Late Effects in Patients Treated for Childhood Craniopharyngioma

Behavioral issues and memory deficits. Although intelligence quotient is usually maintained, behavioral issues and other cognitive domains such as memory, executive function, and attention are commonly impacted.[4,6-8] Memory and neurocognitive effects may be mitigated by the use of proton radiation therapy and conformal plans to avoid surrounding normal brain anatomy such as the hypothalamus and hippocampus.[9]; [10][Level of evidence B3]

Visual disturbances. Visual disturbances, including visual field and acuity defects, have been reported. These deficits may be decreased with less aggressive surgical approaches or radiation therapy alone.[11][Level of evidence C1]; [6,10]

Endocrine abnormalities. Endocrine abnormalities result in the almost universal need for lifelong endocrine replacement with multiple pituitary hormones.[5,8]; [12-14][Level of evidence C1] Similar to visual disturbances, endocrine injury can be offset by limited surgical resection [5,6,15-17] and intracystic therapies that minimize invasive interventions.[18]

Decreased height. Growth hormone replacement therapy is used to improve growth in children treated for craniopharyngiomas. Growth hormone replacement initiated in childhood results in increases in height without impact on OS and progression-free survival when compared with children who did not receive growth hormone.[19][Level of evidence C1]; [20] Growth hormone administration beginning 1 year after diagnosis may be associated with early improvements in quality of life when measured at 3 years postdiagnosis.[21][Level of evidence C1] Published consensus guidelines do not support an increased risk of recurrence with use of growth hormones. They recommend considering growth hormone replacement therapy as early as 3 months after completing cancer therapy in patients who have stable disease and significant growth deficits.[22][Level of evidence D]

Obesity. Obesity, which can be life-threatening, and the development of metabolic syndrome, including nonalcoholic fatty liver disease, can occur.[23,24] Children who undergo complete resection or subtotal resection may develop obesity, suggesting that a predilection to obesity may be a component of the disease itself, not the result of direct hypothalamic injury.[25][Level of evidence C1] Severe obesity seen in patients with craniopharyngiomas is more likely a result of a combination of factors such as tumor location and treatment characteristics, with multifaceted downstream impacts.[26][Level of evidence C1] In a study of 709 patients with craniopharyngiomas, posterior hypothalamic involvement or operative injury to the posterior hypothalamus appeared to be a key factor in the development of severe obesity.[3]

Vasculopathies and stroke. Vasculopathies and subsequent strokes may result from local irradiation.[27,28] Previous studies have suggested that long-term growth hormone replacement may reduce the risk of stroke. Studies have also shown that pretreatment characteristics such as existing vascular injury, vessel location in the surgical field, and larger radiation doses to vascular structures increase the risk of long-term vessel stenosis.[28]; [29][Level of evidence C1] In a study of 94 pediatric patients with craniopharyngiomas who were treated with surgery and 54 Gy of proton therapy, the strongest predictor of postradiation therapy vasculopathy was preexisting vasculopathy.[29] The impact of proton radiation therapy was negligible within the operative corridor. Despite the high incidence (n = 27, 28.7%) of imaging-only evidence of subclinical stenosis events, only five patients required a revascularization procedure. In one of these patients, high-grade stenosis was present before radiation therapy. Two patients had previous tumor recurrences that required multiple resections before radiation therapy.

Subsequent neoplasms. Subsequent neoplasms may result from local irradiation.[27] Secondary malignancies related to radiation therapy that specifically involve the pituitary/sellar region can range from malignant tumors, such as high-grade gliomas, to meningiomas. This risk is increased in patients who are younger at the time of radiation therapy.[30]