Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-05T05:38:10.395Z Has data issue: false hasContentIssue false

Divide and conquer: spatially fractionated radiation therapy

Published online by Cambridge University Press:  12 January 2022

Yolanda Prezado*
Affiliation:
Institut Curie, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer Institut Curie, Université PSL, Orsay, France Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer, 91400Orsay, France
*
Author for correspondence: Yolanda Prezado, E-mail: [email protected]

Abstract

Spatially fractionated radiation therapy (SFRT) challenges some of the classical dogmas in conventional radiotherapy. The highly modulated spatial dose distributions in SFRT have been shown to lead, both in early clinical trials and in small animal experiments, to a significant increase in normal tissue dose tolerances. Tumour control effectiveness is maintained or even enhanced in some configurations as compared with conventional radiotherapy. SFRT seems to activate distinct radiobiological mechanisms, which have been postulated to involve bystander effects, microvascular alterations and/or immunomodulation. Currently, it is unclear which is the dosimetric parameter which correlates the most with both tumour control and normal tissue sparing in SFRT. Additional biological experiments aiming at parametrizing the relationship between the irradiation parameters (beam width, spacing, peak-to-valley dose ratio, peak and valley doses) and the radiobiology are needed. A sound knowledge of the interrelation between the physical parameters in SFRT and the biological response would expand its clinical use, with a higher level of homogenisation in the realisation of clinical trials. This manuscript reviews the state of the art of this promising therapeutic modality, the current radiobiological knowledge and elaborates on future perspectives.

Type
Review
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Borras, JM et al. (2016) How many new cancer patients in Europe will require radiotherapy by 2025? An ESTRO-HERO analysis. Radiotherapy & Oncology 119, 511.CrossRefGoogle ScholarPubMed
Bernier, J, Hall, EJ and Giaccia, A (2004) Radiation oncology: a century of achievements. Nature Reviews Cancer 4, 737747.CrossRefGoogle ScholarPubMed
Mothersill, C, Rusin, A and Seymour, C (2019) Relevance of non-targeted effects for radiotherapy and diagnostic radiology; a historical and conceptual analysis of key players. Cancers (Basel) 11, 12361261.CrossRefGoogle ScholarPubMed
Rodel, F et al. (2015) Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Letters 356, 105113.CrossRefGoogle ScholarPubMed
Park, HJ et al. (2012) Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiation Research 177, 311327.CrossRefGoogle Scholar
Weichselbaum, RR et al. (2017) Radiotherapy and immunotherapy: a beneficial liaison? Nature Reviews. Clinical Oncology 14, 365379.CrossRefGoogle ScholarPubMed
Steel, GG, McMillan, TJ and Peacock, JH (1989) The 5Rs of radiobiology. International Journal of Radiation Biology 56, 10451048.CrossRefGoogle ScholarPubMed
Murshed, H (2019) Fundamentals of Radiation Oncology, 3rd Edn.. Amsterdam, The Netherlands: Elsevier.Google Scholar
Filatenkov, A et al. (2015) Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clinical Cancer Research 21, 37273739.CrossRefGoogle ScholarPubMed
Friedl, AA et al. (2021) Radiobiology of the FLASH effect. Medical Physics, in press.CrossRefGoogle ScholarPubMed
Girdhani, S, Sachs, R and Hlatky, L (2013) Biological effects of proton radiation: what we know and don't know. Radiation Research 179, 257272.CrossRefGoogle ScholarPubMed
Gameiro, SR et al. (2016) Tumor cells surviving exposure to proton or photon radiation share a common immunogenic modulation signature, rendering them more sensitive to T cell-mediated killing. International Journal of Radiation Oncology Biology Physics 95, 120130.CrossRefGoogle ScholarPubMed
