The Cancer Experience of Pediatric Oncology

The Cancer Experience of Pediatric Oncology

Progress in the management of children with cancer has been hailed as one of the success stories of modern medicine. There has been a dramatic improvement in outcome for almost every category of childhood cancer. For childhood acute lymphoblastic leukemia (ALL)—the most common childhood cancer, which accounts for almost 30% of cases—the progress has been most gratifying. This is a disease that was virtually incurable in the 1960s. In the most recent trials, 5-year survival among children with ALL has approached 90%—truly significant progress over five decades.

What are the lessons that can be learned from the experience of pediatric oncology, and what are the implications for cancer care in general? First and foremost, caring for patients with cancer and restoring them to health require wideranging collaboration of diagnosticians, therapists and support services. It takes a village. Unfortunately, for most patients care remains fragmented and uncoordinated.

One of the reasons for its success has been that pediatric oncology pioneered the multidisciplinary approach to patients. There was early recognition of the need to collaborate beyond the confines of individual institutions. Among the most productive collaborations have been partnerships between clinicians and laboratory investigators, which allowed rapid incorporation of laboratory findings into the clinic.

What’s more, Dr. Michael Link notes that a contributing factor may be based on what oncologist Dr. George Sledge calls “stupid” and “smart” cancers. Stupid cancers are responsive to treatment, whereas smart cancers evade therapy by developing resistance. The degree of stupidity can be quantified by the number of detectable mutations in a tumor. Compared with stupid cancers with few mutations, smart cancers, such as melanoma and lung cancer, have a more than 100-fold increase in the number of mutations. A majority of childhood cancers would qualify as stupid in Sledge’s lassification and are responsive to treatment.

Another factor is the maturing immune system in young people that makes it possible for an increasing capacity to prevent and stop neoplasia. This raises the possibility that an encounter with cancer during early life may act as an immunization to that cancer in subsequent years.

Amid good news about progress in the management of childhood cancers, there are sobering reminders that we still have work to do. If we examine the mortality from childhood cancer as the rate plotted against year of diagnosis over time, the progress that has been made is clear. Also clear is that the curve has plateaued since 2000—and that further advancement is more difficult to demonstrate. It is evident that we have squeezed what we can from conventional chemotherapeutic agents.

Link calls for a new paradigm—one that will involve yet further collaboration if we are to make greater progress.2 The genomic era has brought stunning advances in our understanding of the biology of cancer. Understanding tumors on a biologic basis is necessary to determine the most appropriate therapy. If childhood ALL has taught us anything, Link said it is that we should be astonished that our crude, empirical therapies have been successful at all, especially in light of today’s understanding that we have been treating an assortment of diseases with distinct genetic profiles having little relation to each other.

Link added that these lessons from our children emphasize the challenges that face us in caring for adults with cancer. We do not yet understand which molecular pathways are most important; our current clinical trial designs are inadequate for the era of personalized medicine and we are just beginning to realize the potential of health information technology. To address these challenges, ASCO’s 2011 report

Accelerating Progress Against Cancer includes a discussion of new approaches to cancer drug development, to trial designs with participants selected on the basis of the molecular features of their tumors and to what can be harnessed from health information technology.

In the management of cancer, our best strategy would move us from the paradigm of “diagnose and treat” to one of “predict and prevent”. Here, too, pediatricians may hold the key—because the best opportunity to prevent cancers in adults is proper immunization and lifestyle counseling of children. Successful immunization against hepatitis B and human papillomavirus (at ages 11 or 12) presents the prospect of preventing much of hepatocellular carcinoma and cervical cancer and perhaps a substantial portion of oropharyngeal cancers as well. We can only hope for equally successful vaccines against Epstein-Barr virus, hepatitis C and Helicobacter pylori.

Pediatricians also can influence children and families to promote healthy lifestyles and to educate them about the dangers of smoking, obesity and ultraviolet exposure —the major risk factors for preventable adult cancers.

Link concluded: “What really underlies the success of pediatric oncology? It’s the culture of collaboration and learning that permeates our specialty. It’s the seamless integration of clinical research with medical practice, the collection of tissues for study as a key component of research and a remarkable level of participation by physicians and patients in the clinical research process. It’s the understanding by physicians, patients and their families that clinical research is the key vehicle for
progress.”