinical significant reduction in the risk of any of the two primary endpoints (\>= grade 2 observer-rated dysphagia or grade 4 patient-reported xerostomia) after proton therapy compared to photon therapy based on comparison of the individual patient dose plans * No current or earlier malignancies, which may influence treatment, evaluation or outcome of the head-neck cancer * Informed consent as required by law * Above 18 years of age
Exclusion criteria
* Patient with cancers of the glottic larynx (stage I/II), skull base, sino-nasal area, unknown primary tumor and prior malignancies. * Patients with contraindications for proton therapy. Per October 2020, this includes pacemakers, implanted defibrillators and tracheostomy * Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic * Distant metastasis * Previous radiotherapy of the head and neck * Previous surgery for the primary cancer with curative intent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dysphagia >= grade 2 | Six months after end of radiotherapy | The rate of observer-reported dysphagia \>= grade 2 measured by the DAHANCA late toxicity score (grade 0-4, with 0 being best) |
| Xerostomia = grade 4 | Six months after end of radiotherapy | The rate of patient-reported xerostomia measured by the EORTC Quality of life questionnaire (QLQ) Head-Neck (HN) 35 (grade 1-4, with 1 being best) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Loco-regional tumor control | Up to five years after end of radiotherapy | Time to event of local-regional failure, from date of randomization to the date of first documented loco-regional failure. Rates are estimated by the Kaplan-Meier method. Interim analyses after 100, 200 and 300 patients. Will not be reported before the primary endpoint. |
| Overall survival | Up to five years after end of radiotherapy | From date of randomisation to date of death |
| Number of participants with disease-free survival | Up to five years after end of radiotherapy | From date of randomization to date of death (all causes), loco-regional failure or distant failure, whichever comes first |
| Disease-specific survival | Up to five years after end of radiotherapy | From date of randomization to date of death (by loco-regional or distant failure) |
| Acute toxicity | From the beginning of and up to two months after end of radiotherapy | DAHANCA acute toxicity score (grade 0-4, 0 being best) |
| Stimulated whole-mouth salivary flow | Up to five years after end of radiotherapy | Stimulated whole-mouth salivary flow |
| EORTC QLQ-Head-Neck 35 | Up to ten years after end of radiotherapy | Swallowing and social-eating scale and specific HN35 items related to eating and pain (grade 1-4, 1 being best) |
| EORTC C30 | Up to ten years after end of radiotherapy | Specific C30 items related to fatigue, nausea and vomiting (grade 1-4, 1 being best) |
| MD Anderson Dysphagia Index | Up to ten years after end of radiotherapy | MD Anderson Dysphagia Index (MDADI) (grade 1-5, 1 being best) |
| EuroQol Five Dimension Scale (EQ-5D) | Up to ten years after end of radiotherapy | Quality-adjusted life-years |
| Composite time corrected toxicity score (CTCT) | Up to five years after end of radiotherapy | The sum of the time corrected dysphagia score and the time corrected xerostomia score normalised to maximum score across all days using EORTC QLQ-Head-Neck 35. The measure is unit-less. |
| Late toxicity | From two months to five years after end of radiotherapy | DAHANCA late toxicity score (grade 0-4, 0 being best) |
| Modified barium swallowing | One year after end of radiotherapy | Functional swallowing test - DIGEST scale (grade 0-4, 0 being best) |
Countries
Denmark
Contacts
Primary ContactJeppe Friborg, MD, PhD
Backup ContactKenneth Jensen, MD, PhD
Outcome results
None listed