Literature DB >> 22972654

A novel imaging system permits real-time in vivo tumor bed assessment after resection of naturally occurring sarcomas in dogs.

William C Eward1, Jeffrey K Mito, Cindy A Eward, Jessica E Carter, Jorge M Ferrer, David G Kirsch, Brian E Brigman.   

Abstract

BACKGROUND: Treatment of soft tissue sarcoma (STS) includes complete tumor excision. However, in some patients, residual sarcoma cells remain in the tumor bed. We previously described a novel hand-held imaging device prototype that uses molecular imaging to detect microscopic residual cancer in mice during surgery. QUESTIONS/PURPOSES: To test this device in a clinical trial of dogs with naturally occurring sarcomas, we asked: (1) Are any adverse clinical or laboratory effects observed after intravenous administration of the fluorescent probes? (2) Do canine sarcomas exhibit fluorescence after administration of the cathepsin-activated probe? (3) Is the tumor-to-background ratio sufficient to distinguish tumor from tumor bed? And (4) can residual fluorescence be detected in the tumor bed during surgery and does this correlate with a positive margin?
METHODS: We studied nine dogs undergoing treatment for 10 STS or mast cell tumors. Dogs received an intravenous injection of VM249, a fluorescent probe that becomes optically active in the presence of cathepsin proteases. After injection, tumors were removed by wide resection. The tumor bed was imaged using the novel imaging device to search for residual fluorescence. We determined correlations between tissue fluorescence and histopathology, cathepsin protease expression, and development of recurrent disease. Minimum followup was 9 months (mean, 12 months; range, 9-15 months).
RESULTS: Fluorescence was apparent from all 10 tumors and ranged from 3 × 10(7) to 1 × 10(9) counts/millisecond/cm(2). During intraoperative imaging, normal skeletal muscle showed no residual fluorescence. Histopathologic assessment of surgical margins correlated with intraoperative imaging in nine of 10 cases; in the other case, there was no residual fluorescence, but tumor was found at the margin on histologic examination. No animals had recurrent disease at 9 to 15 months.
CONCLUSIONS: These initial findings suggest this imaging system might be useful to intraoperatively detect residual tumor after wide resections. CLINICAL RELEVANCE: The ability to assess the tumor bed intraoperatively for residual disease has the potential to improve local control.

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Year:  2013        PMID: 22972654      PMCID: PMC3563778          DOI: 10.1007/s11999-012-2560-8

Source DB:  PubMed          Journal:  Clin Orthop Relat Res        ISSN: 0009-921X            Impact factor:   4.176


  19 in total

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Authors:  Jennifer A Mahoney; Julie C Fisher; Stacey A Snyder; Marlene L Hauck
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2.  Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence.

Authors:  T P Olson; J Harter; A Muñoz; D M Mahvi; Tm Breslin
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3.  A spatially and temporally restricted mouse model of soft tissue sarcoma.

Authors:  David G Kirsch; Daniela M Dinulescu; John B Miller; Jan Grimm; Philip M Santiago; Nathan P Young; G Petur Nielsen; Bradley J Quade; Christopher J Chaber; Christian P Schultz; Osamu Takeuchi; Roderick T Bronson; Denise Crowley; Stanley J Korsmeyer; Sam S Yoon; Francis J Hornicek; Ralph Weissleder; Tyler Jacks
Journal:  Nat Med       Date:  2007-08-05       Impact factor: 53.440

4.  A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery.

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5.  Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity.

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Review 6.  Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment.

Authors:  Monika M Welle; Carla Rohrer Bley; Judith Howard; Silvia Rüfenacht
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Authors:  Jordi Barretina; Barry S Taylor; Shantanu Banerji; Alexis H Ramos; Mariana Lagos-Quintana; Penelope L Decarolis; Kinjal Shah; Nicholas D Socci; Barbara A Weir; Alan Ho; Derek Y Chiang; Boris Reva; Craig H Mermel; Gad Getz; Yevgenyi Antipin; Rameen Beroukhim; John E Major; Charles Hatton; Richard Nicoletti; Megan Hanna; Ted Sharpe; Tim J Fennell; Kristian Cibulskis; Robert C Onofrio; Tsuyoshi Saito; Neerav Shukla; Christopher Lau; Sven Nelander; Serena J Silver; Carrie Sougnez; Agnes Viale; Wendy Winckler; Robert G Maki; Levi A Garraway; Alex Lash; Heidi Greulich; David E Root; William R Sellers; Gary K Schwartz; Cristina R Antonescu; Eric S Lander; Harold E Varmus; Marc Ladanyi; Chris Sander; Matthew Meyerson; Samuel Singer
Journal:  Nat Genet       Date:  2010-07-04       Impact factor: 38.330

8.  Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging.

