Karen Patterson

A recent and rare look at long-term lung cancer survivors shows breathlessness among them is persistent and common.

The news is not, however, a surprise to Eileen Cody.

Cody, 38, of Foxboro, Mass., had her right lung chipped away over the course of three surgeries. In 2006, she was diagnosed with stage 1B non-small cell lung cancer in the lower lobe. She underwent a lobectomy and four months of chemotherapy for the 5-centimeter tumor.

By December 2007, cancer was confirmed in the upper lobe, and a wedge resection was performed.

After multiple nodules were found in 2008, she underwent more chemo and the rest of the lung was removed. “That was the hardest time to adjust,” says Cody, a registered nurse who at that point saw her breathing decline and went on disability. Now she has to sit and catch her breath after climbing stairs. She finds it hard to take in New England’s frigid winter air—and to enjoy the outdoors with her young sons, ages 6 and 8.

“Even with the simplest of activities, gardening or even talking on the phone, I have to stop and rest,” she says. “I’ve learned to set priorities—I pick what needs to be done right then and there.”

A recent study found that shortness of breath, abbreviated casually as SOB and known technically as dyspnea, afflicted 60 percent of long-term survivors who had undergone surgery for stage 1 non-small cell lung cancer. Almost 40 percent of the patients did not have dyspnea at the time of surgery.

The study of 342 patients treated one to six years earlier, was published in August in the 

“Lung cancer is such a common cancer that even if you assume a 15 percent overall survival rate, that’s about 30- or 40,000 a year, or about half a million survivors out there. And there’s precious little in the literature about how they feel or what they go through,” says Marc Feinstein, MD, of Memorial Sloan-Kettering Cancer Center in New York City, lead author of the study.

The researchers determined patients had dyspnea if tasks, like carrying groceries or climbing a flight or two of stairs, left them breathless. “It can be pretty limiting,” Feinstein says, “and not being able to catch your breath can be very scary.”

However, respiratory therapy can offer some relief, says Debbie Koehl, MS, RRT-NPS, AE-C, chair of the American Association for Respiratory Care’s Continuing Care/Rehabilitation Section. For instance, she notes that people tend to hold their breath during exertion. Instead, therapists advise breathing out on the exertion and breathing in during the rest activity—for example on stairs, exhaling while taking a step and inhaling while pausing atop each one. “Exhale on the exertion,” Koehl urges, “no matter what you’re doing.”

Several years after her lung cancer treatment, retired medical secretary Joan Bourguignon was finding it harder and harder to do daily tasks. Making a bed with fresh sheets would leave her spent for 10 minutes.

Bourguignon, 78, of Calabash, N.C., had been diagnosed in July 2003 with stage 3B non-small cell cancer in her lower right lung. Although the cancer was too far along for surgery, she had radiation and chemotherapy.

“I kept telling my oncologist at checkups every three months that I’m getting short of breath,” Bourguignon recalls. “He said, ‘Your lung is not what it used to be—what do you expect?’ ”

Finally, she saw a pulmonologist. Now she’s on oxygen 24/7, with a 50-foot plastic hose that follows her through her house, and a portable tank for when she goes out.

“It’s hard to travel because there are so many things you have to bring with you,” she says. And the summer heat keeps her indoors. “Even with oxygen it’s still hard to breathe out there,” she says.

In the study of survivors, researchers pondered just what circumstances might be linked to long-term breathlessness, such as obesity and type and extent of surgery.

The research revealed four factors related to development of dyspnea:

> Whether dyspnea was present before surgery

> Whether, in breathing tests before surgery, the patient had a lower diffusing capacity—a measure reflecting how easily the lungs get oxygen from the air to the hemoglobin molecule in the blood

The study could not determine cause and effect—for instance, it is not known whether lack of exercise contributed to breathlessness, or breathlessness prevented people from exercising, Feinstein notes. While researchers figure that out, he suggests it may be helpful for lung cancer survivors to work with their physicians to treat depression and boost their levels of physical activity, where appropriate.

