Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy

Elamir, Ahmed M.; Stanescu, T.; Shessel, Andrea; Tadic, Tony; Yeung, Ivan; Létourneau, D.; Kim, John; Lukovic, Jelena; Dawson, Laura A.; Wong, Rebecca; Barry, Aisling; Brierley, James D.; Gallinger, Steven; Knox, Jennifer J.; O’Kane, Grainne M.; Dhani, Neesha C.; Hosni, Ali; Taylor, Edward

doi:10.1088/1361-6560/ac215c

Cited by 8 publications

(11 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Can we offer any recommendations for improvements, then? One possibility concerns "dose painting", the delivery of higher doses to more hypoxic regions, typically quantified by positron-emission tomography (PET) using specialized hypoxia-sensitive tracers 15,27,70,71,72 . As with pimonidazole (discussed in Sec.…”

Section: Discussionmentioning

confidence: 99%

“…Equation ( 6) is an approximation to the solution of the oxygen reaction-diffusion equation with randomly distributed capillaries acting as (a.) oxygen sources 27,33 . It is approximate since it treats the oxygen "fields" [the shaded circles in Fig.…”

Section: Cyclic Hypoxia Modelmentioning

confidence: 99%

“…This expression extends the binary decomposition used by Carlson et al 20 to include both chronic and cyclic hypoxia compartments, in addition to an oxic one. In reality, the survival fraction is given by a convolution over a continuous spectrum of oxygen tensions 15,27 . The rapid variation of the OER with respect to oxygen tension at low values ( 5 mmHg) 1 justifies the compartmentalization in Eq.…”

Section: Cyclic Hypoxia and Clonogen Survival Fraction During Hypofra...mentioning

confidence: 99%

“…In this paper, we develop a probabilistic model of cyclic hypoxia to quantify its impact on hypofractionated RT. A number of authors have examined the effect of hypoxia on hypofractionated RT 18,19,20,21,22,23,24,25,26,27 . Comparatively little attention seems to have been paid to modelling the specific impact of cyclic hypoxia, however.…”

mentioning

confidence: 99%

See 3 more Smart Citations

A simple mathematical model of cyclic hypoxia and hypofractionated radiotherapy

Taylor¹

2022

Preprint

Self Cite

View full text Add to dashboard Cite

There is now substantial evidence that the population of cells that experience fluctuating oxygen levels ("acute", or, "cyclic" hypoxia) are more radioresistant than chronically hypoxic ones and hence, this population likely determines radiotherapy (RT) response, in particular for hypofractionated RT, where reoxygenation may not be as prominent. A considerable effort has been devoted to examining the impact of hypoxia on hypofractionated RT; however, much less attention has been paid to cyclic hypoxia specifically and the role its kinetics may play in determining the efficacy of these treatments. Here, a simple mathematical model of cyclic hypoxia and fractionation effects was worked out to quantify this. Methods: Cancer clonogen survival fraction was estimated using the linear quadratic model, modified to account for oxygen enhancement effects. An analytic approximation for oxygen transport away from a random network of capillaries with fluctuating oxygen levels was used to model inter-fraction tissue oxygen kinetics. The resulting survival fraction formula was used to derive an expression for the iso-survival biologically effective dose, BED iso−SF . These were computed for some common extra-cranial hypofractionated radiotherapy regimens. Results: Using relevant literature parameter values, inter-fraction fluctuations in oxygenation were found to result in an added 1-2 logs of clonogen survival fraction in going from five fractions to one for the same nominal biologically effective dose (i.e., excluding the effects of oxygen levels on radiosensitivity). BED iso−SF 's for most ultrahypofractionated (five or fewer fractions) regimens in a given tumour site are similar in magnitude, suggesting iso-efficacy for common fractionation schedules. Conclusions: Although significant, the loss of cell-killing with increasing hypofractionation is not nearly as large as previous estimates based on the assumption of complete reoxygenation between fractions. Most ultra-hypofractionated regimens currently in place offer sufficiently high doses to counter this loss of cell killing, although care should be taken in implementing single-fraction regimens.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Cyclic Hypoxia Modelmentioning

confidence: 99%

Section: Cyclic Hypoxia and Clonogen Survival Fraction During Hypofra...mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A simple mathematical model of cyclic hypoxia and hypofractionated radiotherapy

Taylor¹

2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…An additional treatment session had to be scheduled at a later time with a completion plan reflecting the remainder of the planned dose. The pancreas cancer patients were treated with either 30 Gy or 40 Gy in five fractions with the possibility of a simultaneous integrated higher dose to hypoxic sub-volumes defined by FAZA-PET MRI [13]. The prescription specifics per case are shown in Table 1.…”

Section: Reference Planningmentioning

confidence: 99%

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System

Stanescu

Shessel

Carpino-Rocca

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Purpose: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow’s clinical feasibility and early experience in the case of 16 liver and pancreas patients. Methods: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Results: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70–90 min for a single fraction and 55–90 min for five fractions. The pancreas sessions were 54–85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9–96.1% and 99/95.4–100%, respectively. Conclusion: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

show abstract

A simple mathematical model of cyclic hypoxia and its impact on hypofractionated radiotherapy

Taylor

2023

Medical Physics

Self Cite

View full text Add to dashboard Cite

There is evidence that the population of cells that experience fluctuating oxygen levels ("acute," or, "cyclic" hypoxia) are more radioresistant than chronically hypoxic ones and hence, this population may determine radiotherapy (RT) response, in particular for hypofractionated RT, where reoxygenation may not be as prominent. A considerable effort has been devoted to examining the impact of hypoxia on hypofractionated RT; however, much less attention has been paid to cyclic hypoxia specifically and the role its kinetics may play in determining the efficacy of these treatments. Here, a simple mathematical model of cyclic hypoxia and fractionation effects was worked out to quantify this. Methods: Cancer clonogen survival fraction was estimated using the linear quadratic model, modified to account for oxygen enhancement effects. An analytic approximation for oxygen transport away from a random network of capillaries with fluctuating oxygen levels was used to model inter-fraction tissue oxygen kinetics. The resulting survival fraction formula was used to derive an expression for the iso-survival biologically effective dose (BED), BED iso−SF . These were computed for some common extra-cranial hypofractionated RT regimens. Results: Using relevant literature parameter values, inter-fraction fluctuations in oxygenation were found to result in an added 1-2 logs of clonogen survival fraction in going from five fractions to one for the same nominal BED (i.e., excluding the effects of oxygen levels on radiosensitivity). BED iso−SF 's for most ultra-hypofractionated (five or fewer fractions) regimens in a given tumor site are similar in magnitude, suggesting iso-efficacy for common fractionation schedules. Conclusions: Although significant, the loss of cell-killing with increasing hypofractionation is not nearly as large as previous estimates based on the assumption of complete reoxygenation between fractions. Most ultrahypofractionated regimens currently in place offer sufficiently high doses to counter this loss of cell killing, although care should be taken in implementing single-fraction regimens.

show abstract

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy

Cited by 8 publications

References 80 publications

A simple mathematical model of cyclic hypoxia and hypofractionated radiotherapy

A simple mathematical model of cyclic hypoxia and hypofractionated radiotherapy

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System

A simple mathematical model of cyclic hypoxia and its impact on hypofractionated radiotherapy

Contact Info

Product

Resources

About