Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Predicting the Prognosis of Prostate Cancer Bone Metastasis Using the Bone Scan Index and Hot Spots Calculated Using VSBONEⓇ Bone Scan Index from Tc-99m-Hydroxymethylene Diphosphonate Bone Scintigraphy.

INTRODUCTION: The bone scan index (BSI) is widely used as a quantitative indicator of bone metastasis, therapeutic effect assessment, and prognosis prediction in prostate cancer. However, the BONE NAVI, which calculates BSI, only supports bone scintigraphy using Tc-99m-methylene diphosphonate. We developed the VSBONEⓇ BSI, which calculates BSI from bone scintigraphy using Tc-99m-hydroxymethylene diphosphonate (HMDP). The purpose of this study was to demonstrate that the BSI calculated using VSBONEⓇ BSI and hot spots (HS), which indicates the number of abnormal accumulations, are useful prognostic factors for patients with prostate cancer bone metastasis, similar to BONE NAVI. METHODS: We analyzed 322 patients who underwent bone scintigraphy for prostate cancer bone metastasis at our hospital. Initial bone scintigraphy was performed using Tc-99m-HMDP. All cases were retrospectively examined for their outcome and time to the final outcome. The results obtained were compared with the BSI and HS calculated using VSBONEⓇ BSI. RESULTS: When the patients were divided into two groups, HS >2 and HS ≤2, the HS ≤2 group had a significantly longer survival time (p < 0.001). In addition, when divided into two groups, BSI >0.46 and BSI ≤0.46, the survival time of the BSI ≦0.46 group was significantly longer (p < 0.001). CONCLUSION: BSI and HS obtained using VSBONEⓇ BSI may be useful as prognostic predictors, similar to those obtained using BONE NAVI.

Prognostic impact of bone metastatic volume beyond vertebrae and pelvis in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although bone metastasis beyond the vertebrae and pelvis has been a key factor in prognostic models of metastatic hormone-sensitive prostate cancer (mHSPC), the clinical significance of it is still unclear. The present study evaluated the prognostic impact of the volume of bone metastasis beyond the vertebrae and pelvis on the outcomes of mHSPC and created an ideal risk classification based on it. METHODS: We retrospectively reviewed 197 patients with mHSPC who were treated with combined androgen blockade as the initial treatment between June 2003 and October 2019. We calculated the bone scan index (BSI), including the BSI beyond the vertebrae and pelvis (bBSI), using BONENAVI, and investigated the association between the BSI and the overall survival (OS) of mHSPC. RESULTS: According to the CHAARTED criteria, 91 and 106 patients were classified into the low- and high-volume groups, respectively. Of the 79 patients who did not have visceral metastasis in the high-volume group, those with a bBSI ≤ 0.27 (n = 16) showed a favorable OS, as did those in the low-volume group. The modified CHAARTED high-volume group (presence of visceral metastases or 4 bone lesions with a bBSI > 0.27) showed a significantly shorter OS than others, with a hazard ratio (HR) of 4.69 (p < 0.001), which was higher than that observed with the original CHAARTED criteria (HR = 4.33). CONCLUSIONS: Our data suggested that considering the volume of bone metastasis beyond the vertebrae and pelvis may help to improve the accuracy of risk classification. Further large-scale prospective studies are needed to validate our findings.

Prognosis of patients with prostate cancer and bone metastasis from the Japanese Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index cohort study.

OBJECTIVE: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. METHODS: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone-sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration-resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole-body bone scintigraphy using 99m Tc-methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all-cause death including Bone Scan Index, prostate-specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. RESULTS: During a mean follow-up period of 716 ± 404 days, 81 (33%) of the patients died, and 3-year mortality rates were 20% and 52% in the metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone-sensitive prostate cancer group, whereas prostate-specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration-resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate-specific antigen progression in the metastatic hormone-sensitive prostate cancer group. Patients with metastatic hormone-sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. CONCLUSION: The Bone Scan Index and hot spot number are significant determinants of 3-year mortality, and combining the Bone Scan Index with prostate-specific antigen should contribute to the management of prostate cancer patients with bone metastasis.

