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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. Clinical implementation will only be possible with a thorough and stringent Quality Assurance program using in vivo dose reconstruction based on transmission dosimetry during treatment.
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 (n=24) 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, 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 are currently exploring the possible benefits and side effects of ablative stereotactic radiotherapy in a phase II trial and are preparing a phase III trial.
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.