Debbie Colley knows firsthand how quickly life can turn upside down.
“One morning, I arrived at work feeling great and ready to start the day,” says Colley, 56, a recently retired middle school music teacher. “But as soon as the school bell rang, sharp pangs shot through my abdomen. The pain was intense.”
A trip to the emergency room revealed Colley had a strangulated hernia, a medical condition that occurs when a section of the intestine pushes through a weak spot in the abdominal wall. This triggers the abdominal muscle to clamp down, which cuts off blood supply to the intestine, thereby “strangling” it.
Doctors operated and fixed the hernia. But now Colley faced another challenge.
The same CT scan that detected her hernia also showed a suspicious, dime-sized spot on her liver. A biopsy confirmed it was malignant.
“I was completely blindsided,” Colley recalls. “I went in with a stomach ache and came out with cancer.”
Aggressive and rare
Colley’s doctors in her hometown of Victoria, Texas, weren’t sure what type of cancer Colley had. They referred her to MD Anderson, where oncologists performed a myriad of tests, scans and exams. Finally, her diagnosis was revealed: peritoneal mesothelioma – an aggressive and exceptionally rare cancer that attacks the peritoneum, the thin layer of protective tissue that lines the stomach and each of the abdominal organs.
“Less than 400 cases are diagnosed each year in the United States, says Kanwal Raghav, M.D., assistant professor of Gastrointestinal Medical Oncology. “That’s miniscule compared to the more than 200,000 new cases of breast cancer that are identified annually in this country.”
The culprit behind most peritoneal mesothelioma cases is asbestos, a naturally occurring mineral in rocks and soil. Once lauded for its resistance to heat, this “miracle mineral” was used in everything from building materials to car brakes and hair dryers. At the height of its use from the 1930s to the late 1970s, asbestos could be found in more than 3,000 products.
Over time, however, researchers realized that when asbestos materials are disturbed or damaged, the spiny asbestos fibers can be released into the air and breathed in through the nose or mouth. When this happens, the sharp fibers can lodge in the abdomen and cause genetic damage to the cells in the abdominal lining. Over a period of decades, malignant tumors begin to form and multiply.
“My dad worked at an aluminum smelting and refining plant where asbestos was used liberally in insulation and building materials to control the high-heat environment,” Colley explains. “He probably brought asbestos fibers and dust home on his work clothes and I inhaled it as a child.”
Hard to detect
One of the greatest challenges of treating a rare cancer is detecting it in the first place. Some uncommon cancers spread silently, devoid of symptoms. Peritoneal mesothelioma, for instance, typically produces no telltale warning signs until the tumors it creates begin pressing against the abdominal wall or intestines. Only then do patients begin experiencing abdominal pain and swelling, a feeling of fullness, nausea or vomiting, and changes in bowel habits – the same symptoms that occur with gallstones, irritable bowel syndrome, and ovarian cancer.
Most doctors see only a handful – if any – rare cancer cases in their lifetimes. This lack of familiarity can produce disastrous consequences.
“By the time patients come to me,” Raghav says, “they’ve often spent many months going from doctor to doctor, trying to figure out what’s wrong, while their tumors continue to spread. You’d be surprised at the number of women I see who’ve been misdiagnosed with and treated for ovarian cancer, but when we look deeper into their pathology, it turns out they have peritoneal mesothelioma instead.”
Because of these missteps, rare cancers tend to be diagnosed at a later stage, he says, and have lower five-year survival rates than other cancers.
“There’s a saying in medical school: ‘When you hear hoofbeats, think of horses not zebras,’” Raghav explains.
Clinicians are taught that common diseases are more common than rare ones, and therefore the simplest, most common explanation is usually the correct one. But sometimes the rare diagnosis is the right one, Raghav says.
“If you only think of horses, you’ll miss the zebras. That’s the conundrum of diagnosing rare cancers – they’re the zebras.”
Doctors at large academic cancer centers like MD Anderson have more experience in treating “zebras,” he says. “We get the diagnosis right the first time, and we get patients into treatment faster.”
Trial and error
Colley’s treatment began with three courses of chemotherapy to shrink her tumors, followed by a grueling surgery to remove them.
