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

Abstract

PurposeThis 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 MaterialsThirty 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 (α/β = 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.ResultsThe 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.ConclusionsAssuming 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.

Biophysical Analysis of Acute and Late Toxicity of Radiotherapy in Gastric Marginal Zone Lymphoma—Impact of Radiation Dose and Planning Target Volume

“…Published studies on NTCP for other organs at risk after radiation treatment comprise various patient numbers and provide different informative values. Other authors using a similar approach by generating comparable radiation plans with consistent radiation dosage reported similar limited numbers of patients as involved in this study [ 30 ]. Another publication, including a larger number of patients, merged patients from different studies to optimize existing NTCP parameters, but bore limitations, e.g., of slightly to noticeably varying radiation planning between the included studies and usage of vague data on doses for organs at risk [ 23 ].…”

“…In modern approaches, the inaccuracy derived from depending on breath or other motion of organs including the stomach needs to be considered [ 29 ]. Studies showed a significant impact of motion on mean doses and respective NTCP for liver [ 30 , 31 ]. Similarly, in a study by McCulloch et al, NTCP differed between planned and accumulated dose for the stomach and duodenum [ 30 ].…”

“…Studies showed a significant impact of motion on mean doses and respective NTCP for liver [ 30 , 31 ]. Similarly, in a study by McCulloch et al, NTCP differed between planned and accumulated dose for the stomach and duodenum [ 30 ]. This effect grew with higher dosages, and for doses ≥20 Gy, NTCP models derived from planning dose vs. accumulated dose even underestimated toxicity rates.…”

Impact of Interfractional Error on Dosiomic Features

“…The impact of setup errors in dosimetric features has been reported (9)(10)(11)(12). Furthermore, these errors can result in overestimation or underestimation of probability according to the NTCP model (13)(14)(15). In other words, these errors might decrease the reproducibility of dosiomics as well.…”

Adaptive Radiotherapy: Moving Into the Future

“…17 The calculation of the final delivered dose can then be linked to an outcomes database, supporting the refinement of normal tissue complication models, tumor control probabilities, clinical trials, and protocol development. 18 Once the delivered dose is quantified for a population of patients, decision support tools can be developed empowering the clinical team with evidence-driven metrics to guide the decision to replan, Figure 1B.…”