PURPOSE: Noninvasive methods to monitor carbon-ion beams in patients are desired to fully exploit the advantages of carbon-ion radiotherapy. Prompt secondary ions produced in nuclear fragmentations of carbon ions are of particular interest for monitoring purposes as they can escape the patient and thus be detected and tracked to measure the radiation field in the irradiated object. This study aims to evaluate the performance of secondary-ion tracking to detect, visualize, and localize an internal air cavity used to mimic inter-fractional changes in the patient anatomy at different depths along the beam axis. METHODS: In this work, a homogeneous head phantom was irradiated with a realistic carbon-ion treatment plan with a typical prescribed fraction dose of 3 Gy(RBE). Secondary ions were detected by a mini-tracker with an active area of 2 cm2 , based on the Timepix3 semiconductor pixel detector technology. The mini-tracker was placed 120 mm behind the center of the target at an angle of 30 degrees with respect to the beam axis. To assess the performance of the developed method, a 2-mm thick air cavity was inserted in the head phantom at several depths: in front of as well as at the entrance, in the middle, and at the distal end of the target volume. Different reconstruction methods of secondary-ion emission profile were studied using the FLUKA Monte Carlo simulation package. The perturbations in the emission profiles caused by the air cavity were analyzed to detect the presence of the air cavity and localize its position. RESULTS: The perturbations in the radiation field mimicked by the 2-mm thick cavity were found to be significant. A detection significance of at least three standard deviations in terms of spatial distribution of the measured tracks was found for all investigated cavity depths, while the highest significance (six standard deviations) was obtained when the cavity was located upstream of the tumor. For a tracker with an eight-fold sensitive area, the detection significance rose to at least nine standard deviations and up to 17 standard deviations, respectively. The cavity could be detected at all depths and its position measured within 6.5 ± 1.4 mm, which is sufficient for the targeted clinical performance of 10 mm. CONCLUSION: The presented systematic study concerning the detection and localization of small inter-fractional structure changes in a realistic clinical setting demonstrates that secondary ions carry a large amount of information on the internal structure of the irradiated object and are thus attractive to be further studied for noninvasive monitoring of carbon-ion treatments.

Department of Medical Physics in Radiation Oncology German Cancer Research Center Heidelberg Germany

Department of Radiation Oncology Heidelberg University Hospital Heidelberg Germany

Department of Research and Development ADVACAM s r o Prague Czech Republic

Faculty of Physics and Astronomy Heidelberg University Heidelberg Germany

Heidelberg Institute for Radiation Oncology Heidelberg Germany

Heidelberg Ion Beam Therapy Center Heidelberg Germany

Helmholtz Zentrum Dresden Rossendorf Dresden Germany

Medical Faculty Heidelberg University Heidelberg Germany

Technische Universität Dresden Dresden Germany

See more in PubMed

Mohamad O, Sishc BJ, Saha J, et al. Carbon ion radiotherapy: a review of clinical experiences and preclinical research, with an emphasis on DNA damage/repair. Cancers (Basel). 2017;9(6):66. https://doi.org/10.3390/cancers9060066

Fattori G, Riboldi M, Scifoni E, et al. Dosimetric effects of residual uncertainties in carbon ion treatment of head chordoma. Radiother Oncol. 2014;113(1):66-71. https://doi.org/10.1016/j.radonc.2014.08.001

Muraro S, Battistoni G, Collamati F, et al. Monitoring of hadrontherapy treatments by means of charged particle detection. Front Oncol. 2016;6:177. https://doi.org/10.3389/fonc.2016.00177

Bisogni M. The INSIDE bimodal system for range monitoring in particle therapy toward clinical validation. Nucl Instrum Methods Phys Res, Sect A. 2019;936:73-74. https://doi.org/10.1016/j.nima.2018.11.048

Enghardt W, Crespo P, Fiedler F, et al. Charged hadron tumour therapy monitoring by means of PET. Nucl Instrum Methods Phys Res A. 2004;525:284-288. https://doi.org/10.1016/j.nima.2004.03.128

Krimmer J, Dauvergne D, Létang JM, Testa E. Prompt-gamma monitoring in hadrontherapy: a review. Nucl Instrum Methods Phys Res A. 2018;878:58-73. https://doi.org/10.1016/j.nima.2017.07.063

Dauvergne D, Battaglia M, Montarou G, Testa E. New methods of real-time control imaging for ion therapy. Paper presented at: NIRS-ETOILE Joint Symposium on Carbon Ion Therapy, Mar 2009, Lyon, France. ffin2p3-00363382f.

Amaldi U, Hajdas W, Iliescu S, et al. Advanced quality assurance for CNAO. Nucl Instrum Methods Phys Res A. 2010;617(1-3):248-249. https://doi.org/10.1016/j.nima.2009.06.087

Gwosch K, Hartmann B, Jakubek J, et al. Non-invasive monitoring of therapeutic carbon ion beams in a homogeneous phantom by tracking of secondary ions. Phys Med Biol. 2013;58(11):3755-3773. https://doi.org/10.1088/0031-9155/58/11/3755

Gaa T, Reinhart M, Hartmann B, et al. Visualization of air and metal inhomogeneities in phantoms irradiated by carbon ion beams using prompt secondary ions. Phys Medica. 2017;38:140-147. https://doi.org/10.1016/j.ejmp.2017.05.055

