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

Ana M Denis-Bacelar,Sarah J Chittenden,Glenn D Flux,Joe M O’Sullivan,David P Dearnaley,Iain Murray,Bernadette Johnson,Antigoni Divoli,V Ralph Mccready

doi:10.1088/1361-6560/aa5e6f

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.

Highlights

Bone metastases are a common indicator of distant relapse from various cancers, in particular those arising in the prostate, lung and breast (Mundy 2002)
An α parameter of 0.25 Gy−1 reduced the PMADMCP=0.95 by 32% on average, with a median of 125 Gy (IQR: 73–169 Gy)
From all the measures of absorbed dose variability in a given patient, the best correlation with the PMADMCP=0.95 was obtained with the range scaled by the minimum absorbed dose (r = 0.98, P < 0 .0001), shown in figure 1(b)

Summary

Introduction

Bone metastases are a common indicator of distant relapse from various cancers, in particular those arising in the prostate, lung and breast (Mundy 2002). The prospect of further significant improvements in survival is underlined by the limited haematological toxicity resulting from current treatments (Bruland et al 2006, Parker et al 2013) and the practicality of high activity administrations in combination with stem cell transplantation (O’Sullivan et al 2002, O’Sullivan 2006). This indicates the potential for more aggressive administrations if a personalised treatment planning approach is used. Such treatments require quantification of image data to facilitate patient-specific dosimetry and the development of models to explain the clinical significance of the calculated absorbed doses

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Discussion

Conclusion