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Aim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of “Sapienza” University of Rome for BSI calculation.

Background/Aim: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12–14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052–1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040–1.068, p < 0.001). Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center. [ABSTRACT FROM AUTHOR]

There have been several studies on the clinical outcomes of Radium-223 treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) who may have an increased risk of hematologic comorbidities. To the best of our knowledge, this is the first study to explore the potential bone marrow adverse effects (AEs) of Radium-223 administered with specific drugs used for hematologic conditions, such as polycythemia vera (PV). We report the case of a patient with mCRPC who was administered a combined treatment of Radium-223 and hydroxyurea for PV, aiming to support clinicians in predicting eventual AEs. [ABSTRACT FROM AUTHOR]

Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA. 430 consecutive patients treated with Radium-223 alone or in combination with BHA, affected by mCRPC, from January 2015 to July 2019 in six Italian Nuclear Medicine Units, were included. Furthermore, data were collected at baseline, after every Radium-223 administration, and during follow-up, at 3 and 6 months and 1 year after the 6th cycle. Clinical data have been evaluated before starting treatment with Radium-223 and at the end of treatment and/or at progression. Patients who received target bone therapy with BHA before Radium-223 treatment together with patients who did not receive this therapy at all (NO BHA GROUP), were compared to patients treated with concomitant Radium-223 and BHA (BHA GROUP). In univariate models (p <.05) several clinical aspects have an impact on OS: concomitant BHA (p =.018), BMI (p.001), ECOG PS (p =.000), Baseline Hb (p =.000), Baseline PSA (p =.000), Baseline tALP (p =.000), Baseline LDH (p =.000), and Baseline neutrophils (p =.009). Baseline Hb, Baseline tALP, and Baseline LDH have been confirmed as statistically significant parameters in multivariate models. Indeed, concomitant BHA has not a significant impact on OS (p =.244) in multivariate models. At univariate analysis, our data showed that NO BHA GROUP and BHA GROUP differ in OS by 7 months (95%CI: (1–16.4), p =.02). This is not confirmed at multivariate analysis where after adjusting for other baseline factors, BHA is not significant anymore. This is clearly explained as bias by indication: patients with the same levels of tALP, Hb, and LDH receiving or not receiving BHA are expected to have a similar survival. Our results support and confirm the role of Radium-223 therapy on OS and, furthermore, appear to confirm that BHA treatment has not a survival benefit. [ABSTRACT FROM AUTHOR]

Objective: Radium-223 (223Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting radionuclide has a beneficial effect on pain and is also capable to increase overall survival (OS). Several studies evaluated the prognostic value of different biomarkers at baseline, such as serum values, imaging parameters or pain. To date, however, clinicians lack a validated and simple system to assess which patients will most likely benefit from 223Ra treatment. The 3-variable prognostic score (3-PS), proposed in a single-center study in 2017 classifies patients in five prognostic groups with a specific OS. This study aims to validate the 3-PS in a larger multicenter population. Methods: Four hundred and thirty mCRPC patients treated with 223Ra from six different centers were analyzed. The 3-PS score consists of the collection of baseline hemoglobin, prostatic specific antigen and Eastern cooperative oncology group performance status and was initially applied to the whole population (total group). The score was then validated on the 338 patient's subgroup (clean group) obtained by subtracting the 92 patients enrolled for the original study of the 3-PS score. This purified group served as further validation evidence. Results: Statistical analysis showed that the 3-PS score was valid on the total group as well as in the clean group as the AUC estimated (0.74) falls within the CI of the AUC calculated on the validation sample (95% CI 0.66–0.82). Conclusion: This study confirms the validity of the 3-PS score for mCRPC patients. This score is simple, noninvasive and affordable and can be easily used to select patients that will most probably complete 223Ra treatment. In addition, this tool provides an exact estimate of life expectancy in terms of OS. [ABSTRACT FROM AUTHOR]

