Prostate implant evaluation using tumour control probability—the effect of input parameters

Haworth, Annette; Ebert, Martin; Waterhouse, David; Joseph, David; Duchesne, Gillian

doi:10.1088/0031-9155/49/16/012

Cited by 18 publications

(21 citation statements)

References 48 publications

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“…Although there are several sophisticated models for TCP [24][25][26] and NTCP 27 that have been published, the radiotherapy treatment planning software Pinnacle v7.6c has been used to calculate the biological responses in this study for simplicity. The responses are calculated in Pinnacle using the Kallman S-model 28,29 .…”

Section: Theorymentioning

confidence: 99%

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

Deb

Fielding

2009

Australas. Phys. Eng. Sci. Med.

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The main aim of radiotherapy is to deliver a dose of radiation that is high enough to destroy the tumour cells while at the same time minimising the damage to normal healthy tissues. Clinically, this has been achieved by assigning a prescription dose to the tumour volume and a set of dose constraints on critical structures. Once an optimal treatment plan has been achieved the dosimetry is assessed using the physical parameters of dose and volume. There has been an interest in using radiobiological parameters to evaluate and predict the outcome of a treatment plan in terms of both a tumour control probability (TCP) and a normal tissue complication probability (NTCP). In this study, simple radiobiological models that are available in a commercial treatment planning system were used to compare three dimensional conformal radiotherapy treatments (3D-CRT) and intensity modulated radiotherapy (IMRT) treatments of the prostate. Initially both 3D-CRT and IMRT were planned for 2 Gy/fraction to a total dose of 60 Gy to the prostate. The sensitivity of the TCP and the NTCP to both conventional dose escalation and hypo-fractionation was investigated. The biological responses were calculated using the Källman S-model. The complication free tumour control probability (P+) is generated from the combined NTCP and TCP response values. It has been suggested that the alpha/beta ratio for prostate carcinoma cells may be lower than for most other tumour cell types. The effect of this on the modelled biological response for the different fractionation schedules was also investigated.

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Section: Theorymentioning

confidence: 99%

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

Deb

Fielding

2009

Australas. Phys. Eng. Sci. Med.

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“…Haworth et al performed detailed TCP calculations based on the 125 I dose distributions of five patients. 31 Each prostate was subdivided into 12 sectors, with each sector assigned a tumor stem cell clonogen density based on the likelihood of finding cancer in a similar sector in a radical prostatectomy series. In their analysis, TCP was particularly sensitive to small-volume low-dose regions, but ignoring such regions leads to unrealistically high values of TCP.…”

Section: Discussionmentioning

confidence: 99%

A detailed radiobiological and dosimetric analysis of biochemical outcomes in a case‐control study of permanent prostate brachytherapy patients

Butler

Stewart

2009

Medical Physics

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The purpose of this study is to determine dosimetric and radiobiological predictors of biochemical control after recalculation of prostate implant dosimetry using updated AAPM Task Group 43 (TG-43) parameters and the radiobiological parameters recommended by TG-137. All biochemical failures among patients implanted with 125I Or 103Pd sources between 1994 and March 2006 were matched 2:1 with nonfailure controls. The individual matching was by risk group, radionuclide, prescribed dose, and time of implant (one match before and one after the failed patient) resulting in a median follow-up of 10.9 years. Complete dose volume histogram (DVH) data were recalculated for all 55 cases and 110 controls after updating the original source strength by the retrospectively determined ratios of TG-43. Differential DVH data were acquired in 179 increments of prostate volume versus percentage prescribed dose. At each incremental dose level i, the biologically equivalent dose BEDi, equivalent uniform dose EUDi, and tumor control probability TCPi were calculated from the implant dose plus any external beam delivered to the patient. Total BED, EUD, and TCP were then derived from the incremental values for comparison with single point dosimetric quality parameters and DVH-based averages. There was no significant difference between failures and controls in terms of total BED (143 vs 142 Gy), EUD (95 vs 94 Gy), or TCP (0.87 vs 0.89). Conditional logistic regression analysis factored out the matching variables and stratified the cohort into each case and its controls, but no radiobiological parameter was predictive of biochemical failure. However, there was a significant difference between radiobiological parameters of 125I and 103Pd due to less complete coverage of the target volume by the former isotope. The implant BED and TCP were highly correlated with the D90 and natural prescription doses and a series of mean DVH-based doses such as the harmonic mean and expressions of the generalized EUD. In this case-control study of prostate brachytherapy biochemical failures and nonfailures, there were no radiobiological parameters derived from detailed DVH-based analysis that predicted for biochemical control. This may indicate that in our approach, implant dosimetry is at or near the limits of clinically effective dose escalation.

