Mariana Reza

Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy

BackgroundBone Scan Index (BSI) is a quantitative measurement of tumour burden in the skeleton calculated from bone scan images. When analysed at the time of diagnosis,it has been shown to provide prognostic information on survival in men with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic value of BSI during androgen deprivation therapy (ADT).MethodsProstate cancer patients who were at high risk of a poor outcome and who had undergone bone scan at the time of diagnosis and during ADT were recruited from two university hospitals for a retrospective study. BSI at baseline and follow-up were calculated using an automated software package (EXINIbonebsi).Associations between BSI, other prognostic biomarkers and overall survival (OS)were evaluated using a Cox proportional hazards regression model.ResultsOne hundred forty-six PCa patients were included in the study. A total of 102patient deaths were registered, with a median survival time after the follow-up bone scan of 2.4 years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT, BSI was significantly associated with OS in univariate and multivariate analyses. When BSI was added to a prognostic base model including age, prostate-specific antigen, clinical tumour stage and Gleason score, the concordance index increased from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001) during ADT.ConclusionsAutomated BSI during ADT is an independent prognostic indicator of OS in PCa patients with bone metastasis. It represents an emerging imaging biomarker that can be used in a prognostic model for risk stratification of PCa patients at the time of diagnosis and at later stages of the disease. BSI could then help physicians identify patients who could benefit from more aggressive therapies.

Bone Scan Index as an Imaging Biomarker in Metastatic Castration-resistant Prostate Cancer: A Multicentre Study Based on Patients Treated with Abiraterone Acetate (Zytiga) in Clinical Practice

BACKGROUND Abiraterone acetate (AA) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. To measure treatment response accurately in bone, quantitative methods are needed. The Bone Scan Index (BSI), a prognostic imaging biomarker, reflects the tumour burden in bone as a percentage of the total skeletal mass calculated from bone scintigraphy. OBJECTIVE To evaluate the value of BSI as a biomarker for outcome evaluation in mCRPC patients on treatment with AA according to clinical routine. DESIGN, SETTING, AND PARTICIPANTS We retrospectively studied 104 mCRPC patients who received AA following disease progression after chemotherapy. All patients underwent whole-body bone scintigraphy before and during AA treatment. Baseline and follow-up BSI data were obtained using EXINI BoneBSI software (EXINI Diagnostics AB, Lund, Sweden). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between change in BSI, clinical parameters at follow-up, and overall survival (OS) were evaluated using the Cox proportional hazards regression models and Kaplan-Meier estimates. Discrimination between variables was assessed using the concordance index (C-index). RESULTS AND LIMITATIONS Patients with an increase in BSI at follow-up of at most 0.30 (n=54) had a significantly longer median survival time than those with an increase of BSI >0.30 (n=50) (median: 16 vs 10 mo; p=0.001). BSI change was also associated with OS in a multivariate Cox analysis including commonly used clinical parameters for prognosis (C-index=0.7; hazard ratio: 1.1; p=0.03). The retrospective design was a limitation. CONCLUSIONS Change in BSI was significantly associated with OS in mCRPC patients undergoing AA treatment following disease progression in a postchemotherapy setting. BSI may be a useful imaging biomarker for outcome evaluation in this group of patients, and it could be a valuable complementary tool in monitoring patients with mCRPC on second-line therapies. PATIENT SUMMARY Bone Scan Index (BSI) change is related to survival time in metastatic castration-resistant prostate cancer (mCRPC) patients on abiraterone acetate. BSI may be a valuable complementary decision-making tool supporting physicians monitoring patients with mCRPC on second-line therapies.

A Preanalytic Validation Study of Automated Bone Scan Index: Effect on Accuracy and Reproducibility Due to the Procedural Variabilities in Bone Scan Image Acquisition

