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Erschienen in: Clinical Orthopaedics and Related Research® 3/2013

01.03.2013 | Symposium: Highlights from the First Combined 2011 Meeting of the Musculoskeletal Tumor Society and Connective Tissue Oncology Society

A Novel Imaging System Permits Real-time in Vivo Tumor Bed Assessment After Resection of Naturally Occurring Sarcomas in Dogs

verfasst von: William C. Eward, DVM, MD, Jeffrey K. Mito, MD, PhD, Cindy A. Eward, DVM, Jessica E. Carter, Jorge M. Ferrer, PhD, David G. Kirsch, MD, PhD, Brian E. Brigman, MD, PhD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 3/2013

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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 × 107 to 1 × 109 counts/millisecond/cm2. 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.
Literatur
1.
Zurück zum Zitat Allweis TM, Kaufman Z, Lelcuk S, Pappo I, Karni T, Schneebaum S, Spector R, Schindel A, Hershko D, Zilberman M, Sayfan J, Berlin Y, Hadary A, Olsha O, Paran H, Gutman M, Carmon M. A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery. Am J Surg. 2008;196:483–489.PubMedCrossRef Allweis TM, Kaufman Z, Lelcuk S, Pappo I, Karni T, Schneebaum S, Spector R, Schindel A, Hershko D, Zilberman M, Sayfan J, Berlin Y, Hadary A, Olsha O, Paran H, Gutman M, Carmon M. A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery. Am J Surg. 2008;196:483–489.PubMedCrossRef
2.
Zurück zum Zitat Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, Chiang DY, Reva B, Mermel CH, Getz G, Antipin Y, Beroukhim R, Major JE, Hatton C, Nicoletti R, Hanna M, Sharpe T, Fennell TJ, Cibulskis K, Onofrio RC, Saito T, Shukla N, Lau C, Nelander S, Silver SJ, Sougnez C, Viale A, Winckler W, Maki RG, Garraway LA, Lash A, Greulich H, Root DE, Sellers WR, Schwartz GK, Antonescu CR, Lander ES, Varmus HE, Ladanyi M, Sander C, Meyerson M, Singer S. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet. 2010;42:715–721.PubMedCrossRef Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, Chiang DY, Reva B, Mermel CH, Getz G, Antipin Y, Beroukhim R, Major JE, Hatton C, Nicoletti R, Hanna M, Sharpe T, Fennell TJ, Cibulskis K, Onofrio RC, Saito T, Shukla N, Lau C, Nelander S, Silver SJ, Sougnez C, Viale A, Winckler W, Maki RG, Garraway LA, Lash A, Greulich H, Root DE, Sellers WR, Schwartz GK, Antonescu CR, Lander ES, Varmus HE, Ladanyi M, Sander C, Meyerson M, Singer S. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet. 2010;42:715–721.PubMedCrossRef
3.
Zurück zum Zitat Briggs J, Paolini M, Chen QR, Wen X, Khan J, Khanna C. A compendium of canine normal tissue gene expression. PLoS One. 2011;6:e17107.PubMedCrossRef Briggs J, Paolini M, Chen QR, Wen X, Khan J, Khanna C. A compendium of canine normal tissue gene expression. PLoS One. 2011;6:e17107.PubMedCrossRef
4.
Zurück zum Zitat Brinkhof B, Spee B, Rothuizen J, Penning LC. Development and evaluation of canine reference genes for accurate quantification of gene expression. Anal Biochem. 2006;356:36–43.PubMedCrossRef Brinkhof B, Spee B, Rothuizen J, Penning LC. Development and evaluation of canine reference genes for accurate quantification of gene expression. Anal Biochem. 2006;356:36–43.PubMedCrossRef
5.
Zurück zum Zitat Ehrhart N. Soft-tissue sarcomas in dogs: a review. J Am Anim Hosp Assoc. 2005;41:241–246.PubMed Ehrhart N. Soft-tissue sarcomas in dogs: a review. J Am Anim Hosp Assoc. 2005;41:241–246.PubMed
6.
Zurück zum Zitat Haid A, Knauer M, Dunzinger S, Jasarevic Z, Köberle-Wührer R, Schuster A, Toeppker M, Haid B, Wenzl E, Offner F. Intra-operative sonography: a valuable aid during breast-conserving surgery for occult breast cancer. Ann Surg Oncol. 2007;14:3090–3101.PubMedCrossRef Haid A, Knauer M, Dunzinger S, Jasarevic Z, Köberle-Wührer R, Schuster A, Toeppker M, Haid B, Wenzl E, Offner F. Intra-operative sonography: a valuable aid during breast-conserving surgery for occult breast cancer. Ann Surg Oncol. 2007;14:3090–3101.PubMedCrossRef
7.
Zurück zum Zitat Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8:118–127.PubMedCrossRef Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8:118–127.PubMedCrossRef
8.
Zurück zum Zitat Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med. 2007;13:992–997.PubMedCrossRef Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med. 2007;13:992–997.PubMedCrossRef
9.
