[Image from MIT]
Ovarian cancer is typically not diagnosed until it is in its advanced stages, according to the researchers. Most women undergo surgery to remove as many tumors as possible, but some tumors are too small and widespread to be completely removed.
The new debulking method uses a fluorescence imaging system that can find tumors as small as 0.3 mm during surgery. They tested the method in mice and found that the mice that had the image-guided surgery survived 40% longer than mice who didn’t have image-guided surgery.
“What’s nice about this system is that it allows for real-time information about the size, depth and distribution of tumors,” Angela Belcher, a researcher on the project and a member of the Koch Institute for Integrative Cancer Research, said in a press release.
The researchers are now looking for FDA approval for a phase 1 clinical trial to be able to test the system in humans.
Approximately 22,530 women will be diagnosed with ovarian cancer this year and 13,980 women will die from the disease, according to the American Cancer Society. A woman’s risk of developing ovarian cancer in her lifetime is about 1 in 78 and her chance of dying is about 1 in 108.
“We desperately need better upfront therapies, including surgery, for these (ovarian cancer) patients,” Michael Birrer, director of the O’Neal Comprehensive Cancer Center at the University of Alabama and a senior author on the study, said.
The researchers wanted to develop a near-infrared imaging system to help surgeons identify tumors in ovarian cancer surgery by offering continuous, real-time imaging of the abdomen with tumors being highlighted by fluorescence.
Chemical probes using single-walled carbon nanotubes emit fluorescent lights when illuminated by lasers to help make the tumors visible. The nanotubes are coated with a peptide that can bind itself to a protein known as SPARC and is overexpressed by invasive ovarian cancer cells. The chemical probes bind to tumors and make them glow in near-infrared wavelengths to give surgeons a more clear image of where tumors are located in debulking procedures.
The image-guided system was tested in mice that had ovarian tumors implanted in the abdominal cavity. Surgeons found and removed tumors smaller than a poppy seed and 10 days after surgery, the mice showed no signs of detectable tumors. Mice who had non-image-guided surgery had residual tumors.
Three weeks after the surgery, some of the tumors grew back in mice that had image-guided surgery, but their median survival rate was 40% longer than mice in traditional surgery, according to the researchers.
“You can’t have a patient in a CT machine or an MRI machine and have the surgeon perform this surgical debulking procedure at the same time, and you can’t expose the patient to X-ray radiation for multiple hours of the long surgery. This optics-based imaging system allows us to do that in a safe manner,” Neelkanth Bardhan, a lead author on the study, said.
Most ovarian cancer patients who undergo debulking surgery have to have chemotherapy after the surgery. The researchers plan to do another study where they treat mice with chemotherapy after surgery to prevent tiny tumors from spreading.
“We know that the amount of tumor removed at the time of surgery for patients with advanced-stage ovarian cancer is directly correlated with their outcome,” Birrer said. “This imaging device will now allow the surgeon to go beyond the limits of setting tumors visible to the naked eye, and should usher in a new age of effective debulking surgery.”
The researchers now plan to adapt the system for use in human patients.
“In principle, it’s quite doable,” Andrew Siegel, a researcher on the study, said. “It’s purely the mechanics and the ending at this point because this mouse experiment serves as the proof of principle and may actually have been more challenging than building a human-scale system.”
They also hope to use the imaging technique to monitor patients following surgery and develop it into a diagnostic tool to screen women who are at a higher risk of developing ovarian cancer.
“A major focus for us right now is developing the technology to be able to diagnose ovarian cancer early, in stage 1 or stage 2, before the disease becomes disseminated,” Belcher said. “That could have a huge impact on survival rates because survival is related to the stage of detection.”
The research was published in the journal ACS Nano and was funded in part by the Bridge Project and the Koch Institute Support grant from the National Cancer Institute, with support for the development of the system from the Koch Institute Frontier Research Program and the Kathy and Curt Marble Cancer Research Fund.
