Studies conducted investigation into the parameters of Gamma Knife radiosurgery (GKS) in their research. They found that tumor volume played a significant role in predicting tumor progression after GKS, especially when comparing patients with lesions smaller than 5 cm³ to smaller to those with larger lesions exceeding 5 cm³. Moreover, their research identified patients with suprasellar extension as being at heightened risk of tumor progression. In terms of treatment dosage, interestingly, marginal doses smaller than 12 Gy had an impact on tumor progression [1].

Acromegaly, a condition marked by excessive secretion GH, is primarily characterized by persistent GH hypersecretion. Many articles reported that while SRS led to tumor control rates ranging from 94% to 100%, the rates of endocrine remission varied widely, from 14% to 74%, and the time to normalization of hormone levels has been reported to vary from 2 to 5 years [6-10]. Several factors contribute to this variability, including GH and insulin-like growth factor (IGF-1) levels, tumor invasion, and margin dose influencing outcome especially depending on how the definition of endocrine remission is defined. Several consensus statements have been proposed to resolve this ambiguity. The Cortina consensus established criteria for defining remission in acromegaly, stipulating that remission occurs when a patient’s random GH level is less than 1 ng/mL or the nadir GH level after an oral glucose tolerance test (OGTT) is less than 0.4 ng/mL, accompanied by the normalization of age- and sex-adjusted IGF-1 levels [11]. In a more recent acromegaly consensus conference, the requirement for a random GH level was omitted, retaining only the criteria of achieving a nadir GH level after OGTT less than 0.4 ng/mL and normalization of IGF-1 levels adjusted for age and sex [12].

Many studies documented the efficacy of SRS in the management of Cushing’s disease, revealing tumor control rates ranging from 83% to 100% and endocrine remission rates between 6% and 81%, and the normalization of hormone levels generally takes about 20 to 22 months [13-19]. Akin to the case of acromegaly, it’s crucial to note the variable approach taken by researchers in defining endocrine remission across these studies. The parameters used to define endocrine remission varied among these studies, with normalization of 24 hours urinary free cortisol being a prevalent criterion [14]. Alternatively, some authors employed serum cortisol or ACTH levels, either independently or in combination with urinary levels [15,16].

In the management of prolactinomas, dopamine agonists (DAs) stand as the cornerstone of treatment due to effectiveness. However, in cases where patients exhibit resistance to DA, TSS become necessary. Additionally, SRS is employed following TSS in instances of tumor recurrence or residual growth. Studies have showed tumor control rates between 86% and 100%. Endocrine remission rates have shown considerable variability, spanning from 5% to 50%, and generally, it takes around 14 and 20 months for PRL levels to normalize post-treatment [20-23], with criteria for defining remission varying across studies. This is likely due to the fact that the level of PRL after treatment varies between institutions and suggests that further discussion is needed.

One significant complication following SRS for PA is delayed hypopituitarism. This endocrine disorder arises from damage to the surrounding healthy pituitary gland or stalk, which are located in close proximity to the PA. Studies report an incidence of hypopituitarism as high as 24.5% following GKS for NFPA after TSS, and to reduce this, radiation dose to the infundibulum is proposed to be a mean dose of 7.56 Gy and a maximum dose of 12.3 Gy [24]. This underscores the critical role of meticulous dosage planning and treatment strategy in minimizing the risk of this adverse effect. Precise targeting that minimizes radiation exposure to the healthy pituitary gland and stalk is crucial. Careful consideration of treatment protocols, including dose fractionation and margins, is essential for effective management and reducing the incidence of delayed hypopituitarism.

While SRS offers a safe and noninvasive treatment for PA, visual complications remain a potential concern. The reported incidence of visual disturbances following SRS is fortunately low, typically less than 1%. However, meticulous treatment planning is essential to minimize this risk. Stringent dose limitations are applied to the optic pathway to safeguard against radiation-induced neuropathy. The maximum tolerated dose to the optic chiasm and optic nerves is generally considered to be 8-10 Gy [25]. Treatment planning software meticulously calculated the radiation distribution to ensure these critical structures remain below this threshold. Additionally, maintaining a safe distance between the tumor margin and optic apparatus is another crucial strategy to mitigate visual complications. Ideally, 1-5 mm should be maintained between the tumor and the optic structures [26]. This buffer zone helps to minimize the radiation dose delivered to the optic nerve. However, in certain cases with anatomical limitations or complex tumor shapes, maintain this ideal distance may not be feasible. Advanced SRS techniques using GKS, such as dynamic shaping (Perfexion^®) and hypofractionated GKS (ICON^®), offer promising solutions for these challenging scenarios. Hypofractionated SRS involves delivering the prescribed dose in fewer, larger fractions, potentially reducing the overall risk of complications compared to conventional fractionation schemes.

In cases where radiation induced necrosis develops, particularly in invasive PA, necrosis can potentially lead to cranial neuropathies. This risk is heightened due to the close proximity of PA to critical structures such as the ICA, cavernous sinus and brain stem. In case of brain stem, the exposure is designed to be less than 15 Gy [27]. Also, minimizing the risk of vascular injury is crucial in SRS for PA. Irradiation of suprasellar extension can cause irradiation of the circle of Willis, and irradiation effect of the ICA should be considered for covering parasellar extension [28]. Irradiation to each artery promotes atherosclerosis, which increases the risk of cerebrovascular accident and stroke. One approach to prevent this is by limiting the radiation coverage to ensure it does not exceed more than 50% of the vessel diameter [29]. Additionally, exceeding a dose of 30 Gy to the ICA should be avoided. Exposure to such high radiation doses can induce a neo-intimal hyperplasia response in smooth muscle cells lining the vessel, potentially leading to vascular injury. While the risk is relatively low, studies have reported that exposure to radiation doses ranging from 15 to 25 Gy may increase the risk of post-radiosurgical stenosis or occlusion in approximately 1% of patients [30]. This highlights the importance of treatment planning to minimize ICA exposure whenever possible.