Steve Mellon, Post-Gazette Dr. Stanley Marks in a July photo.

Soon after the Fourth of July, oncologist Dr. Stanley Marks heard that his good friend, Mayor Bob O'Connor, had gone to UPMC Shadyside with flu symptoms, so he made plans to pay him a visit.

The two had hit it off immediately when they met several years earlier through a mutual friend, back when Mr. O'Connor was first considering running for mayor. They chatted when they met in the streets of Squirrel Hill, where both lived, and they often went together to Pitt football and Pirates games.

But before Dr. Marks went to say hi, he got a call from Mr. O'Connor's private physician. The mayor's MRI brain scan showed four tumors that indicated he had a rare cancer called primary central nervous system lymphoma.

For the next eight weeks, Mr. O'Connor would need the expert assessment and recommendations of Dr. Marks, director of clinical services at UPMC Hillman Cancer Center, more than he needed to lean on Stan, the good friend.

"This was definitely one of the most difficult situations I've ever had to deal with from a personal and professional standpoint," Dr. Marks said. Yesterday, with permission from the mayor's family, he talked about what happened in the last weeks of the life of his friend and patient.

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"I personally couldn't have done it sooner," the doctor said. "The whole thing was too fresh and raw and difficult for me to talk about over the weekend."

Mr. O'Connor initially sought medical help because of headaches and belly pain, which doctors said was a duodenal ulcer.

"He admitted he'd been having headaches for some time, but he attributed them to stress" and long hours, Dr. Marks said. The aspirin and other anti-inflammatory drugs the mayor took for the headaches possibly triggered the ulcer's development.

"I suspect that this was going on for a while, [perhaps] months," Dr. Marks said. But "I don't want to give the impression that if he had been diagnosed earlier it would have mattered because it would not have. He had very resistant cancer."

On July 10, Mr. O'Connor's medical team, led by Dr. Marks, announced that he had T-cell lymphoma of the brain, although the diagnosis had been confirmed three days earlier, on a Friday.

"By Saturday he was feeling pretty good and he wanted to go home for the weekend," the doctor said. "The plan was to keep him on the steroids and bring him back on Wednesday, after the All-Star Game, to start the chemotherapy with high-dose methotrexate."

		To contribute The University of Pittsburgh Cancer Institute has established a fund in Mr. O'Connor's honor for lymphoma research. It currently holds $10,000. Contributions can be sent to UPCI Development Department, UPMC Cancer Pavilion, Suite 1B, 5150 Centre Ave., Pittsburgh, 15232. Checks should be made out to UPCI and include Mr. O'Connor's name in the memo line. For more information, call 412-623-4700.

But when Mr. O'Connor returned to the hospital for a check-up on Monday, his headaches were worse, and he was having difficulty getting around. Dr. Marks and neuro-oncologist Dr. Frank Lieberman told him that treatment could wait no longer. That day, they made the diagnosis public.

"Bob did not want to let it out until after the All-Star Game," Dr. Marks recalled. "He just didn't want anything taken away from the hype and the excitement" of the festivities.

But the oncologist was already a little concerned that Mr. O'Connor's symptoms had grown worse despite his being on steroids, which typically cause lymphoma tumors to shrink, albeit transiently.

Early optimism

Still, the medical team was largely optimistic about his chances of overcoming the cancer. Most patients respond to high-dose methotrexate, or to radiation, and there was no reason to think the mayor would be any different.

After two doses of methotrexate chemotherapy, they saw an encouraging sign: The number of lymphoma cells in a sample of mayor's spinal fluid dropped from 300 to 13. Also, Mr. O'Connor's headache, neck pain and back pain subsided, raising hopes that the therapy was working.

But before the third dose was given, bleeding from his brain tumors elevated the fluid levels in his brain, leading to urgent surgery to drain the excess with the placement of a shunt.

"We still weren't sure at that time whether the hemorrhage into the tumors was representative of a response [to treatment] or whether it was disease progression," Dr. Marks said. "We couldn't tell."

A third dose of methotrexate was administered, but "thereafter it was just the downhill course," the doctor said. "We did the PET [positron emission tomography] scan that showed these tumors were very active metabolically. Obviously, the methotrexate wasn't treating them."

The medical team told the mayor they wanted to try radiation, initially to the brain as a whole and then with targeted therapy called intensity-modulated radiation therapy, or IMRT.

Studies had shown that some patients who did not respond to high-dose methotrexate were able to get into remission with radiation, Dr. Marks said.

By Friday, a week before he died, Mr. O'Connor had received two whole-brain radiation treatments and five rounds of IMRT.

"He actually looked good," the oncologist said. "It looked like he was coming around. He had some left-sided weakness, but he was awake, alert and talking to us."

The drain limited his mobility, but the mayor was able to get out of bed to sit in a chair.

