A rebirth of radiation therapy with kV X-rays?


Published: Mar 8, 2019
Keywords:
synchrotron radiation radiation therapy microbeam photon activation therapy
J. Kalef-Ezra
Abstract

Novel clinical approaches using kV X-ray beams are currently under study, such as selective dose enhancement in malignant tissues due to the enhanced presence of atoms with high atomic number, Z, in tumors relative to normal tissues or the use of heavily spatially fractionated kV X-ray irradiation.

Local dose enhancement by high Z atoms: A substantial dose gradient between normal and malignant tissues can be achieved by biologic targeting the cells to be “destroyed” with high Z atoms and its irradiation with photons in the energy region of tens of keV, such as synchrotron produced X-rays of energy above the K-edge. The selective accumulation of high Z atoms can be achieved by various techniques, such as by intravenous administration of a) contrast enhancement agents, b) some chemotherapeutic drugs c) nanoparticles and d) DNA precursors loaded with Z-atoms. Taking into account the limited availability and the high cost of GeV synchrotrons, brachytherapy sources could be used.

Microbeam radiation therapy: Studies carried out in experimental models using spatially micro- fractionated beams have shown drastically elevated tissue radiation tolerance, with higher tissue sparing in healthy tissues than in malignant ones. This phenomenon is attributed by some investigators to the proliferation and migration of cells from the “low” dosed regions (~10 Gy) to the adjacent “heavily” dosed regions (many hundreds of grays). Multi-slit collimators allow for the production of X-ray microbeam arrays at 3rd generation synchrotron units. Monte Carlo simulations were tested versus direct dose measurements. Promising preclinical studies carried out so far, trigger studies on the development of alternative less expensive technologies.

