Three rounds of chemotherapy have not whittled down the four tumors in Mayor Bob O'Connor's brain, so starting next week his doctors will try to kill the cancer with radiation therapy.

	Tony Tye, Post-Gazette Dick Skrinjar, director of communication in the mayor's office, speaks at the start of a news conference in the Herberman Conference Center at UPMC Shadyside yesterday. Seated, from left, are Drs. Stanley Marks, Frank Lieberman and Amin Kassam. Click photo for larger image. Related article Analysis: O'Connor weeks away from retaking mayoral reins

Dr. Stanley Marks, director of clinical services at UPMC Hillman Cancer Center, said the high-dose methotrexate treatments the mayor has been getting every two weeks since July 11 to treat primary central nervous system T-cell lymphoma have greatly reduced the number of cancer cells in his spinal fluid.

But a repeat MRI scan performed Monday showed that the four brain lesions have not changed, and a PET scan Tuesday indicated that they still were active.

"Obviously, we're not happy that there wasn't a larger, more dramatic shrinkage of the tumors in response to the methotrexate," said Dr. Frank Lieberman, chief of neuro-oncology at the cancer center. But "I think it's premature to say that treatment ultimately won't have a good outcome."

Instead of chemotherapy, the mayor is expected to get whole-brain irradiation plus intensity-modulated radiation therapy, or IMRT, beginning on Monday. He likely will be treated every weekday for four weeks.

In that process, his entire brain will be treated with radiation in a way that minimizes the dose to normal tissue and boosts the dose to the tumors.

		Listen in Dr. Stanley Marks, Dr. Amin Kassam and Dr. Frank Lieberman discuss the therapy and medical condition of Pittsburgh Mayor Bob O'Connor.   Dr. Marks: Radation therapy to start Monday. Dr. Lieberman: How the radiation therapy will work Dr. Marks: No more chemotherapy for now Dr. Kassam: Pressure on the mayor's brain is relieved Dr. Marks: Some progress is seen Dr. Marks: On regaining strength

"We're in the middle of a complex treatment course for a disease for which there is really very little clinical trial experience," Dr. Lieberman said. "Each step to a certain extent is a step into the unknown in terms of predicting how things are going to turn out."

He added that radiation isn't "a treatment of last resort. I would call it being flexible and adapting to the situations as they arise."

But, "there is a chance that the radiation therapy will not work," Dr. Marks cautioned. "I think we have to be aware of that."

The brain lesions were thought to be shrinking after the first dose of methotrexate, but he now suspects that was a transient effect caused by steroid treatment.

Because this type of T-cell lymphoma is so rare, it's hard to predict treatment response, said Dr. Michael Robertson, director of the lymphoma program at the Indiana University Cancer Center in Indianapolis.

Based on his knowledge of the more common B-cell type, he said the fact that the mayor's tumors have not responded to chemotherapy is not a good sign.

Usually, patients with the B-cell type get better with a combination of steroids and methotrexate, said Dr. Robertson, who does not have direct knowledge of the mayor's condition or treatment.

He would expect the mayor, who is 61, to improve with radiation therapy, at least initially. But the duration of that response or prospects for a cure are not known.

In patients with the B-cell type who are older than 60 and do not respond to methotrexate, the likelihood of a cure generally would be low, Dr. Robertson said.

For those patients, radiation typically provides "only transient benefit," as he put it. Some patients may respond for up to a year or more, "but not likely years," he said. "Tumors shrink, then unfortunately tend to grow again."

If they respond well to radiation, patients can return to "fairly functional status," Dr. Robertson said. He did not rule out the possibility that the mayor might be able to return to his duties, although older patients risk some loss of mental acuity, such as the ability to perform complex math.

He based his comments on patients with the B-cell type who are treated with whole brain radiation.

According to his doctors, Mr. O'Connor will get a uniform whole-brain radiation dose that is lower than what it is typically associated with cognitive side effects, and he will also get IMRT, which delivers high doses of radiation to the tumors.

With IMRT, "you can paint the radiation dose where you want it and limit the amount that gets to normal tissue," said Dr. Jeff Bradley, a radiation oncologist and associate professor at the Alvin J. Siteman Cancer Center at Washington University in St. Louis. CT or other imaging scans are used to develop a treatment plan, he said, and computers help determine a dose distribution that meets a patient's needs.

IMRT has been available for a number of years and currently is offered at most major medical centers and quite a few smaller centers, he said.

Toxic effects from the radiation are more likely in older patients, but don't always occur, Dr. Marks noted. He estimated the risk would be about 10 percent for Mr. O'Connor. Problems usually don't arise until 18 months or more after treatment.

As Dr. Lieberman put it, "The mayor and his family have accepted the reality that there is going to have to be an incremental risk of neurotoxicity accepted in order to get the tumor under control."

Because no chemotherapy will be given, there is a chance that the number of tumor cells in the spinal fluid will rise. If that happens, another chemotherapy drug could be administered directly into the spinal fluid or the oral agent Temodar might be given again after the radiation therapy is completed, Dr. Marks said.

Today, Mr. O'Connor will have a shunt procedure to channel excess fluid from his brain into his abdomen rather than outside his body. That should get him out of the intensive care unit and into a regular ward, where he can get more aggressive physical therapy, explained UPMC neurosurgeon Dr. Amin Kassam.

His recovery from the shunt surgery will dictate whether he'll be able to start radiation treatments on Monday, the surgeon added.

The therapy can be done on an outpatient basis, so when Mr. O'Connor is physically capable of getting to and from the hospital, he will be allowed to go home. It's possible that he will require hospitalization for the duration of the radiation treatment, Dr. Marks said.

The mayor's early symptoms of headache, neck and back pain have improved, likely because he has fewer lymphoma cells in his spinal fluid. His hiccup bouts are shorter and not as severe as they once were.

"When they were bad, the bed was shaking and he couldn't even eat," Dr. Marks said.

Weakness in Mr. O'Connor's left arm and leg improved after last week's surgery to drain excess fluid from his brain, and now he is almost as strong as he is on the right side. The fluid build-up was thought to be caused by bleeding of the brain lesions, which has now cleared.

Also, "we're seeing progressive improvement in communication, thought processes [and] articulation," Dr. Kassam said.

But "he's tired," Dr. Lieberman said. "He's somewhat burdened by the blows he's taken emotionally over the last few weeks."