Malignant Glioma as a Secondary Malignant Neoplasm after Radiation Therapy for Craniopharyngioma. Report of a Case and Review of Reported Cases

Abstract

Background: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment. Case Report: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. Growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital. Case Reports in the Literature: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose. Conclusions: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.

De novo formation of brain tumors in pediatric population following therapeutic cranial irradiation

“…Craniopharyngiomas seemed to be almost always associated with glial tumors, particularly in high grades, following radiation [11,17]. Regarding latency periods, glial tumors were conceived appearing relatively earlier after irradiation, unlike meningiomas [8].…”

Stereotactic Management of Craniopharyngiomas

“…The median number of radiation isocenters per procedure was six (range, 1-9); the median prescription isodose volume was 2.4 cm 3 (range, 0.1-9.2). The median margin radiation dose was 15.5 Gy (range, [12][13][14][15][16][17][18][19][20] whereas the median maximum radiation dose was 31.5 Gy (range, 20-40).…”

“…Patients then undergo fractionated radiation therapy to minimize the chance of tumor progression. Still, radiotherapy of the parasellar region has long-term effects on endocrine function and cognition [10,11], and these patients are at risk for the development of radiationinduced tumors [12]. A third option for a subgroup of craniopharyngioma patients is treatment via stereotactic techniques, either intracavitary irradiation with ß-emitting radioisotopes or radiosurgery [13][14][15][16][17][18][19][20].…”

Is 50 Gy Sufficient to Achieve Long-Term Local Control after Incomplete Resection of Typical Neurocytomas?

“…Since survival of patients with typical neurocytomas is extraordinarily good, these patients may live long enough to develop late radiation toxicity. This risk can be decreased by using the lowest clinically effective dose [9,17].…”

“…Patients with a typical neurocytoma have a long-projected survival and will probably live long enough to be at risk for late radiation effects [11]. The potential risks of leukoencephalopathy or secondary malignancies have to be taken into account [9,17]. Thus, the use of the lowest effective dose of radiation is desirable to minimize these risks.…”