Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy

Abstract

Background Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of a patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced. Results Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14–102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. volume, recovery coefficient, calibration factor, activity, time-activity curve fitting, time-integrated activity and absorbed dose) were estimated. An equation was derived to describe the relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated. Discussion To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.

Validation of Monte Carlo 131I radiopharmaceutical dosimetry workflow using a 3D‐printed anthropomorphic head and neck phantom

“…49 Additionally, uncertainties have been reported to be up to 102% for small targets for 177 Lu in human clinical trials, placing our results in line with other RPT uncertainties. 55 Because the calibration factor depends on the accuracy of scatter and attenuation correction, and they vary with phantom geometry, 49 the shape of the phantom can directly affect the accuracy of quantifying activity in the background compartment. This may be the reason for the calibration factor slightly underpredicting the activity concentration in the background compartment (an ROI in the shoulder containing only water) of the anthropomorphic phantom.…”

Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

“…However, PSA-changes and clinical factors, including quality of life, still have to be taken into account when considering changes in management. Furthermore, dosimetry data for single-lesions has to be interpreted with caution, especially when considering the impact of heterogeneity and variance of single lesions on dosimetry with an uncertainty ranging from 14% to 102% for single index-lesions [ 36 ], which also represents one of the main limitations of our analysis. Further limitations include the retrospective design of this study and the relatively small sample size despite having performed PSMA-RLT in a considerably larger cohort.…”

Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects

“…The EANM provided guidelines for calculating the absorbed dose uncertainty based on the law of propagation of uncertainties [77]. Following those indications, Finocchiaro et al, e.g., estimated the uncertainty associated with the tumor absorbed dose in patient treated with 177 Lu-DOTATATE, which exceeded 100% [78].…”