WITH JUST TWO MONTHS LEFT TO GO in his pol​ice academy program in March 2011, DeWayne Johns was finally past the book work and just starting to put everything he had learned into practice. But a nagging pain in his right leg was getting worse. He had never thought that a lack of strength or stamina would keep him from becoming a police officer. But it soon became clear that he would not make the cut in the running speed tests the academy required of recruits.

The doctor believed Johns’ pain was linked to a routine groin strain or a testicular infection (for which he gave Johns antibiotics) and didn’t think it was anything serious. Nonetheless, with academy graduation on his mind and a spasm in his leg, Johns headed to the emergency room. There the doctors detected a mass near his upper femur—right where the pain was. Unable to pinpoint the problem, an emergency room physician referred him to a local orthopedist, Thomas Bowen, who did an MRI two days later. Thirty minutes after the test, on March 28—a day Johns, now 25, will never forget—Bowen called and asked him to return to the office. The MRI had revealed a tennis-ball-size tumor in his leg.

Bowen referred Johns to Jagadeesh Ramdas, an oncologist at Janet Weis Children’s Hospital at the Geisinger Medical Center in Danville, Pa. Two biopsies later, Johns learned he had a stage IV alveolar soft part sarcoma (ASPS), a cancer that grows in the muscle and connective tissue and is diagnosed in fewer than 200 children and young adults in the U.S. each year. He also learned that this was the first time Ramdas had treated anyone with this type of cancer.

When it comes to cancer care, no one wants to have a doctor say, “You’re the first.” But that’s often the norm for people with rare cancers, a group that accounts for more than a quarter of all new diagnoses in the U.S. each year, according to the National Cancer Institute (NCI). Many people with rare cancers find that doctors, nurses and other cancer patients have never heard of their type of cancer, or that there is little information available to guide their treatment choices. As a result, it’s not uncommon for the more than 400,000 Americans diagnosed with rare cancers each year to feel like outsiders in the cancer community. Yet physicians and patients say that precisely because these cancers are rare, it’s important for patients to take steps to find doctors who understand their disease and other people who can empathize with their concerns.

Identify a Specialist

Like other oncologists who encounter a rare cancer, Ramdas began researching treatment options for his patient. Upon learning there were no ASPS-specific therapies or treatment guidelines, he recommended that Johns take part in a clinical trial led by an investigator at St. Jude Children’s Research Hospital in Memphis that was investigating the efficacy of a chemotherapy regimen of ifosfamide and doxorubicin on a broad range of soft-tissue sarcomas. (The drugs are approved for treating other types of cancer.) Johns enrolled in the study, and began treatment in May 2011.

Although all sarcomas originate from the same cell type, they do not all respond the same to identical treatments, and within two months it was clear the experimental regimen was not working for Johns. Then, at the American Society of Clinical Oncology annual meeting in June 2011, Ramdas heard Shivaani Kummar, a medical oncologist at the NCI, present promising findings from an ongoing clinical trial that was investigating whether the targeted therapy Sutent (sunitinib), which had been used since 2006 for a variety of solid tumors, would be effective for patients with ASPS.

Ramdas couldn’t wait to tell Johns about the trial, but Johns was hesitant. “I felt like my doctors were passing me off,” he says. But Ramdas persuaded him to go see Kummar at the NCI in Bethesda, Md., and Johns enrolled in the trial in July 2011. He is glad he did. He has had a dramatic response, with his tumor shrinking to nearly half its original size.

The uncertainty Johns faced as he searched for care is not uncommon. Getting the best, most appropriate care is the biggest challenge that patients with rare cancers face, says Srdan Verstovsek, a hematologist at M. D. Anderson Cancer Center in Houston. His recommendation to a person diagnosed with a rare cancer: Go all-out to find an oncologist who is familiar with your particular diagnosis. “Patients should try to see someone who has seen their type of cancer many times,” says Verstovsek. “Experience counts.”

Verstovsek, for example, specializes in a rare blood cancer called myelofibrosis, which is diagnosed in about 3,000 adults in the U.S. each year. “A community physician would see one or two cases of myelofibrosis every five years,” he says. “Last year, [at M. D. Anderson] we saw about 150 new cases because we have a focus on the disease. … We [also] have eight myelofibrosis trials available for enrollment right now.” Many other cancer centers have none.

Kummar says her own experience at the NCI has shown her how important a specialist can be to patients with rare cancers. “I think the biggest problems patients voice—and we’ve seen—[are] the lack of information about their disease and the feeling of helplessness that wherever they go, no one really knows about their disease or how to treat it.” In light of these issues, she insists that researchers and specialists have a responsibility not only to find more effective treatments for rare cancers, but also to share their findings with others. She urges doctors to make an effort to educate themselves when treating patients with rare cancers. “I think the biggest thing we can do as a community is communicate,” she says. “There are still physicians treating ASPS with a standard chemotherapy that doesn’t work, just because they don’t know there are other options.”

Research into Rare Cancers

Various obstacles stand in the way of new breakthroughs related to rare cancers​.

