A Review on Tumor Control Probability (TCP) and Preclinical Dosimetry in Targeted Radionuclide Therapy (TRT)

Abstract

Targeted radionuclide therapy (TRT) uses radiopharmaceuticals to specifically irradiate tumor cells while sparing healthy tissue. Response to this treatment highly depends on the absorbed dose. Tumor control probability (TCP) models aim to predict the tumor response based on the absorbed dose by taking into account the different characteristics of TRT. For instance, TRT employs radiation with a high linear energy transfer (LET), which results in an increased effectiveness. Furthermore, a heterogeneous radiopharmaceutical distribution could result in a heterogeneous dose distribution at a tissue, cellular as well as subcellular level, which will generally reduce the tumor response. Finally, the dose rate in TRT is protracted, relatively low, and variable over time. This allows cells to repair more DNA damage, which may reduce the effectiveness of TRT. Within this review, an overview is given on how these characteristics can be included in TCP models, while some experimental findings are also discussed. Many parameters in TCP models are preclinically determined and TCP models also play a role in the preclinical stage of radiopharmaceutical development; however, this all depends critically on the calculated absorbed dose. Accordingly, an overview of the existing preclinical dosimetry methods is given, together with their limitation and applications. It can be concluded that although the theoretical extension of TCP models from external beam radiotherapy towards TRT has been established quite well, the experimental confirmation is lacking. Thus, requiring additional comprehensive studies at the sub-cellular, cellular, and organ level, which should be provided with accurate preclinical dosimetry.

Dynamics of a diffusive model for cancer stem cells with time delay in microRNA-differentiated cancer cell interactions and radiotherapy effects

“…The closer TCP is to one, the greater the probability that all cancer stem cells die out and the tumor is controlled 80 . Spoormans et al 81 discussed that TCP takes into account the total absorbed dose and the radiosensitivity of the tumour tissue, while distinguishing between repairable and sublethal single-strand DNA breaks and irreparable and lethal double-strand DNA breaks. The parameters related to radiotherapeutic values are given in the Table 3 .…”

Tumor Control Probability and Small-Scale Monte Carlo Dosimetry: Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy

“…By measuring at several time points, one might improve the estimate of cumulated activity. In addition, no consideration of DNA damage repair, tumor repopulation, or differences in dose rate, which are relevant (24), is made.…”

A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics with Metabolism, Signaling Networks, and Biomechanics as Plug-In Component Models of a Cancer Digital Twin

“…The first clinical question is addressed by computing the tumor control probability (TCP), which is the probability that no clonogens survive after treatment [72]. We have adopted the Poisson model of TCP, which is considered a good approximation when the surviving fraction is <<1 [72,73], as in our clinical case: TCP = exp(−N), where N is the average number of surviving clonogens or cancer stem cells (CSCs) at the end of treatment. In our case, N is derived based on the execution of the hypermodel.…”