MO‐AB‐BRA‐05: [18F]NaF PET/CT Imaging Biomarkers in Metastatic Prostate Cancer

Abstract

Purpose: Clinical use of 18F‐Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics‐based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. Methods: Fifty‐six metastatic Castrate‐Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen‐receptor (AR) inhibitors (N=39). A novel technology, Quantitative Total Bone Imaging (QTBI), was used for analysis. Employing hybrid PET/CT segmentation and articulated skeletal‐registration, QTBI allows for response assessment of individual lesions. Various SUV metrics were extracted from each lesion (iSUV). Global metrics were extracted from composite lesion‐level statistics for each patient (pSUV). Proportion of detected lesions and those with significant response (%‐increase or %‐decrease) was calculated for each patient based on test‐retest limits for iSUV metrics. Cox proportional hazard regression analyses were conducted between imaging metrics and progression‐free survival (PFS). Results: Functional burden (pSUVtotal) assessed mid‐treatment was the strongest univariate predictor of PFS (HR=2.03; p<0.0001). Various global metrics outperformed baseline clinical markers, including fraction of skeletal burden, mean uptake (pSUVmean), and heterogeneity of average lesion uptake (pSUVhetero). Of 43 patients with paired baseline/mid‐treatment imaging, 40 showed heterogeneity in lesion‐level response, containing populations of lesions with both increasing/decreasing metrics. Proportion of lesions with significantly increasing iSUVmean was highly predictive of clinical PFS (HR=2.0; p=0.0002). Patients exhibiting higher proportion of lesions with decreasing iSUVtotal saw prolonged radiographic PFS (HR=0.51; p=0.02). Conclusion: Technology presented here provides comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden as well as proportions of similarly responding lesions was predictive of PFS. This supports ongoing development of NaF PET/CT based imaging biomarkers in mCRPC. Prostate Cancer Foundation

Computational modelling of resistance and associated treatment response heterogeneity in metastatic cancers

“…Therefore, the theory of polyclonal seeding strongly supports heterogeneity between metastases, which results in heterogeneous treatment response. Indeed, heterogeneous treatment response between patients and between metastases has been reported (Gundem et al 2015, Hong et al 2015, Harmon et al 2016, Morin et al 2017, Nakazawa et al 2017.…”

“…Currently, treatment response is based on measurement of functional and anatomical changes of metastases. Therefore, molecular imaging modalities such as positron-emission tomography (PET), enabling visualization of the mentioned changes, can be successfully used to assess treatment response (Soussan et al 2014, Liu et al 2015, Simoncic et al 2015, Apolo et al 2016, Harmon et al 2016, Morin et al 2017. With quantitative analysis of parametric images, different imaging metrics can be extracted from PET scans, some of which have been shown to be strong predictors of disease progression and patient outcome (Cook et al 2015, Li et al 2017.…”

“…With quantitative analysis of parametric images, different imaging metrics can be extracted from PET scans, some of which have been shown to be strong predictors of disease progression and patient outcome (Cook et al 2015, Li et al 2017. Lastly, treatment response can be quantitatively assessed (Vanderhoek et al 2012, Harmon et al 2016, Lin et al 2016. PET has a special potential in assessing treatment response heterogeneity, because differences in the biological properties of tumours are reflected through heterogeneous accumulation of PET radiotracer (Padhani andMiles 2010, Harmon et al 2016).…”

“…The resulting inter-patient and intrapatient treatment response heterogeneity was modelled based on specific patient input. We focused on an example of metastatic castrate-resistant prostate cancer (mCRPC), which is recognised as a very heterogeneous disease (Vanderhoek et al 2012, Harmon et al 2016, Lin et al 2016. The model was benchmarked with an imaging metric, extracted from patients treated with hormonal therapy and chemotherapy, and imaged with 18 F-NaF PET/CT.…”

A statistically optimized regional thresholding method (SORT) for bone lesion detection in 18F-NaF PET/CT imaging

“…NaF PET/CT additionally provides robust quantitative assessment of tumor burden, which has been shown to relate to clinical outcome, either for progression-free survival (Harmon et al 2017) or overall survival (Lindgren Belal et al 2017). Furthermore, Harmon et al showed that the heterogeneity of responses of individual lesions is highly predictive of progression-free survival, which motivates further assessment of individual lesions (Harmon et al 2016).…”