A Look Ahead: The Next Decade in Pediatric Oncology 

A Conversation with Michael P. Link, MD


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These are the key advances I hope to see over the next decade in pediatric oncology: improvements in the molecular understanding of cancer, more targeted drugs with fewer toxicities, comprehensive survivorship care plans, a multidisciplinary approach to treating pediatric cancers, and a high rate of participation in clinical trials.

—Michael P. Link, MD

The past 10 years have seen dramatic advances in cancer care, especially in better screening methods and earlier detection, genomic sequencing, and more effective therapies, which have led to increased survival rates in both childhood and adult cancers. According to the National Cancer Institute (NCI), among adults, the 5-year relative survival rate for all cancers combined is about 68%, and among children, the 5-year relative survival rate for all childhood cancers combined is nearing 81%.1 The number of cancer survivors in the United States is also at an all-time high at nearly 14 million, and is expected to climb to almost 18 million by 2022.2

However, despite progress in survival rates, the incidence of children diagnosed with all forms of cancer, including difficult-to-treat brain malignancies, has risen from 11.5 cases per 100,000 children in 1975 to 14.8 per 100,000 children in 2004,3 necessitating the need for not just more effective therapies, but ones that are less toxic as well to mitigate potential late effects of cancer treatment.

The ASCO Post talked with Michael P. Link, MD, Past President of ASCO and the Lydia J. Lee Professor in Pediatric Cancer at Stanford University School of Medicine, about how pediatric oncology and long-term survivorship care might change over the next 10 years, resulting in not just more cures but in extended quality of life for young cancer survivors.

Advances to Come

Which areas in pediatric oncology will see the greatest advances over the next decade?

First, we have to realize how well we’ve done. We are now curing close to 80% of children with cancer. We’ve made the greatest progress in leukemia and lymphoma and in solid tumors like Wilms tumor—the most common childhood kidney cancer. However, there are several areas of concern. For example, we have not made as much progress as we would like in childhood brain tumors, which, in aggregate, are the most common solid tumors seen in children.

In neuroblastoma, one of the most common tumors seen in infants and toddlers, we cure many of the patients with early-stage disease, but patients with more advanced-stage disease are still a major challenge. Even with very intensive therapies, including bone marrow transplantation, the majority of those children still die.

Even where we have made progress in treating these tumors, the improvement in outcome has come at a high cost. For children with medulloblastoma, we have a much better understanding of the tumors and we are now curing more patients. But the cost in terms of long-term treatment effects is quite high, so we need better therapies with fewer long-term toxicities. Being cognizant of treatment side effects, particularly long-term effects, and improving on that by modifying our therapies has been a theme for the past couple of decades and will be a continuing theme in the next decade.

Finally, the incorporation of targeted therapies into treatment regimens has already resulted in better treatment for some difficult-to-treat childhood cancers. Improved understanding of childhood cancers on the molecular level, identification of molecular pathways that drive the cancer, and incorporation of new drugs that target those pathways characterize the direction of current research and will lead to better therapies in the future.

Reducing Late Effects

Will progress be made in the ability to reduce the long-term side effects of treatment without jeopardizing potential cures?

Yes. In the management of some tumors we have been able to reduce the exposure to radiation, and in some cases, eliminate radiation entirely. One of the reasons for our focus on radiation is because of its effect on children’s growth and the risk of secondary solid malignancies. We have shown that where we have developed effective chemotherapeutic regimens, such as in lymphoma or Wilms tumor, we have been able to reduce the use of radiation without adversely affecting survival.

Similarly, we have designed successful regimens that reduce exposure to aklylating agents and anthracyclines to reduce the incidence of infertility and cardiomyopathy among survivors.

A big part of why we have been so successful in treating pediatric cancers is our understanding of the underlying molecular biology of these diseases and our ability to categorize patients into high-, low-, and intermediate-risk groups based on the molecular characterization of the tumor. That risk stratification is not ascertainable just from the histology of the cancer.

Acute lymphoblastic leukemia (ALL) is really the prototype for risk stratification. We now know that certain subtypes of the disease are associated with a very favorable prognosis, and for those children, our strategy has been to try to figure out the minimum therapy necessary to cure them while reducing the long-term side ­effects.