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“…EUBED has been supported by TG-137 4 and implemented by several investigators. [13][14][15][16][17] Biologically effective dose (and EUBED) are often used to calculate TCP from binomial (specifically, Poisson) statistics. If n cells are exposed to a dose D, then a fraction S(D) will survive.…”

Section: A Radiobiological Modelsmentioning

confidence: 99%

“…Haworth et al 15 investigated the use of low a cutoffs and log-normal (rather than Gaussian) a distributions, neither of which are used in this work.…”

Section: A Radiobiological Modelsmentioning

confidence: 99%

“…The a broadening factor, representing inter and intratumoral variations in cellular response to radiation, has been suggested to be 0.04 Gy À1 20 or 0.08 Gy À1 21 , but we have assumed a lower value of 0.025 Gy À1 to mitigate overflattening of the TCP B curve. Haworth et al 15 investigated the use of low a cutoffs and log-normal (rather than Gaussian) a distributions, neither of which are used in this work.…”

Section: A Radiobiological Modelsmentioning

confidence: 99%

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Coupling I‐125 permanent implant prostate brachytherapy Monte Carlo dose calculations with radiobiological models

et al. 2017

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Purpose: To investigate the coupling of radiobiological models with patient-specific Monte Carlo (MC) dose calculations for permanent implant prostate brachytherapy (PIPB). To compare radiobiological indices evaluated with different radiobiological models using MC and simulated AAPM TG-43 dose calculations. Methods: Three-dimensional dose distributions previously computed using MC techniques with two types of patient models, TG43sim (AAPM TG-43 water-based conditions) and MCDmm (realistic tissues and interseed effects), for 613 PIPB patients are coupled with biological dose and tumour control probability (TCP) models. Two approaches and their extensions are considered to evaluate biological doses, biologically effective dose (BED) and isoeffective dose (IED), as well as two methods to evaluate TCP. Three novel extensions of equivalent uniform biologically effective dose (EUBED) are suggested which consider the spatial distribution of doses within the target volume. Adopted radiobiological model parameter values (a, b, etc) are those suggested by AAPM TG-137, and sensitivity to parameter choice is discussed. Results: MCDmm dose calculations can reveal low doses in the prostate target volume, due to tissue heterogeneities or inter-seed effects; considering these low doses in EUBED calculations can lower TCP estimates by up to 70%, with largest differences in patients with calcifications. There are large variations in biological doses and TCPs evaluated over the 613 patient cohort for each radiobiological model considered, reflecting the spectrum of physical doses calculated for these patients with either MCDmm or TG43sim. Depending on the model details, BED, IED and EUBED are, on average, 6.0-9.8%, 7.4-9.2% and 1.8-15% higher, respectively, with TG43sim than MCDmm. TCP estimates computed using MCDmm dose distributions are much lower than expected based on past treatment outcome studies, suggesting a need to re-assess model parameters when evaluating radiobiological indices coupled with heterogeneous tissue model-based dose calculations. Conclusions: Cohort average differences in biological dose and TCP estimates between radiobiological models are generally larger than differences for any one radiobiological model evaluated with TG43sim or MCDmm dose calculations. However, heterogeneous tissue dose calculations, like MCDmm, can identify clinically-relevant low dose volumes, e.g., in patients with calcifications, which would otherwise be missed with TG-43. In addition to affecting physical dose distributions, these low dose volumes can largely impact radiobiological dose and TCP estimates, which further motivates the clinical implementation of model-based dose calculations for PIPB.

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Prostate implant evaluation using tumour control probability—the effect of input parameters

Cited by 18 publications

References 48 publications

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

A detailed radiobiological and dosimetric analysis of biochemical outcomes in a case‐control study of permanent prostate brachytherapy patients

Coupling I‐125 permanent implant prostate brachytherapy Monte Carlo dose calculations with radiobiological models

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