Rare Opportunities: Understanding Uncommon Cancers

Cancer is a hot topic, both online and in the press. More than 21 million Web sites are devoted to lung cancer, and Google News lists more than 16,000 entries on breast cancer.            

Type in “kidney cancer,” however, and you’ll notice a drastic difference—only 2,000 stories. Likewise, a search for pancreatic cancer on the Web returns just four million sites.            

When it comes to media attention, not all cancers receive equal time. Much is written and discussed about the so-called “Big Four”—breast, prostate, lung and colorectal cancers—because they are indeed the most common cancers. But there are many types of cancer that receive very little, if any, coverage. Some of these cancers are truly rare; others are simply out of the spotlight and therefore unknown by most of the public.            

There is a place where discussions about uncommon cancers are a common occurrence—in fact, they happen every day. As a National Cancer Institute-designated research and treatment institution, the UAB Comprehensive Cancer Center sees and cares for rare cancers with the same energy, commitment and time that it applies to the “Big Four.” Many of the more than 300 physician-scientists at the center, for instance, have made these diseases the focus of intensive research in an effort to better understand them and develop innovative new treatments. Here is a closer look at three unique cancers and the latest advances against them.  

Kidney Cancer: The Accidental Disease            
“Many kidney cancers are often found by accident,” says Erik Busby, M.D., a UAB urologic oncologist and Cancer Center associate scientist. “Patients come in for a CT scan unrelated to the kidneys, and we find a tumor.” Once that happens, those patients find themselves in a select group; out of more than 1.3 million new cancers diagnosed in the United States in 2008, approximately 54,000 were kidney cancer, according to the American Cancer Society.            

The most common type of kidney cancer is renal cell carcinoma, which represents about 3 percent of all adult cancers. If caught in its early stages, the disease can often be treated solely with surgery. However, it has few symptoms in its early stages and is often diagnosed only after the tumor has grown large and is disrupting the function of other organs. “The good news,” Dr. Busby says, “is that as imaging techniques improve, we are starting to diagnose kidney tumors earlier and earlier.”            

Dr. Busby sees between five and 10 kidney cancer patients every week. Most are treated with minimally invasive surgery to preserve as much of the kidney as possible. New techniques can be used in some cases, including freezing or burning the tumor through processes known as cryoablation and radiofrequency ablation, respectively. Another shift in treatment is the use of targeted therapies, particularly in patients whose cancer has metastasized, or spread, outside the kidney.            

Patients with metastatic disease may be able to participate in the Cancer Center’s clinical trials of new kidney cancer treatments. “Primarily we look at patients to find those at a high risk for metastasis,” Dr. Busby says. “By looking at components such as certain tumor markers, we can identify metastasis risk and determine the patients who would benefit from targeted therapies.”  

Kidney Cancer Spotlight
--More than 54,000 cases were diagnosed in the United States in 2008.
--More than 200,000 survivors are in the United States today.
--Common symptoms are blood in urine, back or flank pain, or a palpable mass or lump that can be seen or felt under the skin.
--Most cases are discovered incidentally while performing imaging studies for other reasons.
--The average age of most people diagnosed with kidney cancer is 65, and it is very uncommon in those younger than 45. The risk is higher for men than women.  

Lymphomas: A Bolt of Lightning            
Lymphoma is a difficult cancer for patients to understand, says James Foran, M.D., UAB hematologist-oncologist and Cancer Center associate scientist. “Lymphoma doesn’t really fit nicely into a category,” he says. “Nobody really understands why they get it, and they have a hard time understanding what kind of cancer it is.”            

Lymphoma affects the cells in the immune system and is the most common type of blood cancer. Depending on the specific cells that are affected, each case is classified as one of two primary types—Hodgkin’s or non-Hodgkin’s—and these two categories break down further into five types of Hodgkin’s lymphoma and more than 40 subtypes of non-Hodgkin’s.            

Of the two main types, non-Hodgkin’s lymphoma is far more common, affecting approximately 55,000 Americans every year, making it the fifth most common cancer in the United States. In general, lymphomas are highly treatable and often respond well to chemotherapy and radiation therapy. While many lymphomas cannot be cured, they can be managed.            

“With cancer, people want to get their treatments, be done with therapy and move into the realm of cancer survivors,” Dr. Foran says. “Because a lot of lymphomas are chronic diseases, the notion of being a lymphoma survivor is slightly different than other cancers.”            

The average survival for the most common low-grade lymphoma is more than a decade. Overall life expectancy is shortened, but at the same time, patients are likely to live more than 10 years. “If you’re 80 years old, that’s not hard to accept; if you’re 30 or 40, that’s hard to believe,” Dr. Foran says. “Telling someone you can’t cure something, but that you can treat it, is a hard concept.”            

Much of Dr. Foran’s research in lymphomas concerns the improvement of outcomes among different patient populations. In particular, he and his colleagues Meredith Kilgore, Ph.D., and Vishnu Reddy, M.D., have been examining epidemiologic outcomes among African-American patients.            

