Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy

Abstract 

: To determine if low-dose craniospinal irradiation (2340 cGy) with chemotherapy is associated with a lower incidence of hypothyroidism compared to standard dose (3600 cGy) with or without chemotherapy in children with medulloblastoma.

: Between 1980 and 1999, 32 patients ≤20 years old survived after craniospinal irradiation with or without chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI), whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a total dose 5040–5580 cGy. The median ages at the time of CSI for those receiving 2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT) was employed in 22 children. All children who received 2340 cGy had CT consisting of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%) patients receiving 3600 cGy had CT; the most common regimen was vincristine, CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone concentrations were measured in all children at variable times after radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin-releasing hormone were assessed in those suspected of having central hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years (range: 2–11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5 years (range: 2.4–20 years).

: Eighteen patients (56%) developed hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months to 18 years). Primary hypothyroidism was more common than central hypothyroidism (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15 (60%) ages 5–10 and 2 of 10 (20%) age >10 years had hypothyroidism (p < 0.001). Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10 (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT (p < 0.025).

: Current treatment regimens consisting of chemotherapy and 2340 cGy craniospinal irradiation followed by a posterior fossa boost for medulloblastoma do not show a reduction of hypothyroidism. Young age and use of chemotherapy were associated with a higher incidence of hypothyroidism.

Keywords:  Hypothyroidism, Craniospinal irradiation, Medulloblastoma, Children, Late effects