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
doi: 10.1371/journal.pone.0224873


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 – Ears – Fractionation – Mouse models – Protons – Radiation therapy – Tissue distribution – Desquamation


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Článek vyšel v časopise


2019 Číslo 11