New probe accurately detects cancer during surgery: A discussion with Dr. Frederic Leblond

Background
Residual cancer cells that are undetected and left behind after surgical resection—if not subsequently destroyed by chemotherapy or radiotherapy—can result in the cancer recurring along with greater risk of death.

“In situ cancer detection is profoundly important because residual cancer following surgery negatively influences the time to cancer recurrence and survival time. There is thus a need for the development of highly sensitive and specific cancer detection instruments that can be seamlessly integrated into clinical practice,” wrote investigators in a new article published in Cancer Research.

Current optical imaging methods to detect cancer include Raman spectroscopy (RS), intrinsic fluorescence spectroscopy (IFS), and diffuse reflectance spectroscopy (DRS). RS can detect multiple cancer pathologies with about 90% accuracy, but that still leaves room for improvement. So, these investigators developed an optical imaging device—a handheld probe that can be used during surgery—that incorporates all three technologies.

During surgery, the probe can be used to interrogate brain tissue. The probe incorporates Raman spectroscopy, intrinsic fluorescence spectroscopy, and diffuse reflectance spectroscopy in one device.

“By combining RS with IFS and DFS, we are excited that our results showed 97% accuracy, 100% sensitivity, and 93% specificity,” said Frédéric Leblond, BEng, PhD, Director of the Laboratory for Radiological Optics and Professor of Engineering Physics at Polytechnique Montreal, and Researcher at the University of Montreal Hospital (CHUM) Research Centre, in Montreal, Canada.

Dr. Leblond developed the imaging tool with Kevin Petrecca, MD, PhD, a neurosurgeon who specializes in neurosurgical oncology at the Montreal Neurological Institute and Hospital, and is Associate Professor of Neurology and Neurosurgery at McGill University in Montreal. “With brain cancer, near-perfect detection is important so that we can remove as much cancer as possible, without removing healthy tissue,” Dr. Petrecca said. “Residual cancer post-surgery is associated with decreased time to recurrence and lower survival.”

This schematic depiction shows the probe as well as Raman spectroscopy and an MRI image, with the red area representing the brain tumor.

He added, “Our findings are novel since optical techniques are not standard in any surgeries at present. The results also indicate a strong potential for this technology to be adapted to a wide range of surgical and detection applications, including laparoscopic and robotic surgeries, and colonoscopy.”

In this interview, Dr. Leblond discusses the development of this device, how it can be implemented, and what’s up next for this technology.

MDLinx: Where did you get the idea to combine RS with IFS and DFS?

Dr. Leblond: The idea for combining Raman with fluorescence is that the molecular information they can provide is complementary, with fluorescence providing information relating to structure and metabolism.

Prior to our initial Raman spectroscopy work in 2015, we had been working for many years on other approaches to detect cancer tissue to improve safety and maximize the volume of tumor resected. Cancer is a very heterogeneous disease, and grade II-IV gliomas are inherently invasive cancers. As the decreasing gradient of cancer cells invades into the brain, it is not possible to distinguish a boundary between cancer and normal brain. Thus, invasive cancer cells are not completely removed during surgery, leading to local recurrence in about 85% of cases.

Specific and sensitive tissue classification requires techniques that are able to highlight several molecular processes simultaneously. Raman spectroscopy allows the identification and quantification of a very large number of molecular species and, as a result, represented an excellent candidate for brain tumor detection. In multiple studies done so far (80 patients) evaluating Raman to detect cancer, we consistently found detection accuracies around 90%, but adding intrinsic tissue fluorescence (in 19 new patients) improved this accuracy toward 100%.

MDLinx: What were the challenges involved in combining these technologies?

Dr. Leblond: There were two main challenges that we met. Introducing fluorescence required the development of new artificial intelligence algorithms for tissue classification, which needed to be trained to recognize cancer based on completely new types of data, combined spectroscopic data from Raman and fluorescence.

On the hardware side, we needed to develop a new probe where a subset of optical fibers are now dedicated to fluorescence detection, and for which miniaturized interference filters are designed to insure specific detection of tissue fluorescence.

MDLinx: What is the next step in this line of research, and when do you think the system will be commercially available to surgeons?

Dr. Leblond: There are multiple next steps:

• We are currently adapting the technology to be integrated into the workflow of other surgical oncologists dealing with prostate, lung, and ovarian cancer. This includes the development of optical biopsy needles as well as surgical robots equipped with our technology. A proof-of-principle has been completed by our group demonstrating prostate and lung cancers can be detected with our technology.
• We have started earlier in June 2017 a randomized controlled trial on 80 patients where the Raman probe is used to guide brain cancer resection.
• We formed a company in 2015 to commercialize the neurosurgical application: ODS Medical Inc. We have initiated the FDA submission process, have been admitted into an expedited path to the FDA.

About Dr. Leblond: Frédéric Leblond, BEng, PhD, Director of the Laboratory for Radiological Optics and Associate Professor at Polytechnique Montreal, and Researcher at CHUM Research Centre, in Montreal, Canada.