Undiagnosed or untreated depression can influence a patient’s overall coping, Koehl adds. Also, depression is commonly accompanied by anxiety. “A lot of times anxiety leads to shortness of breath, and then shortness of breath leads to more anxiety. It’s a vicious cycle,” she says. With rehabilitation, therapists can desensitize patients to that anxious feeling.

Koehl also believes in the benefits of physical activity when possible. Patients in pulmonary rehabilitation—some of whom were treated for chronic obstructive pulmonary disease before they developed lung cancer&mdash;have told her exercise has helped their physical and mental health.

“Exercise improves your overall well-being,” she says. “It improves your muscle strength. You’re taking deeper breaths. You get your heart moving.”

The researchers, meanwhile, note that studies show exercise can improve health for patients with various other lung diseases, and that research in lung cancer patients has shown pulmonary rehabilitation just after surgery can improve the distance they can walk in a set period of time.

Meanwhile, in coming to terms with her limitations, Cody says something else is what really gets her heart moving: her family.

“I may not be able to do the potato sack races,” she says, “but I’ll be at the finish line rooting my kids on.”

Articles

Fighting Breathlessness

Helen Anbinder of Dobbs Ferry, New York, achieved a lot—and much was achieved on her behalf&mdash;in the seven years between her chronic lymphocytic leukemia diagnosis and treatment.

Anbinder, now 68, learned in 2001 that she had early-stage CLL. She consulted a specialist—Kanti R. Rai, MD, at Long Island Jewish Medical Center in New Hyde Park, New York (the Rai staging system for CLL bears his name)&mdash;and because she didn’t need treatment yet, was cared for with a “watch and wait” approach. 

But that doesn’t mean Anbinder sat still. Having sought information about her disease from the Leukemia & Lymphoma Society (LLS)—and having heard of the remarkable success of the drug Gleevec (imatinib) for another type of leukemia, chronic myeloid leukemia&mdash;she had a ready answer months later when her brother- and sister-in-law, Stephen and Madeline Anbinder of New York City, wanted to make a charitable gift of more than $200,000 in her honor. 

“Without hesitation I said I wanted it to go for CLL research,” says Helen, a retired administrator of a local continuing education program. “News had come out about Gleevec, but I could see nothing of that nature in the pipeline for CLL.” 

She met with the LLS and decided to earmark the money for research by The Ohio State University’s John Byrd, MD, and colleagues, who were testing a new CLL treatment protocol combining Fludara (fludarabine) and Rituxan (rituximab) (FR).

In 2004, Helen Anbinder formed a family-and-friends team for the society’s Light The Night Walk, raising $6,100. By the time her CLL needed treatment in 2008, Anbinder’s team had racked up more than $67,000 in the annual events. She also began volunteering in the LLS’s Westchester/Hudson Valley chapter office—she now serves on its board&mdash;and in 2005 appeared in a national video highlighting the society’s work.

As it turns out, the treatment Rai finally recommended for her was the very protocol Byrd was testing. Three cycles of FR and Anbinder was in remission. “It actually worked too well,” she says—her white cell count plummeted after the first round and she was hospitalized for a respiratory infection. Subsequent cycles were shortened from five days to four.

Like Energizer bunnies, the Anbinder clan has kept going. Their fund-raising team’s total now exceeds $111,000. Anbinder helps with LLS donor development and supports newly diagnosed patients through the society’s First Connections program. Her younger son, Jeff, bicycles to raise money for LLS. And her in-laws continue to contribute annually to CLL research.

Although Anbinder reports her white cell count is climbing again, she continues her many travels abroad with her husband, Paul. At some point she expects to need more treatment—very possibly, she says, that same treatment that worked so well for her before.

Helen Anbinder of Dobbs Ferry, New York, achieved a lot&mdash;and much was achieved  on her behalf&mdash;in the seven years between her CLL diagnosis and treatment. 

Watching, Waiting, & More

The term “leukemia” refers to cancers in which the bone marrow makes abnormal white blood cells (leukocytes). These abnormal cells can crowd out healthy blood cells and interfere with their function.

About one in 78 Americans will be diagnosed with some form of leukemia during their lifetimes, and nearly a quarter million Americans have a history of the disease. 

