Second Primary Neoplasms (SPNS) Of The Central Nervous System (CNS) In Survivors Of Childhood Cancer - A Report From The Childhood Cancer Survivor Study (CCSS)

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: J. Neglia
Affiliation: Childhood Caner Survivor Study, University of Minnesota, Minneapolis, MN


  1. Second neoplasms of the CNS are well- recognized events among survivors of childhood cancer, often following leukemia or primary CNS tumors.
  2. The CCSS is a multi-institutional retrospective cohort study created as a resource for the study of late events.

Materials and Methods:

  • 20,245 incident cases of common childhood cancers between 1970 and 1986, under age 21, and surviving 5+ years were identified at the 25 CCSS institutions.
  • 17,344 self-administered questionnaires were mailed.
  • Among 13,581 responded survivors (median age 26 years) included in this analysis, 488 SPNs were confirmed (pathology reports) among 428 individuals.


  • Most common SPNs are: breast ca (17%), thyroid cancer (12.2%), malignant CNS tumor (10.2%) and meningioma (10.3%).
  • Of these, 74 SPNs arose in the CNS-- 36 meningiomas (all benign), 30 glial tumors, 4 primitive neuroectodermal tumors and four other CNS tumors. Thirty-nine followed a primary diagnosis of leukemia; 23 followed a primary CNS tumor.
  • Malignant CNS tumors occurred a median of 9.5 years from the original cancer and meningiomas a median of 13.3 years.
  • Compared to general population, there is a significantly elevated excess risk of CNS tumors may persisted up to 30 years from diagnosis.
  • In multivariate analyses, cranial radiation, age < 5 year, leukemia as an original diagnosis (relative risk of 2.56 vs. non-leukmia) and original diagnosis of CNS tumor (R.R. 2.76 vs. leukemia) were identified as independent predictors for any CNS SPN.
  • Survival was poor following malignant CNS SPNs with only 4 of 17 patients with GBM or anaplastic astrocytoma alive at follow up

Authors' Conclusions

  1. The three most common predictors of developing SPN in this cohort are: youg age, leukemia and CNS tumor as an original diagnosis.
  2. Despite the increased risk observed, the absolute excess risk of secondary malignant tumors of the CNS was low, with 1.1 excess cases occurring per ten thousand person-years of follow up.
  3. Additional investigation of radiation and genetic-specific risk factors are underway and may facilitate the development of more effective primary and secondary preventive strategies.

Clinical/Scientific Implications:

  1. With novel therapeutic approaches, we might be able to modifiy the current treatment modalities in order to decrease the risk of the development of SPN following therapy.
  2. Need to consider the susceptability (ie. genetic, treatment related) of the host for developing SPN and develop specific treatment modalities for these high risk patients.

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