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Soon afterwards, studies were performed in the us, spain and overvecht Germany. Since 1986, iort has been used in clinical studies in the netherlands (Groningen, eindhoven) mainly for colorectal cancer. In many cases, a combination of surgery, external radiotherapy and iort was used. These clinical studies were preceded by extensive animal experiments on the sensitivity of various tissues and organs to a single high dose of radiotherapy. The dog proved to be a reliable and comparable animal model to translate the results to the human situation. . At present, iort is being applied. Gastrointestinal tumours, breast cancer, sarcomas, pancreatic and biliary tumours and head and neck tumours.

Although various studies have indicated a positive effect on survival in gastrointestinal cancer patients, similar effects have not yet been proven at other locations. Well-known problems are the difficulty of setting up prospective randomised trials and the need for multicentre studies: only a few heijn centres are able to apply iort, owing to the need for large infrastructural investments. Chapter 4 describes the current treatment for colorectal liver metastases. The only treatment for liver metastases that has a chance of curing the patient is surgical resection. Increasing experience and improved diagnostics, indications, surgical techniques and perioperative care have resulted in a 5-year survival rate of 21. Nevertheless only 25 of patients with liver metastases are suitable candidates for surgical treatment.

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The liver is composed of connective tissue, blood vessels, bile ducts and specialised cells (hepatocytes) that are responsible for. Removing waste products from the blood and excreting them from the body in the form of bile via the intestines. All these structures have their own individual radio sensitivity. Hepatocytes can be killed directly by irradiation, or they can die during cell division, or die indirectly at a later date as a result of damage to the connective tissue and blood vessels. Particularly regarding the late effects of radiation damage, it is unclear what the influence is of the single high dose used in this study.

In Chapter 3, the development and application of iort are described  iort is the application of a single high dose of (electron) radiation to an operatively exposed tumour or the surgical margins after tumour resection during an elective surgical procedure. Although the biological effectiveness (RBE) of a single does is greater than that of fractionated therapy, the advantages of iort are not so much based on radiobiological principles (see chapter 2) as on physical principles: the irradiation can be applied very accurately and healthy tissues. Iort can also play a role in the treatment of tumour recurrence after conventional radiotherapy, because iort spares earlier irradiated normal 1907, 12 years after the discovery of X-rays, the first description of iort was published in connection with an inoperable stomach tumour. A historical overview is given of the development of radiotherapy from the first treatment for skin diseases with X-rays, to the current wide-ranging applications, such as external radiotherapy with 3-dimensional planning, brachytherapy, radioactive labelled antibodies and iort. It speaks for itself that the results of animal experiments and clinical studies in combination with rapid technological progress have increased the capacity of radiotherapy over the past 100 years. In the period from 1964 to 1976, the first clinical studies were performed in Japan on patients treated with iort.

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The type of tissue also plays an important bestellen role and this chiefly concerns tissue function (read: organ). In addition, attention should be paid to the exposure volume: if even a very small part of the spinal cord is irradiated, total paralysis can occur. In contrast, parenchymal organs such as the liver usually have sufficient remaining capacity. However, radiotherapy after surgical resection might reduce the remaining capacity drastically. Characteristic differences in radio sensitivity exist between normal tissue and tumour tissue. Radiobiology makes use of these differences to kill a maximum number of tumour cells while causing the least possible damage to the healthy tissues. By dividing the total radiation dose into small fractions (fractionation) and by applying the fractions over a number of weeks, the highest possible dose can be given with the smallest possible damage to healthy tissues. Owing to the fact that the iort treatment field does not include online healthy tissues, a high dose can be given in one session.

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The animal model used appeared to be suitable for translation to the oogschaduw human situation. Chapter 2 describes the basic principles of radiobiology. The effect of exposure to radiation depends on the type of radiation (in this study: electrons) and the energy. During the application of radiotherapy, it is necessary to find a balance between fighting the tumour and causing as little damage as possible to the healthy tissues. Each tissue type reacts differently to radiotherapy. In the case of healthy tissues, the response depends strongly on the rate of cell division. The faster a cell divides, the greater its radio sensitivity.


In many of the arts patients who are candidates for surgical resection of the metastases, it is difficult to achieve completely tumour-free excision margins. These patients have the highest risk of tumour recurrence in the liver. With the aid of radiotherapy, it is possible to fight the tumour tissue that is left in situ at the surgical margins. External radiotherapy is laborious owing to the high risk of radiation damage to the liver and other sensitive tissues in the region of the liver, such as the intestines. Intraoperative radiotherapy (iort) comprises the irradiation of the surgical margins with a single high dose of radiation directly following tumour excision. The great advantage of iort is that the radiation dose can be given at precisely the desired location, while shielding any adjacent sensitive structures. Presently, it is not clear how liver tissue reacts to a single high dose of radiation. It is obviously not the intention to seriously damage the remaining liver tissue or cause healing deficits or abscess formation that would threaten organ function. This thesis describes an animal study on the damage that occurs after a single high dose of radiation to normal liver tissue and surgically manipulated liver tissue.

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Summary, chapter 1 describes the aim of the study. In about half of the patients who undergo (successful) surgical treatment for colorectal cancer, metastases to the liver are ontlasting encountered during or after the operation. Application of external radiotherapy or chemotherapy only has a palliative effect, mainly due to the restrictions of side-effects. Newer therapies, such as cryosurgery and brachytherapy, are often applied to inoperable metastases and they appear to have a favourable effect on survival. At present, various treatment options are receiving consideration, such as radiofrequency ablation, laser-induced thermotherapy, gene therapy and monoclonal antibodies with or without radioactive labelling. The only treatment for metastases to the liver that has any chance of curing the patient is surgical resection. About 30 of the patients with metastases are eligible for surgical treatment. Five-year survival in these patients is 30-40.

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