Head and neck cancer

The objective is to develop radiotherapy (RT) to patients with head and neck cancer (HNC) on a biological and physical basis with the aim to deliver RT to the right patients, the right target and with the appropriate dose, fractionation and adjuvant therapy. This will be investigated through national clinical trials with individual patient QA, and prospective collection of all diagnostic, therapeutic and follow up data in the Dahanca database  which is a nationwide clinical quality database that contains prospective data collected since the early 1970s. Our experience will provide support and evidence of the importance of optimal individual RT given to a nationwide cohort of patients with HNC.

Aim

The overall aim of this study is to describe the outcome of the national strategy for multidisciplinary treatment of head and neck cancer in Denmark and to create a basis for clinical trials and treatment recommendations.

Background

Head and neck cancer is a heterogeneous and complex disease entity that includes a variety of tumor sites in the head and neck region, several histology types different with highly variable prognosis. Treatment may be intensive and involves multimodality treatment strategies that have improved cure rates, however also extended recovery and rehabilitation. This calls for a meticulous recording of tumor characteristics, extent of disease, applied treatment modalities, and subsequent outcome, including registration of side-effects which is obtained by reporting to the national clinical DAHANCA quality database.  Outcome has improved substantially over the years, partly due to better treatment as a result of a series of continuous clinical trials and subsequent implementation in our national guidelines. The DAHANCA database has furthermore been used to describe the effect of reduced waiting time, changed epidemiology, and influence of comorbidity and socioeconomic parameters on vital status.
Radiotherapy is prescribed to 70-80 percent of HNC patients, either as the sole treatment, or in conjunction with surgery or chemotherapy. Improvement in outcome is expected to be achieved through a series of clinical trials described below.

Methods

The continuous development and refinement of RT for HNC will happen through a series of nationwide clinical trials, and the results will be implemented in national guidelines, and subsequently the benefit to the full national cohort will be evaluated through patterns of care and phase 4 studies. To facilitate precision medicine will we further identify (biological) predictive parameters for tumor response and normal tissue damage.

All Danish HNC patients should be treated according to evidenced based national guidelines, and treatment and outcome will be recorded in the DAHANCA database. The majority of patients (>80%) with indication for RT will be offered inclusion into a national evidence generating clinical trial. These studies will focus on
1) the interaction between surgery and RT, by exploring the optimal indication for either modality 
2) improved RT of biologically resistant tumors on an individual basis 
3) defining the most appropriate treatment for the large cohort of patients with HPVpos oropharyngeal tumors

These activities currently include:
- Randomized trial of hypoxia-profile guided hypoxic modification of RT of HNC (Dahanca 30)
- Image guided dose-escalated RT to advanced HVPneg HNC (Dahanca 33)
- Randomized trial of Transoral Robotic Surgery vs IMRT for early oropharyngeal carcinoma (Dahanca 34)
- Curatively intended tolerable treatment of borderline palliative patients (national protocol)
- Retreatment of RT-treated patients (national protocol)

The Danish database structure allows epidemiological nationwide cohort studies of the importance of comorbidity and socio-economical factors (ongoing protocols). We will furthermore implement phase 4 studies to evaluate population impact of evidenced-based interventions: Accelerated chemo-radiotherapy, treatment of early glottic cancer, IMRT, hyperfractionation, predictive testing of morbidity, reduced waiting time, etc.

Several projects are ongoing regarding patient-reported outcome (PRO) to define appropriate outcome measures (PROM) and instruments for daily clinical practice, as well as toxicity measures for normal tissue complication probability estimation (NTCP) in collaboration with  the Danish Center for Particle Therapy (Research in Particle Therapy). In this setting, we will established a national dose-plan bank with associated QA evaluation of all patients. We will define dose-response relationships for tumor control and morbidity for various endpoints related to included volume and thereby define indications for proton therapy.

Impact/Relevance/Ethics

The DAHANCA group has been an active and well-established structure for 40 years and has provided a solid foundation for the treatment of head and neck cancer in Denmark with a significant impact, also, on applied treatment strategies and clinical guidelines internationally. Our experimental and clinical results have become recognized throughout the world and DAHANCA stands as one of the major head and neck cancer groups worldwide. The described DAHANCA projects will secure research at the highest international level and allow implementation of head and neck treatment on well-defined criteria and evidence-based knowledge.

  • Eva Samsøe

    Head of Medical Physics, PhD

    Zealand University Hospital, Næstved Sygehus
  • Christian Rønn Hansen

    Radiofysisk Laboratorium og DCPT

    Odense University Hospital
  • Jesper Grau Eriksen

    Professor, overlæge, PhD

    Aarhus University Hospital
  • Morten Horsholt Kristensen

    Reservelæge, PhD-studerende

    Aarhus University Hospital
  • Jens Overgaard

    Professor

    Aarhus University Hospital
  • Jørgen Johansen

    MD, PhD

    Odense University Hospital
  • Maja Bendtsen Sharma

    Physician and PhD student

    Aarhus University Hospital
  • Mette Saksø

    MD

    Aarhus University Hospital