Proton pencil minibeam irradiation of an in-vivo mouse ear model spares healthy tissue dependent on beam size
Autoři:
Matthias Sammer aff001; Esther Zahnbrecher aff002; Sophie Dobiasch aff002; Stefanie Girst aff001; Christoph Greubel aff001; Katarina Ilicic aff002; Judith Reindl aff001; Benjamin Schwarz aff001; Christian Siebenwirth aff001; Dietrich W. M. Walsh aff001; Stephanie E. Combs aff002; Günther Dollinger aff001; Thomas E. Schmid aff002
Působiště autorů:
Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany
aff001; Department of Radiation Oncology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany
aff002; Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München (HMGU), Oberschleißheim, Germany
aff003; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Germany
aff004
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0224873
Souhrn
Proton radiotherapy using minibeams of sub-millimeter dimensions reduces side effects in comparison to conventional proton therapy due to spatial fractionation. Since the proton minibeams widen with depth, the homogeneous irradiation of a tumor can be ensured by adjusting the beam distances to tumor size and depth to maintain tumor control as in conventional proton therapy. The inherent advantages of protons in comparison to photons like a limited range that prevents a dosage of distal tissues are maintained by proton minibeams and can even be exploited for interlacing from different beam directions. A first animal study was conducted to systematically investigate and quantify the tissue-sparing effects of proton pencil minibeams as a function of beam size and dose distributions, using beam widths between σ = 95, 199, 306, 411, 561 and 883 μm (standard deviation) at a defined center-to-center beam distance (ctc) of 1.8 mm. The average dose of 60 Gy was distributed in 4x4 minibeams using 20 MeV protons (LET ~ 2.7 keV/μm). The induced radiation toxicities were measured by visible skin reactions and ear swelling for 90 days after irradiation. The largest applied beam size to ctc ratio (σ/ctc = 0.49) is similar to a homogeneous irradiation and leads to a significant 3-fold ear thickness increase compared to the control group. Erythema and desquamation was also increased significantly 3–4 weeks after irradiation. With decreasing beam sizes and thus decreasing σ/ctc, the maximum skin reactions are strongly reduced until no ear swelling or other visible skin reactions should occur for σ/ctc < 0.032 (extrapolated from data). These results demonstrate that proton pencil minibeam radiotherapy has better tissue-sparing for smaller σ/ctc, corresponding to larger peak-to-valley dose ratios PVDR, with the best effect for σ/ctc < 0.032. However, even quite large σ/ctc (e.g. σ/ctc = 0.23 or 0.31, i.e. PVDR = 10 or 2.7) show less acute side effects than a homogeneous dose distribution. This suggests that proton minibeam therapy spares healthy tissue not only in the skin but even for dose distributions appearing in deeper layers close to the tumor enhancing its benefits for clinical proton therapy.
Klíčová slova:
Cancer treatment – Mouse models – Protons – Radiation therapy – Ears – Tissue distribution – Fractionation – Desquamation
Zdroje
1. Paganetti H, Niemierko A, Ancukiewicz M, Gerweck LE, Goitein M, Loeffler JS, et al. Relative biological effectiveness (RBE) values for proton beam therapy. International Journal of Radiation Oncology* Biology* Physics. 2002;53:407–21.
2. Zlobinskaya O, Girst S, Greubel C, Hable V, Siebenwirth C, Walsh DWM, et al. Reduced side effects by proton microchannel radiotherapy: study in a human skin model. Radiat Environ Biophys. 2013;52:123–33. doi: 10.1007/s00411-012-0450-9 23271171
3. Prezado Y, Fois GR. Proton‐minibeam radiation therapy: A proof of concept. Med Phys. 2013;40:31712.
4. Sammer M, Greubel C, Girst S, Dollinger G. Optimization of beam arrangements in proton minibeam radiotherapy by cell survival simulations. Med Phys. 2017;44:6096–104. doi: 10.1002/mp.12566 28880369
5. Girst S, Greubel C, Reindl J, Siebenwirth C, Zlobinskaya O, Walsh DWM, et al. Proton minibeam radiation therapy reduces side effects in an in vivo mouse ear model. International Journal of Radiation Oncology* Biology* Physics. 2016;95:234–41.
