Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic castration-resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 179-179
Author(s):  
Matthew S. Brown ◽  
Hyun J. Kim ◽  
Gregory H. Chu ◽  
Martin Allen-Auerbach ◽  
Cheryce Fischer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Scan ◽  
Post Treatment ◽  
Whole Body ◽  
Treatment Trial ◽  
Castration Resistant Prostate Cancer ◽  
Lesion Area ◽  
Surrogate Outcome ◽  
Castration Resistant

179 Background: Bone Scan Lesion Area (BSLA) is a biomarker that can be computed semi-automatically from whole-body scintigraphic imaging as a measure of overall bone tumor burden. Initial development and validation, including correlation with outcomes, was performed in trial cohorts from a single drug treatment with controls in subjects with metastatic castrate-resistant prostate cancer (CRPC). A 30% increase/decrease in BSLA was defined as progression/response on bone scan. We hypothesize that, when applied to an independent treatment trial cohort with a different mechanism of drug action, baseline BSLA and Week 12 change post-treatment are predictive of a subject's overall survival. Methods: From an anonymized imaging research database a cohort of 198 CRPC subjects was identified who enrolled in a treatment trial (127 treated, 71 placebo). This cohort was independent of those used for biomarker development and initial validation, and involved a different mechanism of drug action. Subjects underwent standard of care whole-body bone scintigraphy with 99mTc-Methyl diphosphonate (99mTc-MDP). BSLA was calculated at baseline and response at Week 12. Multivariate Cox regression was used to test whether (1) baseline BSLA, and (2) early changes in BSLA (12 weeks post treatment) were predictive of overall survival. Results: BSLA < 2000 mm2 at baseline was a prognostic factor (HR=0.6; p=0.003) and predictive of longer survival (HR=0.4; p<0.001). Subjects without PD by BSLA at Week 12 had significantly longer survival than subjects with PD: median 170 days vs. 186 days in the placebo group and 260 days vs. 392 days in the treatment group. The overall survival rates between non-PD and PD subjects were statistically different (HR=0.64, p=0.007). Conclusions: BSLA is calculated semi-automatically from bone scans and provides a quantitative and objective treatment response assessment. Baseline BSLA and early changes post treatment were found to be predictive of overall survival in patients with metastatic castration-resistant prostate cancer. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different drug treatments.

scholarly journals Cabozantinib in Chemotherapy-Pretreated Metastatic Castration-Resistant Prostate Cancer: Results of a Phase II Nonrandomized Expansion Study

2014 ◽  
Vol 32 (30) ◽  
pp. 3391-3399 ◽  
Author(s):  
Matthew R. Smith ◽  
Christopher J. Sweeney ◽  
Paul G. Corn ◽  
Dana E. Rathkopf ◽  
David C. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Soft Tissue ◽  
Tumor Cells ◽  
Phase Ii ◽  
Bone Scan ◽  
Castration Resistant Prostate Cancer ◽  
Bone Biomarkers ◽  
Castration Resistant ◽  
Analgesic Use

Purpose Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). Patients and Methods Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. Results One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. Conclusion The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.

scholarly journals Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer

2018 ◽  
Vol 5 (01) ◽  
pp. 1 ◽  
Author(s):  
Matthew S. Brown ◽  
Grace Hyun J. Kim ◽  
Gregory H. Chu ◽  
Bharath Ramakrishna ◽  
Martin Allen-Auerbach ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Scan ◽  
Metastatic Prostate Cancer ◽  
Outcome Measure ◽  
Lesion Area ◽  
Surrogate Outcome ◽  
Surrogate Outcome Measure

Interim analysis of a pilot study: Impact of high-dose, single fraction radiation on immunogenicity of sipuleucel-T in metastatic castration resistant prostate cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16538-e16538
Author(s):  
Yuanquan Yang ◽  
Saby George ◽  
Ellis Glenn Levine ◽  
Thomas Schwaab ◽  
Jason Muhitch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Bone Lesion ◽  
Post Treatment ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Incorporation Assay ◽  
The Impact

