Life and Limb: Improving Bone Tumor Treatment

"I never even worried about losing my leg," says bone cancer patient Dominique Johnson.

"I never even worried about losing my leg," says bone cancer patient Dominique Johnson.

Clinical research, key partnerships and the desire to help children keep their limbs are the driving forces behind Children's successful work to improve treatment options — and survival rates — for those with bone tumors.

A lot has changed in the treatment of bone tumors in the last 20 years. As recently as the early 1980s, amputation was the standard of care and survival rates for cancerous bone tumors were less than 50%.

Children diagnosed with bone cancer today not only have an excellent chance of surviving; they can — if treated at the right place — expect to keep their limb.

Many factors have contributed to this dramatic improvement for patients with bone tumors, and the team at Children's Hospital — led by Dr. Ernest "Chappie" Conrad — has played a significant role in these advancements.

Dr. Conrad joined Children's in 1986 with an idea for a clinic that would combine patient care with research and education, and find treatments that would enable children not just to survive, but to flourish. Under his leadership, Children's Pediatric Bone Tumor/Sarcoma Clinic — the first such clinic in North America — has gained international renown.

The program has been a leader in advancing limb-sparing surgeries (also known as limb-salvage surgeries) and improving diagnostic procedures and care for many benign tumors. Ongoing efforts include research and clinical trials aimed at improving chemotherapy regimes, and solving the problem of maintaining limb function in the growing child. The goal is to decrease the number of surgeries on the affected limb of patients who are still growing.

"Twenty years ago, bone tumors were under-diagnosed and under-treated," explains Dr. Conrad. "The introduction of imaging technology, such as CT scans in the early 1980s and MRI technology in the early 1990s, made diagnosis and treatment easier because we got a better look at a tumor's size and location.

"Using chemotherapy as an initial part of treating all cancerous bone tumors also was important. But the biggest change was in the work to save limbs. That just wasn't being done."

To Save a Limb

Excising the tumor from the affected limb is a critical step in saving it. If the tumor is cancerous, chemotherapy is used to shrink it. Surgery to remove the affected part of the bone comes next, followed by an implant involving either a bone graft or metallic prosthesis to replace the area removed.

"Removing the tumor isn't the most challenging task — keeping up with a patient's growth is, because you are trying to mimic Mother Nature," says Dr. Conrad. "Most pediatric patients are still growing, so we have to find ways to elongate the affected limb to match the growth of the rest of the body."

This may require surgery almost every year for some patients. A newer technique to minimize the number of surgeries a child faces is being used here at Children's. It uses a strong electromagnetic field to melt an acrylic implant that releases a spring that stretches the bone.

This type of implant can only be used in young children, but these are the ones needing the greatest amount of limb lengthening. If effective, this process may decrease the number of surgeries to lengthen the bone.

Caring Across Disciplines

Bone tumors require multidisciplinary care from specialists in orthopedics, oncology, surgery, radiology, nursing, physical and occupational therapy and social work, notes Dr. Conrad, and this is where the team at Children's really shines.

"When dedicated providers from different disciplines interact with each other on a regular basis, a mutual respect develops that results in a very stimulating environment. At first, they educate each other in their respective strengths, then they challenge each other to higher achievement. In the end, the oncologist becomes a 'surgeon,' and the surgeon becomes an 'oncologist.'

"It is a wonderful metamorphosis that clearly raises the level of care for our patients. Of all our accomplishments, I am most proud of having a group from many disciplines whom I can count on when I'm not in the room."

Advancing Care Through Research

Children's has built a robust research program that conducts extensive clinical trials to improve therapies. We are an active member of the Children's Oncology Group (COG), an organization of pediatric oncology specialists from around the country that coordinate their efforts to improve survival and cure rates.

Recently, Children's piloted several promising treatment regimens that will be replicated by COG members throughout the United States.

One such study suggests that shortening the time between chemotherapy doses improves treatment results.

In another Children's study, researchers are looking at markers in patients' blood to help determine the possibility of rejection. Other studies seek to develop new approaches — such as the use of very-high-dose chemotherapy with stem-cell support for patients with recurrent sarcomas — to improve outcomes.

"Most children treated at Children's for cancer participate in clinical trials and are treated through formal protocols, or treatment plans, that are consistent with treatment of other patients at other institutions. These protocols enable Children's oncologists to compare a treatment's outcome with colleagues across the country," says Dr. Thomas Pendergrass, pediatric oncologist at Children's and director of medical education.

UW Medicine/SCCA Connection

Dr. Conrad established and leads both UW Medicine's adult sarcoma and Children's pediatric sarcoma programs. This collaboration enables Children's patients and physicians to share access to highly specialized equipment such as the University's positron emission tomography (PET) scan imaging technology.

