PhD ceremony Ms. G. Ghobadi: Pathophysiology of thoracic irradiation

PhD ceremony: Ms. G. Ghobadi, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Pathophysiology of thoracic irradiation

Promotor(s): prof. R.P. Coppes, prof. J.A. Langendijk

Faculty: Medical Sciences

Radiation plays an important role in the treatment of thoracic tumors. The efficacy of treatment is limited by the sensitivity of unavoidably co-irradiated healthy tissues. One of the most common life threatening complications is thoracic radiation-induced respiratory dysfunction. For a more efficient thoracic radiotherapy, reduction of the chance of developing this complication is required.

Our preclinical studies showed that thoracic radiation-induced damage to the lung and the heart are very much inter-related and that respiratory dysfunction becomes manifest through physiological changes in the whole cardio-pulmonary system rather than through changes in the lung only. Lung irradiation leading to pulmonary hypertension may originate from vascular remodeling in the whole lung, possibly initiated by global loss of pulmonary endothelial cells preceding parenchymal inflammation. Radiation-induced pulmonary hypertension secondarily impairs left ventricle diastolic function and promoted pulmonary edema. Both mechanisms may contribute to the development of respiratory dysfunction. Criteria for the assessment of clinical respiratory dysfunction are subjective and non-specific. Using objective quantitative parameters, such as Computed Tomography (CT) scans of the lungs, may improve such assessments. We therefore developed a sensitive CT-based tool to assess radiation-induced lung tissue damage which showed to be superior to the previously used methods. The findings of this thesis suggest new considerations to the optimization of thoracic radiotherapy.