Mohiuddin, M et al. (1999) High-dose spatially-fractionated radiation (GRID): a new paradigm in the management of advanced cancers. International Journal of Radiation Oncology Biology Physics 45, 721727.CrossRefGoogle ScholarPubMed
Laissue, JA, Blattmann, H and Slatkin, DN (2012) [Alban Köhler (1874–1947): inventor of grid therapy]. Zeitschrift fur Medizinische Physik 22, 9099.CrossRefGoogle Scholar
Slatkin, DN et al. (1992) Microbeam radiation therapy. Medical Physics 19, 13951400.CrossRefGoogle ScholarPubMed
Dilmanian, FA et al. (2006) Interlaced x-ray microplanar beams: a radiosurgery approach with clinical potential. Proceedings of the National Academy of Sciences of the USA 103, 97099714.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2011) Dosimetry protocol for the preclinical trials in white-beam minibeam radiation therapy. Medical Physics 38, 50125020.CrossRefGoogle ScholarPubMed
De Marzi, L et al. (2019) Spatial fractionation of the dose in proton therapy: proton minibeam radiation therapy. Cancer Radiotherapie 23, 677681.CrossRefGoogle ScholarPubMed
Amendola, BE et al. (2019) Safety and efficacy of lattice radiotherapy in voluminous non-small cell lung cancer. Cureus 11, e4263.Google ScholarPubMed
Billena, C and Khan, AJ (2019) A current review of spatial fractionation: back to the future? International Journal of Radiation Oncology Biology Physics 104, 177187.CrossRefGoogle ScholarPubMed
Duriseti, S et al. (2021) Spatially fractionated stereotactic body radiation therapy (Lattice) for large tumors. Advances in Radiation Oncology 6, 100639.CrossRefGoogle ScholarPubMed
Yan, W et al. (2020) Spatially fractionated radiation therapy: history, present and the future. Clinical and Translational Radiation Oncology 20, 3038.CrossRefGoogle ScholarPubMed
Bouchet, A et al. (2015) Effects of microbeam radiation therapy on normal and tumoral blood vessels. Physica Medica: PM 31, 634641.CrossRefGoogle ScholarPubMed
Marks, H (1952) Clinical experience with irradiation through a grid. Radiology 58, 338342.CrossRefGoogle ScholarPubMed
Meyer, J et al. (2019) Spatially fractionated proton minibeams. The British Journal of Radiology 92, 20180466.CrossRefGoogle ScholarPubMed
Zhang, X et al. (2016) Application of spatially fractionated radiation (GRID) to helical tomotherapy using a novel TOMOGRID template. Technology in Cancer Research & Treatment 15, 91100.CrossRefGoogle ScholarPubMed
Penagaricano, JA et al. (2010) Evaluation of spatially fractionated radiotherapy (GRID) and definitive chemoradiotherapy with curative intent for locally advanced squamous cell carcinoma of the head and neck: initial response rates and toxicity. International Journal of Radiation Oncology Biology Physics 76, 13691375.CrossRefGoogle ScholarPubMed
Henry, T et al. (2017) Proton grid therapy: a proof-of-concept study. Technology in Cancer Research & Treatment 16, 749757.CrossRefGoogle ScholarPubMed
Gao, M et al. (2018) Spatially fractionated (GRID) radiation therapy using proton pencil beam scanning (PBS): feasibility study and clinical implementation. Medical Physics 45, 16451653.CrossRefGoogle ScholarPubMed
Prezado, Y and Fois, GR (2013) Proton-minibeam radiation therapy: a proof of concept. Medical Physics 40, 031712.CrossRefGoogle Scholar
Mohiuddin, M et al. (2020) Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). The British Journal of Radiology 93, 20190572.CrossRefGoogle Scholar
Wu, X et al. (2020) The technical and clinical implementation of LATTICE radiation therapy (LRT). Radiation Research 194, 737746.CrossRefGoogle Scholar
Xiaodong Wu, MMA et al. (2010) On modern technical approaches of three-dimensional high-dose lattice radiotherapy (LRT). Cureus 2, e9 (1–8).Google Scholar
Teoh, M et al. (2011) Volumetric modulated arc therapy: a review of current literature and clinical use in practice. The British Journal of Radiology 84, 967996.CrossRefGoogle ScholarPubMed
