This past May, a collaborative think tank of researchers was convened at The Ohio State University, Columbus, to share their expertise in a somewhat older treatment that is reemerging on many fronts: photodynamic therapy.
Participants from the United States, Great Britain, and Japan took part in the inaugural International Photodynamic Medicine Symposium, hosted by Patrick Ross, Jr, MD, PhD, Chief of the Division of Thoracic Surgery; John Wilson, PhD, Associate Director; and Michael Caligiuri, MD, CEO of The Ohio State University Comprehensive Cancer Center‒James Cancer Hospital and Solove Research Institute. Clinicians from thoracic surgery, otolaryngology, gastroenterology, neurology, dermatology, radiation oncology, and hepatology joined immunologists, physicists, biochemists, and photobiologists to explore the clinical application of photodynamic therapy and review state-of-the-art research, focusing on the interplay between the laboratory and the clinic.
Speakers from Great Britain represented the University of Leeds, Yorkshire Laser Center, and the University College of London. Speakers from the United States represented the University of Pennsylvania, Roswell Park Cancer Institute, Medical College of Wisconsin, University of Miami, Harvard Medical School, Children’s Hospital of Los Angeles, Wayne State University, Mayo Clinic, Tufts University, and Weill Cornell Medical College, along with The Ohio State University.
Supported by an unrestricted educational grant from Pinnacle Biologics, Inc, the symposium was intended as a forum to stimulate a collaborative exchange of ideas for research projects, developing concepts for clinical trials, and new applications for both diagnosis and therapy for a variety of malignancies. Featuring the most recent and relevant advances in our understanding of photodynamic therapy, the proceedings of this symposium will be published in a supplement to the Journal of the National Comprehensive Cancer Network later this year. The Ohio State University is a charter member of the National Comprehensive Cancer Network (NCCN).
Although approved in Japan since the 1990s, photodynamic therapy is being performed today in approximately 45 medical centers in the United States, according to Dr. Ross, and one photosensitizer—porfimer sodium (Photofrin)—is currently approved here. The technique has been approved for treating early and late endobronchial non–small cell lung cancers as definitive therapy for symptom management and for managing symptoms associated with advanced esophageal cancers that are not suitable for other treatment. Moreover, photodynamic therapy has been approved for treating Barrett’s esophagus with high-grade dysplasia in patients who are not candidates for esophagectomy. It is also used to treat superficial basal cell carcinomas. Although the technique can be used alone, it may prove most useful in conjunction with other cancer treatments, such as surgery, radiotherapy, or chemotherapy.
Various investigational uses of photodynamic therapy have been receiving more attention of late. For instance, speakers at this symposium shared their experiences with photodynamic therapy for superficial oral and laryngeal tumors, as an adjunct to stenting for inoperable cholangiocarcinomas, and as part of lung-sparing surgery for mesothelioma. Along with mesothelioma, other areas for which current treatment options are few and/or ineffective include high-grade gliomas of the brain, for which photodynamic therapy is under investigation.
In addition, phase III studies of photodynamic therapy for prostate cancer are pending. Other ongoing areas of research in photodynamic therapy include its immunologic effects, which are being seen in photodynamic therapy vaccines that may improve antitumor immunity. This new area of photoimmunotherapy is of particular interest to both research scientists and clinicians.
One of the highlights of the symposium was the opening keynote presentation by the internationally renowned leader in the study of photodynamic therapy: Harubumi Kato, MD, PhD, Professor, Department of Surgery, Tokyo Medical University, Japan. Dr. Kato’s research focus has been on the detection and treatment of early-stage lung cancer. In 1980, he was the first person in the world to apply photodynamic therapy clinically to the treatment of lung cancer; since then, Dr. Kato says there has been “much progress” in photodynamic therapy.
For years, Dr. Kato has used photodynamic therapyto treat early-stage centrally located squamous cell carcinoma. “We can see a central tumor by endoscope but not a peripheral cancer,” he explained. Dr. Ross added that perhaps with improvements in the light delivery system, photodynamic therapy may prove to be a useful treatment of peripheral lung tumors in the future as well.
“Selection of patients for photodynamic therapy is extremely important,” reported Dr. Kato. In cases of early-stage lung, esophageal, cervical, head and neck, or skin cancer, photodynamic therapy may offer a curative benefit. Dr. Ross and Dr. Kato agreed that not all patients with lung cancer are candidates for surgery and radiation therapy. Therefore, photodynamic therapy offers these patients a possible curative alternative with no apparent long-term side effects.
Rerouting the Thinking of Oncologists
There are several reasons why photodynamic therapy has not yet moved from a niche option to a more mainstream treatment. For both Drs. Kato and Ross, the main issue may center on perspective. Dr. Kato believes that many oncologists like to treat patients with drugs, although the most effective cancer drug is about 30% effective, he said. In select patients, photodynamic therapy may represent an effective, less expensive alternative than many of the newer targeted agents.
Dr. Ross agreed, adding that oncologists need to recognize the value of this intervention, in curative, multidisciplinary, and palliative settings. In addition, many medical oncologists are not used to thinking about mechanical treatments, such as photodynamic therapy, Dr. Ross explained. “Advances in medical therapies are often based on investment,” Dr. Ross revealed. “And investment comes only when medical companies recognize a downstream market. Utilization drives research, which drives innovation, which drives investment.”
The criticisms surrounding photodynamic therapy include photosensitivity for perhaps 1 month after the procedure. Although this concern is valid, many presenters at the symposium, including Dr. Ross, agree that with the proper precautions, nursing assistance, and patient education, it is a manageable side effect. Also, the long-term efficacy of photodynamic therapy has been questioned. Although long-term outcomes with this treatment are as yet unclear, Dr. Kato noted that the 5-year survival rate is 94% in cases of early superficial bronchial lung cancer.
Although the medical literature contains many reports on the use of photodynamic therapy, and the majority of speakers at this symposium have obtained positive results with it for many malignancies, more formal phase III randomized, controlled trials comparing photodynamic therapy with standard treatment options are needed.
In closing, the future of photodynamic therapy appears bright, particularly with this premier group of experts continuing to share emerging research findings and clinical implications of this treatment alternative. The Ohio State University organizers of this symposium hope that it will become an annual event that continues to include more proponents of photodynamic therapy from the laboratories and the surgical suites, all sharing their expertise, refining techniques, joining in clinical trials, and spreading the word. ■
Disclosure: Dr. Ross is Chairman of the Scientific Advisory Board, Pinnacle Biologics. Dr. Kato reported no potential conflicts of interest.
Photodynamic therapy is a two-step treatment that includes a photosensitizing agent and a light source. In the first step, the photosensitizing agent (porfimer sodium) is injected into the bloodstream and absorbed by all cells. Over 24 to 48 hours, the drug is concentrated in cancer cells. In the...