REVIEW
published: 21 January 2021
Edited by:
Antony John Lomax,
Paul Scherrer Institut (PSI), Switzerland
Reviewed by:
Ulrich W. Langner,
Lifespan, United States
William F. Hartsell,
Northwestern University,
United States
*Correspondence:
Alejandro Mazal
alejandro.mazal@quironsalud.es
Specialty section:
This article was submitted to
Radiation Oncology,
a section of the journal
Frontiers in Oncology
Received: 03 October 2020
Accepted: 02 December 2020
Published: 21 January 2021
Citation:
Mazal A, Vera Sanchez JA,
Sanchez-Parcerisa D, Udias JM,
España S, Sanchez-Tembleque V,
Fraile LM, Bragado P, Gutierrez-
Uzquiza A, Gordillo N, Garcia G,
Castro Novais J, Perez Moreno JM,
Mayorga Ortiz L, Ilundain Idoate A,
Cremades Sendino M, Ares C,
Miralbell R and Schreuder N (2021)
Biological and Mechanical Synergies
to Deal With Proton Therapy Pitfalls:
Minibeams, FLASH, Arcs, and
Gantryless Rooms.
Front. Oncol. 10:613669.
doi: 10.3389/fonc.2020.613669
Frontiers in Oncology | www.frontiersin.org
doi: 10.3389/fonc.2020.613669
Biological and Mechanical Synergies
to Deal With Proton Therapy Pitfalls:
Minibeams, FLASH, Arcs, and
Gantryless Rooms
Alejandro Mazal 1*, Juan Antonio Vera Sanchez 1, Daniel Sanchez-Parcerisa 2,3,4,
Jose Manuel Udias 2,3, Samuel España 2,3, Victor Sanchez-Tembleque 2,3,
Luis Mario Fraile 2,3, Paloma Bragado 3,5, Alvaro Gutierrez-Uzquiza 3,5, Nuria Gordillo 6,7,
Gaston Garcia 7, Juan Castro Novais 1, Juan Maria Perez Moreno 1, Lina Mayorga Ortiz 1,
Amaia Ilundain Idoate 1, Marta Cremades Sendino 1, Carme Ares 1, Raymond Miralbell 1
and Niek Schreuder 8
1 Centro de Protonterapia Quironsalud, Madrid, Spain, 2 Grupo de Fı´sica Nuclear and IPARCOS, U. Complutense Madrid,
CEI Moncloa, Madrid, Spain, 3 Instituto de Investigación Sanitaria del Hospital Clı´nico San Carlos, Madrid, Spain, 4 Sedecal
Molecular Imaging, Madrid, Spain, 5 Department of Biochemistry and Molecular Biology. U. Complutense, Madrid, Spain,
6 Department of Applied Physics, U. Autonoma de Madrid, Madrid, Spain, 7 Center for Materials Microanalysis, (CMAM),
U. Autonoma de Madrid, Madrid, Spain, 8 Leo Cancer Care, Knoxville, TN, United States
Proton therapy has advantages and pitfalls comparing with photon therapy in radiation
therapy. Among the limitations of protons in clinical practice we can selectively mention:
uncertainties in range, lateral penumbra, deposition of higher LET outside the target,
entrance dose, dose in the beam path, dose constraints in critical organs close to the
target volume, organ movements and cost. In this review, we combine proposals under
study to mitigate those pitfalls by using individually or in combination: (a) biological
approaches of beam management in time (very high dose rate “FLASH” irradiations in
the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of
millimetric extent), together with mechanical approaches such as (c) rotational techniques
(optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems.
In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they
are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer
centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to
isocentric gantries. The present proposals to produce fixed lines are somewhat
controversial. Rotational techniques, minibeams and FLASH in proton therapy are
making their way, with an increasing degree of complexity in these three approaches,
but with a high interest in the basic science and clinical communities. All of them must be
proven in clinical applications.
Keywords: proton therapy, FLASH, minibeams, arc therapy, gantry
1 January 2021 | Volume 10 | Article 613669
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Conflict of Interest: NS is the President of proton therapy for Leo Cancer Care,
Ltd.
The remaining authors declare that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential
conflict of interest.
Copyright © 2021 Mazal, Vera Sanchez, Sanchez-Parcerisa, Udias, España, Sanchez-
Tembleque, Fraile, Bragado, Gutierrez-Uzquiza, Gordillo, Garcia, Castro Novais,
Perez Moreno, Mayorga Ortiz, Ilundain Idoate, Cremades Sendino, Ares, Miralbell
and Schreuder. This is an open-access article distributed under the terms of the
Creative Commons Attribution License (CC BY). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) and the
copyright owner(s) are credited and that the original publication in this journal is
cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
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