Amendola, BE et al. (2018) Improved outcome of treating locally advanced lung cancer with the use of lattice radiotherapy (LRT): a case report. Clinical and Translational Radiation Oncology 9, 6871.CrossRefGoogle ScholarPubMed
Amendola NP, BE et al. (2010) Lattice radiotherapy with RapidArc for treatment of gynecological tumors: dosimetric and early clinical evaluations. Cureus 2, 16.Google Scholar
Amendola NP, BE et al. (2019) Safety and efficacy of Lattice radiotherapy in voluminous non-small cell lung cancer. Cureus 11, e4263 (1–11).Google Scholar
Blanco Suarez BA, JM et al. (2015) The use of lattice radiation therapy (LRT) in the treatment of bulky tumors: a case report of a large metastatic mixed Mullerian ovarian tumor. Cureus 7, e389 (1–9).Google Scholar
Pollack, A et al. (2020) Phase I trial of MRI-guided prostate cancer lattice extreme ablative dose (LEAD) boost radiation therapy. International Journal of Radiation Oncology Biology Physics 107, 305315.CrossRefGoogle ScholarPubMed
Jiang, L et al. (2020) Combined high-dose LATTICE radiation therapy and immune checkpoint blockade for advanced bulky tumors: the concept and a case report. Frontiers in Oncology 10, 548132.CrossRefGoogle ScholarPubMed
Yang, D (2021) Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma. preprint.CrossRefGoogle Scholar
Slatkin, DN et al. (1995) Subacute neuropathological effects of microplanar beams of x-rays from a synchrotron wiggler. Proceedings of the National Academy of Sciences of the USA 92, 87838787.CrossRefGoogle ScholarPubMed
Gil, S et al. (2011) Synchrotron radiation in cancer treatments and diagnostics: an overview. Clinical & Translational Oncology 13, 715720.CrossRefGoogle ScholarPubMed
Bouchet, A et al. (2013) Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain. Radiotherapy & Oncology 108, 143148.CrossRefGoogle Scholar
Eling, L et al. (2019) Ultra high dose rate synchrotron microbeam radiation therapy. Preclinical evidence in view of a clinical transfer. Radiotherapy & Oncology 139, 5661.CrossRefGoogle ScholarPubMed
Serduc, R et al. (2008) Characterization and quantification of cerebral edema induced by synchrotron x-ray microbeam radiation therapy. Physics in Medicine and Biology 53, 11531166.CrossRefGoogle ScholarPubMed
Laissue, JA et al. (2007) Prospects for microbeam radiation therapy of brain tumours in children to reduce neurological sequelae. Developmental Medicine & Child Neurology 49, 577581.CrossRefGoogle ScholarPubMed
Schultke, E et al. (2008) Memory and survival after microbeam radiation therapy. European Journal of Radiology 68(3 Suppl), S142S146.CrossRefGoogle ScholarPubMed
Brauer-Krisch, E et al. (2010) Effects of pulsed, spatially fractionated, microscopic synchrotron X-ray beams on normal and tumoral brain tissue. Mutation Research 704, 160166.CrossRefGoogle ScholarPubMed
Fernandez-Palomo, C et al. (2020) Animal models in microbeam radiation therapy: a scoping review. Cancers (Basel) 12, 527553.CrossRefGoogle ScholarPubMed
Fernandez-Palomo, C et al. (2020) Complete remission of mouse melanoma after temporally fractionated microbeam radiotherapy. Cancers (Basel) 12, 26562670.CrossRefGoogle ScholarPubMed
Eling, L et al. (2021) Unexpected benefits of multiport synchrotron microbeam radiation therapy for brain tumors. Cancers (Basel) 13, 936951.CrossRefGoogle ScholarPubMed
Favaudon, V (2019) [Flash radiotheray at very high dose-rate: a brief account of the current situation]. Cancer Radiotherapie 23, 674676.CrossRefGoogle Scholar
Mazal, A et al. (2020) FLASH and minibeams in radiation therapy: the effect of microstructures on time and space and their potential application to protontherapy. The British Journal of Radiology 93, 20190807.CrossRefGoogle ScholarPubMed
Smyth, LML et al. (2018) Comparative toxicity of synchrotron and conventional radiation therapy based on total and partial body irradiation in a murine model. Scientific Reports 8, 12044.CrossRefGoogle ScholarPubMed
