Characteristic of Tumor Regrowth After Gamma Knife Radiosurgery and Outcomes of Repeat Gamma Knife Radiosurgery in Nonfunctioning Pituitary Adenomas

Abstract

Objective: This study aimed to report the characteristic of tumor regrowth after gamma knife radiosurgery (GKRS) and outcomes of repeat GKRS in nonfunctioning pituitary adenomas (NFPAs).

Design and methods: This retrospective study consisted of 369 NFPA patients treated with GKRS. The median age was 45.2 (range, 7.2-84.0) years. The median tumor volume was 3.5 (range, 0.1-44.3) cm³.

Results: Twenty-four patients (6.5%) were confirmed as regrowth after GKRS. The regrowth-free survivals were 100%, 98%, 97%, 86% and 77% at 1, 3, 5, 10 and 15 year, respectively. In multivariate analysis, parasellar invasion and margin dose (<12 Gy) were associated with tumor regrowth (hazard ratio [HR] = 3.125, 95% confidence interval [CI] = 1.318-7.410, p = 0.010 and HR = 3.359, 95% CI = 1.347-8.379, p = 0.009, respectively). The median time of regrowth was 86.1 (range, 23.2-236.0) months. Previous surgery was associated with tumor regrowth out of field (p = 0.033). Twelve patients underwent repeat GKRS, including regrowth in (n = 8) and out of field (n = 4). Tumor shrunk in seven patients (58.3%), remained stable in one (8.3%) and regrowth in four (33.3%) with a median repeat GKRS margin dose of 12 (range, 10.0-14.0) Gy. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.

Conclusions: Parasellar invasion and tumor margin dose (<12 Gy) were independent risk factors for tumor regrowth after GKRS. Repeat GKRS might be effective on tumor control for selected patients. For regrowth in field due to relatively insufficient radiation dose, repeat GKRS might offer satisfactory tumor control. For regrowth out of field, preventing regrowth out of field was the key management. Sufficient target coverage and close follow-up might be helpful.

Keywords: aggressive; gamma knife; nonfunctioning; pituitary adenoma; radiosurgery; regrowth.

Figure 1

A 13-year-old boy with NFPA (max diameter of 7.6 cm) received adjuvant GKRS (10 Gy/35%) after subtotal resection and repeat GKRS (12 Gy/35%) for tumor regrowth at 36.5 months after prior GKRS. (A) contrast-enhanced coronal T1-weighted magnetic resonance imaging (MRI) scans showed residual giant NFPA after surgical resection. (B) MRI showed tumor shrinkage at 24.6 months after GKRS. (C) MRI showed tumor regrowth at 37.9 months after prior GKRS. (D) MRI showed tumor shrinkage at 10.1 months after repeat GKRS. (E) MRI showed tumor shrinkage at 68.8 months after repeat GKRS. (F) MRI showed tumor shrinkage at 205.0 months after repeat GKRS.

Figure 2

A 43-year-old male patient with residual NFPA after surgical resection received GKRS and developed tumor regrowth out of field at 71 months after GKRS. (A) contrast-enhanced coronal T1-weighted magnetic resonance imaging (MRI) scans showed pituitary adenoma. (B) MRI showed subtotal resection for pituitary adenoma after 3.5 months. (C) Dose distribution of adjuvant GKRS after surgical resection. (D) MRI showed tumor regrowth was either in the sellar as well as in the cavernous sinus out of field.

Figure 3

Kaplan–Meier curve of tumor regrowth-free survival.

Figure 4

Kaplan–Meier curve of tumor regrowth-free survival of parasellar invasion (p = 0.000).

Figure 5

Kaplan–Meier curve of tumor regrowth-free survival of tumor margin dose ≥12 Gy vs. <12 Gy. Tumor margin dose <12 Gy showed a lower tumor regrowth-free survival rate (p = 0.000).

Figure 6

Kaplan-Meier curve of tumor control for the 12 patients who undergoing repeat GKRS. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.