Epidemiology, patterns of care, phase IV

Unique opportunities to conduct national studies based on clinical databases exist in Denmark, and the aim is to use these opportunities to address the use of radiotherapy. 1) Primary radiotherapy of head-neck and lung cancer is intensive and associated with a significant risk of dying shortly after the treatment. To prevent this we will analyze and identify risk factors for early death after radiotherapy on a national scale. 2) Studies suggest that Denmark is the European country with the most radiotherapy resources. It is therefore important to clarify why a proportion of patients still don’t receive radiotherapy as specified by national guidelines. 3) Treatment of non-melanoma skin cancer is the most prevalent cause of superficial radiotherapy in Denmark, however, knowledge of treatment patterns and outcome is absent. A systematic collection of treatment and outcome data on a national scale could guide future treatment and ensure treatment quality.


To quantify and identify risk factors for short-term mortality after curative intended radiotherapy. To estimate the proportion of patients not receiving radiotherapy according to guidelines. To characterize patterns of care in non-melanoma skin cancer radiotherapy.

1. Short-term mortality after primary radiotherapy of head-neck and lung cancer

Locally-advanced head-neck and lung cancer are potentially curable diseases and radiotherapy is the primary treatment in most cases. The treatment of both diseases has been intensified significantly the past decades, and standard treatment in many patients now constitutes concurrent radiation and chemotherapy. There is substantial acute toxicity associated with the treatments and a considerable proportion of early non-cancer death in these patients is due to treatment-related factors. There is concern that this proportion is higher outside the world of clinical trials, but population-based studies of short-term mortality are sparse. 90-day mortality from start of treatment has been proposed as a clinical indicator in radiotherapy delivered in a curative setting, and in series from large institutions considerable variation in mortality following treatment has been observed among the different tumor sites, with head-neck and lung cancer associated with the highest short-term mortality. Identification of groups with a high risk of dying from non-cancer related causes associated with the treatment would enable interventions to improve overall survival without further intensification of treatment.
1.1 Excess mortality in head-neck and lung cancer patients in Denmark will be investigated in a cohort design calculating standardized mortality rations using survival time in the study cohort and mortality rates in the Danish population. For head-neck cancer the data sources would be the DAHANCA database (1991 and onwards). Lung cancer patients undergoing radiotherapy with curative intent will be identified through the seven radiotherapy centers, and included from 2008 and onwards.
1.2 Prognostic markers for short-term mortality will be investigated with the emphasis on head-neck cancer. To facilitate the study we suggest a nested case-control study within the DAHANCA database, using patients dying within six months of radiotherapy as cases, and patients alive as controls. Short-term mortality in lung cancer will also be investigated in a case-control study, using the data generated in 1).
1.3 To identify potential causes of death the prevalence of bacteraemia following radiotherapy will be established. As part of the PERSIMUNE data warehouse, microbiology data from all labs in Denmark since 2010 and the capitol region since 2005 can be accessed (http://www.persimune.dk/How-to-get-involved/PERSIMUNE-data-sources). Head-neck and lung cancer patients undergoing radiotherapy will be identified as described earlier, and the prevalence and spectrum of bacteraemia during and after treatment will be investigated.

2. Utilization of radiotherapy.

The international HERO project point to Denmark as the European country with most radiotherapy resources. Analyses worldwide and in European countries have indicated that not all relevant patients may receive radiotherapy in the curative setting, and despite the abundance of resources in Denmark, it has been estimated that the ratio between the actual and optimal number of patients for radiotherapy is around 75%. In Denmark, well-described treatment guidelines exist for most cancer sites through the DMCGs, and the country can, therefore, serve as an example of patterns-of-care in an ‘ideal’ situation with well-established guidelines and no equipment shortcomings. Using the methodology originally described by Barton we will on a national level explore and analyze the radiotherapy patterns of care in Denmark as described by indications and guidelines, in order to characterize the group of patients not receiving radiotherapy.
Cancer sites with well-established national treatment guidelines will be selected, including head-neck, breast, prostate, gynecological and rectal cancer. The indications for radiotherapy for each cancer site will be derived from the national guidelines. Radiotherapy utilization trees for individual cancer sites will be constructed based upon the treatment recommendations obtained from the treatment guidelines. The proportion of patients for whom radiotherapy would be recommended will be calculated for each cancer site by calculating the frequency of each indication for radiotherapy and then summing the frequencies to give the total optimal rate of use. The overall optimal radiotherapy utilization rate was calculated by summing the optimal utilization rates derived for each cancer site, calculated as a proportion of all cancers.

3. Patterns of use in non-melanoma skin cancer radiotherapy

Non-melanoma skin cancer (NMSC) is the most common malignancy arising in European populations and incidence rates are increasing. Radiotherapy use is spanning from very local, superficial treatment with kilovolt equipment to linac-based photon therapy and skin cancer is among the most common tumors treated with radiotherapy. Despite the high number of patients treated in Denmark, no systematic description of the pattern of care has been performed, and treatment schedules, efficiency, and morbidity are unknown on a national level. A database on NMSC established in 2008 exists, but is focused on the dermatological care and does not contain information on a large number of patients treated in the oncological department.
We propose a one-year prospective registration of all non-melanoma skin cancer patients treated with radiotherapy. The variables recorded include patient- and tumor-specific data, schedule and
outcome. This would enable studies on morbidity and outcome on a national level and could serve as an important step towards systematic, prospectively registration.

Impact, relevance, and ethics

All the described projects are unique in the sense that they include the entire population, and given the scale and timeframe offer opportunities not found elsewhere. The results would be highly relevant from both a clinical and health resource perspective. The studies will not interfere with the treatment of individual patients and permission will be obtained from the Danish Data Protection Agency, RKKP and the National Board of Health.

  • Jens Overgaard


    Aarhus University Hospital
  • Jeppe Friborg

    MD PhD

    Rigshospitalet, Copenhagen
  • Kristian Hastoft Jensen


    Rigshospitalet, Copenhagen