Leukemias are labeled according to how quickly they progress. Chronic leukemias worsen slowly, and are often detected by routine blood tests before symptoms arise. By contrast, acute leukemias progress quickly.

Different forms of the disease are also named according to which type of white blood cell is affected, and each is evaluated and treated differently. Disease that affects lymphocytic cells is labeled “lymphocytic,” “lymphoid,” or “lymphoblastic,” whereas disease that affects myeloid cells is called “myeloid,” “myelogenous,” or “myeloblastic.” Hence, chronic lymphocytic leukemia (CLL) is a slow-developing cancer affecting lymphocytic white cells.

CLL is one of four common types of leukemia. The others are:

 a fast-growing cancer that accounts for more than 5,000 new cases of leukemia in the U.S. each year. ALL is the most common type of leukemia in young children, accounting for about three out of every four cases, although it also affects adults.

 a slow-developing leukemia that is diagnosed in about 5,000 Americans each year. CML mainly affects adults.

 a fast-growing disease that accounts for more than 13,000 new cases each year and affects both adults and children. After ALL, AML accounts for most other cases of childhood leukemia.

A slew of rarer leukemias account for less than 6,000 new cases each year. One example is hairy cell leukemia, a chronic leukemia named for the microscopic, hairlike extensions on the outside of the cancer cell. Another is large granular lymphocyte leukemia (LGLL), a form of chronic leukemia. Yet another is chronic myelomonocytic leukemia (CMML), which affects primarily older adults. 

CMML and a similar childhood leukemia known as juvenile myelomonocytic leukemia (JMML), which arises most often in infants and children under age six, have features of two other types of blood cancer, myelodysplastic syndromes and myeloproliferative disorders. Also rare in children are acute hybrid leukemias, which mix features of ALL and AML.  

Other Leukemias

Bruce Lantry is not a typical CLL patient.

People with chronic lymphocytic leukemia—a cancer that occurs when abnormal white blood cells accumulate in the blood and bone marrow&mdash;commonly have no symptoms at diagnosis. But in early 2009, Lantry, a piano tuner, was exhausted, short of breath, and felt like his ears were plugged. The first doctor he’d seen in a long time took one look, saw enlarged lymph glands, and ordered blood work.

When results showed a perilously low red blood cell count and a soaring white count, Lantry recalls saying, “‘I guess I’m still alive.’ And she said, ‘Just barely.’” 

For Lantry, who lives in rural southwest Nebraska, the urgent treatment he needed was 100 miles away in North Platte, where he was sent by ambulance for immediate blood transfusions and bone marrow testing.

The next week he returned to North Platte and learned, at age 62, that he had stage 4 CLL, which had shut down his bone marrow’s ability to produce healthy blood and immune cells. In mid-March he started his six months of treatment, which he took for three days every 28 days.  

Lantry’s treatment combination was called FCR, for the chemotherapy drugs Fludara (fludarabine) and Cytoxan (cyclophosphamide), plus an antibody called Rituxan (rituximab). “Everyone I talked to was given those,” Lantry says of his fellow CLL patients.

Ultimately his lymph glands shrank and his cancer, once rampant, was virtually gone from his bone marrow.

CLL is the most common form of adult leukemia in the Western Hemisphere, with some 15,000 U.S. patients diagnosed each year. Its effects on white cells can impair the immune system and leave patients more vulnerable to infections and even secondary cancers. Research has found about a third of patients never need treatment and have a long survival time with the disease, while another third have disease that eventually progresses. The remaining third have an aggressive disease at onset and need treatment quickly, like Lantry.

On diagnosis, early-stage patients do not yet need treatment, says Kenneth Foon, MD, chair of hematological malignancies at the Nevada Cancer Institute in Las Vegas, and can be followed for years with a “watch and wait” approach. 

Symptoms may include unexplained fever, chills, night sweats, or weight loss (fatigue by itself is a vague symptom, Foon says); “bulky” lymph nodes or organs, meaning they are dramatically enlarged; or bone marrow failure has left a patient anemic or with a low platelet count. Rapidly escalating lymphocyte counts might also be a sign treatment is necessary. Treatment usually involves chemotherapy or other medicines.