Article Details
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  • Oral contributions
References
Meada H, Fang J, Inutsuka T, Kitamoto Y. Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications International Immunopharmacology 3 319 (2003)
Obeid L, Deman P, Tesier A, Balosso J, Esteve F, Adam J-F. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy Journal of Cerebral Blood Flow and Metabolism 34 638 (2014)
Laster B, Dixon WD, Novick S, Feldman J, Seror V, Goldbart Z, Kalef-Ezra J. Photon activation therapy and brachytherapy Brachytherapy 8 324 (2009)
Laster B, Isaaccson C, Msamra M, Prerets E, Kost J, Priel E, Kalef-Ezra J. Keeping those telomeres short! An innovative intratumoral long-term drug delivery system Journal of Cancer Research and Clinical Oncology 141 23 (2015)
Esteve F, Corde S, Elleaume H, Adam JF, Joubert A, Charvet AM, Biston MC, Balosso J, Le Bas JF. Enhanced radiosensitivity with iodinated contrast agents using monochromatic synchrotron Xrays on human cancerous cells. Acad Radiol 9S 540 (2002)
Adam JF, Joubert A, Biston M-C, Charvte A-M, Peoch M, Le-Bas J-F, Ballosso J, Esteve F, Ellemaume H. Prolonged survival of Fisher rats bearing F98 glioma after iodine-enhanced synchrotron radiation therapy. Intern. Journal of Radiation Oncology Biology and Physics 64 603 (2006)
Rose HJ, Norman A, Ingram M, Aoki C, Solberg T, Mesa A. First radiotherapy of human metastatic brain tumors delivered by a computed tomography scanner (CTRx). International Journal of Radiation Oncology Biology and Physics 45 1127 (1995)
Prezado Y, Vautrin M, Martinez-Rovira I, Bravin A, Esteve F, Elleaume H, Bekevens P, Adam JF. Dosimetry protocol for forthcoming clinical trial in synchrotron stereotactic radiation therapy (SSRT) Medical Physics 38 (2011) doi. 10.1118/1.3556561
Bräuer-Krisch E., Adam J. F, Alagoz E, Bartzsch S, Crosbie J, DeWagter C, Dipuglia A, Donzelli M, Doran S, Fournier P, Kalef-Ezra J, et al. Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT) Physica Medica (2015) doi:10.1016/j.ejmp.2015. 04.016.
Hainfeld FJ, Dilmanian FA, Zhong Z, Slatkin DN, Kalef-Ezra JA, Smilowitz MY. Gold nanoparticles enhance radiation therapy of a murine squamous cell carcinoma Physics in Medicine and Biology 55 3045 (2010)
Fairchild GR, Brill BA, Ettinger VK. Radiation enhancement with iodianed deoxyuridine Investigative Radiology 17 407 (1982)
Laster B, Thomlinson CW, Fairchild GR. Photon activation of iododeoxyuridine: biological efficacy of Auger electrons Radiation Research 133 219 (1993)
Slatkin DN, Spanne P, Dilmanian FA, Sanborg M. Microbeam radiation therapy. Medical Physics 19 1395 (1992)
Slatkin DN, Dilmanian FA, Nawrocky NM, Spanne P. Gebbers J O, Archer DW, Laissue JA. Design of a multislite, variable width collimator for microplanar beam radiotherapy. Rev Sci Instr 66 1459 (1995)
Ohno Y, Torikoshi M, Suzuki M, Umetani K, Imai Y. Uesugi K, Yagi N. Dose distribution of a 125 keV mean energy microplanar x-ray beam for basic studies on microbeam radiotherapy Medical Physics 35 3252 (2008)
Dilmanian FA, Romanelli P, Zhong Z, Wang R, Wagshul ME, Kalef-Ezra J, Maryanski MJ, Rosen EM, Anchel DJ. Microbeam radiation therapy: tissue dose penetration and bang-gel dosimetry of thick-beams’ array interlacing European Journal of Radiology 68 S129 (2008)
Harty DR, Lye EJ, Hall JC, Stevenson WM, Johnston NP. Absolute x-ray dosimetry on a synchrotron medical beam line with graphite calorimeter Medical Physics 41 (2014) doi.10.1118/1.48070387
Slatkin DN, Spanne P, Dilmanian FA, Gebbers JO, Laissue JA. Subacute neuropatho-logical effects of microplanar beams of X-rays from synchrotron wiggler Proceedings of the National Academy of Sciences (USA) 92 8783 (1995)
Dilmanian FA, Morris GM, LeDuc G, Huang X, Ren B, Bacarian T, Allen J, Kalef-Ezra J, Orion I, Sandhu T, Wu XY, Zhong Z, Shivaprasad HL: Response of avian embryonic brain to spatially segmented X-ray microbeams Cellular and Molecular Biology 47 485 (2001)
Zhong N, Morris GM, Bacarian T, Rosen EM, Dilmanian A. Response of rat skin to high dose unidirectional X-ray microbeams Radiation Research 160 133 (2003)
Dilmanian FA., Kalef-Ezra J, Petersen MJ, Bozios G, Voswinkel J, Giron F, Ren B, Yakupov R, Antonakopoulos G: Could X-ray microbeams inhibit angioplasty induced restenosis in the rat carotid artery? Cardiovascular Radiation Medicine 4 139 (2003)
Dilmanian FA, Qu Y, Feinendegen LE, Pena LA, Bacarian T, Henn FA, Kalef-Ezra J, Liu S, Zhong Z, McDonald JW Tissue-sparing effect of x-ray microplanar beams particular in CNS: is a bystander involved? Experimental Hematology 3 69 (2007)
Van der Sanden B, Bräuer-Krisch E, Siegban A, Ricard C, Vila J-C, Laissue J. Tolerance of arteries to microplanar X-ray beams International Journal of Radiation Oncology, Biology and Physics 77 1545 (2010)
Laissue JA, Bartzch S, Blattmann H, Bräuer-Krisch E, Bravin A, et al. Response of rat spinal chord to X-ray microbeams Radiation Oncology 106 106 (2013)
Bouchet A, Serduc R, Laissue JA, Djonov V. Effects of microbeam radiation therapy on normal and tumor blood vessels. Physica Medica 31 634 (2015)
Laissue JA, Geiser G, Spanne PO, Dilmanian FA Gebbers JO, Geiser M, et al. Neuro-pathology of ablation of rat glioblastomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X-rays. International Journal of Cancer 78 654 (1998)
Dilmanian A, Button TM, LeDuc G, Zhong N, Pena LA, Martinez S, Bacarian T, Tammam J, Ren B, Farmer P, Kalef-Ezra J, et al. Response of the rat intracranial 9L gliosacroma to microbeam radiation therapy Neuro-Oncology 4 26 (2002)
Dilmanian A, Button TM, LeDuc G, Zhong N, Pena LA, Martinez S, Bacarian T, Tammam J, Ren B, Farmer P, Kalef-Ezra J, Micca P, et al. Response of the rat intra-cranial 9L gliosacroma to nmicrobeam radiation therapy Neuro-Oncology 4 26 (2002)
Dilmanian FA, Morris GM, Zhong N, Bacarian T, Hainfeld JF, Kalef-Ezra J, Brewington JL, Tammam J, Rosen EM. Murine EMT-6 carcinomas: High therapeutic efficacy of micro- beam radiation therapy (MRT) Radiation Research 159 632 (2003)
Miura M, Blattmann H, Brauer –Krisch E, Bravin A, Hanson AL, Nawrocky MM, Micca PL, Slatkin DN, Laissue J. Radiosurgical palliation of agressive murine SCCVII squamous cell carcinomas using synchrotron-generated X-ray microbeams British Journal of Radiology 79 71 (2006)
Anchel DJ, Romanelli P, Benveniste H, Foerster B, Kalef-Ezra J, Zhong Z, Dilmanian AF. Evolution of focal brain lesion produced by interlaced microplanar X-rays Minimally Invasive Neurosurgery 50 43 (2007)
Laissue JA, Blattmann H, Wagner HP, Grotzer MA, Slatkin DN. Prospects for microbeam radiation therapy of brain tumours in children to reduce neurological sequelae Developmental Medicine and Child Neurology 49 577 (2007)
Schultkis E, Juurlink N, Atalelmannan K, Laissue J, Blattmann H, Brauer-Krisch E, Bravin A, et al. Memory and survival after microbeam radiation therapy European Journal of Radiology 68S 142 (2008)
Serduc R, Bouchet A, Brauer-Krisch E, Laissue J, Spiga J, Bravin A, Fonta C, Renaud L, et al. Sunchrotron microbeam radiation therapy for rat brain palliation-influence of the microbeam width at constant valley dose Physics in Medicine and Biology 54 6711 (2009)
Grotzer AM, Schultke E, Brauer-Kirsch E, Laissue AJ. Microbeam radiation therapy Physica Medica 31 564 (2015)
Hadsell M, Cao G, Zhang J, Burk L, Schreiber T, Schreiber E, et al. Pilot study of compact microbeam radiation therapy using carbon nanotube field emission micro-scanner Medical Physics 41 061710-1 (2014)
Jaquet M, Suorti P. Radiation therapy at compact Compton sources Physica Medica 31 596 (2015)