Prognostic value of the bone scan index in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Many studies have reported the prognostic significance of the bone scan index (BSI) for metastatic castration-resistant prostate cancer (mCRPC); however, these reports are controversial. This study investigated the BSI in mCRPC and its relationship with prognosis. METHODS: The PubMed, Cochrane, and Embase databases were searched systematically for relevant articles published before September 1, 2019. Hazard ratios (HRs) were used to investigate the prognostic value. RESULTS: This study finally identified 9 eligible studies. The results suggested that high baseline BSI predicted poor OS (HR = 1.331, 95% CI: 1.081-1.640) and that elevated ΔBSI also predicted poor OS (HR = 1.220, 95% CI: 1.015-1.467). The subgroup analysis stratified by ethnicity showed that the baseline BSI and ΔBSI predicted poor OS in the Asian population but not in the Caucasian population. We also performed a subgroup analysis based on the different cut-off values of baseline BSI. The subgroup of ≤1 showed a significant association with OS in mCRPC patients. CONCLUSION: Our study demonstrated that high baseline BSI and elevated ΔBSI predicted poor OS in patients with mCRPC. Hence, the BSI can serve as a prognostic indicator for mCRPC patients and may therefore guide clinical treatment in the future.

Correlation between Automated Bone Scan Index Change after Cabazitaxel and Survival among Men with Castration-Resistant Prostate Cancer.

BACKGROUND: Automated bone scan index (aBSI) change (ΔBSI) after treatment and survival in men with prostate cancer remains unclear. We evaluated the correlation between ΔBSI after cabazitaxel and overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (CRPC). METHODS: We retrospectively enrolled 32 men with bone metastatic CRPC who had received cabazitaxel. The correlation between ΔBSI from baseline to 16 weeks after starting cabazitaxel and OS was analyzed by multivariate analysis. RESULTS: Median age and time to CRPC were 70.7 years and 9.5 months, respectively. The median cycles of docetaxel before cabazitaxel were eight. Ten (31.2%) patients had visceral metastases at baseline. Median baseline prostate-specific antigen (PSA) was 123.0 ng/mL. The median aBSIs at baseline and 16 weeks after cabazitaxel were 3.2 and 4.4%, respectively. Improvements in aBSI and PSA after 16 weeks of cabazitaxel occurred in 7 (21.9%) and 12 patients (37.5%), respectively. There were no correlations between ΔBSI and OS (p = 0.55), but PSA change was significantly correlated with OS (p = 0.03) by multivariate analysis. CONCLUSIONS: This study demonstrated that ΔBSI from baseline to16 weeks after starting cabazitaxel was not correlated with OS among men with bone metastatic CRPC. Further prospective studies may be warranted to confirm the limited utility of aBSI in this setting.

Prognostic value of an automated bone scan index for men with metastatic castration-resistant prostate cancer treated with cabazitaxel.

BACKGROUND: A computer-assisted diagnostic system for analyzing bone scans (BONENAVI) calculates the automated bone scan index (aBSI). Here we evaluated the aBSI as a prognostic imaging biomarker for men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. METHODS: We retrospectively analyzed 48 patients who received cabazitaxel for mCRPC and evaluated the ability of the aBSI to predict overall survival (OS). The Cox proportional hazards model was used to investigate the associations between baseline aBSI at cabazitaxel treatment and OS with the clinical variables as follows: age, number of cycles of docetaxel, serum prostate-specific antigen, hemoglobin (Hb), lactate dehydrogenase (LDH), and alkaline phosphatase. We determined the C-index to evaluate the discriminatory ability of our models when we included or excluded the aBSI from the analyses. RESULTS: The median OS after cabazitaxel treatment was 10.0 months, and patients with aBSI ≤1% achieved significantly longer OS compared with patients with aBSI ≥1%. Multivariate analysis showed that age, Hb, LDH, and aBSI were independent prognostic factors of OS. Adding aBSI to the base model increased the C-index from 0.78 to 0.80. CONCLUSIONS: The aBSI may serve as a useful imaging biomarker for predicting OS among men with mCRPC treated with cabazitaxel. Prospective studies are required to establish the value of aBSI as prognostic imaging biomarker.

A prospective study to evaluate the intra-individual reproducibility of bone scans for quantitative assessment in patients with metastatic prostate cancer.

