CNS tumors

The risk of meningioma after radiation increases with radiation dose,[9,61] and in some studies is further potentiated with increased exposure to intrathecal methotrexate.[26] However, this finding has not been consistently replicated.[10]

Cavernomas have also been reported with considerable frequency after CNS irradiation but have been speculated to result from angiogenic processes as opposed to true tumorigenesis.[64-66]

In 6,015 childhood cancer survivors from the LATER cohort, 1,551 of whom had prior cranial radiation therapy, 93 survivors developed meningiomas.

Of these patients, 89 (95.7%) were treated with prior cranial radiation therapy. The median age at diagnosis was 31.8 years (range, 13.2–50.5 years).

Thirty of the survivors presented with synchronous meningiomas, and 84 survivors presented with symptoms. Only 16% of the meningiomas were detected in late effects clinics.

All survivors underwent surgery, and one-third (n = 31) of them also received radiation therapy. Twelve survivors had three or more surgeries for growth of residual tumor, recurrences, and new meningiomas. Although the extent of surgical resection was not described, the indications for radiation therapy during follow-up after surgical resection included residual tumor, recurrences, location, or new meningioma. During follow-up, 38 survivors (40.9%) developed new meningiomas, 22 (23.7%) had recurrences, and at least 4 died because of the meningioma.

In 69,460 survivors, 279 developed gliomas, and 761 developed meningiomas.

Gliomas and meningiomas were most frequently observed after any CNS tumor or leukemia, accounting for more than 70% of all observed gliomas and 80% of all meningiomas.

Among patients with known cranial radiation status who developed a glioma, 61% had received prior cranial radiation therapy. Among patients who developed a meningioma, 64.7% had received cranial radiation therapy.

CNS tumor survivors treated with cranial radiation therapy were at the highest risk of developing gliomas, at 27 times the risk of the general population (95% CI, 21.5–33.2). CNS tumor survivors who did not receive cranial radiation were at 8.3 times the risk of the general population (95% CI, 4.9–14.1).

Among CNS tumor survivors, the relative risk for patients who received cranial radiation therapy was 13 times the risk for patients who did not receive cranial radiation therapy (95% CI, 6.7–25.4). Among leukemia survivors, those who received cranial radiation therapy were at a 5-fold increased risk compared with those treated without cranial radiation therapy (95% CI, 2.9–9.9).

A significant dose-response relationship was reported for CNS subsequent meningiomas (excess relative ratio [ERR]/Gy, 0.44).

Younger age at the time of primary diagnosis was associated with a higher risk of subsequent meningiomas.

Females had a higher risk of subsequent meningiomas than males (odds ratio, 1.46; P < .0001).

Median latency time to the development of meningiomas was 21 years.

At 10 years, eight patients (4.5%) developed a secondary tumor (benign or malignant), with median follow up of 9.1 years. Three patients (1.7%) developed a secondary malignancy.

In-field second malignancies were glioblastoma (n = 2), meningioma (n = 2), and high-grade glioma (n = 1). The other malignancies were one each of ovarian fibroma, plexiform fibromyxoma of the esophagus, and papillary thyroid carcinoma.

Four patients developed brain stem injury at a median of 4.2 years. The 5-year cumulative incidence of brain stem injury was 1.1%, and the 10-year cumulative incidence was 1.9%.