Steel, H et al. (2021) Quantification of differential response of tumour and normal cells to microbeam radiation in the absence of FLASH effects. Cancers (Basel) 13, 32383252.CrossRefGoogle ScholarPubMed
Vozenin, MC et al. (2019) The advantage of FLASH radiotherapy confirmed in Mini-pig and Cat-cancer patients. Clinical Cancer Research 25, 3542.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2009) X-ray energy optimization in minibeam radiation therapy. Medical Physics 36, 48974902.CrossRefGoogle ScholarPubMed
Martinez-Rovira, I, Fois, G and Prezado, Y (2015) Dosimetric evaluation of new approaches in GRID therapy using nonconventional radiation sources. Medical Physics 42, 685693.CrossRefGoogle ScholarPubMed
Manchado de Sola, F et al. (2018) Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy. Medical Physics 45, 33793390.CrossRefGoogle ScholarPubMed
Hadsell, M et al. (2013) A first generation compact microbeam radiation therapy system based on carbon nanotube X-ray technology. Applied Physics Letters 103, 183505.CrossRefGoogle ScholarPubMed
Winter, J et al. (2020) Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube. Physics and Imaging in Radiation Oncology 14, 7481.CrossRefGoogle ScholarPubMed
Prezado JFA, Y et al. (2010) Synchrotron radiation therapy from a medical physics point of view. AIP Conference Proceedings 1266, 3.Google Scholar
Bouchet, A et al. (2016) Better efficacy of synchrotron spatially microfractionated radiation therapy than uniform radiation therapy on glioma. International Journal of Radiation Oncology Biology Physics 95, 14851494.CrossRefGoogle ScholarPubMed
Sabatasso, S et al. (2021) Transient and efficient vascular permeability window for adjuvant drug delivery triggered by microbeam radiation. Cancers (Basel) 13, 1–16.CrossRefGoogle ScholarPubMed
Serduc, R et al. (2010) High-precision radiosurgical dose delivery by interlaced microbeam arrays of high-flux low-energy synchrotron X-rays. PLoS ONE 5, e9028.CrossRefGoogle ScholarPubMed
Romanelli, P et al. (2013) Synchrotron-generated microbeam sensorimotor cortex transections induce seizure control without disruption of neurological functions. PLoS ONE 8, e53549.CrossRefGoogle ScholarPubMed
Fardone, E et al. (2018) Synchrotron-generated microbeams induce hippocampal transections in rats. Scientific Reports 8, 184.CrossRefGoogle ScholarPubMed
Pouyatos, B et al. (2016) Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas. Scientific Reports 6, 27250.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2017) Transfer of minibeam radiation therapy into a cost-effective equipment for radiobiological studies: a proof of concept. Scientific Reports 7, 17295.CrossRefGoogle Scholar
Bazyar, S et al. (2017) Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies. Physics in Medicine and Biology 62, 89248942.CrossRefGoogle ScholarPubMed
Deman, P et al. (2011) Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for preclinical treatment plans. Physics in Medicine and Biology 56, 44654480.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2015) Tolerance to dose escalation in minibeam radiation therapy applied to normal rat brain: long-term clinical, radiological and histopathological analysis. Radiation Research 184, 314321.CrossRefGoogle ScholarPubMed
Deman, P et al. (2012) Monochromatic minibeams radiotherapy: from healthy tissue-sparing effect studies toward first experimental glioma bearing rats therapy. International Journal of Radiation Oncology Biology Physics 82, e693e700.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2012) Increase of lifespan for glioma-bearing rats by using minibeam radiation therapy. Journal of Synchrotron Radiation 19, 6065.CrossRefGoogle ScholarPubMed
Sotiropoulos, M et al. (2021) X-rays minibeam radiation therapy at a conventional irradiator: pilot evaluation in F98-glioma bearing rats and dose calculations in a human phantom. Clinical and Translational Radiation Oncology 27, 4449.CrossRefGoogle Scholar
