<p>Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies.</p><p>Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment.</p><p>Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV.</p><p>Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.</p>

Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies. Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment. Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV. Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.

Radiofrequency ablation (RFA) is a clinic tool for the treatment of various target tissues. However, one of the major limitations with RFA is the ‘small’ size of target tissues that can be effectively ablated. By small it is meant the size of the target tissue is less than 3 cm in diameter of the tissue otherwise ‘large’ size of tissue in this thesis. A typical problem with RFA for large target tissue is the incompleteness of tumour ablation, which is an important reason for tumour recurring. It is widely agreed that two reasons are responsible for the tumour recurring: (1) the tissue charring and (2) the ‘heat-sink’ effect of large blood vessels (i.e. ≥3 mm in diameter). This thesis study was motivated to more quantitatively understand tissue charring during the RFA procedure and to develop solutions to increase the size of target tissues to be ablated. The thesis study mainly performed three tasks: (1) evaluation of the existing devices and protocols to give a clear understanding of the state of arts of RFA devices in clinic, (2) development of an accurate mathematical model for the RFA procedure to enable a more quantitative understanding of the small target tissue size problem, and (3) development of a new protocol based on the existing device to increase the size of target tissues to be ablated based on the knowledge acquired from (1) and (2). In (1), a design theory called axiomatic design theory (ADT) was applied in order to make the evaluation more objective. In (2), a two-compartment finite element model was developed and verified with in vitro experiments, where liver tissue was taken and a custom-made RFA system was employed; after that, three most commonly used internally cooled RFA systems (constant, pulsed, and temperature-controlled) were employed to demonstrate the maximum size of tumour that can be ablated. In (3) a novel feedback temperature-controlled RFA protocol was proposed to overcome the small target tissue size problem, which includes (a) the judicious selection of control areas and target control temperatures and (b) the use of the tissue temperature instead of electrode tip temperature as a feedback for control. The conclusions that can be drawn from this thesis are given as follows: (1) the decoupled design in the current RFA systems can be a critical reason for the incomplete target tissue necrosis (TTN), (2) using both the constant RFA and pulsed RFA, the largest TTN can be achieved at the maximum voltage applied (MVA) without the roll-off occurrence. Furthermore, the largest TTN sizes for both constant RFA and pulsed RFA are all less than 3 cm in diameter, (3) for target tissues of different sizes, the MVA without the roll-off occurrence is different and it decreases with increase of the target tissue size, (4) the largest TTN achieved by using temperature-controlled RFA under the current commercial protocol is still smaller 3 cm in diameter, and (5) the TTN with and over 3 cm in diameter can be obtained by using temperature-controlled RFA under a new protocol developed in this thesis study, in which the temperature of target tissue around the middle part of electrode is controlled at 90 ℃ for a standard ablation time (i.e. 720 s). There are a couple of contributions with this thesis. First, the underlying reason of the incomplete TTN of the current commercially available RFA systems was found, which is their inadequate design (i.e. decoupled design). This will help to give a guideline in RFA device design or improvement in the future. Second, the thesis has mathematically proved the empirical conclusion in clinic that the limit size of target tissue using the current RFA systems is 3 cm in diameter. This has advanced our understanding of the limit of the RFA technology in general. Third, the novel protocol proposed by the thesis is promising to increase the size of TTN with RFA technology by about 30%. The new protocol also reveals a very complex thermal control problem in the context of human tissues, and solving this problem effectively gives implication to similar problems in other thermal-based tumour ablation processes.