Biological mechanisms of normal tissue damage: Importance for the design of NTCP models.
ABSTRACT The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited. This paper examines the radiobiological mechanisms underlying the most important complications induced by radiotherapy, with the aim of identifying the essential parameters and functional relationships needed for effective predictive NTCP models. The clinical features of the complications are identified and reduced as much as possible into component parts. In a second step, experimental and clinical data are considered in order to identify the gross anatomical structures involved, and which dose distributions lead to these complications. Finally, the pathogenic pathways and cellular and more specific anatomical parameters that have to be considered in this pathway are determined. This analysis is carried out for some of the most critical organs and sites in radiotherapy, i.e. spinal cord, lung, rectum, oropharynx and heart. Signs and symptoms of severe late normal tissue complications present a very variable picture in the different organs at risk. Only in rare instances is the entire organ the critical target which elicits the particular complication. Moreover, the biological mechanisms that are involved in the pathogenesis differ between the different complications, even in the same organ. Different mechanisms are likely to be related to different shapes of dose effect relationships and different relationships between dose per fraction, dose rate, and overall treatment time and effects. There is good reason to conclude that each type of late complication after radiotherapy depends on its own specific mechanism which is triggered by the radiation exposure of particular structures or sub-volumes of (or related to) the respective organ at risk. Hence each complication will need the development of an NTCP model designed to accommodate this structure.
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ABSTRACT: Background. The percentage of people living with a diagnosis of cancer is rising globally. Between 20% and 25% of people treated for cancer experience a consequence of cancer which has an adverse impact on the quality of their life. Gastrointestinal (GI) symptoms are the most common of all consequences of cancer treatment and have the greatest impact on daily activity. Pathophysiology of long-term bowel damage after pelvic radiotherapy. Long-term damage to the bowel after radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of radiotherapy causes a series of repetitive injuries to the intestinal tissue resulting in an altered healing process, which affects the integrity of the repair and changes the architecture of the bowel wall. The nature of GI symptoms that develop. Patient-reported outcome measures show that diarrhoea, urgency, increased bowel frequency, tenesmus and flatulence are the five most prevalent GI symptoms with a moderate or severe impact on patients' daily lives after treatment with pelvic radiotherapy. Many patients also experience fatigue, urinary problems and have sexual concerns. Systematic assessment and management. The complex nature of those symptoms warrants systematic assessment and management. The use of a tested algorithm can assist in achieving this. The most common contributing factors to ongoing bowel problems after pelvic radiotherapy are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic insufficiency, rectal bleeding and its impact on bone health. The wider context. Symptom burden, socio-psychosocial impact, memory and cognitive function, fatigue, urinary problems and sexual concerns need to be taken into account when thinking about consequences of cancer treatment. Conclusion. As our understanding of consequences of cancer treatments continues to emerge and encompass a wide variety of specialties, a holistic, multifaceted and multidisciplinary approach is required to manage those consequences long-term.Acta oncologica (Stockholm, Sweden) 01/2014; · 2.27 Impact Factor
- Acta oncologica (Stockholm, Sweden) 05/2014; 53(5):577-9. · 2.27 Impact Factor
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ABSTRACT: Decision Support Systems, based on statistical prediction models, have the potential to change the way medicine is being practiced, but their application is currently hampered by the astonishing lack of impact studies. Showing the theoretical benefit of using these models could stimulate conductance of such studies. In addition, it would pave the way for developing more advanced models, based on genomics, proteomics and imaging information, to further improve the performance of the models.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 05/2014;