The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy

Abstract

Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in the treatment of an increasing number of cancers. As with other treatment modalities, there is related toxicity to a number of organs at risk. Despite the large number of clinical trials over the past several decades, considerable uncertainties still remain regarding the optimization of this therapeutic approach and one of the vital issues to be answered is whether an absorbed radiation dose-response exists that could be used to guide personalized treatment. There are only limited and sporadic data investigating MRT dosimetry. The determination of dose-effect relationships for MRT has yet to be the explicit aim of a clinical trial. The aim of this article was to collate and discuss the available evidence for an absorbed radiation dose-effect relationships in MRT through a review of published data. Based on a PubMed search, 92 papers were found. Out of 79 studies investigating dosimetry, an absorbed dose-effect correlation was found in 48. The application of radiobiological modelling to clinical data is of increasing importance and the limited published data on absorbed dose-effect relationships based on these models are also reviewed. Based on National Cancer Institute guideline definition, the studies had a moderate or low rate of clinical relevance due to the limited number of studies investigating overall survival and absorbed dose. Nevertheless, the evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.

Radiopeptides for Imaging and Therapy: A Radiant Future

“…They recommended collecting data on several parameters to construct a patient-specific treatment plan, taking into account various patient-specific characteristics to predict the probability of response and predisposition to toxicity. Dosimetry can be used as a predictor of therapy response and toxicity; a relationship between tumor-absorbed dose and response has already been demonstrated for 90 Y-DOTATOC (23).…”

Dose optimization in nuclear medicine

“…As has been stated in a recent review article on the evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy by Strigari et al [3], this evidence implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.…”

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…Despite a correlation between absorbed doses and treatment response and toxicity [9], all evidence supporting a dose response relationship from dosimetry in 90 Y-RE is based on either non-controlled prospective or retrospective studies.…”

“…A recent review by the EANM Dosimetry Committee identified 48 papers (out of 79 surveyed) employing the use of radionuclide dosimetry showing a strong correlation between absorbed dose and the tumour response & toxicity over a wide range of radionuclide treatments (including 90 Y-RE) [9], and many works have noted the lack of randomized trials comparing dosimetry-based radionuclide therapy to fixed dosing, or dosing per kg body weight [10,11]. For routine use, there is a requirement of standardized procedures for absorbed dose calculations [12] and improved reliability of radiobiological models used to convert dosimetric data to biologic endpoints [13].…”