Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review

Anita Mahajan, Peter L. Stavinoha, Warissara Rongthong, N. Patrik Brodin, Susan L. McGovern, Issam El Naqa, Joshua D. Palmer, Sabina Vennarini, Daniel J. Indelicato, Paul Aridgides, Daniel C. Bowers, Leontien Kremer, Cecile Ronckers, Louis Constine, Michele Avanzo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Purpose: A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities. Methods and Materials: A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models. Results: The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 59.8 Gy or 63.6 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively. Conclusions: This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.

Original languageEnglish (US)
Pages (from-to)401-416
Number of pages16
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number2
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


Dive into the research topics of 'Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review'. Together they form a unique fingerprint.

Cite this