Authors:  Jeffrey K Mito; Jorge M Ferrer; Brian E Brigman; Chang-Lung Lee; Rebecca D Dodd; William C Eward; Lisa F Marshall; Kyle C Cuneo; Jessica E Carter; Shalini Ramasunder; Yongbaek Kim; W David Lee; Linda G Griffith; Moungi G Bawendi; David G Kirsch
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9.  A compendium of canine normal tissue gene expression.

Authors:  Joseph Briggs; Melissa Paoloni; Qing-Rong Chen; Xinyu Wen; Javed Khan; Chand Khanna
Journal:  PLoS One       Date:  2011-05-31       Impact factor: 3.240

10.  Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma.

Authors:  Jeffrey K Mito; Richard F Riedel; Leslie Dodd; Guy Lahat; Alexander J Lazar; Rebecca D Dodd; Lars Stangenberg; William C Eward; Francis J Hornicek; Sam S Yoon; Brian E Brigman; Tyler Jacks; Dina Lev; Sayan Mukherjee; David G Kirsch
Journal:  PLoS One       Date:  2009-11-30       Impact factor: 3.240

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  8 in total

1.  Intra-operative imaging of surgical margins of canine soft tissue sarcoma using optical coherence tomography.

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2.  A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

Authors:  Jenna L Mueller; Henry L Fu; Jeffrey K Mito; Melodi J Whitley; Rhea Chitalia; Alaattin Erkanli; Leslie Dodd; Diana M Cardona; Joseph Geradts; Rebecca M Willett; David G Kirsch; Nimmi Ramanujam
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Review 3.  The status of contemporary image-guided modalities in oncologic surgery.

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4.  Intraoperative Raman spectroscopy of soft tissue sarcomas.

Authors:  John Q Nguyen; Zain S Gowani; Maggie O'Connor; Isaac J Pence; The-Quyen Nguyen; Ginger E Holt; Herbert S Schwartz; Jennifer L Halpern; Anita Mahadevan-Jansen
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5.  Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents.

Authors:  Kyle C Cuneo; Jeffrey K Mito; Melodi P Javid; Jorge M Ferrer; Yongbaek Kim; W David Lee; Moungi G Bawendi; Brian E Brigman; David G Kirsch
Journal:  Int J Radiat Oncol Biol Phys       Date:  2013-02-04       Impact factor: 7.038

6.  A Novel Imaging System Distinguishes Neoplastic from Normal Tissue During Resection of Soft Tissue Sarcomas and Mast Cell Tumors in Dogs.

Authors:  Suzanne Bartholf DeWitt; William C Eward; Cindy A Eward; Alexander L Lazarides; Melodi Javid Whitley; Jorge M Ferrer; Brian E Brigman; David G Kirsch; John Berg
Journal:  Vet Surg       Date:  2016-06-09       Impact factor: 1.495

Review 7.  Molecular probes for selective detection of cysteine cathepsins.

Authors:  Kelton A Schleyer; Lina Cui
Journal:  Org Biomol Chem       Date:  2021-07-21       Impact factor: 3.890

8.  A Fluorescence-Guided Laser Ablation System for Removal of Residual Cancer in a Mouse Model of Soft Tissue Sarcoma.

Authors:  Alexander L Lazarides; Melodi J Whitley; David B Strasfeld; Diana M Cardona; Jorge M Ferrer; Jenna L Mueller; Henry L Fu; Suzanne Bartholf DeWitt; Brian E Brigman; Nimmi Ramanujam; David G Kirsch; William C Eward
Journal:  Theranostics       Date:  2016-01-01       Impact factor: 11.556

  8 in total

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