"The UW's PET imaging program, led by Dr. Janet Eary, is the highest-rated cancer imaging program in the world. It allows us to evaluate a patient's response to chemotherapy almost immediately and to evaluate high-risk patients more carefully," says Dr. Conrad.

"Our program is the only one in the nation that has a highly collaborative relationship between the pediatric and adult programs," says Dr. Doug Hawkins, a pediatric oncologist at Children's and professor of pediatrics at the University of Washington. "Some of the chemotherapy used at UW Medical Center was developed through the protocols used in Children's research."

"This is a huge advantage," adds Dr. Conrad, "because new protocols don't need to be created from scratch and we can deliver more effective treatment to children and adults faster."

Children's also partnered with the Fred Hutchinson Cancer Research Center and UW Medicine to form the Seattle Cancer Care Alliance (SCCA), which aims to bring research from the bench to the bedside more quickly to improve outcomes for all kinds of cancer.

Collaborations like these are the force that drives advancement in cancer research and treatment. "By pooling our community resources, we can better achieve our common goals: developing innovative treatments and eliminating problems with treatments of pediatric cancer," says Dr. Pendergrass.

A Disruptive Disease

Of the 300 new patients seen each year at Children's Bone Tumor/Sarcoma Clinic, about 95% have benign (non-cancerous) tumors rather than malignant (cancerous) ones.

In either case, the treatment can be long-lasting and disruptive to their lives. "A lot of the children spend their entire childhoods being treated for benign bone tumors," says Dr. Conrad, director of the limb-sparing programs at Children's and UW Medical Center.

Although benign bone (and soft tissue) tumors do not metastasize or threaten a patient's life, they do have a much higher risk of local recurrence in the tissue of origin. So, children with benign tumors have a higher risk of multiple surgeries to combat tumor recurrences.

"I'm awed by the courage of my young patients and their families," says Dr. Conrad. "It's a privilege to be associated with them in the midst of an enormously emotional time in their lives. You never forget the children you treat. They are uplifting to be around."

Gaining international recognition for limb salvage surgery and improving diagnosis and care for a large number of benign tumors and dysplasias are among the Bone Tumor/Sarcoma Clinic's greatest contributions.

Endowed Chair in Pediatric Cancer Honors Survivor

When 3-year-old Eloise Evans felt extreme discomfort in her ears over several days, her parents, Dan and Celia Evans, immediately turned to Children's for help. A CT scan revealed a rare, inoperable sarcoma next to Eloise's brain. After a year of chemotherapy and radiation at Children's, Eloise is now a happy and active child with an 85% chance of full recovery.

"To see Eloise at her lowest point ripped our hearts out, but to see her now makes each day a priceless treasure," says her father, Dan Evans Jr.

Eloise's grandparents, Dan Sr. and Nancy Evans, created the Evans Family Endowed Chair in Pediatric Cancer in gratitude for Eloise's care. The chair provides a permanent source of funding to improve cancer treatment, attract and retain the highest-caliber pediatric oncologists and further cancer research at Children's. Dr. Russ Geyer is the current holder of the Endowed Chair.

"Our family has seen firsthand why Children's cancer program is one of the best in the country, and we hope this endowment makes a lasting difference," says Dan Evans Sr., a former Washington state governor and U.S. senator.

Radiation Therapy Delivered Directly to Bone Tumors

Researchers at Children's are developing sophisticated new treatment plans for Ewing's sarcoma patients using an injectable radiation therapy called HoDOTMP — a compound that delivers targeted radiation directly to bones.

"We need to measure the distribution of the drug and response of the patient," says Dr. Hawkins, who directs the research program, which is available only at Children's. "We inject a small amount through a patient's IV line and then take multiple nuclear images with a gamma camera over time. These images show the radioactivity in the body. We then input the information into formulas to calculate a patient-specific dose of HoDOTMP. We hope this will maximize its effectiveness while minimizing the side effects in each particular patient."

Currently an investigational medicine, this therapy is used only in patients where other therapies do not have a high likelihood of success. Dr. Hawkins hopes to start a successor study in the spring of 2004.

"I thought the pain I was feeling in my leg was from an old volleyball injury. But it was cancer," says Dominique Johnson, 18, who was diagnosed last March with bone cancer below her left knee.

After administering chemotherapy, Dr. Conrad replaced the cancerous section of her tibia with an allograft from the Northwest Tissue Center bone bank. He then attached a metal plate to the surrounding bone with screws to stabilize the bone so calcium deposits will build up to connect old bone to new bone.

Though she can no longer participate in active sports, her new bone will fully connect and heal in about a year.

Dominique took her treatment in stride.

"I never worried about losing my leg," she says, "and my other doctors even planned my chemotherapy so I could be out of the hospital for prom and graduation."