Nearly 1.6 million Americans were diagnosed with cancer last year, and nearly 600,000 died from the disease, according to the National Cancer Institute. Experts estimate that as many as 90 percent of those deaths were from metastases, when the cancer has spread from the original disease site to other organs. These data seem to support conventional wisdom about cancer — that once it appears in a different location from where it began it is systemic, and can only be treated palliatively, usually with chemotherapy alone.
This line of thought is being challenged by some visionary oncologists who don’t believe all tumors are alike. They reject the notion that a diagnosis of metastatic cancer is an automatic terminal diagnosis.
“The dogma is that this type of disease is incurable and that if there’s a metastatic tumor in one organ, then others must be present throughout the body,” said Paul Okunieff, M.D., director of the UF Shands Cancer Center and chairman of the UF College of Medicine’s department of radiation oncology. “It’s considered an all-or-none phenomenon, but the fact is, this view is probably not correct. We need to think about metastasis like we think about the primary tumor: determine how much it has spread, then decide whether it’s treatable based on existing technology.”
Dr. Okunieff and co-authors have recently described how some patients who have only a few metastatic tumors can be successfully treated with curative intent in their article titled “Oligometastases Treated With Stereotactic Body Radiotherapy,” currently in-press in the International Journal of Radiation Oncology, Biology and Physics.
In their paper, Dr. Okunieff and his colleagues analyzed the long-term survival of 121 cancer patients with five or fewer well-defined metastatic lesions after treating these metastases with stereotactic radiation therapy. Cumulative overall survival using life-table methods was 74% at two years and 47% at six years. Because this was not a randomized trial (in which some patients would have been randomly assigned to a group that would have received “standard care” — i.e., no stereotactic radiotherapy), the study is not definitive. Based on previously reported survival results of patients with metastatic cancer, however, the expected two-year and six-year survival would have been much lower with standard treatment — optimistically under 50% and under 10%, respectively.
The idea of successfully treating metastatic tumors with curative intent was first conceived in 1968 by Dr. Phillip Rubin and Dr. Jerold Green in their book, “Solitary Metastases.” This was one of the first medical texts to present data in support of the notion that one should aggressively treat solitary metastases. Later, in an article published in the Journal of Clinical Oncology in 1995, Hellman and Weichselbaum coined the term oligometastases — “oligo” meaning few — to describe a defined state of metastatic disease involving a small number of discrete metastases that would potentially be amenable to curative radiation treatment.
Since that time, technology has helped us outstrip the confines of conventional wisdom. The development of highly accurate imaging systems to identify tumors at very early stages, also combined into three-dimensional systems and other technologies that allow a more stereotactic and precise approach to lesion obliteration while preserving adjacent healthy tissue has changed the way we approach the potential benefit of treating oligometastases to improve survival. The groundbreaking work of Dr. Okunieff, and others like him, using these technologies to successfully treat metastatic disease is opening the door to a new and very exciting way of treating patients.
Jane Plummer is living proof that a diagnosis of metastatic cancer is not a death sentence. She was diagnosed with colon cancer for which she had surgery and chemotherapy, but then developed three dime-sized metastatic lesions in her liver. “Living with cancer,’” she says, “is like living with your mortality and having it always right there. I’ve never counted them, but I’d gone to a number of oncologists. I had one who told me that all I could do was palliative treatment — I would never get better. Fortunately I then saw Dr. Okunieff who told me ‘Oh no, you’ll be fine!’
Ms. Plummer’s three lesions were treated with stereotactic radiotherapy and she is now alive and well seven years later, and she has no detectable disease. Dr. Okunieff comments: “The excellence of our new imaging technologies for detecting these small lesions now gives us the opportunity to treat such lesions successfully … in the vast majority of cases, we can pinpoint them and treat them with curative intent.
Dr. Okunieff is developing what we believe to be the first multidisciplinary program and clinic devoted to the treatment of metastatic disease. Dr. Roi Dagan, the program leader, will work with Dr. Okunieff to develop surgical, medical and radiation approaches for comprehensive treatment of patients with oligometastases. This joint program between Gainesville and UF Proton Therapy Institute in Jacksonville will include the commissioning of a VERO system, the second in the United States. VERO allows for robotically controlled, real-time stereotactic targeting of moving objects within the body. It does this with fluoroscopy, cone beam imaging and infrared monitoring. Better targeting means that a higher dose can be delivered to the tumor with a lower dose to the adjacent normal tissue. The clinical program will be complemented by a basic science program aimed at identifying molecular markers predictive of metastases, developing interventions that can prevent subclinical metastases from progressing, and selecting screening programs for cancer patients at high risk for oligometastases.
Mitch Bloomberg is another patient who has benefited from the metastatic treatment program. “… it’s scary, depressing,” he says. “Obviously, there is the ‘why me?’ And in my case, I said, ‘I’m not ready to die. Cancer is tough, I’m tougher.’” Dr. Okunieff explains that “Mr. Bloomberg had a really challenging problem. He had lung cancer that had failed initial surgery and chemotherapy. With six tumors in his lung he convinced a surgeon in Boston to try and remove the tumors from both lungs. Mid-surgery, they found an inoperable lymph node and aborted the surgery. Two-year survivals for this stage of disease are under 10% to 20% and five-year survivals are extremely rare. Mr. Bloomberg says, quite poignantly: “There was nobody that gave me any hope. Although I don’t like to use the word “cured,” with me, they’ve effectively cured the incurable.” Mr. Bloomberg appears to be disease-free at over eight years since his treatment.
John Kenneth Galbraith popularized the phrase “the conventional wisdom” in his book, The Affluent Society (1958), as “ideas which are esteemed at any time for their acceptability [and]…predictability.” He repeatedly refers to “the conventional wisdom throughout this
monograph, invoking it to explain the high degree of resistance in academic economics to new ideas. But the phrase and concept also applies to the resistance in medical practice to new ideas.
Dr. Okunieff thinks of the future this way: “Our new technologies can actually follow in three dimensions with sub-millimeter accuracy, and in real time, a lesion that is moving while you breathe or while your heart is beating. I have a vision, which we will be implementing soon, that our cancer patients will be treated quickly, accurately and curatively. Imagine you are the physician. A patient has a PET scan, and you find they have one new tumor. You target it, you send them into the second room, you kill it and you send them home. With that technology, before that patient even gets home, the tumor is dead — with at least an 80% likelihood. This
changes the entire dynamic. Imagine now being the cancer patient and your spouse asks: ‘How did your visit go today?’ And you say, ‘I had one spot and they killed it. Let’s have dinner.’
“It’s a much better way to go home. It’s very reasonable to expect and to dream that the UF Shands Cancer Center will become the pre-eminent cancer center for the treatment of metastatic disease in the country. I think we can be as great as we dream to be. And so I’m dreaming big.
I will close with two pertinent quotes from the highly quotable John Kenneth Galbraith:
- “Faced with the choice between changing one’s mind and proving there is no need to do so, almost everyone gets busy on the proof.”
- “The enemy of the conventional wisdom is not ideas but the march of events.”
Let’s hope for the sake of our cancer patients that the march of events in this case is the accumulation of data, including definitive randomized trials, in support of the efficacy of stereotactic radiotherapy of metastatic disease.
David S. Guzick, M.D., Ph.D.
Senior Vice President, Health Affairs
President, UF & Shands Health System