At the other end of the spectrum, we have children with very high-risk subtypes of ALL. When we’ve used more intensive therapies to treat those patients, we’ve been able to cure many of them. The biology of the tumor on a molecular level often tells us a lot about the individual case and allows us to tailor treatment to the patient’s risk of treatment failure. So that is a paradigm we hope to apply to all of the pediatric cancers.

Cancer Causes

Is there now a better understanding of the causes of childhood cancers?

A major hope in treating adult cancers is based on understanding the causes of those cancers and then using that information to do something about preventing them. But it doesn’t work that way in childhood cancers. For example, many cases of childhood ALL actually begin in utero; thus, strategies for prevention would have to target the pregnant mother. If we had convincing evidence that some environmental exposure was a key predisposing factor to the cancer, we could do something about that, but I don’t think there is much hope for that in the near future.

Key to the prevention of some childhood cancers is our understanding of cancer predisposition genes. As we understand more about what makes people susceptible to cancers, we may be able to screen those people more carefully and detect cancers at an earlier stage, when they are more treatable.

There is probably more that pediatricians can do to prevent cancer in adults than to prevent childhood cancers. If we immunize children against hepatitis B and human papillomavirus, we can do a lot about preventing liver cancer, cervical cancer, and much of oropharyngeal cancer. I am not sure we have the same weapons to prevent any childhood cancers, unless and until we get a suitable vaccine against Epstein-Barr virus.

Survivorship Care

How might long-term survivorship care planning and surveillance be improved in the next decade for children with cancer?

This is a critical area because as we have more and more cancer survivors in the general population, they really need to be cared for appropriately. A key advance will be the development of a model of care for how best to do this.

For example, it would be good to have clinics that incorporate internists as well as pediatric oncologists on staff who can look at a person’s health-care history, including treatment for cancer. The problem with transferring a patient to a family practitioner after a child is cured of cancer is that the primary care practitioner may not understand the long-term ramifications of the childhood cancer and its treatment.

One way we are trying to improve care is by giving patients passports that they take with them after they leave our care, which outline the diagnosis and treatment exposures that the patient has experienced, as well as the late effects the internist needs to look for based on the patient’s treatment regimen and what health screening tests might be appropriate. Hopefully, widespread use of electronic medical records will help make certain that survivors get more appropriate care.

Hallmarks of Pediatric Care

How does cancer care for children and young adults differ from cancer care for older adults, and how might that change over the next 10 years?

One of the programs we have pioneered is a very comprehensive family-centered, multidisciplinary approach to treating pediatric cancers, which is now becoming the standard for adult medical oncology as well. In the past, patients saw different practitioners at different times, but it is a model that pediatricians abandoned a long time ago. Now, patients are seen by all of the specialists right from the start, and a therapy plan is agreed on, with all of the physicians involved in the decision-making together as opposed to sequentially. That has become one of the hallmarks of pediatric cancer care.

A second hallmark is the importance of participation in clinical trials, and this is a major factor underpinning the progress we have made in pediatric cancers. I hope that those elements will continue.

I also hope that children—and adolescents and young adults—are referred to cancer centers that provide the most comprehensive care for their specific types of cancer. These patients could do better if they get the right therapy in the right place, as well as supportive care appropriate to their psychosocial needs. That’s another area to be targeted in the future.

In summary, these are the key factors I hope to see over the next decade in pediatric oncology: improvements in the molecular understanding of cancer, more targeted drugs with fewer toxicities, comprehensive survivorship care plans, a multidisciplinary approach to treating pediatric cancers, and a high rate of participation in clinical trials.

One other element essential to improved cancer care is the importance of research funding for progress against childhood cancers. Although we cure the majority of children with cancer, I do not want people to think that we have solved the problem of pediatric cancers. We haven’t. ■

Disclosure: Dr. Link reported no potential conflicts of interest.

References

1. National Institutes of Health: Yesterday, Today & Tomorrow: NIH Research Timelines. Available at http://report.nih.gov/nihfactsheets/default.aspx?csid=75. Accessed July 19, 2013.

2. National Cancer Institute: Cancer Survivorship Research/Cancer Control and Populations Sciences: Survivorship-related statistics and graphs. Available at cancercontrol.cancer.gov/ocs/prevalence. Accessed July 19, 2013.

3. National Cancer Institute FactSheet: Childhood cancers. Available at cancer.gov/cancertopics/factsheet/sites-types/childhood. Accessed July 19, 2013.



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