Kundapur, V (2019) New kid on the block – mini beam radiation treatment- final report of a randomized phase III study of treating canine denovo brain tumors. International Journal of Radiation Oncology, Biology, Physics 105, 2.CrossRefGoogle Scholar
Tinganelli, W and Durante, M (2020) Carbon ion radiobiology. Cancers (Basel) 12, 30223059.CrossRefGoogle ScholarPubMed
Potez, M et al. (2019) Synchrotron microbeam radiation therapy as a new approach for the treatment of radioresistant melanoma: potential underlying mechanisms. International Journal of Radiation Oncology Biology Physics 105, 11261136.CrossRefGoogle ScholarPubMed
Zlobinskaya, O et al. (2013) Reduced side effects by proton microchannel radiotherapy: study in a human skin model. Radiation and Environmental Biophysics 52, 123133.CrossRefGoogle Scholar
Girst, S et al. (2016) Proton minibeam radiation therapy reduces side effects in an in vivo mouse ear model. International Journal of Radiation Oncology Biology Physics 95, 234241.CrossRefGoogle Scholar
Lamirault, C et al. (2020) Short and long-term evaluation of the impact of proton minibeam radiation therapy on motor, emotional and cognitive functions. Scientific Reports 10, 13511.CrossRefGoogle Scholar
Prezado, Y et al. (2017) Proton minibeam radiation therapy spares normal rat brain: long-term clinical, radiological and histopathological analysis. Scientific Reports 7, 14403.CrossRefGoogle ScholarPubMed
Lamirault, C et al. (2020) Spatially modulated proton minibeams results in the same increase of lifespan as a uniform target dose coverage in F98-glioma-bearing rats. Radiation Research 194, 715723.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2018) Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas. Scientific Reports 8, 16479.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2019) Tumor control in RG2 glioma-bearing rats: a comparison between proton minibeam therapy and standard proton therapy. International Journal of Radiation Oncology Biology Physics 104, 266271.CrossRefGoogle ScholarPubMed
Bertho, A et al. (2021) First evaluation of temporal and spatial fractionation in proton minibeam radiation therapy of glioma-bearing rats. Cancers (Basel) 13, 48654879.CrossRefGoogle ScholarPubMed
Annaig Bertho, EB et al. (2021) Role of the immune system in anti-tumoral response to proton minibeam radiation therapy. Radiotherapy and Oncology 161, 1.Google Scholar
Lansonneur, P et al. (2020) First proton minibeam radiation therapy treatment plan evaluation. Scientific Reports 10, 7025.CrossRefGoogle ScholarPubMed
Sotiropoulos, M and Prezado, Y (2021) A scanning dynamic collimator for spot-scanning proton minibeam production. Scientific Reports 11, 18321.CrossRefGoogle ScholarPubMed
Schneider, T et al. (2020) Advancing proton minibeam radiation therapy: magnetically focussed proton minibeams at a clinical centre. Scientific Reports 10, 1384.CrossRefGoogle Scholar
Schneider, T et al. (2021) Conceptual design of a novel nozzle combined with a clinical proton linac for magnetically focussed minibeams. Cancers (Basel) 13, 46574671.CrossRefGoogle ScholarPubMed
Dilmanian, FA, Eley, JG and Krishnan, S (2015) Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation. International Journal of Radiation Oncology Biology Physics 92, 469474.CrossRefGoogle ScholarPubMed
Schneider, T, Patriarca, A and Prezado, Y (2019) Improving the dose distributions in minibeam radiation therapy: helium ions vs protons. Medical Physics 46, 36403648.CrossRefGoogle ScholarPubMed
Gonzalez, W, Peucelle, C and Prezado, Y (2017) Theoretical dosimetric evaluation of carbon and oxygen minibeam radiation therapy. Medical Physics 44, 19211929.CrossRefGoogle ScholarPubMed
Gonzalez, W and Prezado, Y (2018) Spatial fractionation of the dose in heavy ions therapy: an optimization study. Medical Physics 45, 26202627.CrossRefGoogle Scholar