Widely used risk categories can help guide treatment decisions. Patients at low risk for needing immediate treatment have a high lymphocyte count in the blood or marrow but usually lack symptoms. Intermediate-risk patients likewise have a high lymphocyte count and might lack symptoms, but they also have enlarged lymph nodes, spleen, or liver—which may or may not warrant treatment. High-risk patients, like Lantry, have the elevated lymphocyte count plus anemia or a low platelet count, and usually need immediate treatment.

Patients who don’t yet require treatment of the leukemia itself might still need medicine. Typically steroids or Rituxan are prescribed for side effects resulting from the abnormal activity of lymphocytes—such as autoimmune hemolytic anemia, where the immune system destroys red blood cells, or autoimmune thrombocytopenia, where it destroys platelets.

John Byrd, MD, professor of medicine and medicinal chemistry and associate director for translational research at The Ohio State University Comprehensive Cancer Center, says one significant CLL complication he sees is diagnosis anxiety. Patients, often feeling healthy, abruptly learn they have cancer but that instead of treating it, the plan is to watch and wait.

We have very effective treatments that may not cure patients but will prolong their life and their quality of life.

Although CLL is rarely cured, newly available treatments—often combining drugs and immune-based medicines called monoclonal antibodies&mdash;are making the disease more manageable. Even for patients whose condition is advanced, “there’s absolutely reason to be optimistic,” Foon says. “We have very effective treatments that may not cure patients but will prolong their life and their quality of life.”

Progress has been marked in the last quarter century, since the advent of Fludara to treat CLL, says Michael J. Keating, MB, professor of medicine in hematology at M.D. Anderson Cancer Center in Houston, whose research helped lead to widespread use of that drug.

Few other options were available until about 15 years ago, when studies showed better outcomes by combining Fludara and Cytoxan. More recently, the monoclonal antibody Rituxan proved a worthy addition, and the FCR regimen that Keating and colleagues developed was approved in February for front-line treatment and for patients whose previous therapies failed.

Recent data show the addition of Rituxan to chemotherapy is not only improving many patients’ condition but extending their lives. After six months of FCR, patients who responded achieved longer remissions, Keating says. “On average, the time to relapse of patients that achieve a response is of the order of five years or so. During that time the patients are on no treatment and only have to go see their local doctors.”

The new medicines are allowing oncologists to increasingly adapt therapy to a patient’s risks. For instance, FCR is an aggressive approach that can be hard on people who are over 65 (the majority of CLL patients are 65 or older at diagnosis) or have other illnesses.

An alternative, called “FCR-Lite,” uses lower doses of the FCR drugs. Another option is replacing the Fludara in FCR with a similar drug, Pentostatin (deoxycoformycin), which may suppress immunity less. Other alternatives include using Treanda or Campath alone.

Doctors can also tailor treatment by looking for a chromosomal variation called the 11q23 deletion. That variation makes CLL vulnerable to Cytoxan, Byrd says; patients lacking the deletion may be able to receive just Fludara and Rituxan (FR).

The goal is to avoid long-term complications. For instance, patients who receive FCR have about a 3 percent risk of developing a secondary leukemia, acute myeloid leukemia (see sidebar), compared with virtually no risk on FR, Byrd says. While neither strategy is wrong, “Our approach is when we don’t have clear evidence that more is better, generally we do less.”

Patients can undergo testing called FISH, or fluorescence in situ hybridization, which can detect 11q as well as other chromosomal deletions, such as 17p13. The 17p deletion indicates more aggressive disease, while patients with an 11q deletion tend to respond well to treatment but have shorter remissions, Keating says. A study of CLL patients, most of whom had not received any treatment, found about 18 percent had an 11q deletion and 7 percent had a 17p deletion.

Another test identifies patients who have a mutation in a gene called IgVH (about half have it). Without the mutation, patients often need treatment sooner and have shorter remissions. Patients should discuss these tests with their physicians.

