Abstract: The invention is in the art of medical treatments, in particular the treatment of tumors with ionizing radiation. It provides means and methods for predicting whether a subject is likely to develop radiation damage upon radiotherapy. The invention provides tools that allow individualized and optimized radiation treatment of a subject in need of a radiation treatment. The invention also provides methods of determining the risk of developing severe dyspnea after radiation treatment. More in particular, the invention relates to an in vitro method for predicting the risk of developing radiation induced toxicity comprising the steps of obtaining mitochondrial DNA from a sample of a subject, determining the number of non-synonymous variations present in at least one gene encoding a mitochondrial protein, attributing a value to the number of non-synonymous variations, wherein a higher value corresponds to a higher risk of developing radiation induced lung toxicity.