And "then everything went into a tailspin after that," Dr. Marks said.

The next day, Mr. O'Connor's alertness started to decline. On Saturday evening, he developed "a shaking chill," as the doctor put it, and his temperature was lower than normal. Tests showed he had a urinary tract infection, which the medical team feared might have spread to his spinal fluid. The drain was replaced with a new one, just to be on the safe side.

Multiple tests showed that his spinal fluid and drain were never infected, although a statement issued by the medical team to the media suggested otherwise, Dr. Marks said. But before the error could be corrected, the O'Connor family asked the hospital to stop releasing to the public information about the mayor's health.

At the same time, Mr. O'Connor began to have seizures, which occur in about 10 percent of CNS lymphoma patients, the doctor said. The medical team hoped it was a consequence of infection because that should respond to treatment.

The seizures, a variety called Jacksonian, began in the mayor's right hand and spread up his arm. He also experienced tremors, jerking movements called multifocal myoclonus, and some cogwheel rigidity, in which muscles seem to ratchet as they are stretched, rather than move smoothly.

Each of those problems pointed to difficulties in different areas of the brain. Even the hiccups that plagued Mr. O'Connor since the first week of his diagnosis are now thought to be caused by a malfunction in the brain stem, rather than a side effect of steroids.

Despite tapering of the steroids and numerous medications, the hiccups "never went away for more than a day or two," Dr. Marks said. "There were times he literally hiccupped himself to sleep."

After a long absence, Mr. O'Connor's neck and back pain began making a comeback around mid-August. Typically, he played it down.

"We had to pretty much insist that he take something for pain," Dr. Marks said. "We think he had more pain than he ever acknowledged."

On Tuesday, three days before his death, Mr. O'Connor was put on a respirator because disease in his brain stem had impaired his ability to breathe on his own. Brain scans showed the four tumors had neither grown nor shrunk.

But "he had more widespread disease in his brain than we were actually seeing on the MRI," Dr. Marks explained. "He had small areas of tumor throughout the brain, microscopic involvement that was not large enough to be seen on the MRI."

A hopeless situation

He ordered a scan of the mayor's spine on Wednesday, which hadn't been repeated since he first entered the hospital. Then, it looked normal. The latest one was astoundingly different. Top to bottom, the protective coverings of his spinal cord were caked in tumor cells.

"It was absolutely astonishing how the disease ... in his spinal canal had just taken off after we stopped the methotrexate," Dr. Marks said. Tests of spinal fluid taken directly from the spine, rather than from the drain, drove the tragic point home.

The cause of Mr. O'Connor's deterioration last week "ultimately proved to be the rampant disease and the rapid progression, particularly throughout his spine," Dr. Marks said. "We all concluded this was a hopeless situation."

After taking some time to process the bad news, Mr. O'Connor's family decided to discontinue life support at around 8 p.m. Thursday. The mayor died of respiratory failure about 24 hours later.

Mr. O'Connor's cancer was unusual in several ways, the oncologist said. First, it didn't respond to steroids, chemotherapy or radiation. At one point, the tumors bled, leaving doctors perplexed, because they didn't know what was causing them to hemorrhage.

Also, he had seizures, which are uncommon in CNS lymphoma patients.

"Although this is a rare tumor, we've all seen them," Dr. Marks said. But neither he nor his colleagues on the medical team had seen the cancer "act in this way or be so aggressive, where there was no response to anything. It's very unusual."

Other doctors who did not have direct knowledge of the mayor's illness or his treatment said he apparently fell victim to an unusual and especially virulent cancer.

Dr. Paul Zeltzer, a professor of neurosurgery at the University of California, Los Angeles, said he has been involved in treating just two patients with primary CNS T-cell lymphoma, one who responded to treatment and one who did not.

He did not know of any clinical trials establishing a preferred therapy because the T-cell type is so rare. Although the mayor's treatment was not successful, he appeared to receive optimum care, Dr. Zeltzer said.

High-dose methotrexate is often used to treat the cancer, and the fact that doctors turned to radiation when the chemotherapy did not shrink the tumors was "a reasonable rationale," he said.

While progress has been made in treating CNS lymphoma, "sometimes, people don't respond well to therapy," said Dr. Virginia Stark-Vance, a neuro-oncologist in the Dallas-Fort Worth area.

Dr. Marks said Dr. Lieberman might prepare a paper about Mr. O'Connor's case for medical journals. They also have samples of his cancer cells, collected from his spinal fluid, which may aid research. Early on, they anticipated making a vaccine out of those cells to potentially prolong the remission they once hoped to achieve for him.

One lesson they've already learned from the mayor's ordeal, said his friend and oncologist, is humility. For all their knowledge and technology, they were powerless against Mr. O'Connor's cancer.