Abstract
AimsThis study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches.MethodsIMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control.ResultsThe planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning.ConclusionsIt was concluded that varying the dose distribution within the prostate to take account for each patient’s clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.
Highlights
During typical radiotherapy of prostate cancer (PCa), a uniform spatial distribution of a specific dose is prescribed to the entire prostate gland, without customisation of dose prescription and distribution to the actual characteristics of an individual’s tumour
Spatial distributions of tumour characteristics may be accommodated in treatment planning through the use of non-invasive quantitative imaging
Whilst our sample size was small, this study illustrated the potential advantage of biological optimisation in yielding an improved expected probability of tumour control while achieving better sparing of organs at risk (OAR)
Summary
During typical radiotherapy of prostate cancer (PCa), a uniform spatial distribution of a specific dose is prescribed to the entire prostate gland, without customisation of dose prescription and distribution to the actual characteristics of an individual’s tumour. Spatial distributions of tumour characteristics may be accommodated in treatment planning through the use of non-invasive quantitative imaging. Several clinical trials that aimed to explore the feasibility of imaging-informed focal dose escalation and dose-painting have completed (NCT01168479, NCT01208883, NCT01190527). Results of these studies are very promising [8, 37]. The ways in which quantitative imaging is used in treatment planning are variable and often fail to utilise the resulting information for objective dose prescription. Many studies applied a focal boost dose to sub-volumes identified as abnormal regions on quantitative images [7, 14, 50, 60], including the FLAME-trial [37]. Ideal biological optimisation methods require accurately defined relationships between imaging parameter, derived radiobiological parameters and validated dose-response
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