BACKGROUND: The Bone Scan Index (BSI) is used to quantitatively assess the total tumour burden in bone scans of patients with metastatic prostate cancer. The clinical utility of BSI has recently been validated as a prognostic imaging biomarker. However, the clinical utility of the on-treatment change in BSI is dependent on the reproducibility of bone scans. The objective of this prospective study is to evaluate the intra-patient reproducibility of two bone scan procedures performed at a one-week interval. METHODS: We prospectively studied prostate cancer patients who were referred for bone scintigraphy at our centres according to clinical routine. All patients underwent two whole-body bone scans: one for clinical routine purposes and a second one as a repeated scan after approximately one week. BSI values were obtained for each bone scintigraph using EXINI boneBSI software. RESULTS: A total of 20 patients were enrolled. There was no statistical difference between the BSI values of the first (median = 0.66, range 0-40.77) and second (median = 0.63, range 0-22.98) bone scans (p = 0.41). The median difference in BSI between the clinical routine and repeated scans was - 0.005 (range - 17.79 to 0). The 95% confidence interval for the median value was - 0.1 to 0. A separate analysis was performed for patients with BSI ≤ 10 (n = 17). Differences in BSI were smaller for patients with BSI ≤ 10 compared to the whole cohort (median - 0.1, range - 2.2-0, 95% confidence interval - 0.1 to 0). CONCLUSIONS: The automated BSI demonstrated high intra-individual reproducibility for BSI ≤ 10 in the two repeated bone scans of patients with prostate cancer. The study supports the use of BSI as a quantitative parameter to evaluate the change in total tumour burden in bone scans.

Clinical Correlates of Benefit From Radium-223 Therapy in Metastatic Castration Resistant Prostate Cancer.

BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods. Bone Scan Index (BSI) was derived from available bone scans using EXINI software. RESULTS: One hundred and forty-five patients were included. Radium-223 was administered for six cycles in 74 patients (51%). One-year survival in this heavily pre-treated population was 64% (95%CI: 54-73%). In univariate and multivariate analysis, survival was highly associated with receiving all six doses of Radium-223. Receipt of six doses was associated with ECOG PS of 0-1, lower baseline PSA & pain level, no prior abiraterone/enzalutamide, <5 BSI value, and normal alkaline phosphatase. In patients who reported baseline pain (n = 72), pain declined in 51% after one dose and increased in 7%. PSA declined ≥50% in 16% (18/110). Alkaline phosphatase declined ≥25% in 48% (33/69) and ≥50% in 16/69 patients. BSI declined in 17 (68%) of the 25 patients who had bone scan available at treatment follow-up. Grade ≥3 neutropenia, anemia, and thrombocytopenia occurred in 4% (n = 114), 4% (n = 125), and 5% (n = 123), respectively. CONCLUSIONS: Patients earlier in their disease course with <5 BSI, low pain score, and good ECOG performance status are optimal candidates for radium-223. Radium-223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479-488, 2017. © 2016 Wiley Periodicals, Inc.

Association between bone scan index and activities of daily living in patients with advanced non-small cell lung cancer.

PURPOSE: The aim of this retrospective cross-sectional study was to investigate the association between the bone scan index (BSI) and activities of daily living (ADL) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Among patients with advanced NSCLC, subjects who underwent bone scintigraphy were recruited from this study. Clinical information about patients, including the Barthel Index of ADL, was extracted from their medical charts. Variables including the age, sex, BSI, presence/absence skeletal-related events (SREs), diagnostic state (initial vs. relapse), and history of use of certain medications (e.g. opiates) were evaluated as factors possibly associated with the Barthel Index. In Addition, associations between these factors, including the Barthel Index, with the overall survival were also assessed. RESULTS: A total of 111 patients with bone metastases were selected. The BSI and Barthel Index of the patients were 1.59 ± 2.25 and 69.7 ± 19.6, respectively. Multivariable analysis identified age (≥70 years), a high BSI (≥1.0), and presence of SREs were as factors statistically significantly associated with lower values of the Barthel Index (<75). On the other hand, Cox proportional hazards analysis identified low values of the Barthel Index (<75), use of opiates, and male sex as significant factors associated with a shorter overall survival; the BSI was not associated with the overall survival in the patients with advanced NSCLC in this study. CONCLUSION: The results suggest that a high BSI (≥1.0) is an independent predictor of poor ADL in patients with NSCLC, while showing no correlation with the overall survival.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer.

BACKGROUND: The purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts' readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging. METHODS: A total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging. RESULTS: Software analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1. CONCLUSION: The diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer.

