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    Ion beam therapy allows for substantial sparing of normal tissues. Besides deterministic normal-tissue complications, stochastic long-term effects like secondary cancer (SC) induction are of importance when comparing different treatment modalities. To develop a modeling approach for comparison of SC risk in proton and carbon ion therapy. The local effect model (LEM) is used to predict the relative biological effectiveness (RBE) of SC induction after particle therapy. A key feature of the new approach is the double use of the LEM, reflecting the competition between the two processes of mutation induction (leading to cancer development) and cell inactivation (leading to suppression of cancer development). Based on previous investigations, treatment plans were in this work analyzed for an idealized geometry in order to assess the underlying systematic dependencies of cancer induction. In a further step, relative SC risks were predicted for proton and carbon ion treatment plans prepared for 10 prostate cancer patients. We investigated the impact of factors such as treatment plan geometry, fractionation scheme, and tissue radiosensitivity to photon irradiation on the ion beam SC risk. Our model studies do not result in a clear preference for either protons or carbon ions, but rather indicate a complex interplay of different aspects. Reduced lateral scattering leads to a lower SC risk for carbon ions compared to protons at the lateral field margins in the entrance channel, while an increased risk was found closely behind the tumor due to projectile fragmentation. The fractionation scheme had little impact on the expected risk ratio. With respect to sensitivity parameters, those characterizing RBE for cell killing of potentially cancerous cells as well as of the primary tumor had the most significant impact. The observed general systematic dependencies are in agreement with results from previous model studies. The prostate patient study reveals reduced SC risks predictions for skin and bones for carbon ions as compared to protons, but higher mean risks for bladder and rectum. The methods established in this work provide a basis for further investigating treatment optimizing strategies for ion beam therapy with regard to SC risk comparisons. © 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.


    Antonia Hufnagl, Gracinda Johansson, Albert Siegbahn, Marco Durante, Thomas Friedrich, Michael Scholz. Modeling secondary cancer risk ratios for proton versus carbon ion beam therapy: A comparative study based on the local effect model. Medical physics. 2022 Aug;49(8):5589-5603

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    PMID: 35717591

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