Use of the LQ model with large fraction sizes results in underestimation of isoeffect doses

Sheu, Tommy; Molkentine, Jessica M.; Transtrum, Mark K.; Buchholz, Thomas A.; Withers, H.R.; Thames, Howard D.; Mason, Kathryn A.

doi:10.1016/j.radonc.2013.08.027

Cited by 47 publications

(27 citation statements)

References 21 publications

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“…We now consider a model to predict the survival of jejunal crypt clonogens after radiotherapy as in reference [55]. The model used is the linear-quadratic (LQ) model [56] combined with Curtis' lethal-potentially lethal (LPL) [57] and Kiefer's repair-saturation (RS) [58] models of post-radiation DNA repair.…”

Section: Dna Repair Modelsmentioning

confidence: 99%

“…There are a total of six parameters in the composite model, including 3 that are absent from the LPL formulation and 2 that are absent in the RS formulation. Data from reference [55] explored survival rate for split doses. It reported a statistically significant difference between those cells irradiated initially by a large and then a small dose and vice versa.…”

Section: Dna Repair Modelsmentioning

confidence: 99%

“…Experimental methods are the same as in reference [55]. C3Hf/KamLaw mice were exposed to whole body irradiation using 300 kVp X-rays at a dose rate of 1.84 Gy/min, and the number of viable jejunal crypts was determined using the microcolony assay.…”

Section: Radiation Experimentsmentioning

confidence: 99%

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The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems

White¹,

Tolman²,

Thames³

et al. 2016

PLoS Comput Biol

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We explore the relationship among experimental design, parameter estimation, and systematic error in sloppy models. We show that the approximate nature of mathematical models poses challenges for experimental design in sloppy models. In many models of complex biological processes it is unknown what are the relevant physical mechanisms that must be included to explain system behaviors. As a consequence, models are often overly complex, with many practically unidentifiable parameters. Furthermore, which mechanisms are relevant/irrelevant vary among experiments. By selecting complementary experiments, experimental design may inadvertently make details that were ommitted from the model become relevant. When this occurs, the model will have a large systematic error and fail to give a good fit to the data. We use a simple hyper-model of model error to quantify a model’s discrepancy and apply it to two models of complex biological processes (EGFR signaling and DNA repair) with optimally selected experiments. We find that although parameters may be accurately estimated, the discrepancy in the model renders it less predictive than it was in the sloppy regime where systematic error is small. We introduce the concept of a sloppy system–a sequence of models of increasing complexity that become sloppy in the limit of microscopic accuracy. We explore the limits of accurate parameter estimation in sloppy systems and argue that identifying underlying mechanisms controlling system behavior is better approached by considering a hierarchy of models of varying detail rather than focusing on parameter estimation in a single model.

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Section: Dna Repair Modelsmentioning

confidence: 99%

Section: Dna Repair Modelsmentioning

confidence: 99%

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The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems

White¹,

Tolman²,

Thames³

et al. 2016

PLoS Comput Biol

Self Cite

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“…However, other clinical studies, which have been done by other research groups express that by utilizing an extreme hypofractionation, we could validate the LQ model (23)(24)(25)(26). There is also some clinical research, which has been done 2 Int J Cancer Manag.…”

Section: Possible Cell-killing Scenariosmentioning

confidence: 99%

Effect of Hypofractionation on Prostate Cancer Radiotherapy

Arabpour

Shahbazi‐Gahrouei

2017

Int J Cancer Manag

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Context: Prior research over the past few decades has shown that the hypofractionated external beam radiation therapy could be a valuable method with an outstanding potential to treat the prostate cancer. The alpha-beta ratio (α/β) is an indication of the fractionation sensitivity of a particular cell type. Values of α/β ≥ 10 Gy are responsible for early-responding normal tissues and most tumors, while values of α/β < 5 Gy are for late-responding normal tissues. The α/β ratio could be raised by either a local tumor control increase or a decrease of normal tissue late effects through the application of an unconventional fractionation schedules. Evidence Acquisition: This review article aimed to investigation the details of radiobiological and clinical trials which are reported to highlight the characteristics of hypofractionation for the prostate cancer treatment based on the investigation of clinical results from hypofractionated treatments. Results:With the sufficient radiobiological and physiological research studies, it may be claimed that if α/β value for prostate cancer is less than the adjacent surrounding organs at risk and by applying fewer and larger fractions; a better therapeutic ratio can be achieved for the patient. Conclusions: Radiobiological modeling can play a major role in the design of new protocols. Also, one should be aware that in modeling the hypofractionated treatment, normal tissue iso-effects are significantly important and some assumptions needed to be made regarding α/β values for the critical normal tissue complication endpoint.

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“…These assays remain (together with spleen colony) today the only assays which directly measure survival of stem cells remaining in their environment after irradiation or other treatment. They remain in use today as the gold-standard [9].…”

mentioning

confidence: 99%

The origins of translational radiation oncology – In memoriam H. Rodney Withers (21 September 1932–25 February 2015)

Peters

McBride²,

Mason

2015

Radiotherapy and Oncology

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Use of the LQ model with large fraction sizes results in underestimation of isoeffect doses

Cited by 47 publications

References 21 publications

The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems

The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems

Effect of Hypofractionation on Prostate Cancer Radiotherapy

The origins of translational radiation oncology – In memoriam H. Rodney Withers (21 September 1932–25 February 2015)

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