6. Schell S, Wilkens JJ. Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams. Med Phys. 2010;37:5330–40. doi: 10.1118/1.3491406 21089768
7. Deasy JO, Blanco AI, Clark VH. CERR: a computational environment for radiotherapy research. Med Phys. 2003;30:979–85. 12773007
8. Prezado Y, Sarun S, Gil S, Deman P, Bouchet A, Le Duc G. Increase of lifespan for glioma-bearing rats by using minibeam radiation therapy. Journal of synchrotron radiation. 2012;19:60–5. doi: 10.1107/S0909049511047042 22186645
9. Prezado Y, Jouvion G, Hardy D, Patriarca A, Nauraye C, Bergs J, et al. Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis. Scientific reports. 2017;7:14403. doi: 10.1038/s41598-017-14786-y 29089533
10. Prezado Y, Jouvion G, Patriarca A, Nauraye C, Guardiola C, Juchaux M, et al. Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas. Scientific reports. 2018;8:16479. doi: 10.1038/s41598-018-34796-8 30405188
11. Sammer M, Teiluf K, Girst S, Greubel C, Reindl J, Ilicic K, et al. Beam size limit for pencil minibeam radiotherapy determined from side effects in an in-vivo mouse ear model. PloS one. 2019;14:e0221454. doi: 10.1371/journal.pone.0221454 31483811
12. Dombrowsky AC, Schauer J, Sammer M, Blutke A, Walsh DWM, Schwarz B, et al. Acute Skin Damage and Late Radiation-Induced Fibrosis and Inflammation in Murine Ears after High-Dose Irradiation. Cancers. 2019;11:727.
13. Hauptner A, Dietzel S, Drexler GA, Reichart P, Krücken R, Cremer T, et al. Microirradiation of cells with energetic heavy ions. Radiation and environmental biophysics. 2004;42:237–45. doi: 10.1007/s00411-003-0222-7 14735370
14. Greubel C, Hable V, Drexler GA, Hauptner A, Dietzel S, Strickfaden H, et al. Quantitative analysis of DNA-damage response factors after sequential ion microirradiation. Radiation and environmental biophysics. 2008;47:415–22. doi: 10.1007/s00411-008-0181-0 18648840
15. Greubel C, Assmann W, Burgdorf C, Dollinger G, Du G, Hable V, et al. Scanning irradiation device for mice in vivo with pulsed and continuous proton beams. Radiation and environmental biophysics. 2011;50:339–44. doi: 10.1007/s00411-011-0365-x 21556847
16. Liao W, Hei TK, Cheng SK. Radiation-induced dermatitis is mediated by IL17-expressing γδ T cells. Radiation research. 2017;187:464–74.
17. Parkinson EK, Hume WJ, Potten CS. The radiosensitivity of keratinocytes from tongue and skin; enhanced radioresistance following serial cultivation. The British journal of cancer. Supplement. 1986;7:81.
18. Dilmanian FA, Rusek A, Fois GR, Olschowka J, Desnoyers NR, Park JY, et al. Interleaved carbon minibeams: An experimental radiosurgery method with clinical potential. International Journal of Radiation Oncology* Biology* Physics. 2012;84:514–9.
19. Dilmanian FA, Eley JG, Rusek A, Krishnan S. Charged particle therapy with mini-segmented beams. Frontiers in oncology. 2015;5:269. doi: 10.3389/fonc.2015.00269 26649281
20. Bräuer‐Krisch E, Bravin A, Lerch M, Rosenfeld A, Stepanek J, Di Michiel M, et al. MOSFET dosimetry for microbeam radiation therapy at the European Synchrotron Radiation Facility. Med Phys. 2003;30:583–9. doi: 10.1118/1.1562169 12722810
21. Prezado Y, Thengumpallil S, Renier M, Bravin A. X‐ray energy optimization in minibeam radiation therapy. Med Phys. 2009;36:4897–902. doi: 10.1118/1.3232000 19994498
Článok vyšiel v časopise
PLOS One
2019 Číslo 11
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Dlouhodobá recidiva a komplikace spojené s elektivní operací břišní kýly
Najčítanejšie v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF