Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy

Griffin, Robert J.; Ahmed, Mansoor M.; Amendola, Beatriz E.; Belyakov, O.V.; Bentzen, Søren M.; Butterworth, Karl T.; Chang, S; Coleman, C. Norman; Djonov, Valentin; Formenti, S.C.; Glatstein, Eli; Guha, Chandan; Le, Quynh Thu; Loo, Billy W.; Mahadevan, Anand; Massaccesi, Mariangela; Maxim, Peter G.; Mohiuddin, Majid; Mohiuddin, Mohammed; Mayr, Nina A.; Obcemea, Ceferino; Petersson, Kristoffer; Regine, William F.; Roach, Mack; Romanelli, Pantaleo; Simone, Charles B.; Snider, J.W.; Spitz, Douglas R.; Vikram, Bhadrasain; Vozenin, Marie Catherine; Abdel‐Wahab, May; Welsh, James S.; Wu, Xiaodong; Limoli, Charles L.

doi:10.1016/j.ijrobp.2020.03.028

Cited by 78 publications

(77 citation statements)

References 72 publications

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“…Since its early inception over 100 years ago by Kohler (1)(2)(3)(4), spatially fractionated radiation therapy (SFRT) in the form of 2D GRID has been applied clinically, although not as a mainstream radiation therapy modality. While conducting systemic clinical trials has been practically difficult, the reported clinical data have suggested favorable outcomes and clinical value of GRID therapy for the treatment of advanced bulky tumors (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). A recent workshop sponsored by the National Cancer Institute (NCI) and Radiosurgery Society (RSS) for assessment of, and discussion on, the techniques and clinical merits of SFRT resulted in a comprehensive summary report (6).…”

Section: Introductionmentioning

confidence: 99%

“…While conducting systemic clinical trials has been practically difficult, the reported clinical data have suggested favorable outcomes and clinical value of GRID therapy for the treatment of advanced bulky tumors (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). A recent workshop sponsored by the National Cancer Institute (NCI) and Radiosurgery Society (RSS) for assessment of, and discussion on, the techniques and clinical merits of SFRT resulted in a comprehensive summary report (6). The physical 2D GRID blocks or apertures, evolving from the early kV X-ray delivery systems to the modern-day megavoltage accelerators, with the same intention of normal tissue sparing, generate similar patterns of peak-to-valley dose distribution.…”

Section: Introductionmentioning

confidence: 99%

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The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT)

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Zheng

et al. 2020

Radiation Research

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The concept of spatially fractionated radiation therapy (SFRT) was conceived over 100 years ago, first in the form of GRID, which has been applied to clinical practice since its early inception and continued to the present even with markedly improved instrumentation in radiation therapy. LATTICE radiation therapy (LRT) was introduced in 2010 as a conceptual 3D extension of GRID therapy with several uniquely different features. Since 2014, when the first patient was treated, over 150 patients with bulky tumors worldwide have received LRT. Through a brief review of the basic principles and the analysis of the collective clinical experience, a set of technical recommendations and guidelines are proposed for the clinical implementation of LRT. It is to be recognized that the current clinical practice of SFRT (GRID or LRT) is still largely based on the heuristic principles. With advancements in basic biological research and the anticipated clinical trials to systemically assess the efficacy and risk, progressively robust optimizations of the technical parameters are essential for the broader application of SFRT in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT)

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Zheng

et al. 2020

Radiation Research

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“…Non-conventional radiotherapeutic techniques, such as FLASH, are now in clinical focus in order to design pioneering, biologically based clinical trials [57].…”

Section: Clinical Advantages Of Flash Radiotherapy Derived From Currementioning

confidence: 99%

Translational Research in FLASH Radiotherapy—From Radiobiological Mechanisms to In Vivo Results

et al. 2021

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FLASH radiotherapy, or the administration of ultra-high dose rate radiotherapy, is a new radiation delivery method that aims to widen the therapeutic window in radiotherapy. Thus far, most in vitro and in vivo results show a real potential of FLASH to offer superior normal tissue sparing compared to conventionally delivered radiation. While there are several postulations behind the differential behaviour among normal and cancer cells under FLASH, the full spectra of radiobiological mechanisms are yet to be clarified. Currently the number of devices delivering FLASH dose rate is few and is mainly limited to experimental and modified linear accelerators. Nevertheless, FLASH research is increasing with new developments in all the main areas: radiobiology, technology and clinical research. This paper presents the current status of FLASH radiotherapy with the aforementioned aspects in mind, but also to highlight the existing challenges and future prospects to overcome them.

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“…Degrees of freedom that need to be optimized are the radiation dose, the fractionation schedule, radiation type, geometry of the irradiation field(s), irradiation angles, antibody type, drug concentration and drug delivery schedule. This also includes exhibiting the role of emerging radiation therapy modalities such as FLASH or spatial fractionation, which may also spare the blood pool efficiently, but for which the interaction with the immune system is unclear at the moment ( 91 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

Modeling Radioimmune Response—Current Status and Perspectives

2021

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The combination of immune therapy with radiation offers an exciting and promising treatment modality in cancer therapy. It has been hypothesized that radiation induces damage signals within the tumor, making it more detectable for the immune system. In combination with inhibiting immune checkpoints an effective anti-tumor immune response may be established. This inversion from tumor immune evasion raises numerous questions to be solved to support an effective clinical implementation: These include the optimum immune drug and radiation dose time courses, the amount of damage and associated doses required to stimulate an immune response, and the impact of lymphocyte status and dynamics. Biophysical modeling can offer unique insights, providing quantitative information addressing these factors and highlighting mechanisms of action. In this work we review the existing modeling approaches of combined ‘radioimmune’ response, as well as associated fields of study. We propose modeling attempts that appear relevant for an effective and predictive model. We emphasize the importance of the time course of drug and dose delivery in view to the time course of the triggered biological processes. Special attention is also paid to the dose distribution to circulating blood lymphocytes and the effect this has on immune competence.

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Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy

Cited by 78 publications

References 72 publications

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT)

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT)

Translational Research in FLASH Radiotherapy—From Radiobiological Mechanisms to In Vivo Results

Modeling Radioimmune Response—Current Status and Perspectives

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