Using Fluorescence to Clear Cancer
One of the most common forms of cancer surgery is called a lumpectomy, the removal of a tumor from the breast. Along with removing this “lump”, the surgeon also removes a small margin of the surrounding normal breast tissue. The assumption here is that cancer cells may be lurking in the surrounding tissue—cancer that’s invisible to the naked eye.
Because surgeons cannot see those spots of cancer in the margin, they must rely on the pathologist to check to make sure the tissue margins are “clear”, meaning no cancer is present in the outermost edges of the breast tissue sample. A preliminary check of the margins can be done while the patient is still in the operating room, enabling the surgeon to obtain “clear margins” during the same operation.
But even this is only a preliminary reading, and the final results of a pathology report will take a few days to reveal whether any residual cancer is in the margins. If the answer is yes, then additional surgery is usually recommended to try to remove the remaining cancer. Otherwise a mastectomy is often offered as an alternative. Radiotherapy is also recommended after lumpectomy in case the pathologist, too, missed some spot of cancer.
But is there a better way to determine whether the edges of the surgical sample are free of cancer cells? The answer is a resounding yes! The solution is fluorescence-guided surgery or FGS (also called fluorescence-guided resection).
This is a type of “image-guided surgery”, and it enables the surgeon to visualize the tumor and its edges for optimal removal of all the cancer in and around the tumor. In order to image the tumor, FGS is currently practiced using photosensitizers or fluorescing agents. The entire approach and its benefits have recently been reviewed by medical oncologist Ron Allison, who currently serves as Editor-in-Chief of the peer-reviewed medical journal, Photodiagnosis and Photodynamic Therapy.
“Potentially this may not only allow the surgeon a greater chance of complete lesion resection but also prevent or minimize resection of normal tissues, which generally do not light up,” writes Drl Allison in the March 2016 issue of Photodiagnosis and Photodynamic Therapy. “Essentially a fluorescent probe is applied and if successful, this probe will concentrate in the tumor. An external light source is then used to illuminate the surgical field and through the phenomena of flourescence, the tumor literally lights up. Normal surrounding tissue, as it does not contain the fluorescent probe, does not.”
Dr. Allison notes that the ability of FGS to accurately remove cancerous tissue while better sparing normal, healthy tissue is what makes this approach such an attractive and sensible treatment option. It also explains the remarkable results of human studies comparing FGS to standard “white light” surgery (i.e., surgery without the advantage of visualization facilitated by fluorescence).
Proof from Clinical Trials
In clinical trials, significantly improved survival has been reported with FGS for tumors of the brain and bladder. With bladder cancer, FGS has led to marked reductions in recurrence rates—a very serious and costly issue for many bladder cancer survivors. A meta-analysis of randomized trials showed that FGS significantly improves the chances of having clear margins and decreases local recurrence rates for bladder cancer survivors.
With brain cancer, the treatment allows for more complete removal of cancer, because the laser light can reach delicate parts fo the brain that otherwise would be damaged by surgery. Allison cites a recent meta-analysis concluding that FGS enables “an extraordinary six months average survival advantage over white light procedures” in patients with advanced brain tumors.
FGS has also been evaluated as a treatment for primary lung tumors. Several studies have shown an ability to spare normal lung tissue, as evidenced by complete removal of the fluorescing tumor—while sparing the nonfluorescent lung tissues.
“This is critical as most individuals with lung cancer have poor pulmonary reserve, and sparing normal lung translates into improved pulmonary status,” Allison writes. He goes on to note that fluorescence helps reveal “satellite metastatic lesions” that would otherwise be missed in about 1 out of 10 lung cancer patients. “These satellite tumors, not seen on preoperative imaging studies, fluoresced during surgery,” he notes.
Finally, Allison notes that a small group of patients have undergone FGS for liver metastasis. The findings again showed an increased ability to achieve clear margins around the surgical site. Moreover, an unexpectedly high number of metastatic yet operable lesions were revealed during FGS that could not have been visualized without fluorescence. Thus, the surgeon can now see and treat deadly liver metastases as never before.
From Flourescence to Light Treatment
One underappreciated aspect of FGS is that some of the photosensitizers used to illuminate the cancer can also be activated to destroy the cancer. In other words, the fluorescence serves a dual purpose of diagnosis and treatment. After lighting up a particular area to reveal the presence of cancer, it can then be treated with simple adjustmens in the light dosage or intensity.
“This would mainly require more intense light of the appropriate wavelengths for the particular photosensitizer,” Allison writes. “Therefore the surgeon could use FGS as an enhanced means to improve resection, followed immediately by photodynamic therapy (PDT) to wipe up any residual tumor.”
In summary, FGS has tremendoous potential for both patients and physicians. But as Allison notes, “Only time and effort will tell what it will truly achieve.”
Allison RR. Fluorescence guided resection (FGS): A primer for oncology. Photodiagnosis Photodyn Ther. 2015 Nov 28. [Epub ahead of print]
DeLong JC, Hoffman RM, Bouvet M. Current status and future perspectives of fluorescence-guided surgery for cancer. Expert Rev Anticancer Ther. 2016 Jan;16(1):71-81.