“That helped,” she says. “The cancer was gone and it stayed away for six months. Then it popped right back up again.”
Next, she tried brachytherapy, a type of internal radiation where pellets containing radioactive material are placed in and around tumors to destroy cancer cells. Her cancer disappeared again, but came back.
Through it all, Colley continued to teach. Doctors at MD Anderson dubbed her “Wonder Woman.”
“I didn’t want to let the kids down,” she says. “Sure, I was tired, but I kept going.”
Nothing was working and Colley was running out of options.
“We’d tried everything, Colley says. “This disease is usually fatal if left untreated. I thought I was done for.”
Then Raghav threw Colley a Hail Mary pass. He invited her to participate in a new clinical trial that would gauge the effectiveness of two drugs to treat peritoneal mesothelioma. The medications would be given simultaneously to deliver a one-two punch against the disease. Bevacizumab would prevent the growth of new blood vessels that feed tumors, while the immunotherapy drug atezolizumab would energize the immune system and help it recognize and attack cancer.
“I want you to try this, but there are no guarantees,” Raghav cautioned Colley.
“Sign me up,” she responded. “I’m not ready to die.”
When Raghav explained that even if the drugs didn’t work for her, other patients would benefit down the line from her participation, Colley says she was sold.
“No question about it,” she says. “I had to do this.”
Colley began the two-drug combo the first week of April 2018. By December, her tumors had shrunk nearly 70 percent.
Raghav is elated with his patient’s progress.
“Immunotherapy, in combination with other drugs, is opening up a host of new therapeutic options for treating peritoneal mesothelioma and other rare cancers,” he says.
No standard treatments
People with rare cancers have been at a disadvantage for years, Raghav says.
“There’s a lack of tried-and-true treatments,” he says. “Drug companies don’t have an incentive to fund studies that will help only a small number of people.”
With more common cancers like the “big four” – breast, colon, lung and prostate – scientists can recruit patients for clinical trials and determine which treatments do or don’t work, Raghav explains. But there simply aren’t enough people with rare cancers to participate in studies that lead to valid scientific conclusions, without large collaborative efforts, which are lacking.
“We have well-established methods of treating more common cancers,” Raghav says, “but rare cancers don’t have that luxury.”
So what’s a doctor to do when a rare cancer patient seeks treatment?
“Most resort to talking with colleagues who’ve handled a similar case at another cancer center,” Raghav says, “or looking in the medical literature for an example where a patient responded well to a particular therapy.”
Raghav calls the lack of a standard method for dealing with rare cancers “concerning.”
Now, MD Anderson is launching a new effort to close this gap. The cancer center’s Rare Tumor Profiling Initiative is bringing together all faculty involved in rare tumor research and treatment, and assembling them into working groups by cancer type.
“Investigators from across the institution are invited to participate,” explains Andy Futreal, Ph.D., chair of Genomic Medicine. “Their data and their patients’ biological samples will be placed in a central repository shared by all. This is team science at its best.”
The group effort will yield enough samples to conduct robust, reliable studies, Futreal says.
“Aggregating as much information as we can about the rarest cancers will help us determine which patients should have which treatments,” Futreal says. “We’ll also identify and follow up on new ideas.”
Eventually, MD Anderson researchers will team with other academic cancer centers to broaden this effort.
“With more patients, more data and more results, pharmaceutical companies will have an incentive to fund more rare cancer studies,” Futreal says.
Colley is just glad more people are talking about rare cancers – which the National Cancer Institute defines as those that occur in about 15 out of 100,000 people.
“Getting any cancer diagnosis is daunting,” she says, “but learning you have a rare cancer is particularly isolating. Not many people are going through what I am. The more awareness, the better.”
Every three weeks, Colley returns to MD Anderson for check-ups. During her two-hour commute, she thinks about her dad who passed away 15 years ago. Prostate cancer caused his death, but he also had asbestosis – lung tissue scarring caused by inhaling asbestos fibers.
“He worked so hard to support his family,” she says. “I wish we’d known then what we know now.”
When the clinical trial Colley’s participating in ends next year, she expects she’ll be put on maintenance drugs for the rest of her life to keep her cancer at bay.
“That’s just fine by me,” she says.