e16538 Background: Sipuleucel-T is known to have modest anti-tumor activity in pts with metastatic castration resistant prostate cancer (mCRPC). Synergy of radiotherapy and immunotherapy has been reported. We conducted a pilot study to assess the impact of radiation on immunogenicity of Sipuleucel-T. Methods: Pts with minimally symptomatic mCRPC and bone metastases were eligible. Pts received Sipuleucel-T every 2 wks x 3 infusions. 8 Gy RT to 1 bone lesion was given 2 days after the first infusion. Peripheral blood was collected at D0, 7d after each infusion, 3 and 6 m. Primary endpoint is the effect of RT on immunogenicity of Sipuleucel-T. Secondary endpoints were safety, PSA changes and survival. We will evaluate T cell proliferation and cytolytic response at baseline and post-treatment using thymidine incorporation assay, IFN-y ELISPOT and flow cytometry. Results: From 10/2013 to 7/2018, a total of 15 pts were enrolled. Median age was 69 years (59-77). 10 pts (67%) had GS > = 8 disease. 7 pts (47%) failed prior abiraterone or enzalutamide. 13 pts completed treatment per protocol (2 withdrew). During a median follow-up of 48 mos, the 3-year overall survival was 48% (95% CI, 21-71); median survival was 30.7 mos (95% CI, 14.6-NR). No PSA responses were observed. 11 pts had post-treatment imaging (non-mandatory). 10 had PD and 1 had SD. 10 pts (67%) had Grade 1-2 drug-related AEs (most common: dizziness and hematoma 20%). No DLT or grade 3-5 drug-related AEs were observed. Conclusions: Sipuleucel-T plus RT is well tolerated. Median overall survival in this limited subset of pts was encouraging, when compared with historical data (25.8 mos in IMPACT trial). The evaluation of immune response is ongoing. (Funded by DENDREON; ClinicalTrials.gov ID: NCT01833208) Clinical trial information: NCT01833208.

scholarly journals Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

2019 ◽  
Vol 54 (1) ◽  
pp. 40-47
Author(s):  
Viviana Frantellizzi ◽  
Arianna Pani ◽  
Maria Dea Ippoliti ◽  
Alessio Farcomeni ◽  
Irvin Aloise ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Disease ◽  
Bone Scan ◽  
Treatment Effectiveness ◽  
Prognostic Score ◽  
Cost Optimization ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Bone Scan Index ◽  
Castration Resistant

AbstractBackgroundAim 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 methods127 mCRPC patients bone scan images were processed with DASciS software, and BSI was tested as OS predictor.Results546 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.ConclusionsThis 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.

Value of bone scan index for predicting overall survival among patients treated with radium-223 for bone metastatic castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Shuko Yoneyama ◽  
Yasuhide Miyoshi ◽  
Sohgo Tsutsumi ◽  
Takashi Kawahara ◽  
Yusuke Hattori ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Bone Scan ◽  
Continuous Variables ◽  
Castration Resistant Prostate Cancer ◽  
Bone Scan Index ◽  
Entire Cohort ◽  
Castration Resistant ◽  
Radium 223

216 Background: The objective of this study was to evaluate the bone scan index (BSI) as a prognostic biomarker for overall survival (OS) among patients treated with radium-223 (Ra-223) for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 42 men who had been treated with Ra-223 for bone metastatic CRPC between 2012 and 2017 and investigated correlations between the baseline clinical factors of age, time to CRPC, previous use of docetaxel, PSA, Gleason score, alkaline phosphatase (ALP), and BSI and OS by multivariate analysis using the Cox proportional hazard model. We also analyzed the correlations between OS and absolute BSI value or BSI change from baseline after 12 weeks of treatment. Continuous variables were classified as dichotomous. Results: The median age, PSA, and time to CRPC were 75.5 years, 42.8 ng/mL, and 11.2 months, respectively. The median observation period was 11.7 months. Twenty-five (59.5 %) of the 42 patients had completed six cycles of Ra-223 treatment. Twenty-two patients (52.4 %) had died, including 20 (47.6 %) of cancer, by the time of analysis. The median OS in the entire cohort was 20.7 months. Multivariate analysis also showed that only BSI (≥1.5 vs. < 1.5, HR 3.72, 95% CI 1.17–11.79, p = 0.026) was significantly correlated with OS. The BSI had decreased in 16 (51.6%) of the 31 patients who had undergone bone scans after 12 weeks of treatment . Multivariate analysis showed that absolute BSI value after 12 weeks treatment was significantly correlated with OS (BSI (≥2.0 vs. < 2.0%, HR 13.07, 95% CI 2.61–65.53, p = 0.002). No correlation was found between BSI change from baseline after 12 weeks and OS. Conclusions: According to multivariate analysis, both baseline BSI and PSA were significant prognostic factors for OS among men treated with Ra-223. Absolute BSI value after 12 weeks of Ra-223 treatment was also found to be an independent prognostic factor for OS.

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