Research the driving force behind curing pediatric cancers
Cure rates for many pediatric cancers have doubled in the past 30 years, going from 48 percent in 1980 to 86 percent in 2005.
Yet 1980 was the last time a new chemotherapy agent was introduced to treat these cancers, which affect nearly 13,500 children and adolescents who are diagnosed each year.
So why the improvement for such pediatric cancers as leukemia, lymphoma and sarcoma?
"The only logical reason is the research and a cooperative attitude among pediatric oncologists across the world to share research and data," says Paul Kent, MD, a pediatric hematologist/oncologist at Rush University Medical Center. "Through research we have figured out how to use existing drugs in different ways and combinations, and as a result, we've been able to double the cure rate."
Rush is a member of the Children's Oncology Group (COG), a National Cancer Institute-supported clinical trials cooperative group devoted exclusively to childhood and adolescent cancer research. COG comprises 242 institutions worldwide, and 90 percent of pediatric hematologists and oncologists in the U.S. are members.
What effects does the COG have on cure rates? It enables clinical researchers to conduct studies on large enough patient samples to produce statistically significant results to improve screening, diagnosis and treatment.
When divided into the specific cancer types, the number of children with each is relatively small. But by implementing collaborative research across member institutions, COG researchers are able to enroll patients from many hospitals in the same trial.
Every member of the COG uses the same protocols to treat childhood cancers. "As part of the COG, Rush uses the same advanced treatment protocol for treating all cancers as St. Jude Children's Research Hospital, the University of Texas MD Anderson Cancer Center, Memorial Sloan-Kettering Cancer Center and every other COG institution across the country," says Kent.
"We all work together for the good of the patients at an international and national level. Striving to enroll every patient we see on a multi-institutional cooperative group study is seen as an ethical obligation by us. This high level of national cooperation, organization and real time engagement for every patient is a distinctly different approach than you'll see in any other medical field, cancer or otherwise."
Access for survival
The goal of this approach is to extend the likelihood of survival to as many children and adolescents as possible. That's why 95 percent of the pediatric cancer patients who come to Rush are enrolled in some kind of COG/NCI protocol — an impressive proportion considering that only 2 to 5 percent of patients with nonpediatric cancers participate in national/collaborative protocols.
"Our overwhelming message is access, access, access. Having access to COG/NCI studies is what cures people, and we need to do everything we can to make that possible," says Kent.
Rush is able to enroll even more pediatric cancer patients in COG/NCI trials thanks to a partnership with John H. Stroger, Jr. Hospital of Cook County and the University of Illinois Medical Center. When it comes to pediatric cancers, the three institutions function as one to keep trials open and enroll patients.
"We share all of our resources," says Kent. "All of the patients have access to the most cutting-edge treatments, and we're able to help kids and young adults who wouldn't otherwise be able to receive these treatments due to insurance or financial issues."
Casting a wider net
While cure rates for pediatric cancers in young children and cancer among adults over 40 continue to increase, patients in the 15- to 40-year-old age group have not fared as well, with cure rates not improving in 30 years, especially for lymphoblastic leukemia.
The problem, according to Kent, is that adolescents and young adults are not being enrolled in COG clinical trials and are not being treated on pediatric protocols, which are more intense and specifically designed for pediatric cancers.
Kent is looking to join forces with adult oncologists to offer young adults with pediatric cancers access to COG trials and pediatric protocols — treatments that have been shown to dramatically improve cure rates for patients between the ages of 15 and 40 for certain types of cancer.
"We want young adults to realize that for certain disease types — primarily leukemia and sarcoma — they have a choice for much more intensive therapy with significantly higher predicted cure rates as part of a COG/NCI study," says Kent.
At Rush, this kind of collaboration is thriving in the treatment of bone sarcomas and soft tissue sarcomas. Kent works closely with Marta Batus, MD, an adult oncologist, as part of the Rush Sarcoma Tumor Conference.
Every Wednesday morning pediatric and adult surgeons, orthopedic oncologists, medical oncologists, radiation oncologists and pathologists come together as a multidisciplinary team to determine the best course of care for each sarcoma patient at Rush.
"This collaboration and cooperation is great for the patients and gives them the best possible chance to survive. It is a model for how cancer in young adults should be approached," says Kent.
A tolerable cure
COG protocols and cooperative approaches have a direct positive effect on cure rates; and, through clinical trial findings, they have important indirect effects on improving the treatments themselves. "In many of the pediatric cancers, we have such high cure rates that the focus has shifted to how we can decrease the toxicity of the treatments," says Kent.
Though the cure rates are high in pediatric cancers today, the treatment itself is sometimes grueling. Chemotherapy is typically administered on an inpatient basis, on a tight schedule (often weekly or every two weeks).
And while the combined therapy is effective at curing the cancer, it often leads to other long-term health problems, including cognitive impairment and cardiovascular conditions. In fact, approximately two-thirds of childhood cancer survivors have some type of medical issue, and of those about 20 percent have serious disabilities.
Therefore, the pressing question in pediatric cancers research today is whether it's possible to continue successfully curing the cancer while also decreasing the therapy and toxicity of the therapy. Like all of the other advances in treating and curing pediatric cancers, the answer will be determined through research.
Despite the rarity of all forms of pediatric cancers (most are only a few hundred per year in the United States), the large numbers of patients enrolled in COG protocols give the data necessary for determining these advancements.
The outlook is promising. Over the past 10 years, the COG has been working on clinical trials that eliminate radiation in the treatment of Hodgkin lymphoma. Radiation has serious long-term consequences, such as a high risk for girls developing breast cancer.
"So far we have found a group of Hodgkin disease patients for whom it is safe not to give radiation," says Kent. "We figured this out through carefully designed studies with lots of participation and very close follow-up."
As collaborative research in pediatric cancers continues to advance treatments, the future for children and young adults with cancer will continue to get brighter.