Martinez-Rovira, I et al. (2017) Carbon and oxygen minibeam radiation therapy: an experimental dosimetric evaluation. Medical Physics 44, 42234229.CrossRefGoogle ScholarPubMed
Dilmanian, FA et al. (2012) Interleaved carbon minibeams: an experimental radiosurgery method with clinical potential. International Journal of Radiation Oncology Biology Physics 84, 514519.CrossRefGoogle ScholarPubMed
Castro, JR et al. (1994) Experience in charged particle irradiation of tumors of the skull base: 1977–1992. International Journal of Radiation Oncology Biology Physics 29, 647655.CrossRefGoogle ScholarPubMed
Peucelle, C, Martinez-Rovira, I and Prezado, Y (2015) Spatial fractionation of the dose using neon and heavier ions: a Monte Carlo study. Medical Physics 42, 59285936.CrossRefGoogle ScholarPubMed
Prezado, Y et al. (2021) A potential renewed use of very heavy ions for therapy: neon minibeam radiation therapy. Cancers (Basel) 13, 13561370.CrossRefGoogle ScholarPubMed
Sabatasso, S et al. (2011) Microbeam radiation-induced tissue damage depends on the stage of vascular maturation. International Journal of Radiation Oncology Biology Physics 80, 15221532.CrossRefGoogle ScholarPubMed
Serduc, R et al. (2006) In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature. International Journal of Radiation Oncology Biology Physics 64, 15191527.CrossRefGoogle ScholarPubMed
Bouchet, A et al. (2010) Preferential effect of synchrotron microbeam radiation therapy on intracerebral 9L gliosarcoma vascular networks. International Journal of Radiation Oncology Biology Physics 78, 15031512.CrossRefGoogle ScholarPubMed
Griffin, RJ et al. (2012) Microbeam radiation therapy alters vascular architecture and tumor oxygenation and is enhanced by a galectin-1 targeted anti-angiogenic peptide. Radiation Research 177, 804812.CrossRefGoogle ScholarPubMed
Bronnimann, D et al. (2016) Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo. Scientific Reports 6, 33601.CrossRefGoogle ScholarPubMed
Sathishkumar, S et al. (2005) Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: implications for endothelial apoptosis. Cancer Biology & Therapy 4, 979986.CrossRefGoogle ScholarPubMed
Garcia-Barros, M et al. (2003) Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science (New York, N.Y.) 300, 11551159.CrossRefGoogle ScholarPubMed
Kanagavelu, S et al. (2014) In vivo effects of lattice radiation therapy on local and distant lung cancer: potential role of immunomodulation. Radiation Research 182, 149162.CrossRefGoogle ScholarPubMed
Wang, R et al. (2018) Molecular mechanism of bystander effects and related abscopal/cohort effects in cancer therapy. Oncotarget 9, 1863718647.CrossRefGoogle ScholarPubMed
Asur, RS et al. (2012) Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells. Radiation Research 177, 751765.CrossRefGoogle ScholarPubMed
Sathishkumar, S et al. (2002) The impact of TNF-alpha induction on therapeutic efficacy following high dose spatially fractionated (GRID) radiation. Technology in Cancer Research & Treatment 1, 141147.CrossRefGoogle ScholarPubMed
Shareef, MM et al. (2007) Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma. Cancer Research 67, 1181111820.CrossRefGoogle ScholarPubMed
Lobachevsky, P et al. (2021) Synchrotron X-ray radiation-induced bystander effect: an impact of the scattered radiation, distance from the irradiated site and p53 cell status. Frontiers in Oncology 11, 685598.CrossRefGoogle ScholarPubMed
Lobachevsky, P et al. (2015) Assessment and implications of scattered microbeam and broadbeam synchrotron radiation for bystander effect studies. Radiation Research 184, 650659.CrossRefGoogle ScholarPubMed
Smith, R et al. (2018) Homogenous and microbeam X-ray radiation induces proteomic changes in the brains of irradiated rats and in the brains of nonirradiated cage mate rats. Dose-Response 16, 1559325817750068.CrossRefGoogle ScholarPubMed
