Cranial radiotherapy linked to subsequent meningiomas in childhood cancer survivors

The diagnosis of meningioma in childhood cancer survivors exposed to cranial radiotherapy increased risk for neurologic morbidity, according to a cohort study published in Journal of Clinical Oncology.

Diagnosis of subsequent meningiomas appeared linked to higher doses of cranial radiotherapy (CRT), and female survivors diagnosed with cancer at a younger age or exposed to higher radiotherapy doses of were found to be at especially high risk, results showed.

“Importantly, this study demonstrates that survivors with subsequent meningiomas have high rates of neurologic sequalae and increased mortality,” Daniel C. Bowers, MD, a neuro-oncologist in the department of pediatrics at UT Southwestern Medical Center, and colleagues wrote. “Although it has not yet proven to reduce morbidity or mortality, surveillance of cancer survivors who have been exposed to CRT will identify asymptomatic meningiomas and will possibly allow for a reduction in neurologic morbidity.”

Meningiomas and high-grade gliomas are commonly found in the central nervous system among childhood cancer survivors exposed to CRT. Because of the benign nature of most meningiomas, cancer survivors with subsequent meningiomas have higher survival rates than those with subsequent high-grade gliomas.

Researchers examined meningioma-related morbidity and mortality in childhood cancer survivors and the potential benefits derived from periodic screenings.

Among 4,221 survivors of childhood cancer who were exposed to CRT (median age at time of analysis, 32 years), 169 developed 199 subsequent meningiomas (59.2% female).

The primary cancer diagnoses of survivors with subsequent meningiomas (n = 169) were leukemia (58%), CNS tumor (36.1%) and other cancers (5.9%). Of the survivors, 85.2% developed one meningioma and 14.8% developed two or more meningiomas.

Median age at first diagnosis of subsequent meningiomas was 28 years (range, 7-50) and median interval from primary cancer diagnosis to first meningioma was 22 years (range, 5-37; median age at cancer diagnosis, 4 years).

Three percent (n = 5) of subsequent meningiomas were malignant. Of survivors who developed meningioma, 44.3% had received CRT doses of 30 Gy or greater; 42% received doses of 20 Gy to20.9 Gy; and 13.6% received doses of 1.5 Gy to 19 Gy.

Cumulative incidence of subsequent meningiomas was 5.6% (95% CI, 4.7-6.7) by age 40 years after primary diagnosis and 5.8% (95% CI, 4.8-6.8) at 30 years. Incidence was greater among women than men (7% vs. 4.4%).

Cumulative incidence of meningiomas by age 40 years was higher for those who received radiation doses of 20 Gy to 29.9 Gy (6.3%) or 30 or higher Gy (6.2%) than those treated with 1.5 to 19 Gy (3%).

Cancer survivors who were first diagnosed when aged younger than 5 years were more likely to develop subsequent meningiomas by age 40 years (10.4%) than those diagnosed between 5 and 10 years (6.2%), 11 to 15 years (2.7%), and older than 15 years (1.5%).

Female survivors showed an increased risk of meningiomas (HR = 1.7; 95% CI, 1.2-2.3). Higher CRT doses — including doses of 20 Gy to 29.9 Gy (HR = 1.6; 95% CI, 1-2.6) and 30 Gy or greater (HR = 2.6; 95% CI, 1.6-4.2) — also increased risk for meningiomas.

Additionally, 149 survivors diagnosed with subsequent meningiomas reported at least one neurologic sequela beyond 5 years from primary cancer diagnosis, with 56.8% experiencing focal neurologic dysfunction; 53.8% with auditory-vestibular-visual deficits or severe headaches; and 39% with seizures.

An analysis adjusted for sex and CRT dose showed survivors had an increased risk for neurologic sequelae within 6 months of meningioma diagnosis, including risk for seizures (HR = 10; 95% CI, 7-15.3), auditory-vestibular-visual sensory deficits (HR = 2.3; 95% CI, 1.3-4), focal neurologic dysfunction (HR = 4.9; 95% CI, 3.2-7.5) and severe headaches (HR = 3.2; 95% CI, 1.9-5.4).

During a median follow-up of 72 months (range, 3.8-395) after meningioma diagnosis, 22 participants (13%) had died. Six of those deaths were attributed to meningioma.

The 3-year OS after a subsequent meningioma was 95% (95% CI, 90-97) and 5-year OS was 91% (95% CI, 85-95).

“This large cohort study demonstrates that nearly 6% of childhood cancer survivors exposed to CRT will be diagnosed with a meningioma by age 40 years, with no plateau in incidence, and that diagnosis of a meningioma is associated with considerable neurologic sequelae,” Bowers and colleagues wrote. “The study demonstrates that the onset of neurologic morbidity seems to be associated temporally with the diagnosis of a subsequent meningioma ... [and] that childhood cancer survivors diagnosed with subsequent meningiomas have considerable mortality, suggesting a harbinger of future problems.” – by Chuck Gormley

Disclosure: The researchers report no relevant financial disclosures.