Young Children At Risk For Impaired Reading Skills Following Medulloblastoma Irradiation

The researchers found that the greatest rates of decline in IQ andreading skills occurred in patients who were younger than 7 years oldat diagnosis. Patients who were at either high or average risk oftreatment failure suffered significant loss of reading skills over timefollowing treatment.

The study used "risk-adapted" radiation therapy in which thedose of radiation was adjusted according to whether the patient'scancer had already spread and how much tumor was left following initialsurgery to remove the cancer. Patients in the study were classified ashigh risk (HR, 37 patients) or average risk (AR, 74 patients) dependingon whether they had those risk factors. HR patients were consideredmore likely to experience treatment failure and therefore receivedhigher doses of radiation.

The loss of reading and spelling skills among both AR and HRchildren apparently is caused by impairments of the fundamentalcognitive processes that are critical to the early development of theseskills in a child, according to Amar Gajjar, M.D., a member of theHematology-Oncology department and director of Neuro-Oncology at St.Jude. Gajjar is the senior author of a report on this study thatappears in the August 20 issue of Journal of Clinical Oncology.

In addition to confirming that younger age increases the riskof neurocognitive deficits, the current study also allowed theresearchers to develop a way to predict the number of IQ points thatwould be lost by both HR and AR patients depending on whether they wereolder (at least 7 years of age) or younger (less than 7 years) at timeof diagnosis and treatment.

The investigators are now using results of this study toidentify and help children in need of special training to enhance theircognitive functioning following treatment for medulloblastoma.

The study, which included 111 children (age 3-20 at time ofdiagnosis), was unprecedented because it followed a larger number ofpatients than any previous such investigation, Gajjar said. Inaddition, the investigators conducted neurocognitive testing ofchildren for up to six years after diagnosis--that is, both before andafter treatment, he added. Moreover, no other such previous prospectivestudy (a study following patients over the course of time) has comparedthe outcome of children receiving risk-adapted radiation therapy doses.

Risk-adapted treatment included surgery to remove as much ofthe tumor as possible, followed within 28 days by initialpost-operative craniospinal irradiation therapy (CSI) plus a radiationtherapy "boost" to the primary (original) tumor site delivered by 3-Dconformal radiation therapy (CRT). Six weeks after completion ofradiation therapy, children underwent four rounds of chemotherapy withcyclophosphamide, cisplatin and vincristine. The investigators observedthe patients every three months for two years and every six monthsthereafter for a total of five years.

CRT combines CAT scans and MRI to create pictures of thecancer that a computer then turns into three-dimensional images of thetumor. These images are combined with computer-controlled radiationbeams and meticulous positioning of the treatment table on which thepatient lies. Radiation hits the tumor at precisely calculated anglesand depths matching the 3-D image of the tumor, obliterating the cancerand sparing healthy tissue.

All children underwent neurocognitive testing after surgery andat approximately one, two and five years after diagnosis. The IQ of the104 patients who were at least 3 years old was evaluated using theage-appropriate Wechsler Intelligence Scale; and academic achievementwas measured in patients at least 5 years of age using a variety oftests that measured reading, math and spelling skills.

"This study significantly adds to our understanding of thelong-term neurocognitive development of these children. It also helpsus develop and test intervention programs that aim at reducing thedeficits these children experience," said Shawna Palmer, Ph.D., one oftwo lead neuropsychologists on the study.

Other authors of the study include Raymond K. Mulhern, ThomasE. Merchant, Dana Wallace, Mehmet Kocak, Vida L. Tyc, Larry Kun andJames Boyett (St. Jude); Murali Chintagumpala, Pim Brouwers, KevinKrull (Texas Children's Cancer Center); David Ashley and Robyn Stargatt(Royal Children's Hospital, Melbourne, Australia).

This work was supported inpart by Musicians Against Childhood Cancer, the Noyes Foundation, aCancer Center Support grant, the National Cancer Institute and ALSAC.

St. Jude Children's Research Hospital
St. JudeChildren's Research Hospital is internationally recognized for itspioneering work in finding cures and saving children with cancer andother catastrophic diseases. Founded by late entertainer Danny Thomasand based in Memphis, Tenn., St. Jude freely shares its discoverieswith scientific and medical communities around the world. No familyever pays for treatments not covered by insurance, and families withoutinsurance are never asked to pay. St. Jude is financially supported byALSAC, its fund-raising organization. For more information, pleasevisit www.stjude.org.