A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

Abstract

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r = 0.98, P < 0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

Figure 1.

Relationships between the target dose scaling factor and the minimum lesion absorbed dose in a given patient (a), and between the patient mean absorbed dose required to eradicate all the lesions (PMAD_MCP=0.95) and the variability of the distribution of absorbed doses delivered to the lesions in a given patient represented by the relative difference between minimum and maximum lesion absorbed doses (b). The 95% confidence bands are shown.

Figure 2.

Predicted metastatic burden reduction curves obtained for a cohort of 22 patients as a function of the patient mean absorbed dose. Patients 3 (*) and 4 (**) are indicated.

Figure 3.

Range of predicted PMAD_MCP=0.95 and PMAD_MBR=0.5, and delivered PMAD_delivered for the 22 patients. The median and inter-quartile range is shown.