title: Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma.
abstract: OBJECTIVE
  To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects.
  
  
  METHODS
  Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm(2)). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment.
  
  
  RESULTS
  A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age.
  
  
  CONCLUSIONS
  The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation.
authors.affiliation: Division of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: thomas.merchant@stjude.org.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.affiliation: Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Schreiber
authors.affiliation: Department of Biostatistcs, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Wu
authors.affiliation: Division of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Renin
authors.initials: R
authors.lastname: Lukose
authors.affiliation: Department of Biostatistcs, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D001921:Brain / Q000528:radiation effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002557:Cerebrospinal Fluid Shunts / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D061888:Craniospinal Irradiation / Q000009:adverse effects* / Q000379:methods; D004522:Educational Status; D005260:Female; D006801:Humans; D007360:Intelligence / Q000528:radiation effects*; D008297:Male; D008433:Mathematics; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D011932:Reading; D012737:Sex Factors; D055815:Young Adult