Reinhart AM, Spindeldreier CK, Jakubek J, Martišíková M. Three dimensional reconstruction of therapeutic carbon ion beams in phantoms using single secondary ion tracks. Phys Med Biol. 2017;62(12):4884-4896. https://doi.org/10.1088/1361-6560/aa6aeb

Rucinski A, Battistoni G, Collamati F, et al. Secondary radiation measurements for particle therapy applications: charged particles produced by 4He and 12C ion beams in a PMMA target at large angle. Phys Med Biol. 2018;63(5):055018. https://doi.org/10.1088/1361-6560/aaa36a

Félix-Bautista R, Gehrke T, Ghesquiere-Diérickx L, et al. Experimental verification of a non-invasive method to monitor the lateral pencil beam position in an anthropomorphic phantom for carbon-ion radiotherapy. Phys Med Biol. 2019;64(17):175019. https://doi.org/10.1088/1361-6560/ab2ca3

Félix-Bautista R, Ghesquière-Diérickx L, Marek L, et al. Quality assurance method for monitoring of lateral pencil beam positions in scanned carbon-ion radiotherapy using tracking of secondary ions. Med Phys. 2021;48(8):4411-4424. https://doi.org/10.1002/mp.15018

Traini G, Mattei I, Battistoni G, et al. Review and performance of the Dose Profiler, a particle therapy treatments online monitor. Phys Medica. 2019;65:84-93. https://doi.org/10.1016/j.ejmp.2019.07.010

Fischetti M, Baroni G, Battistoni G, et al. Inter-fractional monitoring of 12 C ions treatments: results from a clinical trial at the CNAO facility. Sci Rep. 2020;10(1):20735. https://doi.org/10.1038/s41598-020-77843-z

Combs SE, Jäkel O, Haberer T, Debus J. Particle therapy at the Heidelberg Ion Therapy Center (HIT) - integrated research-driven university-hospital-based radiation oncology service in Heidelberg, Germany. Radiother Oncol. 2010;95(1):41-44. https://doi.org/10.1016/j.radonc.2010.02.016

Haberer T, Becher W, Schardt D, Kraft G. Magnetic scanning system for heavy ion therapy. Nucl Instrum Methods Phys Res A. 1993;330(1-2):296-305. https://doi.org/10.1016/0168-9002(93)91335-K

Schoemers C, Feldmeier E, Naumann J, Panse R, Peters A, Haberer T. The intensity feedback system at Heidelberg Ion-Beam Therapy Centre. Nucl Instrum Methods Phys Res A. 2015;795:92-99. https://doi.org/10.1016/j.nima.2015.05.054

Rietzel E, Schardt D, Haberer T. Range accuracy in carbon ion treatment planning based on CT-calibration with real tissue samples. Radiat Oncol. 2007;2(1):14. https://doi.org/10.1186/1748-717X-2-14

Combs SE, Kessel K, Habermehl D, Haberer T, Jäkel O, Debus J. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Acta Oncol. 2013;52(7):1504-1509. https://doi.org/10.3109/0284186X.2013.818255

Haettner E, Iwase H, Krämer M, Kraft G, Schardt D. Experimental study of nuclear fragmentation of 200 and 400 MeV/u 12C ions in water for applications in particle therapy. Phys Med Biol. 2013;58(23):8265-8279. https://doi.org/10.1088/0031-9155/58/23/8265

Poikela T, Plosila J, Westerlund T, et al. Timepix3: a 65K channel hybrid pixel readout chip with simultaneous ToA/ToT and sparse readout. J Instrum. 2014;9(5):C05013. https://doi.org/10.1088/1748-0221/9/05/C05013

Marek L. Directional and Spectrometric Mapping of Secondary Radiation Induced During Hadron Radiotherapy with Miniaturized Particle Trackers. Dissertation. Czech Technical University In Prague; 2020.

Böhlen TT, Cerutti F, Chin MPW, et al. The FLUKA code: developments and challenges for high energy and medical applications. Nucl Data Sheets. 2014;120:211-214. https://doi.org/10.1016/j.nds.2014.07.049

Ferrari A, Sala PR, Fasso A, Ranft J. FLUKA: a multi-particle transport code. Cern Yellow Rep. 2005. https://doi.org/10.2172/877507

Battistoni G, Cerutti F, Fassò A, et al. The FLUKA code: description and benchmarking. AIP Conf Proc. 2007; 896:31-49. https://doi.org/10.1063/1.2720455

Battistoni G, Bauer J, Boehlen TT, et al. The FLUKA code: an accurate simulation tool for particle therapy. Front Oncol. 2016;6:116. https://doi.org/10.3389/fonc.2016.00116

Vlachoudis V. Flair: a powerful but user friendly graphical interface for FLUKA. Paper presented at: International Conference on Mathematics, Computational Methods and Reactor Physics 2009; May 3-7, 2009; Saratoga Springs, NY. https://inis.iaea.org/search/search.aspx?orig_q=RN:42064858.

Tessonnier T, Mairani A, Brons S, Haberer T, Debus J, Parodi K. Experimental dosimetric comparison of 1H, 4He, 12C and 16O scanned ion beams. Phys Med Biol. 2017;62(10):3958-3982. https://doi.org/10.1088/1361-6560/aa6516

Experimental validation of a FLUKA Monte Carlo simulation for carbon-ion radiotherapy monitoring via secondary ion tracking

An in-vivo treatment monitoring system for ion-beam radiotherapy based on 28 Timepix3 detectors