Personalizing Pediatric Oncology

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November 14, 2018
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November 19, 2018

The term “personalized medicine” is used frequently today throughout medical publications and in marketing materials and can be defined in a variety of ways. Most often, we think of personalized medicine as the relatively new process of sequencing tumor DNA and then trying to identify a new agent to target the identified genetic mutation.  However, I think of the personalization of childhood cancer treatment as starting 5 or 6 decades ago and continuing to evolve today.

Treatment was first targeted to the histology of the tumor and then to the disease stage or risk group.   Many factors are considered when determining a patient’s risk group, and these factors may include the physical location of the tumor, the age of the patient, and prior therapy.  Beyond the impact age may have on risk group, the age of the patient should also be taken into consideration when developing a treatment plan and consulting services for patient support.  As Drs Allen-Rhoades, Whittle and Rainusso1 note in their overview of pediatric solid tumors, treatment of cancer in an adolescent or young adult patient is not likely to be successful unless accompanied by specialized support services.

Treatment with corticosteroids prior to the diagnosis of lymphoma or leukemia can lead to drug resistance and place the affected patient in a higher risk group leading to intensified treatment and a greater risk of treatment-related side effects.  Drs Weinstock, Patel and Smith2 provide a comprehensive overview of how to differentiate between benign and malignant causes of cervical adenopathy, but I would add one point of caution, which is to avoid prescribing steroids when the diagnosis in not certain.

Another level of personalization of treatment occurs when modifying chemotherapy doses based on toxic side effects.  Currently, we most often assess the patient’s rate of metabolism in a rudimentary fashion by prescribing a standard dose of chemotherapy and then changing the dose based upon how the patient tolerates it.  We are beginning to understand the genetic basis for this variation in metabolism, and I suspect in the near future we will be able to assess a patient’s ability to metabolize a certain medication through genetic testing and use this information to customize dosing from the onset of therapy.

In the Index of Suspicion discussion of a 6-year-old boy with sickle cell disease who was also diagnosed with Hodgkin lymphoma, Drs Zaidi, Henry and Callaghan3 note that the duration and intensity of therapy may be personalized based on an individual patient’s response to therapy.  The duration of therapy for Hodgkin lymphoma is influenced by how long it takes for a patient’s PET scan to become negative.  This individualized response-based therapy has allowed for both continued excellent outcomes as well a reduction in treatment-related toxicity.  Such response-based treatment planning has also become standard in the treatment of other malignancies.

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