Stroke a Late Effect of RT for Medulloblastoma

SEATTLE—Strokes (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 patients.

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

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 therapy.

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 childhood cancer.