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10 pages, 845 KiB

Open AccessArticle

Impressive Results after “Metabolism-Guided” Lattice Irradiation in Patients Submitted to Palliative Radiation Therapy: Preliminary Results of LATTICE_01 Multicenter Study

by Gianluca Ferini, Silvana Parisi, Sara Lillo, Anna Viola, Fabio Minutoli, Paola Critelli, Vito Valenti, Salvatore Ivan Illari, Anna Brogna, Giuseppe Emmanuele Umana, Giacomo Ferrantelli, Gabriele Lo Giudice, Chiara Carrubba, Valentina Zagardo, Anna Santacaterina, Salvatore Leotta, Alberto Cacciola, Antonio Pontoriero and Stefano Pergolizzi

Cancers 2022, 14(16), 3909; https://doi.org/10.3390/cancers14163909 - 12 Aug 2022

Cited by 18 | Viewed by 2097

Abstract

Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All [...] Read more.

Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher ¹⁸F-FDG uptake (>75% SUV max) and areas with lower ¹⁸F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10–27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: “Metabolism-guided” lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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17 pages, 3245 KiB

Open AccessArticle

A Dosimetric Parameter Reference Look-Up Table for GRID Collimator-Based Spatially Fractionated Radiation Therapy

by Hualin Zhang, Michael P. Grams, Joseph J. Foy and Nina A. Mayr

Cancers 2022, 14(4), 1037; https://doi.org/10.3390/cancers14041037 - 18 Feb 2022

Cited by 13 | Viewed by 2251

Abstract

Computations of heterogeneity dose parameters in GRID therapy remain challenging in many treatment planning systems (TPS). To address this difficulty, we developed reference dose tables for a standard GRID collimator and validate their accuracy. The .decimal Inc. GRID collimator was implemented within the [...] Read more.

Computations of heterogeneity dose parameters in GRID therapy remain challenging in many treatment planning systems (TPS). To address this difficulty, we developed reference dose tables for a standard GRID collimator and validate their accuracy. The .decimal Inc. GRID collimator was implemented within the Eclipse TPS. The accuracy of the dose calculation was confirmed in the commissioning process. Representative sets of simulated ellipsoidal tumours ranging from 6–20 cm in diameter at a 3-cm depth; 16-cm ellipsoidal tumours at 3, 6, and 10 cm in depth were studied. All were treated with 6MV photons to a 20 Gy prescription dose at the tumour center. From these, the GRID therapy dosimetric parameters (previously recommended by the Radiosurgery Society white paper) were derived. Differences in D5 through D95 and EUD between different tumour sizes at the same depth were within 5% of the prescription dose. PVDR from profile measurements at the tumour center differed from D10/D90, but D10/D90 variations for the same tumour depths were within 11%. Three approximation equations were developed for calculating EUDs of different prescription doses for three radiosensitivity levels for 3-cm deep tumours. Dosimetric parameters were consistent and predictable across tumour sizes and depths. Our study results support the use of the developed tables as a reference tool for GRID therapy. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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12 pages, 3443 KiB

Open AccessArticle

Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data

by Kim Melanie Kraus, Johanna Winter, Yating Zhang, Mabroor Ahmed, Stephanie Elisabeth Combs, Jan Jakob Wilkens and Stefan Bartzsch

Cancers 2022, 14(3), 685; https://doi.org/10.3390/cancers14030685 - 28 Jan 2022

Cited by 5 | Viewed by 3255

Abstract

Microbeam radiotherapy (MRT) is a novel, still preclinical dose delivery technique. MRT has shown reduced normal tissue effects at equal tumor control rates compared to conventional radiotherapy. Treatment planning studies are required to permit clinical application. The aim of this study was to [...] Read more.

Microbeam radiotherapy (MRT) is a novel, still preclinical dose delivery technique. MRT has shown reduced normal tissue effects at equal tumor control rates compared to conventional radiotherapy. Treatment planning studies are required to permit clinical application. The aim of this study was to establish a dose comparison between MRT and conventional radiotherapy and to identify suitable clinical scenarios for future applications of MRT. We simulated MRT treatment scenarios for clinical patient data using an inhouse developed planning algorithm based on a hybrid Monte Carlo dose calculation and implemented the concept of equivalent uniform dose (EUD) for MRT dose evaluation. The investigated clinical scenarios comprised fractionated radiotherapy of a glioblastoma resection cavity, a lung stereotactic body radiotherapy (SBRT), palliative bone metastasis irradiation, brain metastasis radiosurgery and hypofractionated breast cancer radiotherapy. Clinically acceptable treatment plans were achieved for most analyzed parameters. Lung SBRT seemed the most challenging treatment scenario. Major limitations comprised treatment plan optimization and dose calculation considering the tissue microstructure. This study presents an important step of the development towards clinical MRT. For clinical treatment scenarios using a sophisticated dose comparison concept based on EUD and EQD2, we demonstrated the capability of MRT to achieve clinically acceptable dose distributions. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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15 pages, 2215 KiB

