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A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

ABSTRACT: Purpose:This study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models. Methods and Materials:Thirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2?Gy per fraction and generalized equivalent uniform dose were calculated for planned and accumulated doses. Stomach and duodenal Lyman-Kutcher-Burman NTCP models (?/??=?2.5; n?=?.09) were developed on the basis of planned and accumulated generalized equivalent uniform doses and the differences between the models assessed. In addition, the error in determining the probability of toxicity on the basis of the planned dose was evaluated by comparing planned doses in the NTCP model that were created from accumulated doses. Results:The standard, planned-dose NTCP model overestimates toxicity risk for both the duodenal and stomach models at doses that are below approximately 20?Gy (6 fractions) and underestimates toxicity risk for doses above approximately 20?Gy (6 fractions). Building NTCP models with accumulated rather than planned doses changes the predicted risk by up to 16% (mean: 6%; standard deviation: 7%) for duodenal toxicity and 6% (mean: 2%; standard deviation: 2%) for stomach toxicity. For a protocol that plans a 10% iso-toxicity risk to the duodenum, a 15.7?Gy (6 fractions) maximum dose constraint would be necessary when using standard NTCP models on the basis of a planned dose and a 17.6?Gy (6 fractions) maximum dose would be allowed when using NTCP models on the basis of accumulated doses. Conclusions:Assuming that accumulated dose is a more accurate representation of the true delivered dose than the planned dose, this simulation study indicates the need for prospective clinical trials to evaluate the impact of building NTCP models on the basis of accumulated doses.

SUBMITTER: McCulloch MM

PROVIDER: S-EPMC6200914 | biostudies-other | 2018 Oct-Dec

REPOSITORIES: biostudies-other

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A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

McCulloch Molly M MM Muenz Daniel G DG Schipper Matthew J MJ Velec Michael M Dawson Laura A LA Brock Kristy K KK

Advances in radiation oncology 20180516 4

<h4>Purpose</h4>This study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models.<h4>Methods and materials</h4>Thirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2 Gy per fraction and generalized eq ...[more]

PMID: 30370368

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Project description:PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 - 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 - 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.

Project description:The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion.The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a "pulsed beam"; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a "continuous beam." A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam.The numerical simulations confirmed that the number of deliveries for each phase converges to K∕N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and∕or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation.Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and∕or total deliver time was also established.

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A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

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A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

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