Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy

Etchebehere, Elba; Araujo, John C.; Milton, Denái R.; Erwin, William D.; Wendt, Richard; Swanston, Nancy; Fox, Patricia S.; Macapinlac, Homer A.; Rohren, Eric M.

doi:10.1097/rlu.0000000000001118

Cited by 32 publications

(20 citation statements)

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“…The extent of disease graded by counting lesions did not show a significant independent association with clinical outcome. This finding is in accordance with the results of quantification of skeletal tumor burden by 18 F-fluoride PET, which performed better than visual grading for the prognostication of OS and bone marrow failure (14,22). Likewise, a small study of 14 patients with a high BSI reported short median survival after 223 RaCl 2 therapy (23).…”

Section: Discussionsupporting

confidence: 83%

“…The advanced extent of disease of the study population could have been the reason for the high incidence of hematologic toxicity relative to that in the existing literature (14,(24)(25)(26). In particular, thrombocytopenia was frequent and was associated with a complete lack of recovery within 6 mo despite the discontinuation of 223 RaCl 2 .…”

Section: Discussionmentioning

confidence: 95%

“…However, this finding was not validated in a multivariate analysis, and the BSI was not compared with a conventional evaluation of the extent of skeletal disease (13). Quantification of skeletal tumor burden from 18 F-fluoride PET/CT has also been demonstrated to be a significant independent predictor of bone marrow failure after 223 RaCl 2 therapy (14). Likewise, the BSI may be a valuable aid for identifying mCRPC patients with a high risk of hematologic toxicity before the initiation of therapy.…”

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confidence: 99%

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²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

et al. 2017

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The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving RaCl We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with RaCl This study was a retrospective investigation of a Danish cohort of mCRPC patients who received RaCl therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI Bone) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. A total of 88 patients were included. The median number of completedRaCl cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; = 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; = 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of RaCl ( = 52) and in 84% of the patients after the end of therapy ( = 32). There was no significant association between a change in the BSI during therapy and OS. The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receivingRaCl Further prospective studies are needed to evaluate the potential of the BSI for response assessment in RaCl therapy.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 95%

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confidence: 99%

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²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

et al. 2017

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“…In contrast to the ALSYMPCA trial, in which the bone scan response to treatment with 223 Ra was not evaluated, there are some studies that have focused on the utility of bone scans (scintigraphy and PET) to assess the response and toxicity associated with this therapy (36)(37)(38). In recent years, PSMA PET/CT has been making ground-breaking changes in the diagnosis and staging of PC patients, and this imaging modality is superior to choline PET (16,18,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…The concurrent use of 223 Ra with chemotherapy is currently not recommended; however, the concomitant use of these treatments in selected patients seems to be safe and beneficial (36).…”

Section: Discussionmentioning

confidence: 99%

⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept

et al. 2016

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We retrospectively evaluated the utility of 68 Ga-PSMA-11 PET for planning 223 RaCl 2 therapy of patients with metastatic prostate cancer and its impact on the therapeutic response as determined by prostatespecific antigen (PSA) and alkaline phosphatase (ALP), as well as the correlation of PSA changes with the results of prostate-specific membrane antigen (PSMA) PET follow-up scans. Methods: Sixtythree patients with a median age of 73 y who underwent 307 cycles of therapy with 223 RaCl 2 were analyzed. In 31 patients, bone scanning and radiologic imaging were performed for pretherapeutic imaging (group 1). In 32 patients, bone scanning and PSMA PET were performed before therapy (group 2). Patients with small lymph node metastases and local recurrence were not excluded from treatment, consistent with current guidelines. PSA and ALP were measured before each treatment cycle and 4 wk after the final cycle. Thirteen patients from group 2, who underwent a second PSMA PET scan as a followup, were evaluated to determine the significance of PSA changes as a follow-up marker. Results: In group 1, 4 patients (12.9%) showed a PSA decline, of whom 2 patients and 1 patient showed a PSA decline of more than 30% and more than 50%, respectively. In contrast, in group 2, 14 patients (43.8%) showed a PSA decline, of whom 10 and 8 patients showed a decline of more than 30% and more than 50%, respectively (P 5 0.007). Thirty-seven patients had a high ALP level (19 from group 1 and 18 from group 2). Twelve (63.2%) and 16 (88.9%) patients in groups 1 and 2, respectively, showed an ALP decline. This difference was not significant; however, 7 (36%) and 13 (72.2%) patients in groups 1 and 2, respectively, showed an ALP decline of more than 30% (P 5 0.04). Considering any ALP decline as a response, no patient with increasing ALP showed a PSA response (P 5 0.036). There was a significant correlation between the PSA changes and the therapeutic response according to follow-up PSMA PET. Conclusion: When PSMA PET is used as the gatekeeper in addition to bone scanning, radionuclide therapy with 223 Ra may be more effective and have more success regarding changes in the PSA. An increase in PSA during therapy cycles occurs because of disease progression.

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Functional and Hybrid Imaging of Bone Metastases

Cook

2018

Journal of Bone and Mineral Research

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Bone metastases are common, cause significant morbidity, and impact on healthcare resources. Although radiography, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy have frequently been used for staging the skeleton, these methods are insensitive and nonspecific for monitoring treatment response in a clinically relevant time frame. We summarize several recent reports on new functional and hybrid imaging methods including single photon emission CT/CT, positron emission tomography/CT, and whole-body MRI with diffusion-weighted imaging. These modalities generally show improvements in diagnostic accuracy for staging and response assessment over standard imaging methods, with the ability to quantify biological processes related to the bone microenvironment as well as tumor cells. As some of these methods are now being adopted into routine clinical practice and clinical trials, further evaluation with comparative studies is required to guide optimal and cost-effective clinical management of patients with skeletal metastases. © 2018 American Society for Bone and Mineral Research.

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Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy

Abstract: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

Cited by 32 publications

References 20 publications

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept

Functional and Hybrid Imaging of Bone Metastases

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Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy

Abstract: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

Cited by 32 publications

References 20 publications

223Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

223Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

68Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with 223Ra: Proof of Concept

Functional and Hybrid Imaging of Bone Metastases

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Product

Resources

About

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept