Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial

Breast Cancer Research

Zhihui ( Amy) Liu¹  Tony Panzarella¹  Cheryl F. Rosen²  Philip J. Medeiros³  Stephanie DeLuca³  Iris Kulbatski³  Emilie Chamma³  Ashley Chu³  Shirley C. Wang³  Liis Lindvere Teene³  Christopher Gibson³  Safa Majeed³  Anam Shahid³  Sara Rapic³  Danielle Starr-Dunham³  Kathryn Ottolino-Perry³  Nayana Thalanki Anantha³  Olivia Wignall³  Alessandra Pizzolato³  Ralph S. DaCosta⁴  Mayleen Sukhram⁵  Viktor Son⁵  Fannong Meng⁵  Susan J. Done⁶  Alexandra M. Easson⁷  Wey L. Leong⁷ 

[1] Biostatistics Department, University Health Network, 610 University Ave, M5T 2M9, Toronto, Ontario, Canada;Dermatology Department, Toronto Western Hospital, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, Ontario, Canada;Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Department of Medical Biophysics, Faculty of Medicine, University of Toronto, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Techna Institute, University Health Network, 124-100 College Street, M5G 1P5, Toronto, Ontario, Canada;Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Laboratory Medicine Program, University Health Network, 200 Elizabeth Street, 11th Floor Eaton Wing, M5G 2C4, Toronto, Ontario, Canada;Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Laboratory Medicine Program, University Health Network, 200 Elizabeth Street, 11th Floor Eaton Wing, M5G 2C4, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, M5S 1A8, Toronto, Ontario, Canada;Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute, 101 College Street, M5G 1L7, Toronto, Ontario, Canada;Surgical Oncology Department, Princess Margaret Cancer Centre of University Health Network, 610 University Ave, M5T 2M9, Toronto, Ontario, Canada;

关键词: Breast cancer;    Breast-conserving surgery;    Fluorescence imaging;    Intraoperative imaging;    Aminolevulinic acid;    Margin assessment;    Optical imaging;    Handheld intraoperative imaging device;   

DOI  :  10.1186/s13058-021-01442-7

来源: Springer

【 摘 要 】

BackgroundRe-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS.MethodsFifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology.ResultsIn the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed.ConclusionsThis is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device.Trial registrationClinicaltrials.gov identifier NCT01837225. Registered 23 April 2013.

【 授权许可】

CC BY