High-dose and fractionation effects in stereotactic radiation therapy: Analysis of tumor control data from 2965 patients

Shuryak, Igor; Carlson, David J.; Brown, J. Martin; Brenner, David J.

doi:10.1016/j.radonc.2015.05.013

Cited by 116 publications

(110 citation statements)

References 78 publications

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“…In non-small cell lung cancer, BED calculated using the linear quadratic model correlates strongly with tumor control probability regardless of the fractionation scheme 9 . Similar results have been observed in patients treated for brain metastases 11 . Because the linear quadratic model does not take into account distinct biological mechanisms at higher radiation doses, these correlative studies do not support the idea that there are fundamental differences in tumor response to radiation therapy at the high doses per fraction used for SBRT 4 .…”

Section: Sbrt Mechanisms Of Actionsupporting

confidence: 88%

Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era

Moding¹,

Mowery²,

Kirsch³

2016

The Cancer Journal

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Stereotactic body radiation therapy (SBRT) utilizing a small number of high dose radiation therapy fractions continues to expand in clinical application. Though many approaches have been proposed to radiosensitize tumors with conventional fractionation, how these radiosensitizers will translate to SBRT remains largely unknown. Here, we review our current understanding of how SBRT eradicates tumors, including the potential contributions of endothelial cell death and immune system activation. In addition, we identify several new opportunities for radiosensitization generated by the move toward high dose per fraction radiation therapy.

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Section: Sbrt Mechanisms Of Actionsupporting

confidence: 88%

Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era

Moding¹,

Mowery²,

Kirsch³

2016

The Cancer Journal

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“…2 Although the mathematical models are useful, there may be unexplored benefits from studying the molecular and cellular effects of different doses and schedules, particularly when major alterations in therapy are undertaken as with the current use of hypofractionation. The articles by Brown et al, 3 Shuryak et al, 5 and McKenna et al 63 conclude that no additional tumoricidal mechanisms are needed to explain the tumor control at higher doses compared with lower doses. Firstly, an important caveat from clinical experience is that significant late effects may not occur for years or decades as seen with standard fractionation.…”

Section: Resultsmentioning

confidence: 99%

“…The difference in the shape of the radiation survival curve using various radiobiological models from clinical data helps to explain the clinical outcome from both dose size and fractionation scheme. 5,6 Conventional RT (ConvRT) is administered in 1.8–2.2 Gy single fractions per day, 5 days per week for a total of 3–9 weeks, and maximum dose between 60 and 90 Gy. 7–9 In contrast, hyperfractionated RT (HyperRT) is administered in smaller doses of 0.5–1.8 Gy with multiple fractions per day for 2–4 weeks, and hypofractionated RT (HypoRT) as single daily fractions 3–20 Gy with a small number of fractions usually over a week.…”

Section: Introductionmentioning

confidence: 99%

“…Overall, advances in technology such as intensity-modulated RT, image-guided RT, stereotactic body RT, stereotactic radiosurgery, and protons and carbon RT have improved the ability to deliver higher radiation dose more accurately to tumors. 3,5 With these technologies, there is still some dose heterogeneity, especially with intensity-modulated RT and image-guided RT, which often by design, include a greater volume of surrounding normal tissue around the target area receiving a smaller overall dose. 1,3,10 …”

Section: Introductionmentioning

confidence: 99%

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Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy

Makinde

Eke

Aryankalayil

et al. 2016

Seminars in Radiation Oncology

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The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy. We discuss the potential of using different radiation doses and MF adaptation for targeting transcription factors, immune and inflammatory response, and cell “stemness.” Given the complex genetic composition of tumors before treatment and their adaptation to drug treatment, innovative combinations using both the pretreatment molecular data and also the MF-adaptive response to radiation may provide an important role for focused radiation therapy as an integral part of precision medicine and immunotherapy.

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“…For example, there is evidence that single-fraction stereotactic RT lacks a dose-response relationship and achieves lower tumor control rates than 3 or more fractions even if the same ‘biologically effective doses' are applied [105,106], which is consistent with a detrimental effect of missing re-oxygenation [107]. Oxygen is required for the production of superoxide from cell water radiolysis products, which greatly enhances the toxicity of IR [57].…”

Section: Combining Ketogenic Metabolic Therapy With Radiotherapy To Ementioning

confidence: 99%

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

Klement¹

2017

Complement Med Res

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Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by physicochemical reactions inducing oxidative stress in cells. Because in practice the efficacy of RT is limited by its toxicity to normal tissues, any strategy that selectively increases the radiosensitivity of tumor cells or boosts the radioresistance of normal cells is a valuable adjunct to RT. In this review, I summarize preclinical and clinical data supporting the hypothesis that ketogenic therapy through fasting and/or ketogenic diets can be utilized as such an adjunct in order to improve the outcome after RT, in terms of both higher tumor control and lower normal-tissue complication probability. The first effect relates to the metabolic shift from glycolysis towards mitochondrial metabolism, which selectively increases reactive oxygen species (ROS) production and impairs adenoside triphosphate (ATP) production in tumor cells. The second effect is based on the differential stress resistance phenomenon describing the reprogramming of normal cells, but not tumor cells, from proliferation towards maintenance and stress resistance when glucose and growth factor levels are decreased and ketone body levels are elevated. Underlying both effects are metabolic differences between normal and tumor cells. Ketogenic therapy is a non-toxic and cost-effective complementary treatment option that exploits these differences and deserves further clinical investigation.

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High-dose and fractionation effects in stereotactic radiation therapy: Analysis of tumor control data from 2965 patients

Abstract: Our analysis suggests that distinct tumoricidal mechanisms do not determine tumor control at high doses/fraction. In addition, there is evidence suggesting that multi-fraction SRT is superior to single-dose SRT.

Cited by 116 publications

References 78 publications

Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era

Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era

Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

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