The Many Levels of Personalized Pediatric Oncology Treatmentby Jeffrey D. Hord MD, Editorial Board Member, Pediatrics in Review

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

Treatment was first targeted to the histology of the tumor and then to the disease stage or risk group.   Manyfactors are considered when determining a patient's risk group, and these factors may include the physicallocation 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 consultingservices for patient support.  As Drs Allen-Rhoades, Whittle and Rainusso1 note in their overview of pediatricsolid tumors, treatment of cancer in an adolescent or young adult patient is not likely to be successful unlessaccompanied by specialized support services. 

Treatment with corticosteroids prior to the diagnosis of lymphoma or leukemia can lead to drug resistance andplace 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 differentiatebetween benign and malignant causes of cervical adenopathy, but I would add one point of caution, which is toavoid prescribing steroids when the diagnosis in not certain. 

Another level of personalization of treatment occurs when modifying chemotherapy doses based on toxic sideeffects.  Currently, we most often assess the patient's rate of metabolism in a rudimentary fashion by prescribinga standard dose of chemotherapy and then changing the dose based upon how the patient tolerates it.  We arebeginning to understand the genetic basis for this variation in metabolism, and I suspect in the near future wewill be able to assess a patient's ability to metabolize a certain medication through genetic testing and use thisinformation 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 withHodgkin lymphoma, Drs Zaidi, Henry and Callaghan3 note that the duration and intensity of therapy may bepersonalized based on an individual patient's response to therapy.  The duration of therapy for Hodgkinlymphoma is influenced by how long it takes for a patient's PET scan to become negative.  This individualizedresponse-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 othermalignancies.    

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So, while we have moved into the age of molecular characterization of tumors and are starting to use this"fingerprint" to influence treatment recommendations, this is not the start of personalized medicine in pediatriconcology; it is just the next level of personalization.

REFERENCES

Allen-Rhoades W, Whittle SB, Rainusso N.  Pediatric Solid Tumors in Children and Adolescents: An

Overview.  Pediatr Rev. 2018 Sept;39(9):444-452. doi: 10.1542/pir.2017-0268.

1.

Weinstock MS, Patel NA, Smith LP.  Pediatric Cervical Lymphadenopathy.  Pediatr Rev.  2018

Sept;39(9):433-441.  doi: 10.1542/pir.2017-0249.

2.

Zaidi AU, Henry M, Callaghan MU.  Index of Suspicion: Persistent Lung Lesion in a 6-year old Boy with

Sickle Cell Disease.  Pediatr Rev.  2018 Sept;39(9):473-475.  doi: 10.1542/pir.2017-0084.

3.

Pediatric Lymphoma●

Pediatric Solid Tumors in Children and Adolescents: An Overview●

Pediatric Solid Tumors of Infancy: An Overview●

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Copyright © 2018 American Academy of Pediatrics