SEATTLEStrokes (cerebro-vascular accidents) and second
malignancies, especially thyroid carcinoma, are among the many late effects of
radiation therapy in children with medulloblastoma, according to the 42-year
experience at one institution. Maria Spavor, MD, a clinical fellow in
pediatric hematology/oncology, British Columbia Children’s Hospital,
Vancouver, presented the findings at the 16th Annual Meeting of the American
Society of Pediatric Hematology/Oncology (abstract 1557).
Dr. Spavor and her colleagues used a database to identify
children aged 0 to 18 years in whom medulloblastoma was diagnosed between 1950
and 1992 and who were treated at the British Columbia Children’s Hospital. A
total of 52 patients had received radiation therapy and were included in the
study; 79% had localized disease and the remainder had disseminated disease.
Seventy-one percent of the patients were still alive 10
years after being diagnosed; 21% of all patients included in the study died of
medulloblastoma, while 17% died of other causes. The minimum follow-up among
living patients was 10 years.
Endocrine late effects included abnormal thyroid function
(abnormal thyroid-stimulating hormone and/or total thyroxine levels) in 73% of
41 evaluated patients and growth hormone deficiency in 55% of 40 evaluated
Cognitive late effects, assessed in 39 patients, revealed
no deficits in 23%, mild deficits in 28%, moderate deficits in 18%, and severe
deficits in 31%. The likelihood of severe cognitive deficits decreased with
increasing age at the diagnosis of medulloblastoma; among 12 patients with
severe deficits, 7 had undergone radiation therapy for their disease before
the age of 5.
An analysis of highest academic achievement in 39 patients
aged 18 years or older indicated that 38% had completed special education, 15%
had completed grade 12, 26% had completed postsecondary education, and the
remainder had an unknown academic achievement.
An analysis of employment capability among 38 patients aged
16 years or older revealed that although 21% were unable to work, more than
half were working; 26% of the 38 patients had minimum wage occupations, 18%
had manual labor occupations, and 11% had professional occupations.
CNS Late Effects
Central nervous system (CNS) late effects were common and
sometimes fatal. Six of the 52 patients (12%) had a cerebrovascular accident a
mean of 13 years after diagnosis. All of the cerebrovascular accidents
occurred in the radiation field; half were thrombotic and half were
hemorrhagic. Three of the patients died from their cerebrovascular accident.
Eleven patients (21%) developed seizure disorder more than 5 years after
diagnosis. Of 24 patients who underwent auditory testing, 16 (67%) were found
to have hearing loss.
Second malignancies were diagnosed in seven patients (13%).
The most common was thyroid carcinoma, diagnosed in four patients; less common
second malignancies were non-Hodgkin’s lymphoma, acute myeloid leukemia, and
breast carcinoma, each diagnosed in a single patient. The mean time to
occurrence of the second malignancies after the diagnosis of medulloblastoma
was 13 years (range, 4 to 28 years). Two of the patients with second
malignancies died from them.
"We knew from reviewing the literature that patients
who have been treated with radiotherapy for medulloblastoma can develop
significant late effects later on in life," Dr. Spavor commented. She
cited two surprising findings: that 13% of the 52 patients were diagnosed with
a second malignancy and that 6 patients had a cerebrovascular accident in the
radiation field a mean of 13 years after they were treated.
"It is unlikely that we will be able to completely
eliminate radiotherapy as treatment for medulloblastoma because it is one of
the most effective modalities available for this disease," she said.
"We need to be aware that significant late effects can occur in
survivors. We must screen for these late effects regularly and intervene early
with strategies to lessen their severity."
Dr. Spavor and her colleagues recommend regular auditory
testing, annual thyroid function and growth hormone testing, and vocational
counseling for all survivors of medulloblastoma who have received radiation
In addition, they recommend early identification of and
intervention for survivors with cognitive deficits, consideration of stroke
prevention strategies, lifelong follow-up to detect secondary cancers, and
education of primary care providers about the late effects of treatments for