Andrew J Armstrong1, Reza Kaboteh2, Michael A Carducci3, Jan-Erik Damber4, Walter M Stadler5, Mats Hansen6, Lars Edenbrandt7, Göran Forsberg6, Örjan Nordle6, Roberto Pili8, Michael J Morris9. 1. Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, NC. Electronic address: andrew.armstrong@duke.edu. 2. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. 4. Department of Urology, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden. 5. Department of Medicine, University of Chicago, Chicago, IL. 6. Active Biotech AB, Lund, Sweden. 7. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden; EXINI Diagnostics AB, Lund, Sweden. 8. Roswell Park Cancer Institute Genitourinary Program, Buffalo, NY. 9. Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
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 EXINIbone(BSI), 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 28placebo), 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.
RCT Entities:
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 EXINIbone(BSI), 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.
Authors: Charles J Ryan; Shreya Shah; Eleni Efstathiou; Matthew R Smith; Mary-Ellen Taplin; Glenn J Bubley; Christopher J Logothetis; Thian Kheoh; Christine Kilian; Christopher M Haqq; Arturo Molina; Eric J Small Journal: Clin Cancer Res Date: 2011-06-01 Impact factor: 12.531
Authors: Roberto Pili; Michael Häggman; Walter M Stadler; Jeffrey R Gingrich; Vasileios J Assikis; Anders Björk; Orjan Nordle; Goran Forsberg; Michael A Carducci; Andrew J Armstrong Journal: J Clin Oncol Date: 2011-09-19 Impact factor: 44.544
Authors: Gustavo S P Meirelles; Heiko Schöder; Gregory C Ravizzini; Mithat Gönen; Josef J Fox; John Humm; Michael J Morris; Howard I Scher; Steven M Larson Journal: Clin Cancer Res Date: 2010-10-25 Impact factor: 12.531
Authors: John T Isaacs; Roberto Pili; David Z Qian; Susan L Dalrymple; Jason B Garrison; Natasha Kyprianou; Anders Björk; Anders Olsson; Tomas Leanderson Journal: Prostate Date: 2006-12-01 Impact factor: 4.104
Authors: Elizabeth R Dennis; Xiaoyu Jia; Irina S Mezheritskiy; Ryan D Stephenson; Heiko Schoder; Josef J Fox; Glenn Heller; Howard I Scher; Steven M Larson; Michael J Morris Journal: J Clin Oncol Date: 2012-01-09 Impact factor: 44.544
Authors: May Sadik; Madis Suurkula; Peter Höglund; Andreas Järund; Lars Edenbrandt Journal: Eur J Nucl Med Mol Imaging Date: 2008-03-29 Impact factor: 9.236
Authors: Howard I Scher; Susan Halabi; Ian Tannock; Michael Morris; Cora N Sternberg; Michael A Carducci; Mario A Eisenberger; Celestia Higano; Glenn J Bubley; Robert Dreicer; Daniel Petrylak; Philip Kantoff; Ethan Basch; William Kevin Kelly; William D Figg; Eric J Small; Tomasz M Beer; George Wilding; Alison Martin; Maha Hussain Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: Per Björk; Anders Björk; Thomas Vogl; Martin Stenström; David Liberg; Anders Olsson; Johannes Roth; Fredrik Ivars; Tomas Leanderson Journal: PLoS Biol Date: 2009-04-28 Impact factor: 8.029
Authors: Aseem Anand; Michael J Morris; Reza Kaboteh; Lena Båth; May Sadik; Peter Gjertsson; Milan Lomsky; Lars Edenbrandt; David Minarik; Anders Bjartell Journal: J Nucl Med Date: 2015-08-27 Impact factor: 10.057
Authors: Howard I Scher; Michael J Morris; Walter M Stadler; Celestia Higano; Ethan Basch; Karim Fizazi; Emmanuel S Antonarakis; Tomasz M Beer; Michael A Carducci; Kim N Chi; Paul G Corn; Johann S de Bono; Robert Dreicer; Daniel J George; Elisabeth I Heath; Maha Hussain; Wm Kevin Kelly; Glenn Liu; Christopher Logothetis; David Nanus; Mark N Stein; Dana E Rathkopf; Susan F Slovin; Charles J Ryan; Oliver Sartor; Eric J Small; Matthew Raymond Smith; Cora N Sternberg; Mary-Ellen Taplin; George Wilding; Peter S Nelson; Lawrence H Schwartz; Susan Halabi; Philip W Kantoff; Andrew J Armstrong Journal: J Clin Oncol Date: 2016-02-22 Impact factor: 44.544
Authors: Guru Sonpavde; Gregory R Pond; Melissa Plets; Catherine M Tangen; Maha H A Hussain; Primo N Lara; Amir Goldkorn; Mark G Garzotto; Philip C Mack; Celestia S Higano; Nicholas J Vogelzang; Ian M Thompson; Przemyslaw W Twardowski; Peter J Van Veldhuizen; Neeraj Agarwal; Michael A Carducci; J Paul Monk; David I Quinn Journal: Clin Genitourin Cancer Date: 2017-05-10 Impact factor: 2.872
Authors: Guru Sonpavde; Ankit Madan; Mary K Baker; Jori E May; Gurudatta Naik; Sejong Bae Journal: Clin Genitourin Cancer Date: 2017-04-26 Impact factor: 2.872
Authors: Aseem Anand; Michael J Morris; Steven M Larson; David Minarik; Andreas Josefsson; John T Helgstrand; Peter S Oturai; Lars Edenbrandt; Martin Andreas Røder; Anders Bjartell Journal: EJNMMI Res Date: 2016-03-09 Impact factor: 3.138