OBJECTIVE: To evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer-specific survival (PCSS). In this retrospective study, we used novel computer-assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M-staged by whole-body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use. PATIENTS AND METHODS: In all, 88 patients with prostate cancer awaiting initiation of androgen-deprivation therapy due to metastases were included. WBS was performed using a two-headed γ-camera. BSI was obtained using the automated platform EXINI bone (EXINI Diagnostics AB, Lund, Sweden). In Cox proportional hazard models, time to castration-resistant prostate cancer (CRPC) and PCSS were modelled as the dependent variables, whereas prostate-specific antigen (PSA) level, Gleason score and BSI were used as explanatory factors. For Kaplan-Meier estimates, BSI groups were dichotomously split into: BSI <1 and BSI ≥1. Discrimination between prognostic models was explored using the concordance index (C-index). RESULTS: The mean (range) age of the patients was 72 (52-92) years, the median (range) PSA level was 73 (4-5 740) ng/mL, the mean (range) Gleason score was 7.7 (2-10), and the mean (range) BSI was 1.0 (0-9.2). During a mean (range) follow-up of 26 (8-49) months, 48 patients became castration resistant and 15 had died; most (13) from prostate cancer. In multivariate analysis including PSA level, Gleason score and BSI, only prediction by BSI was statistically significant. This was true both for time to CRPC (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.22-1.74; C-index increase from 0.49 to 0.69) and for PCSS (HR 1.34, 95% CI 1.07-1.67; C-index increase from 0.76 to 0.95). CONCLUSION: BSI obtained using a novel automated computer-assisted algorithm appears to be a useful predictor of outcome for time to CRPC and PCSS in patients with hormone-sensitive metastatic prostate cancer.

Flare phenomenon visualized by 99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from 99mTc-methylenediphosphonate (MDP) bone scintigraphy images. METHODS: We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2 years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3 months of starting chemotherapy, followed by > 10% improvement within the next 3 months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses. RESULTS: The flare phenomenon was found in 26 (36%) of the 72 patients. Prostate-specific antigen (PSA), alkaline phosphatase (ALP), and hemoglobin (Hb) levels steadily increased, then deteriorated in patients with and without flare, respectively. Elevated BSI and PSA values at 3 months after starting therapy and the absence of abiraterone or/and enzalutamide therapy led to poor 2-year overall survival (OS) in the group without flare. In contrast, no influence was noticeable in the group with flare. The results of multivariable analyses that included only factors associated with PSA and BSI showed that increased baseline BSI (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = 0.023) and PSA (HR, 7.15; 95% CI 2.13-24.04; P = 0.0015) values could be independent risk factors for patients with mCRPC without flare. However, these factors lost significance during flare. The risk for all-cause death was significantly higher among patients with BSI > 4 without, than with flare. The results of univariable analyses indicated that flare positively impacted survival (HR, 0.24; 95% CI 0.06‒0.91; P = 0.035). Multivariable analysis did not identify any factors that could predict outcomes. CONCLUSION: Favorable prognosis, with fewer disturbances from other factors such as the use of abiraterone or/and enzalutamide, PSA changes, and BSI, was attainable in cases when the mCRPC patient demonstrated flare phenomenon. Follow-up bone scintigraphy at least every 3 months could help to determine the prognosis of patients with bone metastasis of mCRPC.

Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

OBJECTIVE: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. METHODS: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. RESULTS: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). CONCLUSIONS: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

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.

Evaluation of Bone Scan Index as a Prognostic Tool in Breast Cancer Patients with Bone Metastasis.

BACKGROUND: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. OBJECTIVE: The aim of this study was to associate BSI with OS in bone metastatic BC patients. METHODS: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. RESULTS: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). CONCLUSION: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Bone scan index on bone scintigraphy and radiation therapy for bone metastases from cancers other than prostate and breast cancers: A retrospective observational study.

Objective: In this study, we aimed to use new automatic analysis software (VSBONE bone scan index (BSI); Nihon Medi-Physics, Tokyo, Japan) to investigate whether the pre-radiation therapy (RT) BSI, derived from bone scintigraphy (BS) images, is a prognostic indicator in patients undergoing RT for bone metastases from cancers other than breast or prostate cancer. Materials and Methods: In this retrospective single-institution study, we analyzed data of 51 patients who had undergone whole-body scintigraphy before receiving RT for bone metastases from cancers other than breast and prostate cancer between 2013 and 2019. Their bone metastases preradiation BSI were automatically calculated using newly developed software (VSBONE BSI; Nihon Medi-Physics, Tokyo, Japan). Univariate and multivariate analyses were performed to identify associations between selected clinical variables and overall survival (OS). Results: We did not find a significant association between BSI and OS. However, we did find that younger patients had significantly better OS than older patients (P = 0.016 and P = 0.036, respectively). In addition, BSI were significantly lower in patient with solitary or osteolytic bone metastases than in those with osteoblastic or mixed bone metastases (P = 0.035 and P ≤ 0.001, respectively), and significantly higher in those with lung cancer than in those with other types of cancer (mean BSI 3.26% vs. 1.97%; P = 0.009). Conclusion: The only significant association with survival identified in this study was for age at the time of BS and at time of diagnosis of bone metastases.

