The location of a tumor within the CNS, the surgical procedure necessary to biopsy or resect these lesions, as well as subsequent radiation or chemotherapy, place patients at high risk for long-term neurological morbidity. Location of the tumor in the diencephalon, at or near the hypothalamus, may increase the risk for multiple endocrinopathies. In addition, use of craniospinal radiation, that may include some part of the heart border near the radiation field, may place certain patients at increased risk for subsequent cardiomyopathy or coronary vascular compromise. For these reasons, survivors of CNS tumors may have multiple chronic medical conditions developing any time from tumor presentation through treatment and long-term follow-up. The CCSS has used the Common Terminology Criteria for Adverse Events scoring system, developed by the National Cancer Institute, to determine the severity of these conditions.23
At the time of study eligibility (5 years from diagnosis), 82% of CNS tumor survivors reported at least one chronic medical condition of any grade and were more likely than siblings to have chronic medical conditions, including: endocrine complications (Prevalence Ratio [PR] 49.1, 95% CI 27.6-87.2), neurologic complications (PR 37.1, 95% CI 28.3-48.7), or any complication (PR 29.5, 95% CI 23.8-87.2).14
Importantly, however, 5-year survival does not mark the end of such medical problems. Beyond the 5-year time point, survivors are also at greater risk than their siblings of developing new onset of medical conditions including: endocrine complications (Hazard Ratio [HR] 19.8, 95% CI 14.5-27.1), neurologic complications (HR 5.6, 95% CI 4.8-6.7), and any condition (HR 6.4, 5.4-7.5).
Considering the multi-modality therapy CNS survivors receive, assessing the independent role of radiotherapy in development of late endocrine effects is difficult due to multiple confounding factors. Gurney et. al. showed that CNS survivors who had surgery alone had a lower risk for developing hypothyroidism (RR 0.3, 95% CI 0.2-0.7) and growth hormone deficiency (RR 0.2, 95% CI 0.1-0.5), compared to survivors who received surgery and radiation therapy.24
RT to the hypothalamic-pituitary axis was also demonstrated to be associated with an increased risk for short stature (ht <10th
percentile of population norms).25
Notably, almost 40% of CNS tumor survivors had short stature.
Female CNS survivors who received RT are also at increased risk for abnormal timing of menarche.26
A population of 235 survivors diagnosed and treated prior to menarche had higher rates than siblings of both early onset of menarche (before 10 years of age, 11.9% vs. 1%, OR 14.1, 95% CI 7.0-30.9) and delayed menarche (10.6% vs. 1.9%, OR 6.6, 95% CI 3.4-11.4). Those who receive radiation directed at the hypothalamic-pituitary axis had a higher risk for early menarche (OR 3.8, 95% CI 1.2-16.5) than survivors with no radiation exposure. Those who had ≥50 Gy to this axis had an increased risk (OR 6.90, 95% CI 1.46-49.57) for delayed menarche, and this risk was almost doubled in those who additionally received spinal radiation (OR 12.40, 95% CI 2.66-89.64).
Late neurologic conditions are common in this population and continue to increase with time well beyond the 5-year time point. Survivors are at a continued increased risk for new onset of seizures (HR 15.1, 95% CI 10.7-21.2), weakness in arms or legs (HR 12.2, 95% CI 9.1-16.3), blindness (HR 7.5, 95% CI 4.1-13.5), and hearing loss (HR 21.0, 95% CI 12.9-34.2).14
In fact, among the population of survivors who had not had a previous seizure by 5 years from diagnosis, 33% would report a new onset of seizure beyond the 5-year time point. Similarly, 16% would report new onset of blindness. In additional analysis by Packer et. al. those who received more than 50 Gy radiation to the posterior fossa had a higher likelihood of developing hearing impairment (RR 3.7, 95% CI 1.8-7.8) compared to those who received <30 Gy.15
Additionally, radiation dose of ≥30 Gy or more to any cortical region was associated with a two-fold elevated risk of seizure.