Objective. Bone secondary localizations from metastatic castration-resistant prostate cancer are associated with an increase in mortality and a reduction in the patient’s quality of life. Radium-223 is a targeted alpha-therapy approved for the treatment of mCRPC (metastatic castration resistant prostate cancer) patients with symptomatic bone metastases. To our knowledge, no previous study has been performed assessing the bone pain palliation outcomes following Radium-223 therapy. Materials and Methods. A mCRPC patient with symptomatic bone localizations and relevant bone pain symptoms has been subjected to Radium-223 treatment. Pain was assessed over time from the first administration of Radium-223 to follow-up. Results. After Radium-223 treatment, patient showed a significant BPI (Brief Pain Inventory) decline from 7 to 4 and a concomitant partial regression of multiple bone hot spots in the bone scan exam. Three months after the last infusion of Radium-223, further BPI decline (from 4 to 2) with bone scan depicting stable disease was observed. However, after 6 months from Radium-223 treatment end, BPI increased from 2 to 10. Conclusions. Taking into account the effectiveness on bone pain relief and the low toxicity profile showed by Radium-223 treatment, we encourage further analysis on large cohort to investigate the clinical outcome after Radium-223 treatment, in terms of bone pain palliation, together with the possibility of Radium-223 re-treatment in selected patients. [ABSTRACT FROM AUTHOR]

Background: Aim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of "Sapienza" University of Rome for BSI calculation. Patients and methods: 127 mCRPC patients bone scan images were processed with DASciS software, and BSI was tested as OS predictor. Results: 546 bone scans were analyzed revealing that the extension of disease is a predictor of OS (0–3% = 28 months of median survival (MoMS]; 3%–5% = 11 MoMS, > 5% = 5 MoMS). BSI has been analyzed as a single parameter for OS, determining an 88% AUC. Moreover, the composition between the BSI and the 3-PS (3-variable prognostic score) determines a remarkable improvement of the AUC (91%), defining these two parameters as the best OS predictors. Conclusions: This study suggests that OS is inversely correlated with the load of bone disease in mCRPC Ra-223-treated subjects. DASciS software appears a promising tool in identifying mCRPC patients that more likely take advantage from Ra-223 treatment. BSI is proposed as a predictive variable for OS and included to a multidimensional clinical evaluation permits to approach the patients' enrollment in a rational way, allowing to enhance the treatment effectiveness together with cost optimization. [ABSTRACT FROM AUTHOR]

Objective: In mCRPC patients treated with 223Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving 223Ra treatment.Methods: 92 consecutive CRPC patients with symptomatic bone metastases receiving 223Ra treatment were included. Available baseline clinical data relevant to the survival analysis were retrospectively collected. The primary end-point of the study was overall survival, which was established from the first 223Ra administration until date of death from any cause.Results: Median follow-up time from the first 223Ra administration was 6 months (range 1-31 months). The univariate analysis evaluating the prognostic value of all baseline clinical variables showed that patients' weight, BMI, ECOG PS, Hb and tALP values were independently associated with OS. On multivariable analysis only baseline Hb value and ECOG PS remained significantly correlated with OS. To determine reliable baseline predictive factors for survival in patients receiving 223Ra treatment, we produced a predictive score. We tried all possible variable combinations, and found that the best score was obtained by combining baseline ECOG PS with Hb < 12 g/dl and PSA ≥ 20 ng/ml. This resulted in a score ranging from 0 to 4, with AUC 78.4% (p < 0.001).Conclusions: We propose a multidimensional clinical evaluation to select those mCRPC subjects suitable to receive the maximum benefit from 223Ra treatment. [ABSTRACT FROM AUTHOR]

Objective: Painful bone metastases cause reduced quality of life (QoL) in patients with castration‐resistant prostate cancer (CRPC). Alpha‐emitter 223Radium is associated with a clear survival benefit and significant bone pain palliation in CRPC patients with symptomatic bone metastases. The aim of this study was to evaluate the association between pain relief and psychological distress during the time course of therapy in patients treated with 223Radium. Methods: A total of 63 patients with mCRPC undergoing 223Radium treatment in our Nuclear Medicine Unit, carefully instructed on the possibility of improving the pain and increasing the survival by the treatment, were retrospectively evaluated. Pain response during treatment was assessed with the Brief Pain Inventory Numeric Rating Scale. Psychological distress was evaluated through the analysis of specific items from EORTC QoL questionnaires C30 and BM22, submitted to patients at baseline and after each 223Radium cycle. Results: Pain intensity showed a significant decrease after first 223Radium administration (−1.03 points, p = 0.0032), with a subsequent stability through the course of treatment (−1.30 points, p = <0.001). Psychological status did not show significant variations during 223Radium treatment, and no association was found between psychological status and pain relief in our population. Conclusions: In our experience, bone pain palliation provided by 223Radium do not correlate with an improved psychological status in patients with advanced PC. This observation emphasises the role of the psychological aspect in the evaluation of the QoL and the necessity of a multidisciplinary approach in which the emotional aspect of the patient is carefully evaluated. [ABSTRACT FROM AUTHOR]