​Researchers who study rare cancers face a range of hurdles—from a lack of support for basic science and a dearth of candidate drugs to challenges in designing clinical trials and enrolling patients. Finding the funding for this work is also hard: Grants can be difficult to get. And pharmaceutical companies are often less interested in developing drugs for rare diseases; a drug used by only a few thousand patients a year won’t be as profitable as one for, say, breast cancer, which is diagnosed in roughly 229,000 women each year.

Common cancers also have a larger patient pool from which researchers can recruit study participants, allowing them to run multiple types of trials to get the answers they need. But for researchers studying less common cancers, each patient is a rare resource. “When you’re doing a [clinical] trial in a rare disease, you really have to get the most out of it,” says Shivaani Kummar, an oncologist specializing in early drug development at the National Cancer Institute (NCI). “There is more planning involved with a rare cancer trial. With a limited population, you need a strategy for accrual and you need to collaborate with major cancer centers.”

Patient advocate groups like the Multiple Myeloma Research Foundation (MMRF) have tried to help fill the funding gap. The MMRF, for example, has funded more than 250 researchers at nearly 120 institutions worldwide since it was founded in 1998, and its work with the U.S. Food and Drug Administration (FDA) led to the approval of four multiple myeloma drugs between 2003 and 2007.

Another area that has the potential to open new avenues of treatment for rare cancers: The relatively recent discoveries that specific molecular mechanisms drive tumors’ growth. These insights have fueled the development of new targeted therapies. And they are changing how clinical trials can be structured, with more trials enrolling patients based on the proteins or molecular pathways promoting a tumor’s growth, rather than on its location in the body.

Kummar’s team first saw hints that a new drug, cediranib, might be able to control alveolar soft part sarcoma (ASPS) after a couple of ASPS patients showed remarkable responses to the drug in a phase I trial evaluating the safety of the drug among patients with many types of solid tumors. Kummar’s team seized the opportunity, opening a phase II trial solely for patients with ASPS. (Cediranib is also being studied in phase II trials to investigate its effectiveness in slowing or stopping the growth of other types of solid tumors.)

But like many other rare-cancer researchers, Kummar found it difficult to recruit patients. Those she initially found were ready and willing, but with fewer than 200 new ASPS patients diagnosed each year, there simply aren’t many available. It took her team three years to enroll 46 patients, even with the NCI’s ability to pay for patients’ travel expenses. To try to overcome recruitment problems, rare-cancer researchers almost always establish multiple trial sites nationally and internationally. For example, COMFORT-I—one of two phase III trials that led to the approval of the targeted therapy Jakafi (ruxolitinib) for the rare blood cancer myelofibrosis—opened enrollment at 89 trial sites across the U.S., Canada and Australia to recruit 309 patients.

Yet even with international recruitment, it can be difficult, if not impossible, for rare-
cancer researchers to design a study that evaluates a drug’s benefit using standard measures, such as progression-free or overall survival. Statistically speaking, there frequently just aren’t enough patients for researchers to confidently determine whether or how well a drug prevents the disease from getting worse by those measures. For that reason, researchers often work with the FDA to establish alternate criteria that can be used in a rare-cancer clinical trial to determine a drug’s benefit. For instance, COMFORT-I relied on two atypical measures of benefit: decrease in spleen size (spleen swelling is associated with myelofibrosis) and reduction in the main symptoms related to the disease. This was “the first time ever … that a [blood cancer] drug was approved based on these two things,” says Srdan Verstovsek, a hematologist at M. D. Anderson Cancer Center in Houston who led the trial.

The expanding focus on targeted therapies, along with the FDA’s willingness to establish alternate methods of evaluating drug effectiveness in rare cancers, and the involvement of patient organizations, could result in more drugs like recently approved Jakafi, Kyprolis (carfilzomib) for multiple myeloma and Adcetris (brentuximab vedotin) for systemic anaplastic large cell lymphoma. But it can’t happen without coordination and funding. “There has to be a real effort because there are a slew of rare diseases,” Kummar says. “There has to be an effort to study the biology and identify targets [and to then develop] agents that could hit those targets.”​

Do Your Own Research

When Carolyn Langlie-Lesnik, a nurse in Crown Point, Ind., was diagnosed with an aggressive form of appendix cancer 11 years ago, at age 41, she quickly learned the value of assembling the right team of physicians to treat a rare cancer. Her first surgeon was unfamiliar with the disease, so he suggested someone at a regional cancer center. But doctors there had little encouragement or knowledge to offer: They told her that her cancer was too advanced and too aggressive to treat.

With two young children, Langlie-Lesnik wasn’t willing to accept that conclusion. She spent hours on the internet, trying to learn more about her disease than just its dismal survival statistics. Finally, she found a research group at Memorial Sloan-Kettering Cancer Center, in New York City, that reported a 28 percent survival rate at five years for 64 patients treated over a 12-year perio​d. The treatment was aggressive: major abdominal surgery to remove the bulk of the tumor, followed by a chemotherapy regimen delivered directly into her abdomen. But Langlie-Lesnik was undaunted; she called and made an appointment for an initial consultation. She began treatment six weeks later, flying from Indiana to New York and back home six times over the next year.

