Question 1: Which of the following is NOT a potential biological advantage of using heavy charged particles compared to protons in cancer therapy? |
Reference: | Held KD, Kawamura H, Kaminuma T, Paz AE, Yoshida Y, Liu Q, Willers H, Takahashi A. Effects of Charged Particles on Human Tumor Cells. Front Oncol 2016 Feb 12;6:23. |
Choice A: | Decreased OER. |
Choice B: | Less dependence on dose rate. |
Choice C: | More effective killing of cells in normal tissues. |
Choice D: | Increased killing of cancer stem cells. |
Question 2: If defects in specific DNA repair pathways could be identified in a patient’s tumor that would result in higher RBE values, how could this information be utilized in that patient's treatment? |
Reference: | Liu Q, Ghosh P, Magpayo N, Tang S, Testa M, Biggs P, Paganetti H, Efstathiou JA, Lu HM, Held KD, Willers H. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation. Int J Radiat Oncol Biol Phys. 2015; 91(5):1081-1089.
Held KD, Kawamura H, Kaminuma T, Paz AE, Yoshida Y, Liu Q, Willers H, Takahashi A. Effects of Charged Particles on Human Tumor Cells. Front Oncol 2016 Feb 12;6:23.
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Choice A: | It might allow de-escalation of the charged particle dose if normal tissue damage is a particular concern. |
Choice B: | It could guide selection of patients whose tumors might be most effectively treated with particles. |
Choice C: | Biologically optimized tumor-directed therapy could be used to improve local tumor control. |
Choice D: | All of the above. |
Question 3: Limitations of in vitro clonogenic survival assays include which of the following? |
Reference: | Guan F, Bronk L, Titt U, et al. Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy. Sci Rep 2015; 5:9850.(doi): 10.1038/srep09850. |
Choice A: | Clonogenic assays can only provide information on cell lines that can grow in culture. |
Choice B: | Studies are commonly in a limited number of cell lines, often including non-patient derived cell lines. |
Choice C: | Clonogenic survival experiments are labor and time intensive. |
Choice D: | All of the above. |
Question 4: Potential benefits of collaborations between physicists and radiation biologist when designing experimental setups for study of particle therapy biology include which if the following? |
Reference: | McNamara AL, Schuemann J, Paganetti H. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Phys Med Biol 2015; 60(21): 8399-416. doi: 10.1088/0031-9155/60/21/8399. Epub 2015 Oct 13. |
Choice A: | Accurate data regarding doses delivered. |
Choice B: | Data regarding linear energy transfer (LET values). |
Choice C: | Minimization of uncertainties. |
Choice D: | All of the above. |
Question 5: Relative biological effectiveness (RBE) of protons compared to photons is? |
Reference: | Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol 2014; 59(22): R419-72. doi: 10.1088/0031-9155/59/22/R419. Epub 2014 Oct 31. |
Choice A: | Variable and increases as a function depth of penetration. |
Choice B: | Fixed and lower. |
Choice C: | Fixed and higher. |
Choice D: | Same. |
Question 6: Which of the following does NOT provide a plausible biological explanation for higher RBE values? |
Reference: | Carlson DJ, Stewart RD, Semenenko VA Sandison GA. Combined use of Monte Carlo DNA damage
simulations and deterministic repair models to examine putative mechanisms of cell killing. Radiat. Res. 169: 447-459 (2008).
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Choice A: | An increase in the complexity of DNA double-strand breaks (DSBs) as particle energy decreases. |
Choice B: | An increase in the absolute yield of DNA double-strand breaks (DSBs) [per Gy per cell] as particle energy decreases. |
Choice C: | A decrease in the frequency of exchange-type chromosome aberrations as particle energy decreases. |
Choice D: | Defects in specific DNA repair pathways in some solid tumors. |
Question 7: Which of the following statements about biophysical modeling for heavy ion treatment planning is correct? |
Reference: | Kamp F, Cabal G, Mairani A, Parodi K, Wilkens JJ, Carlson DJ. Fast biological modeling for voxel-based heavy ion therapy treatment planning using the mechanistic repair-misrepair-fixation (RMF) model and nuclear fragment spectra. Int. J. Radiat. Oncol. Biol. Phys. 93: 557-568 (2015). |
Choice A: | Neglecting nuclear fragments in carbon ion simulations results in larger RBE predictions within an SOBP. |
Choice B: | Neglecting nuclear fragments in carbon ion simulations results in smaller RBE predictions within an SOBP |
Choice C: | Choice of biological model and input parameter assumptions do not impact the estimated RBE-weighted dose-volume histogram for critical normal structures. |
Choice D: | Inter-patient variation in radiosensitivity is less important for carbon ion radiotherapy compared to proton therapy. |
Question 8: Which of the following statements about proton RBE is correct? |
Reference: | Paganetti H: Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Physics in Medicine and Biology 2014 59: R419-R472 |
Choice A: | The RBE increases with increasing LET, with increasing dose, and with increasing alpha/beta. |
Choice B: | The RBE increases with increasing LET, with decreasing dose, and with increasing alpha/beta. |
Choice C: | The RBE increases with increasing LET, with increasing dose, and with decreasing alpha/beta. |
Choice D: | The RBE increases with increasing LET, with decreasing dose, and with decreasing alpha/beta. |
Choice E: | The RBE increases with decreasing LET, with decreasing dose, and with increasing alpha/beta. |
Question 9: Which of the following statements about clinical relevance of proton RBE is correct? |
Reference: | Giantsoudi D; Sethi RV; Yeap BY; Eaton BR; Ebb DH; Caruso PA; Rapalino O; Chen YLE; Adams J; Yock TI; Tarbell NJ; Paganetti H and MacDonald SM: Incidence of CNS Injury for a Cohort of 111 Patients Treated with Proton Therapy for Medulloblastoma; LET and RBE Associations for Areas of Injury. International Journal of Radiation Oncology, Biology and Physics 2016; online ahead of print |
Choice A: | There is clear clinical evidence for RBE being higher than 1.1 in some cases. |
Choice B: | Patient variability in biological parameters may hide LET dependency of RBE. |
Choice C: | Elevated LET values indicating an RBE>1.1 are outside of the target volume. |
Choice D: | Treatment planners should try to maximize LET in organs at risk. |
Choice E: | The RBE for clinical endpoints is either equal or higher than 1.1. |
Question 10: Which of the following statements about LET based treatment planning is correct? |
Reference: | Giantsoudi D; Grassberger C; Craft D; Niemierko A; Trofimov AV and Paganetti H: Linear energy transfer (LET)-Guided Optimization in intensity modulated proton therapy (IMPT): feasibility study and clinical potential. International Journal of Radiation Oncology, Biology, Physics 2013 87: 216-222 |
Choice A: | When applying LET based optimization both LET and dose need to be considered simultaneously. |
Choice B: | Proton beam scanning will reduce our ability to do LET driven optimization. |
Choice C: | When applying LET based optimization both LET and RBE need to be considered simultaneously. |
Choice D: | LET based optimization results in treatment fields that fully penetrate critical structures. |
Choice E: | LET or RBE based optimization are irrelevant in proton therapy. |