In looking at 40,000 lymphoma patients on the SEER (Surveillance, Epidemiology and End Results) program registry, Drs. Foran, Kilgore and Reddy found that African Americans had a lower survival rate than whites when receiving standard therapy, despite a lower incidence rate of the disease among African-Americans. “A lot of that is explained by socioeconomic status, but I don’t think that’s the whole story,” says Dr. Foran, who is currently writing a study to examine this discrepancy further.            

The Cancer Center sees and treats numerous lymphoma patients, including many who have one of the rare subtypes of the disease. Lymphoma patients are often different than most other cancer patients, Dr. Foran says. “I find that every cancer has its own psychology and personality,” he explains. “In lymphoma, it’s like a bolt of lightning. You’re well and then all of a sudden, you’ve got lymphoma. It’s a lot to deal with.”  

Lymphoma Spotlight
--Two main types: Hodgkin’s and non-Hodgkin’s.
--More than 8,000 cases of Hodgkin’s lymphoma and more than 66,000 cases of non-Hodgkin’s lymphoma were diagnosed in 2008.
--Hodgkin’s lymphoma mainly occurs in young adults, while the average age of non-Hodgkin’s patients is 65.
--Symptoms for both types of lymphoma include fatigue, unexplained weight loss, fever, drenching night sweats and severe itchiness.  

Pancreatic Cancer: Challenge and Promise            
Pancreatic cancer is certainly one of the truly rare cancers—a person has only about a one in 76 chance of developing it in his or her lifetime. But while its incidence is relatively uncommon—ranking around ninth among cancers—pancreatic cancer is one of the most deadly forms of the disease. With a 95-percent mortality rate, it rates as the fourth-leading cause of cancer death in the United States.            

Survival rates for pancreatic cancer are so poor in large part because it is often not diagnosed until its later stages, and the few symptoms it exhibits do not usually appear early. In addition, doctors are not 100-percent certain of the risk factors that lead to the disease.            

“We know of some risk factors, such as smoking, excessive alcohol use and obesity, but these don’t allow us to identify high-risk groups,” says James Posey, M.D., a UAB gastrointestinal oncologist and Cancer Center scientist. “Our ability to diagnose pancreatic cancer in its early stages depends on a better understanding of the disease process so that we can identify high-risk groups and screen them for the disease.”            

As for new treatments, the Cancer Center is conducting a variety of clinical trials, many of which are connected with the center’s pancreatic cancer SPORE (Specialized Program of Research Excellence) grant. The prestigious grant—one of only three in the country—enables researchers and clinicians to speed the development of scientific breakthroughs into innovative treatments. Several of these trials combine gemcitabine, a chemotherapy drug that is essentially the standard of care for treating pancreatic cancer, with other therapeutic agents. The goal is to find new agents that will make pancreatic cancer cells more sensitive to treatment and to examine exactly how the disease responds to each agent.             In one study, patients receive the drug Tarceva® for 10 days prior to surgery.

Then, following their operation, they are given Tarceva® in conjunction with gemcitabine. “We hope this will allow us to understand more about the pathway in pancreatic cancer that Tarceva® disrupts and the factors in patients that this therapy is most likely to provide benefit,” Dr. Posey says, adding that this applies to patients with more advanced disease.            

In another study, gemcitabine is paired with a ras vaccine, which is designed to jump-start the body’s immune system to attack cells containing a mutated gene found to facilitate cancer. Another current clinical trial teams gemcitabine with chemotherapy agent Abraxane® for patients with metastatic disease. “We’ve seen a number of positive responses from the phase II trial and are encouraged that this might be an effective therapy for patients with less advanced disease, which is not the majority of our pancreatic cancer patients at UAB,” Dr. Posey says.            

Improved imaging techniques are also offering physicians a new advantage, even though pancreatic cancer continues to be diagnosed most frequently in its later stages. Procedures such as CT scans and endoscopic ultrasounds allow doctors to better evaluate questionable or suspicious areas within the pancreas when symptoms do arise. With the slow increase in the incidence of pancreatic cancer over the past decade, clinicians and researchers hope to develop a screening method that could make a major impact on diagnosis. The key, Dr. Posey says, will be to define the patients who are at high risk for the disease.

“Until we better understand the pathogenesis of pancreatic cancer and can begin to intervene at early steps in patients likely to develop the disease, it is going to be difficult to develop screening tools that would allow us to detect pancreatic cancer at an earlier stage,” Dr. Posey explains. “It’s a challenging arena, and we are slowly making progress. Hopefully that results in better benefits for the patient.”  

Pancreatic Cancer Spotlight
--More than 37,000 Americans were diagnosed with pancreatic cancer in 2008, and more than 34,000 will die from the disease.
--Men are 20 percent more likely to develop pancreatic cancer, and the majority of cases occur in people older than 65.
--African Americans have an incidence rate 40 to 50 percent higher than other ethnic groups.
-- Symptoms include jaundice, pain in the abdomen or middle of the back, unexplained weight loss and digestive problems, particularly nausea, vomiting and the inability to digest fatty foods.