8  The oxygen effect

Jones, Bleddyn; Carabe‐Fernandez, A; Dale, Roger G.

doi:10.1259/9780905749839.chapter08

Cited by 6 publications

(8 citation statements)

References 40 publications

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“…The inverse relationship between RBE and dose per fraction is a further complication, which could potentially influence the magnitude of the oxygen effect in high-LET beams: further work is required in this respect, with realtime monitoring of oxygen tensions. There is evidence that, for X-rays, there is a reduction in the oxygen enhancement ratio as the exposure dose is reduced [23]. The magnitude and direction of changes in radiosensitivity due to oxygen depletion or replenishment effects, as well as the influence of the more complex DNA damage and its repair proficiency during high-LET charged particle exposures, remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…For example, if h510% and x57%, the effect of a dose over 5 Gy would be to produce a new hypoxic fraction (h) of 17%. Such changes in hypoxia can, in principle, influence tumour cell kill and cure in extensive modelling studies, as well as contribute to worse clinical outcomes in terms of local tumour control [22][23][24][25][26].…”

Section: Impact Of Oxygen Depletion On the Percentage Of Radiologicalmentioning

confidence: 99%

“…where PO 2 is the oxygen tension, K is the parameter that defines the value of pO 2 at which the radiosensitivity is ''halfway'' between r max , the maximum value, and the baseline value of 1 [19,23].…”

Section: Appendix Amentioning

confidence: 99%

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Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Wilson

Jones²,

Yokoi³

et al. 2012

BJR

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Objective: To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy. Methods: A literature search of cellular UHDRR exposures was performed. Standard oxygen diffusion equations were used to estimate the time taken to replace UHDRRrelated oxygen depletion. Dose rates from conventional and novel methods of hadrontherapy accelerators were considered, including spot scanning beam delivery, which intensifies dose rate. Results: The literature findings were that, for X-ray and electron dose rates of around 10 9 Gy s -1 , 5-10 Gy depletes cellular oxygen, significantly changing the radiosensitivity of cells already in low oxygen tension (around 3 mmHg or 0.4 kPa). The time taken to reverse the oxygen depletion of such cells is estimated to be over 20-30 s at distances of over 100 mm from a tumour blood vessel. In this time window, tumours have a higher hypoxic fraction (capable of reducing tumour control), so the next application of radiation within the same fraction should be at a time that exceeds these estimates in the case of scanned beams or with ultra-fast laser-generated particles. Conclusion: This study has potential implications for particle therapy, including lasergenerated particles, where dose rate is greatly increased. Conventional accelerators probably do not achieve the critical UHDRR conditions. However, specific UHDRR oxygen depletion experiments using proton and ion beams are indicated.

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Section: Discussionmentioning

confidence: 99%

Section: Impact Of Oxygen Depletion On the Percentage Of Radiologicalmentioning

confidence: 99%

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Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Wilson

Jones²,

Yokoi³

et al. 2012

BJR

View full text Add to dashboard Cite

show abstract

“…There is some evidence that effective OERs become smaller with reduced fraction sizes, especially at those significantly less than about 2 Gy although to incorporate that possibility requires the assumption of separate OER factors for alpha and beta 30,31,32,33 . The methodology for achieving this has been disused in more depth by Jones et al, but the required factors usually need to be derived from invitro studies, in-vivo based data being rarely available and/or difficult to derive 34 . Furthermore, some more recent in-vitro studies suggest that OERs may increase, decrease or remain the same as…”

Section: Delivery Of a Proportionally Higher Total Dose With A High Dose Per Fraction After 4 Weeksmentioning

confidence: 99%

“…Modelling the effects of reoxygenation on a tumour with oxic and anoxic components could be achieved by an iterative approach as shown by the work of Denekemp et al and Jones et al 34,36 .…”

Section: B J R U N C O R R E C T E D P R O O F Smentioning

confidence: 99%

Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia

Joseph

Kirkby

Hoskin

et al. 2020

The British Journal of Radiology

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Objective: As a fractionated course of radiotherapy proceeds tumour shrinkage leads to resolution of hypoxia and the initiation of accelerated proliferation of radioresistant cancer cells with better repair capacity. We hypothesise that, in tumours with significant hypoxia, improved tumour control could be achieved with biphasic fractionation schedules that either use acceleration after 3–4 weeks of conventional radiotherapy or deliver a higher proportional dose towards the end of a course of treatment. We conducted a modelling study based on the concept of biological effective dose (BED) comparing such novel regimens with conventional fractionation. Methods: The comparator conventional fractionation schedule 70 Gy in 35 fractions delivered over 7 weeks was tested against the following novel regimens, both of which were designed to be isoeffective in terms of late normal tissue toxicity. 40 Gy in 20 fractions over 4 weeks followed by 22.32 Gy in 6 consecutive daily fractions (delayed acceleration) 30.4 Gy in 27 fractions over 4 weeks followed by 40 Gy in 15 fractions over 3 weeks (temporal dose redistribution) The delayed acceleration regimen is exactly identical to that of the comparator schedule over the first 28 days and the BED gains with the novel schedule are achieved during the second phase of treatment when reoxygenation is complete. For the temporal redistribution regimen, it was assumed that the reoxygenation fraction progressively increases during the first 4 weeks of treatment and an iterative approach was used to calculate the final tumour BED for varying hypoxic fractions. Results: Novel fractionation with delayed acceleration or temporal fractionation results in tumour BED gains equivalent to 3.5–8 Gy when delivered in 2 Gy fractions. Conclusion: In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation. Advances in knowledge: We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.

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Modelling of the oxygen enhancement ratio for ion beam radiation therapy

2011

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The poor treatment prognosis for tumours with oxygen-deficient areas is usually attributed to the increased radioresistance of hypoxic cells. It can be expressed by the oxygen enhancement ratio (OER), which decreases with increasing linear energy transfer (LET) suggesting a potential clinical advantage of high-LET radiotherapy with heavy ion beams compared to low-LET photon or proton irradiation. The aim of this work is to review the experimental cell survival data from the literature and, based on them, to develop a simple OER model to estimate the clinical impact of OER variations. For this purpose, the standard linear-quadratic model and the Alper-Howard-Flanders model are used. According to our calculations for a carbon ion spread-out Bragg peak at clinically relevant intermediate oxygen levels (0.5-20 mmHg), the advantage of carbon ions might be relatively moderate, with OER values about 1%-15% smaller than for protons. Furthermore, the variations of OER with LET are much smaller in vivo than in vitro due to different oxygen partial pressures used in cell experiments or measured inside tumours. The proposed OER model is a simple tool to quantify the oxygen effect in a practical way and provides the possibility to do hypoxia-based biological optimization in treatment planning.

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8 The oxygen effect

Cited by 6 publications

References 40 publications

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia

Modelling of the oxygen enhancement ratio for ion beam radiation therapy

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