Open AccessArticle

Immune-Mediated Effects of Microplanar Radiotherapy with a Small Animal Irradiator

by Soha Bazyar, Edward Timothy O’Brien III, Thad Benefield, Victoria R. Roberts, Rashmi J. Kumar, Gaorav P. Gupta, Otto Zhou and Yueh Z. Lee

Cancers 2022, 14(1), 155; https://doi.org/10.3390/cancers14010155 - 29 Dec 2021

Cited by 7 | Viewed by 2605

Abstract

Spatially fractionated radiotherapy has been shown to have effects on the immune system that differ from conventional radiotherapy (CRT). We compared several aspects of the immune response to CRT relative to a model of spatially fractionated radiotherapy (RT), termed microplanar radiotherapy (MRT). MRT [...] Read more.

Spatially fractionated radiotherapy has been shown to have effects on the immune system that differ from conventional radiotherapy (CRT). We compared several aspects of the immune response to CRT relative to a model of spatially fractionated radiotherapy (RT), termed microplanar radiotherapy (MRT). MRT delivers hundreds of grays of radiation in submillimeter beams (peak), separated by non-radiated volumes (valley). We have developed a preclinical method to apply MRT by a commercial small animal irradiator. Using a B16-F10 murine melanoma model, we first evaluated the in vitro and in vivo effect of MRT, which demonstrated significant treatment superiority relative to CRT. Interestingly, we observed insignificant treatment responses when MRT was applied to Rag^−/− and CD8-depleted mice. An immuno-histological analysis showed that MRT recruited cytotoxic lymphocytes (CD8), while suppressing the number of regulatory T cells (Tregs). Using RT-qPCR, we observed that, compared to CRT, MRT, up to the dose that we applied, significantly increased and did not saturate CXCL9 expression, a cytokine that plays a crucial role in the attraction of activated T cells. Finally, MRT combined with anti-CTLA-4 ablated the tumor in half of the cases, and induced prolonged systemic antitumor immunity. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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13 pages, 2457 KiB

Open AccessArticle

Proton Minibeam Radiation Therapy and Arc Therapy: Proof of Concept of a Winning Alliance

by Ramon Ortiz, Ludovic De Marzi and Yolanda Prezado

Cancers 2022, 14(1), 116; https://doi.org/10.3390/cancers14010116 - 27 Dec 2021

Cited by 3 | Viewed by 2918

Abstract

(1) Background: Proton Arc Therapy and Proton Minibeam Radiation Therapy are two novel therapeutic approaches with the potential to lower the normal tissue complication probability, widening the therapeutic window for radioresistant tumors. While the benefits of both modalities have been individually evaluated, their [...] Read more.

(1) Background: Proton Arc Therapy and Proton Minibeam Radiation Therapy are two novel therapeutic approaches with the potential to lower the normal tissue complication probability, widening the therapeutic window for radioresistant tumors. While the benefits of both modalities have been individually evaluated, their combination and its potential advantages are being assessed in this proof-of-concept study for the first time. (2) Methods: Monte Carlo simulations were employed to evaluate the dose and LET distributions in brain tumor irradiations. (3) Results: a net reduction in the dose to normal tissues (up to 90%), and the preservation of the spatial fractionation of the dose were achieved for all configurations evaluated. Additionally, Proton Minibeam Arc Therapy (pMBAT) reduces the volumes exposed to high-dose and high-LET values at expense of increased low-dose and intermediate-LET values. (4) Conclusions: pMBAT enhances the individual benefits of proton minibeams while keeping those of conventional proton arc therapy. These results might facilitate the path towards patients’ treatments since lower peak doses in normal tissues would be needed than in the case of a single array of proton minibeams. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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14 pages, 2327 KiB

Open AccessArticle

Converging Proton Minibeams with Magnetic Fields for Optimized Radiation Therapy: A Proof of Concept

by Marco Cavallone, Yolanda Prezado and Ludovic De Marzi

Cancers 2022, 14(1), 26; https://doi.org/10.3390/cancers14010026 - 22 Dec 2021

Cited by 4 | Viewed by 2925

Abstract

Proton MiniBeam Radiation Therapy (pMBRT) is a novel strategy that combines the benefits of minibeam radiation therapy with the more precise ballistics of protons to further optimize the dose distribution and reduce radiation side effects. The aim of this study is to investigate [...] Read more.