Keating says along with FISH results and mutation status, he focuses on a patient’s age and levels of a protein on CLL cells called beta-2 microglobulin (younger patients and those with lower levels of the protein usually fare better). “With those four things you can get a very good idea of how likely people are to respond and how likely a response is to last,” he says.

Meanwhile, as thousands of Americans with CLL watch and wait, and thousands more are in treatment or remission, drug development marches on.

One medicine that might help soon is Revlimid (lenalidomide)—a pill already available for multiple myeloma and in phase 3 testing for CLL. Rather than suppressing the immune system, as many chemotherapy drugs do, Revlimid activates it to seek and destroy CLL cells.

Medical Illustration: Deciding on Treatment

“Patients refer to it as ‘watch and worry,’” Byrd says. “You know there’s something in you that’s not right, so when is it going to hit?”

He encourages patients to do everything they can, including consulting a physician who frequently treats CLL, to fully understand the disease’s course. “By getting information early, patients can become comfortable with how the disease is managed, and get on with their lives.”

Lantry agrees information is a lifeline. Despite his rural residence, he has learned about CLL from connections he made through the Leukemia & Lymphoma Society (

; 800-955-4572)—including ongoing online support, a telephone group on blood cancers, and the society’s First Connections program that has linked him to “phone buddies” in New Jersey and Nebraska.

“I got more support and comfort from them than through anything else at the beginning,” he says. “When you’re first diagnosed … you don’t know what on earth is going to happen.”

Meanwhile, other medicines have emerged to fight CLL, including additional monoclonal antibodies, which target specific proteins on the cancer cell. One such antibody is Campath (alemtuzumab), which received accelerated approval in 2001 and regular approval in 2007. Campath is typically used alone, sometimes for initial treatment but often in patients who experience relapse, Keating says. Another monoclonal antibody, Arzerra (ofatumumab), approved last October, has been promising in patients whose CLL doesn’t respond to Fludara and Campath. 

Another medicine is Treanda (bendamustine), a chemotherapy drug used for decades in Eastern Europe but not approved in the U.S. until 2008. Treanda is more potent than Cytoxan and is being used alone and with Rituxan.

There are many, many patients now staying in remission for more than 10 years. And it’s likely in the next five years we will develop immune therapy  approaches which will hopefully control the disease over the long term.

An alphanumeric soup of other possible treatments is mostly in early stages of development. Among them are CAL-101 and PCI-32765, both oral medications that Byrd says don’t suppress bone marrow activity or cause common chemo side effects. ABT-263, meanwhile, is being tested alone for patients whose previous treatment failed and will be tested with Rituxan as first-line therapy. The monoclonal antibody lumiliximab has shown promise when added to FCR, and the monoclonal antibody GA101 likewise may complement existing antibodies. Two drugs in development, Flavopiridol (alvocidib) and SCH 727965, may especially help patients who have the troublesome 17p deletion, Byrd says.

Patients who relapse shortly after therapy, or don’t respond as well, are particularly challenging. Relatively few—those who are young and healthy&mdash;might qualify for allogeneic stem cell transplantation, designed to permanently restore the bone marrow. Transplant recipients, usually in a clinical trial, first receive high-dose chemotherapy and/or radiation, then donor stem cells are introduced into the blood. 

Foon notes the procedure is very high-risk, with complications including graft-versus-host disease, where the newly transplanted immune system can attack the organs or cause a chronic skin condition. Rarely do CLL patients reach the point where they need to take this path, he says.

However, recent development of a “reduced-intensity transplant,” which uses lower doses of chemotherapy, has made the therapy more tolerable (though somewhat less effective) and broadened the list of potential recipients to people in their mid-70s, Keating says.

Overall, Keating tells patients with CLL to remain hopeful. “There are many, many patients now staying in remission for more than 10 years,” he says. “And it’s likely in the next five years we will develop immune therapy approaches which will hopefully control the disease over the long term.” 

A wave of new treatments for chronic lymphocytic leukemia can help keep the disease at bay.

Karen Patterson

Fighting Breathlessness

Watching, Waiting, & More

Other Leukemias

Progress That's Worth the Wait

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