Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC)1A.J.A. and R.K. contributed equally to this work

Andrew J. Armstrong, Reza Kaboteh, Michael A. Carducci, Jan Erik Damber, Walter M. Stadler, Mats Hansen, Lars Edenbrandt, Göran Forsberg, Örjan Nordle, Roberto Pili, Michael J. Morris

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Introduction: Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC). Methods: Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIboneBSI, an automated software package for BSI calculation. Associations between BSI and other prognostic biomarkers, progression-free survival, OS, and treatment were evaluated over time. Results: Of 201 men (57 TASQ and 28 placebo), 85 contributed scans at baseline and week 12 of sufficient quality. Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate (hazard ratio [HR] = 1.42, P = 0.013) and multivariate (HR = 1.64, P<0.001) analyses. BSI worsening at 12 weeks was prognostic for progression-free survival (HR = 2.14 per BSI doubling, P<0.001) and OS (HR = 1.58, P = 0.033) in multivariate analyses including baseline BSI and TASQ treatment. TASQ delayed BSI progression. Conclusions: BSI and BSI changes over time were independently associated with OS in men with mCRPC. A delay in objective radiographic bone scan progression with TASQ is suggested; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted.

Original languageEnglish (US)
Pages (from-to)1308-1316
Number of pages9
JournalUrologic Oncology: Seminars and Original Investigations
Volume32
Issue number8
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Castration
Prostatic Neoplasms
Randomized Controlled Trials
Placebos
Bone and Bones
Survival
tasquinimod
Disease-Free Survival
Biomarkers
Prostate-Specific Antigen
Tumor Burden

Keywords

  • Automated detection
  • Bone metastases
  • Computer-assisted diagnosis
  • Image analysis
  • Progression-free survival
  • Prostate cancer
  • Radionuclide imaging
  • Tasquinimod

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Medicine(all)

Cite this

Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC)1A.J.A. and R.K. contributed equally to this work. / Armstrong, Andrew J.; Kaboteh, Reza; Carducci, Michael A.; Damber, Jan Erik; Stadler, Walter M.; Hansen, Mats; Edenbrandt, Lars; Forsberg, Göran; Nordle, Örjan; Pili, Roberto; Morris, Michael J.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 32, No. 8, 2014, p. 1308-1316.

Research output: Contribution to journalArticle

Armstrong, Andrew J. ; Kaboteh, Reza ; Carducci, Michael A. ; Damber, Jan Erik ; Stadler, Walter M. ; Hansen, Mats ; Edenbrandt, Lars ; Forsberg, Göran ; Nordle, Örjan ; Pili, Roberto ; Morris, Michael J. / Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC)1A.J.A. and R.K. contributed equally to this work. In: Urologic Oncology: Seminars and Original Investigations. 2014 ; Vol. 32, No. 8. pp. 1308-1316.
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abstract = "Introduction: Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC). Methods: Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIboneBSI, an automated software package for BSI calculation. Associations between BSI and other prognostic biomarkers, progression-free survival, OS, and treatment were evaluated over time. Results: Of 201 men (57 TASQ and 28 placebo), 85 contributed scans at baseline and week 12 of sufficient quality. Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate (hazard ratio [HR] = 1.42, P = 0.013) and multivariate (HR = 1.64, P<0.001) analyses. BSI worsening at 12 weeks was prognostic for progression-free survival (HR = 2.14 per BSI doubling, P<0.001) and OS (HR = 1.58, P = 0.033) in multivariate analyses including baseline BSI and TASQ treatment. TASQ delayed BSI progression. Conclusions: BSI and BSI changes over time were independently associated with OS in men with mCRPC. A delay in objective radiographic bone scan progression with TASQ is suggested; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted.",
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T1 - Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC)1A.J.A. and R.K. contributed equally to this work

AU - Armstrong, Andrew J.

AU - Kaboteh, Reza

AU - Carducci, Michael A.

AU - Damber, Jan Erik

AU - Stadler, Walter M.

AU - Hansen, Mats

AU - Edenbrandt, Lars

AU - Forsberg, Göran

AU - Nordle, Örjan

AU - Pili, Roberto

AU - Morris, Michael J.

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N2 - Introduction: Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC). Methods: Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIboneBSI, an automated software package for BSI calculation. Associations between BSI and other prognostic biomarkers, progression-free survival, OS, and treatment were evaluated over time. Results: Of 201 men (57 TASQ and 28 placebo), 85 contributed scans at baseline and week 12 of sufficient quality. Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate (hazard ratio [HR] = 1.42, P = 0.013) and multivariate (HR = 1.64, P<0.001) analyses. BSI worsening at 12 weeks was prognostic for progression-free survival (HR = 2.14 per BSI doubling, P<0.001) and OS (HR = 1.58, P = 0.033) in multivariate analyses including baseline BSI and TASQ treatment. TASQ delayed BSI progression. Conclusions: BSI and BSI changes over time were independently associated with OS in men with mCRPC. A delay in objective radiographic bone scan progression with TASQ is suggested; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted.

AB - Introduction: Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC). Methods: Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIboneBSI, an automated software package for BSI calculation. Associations between BSI and other prognostic biomarkers, progression-free survival, OS, and treatment were evaluated over time. Results: Of 201 men (57 TASQ and 28 placebo), 85 contributed scans at baseline and week 12 of sufficient quality. Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate (hazard ratio [HR] = 1.42, P = 0.013) and multivariate (HR = 1.64, P<0.001) analyses. BSI worsening at 12 weeks was prognostic for progression-free survival (HR = 2.14 per BSI doubling, P<0.001) and OS (HR = 1.58, P = 0.033) in multivariate analyses including baseline BSI and TASQ treatment. TASQ delayed BSI progression. Conclusions: BSI and BSI changes over time were independently associated with OS in men with mCRPC. A delay in objective radiographic bone scan progression with TASQ is suggested; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted.

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