Bottom Line: A high-resolution, three-dimensional imaging technique, when combined with quantitative measurement of tissue elasticity, could accurately detect cancer within the resected margins of surgical specimens taken from patients undergoing breast-conserving surgery.
Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research
Authors: Brendan F. Kennedy, PhD, associate professor in the School of Engineering at The University of Western Australia (UWA) and laboratory head of BRITElab at the Harry Perkins Institute of Medical Research in Perth, Western Australia; and Christobel Saunders, MBBS, professor in the School of Medicine at UWA
Background: "Despite living in the 'digital age,' surgeons must routinely rely on their eyesight and sense of touch to determine if they have removed the entire tumor during breast-conserving surgery," said Kennedy. "Due to lack of adequate tools, 20 to 30 percent of patients must return for additional surgery, resulting in substantial physical and financial burdens and increased risk of complications."
Beyond surgeons' native senses of sight and touch, X-rays are often used for the intraoperative detection of tumor in the margin of surgical specimens, said Saunders. "While useful in some cases, this method can't detect small microscopic traces of tumor that surgeons often miss," she said. "As a result, it is widely accepted that higher-resolution intraoperative detection techniques are needed."
Optical coherence tomography (OCT) is a type of imaging technique that generates three-dimensional images of tissue. "OCT can be described as the optical equivalent of ultrasound, using reflections of light waves rather than sound waves to form images of tissue microstructure," Kennedy explained. The images generated by OCT can be used to visualize and detect cancer in mastectomy tissues, but the sensitivity and specificity of this technique in breast-conserving surgery specimens in several recent studies was relatively low.
Cancer and its associated stroma are stiffer than benign tissues, Kennedy explained. OCT technology can also be used to measure tissue deformation under an applied force, allowing for clinicians to ascertain the elasticity, or stiffness, of the surgical specimen. Quantitative micro-elastography (QME) is a variant of OCT that can generate three-dimensional maps of local elasticity. "We wanted to determine the diagnostic accuracy of QME for detecting tumor in the margins of breast-conserving surgical specimens, and compare this technique with images generated by OCT alone," Kennedy said.
How the Study was Conducted: In this study by Kennedy, Saunders, and colleagues, 90 patients were recruited who were undergoing surgical treatment for breast cancer. Of these patients, 83 received breast-conserving surgery, and seven received a mastectomy. Following surgery, simultaneous OCT and QME analyses were conducted on the resection margins of the freshly excised specimens. After imaging, the surgical specimens were submitted for standard histopathological processing. Histology sections were co-registered with the OCT and QME images to determine the types of tissue present in each scan.
To facilitate the comparison of OCT and QME images with histopathology, three-dimensional regions of interest (ROI) were selected from the scans. At least one ROI was selected for every surgical margin used in the study. Each ROI was determined to be positive for cancer if the pathologist identified tumor within 1 millimeter (mm) of the margin of the corresponding histology section.
To generate a set of pilot data, the researchers used all mastectomy surgical samples and surgical samples from 12 patients who received breast-conserving surgery. These data were used to train seven readers (two surgeons, two engineers, one medical sonographer, one pathology assistant, and one medical resident) to determine if images generated by OCT and QME indicated the presence of cancer in the surgical margins.
Surgical samples from the remaining 71 patients who received breast-conserving surgery were used to determine the ability of OCT and QME to detect cancer within 1mm of the surgical margins, as compared with gold-standard post-operative histology. Readers were blinded to the histopathology results. Sensitivity, specificity, and accuracy of each method was calculated for each reader, and aggregate results for all of the readers were determined. While inter-reader agreement was nearly perfect for QME, agreement was only moderate for OCT, Kennedy noted.
Results: Based on the aggregate results, OCT images resulted in a 69.0 percent sensitivity, 79.0 percent specificity, and 77.5 percent accuracy for detecting cancer within 1mm of the surgical margin. QME images resulted in a 92.9 percent sensitivity, 96.4 percent specificity, and 95.8 percent accuracy for detecting cancer within 1mm of the surgical margin.
Author's Comments: "Imaging the microscale stiffness of tissue using QME has the potential to reduce re-excision rates in breast-conserving surgery," Kennedy said. "Further, by quantifying tissue stiffness, we remove the subjectivity that is inherent to the surgeon's sense of touch.
"The ideal scenario would be to perform the imaging in the surgical cavity immediately after the specimen has been removed," Kennedy continued. "This would give surgeons a direct indication of whether any tumor had been missed. As such, our next goal is to develop a handheld QME probe to enable intraoperative imaging."
Study Limitations: Roughly 12 percent of the selected ROIs were excluded from the study for a variety of reasons, including extensive thermal damage, imaging artifacts, or the presence of a rare form of mucinous ductal carcinoma in situ (DCIS), representing a limitation of the study. "We are working on ways to accommodate for each of these excluded ROIs to ensure that the technique is as robust as possible," Kennedy said.
Funding & Disclosures: This study was sponsored by OncoRes Medical Pty Ltd, in which Kennedy discloses financial interest.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes 46,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 127 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 22,500 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org.