Proton MiniBeam Radiation Therapy (pMBRT) is a novel strategy that combines the benefits of minibeam radiation therapy with the more precise ballistics of protons to further optimize the dose distribution and reduce radiation side effects. The aim of this study is to investigate possible strategies to couple pMBRT with dipole magnetic fields to generate a converging minibeam pattern and increase the center-to-center distance between minibeams. Magnetic field optimization was performed so as to obtain the same transverse dose profile at the Bragg peak position as in a reference configuration with no magnetic field. Monte Carlo simulations reproducing realistic pencil beam scanning settings were used to compute the dose in a water phantom. We analyzed different minibeam generation techniques, such as the use of a static multislit collimator or a dynamic aperture, and different magnetic field positions, i.e., before or within the water phantom. The best results were obtained using a dynamic aperture coupled with a magnetic field within the water phantom. For a center-to-center distance increase from 4 mm to 6 mm, we obtained an increase of peak-to-valley dose ratio and decrease of valley dose above 50%. The results indicate that magnetic fields can be effectively used to improve the spatial modulation at shallow depth for enhanced healthy tissue sparing. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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30 pages, 7102 KiB

Open AccessArticle

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

by Mariele Romano, Alberto Bravin, Alberto Mittone, Alicia Eckhardt, Giacomo E. Barbone, Lucie Sancey, Julien Dinkel, Stefan Bartzsch, Jens Ricke, Marianna Alunni-Fabbroni, Heidrun Hirner-Eppeneder, Dmitry Karpov, Cinzia Giannini, Oliver Bunk, Audrey Bouchet, Viktoria Ruf, Armin Giese and Paola Coan

Cancers 2021, 13(19), 4953; https://doi.org/10.3390/cancers13194953 - 1 Oct 2021

Cited by 4 | Viewed by 3105

Abstract

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats [...] Read more.

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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13 pages, 18744 KiB

Open AccessArticle

First Evaluation of Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy of Glioma-Bearing Rats

by Annaïg Bertho, Ramon Ortiz, Marjorie Juchaux, Cristèle Gilbert, Charlotte Lamirault, Frederic Pouzoulet, Laura Polledo, Alethea Liens, Nils Warfving, Catherine Sebrie, Laurène Jourdain, Annalisa Patriarca, Ludovic de Marzi and Yolanda Prezado

Cancers 2021, 13(19), 4865; https://doi.org/10.3390/cancers13194865 - 28 Sep 2021

Cited by 24 | Viewed by 2608

Abstract

(1) Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy technique using spatially modulated narrow proton beams. pMBRT results in a significantly reduced local tissue toxicity while maintaining or even increasing the tumor control efficacy as compared to conventional radiotherapy in small [...] Read more.

(1) Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy technique using spatially modulated narrow proton beams. pMBRT results in a significantly reduced local tissue toxicity while maintaining or even increasing the tumor control efficacy as compared to conventional radiotherapy in small animal experiments. In all the experiments performed up to date in tumor bearing animals, the dose was delivered in one single fraction. This is the first assessment on the impact of a temporal fractionation scheme on the response of glioma-bearing animals to pMBRT. (2) Methods: glioma-bearing rats were irradiated with pMBRT using a crossfire geometry. The response of the irradiated animals in one and two fractions was compared. An additional group of animals was also treated with conventional broad beam irradiations. (3) Results: pMBRT delivered in two fractions at the biological equivalent dose corresponding to one fraction resulted in the highest median survival time, with 80% long-term survivors free of tumors. No increase in local toxicity was noted in this group with respect to the other pMBRT irradiated groups. Conventional broad beam irradiations resulted in the most severe local toxicity. (4) Conclusion: Temporal fractionation increases the therapeutic index in pMBRT and could ease the path towards clinical trials. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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15 pages, 584 KiB

Open AccessArticle

Conceptual Design of a Novel Nozzle Combined with a Clinical Proton Linac for Magnetically Focussed Minibeams

by Tim Schneider, Annalisa Patriarca, Alberto Degiovanni, Manuel Gallas and Yolanda Prezado

Cancers 2021, 13(18), 4657; https://doi.org/10.3390/cancers13184657 - 16 Sep 2021

Cited by 9 | Viewed by 2101

Abstract

(1) Background: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach with the potential to significantly increase normal tissue sparing while providing tumour control equivalent or superior to standard proton therapy. For reasons of efficiency, flexibility and minibeam quality, the optimal implementation [...] Read more.