Dilmanian, FA et al. (2007) Tissue-sparing effect of x-ray microplanar beams particularly in the CNS: is a bystander effect involved? Experimental Hematology, 35–4(Suppl 1), 6977.CrossRefGoogle Scholar
Fernandez-Palomo, C et al. (2013) Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays. International Journal of Radiation Biology 89, 445453.CrossRefGoogle ScholarPubMed
Forrester, HB et al. (2020) Abscopal gene expression in response to synchrotron radiation indicates a role for immunological and DNA damage response genes. Radiation Research 194, 678687.CrossRefGoogle ScholarPubMed
Ventura, J et al. (2017) Localized synchrotron irradiation of mouse skin induces persistent systemic genotoxic and immune responses. Cancer Research 77, 63896399.CrossRefGoogle ScholarPubMed
Grass, GD, Krishna, N and Kim, S (2016) The immune mechanisms of abscopal effect in radiation therapy. Current Problems in Cancer 40, 1024.CrossRefGoogle ScholarPubMed
Griffin, RJ et al. (2020) History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, Microbeam & FLASH radiotherapy. The British Journal of Radiology 93, 20200217.CrossRefGoogle ScholarPubMed
Bouchet, A et al. (2013) Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy. PLoS ONE 8, e81874.CrossRefGoogle ScholarPubMed
Sprung, CN et al. (2012) Genome-wide transcription responses to synchrotron microbeam radiotherapy. Radiation Research 178, 249259.CrossRefGoogle ScholarPubMed
Johnsrud, AJ et al. (2020) Evidence for early stage anti-tumor immunity elicited by spatially fractionated radiotherapy-immunotherapy combinations. Radiation Research 194, 688697.CrossRefGoogle ScholarPubMed
Savage, T, Pandey, S and Guha, C (2020) Postablation modulation after single high-dose radiation therapy improves tumor control via enhanced immunomodulation. Clinical Cancer Research 26, 910921.CrossRefGoogle ScholarPubMed
Markovsky, E et al. (2019) An antitumor immune response is evoked by partial-volume single-dose radiation in 2 murine models. International Journal of Radiation Oncology Biology Physics 103, 697708.CrossRefGoogle ScholarPubMed
Smilowitz, HM et al. (2006) Synergy of gene-mediated immunoprophylaxis and microbeam radiation therapy for advanced intracerebral rat 9L gliosarcomas. Journal of Neuro-Oncology 78, 135143.CrossRefGoogle ScholarPubMed
Dilmanian, FA et al. (2002) Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy. Neuro-Oncology 4, 2638.CrossRefGoogle ScholarPubMed
Crosbie, JC et al. (2010) Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues. International Journal of Radiation Oncology Biology Physics 77, 886894.CrossRefGoogle ScholarPubMed
Fukunaga, H et al. (2019) High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation. Scientific Reports 9, 12618.CrossRefGoogle ScholarPubMed
Omar Desoukya, ND and Zhoub, G (2015) Targeted and non-targeted effects of ionizing radiation. Journal of Radiation Research and Applied Sciences 8, 7.Google Scholar
Riccardo Dal Bello, TB et al. (2020) Proposal of a chemical mechanism for mini-beam and micro-beam efficacy. Frontiers in Physics 22, 11.Google Scholar
Azzam, EI et al. (2002) Oxidative metabolism modulates signal transduction and micronucleus formation in bystander cells from alpha-particle-irradiated normal human fibroblast cultures. Cancer Research 62, 54365442.Google ScholarPubMed
Alan Mitteer, R et al. (2015) Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species. Scientific Reports 5, 13961.CrossRefGoogle ScholarPubMed
Zhang, H et al. (2020) Photon GRID radiation therapy: a physics and dosimetry white paper from the radiosurgery society (RSS) GRID/LATTICE, microbeam and FLASH radiotherapy working group. Radiation Research 194, 665677.CrossRefGoogle ScholarPubMed
Rivera, JN et al. (2020) Conventional dose rate spatially-fractionated radiation therapy (SFRT) treatment response and its association with dosimetric parameters-A preclinical study in a Fischer 344 rat model. PLoS ONE 15, e0229053.CrossRefGoogle Scholar