Langlie-Lesnik acknowledges that because she is a nurse, it was probably easier for her to research her disease than for many other patients to research theirs. Yet she is emphatic about how necessary it is for people with a rare disease to either learn to do their own research or find a friend or family member who can do it for them. “If you have a rare cancer, you have to be your own advocate,” she says. “You have to do your own research—and do a lot of it—to find information and find a specialist.”

​​​Get to the Experts (Even Remotely)

Locating a specialist may not be easy, but for many patients, neither is seeing one—especially for those who live in rural areas, are uninsured or underinsured, or cannot afford the travel costs. But there is help. Some patient organizations provide travel assistance, and certain cancer centers offer long-distance second opinions or consultations. As Verstovsek explains, most major cancer centers, like M. D. Anderson, are equipped to provide second opinions from a distance and can utilize a team approach that draws on the expertise of pathologists, oncologists and surgeons.

Rare Cancers Quick Guide

Resources that will bring you up to speed on rare cancers.
Physicians and Treatments

It can be challenging to find the right doctor—and a second opinion—if you’ve been diagnosed with a rare cancer. The National Cancer Institute fact sheet “How to Find a Doctor or Treatment Facility if You Have Cancer” is a good place to start.

You can also find experts who treat rare cancers at clinicalt​rials.gov. Even if a trial isn’t actively recruiting patients, look for information about who is conducting the study, which may help you find a doctor who specializes in your cancer.

Travel Costs

Getting to specialized treatment for a rare cancer or to an appointment for a second opinion may require travel, which can be costly. Ask a cancer center if it can provide a second opinion through telemedicine. If you need financial assistance to travel try contacting:

Psychosocial Support

Patients with rare cancers may have trouble finding a support group specific to their disease. For some patients, general support groups that don’t focus on a single cancer type can be helpful. Ask what groups are available at your hospital or cancer center or try the Cancer Support Community.

​​Many health insurance plans cover this type of second opinion. If it’s not covered though, says Langlie-Lesnik, patients should explain to their insurance provider that they have been diagnosed with a rare disease, and find out how they might get coverage for seeing someone out of the area or outside their normal provider list. Langlie-Lesnik encourages patients to argue their case and notes that even a relevant scientific meeting abstract—a published summary of a doctor’s presentation related to their cancer—might be persuasive to an insurance company.

For more advice, she recommends Fight Your Health Insurer and Win, a book by Laurie Todd, an appendix cancer survivor, which explains how to get your care covered, even when it’s out of your insurance network. “When people run into that problem,” says Langlie-Lesnik, who now blogs about her experience with a rare cancer, “I right away send them to Laurie or her book.”​

Find Support

Being diagnosed with a rare cancer can also pose emotional challenges, says Sara Goldberger, a senior program director for the Washington, D.C.–based Cancer Support Community. “Everybody feels alone when they are diagnosed with cancer,” she says. “This is particularly true for someone with a rare disease.” That’s why people reach out for support—which for those with a rare cancer can be even harder to find.

“Everyone wants to be in that little pond where everybody else is just like them,” Goldberger says. “If you’ve got breast cancer you can probably do that, unless you live in a really rural area. But if you have a rare cancer, it is much harder, so you have to compromise.” For most people, “a general support group is going to be better than nothing.”

Programs that connect newly diagnosed cancer patients with long-term cancer survivors can also be a resource for individuals with rare cancers. So can individual patients who doctors know will help others. Mike Harris, 69, of Kingwood, Texas, was diagnosed 18 years ago with myelofibrosis, the rare blood cancer Verstovsek studies. Whenever possible, Harris shares information with other myelofibrosis patients at M. D. Anderson Cancer Center about his experience in Verstovsek’s clinical trial of Jakafi (ruxolitinib), which went on to become the first drug approved for myelofibrosis. “I was the 37th patient to take the drug,” he says proudly.

Now semiretired, Harris sees his primary job as giving other people with cancer the same type of support he received. “Lots of people helped me over the years,” he says. “I’ve met patients from all over the world. Recently, a woman from Dallas called me. She was really worried about her diagnosis of myelofibrosis. We talked for about an hour, and I think she felt better.”

Johns is also thinking about how to help others. It’s been a year since he started Sutent and his disease is under control, for now. But he’s not planning to return to the police academy. Instead, he signed up for classes in phlebotomy (the technique of drawing blood) and is interested in a career in medicine. He’s also looking for ways to pay back a bit of the kindness he’s received by supporting other patients who are having a hard time coping with their diagnosis. “The only thing that has helped me get through this,” says Johns, “has been my support network, my community.” He has even been fortunate enough to meet an ASPS patient—one whose disease is in remission—who also lives in Pennsylvania. “There are so few people diagnosed with this throughout the world, and two of us live 45 minutes apart.”​ 

Rabiya S. Tuma is a freelance medical and science writer in Oakland, Calif.