Clinical Significance of the Highest Regional Bone Scan Index in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: This study evaluated the clinical utility of the highest bone scan index (BSI), among other BSIs, for each bone metastatic site in patients with bone metastatic castration-resistant prostate cancer (bmCRPC). Methods: Thirty patients, diagnosed with bmCRPC by bone scintigraphy, were included. Total BSI, the number of hot spots, and regional BSI on each hot spot from bone scintigraphy at diagnosis with bmCRPC were evaluated by VSBONE BSI®. Highest regional BSI was defined as the highest value among regional BSIs on each hot spot in each patient. Related factors to overall survival and skeletal-related events (SREs) were evaluated using the Cox proportional-hazards model. Results: The median follow-up time from diagnosis with bmCRPC was 29.0 months. During this time, 24 patients died, of which 22 patients died from prostate cancer. On univariate analysis, alkaline phosphatase (ALP) [Hazard ratio (HR): 5.96, 95% confidence interval (CI): 2.05-17.3] and highest regional BSI (HR: 2.01, 95% CI: 1.17-7.05) had significant correlation with overall survival. On multivariate analysis, ALP (HR: 4.79, 95% CI: 1.61-14.2) had significant correlation with overall survival. SREs were found in eight patients. Only the highest regional BSI (HR: 9.99, 95% CI: 2.46-40.6) significantly correlated with SREs on univariate analysis. Conclusion: Highest regional BSI may provide important information regarding prognosis and SREs in patients with bmCRPC.

Development of a Prognostic Model of Overall Survival for Metastatic Hormone-Naïve Prostate Cancer in Japanese Men.

BACKGROUND: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer (mHNPC). There is a need to identify prognostic factors for the appropriate choice of treatment for patients with mHNPC, and we retrospectively examined these factors. METHODS: Patients with mHNPC treated at our institution from 2000 to 2019 were included in this study. Overall survival (OS) was estimated retrospectively using the Kaplan-Meier method, and factors associated with OS were identified using univariate and multivariate analyses. A prognostic model was then developed based on the factors identified. Follow-up was terminated on 24 October 2021. RESULTS: The median follow-up duration was 44.2 months, whereas the median OS was 85.2 months, with 88 patients succumbing to their disease. Multivariate analysis identified Gleason pattern (GP) 5 content, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) levels ≥ 300 IU/L as prognostic factors associated with OS. We also developed a prognostic model that classified patients with mHNPC as low risk with no factor, intermediate risk with one factor, and high risk with two or three factors. CONCLUSIONS: Three prognostic factors for OS were identified in patients with mHNPC, namely GP5 inclusion, BSI ≥ 1.5, and LDH ≥ 300. Using these three factors, we developed a new prognostic model for OS that can more objectively predict patient prognosis.

Comparison of skeletal segmentation by deep learning-based and atlas-based segmentation in prostate cancer patients.

OBJECTIVE: We aimed to compare the deep learning-based (VSBONE BSI) and atlas-based (BONENAVI) segmentation accuracy that have been developed to measure the bone scan index based on skeletal segmentation. METHODS: We retrospectively conducted bone scans for 383 patients with prostate cancer. These patients were divided into two groups: 208 patients were injected with 99mTc-hydroxymethylene diphosphonate processed by VSBONE BSI, and 175 patients were injected with 99mTc-methylene diphosphonate processed by BONENAVI. Three observers classified the skeletal segmentations as either a "Match" or "Mismatch" in the following regions: the skull, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, pelvis, sacrum, humerus, rib, sternum, clavicle, scapula, and femur. Segmentation error was defined if two or more observers selected "Mismatch" in the same region. We calculated the segmentation error rate according to each administration group and evaluated the presence of hot spots suspected bone metastases in "Mismatch" regions. Multivariate logistic regression analysis was used to determine the association between segmentation error and variables like age, uptake time, total counts, extent of disease, and gamma cameras. RESULTS: The regions of "Mismatch" were more common in the long tube bones for VSBONE BSI and in the pelvis and axial skeletons for BONENAVI. Segmentation error was observed in 49 cases (23.6%) with VSBONE BSI and 58 cases (33.1%) with BONENAVI. VSBONE BSI tended that "Mismatch" regions contained hot spots suspected of bone metastases in patients with multiple bone metastases and showed that patients with higher extent of disease (odds ratio = 8.34) were associated with segmentation error in multivariate logistic regression analysis. CONCLUSIONS: VSBONE BSI has a potential to be higher segmentation accuracy compared with BONENAVI. However, the segmentation error in VSBONE BSI occurred dependent on bone metastases burden. We need to be careful when evaluating multiple bone metastases using VSBONE BSI.