Ethan Walker1, Margaret Mann2, Kord Honda2, Allison Vidimos3, Mark D Schluchter4, Brian Straight5, Matthew Bogyo6, Daniel Popkin2, James P Basilion7. 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. 2. Department of Dermatology, University Hospital, Cleveland, Ohio. 3. Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio. 4. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. 5. Akrotome Imaging Inc, Cleveland, Ohio. 6. Department of Pathology, Stanford University, Stanford, California; Department of Microbiology and Immunology, Stanford University, Stanford, California. 7. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; Department of Radiology, Case Western Reserve University, Cleveland, Ohio; National Foundation for Cancer Research Center for Molecular Imaging, Case Western Reserve University, Cleveland, Ohio. Electronic address: james.basilion@case.edu.
Abstract
BACKGROUND: Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence. OBJECTIVE: We sought to examine the utility of quenched activity-based probe imaging to discriminate cancerous versus normal-appearing skin tissue. METHODS: The quenched activity-based probe GB119 was applied to NMSC excised from 68 patients. We validated activation of the probe for hematoxylin-eosin-confirmed cancerous tissue versus normal-appearing skin tissue. RESULTS: Topical application of the probe differentiated basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with overall estimated sensitivity and specificity of 0.989 (95% confidence interval 0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe activation accurately defined peripheral margins of NMSC as compared with conventional hematoxylin-eosin-based pathology. LIMITATIONS: This study only examined NMSC debulking excision specimens. The sensitivity and specificity for this approach using final NMSC excision margins will be clinically important. CONCLUSIONS: These findings merit further studies to determine whether quenched activity-based probe technology may enable cost-effective increased cure rates for patients with NMSC by reducing re-excision and recurrence rates with a rapid and easily interpretable technological advance.
BACKGROUND: Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence. OBJECTIVE: We sought to examine the utility of quenched activity-based probe imaging to discriminate cancerous versus normal-appearing skin tissue. METHODS: The quenched activity-based probe GB119 was applied to NMSC excised from 68 patients. We validated activation of the probe for hematoxylin-eosin-confirmed cancerous tissue versus normal-appearing skin tissue. RESULTS: Topical application of the probe differentiated basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with overall estimated sensitivity and specificity of 0.989 (95% confidence interval 0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe activation accurately defined peripheral margins of NMSC as compared with conventional hematoxylin-eosin-based pathology. LIMITATIONS: This study only examined NMSC debulking excision specimens. The sensitivity and specificity for this approach using final NMSC excision margins will be clinically important. CONCLUSIONS: These findings merit further studies to determine whether quenched activity-based probe technology may enable cost-effective increased cure rates for patients with NMSC by reducing re-excision and recurrence rates with a rapid and easily interpretable technological advance.
Authors: Galia Blum; Stefanie R Mullins; Kinneret Keren; Marko Fonovic; Christopher Jedeszko; Mark J Rice; Bonnie F Sloane; Matthew Bogyo Journal: Nat Chem Biol Date: 2005-08-14 Impact factor: 15.040
Authors: Suzanne M Connolly; Diane R Baker; Brett M Coldiron; Michael J Fazio; Paul A Storrs; Allison T Vidimos; Mark J Zalla; Jerry D Brewer; Wendy Smith Begolka; Timothy G Berger; Michael Bigby; Jean L Bolognia; David G Brodland; Scott Collins; Terrence A Cronin; Mark V Dahl; Jane M Grant-Kels; C William Hanke; George J Hruza; William D James; Clifford Warren Lober; Elizabeth I McBurney; Scott A Norton; Randall K Roenigk; Ronald G Wheeland; Oliver J Wisco Journal: J Am Acad Dermatol Date: 2012-09-05 Impact factor: 11.527
Authors: Martijn Verdoes; Laura E Edgington; Ferenc A Scheeren; Melissa Leyva; Galia Blum; Kipp Weiskopf; Michael H Bachmann; Jonathan A Ellman; Matthew Bogyo Journal: Chem Biol Date: 2012-05-25
Authors: Makoto Mitsunaga; Nobuyuki Kosaka; Peter L Choyke; Matthew R Young; Christopher R Dextras; Shakir M Saud; Nancy H Colburn; Masayo Sakabe; Tetsuo Nagano; Daisuke Asanuma; Yasuteru Urano; Hisataka Kobayashi Journal: Gut Date: 2012-06-14 Impact factor: 23.059
Authors: Ethan Walker; Yiqiao Liu; InYoung Kim; David L Wilson; James P Basilion; Daniel L Popkin; Mark Biro; Sukanya Raj Iyer; Harib Ezaldein; Jeffrey Scott; Miesha Merati; Rachel Mistur; Bo Zhou; Brian Straight; Joshua J Yim; Matthew Bogyo; Margaret Mann Journal: Cancer Res Date: 2020-03-04 Impact factor: 12.701
Authors: Samantha L Schneider; Indermeet Kohli; Iltefat H Hamzavi; M Laurin Council; Anthony M Rossi; David M Ozog Journal: J Am Acad Dermatol Date: 2018-12-04 Impact factor: 11.527
Authors: Yiqiao Liu; Ethan Walker; Sukanya Raj Iyer; Mark Biro; InYoung Kim; Bo Zhou; Brian Straight; Matthew Bogyo; James P Basilion; Daniel L Popkin; David L Wilson Journal: J Med Imaging (Bellingham) Date: 2019-03-18
Authors: Ethan Walker; Daan G J Linders; Eric Abenojar; Xinning Wang; Hans Marten Hazelbag; Marieke E Straver; Okker D Bijlstra; Taryn L March; Alexander L Vahrmeijer; Agata Exner; Matthew Bogyo; James P Basilion; Brian Straight Journal: Cancers (Basel) Date: 2022-07-16 Impact factor: 6.575