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Evaluation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
Stockholm University, Faculty of Science, Department of Physics. Eduardo Mondlane University, Mozambique.ORCID iD: 0000-0002-9904-7217
Stockholm University, Faculty of Science, Department of Physics.ORCID iD: 0000-0002-1099-733X
Karolinska Institutet, Sweden.
Södersjukhuset, Sweden; Karolinska Institutet, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Radiotherapy of liver metastases is being performed with photon-beam stereotactic body radiation therapy (SBRT). However, the high risk for radiation-induced liver disease (RILD) is the treatment limiting factor. The use of proton beams in these treatments could improve the sparing of the healthy part of the liver. The aim of this study was to evaluate the use of estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD. Methods: Ten liver metastases patients, previously treated with photon-beam radiosurgery, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties) combined with PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V95%>98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCPIMPT - NTCPSBRT) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5 % were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams. Results: For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin, was achieved with the IMPT plans. Mean liver doses larger than the threshold value of 32 Gy led to values of NTCP for RILD exceeding 5 % (7 patients for SBRT and 3 patients for IMPT). ΔNTCP values (RILD) ranging between -98% and -17 % (7 patients) and between 0 % and 2 % (3 patients) were estimated. Conclusions: In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, could be identified. The clinical implementation of such model-based approach to select liver metastases patients to proton therapy needs to be made with caution and considering the uncertainties involved in the NTCP estimations.

Keywords [en]
RILD, liver metastases, SBRT, IMPT, patient selection
National Category
Other Natural Sciences
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-158223OAI: oai:DiVA.org:su-158223DiVA, id: diva2:1235651
Available from: 2018-07-26 Created: 2018-07-26 Last updated: 2018-08-17
In thesis
1. Radiation therapy of upper gastrointestinal cancers with scanned proton beams: A treatment planning study
Open this publication in new window or tab >>Radiation therapy of upper gastrointestinal cancers with scanned proton beams: A treatment planning study
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Proton beam therapy (PBT), using scanned beams, is an emerging modality used for the treatment of cancer. The clinical advantages of PBT, compared to commonly used photon beam therapy, have been demonstrated in different studies. However, the techniques used for planning and delivering treatments with photon beams have gradually been improved over the years. With the introduction of PBT in the clinic, guidelines to select patients to photon- or proton-beam therapy are indispensable.

A simple approach used for selecting patients for PBT is based on the patient age. The paediatric patient group is considered to be the most radiosensitive and, therefore, in larger need of RT techniques that provide improved sparing of the organs at risk (OARs). With the increasing number of cancer clinics with access to PBT, combined with the constant clinical need of reducing the frequency of acute and late toxicities, there has been an increased use of PBT also for adult patients. At present, there is only limited clinical follow-up data available regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumours. The use of photon beams for such cancer treatments is, on the other hand, well-established. Therefore, the expected benefit of using proton beams in cancer therapy can be translated from the results obtained in the clinical experience attained from photon-beam treatments. The evaluation of the different uncertainties influencing the radiotherapy (RT) of different tumour sites carried out with photon- or proton-beams, will also create an improved understanding of the feasibility of treating cancer with scanned proton beams instead of with photon beams. 

The comparison of two distinct RT modalities is normally performed by studying the calculated dose distributions superimposed on the patient CT images and by evaluating the dosimetric values obtained from the dose volume histograms (DVHs). The dosimetric evaluation can be complemented with treatment outcome predictions in terms of local disease control and normal tissue toxicity. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. These estimates can in turn be used in the decision process for selecting patients for treatments with a specific RT modality.

This thesis consists of five articles. In these studies, treatment plans for RT with scanned proton-beams have been prepared and compared with clinical plans used for photon-beam based RT. For this purpose, dosimetric and biological-model based evaluations of these plans were performed. These studies were carried out for two distinct upper gastrointestinal (GI) cancers, namely, gastric cancer (GC) and liver metastases. RT treatments with both conventional fractionation schemes (implemented in the planning for the GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. For the GC cases, the impact of changes in tissue density, resulting from a variable gas content (which can be observed inter-fractionally), was investigated. Proton therapy was found to provide the possibility to reduce the doses given to normal tissues surrounding the target volumes, compared to photon RT. This dose reduction with PBT resulted in reduced risks for both treatment-induced normal tissue toxicities and secondary malignancies. The impact of the introduced density changes on the dose distributions were found to be more pronounced for the PBT plans, if plan robustness approaches were disregarded. The findings presented in this thesis can be of clinical importance in the selection process between different RT modalities.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm University, 2018. p. 141
Keywords
Treatment planning, gastric cancer, liver metastases, photon beam therapy, proton beam therapy, dosimetric comparison, normal tissue complication probability, risk of radiation-induced secondary cancer, patient selection
National Category
Physical Sciences
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-158411 (URN)978-91-7797-378-2 (ISBN)978-91-7797-379-9 (ISBN)
Public defence
2018-09-14, Radiumhemmets föreläsningssal, P1:01, Karolinska Universitetssjukhuset, Solna, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Sida - Swedish International Development Cooperation Agency
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Submitted.

Available from: 2018-08-22 Created: 2018-07-31 Last updated: 2018-09-26Bibliographically approved

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