(1) Background: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach with the potential to significantly increase normal tissue sparing while providing tumour control equivalent or superior to standard proton therapy. For reasons of efficiency, flexibility and minibeam quality, the optimal implementation of pMBRT should use magnetically focussed minibeams which, however, could not yet be generated in a clinical environment. In this study, we evaluated our recently proposed minibeam nozzle together with a new clinical proton linac as a potential implementation. (2) Methods: Monte Carlo simulations were performed to determine under which conditions minibeams can be generated and to evaluate the robustness against focussing magnet errors. Moreover, an example of conventional pencil beam scanning irradiation was simulated. (3) Results: Excellent minibeam sizes between 0.6 and 0.9 mm full width at half maximum could be obtained and a good tolerance to errors was observed. Furthermore, the delivery of a 10 cm × 10 cm field with pencil beams was demonstrated. (4) Conclusion: The combination of the new proton linac and minibeam nozzle could represent an optimal implementation of pMBRT by allowing the generation of magnetically focussed minibeams with clinically relevant parameters. It could furthermore be used for conventional pencil beam scanning. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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14 pages, 769 KiB

Open AccessArticle

Quantification of Differential Response of Tumour and Normal Cells to Microbeam Radiation in the Absence of FLASH Effects

by Harriet Steel, Sarah C. Brüningk, Carol Box, Uwe Oelfke and Stefan H. Bartzsch

Cancers 2021, 13(13), 3238; https://doi.org/10.3390/cancers13133238 - 29 Jun 2021

Cited by 10 | Viewed by 2455

Abstract

Microbeam radiotherapy (MRT) is a preclinical method of delivering spatially-fractionated radiotherapy aiming to improve the therapeutic window between normal tissue complication and tumour control. Previously, MRT was limited to ultra-high dose rate synchrotron facilities. The aim of this study was to investigate in [...] Read more.

Microbeam radiotherapy (MRT) is a preclinical method of delivering spatially-fractionated radiotherapy aiming to improve the therapeutic window between normal tissue complication and tumour control. Previously, MRT was limited to ultra-high dose rate synchrotron facilities. The aim of this study was to investigate in vitro effects of MRT on tumour and normal cells at conventional dose rates produced by a bench-top X-ray source. Two normal and two tumour cell lines were exposed to homogeneous broad beam (BB) radiation, MRT, or were separately irradiated with peak or valley doses before being mixed. Clonogenic survival was assessed and compared to BB-estimated surviving fractions calculated by the linear-quadratic (LQ)-model. All cell lines showed similar BB sensitivity. BB LQ-model predictions exceeded the survival of cell lines following MRT or mixed beam irradiation. This effect was stronger in tumour compared to normal cell lines. Dose mixing experiments could reproduce MRT survival. We observed a differential response of tumour and normal cells to spatially fractionated irradiations in vitro, indicating increased tumour cell sensitivity. Importantly, this was observed at dose rates precluding the presence of FLASH effects. The LQ-model did not predict cell survival when the cell population received split irradiation doses, indicating that factors other than local dose influenced survival after irradiation. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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14 pages, 53309 KiB

Open AccessArticle

A Potential Renewed Use of Very Heavy Ions for Therapy: Neon Minibeam Radiation Therapy

by Yolanda Prezado, Ryochi Hirayama, Naruhiro Matsufuji, Taku Inaniwa, Immaculada Martínez-Rovira, Olivier Seksek, Annaïg Bertho, Sachiko Koike, Dalila Labiod, Frederic Pouzoulet, Laura Polledo, Nils Warfving, Aléthéa Liens, Judith Bergs and Takashi Shimokawa

Cancers 2021, 13(6), 1356; https://doi.org/10.3390/cancers13061356 - 17 Mar 2021

Cited by 13 | Viewed by 3593

Abstract

(1) Background: among all types of radiation, very heavy ions, such as Neon (Ne) or Argon (Ar), are the optimum candidates for hypoxic tumor treatments due to their reduced oxygen enhancement effect. However, their pioneering clinical use in the 1970s was halted due [...] Read more.

