An RSNA Research Scholar is leading a team of University of Pennsylvania Medical Center (Penn) researchers working to extend a treatment with proven success in lung cancer to the particularly aggressive and often fatal peritoneal carcinomatosis.

Stephen Hahn, M.D.
University of Pennsylvania

Stephen Hahn, M.D., began his research in the late 1990s when, as a radiation oncology resident at the National Cancer Institute (NCI), his mentor Eli Glatstein, M.D., investigated a new treatment called photodynamic therapy (PDT). Their initial research showed that administering a photosensitizing drug intravenously and then applying a laser light superficially to surface malignancies safely and effectively killed cancer cells.

When Dr. Glatstein became vice-chair and clinical director of the Department of Radiation Oncology at Penn, he recruited Dr. Hahn to develop a PDT program. Dr. Hahn's work was immediately boosted by RSNA Research Scholar Grants to study "PDT of Peritoneal and Pleural Surfaces" in 1998 and "PDT for Peritoneal Carcinomatosis" in 1999.

Peritoneal carcinomatosis spreads over the surfaces and through the lining of organs, making it extremely complicated to treat.

"The RSNA grants helped to fund the start up of our clinical trials, which focused experimentally on treating these cancers in the peritoneum and the lining of the pleura," said Dr. Hahn, now chair of the Department of Radiation Oncology at Penn. "Ovarian cancer, sarcomas and several gastrointestinal cancers like colon and pancreatic spread like this.

"We wouldn't have been able to get our initial trials done and understand the biology and the patient care aspects of PDT without the RSNA grants. They got us to where we are today," added Dr. Hahn.

Physicians at the University of Pennsylvania (Penn) deliver intraoperative photodynamic therapy (PDT). Having had success using PDT—which involves an intravenous injection of a photosensitizing drug followed by application of a laser light to surface malignancies—on cancer of the pleura, Penn researchers are determined to obtain similar results with peritoneal cancer.
Image courtesy of Stephen Hahn, M.D.

Absorption Differences Produced Toxic Side Effects

While the medical literature suggested that the photosensitizing drug used in PDT seemed to stay in tumors longer than normal tissues—a fact borne out in animal models—Dr. Hahn and his team found that there was very little difference in drug uptake between tumor and normal tissue in the peritoneum of humans, which resulted in toxic side effects. However, they found that less severe side effects occurred when PDT was used on cancer of the pleura.

"We published a paper in the Journal of Clinical Oncology a couple of years ago where we had superb preliminary results in non-small cell lung cancer where patients had disease spread to the lining of the lung—a very difficult problem and quite deadly," said Dr. Hahn. "The median survival for patients we had treated on the trial was 25 months, where historically the survival was more in the 9 to 12 month range."

According to Dr. Hahn, board certified in internal medicine and medical and radiation oncology, the differences between the peritoneum and the pleura is a matter of logistics. "The abdomen is a very complicated area with lots of loops of bowel and it is very difficult to get a homogeneous dose of light to all of the nooks and crannies," he said. "With the lung, there aren't as many critical structures that limit the dose. You do have heart and esophagus, but they tend to be a bit more shielded than the other organs."

Dr. Hahn is determined to see better success with PDT in peritoneal cancer. Since being appointed radiation oncology chair in 2005, Dr. Hahn has designated Keith Cengel, M.D., Ph.D., an assistant professor of radiation oncology, to move the PDT project forward. Dr. Cengel received an RSNA Research Resident Grant sponsored by Philips Medical Systems in 2003.

Molecular Targeting Agent Investigated

While work has continued on the PDT pleura research during the last few years, peritoneal trials have been on hiatus while Drs. Hahn and Cengel have worked with colleagues to find ways to reduce the toxic side effects and increase the overall effectiveness of the therapy.

"PDT has done some things we're pleased with and it hasn't done some things that we think it can do," said Dr. Glatstein, now a professor of radiation oncology at Penn. "In the pleura, it looks good. In the peritoneal, it hasn't been as good and so we have a plan to tweak it."

That "tweak" involves adding a molecular target agent to enhance PDT's effect on tumors while sparing normal tissue. This next phase of PDT research, funded by a recently renewed National Institutes of Health, NCI Program Project Grant, is scheduled to start later this year.

"PDT is already an FDA-approved treatment for several diseases, including obstructing lung cancer and esophageal cancer, and is particularly used for Barrett's esophagus," said Dr. Hahn. "We're trying to extend the indications for PDT, particularly because it doesn't seem to have the late effects that radiotherapy has on patients. I think the addition of the molecular targeting agent is a really exciting approach and will pull us in a good direction."

Feeling that they are making a personal impact is one of the most satisfying parts of the research, said both Drs. Hahn and Cengel.

"I was talking to one of our patients yesterday who said that her home state medical oncologist told her to essentially go home and die," said Dr. Cengel. "What we're trying to do is to change the end of the story. We're cowboy optimists. We're trying to cure her. And while our peritoneal work has prolonged some patient lives, we haven't cured anyone yet, but we think it's possible. We think this is a potentially curable population."