Risk of Second Brain Tumor after Conservative Surgery and Radiotherapy for Pituitary Adenoma: Update after an Additional 10 Years

Abstract

We assessed the risk of second brain tumors in a cohort of patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. Four hundred and twenty-six patients (United Kingdom residents) with pituitary adenomas received radiotherapy at the Royal Marsden Hospital (RMH) between 1962 and 1994. They were followed up for 5749 person-years. The cumulative incidence of second intracranial tumors and systemic malignancy was compared with population incidence rates through the Thames Cancer Registry and the National Health Service Central Register (previously OPCS) to record death and the potential causes. Eleven patients developed a second brain tumor, including five meningiomas, four high grade astrocytomas, one meningeal sarcoma, and one primitive neuroectodermal tumor. The cumulative risk of second brain tumors was 2.0% [95% confidence interval (CI), 0.9-4.4%] at 10 yr and 2.4% (95% CI, 1.2-5.0%) at 20 yr, measured from the date of radiotherapy. The relative risk of second brain tumor compared with the incidence in the normal population was 10.5 (95% CI, 4.3-16.7). The relative risk was 7.0 for neuroepithelial and 24.3 for meningeal tumors. The relative risks were 24.2 (95% CI, 4.8-43.5), 2.9 (95% CI, 0-8.5), and 28.6 (95% CI, 0.6-56.6) during the intervals 5-9, 10-19, and more than 20 yr after radiotherapy (four cases occurred >20 yr after treatment). There was no evidence of excess risk of second systemic malignancy. An additional 10-yr update confirmed our previous report of an increased risk of second brain tumors in patients with pituitary adenoma treated with surgery and radiotherapy. The 2.4% risk at 20 yr remains low and should not preclude the use of radiotherapy as an effective treatment option. However, an increased risk of second brain tumors continues beyond 20 and 30 yr after treatment.

Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: a study of 142 patients

“…However, although radiotherapy is clearly effective in preventing recurrence/regrowth in this setting (5-7, 11, 31, 42, 43) (Table 4), its place in the management of patients with pituitary tumors is controversial. Indeed, radiotherapy, at least when delivered with conventional modalities, carries a risk of hypopituitarism, secondary brain tumors, stroke, and possibly neurocognitive or neuropsychological impairment (13,17,44). We observed no neurological adverse effects in this series, likely because conformational fractionated irradiation was used in the majority of cases.…”

“…However, even after complete or near complete surgical resection, NFMAs regrow in 12-58% of patients within 5 years (5)(6)(7)(8), and medical therapy with dopamine agonists or somatostatin analogs has a variable and often limited impact on the risk of recurrence (9). Some centers consider immediate postoperative radiation therapy in an attempt to prevent tumor regrowth (6,(10)(11)(12), but this approach carries a risk of complications such as hypopituitarism (13), cerebrovascular disease (14,15), potential neurocognitive dysfunction (16), and a low but welldocumented long-term risk of secondary intracranial tumors (17).…”

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

“…Second brain tumors have been described long before exposure (2-30 years) in 2.4% of cases (Minniti et al 2005b). The prevalence of cerebrovascular accidents increases with time from exposure: 4% at 5 years, 11% at 10 years, and 21% at 20 years (Brada et al 1999).…”

Safety aspects of GH replacement

“…Therefore, the results of some studies suggest that other forms of cancer may be associated with pituitary tumours and/or its treatment independent of GH status. Furthermore, there is also evidence that surgery of pituitary tumours followed by radiotherapy can increase the risk of secondary brain tumours independent of GH status (87,88).…”