Zurück zum Zitat Kuntz CA, Dernell WS, Powers BE, Devitt C, Straw RC, Withrow SJ. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc. 1997;211:1147–1151.PubMed Kuntz CA, Dernell WS, Powers BE, Devitt C, Straw RC, Withrow SJ. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc. 1997;211:1147–1151.PubMed
10.
Zurück zum Zitat Lewis JJ, Leung D, Casper ES, Woodruff J, Hajdu SI, Brennan MF. Multifactorial analysis of long-term follow-up (more than 5 years) of primary extremity sarcoma. Arch Surg. 1999;134:190–194.PubMedCrossRef Lewis JJ, Leung D, Casper ES, Woodruff J, Hajdu SI, Brennan MF. Multifactorial analysis of long-term follow-up (more than 5 years) of primary extremity sarcoma. Arch Surg. 1999;134:190–194.PubMedCrossRef
11.
Zurück zum Zitat Mahoney JA, Fisher JC, Snyder SA, Hauck ML. Feasibility of using gene expression analysis to study canine soft tissue sarcomas. Mamm Genome. 2010;21:577–582.PubMedCrossRef Mahoney JA, Fisher JC, Snyder SA, Hauck ML. Feasibility of using gene expression analysis to study canine soft tissue sarcomas. Mamm Genome. 2010;21:577–582.PubMedCrossRef
12.
Zurück zum Zitat Mito JK, Ferrer JM, Brigman BE, Lee CL, Dodd RD, Eward WC, Marshall LF, Cuneo KC, Carter JE, Ramasunder S, Kim Y, Lee WD, Griffith LG, Bawendi MG, Kirsch DG. Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer. 2012. doi:10.1002/cncr.27458. Mito JK, Ferrer JM, Brigman BE, Lee CL, Dodd RD, Eward WC, Marshall LF, Cuneo KC, Carter JE, Ramasunder S, Kim Y, Lee WD, Griffith LG, Bawendi MG, Kirsch DG. Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer. 2012. doi:10.​1002/​cncr.​27458.
13.
Zurück zum Zitat Mito JK, Riedel RF, Dodd L, Lahat G, Lazar AJ, Dodd RD, Stangenberg L, Eward WC, Hornicek FJ, Yoon SS, Brigman BE, Jacks T, Lev D, Mukherjee S, Kirsch DG. Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma. PLoS One. 2009;4:e8075.PubMedCrossRef Mito JK, Riedel RF, Dodd L, Lahat G, Lazar AJ, Dodd RD, Stangenberg L, Eward WC, Hornicek FJ, Yoon SS, Brigman BE, Jacks T, Lev D, Mukherjee S, Kirsch DG. Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma. PLoS One. 2009;4:e8075.PubMedCrossRef
14.
Zurück zum Zitat Olson TP, Harter J, Munoz A, Mahvi DM, Breslin T. Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol. 2007;14:2953–2960.PubMedCrossRef Olson TP, Harter J, Munoz A, Mahvi DM, Breslin T. Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol. 2007;14:2953–2960.PubMedCrossRef
15.
Zurück zum Zitat Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14:859–868.PubMed Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14:859–868.PubMed
16.
Zurück zum Zitat Reich M, Liefield T, Gould J, Lerner J, Tamavo P, Mesirov JP. GenePattern 2.0. Nat Genet. 2006;38:500–501.PubMedCrossRef Reich M, Liefield T, Gould J, Lerner J, Tamavo P, Mesirov JP. GenePattern 2.0. Nat Genet. 2006;38:500–501.PubMedCrossRef
17.
Zurück zum Zitat Sabolch A, Feng M, Griffith K, Rzasa C, Gadzala L, Feng F, Biermann JS, Chugh R, Ray M, Ben-Josef E. Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity. Am J Clin Oncol. 2012;35:151–157.PubMedCrossRef Sabolch A, Feng M, Griffith K, Rzasa C, Gadzala L, Feng F, Biermann JS, Chugh R, Ray M, Ben-Josef E. Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity. Am J Clin Oncol. 2012;35:151–157.PubMedCrossRef
18.
Zurück zum Zitat Sadoski C, Suit HD, Rosenberg A, Mankin H, Efird J. Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol. 1993;52:223–230.PubMedCrossRef Sadoski C, Suit HD, Rosenberg A, Mankin H, Efird J. Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol. 1993;52:223–230.PubMedCrossRef
19.
Zurück zum Zitat Welle MM, Bleyt CR, Howard J, Rufenacht S. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology, and treatment. Vet Dermatol. 2008;19:321–339.PubMedCrossRef Welle MM, Bleyt CR, Howard J, Rufenacht S. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology, and treatment. Vet Dermatol. 2008;19:321–339.PubMedCrossRef
Metadaten
Titel
A Novel Imaging System Permits Real-time in Vivo Tumor Bed Assessment After Resection of Naturally Occurring Sarcomas in Dogs
verfasst von
William C. Eward, DVM, MD
Jeffrey K. Mito, MD, PhD
Cindy A. Eward, DVM
Jessica E. Carter
Jorge M. Ferrer, PhD
David G. Kirsch, MD, PhD
Brian E. Brigman, MD, PhD
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Clinical Orthopaedics and Related Research® / Ausgabe 3/2013
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-012-2560-8

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