Comparison of Adaptive Dose Painting by Numbers With Standard Radiotherapy for Head and Neck Cancer.

Study Overview
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Brief Summary
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The investigators hypothesize that treatment adaptation to biological and anatomical changes, occurring during treatment, can increase the chance of cure at minimized or equal radiation-induced toxicity in head and neck cancer patients. This trial compares standard intensity-modulated radiotherapy (IMRT), using only pre-treatment planning 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to adaptive 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography voxel intensity based IMRT or volumetric-modulated arc therapy (VMAT) using repetitive per-treatment planning 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography for head and neck cancer.

Official Title
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A Two-arm Phase II Randomized Study, Comparing Adaptive Biological Imaging - Voxel Intensity - Based Radiotherapy (Adaptive Dose Escalation) Versus Standard Radiotherapy for Head and Neck Cancer.

Conditions
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Primary Non-operated Squamous Cell Carcinoma of Oral Cavity, Primary Non-operated Squamous Cell Carcinoma of Oropharynx, Primary Non-operated Squamous Cell Carcinoma of Hypopharynx, Primary Non-operated Squamous Cell Carcinoma of Larynx

Intervention / Treatment
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* Radiation: Adaptive dose-painting-by-numbers
* Radiation: standard intensity-modulated radiotherapy (IMRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell carcinoma of oral cavity, oropharynx, hypopharynx or larynx Primary unresectable tumor and/or patients that refused surgery Stages T1-4; T3-4 N0 or T(any) N1-3 for glottic cancer Multidisciplinary decision of curative radiotherapy or radiochemotherapy Karnofsky performance status >= 70 % Age >= 18 years old Informed consent obtained, signed and dated before specific protocol procedures Exclusion Criteria: High risk Human Papilloma Virus (HPV) Treatment combined with brachytherapy Prior irradiation to the head and neck region History of prior malignancies, except for cured non-melanoma skin cancer, curatively treated in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years. Distant metastases Pregnant or lactating women Creatinine clearance (Cockcroft-Gault) =< 60 mL/min Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: adaptive DPBN<br>This patient group will be treated by adaptive dose-painting-by-numbers, while patients in the control arm will receive standard treatment. Patients will have a 50 % chance of being allocated to the experimental arm and a 50 % chance of being allocated to the control arm. | Radiation: Adaptive dose-painting-by-numbers<br>* Adaptive dose escalation by dose-painting-by-numbers.<br>|
| Active Comparator: standard IMRT<br>This patient group will be treated by standard intensity-modulated radiotherapy (IMRT), while patients in the experimental arm will receive adaptive dose-painting-by-numbers. Patients will have a 50 % chance of being allocated to the experimental arm and a 50 % chance of being allocated to the control arm. | Radiation: standard intensity-modulated radiotherapy (IMRT)<br>* Standard radiotherapy for head and neck cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To obtain 25 % increase in local control at 1 year with adaptive dose escalation comparing to standard treatment. | 18F-FDG-PET/CT scans will be performed. | at 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional (elective neck) and distant control. | 18F-FDG-PET/CT scans will be performed. | after 1 year | 
| Topography of local and/or regional relapse. | 18F-FDG-PET/CT scans will be performed during the first year post-treatment time point of local and/or regional relapse | during the first year post-treatment | 
| Tumor response | 18F-FDG-PET/CT scans will be performed | 3 months post-treatment | 
| Acute toxicity |  | up to 12 months of follow-up | 
| Overall disease-specific, disease-free survival. |  | at 1 year | 
| Late toxicity |  | up to 12 months of follow-up | 
| Time point of local and/or regional relapse. | 18F-FDG-PET/CT scans will be performed. | during the first year post-treatment |