(1) Background: among all types of radiation, very heavy ions, such as Neon (Ne) or Argon (Ar), are the optimum candidates for hypoxic tumor treatments due to their reduced oxygen enhancement effect. However, their pioneering clinical use in the 1970s was halted due to severe side effects. The aim of this work was to provide a first proof that the combination of very heavy ions with minibeam radiation therapy leads to a minimization of toxicities and, thus, opening the door for a renewed use of heavy ions for therapy; (2) Methods: mouse legs were irradiated with either Ne MBRT or Ne broad beams at the same average dose. Skin toxicity was scored for a period of four weeks. Histopathology evaluations were carried out at the end of the study; (3) Results: a significant difference in toxicity was observed between the two irradiated groups. While severe da-mage, including necrosis, was observed in the broad beam group, only light to mild erythema was present in the MBRT group; (4) Conclusion: Ne MBRT is significantly better tolerated than conventional broad beam irradiations. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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15 pages, 8125 KiB

Open AccessArticle

Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors

by Laura Eling, Audrey Bouchet, Alexandre Ocadiz, Jean-François Adam, Sarvenaz Kershmiri, Hélène Elleaume, Michael Krisch, Camille Verry, Jean A. Laissue, Jacques Balosso and Raphaël Serduc

Cancers 2021, 13(5), 936; https://doi.org/10.3390/cancers13050936 - 24 Feb 2021

Cited by 25 | Viewed by 2461

Abstract

Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, [...] Read more.

Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose. An increased number of ports and an accumulated valley dose maintained at 10 Gy delayed tumor growth and improved survival. Histopathologically, cell death, vascular damage, and inflammatory response increased in tumors. At identical valley isodose, each additional MRT port extended survival, resulting in an exponential correlation between port numbers and animal lifespan (r² = 0.9928). A 10 Gy valley dose, in MRT mode, delivered through 5 ports, achieved the same survival as a 25 Gy BB irradiation because of tumor dose hot spots created by intersecting microbeams. Conversely, normal tissue damage remained minimal in all the single converging extratumoral arrays. Multiport MRT reached exceptional ~2.5-fold biological equivalent tumor doses. The unique normal tissue sparing and therapeutic index are eminent prerequisites for clinical translation. Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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Review

Jump to: Research

13 pages, 820 KiB

Open AccessReview

Should Peak Dose Be Used to Prescribe Spatially Fractionated Radiation Therapy?—A Review of Preclinical Studies

by Cristian Fernandez-Palomo, Sha Chang and Yolanda Prezado

Cancers 2022, 14(15), 3625; https://doi.org/10.3390/cancers14153625 - 26 Jul 2022

Cited by 20 | Viewed by 2667

Abstract

Spatially fractionated radiotherapy (SFRT) is characterized by the coexistence of multiple hot and cold dose subregions throughout the treatment volume. In preclinical studies using single-fraction treatment, SFRT can achieve a significantly higher therapeutic index than conventional radiotherapy (RT). Published clinical studies of SFRT [...] Read more.

Spatially fractionated radiotherapy (SFRT) is characterized by the coexistence of multiple hot and cold dose subregions throughout the treatment volume. In preclinical studies using single-fraction treatment, SFRT can achieve a significantly higher therapeutic index than conventional radiotherapy (RT). Published clinical studies of SFRT followed by RT have reported promising results for bulky tumors. Several clinical trials are currently underway to further explore the clinical benefits of SFRT. However, we lack the important understanding of the correlation between dosimetric parameters and treatment response that we have in RT. In this work, we reviewed and analyzed this important correlation from previous preclinical SFRT studies. We reviewed studies prior to 2022 that treated animal-bearing tumors with minibeam radiotherapy (MBRT) or microbeam radiotherapy (MRT). Eighteen studies met our selection criteria. Increased lifespan (ILS) relative to control was used as the treatment response. The preclinical SFRT dosimetric parameters analyzed were peak dose, valley dose, average dose, beam width, and beam spacing. We found that valley dose was the dosimetric parameter with the strongest correlation with ILS (p-value < 0.01). For studies using MRT, average dose and peak dose were also significantly correlated with ILS (p-value < 0.05). This first comprehensive review of preclinical SFRT studies shows that the valley dose (rather than the peak dose) correlates best with treatment outcome (ILS). Full article

(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)

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