The effect of the procedural variability in image acquisition on the quantitative assessment of bone scan is unknown. Here, we have developed and performed preanalytical studies to assess the impact of the variability in scanning speed and in vendor-specific γ-camera on reproducibility and accuracy of the automated bone scan index (BSI). Methods: Two separate preanalytical studies were performed: a patient study and a simulation study. In the patient study, to evaluate the effect on BSI reproducibility, repeated bone scans were prospectively obtained from metastatic prostate cancer patients enrolled in 3 groups (Grp). In Grp1, the repeated scan speed and the γ-camera vendor were the same as that of the original scan. In Grp2, the repeated scan was twice the speed of the original scan. In Grp3, the repeated scan used a different γ-camera vendor than that used in the original scan. In the simulation study, to evaluate the effect on BSI accuracy, bone scans of a virtual phantom with predefined skeletal tumor burden (phantom-BSI) were simulated against the range of image counts (0.2, 0.5, 1.0, and 1.5 million) and separately against the resolution settings of the γ-cameras. The automated BSI was measured with a computer-automated platform. Reproducibility was measured as the absolute difference between the repeated BSI values, and accuracy was measured as the absolute difference between the observed BSI and the phantom-BSI values. Descriptive statistics were used to compare the generated data. Results: In the patient study, 75 patients, 25 in each group, were enrolled. The reproducibility of Grp2 (mean ± SD, 0.35 ± 0.59) was observed to be significantly lower than that of Grp1 (mean ± SD, 0.10 ± 0.13; P < 0.0001) and that of Grp3 (mean ± SD, 0.09 ± 0.10; P < 0.0001). However, no significant difference was observed between the reproducibility of Grp3 and Grp1 (P = 0.388). In the simulation study, the accuracy at 0.5 million counts (mean ± SD, 0.57 ± 0.38) and at 0.2 million counts (mean ± SD, 4.67 ± 0.85) was significantly lower than that observed at 1.5 million counts (mean ± SD, 0.20 ± 0.26; P < 0.0001). No significant difference was observed in the accuracy data of the simulation study with vendor-specific γ-cameras (P = 0.266). Conclusion: In this study, we observed that the automated BSI accuracy and reproducibility were dependent on scanning speed but not on the vendor-specific γ-cameras. Prospective BSI studies should standardize scanning speed of bone scans to obtain image counts at or above 1.5 million.

Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study

BACKGROUND ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. OBJECTIVE To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. DESIGN, SETTING, AND PARTICIPANTS From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n=47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). RESULTS AND LIMITATIONS In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07-0.58; p=0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17-0.74; p=0.006) than those who had a BSI increase >20% during treatment. CONCLUSIONS The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. PATIENT SUMMARY An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer.

Evaluation of changes in Bone Scan Index at different acquisition time-points in bone scintigraphy

Bone Scan Index (BSI) is a validated imaging biomarker to objectively assess tumour burden in bone in patients with prostate cancer, and can be used to monitor treatment response. It is not known if BSI is significantly altered when images are acquired at a time difference of 1 h. The aim of this study was to investigate if automatic calculation of BSI is affected when images are acquired 1 hour apart, after approximately 3 and 4 h. We prospectively studied patients with prostate cancer who were referred for bone scintigraphy according to clinical routine. The patients performed a whole‐body bone scan at approximately 3 h after injection of radiolabelled bisphosphonate and a second 1 h after the first. BSI values for each bone scintigraphy were obtained using EXINI boneBSI software. A total of 25 patients were included. Median BSI for the first acquisition was 0·05 (range 0–11·93) and for the second acquisition 0·21 (range 0–13·06). There was a statistically significant increase in BSI at the second image acquisition compared to the first (P<0·001). In seven of 25 patients (28%) and in seven of 13 patients with BSI > 0 (54%), a clinically significant increase (>0·3) was observed. The time between injection and scanning should be fixed when changes in BSI are important, for example when monitoring therapeutic efficacy.

213PRELATIONSHIP OF BONE SCAN INDEX AND PROGRESSION-FREE SURVIVAL DATA FOR METASTATIC CRPC PATIENTS WHO RECEIVED ODM-201

ABSTRACT Aim: ODM-201 is an androgen receptor (AR) inhibitor with high nonclinical and clinical efficacy. Bone scan index (BSI) is an imaging biomarker that reflects the percent of skeletal mass affected by tumor. Methods: We retrospectively studied a consecutive series of 47 metastatic CRPC (mCRPC) patients (pts), who received ODM-201 in ARADES trial. Total of 36/113 mCRPC pts (median age 68, range 55-82) with baseline and 12-week bone metastases were randomly selected to this evaluation. BSI data was obtained by using the automated quantification software EXINI boneBSI (EXINI Diagnostics AB, Lund, Sweden). Cox proportional-hazards regression models and Kaplan-Meier estimates of the survival function were used to investigate the association between changes in BSI and PSA from baseline to 12 weeks follow-up and progression data. Results: Using Pearson correlation, BSI change from baseline correlated with RECIST target lesion response (r = 0.50; p = 0.0418), and CTC change from baseline (r = 0.66; p 1 had significantly shorter median time to radiographic progression than pts with baseline BSI ≤ 1, 23 weeks and not reached, respectively (p = 0.0186). Conclusions: The on-treatment change in BSI was related to progression-free survival (PFS) in pts with mCRPC and bone metastases, and increase in BSI was significantly associated with reduced PFS. BSI for quantification of bone metastases could be a valuable complement to the traditional methods for evaluation of treatment response in mCRPC pts. Disclosure: C. Massard is a member of Orion Pharma advisory board; J. Aspegren is an employee of Orion Pharma; L. Mattila is an employee of Orion Pharma; L. Edenbrandt is employed and shareholder in EXINI Diagnostics AB (Lund, Sweden), which provides the software EXINIbonebsi used in this study; M. Mustonen is an employee of Orion Pharma; K. Fizazi is a member of Orion Pharma advisory board.All other authors have declared no conflicts of interest.