Arterial thrombosis and pediatric cancer- should cancer associated pediatric stroke be studied?

 

While knowledge of arterial thromboembolism prevalence and risk factors among adult cancer patients is currently growing, there seems to be only scarce information regarding arterial thrombosis in general or stroke in particular, among patients and survivors of pediatric cancer.

Cancer is an important risk factor for childhood stroke. Childhood cancer-associated stroke has been studied using large databases of cancer survivors (such as the Childhood Cancer Survivor Study, or CCSS, and the Teenage and Young Adult Cancer Survivor Study, or TYACSS)[1,2].   However, it has not been specifically analyzed in a pediatric stroke population. While many of the oncologic risk factors for stroke have been well described, there remains a knowledge gap about stroke characteristics and mechanisms in this population given the paucity of stroke-specific variables in cancer survivor databases.

The number of childhood arterial ischemic stroke (AIS) patients that have or had cancer as a risk factor is unknown, and the mechanisms by which cancer puts children at risk for stroke are not well understood. Cancer may be an underlying cause of many of the most common risk factors for pediatric stroke previously described. Mackay et al.[3], provided a risk/ etiology scheme, showing that cancer and its treatment can increase risk for stroke in the following ways:

  1. Cerebral arteriopathy (and specifically an increased risk for Moya Moya disease) has been well described in association with cranial irradiation, which is the mainstay of treatment for many childhood brain tumors and high-grade hematologic malignancies, eg. Cytarabine[4].
  2. Cardioembolic stroke may result from chemotherapy-associated cardiomyopathy, for example, due to administration of anthracyclines.
  3. Infection, an important stroke risk factor, is common in cancer patients, given their immunocompromised status.
  4. Neurosurgical procedures performed for brain tumors, may complement additional risk for stroke in this population.
  5. Acquired prothrombotic risk factors, either due to cancer-associated coagulopathy or L-asparaginase treatment, may increase the risk for stroke in the pediatric cancer population.

The relative impact of each of these underlying risk factors in pediatric stroke has not been studied.

Recently, an analysis using the international pediatric stroke study (IPSS) database, found that there are 81 children (2.8-2.9% out of 2866 patients with documented pediatric and perinatal stroke) who had strokes that had cancer listed as a co-morbidity. Specifically, there were 18 children with brain tumors, 60 children with hematologic malignancies, and 3 with malignant solid extracranial tumor. 

Overall, there seems to be a much lower incidence of arterial stroke among pediatric cancer patients, as compared to adults. This may stem from different tumor types and treatments as well as the lack or paucity of metabolic cardio-vascular risk factors among children. Prospective registries and future studies are certainly warranted to resolve this issue.

 


REFERENCES

  1. Mueller S, Sear K, Hills NK, Chettout N, Afghani S, Gastelum E, Haas-Kogan D, Fullerton HJ. Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):643-8.
  2. Bright CJ, Hawkins MM, Guha J, Henson KE, Winter DL, Kelly JS, Feltbower RG, Hall M, Cutter DJ, Edgar AB, Frobisher C, Reulen RC. Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study). Circulation. 2017 Mar 28;135(13):1194-1210.
  3. Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V; International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol. 2011 Jan;69(1):130-40.
  4. Tibussek D, Natesirinilkul R, Sun LR, Wasserman BA, Brandão LR, deVeber G. Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine. Pediatrics. 2016 Feb;137(2):e20152143.
  • Gili Kenet

    Gili Kenet

    Sackler Medical School, Tel Aviv University and the Israel National Hemophilia Center and Thrombosis Institute, Tel Hashomer, Israel
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