Radiotherapy is not prescribed on the tumor itself, but on a volume surrounding the tumor, which encompasses a 3 dimensional (3D) safety margin. The 3D safety margin ensures a daily coverage of the tumor by a tumoricidal dose of radiation, taking into account setup errors, changes in internal anatomy, such as bladder filling and movements/motion during radiotherapy, such as respiration. But, the 3D safety margin consists by definition of healthy tissue, which is daily intentionally irradiated till high doses. Recent developments in image-guided radiotherapy (IGRT) allow accurate positioning of patients by infrared skinmarks (GPS of the patient), orthogonal scopy & CT scan, thereby reducing the 3D safety margin.
To control the motion of lung- and liver tumors with respiration, radio opaque markers can be implanted in the tumor, the movement of the tumor can be registered as a function of the respiratory cycle, and radiation can be temporary interrupted when the tumor moves outside the radiation field. This “respiratory-gating” technique allows reducing the 3D safety margin, but is patient unfriendly and time consuming. Our department will in the next years develop “tumor tracking”, with the financial support of the “Hercules Stichting”. The VERO system is equipped with a dynamic radiation head, which allows following tumor motion during radiation, minimizing the 3 D safety margin. High precision radiotherapy allows delivering the same radiation schedule with less toxicity and treating patients with more effective treatment schemes, resulting in a comparable local control than surgery in for instance stage I/II lung cancer, prostate cancer and livermetastases.
Stereotactic radiosurgery (SRS) is a well-established technique for the treatment of both benign and malignant lesions of the brain. The concept is defined as a single ablative dose of radiation stereotactically directed to an intracranial region of interest, thereby minimizing exposure to normal healthy tissue and maximizing local control. The requirement for precise localization and immobilization of the targeted lesion classically requires the use of a rigid, invasive stereotactic head-ring. Although this provides high accuracy, the disadvantages of standard invasive head-rings include pain and general discomfort. That is why non-invasive stereotactic systems have been developed. To compensate for the possible accuracy loss of non-invasive techniques, systems were equipped with various forms of image-guided radiotherapy (IGRT) for localization. These imaging modalities apply internal anatomy rather than external landmarks to avoid geographic miss. Our department implemented and validated this “frameless” approach and found that with proper mask immobilization and target localization using stereoscopic x-ray images of the Novalis system (Brainlab AG, Feldkirchen, Germany) comparable treatment accuracy can be achieved as with the invasive head-ring. Clinically, frameless radiosurgery is already performed for brain metastases and will further be implemented for other lesions.
Our department developed a particular interest in the diagnosis and treatment of colorectal cancer. We implemented as first worldwide intensity-modulated and image-guided radiotherapy (IMRT-IGRT) in the preoperative treatment of rectal cancer, on the Tomotherapy Hi Art II system. Our initial experience was summarized in 3 manuscripts and shows that (1) IMRT-IGRT reduces the digestive adverse effects, (2) the use of an integrated megavolt CT-scan allows reducing the 3D safety margin and (3) a simultaneous integrated radiation boost results in a higher metabolic response rate without increased toxicity. Considering these promising results, this phase II study was extended to 108 patients and an international multicentric phase III study is ongoing.
Despite the progress in the systemic treatment of metastatic colorectal cancer, there are no long-term survivors unless the metastases are surgically resected. Numerous patients however do not undergo surgery despite a limited number of metastases, mostly because of comorbidity or the location of their lesions. We recently demonstrated that helical tomotherapy results in a promising disease free survival and low toxicity in patients with oligometastatic colorectal cancer.
Solid tumors have a deficient oxygen supply (hypoxia), since the neovasculature cannot follow the tumor growth and is of poor quality. Oxygen reacts with the DNA radicals that are induced by radiation, leading to fixation of radiation induced DNA damage and mitotic cell death. In the absence of oxygen, tumor cells are 3 times more resistant to radiation. Tumor hypoxia is considered being the single most important cause of clinical radioresistance, and several strategies have been evaluated the last decennia’s. Our research unit developed a strategy to radiosensitize hypoxic tumor cells by nitric oxide (NO), which chemically resembles oxygen and reacts with DNA radicals. Since administration of NO leads to hypotension and shock, we developed protocols for intratumoral production of NO, either by tumor cells, tumor-associated immune cells and hepatocytes. This strategy is currently under evaluation in breast and colorectal cancer models. The department of Medical Imaging and Radiotherapy (BEFY) of the Vrije Universiteit Brussel has one of the few radiobiological research units. With the introduction of high precision radiotherapy and individualized treatment schedules, the clinical relevance of radiobiology and the opportunities for collaborations with the pharmaceutical industry are increasing.