Pituitary adenoma (PA) is a space-occupying tumor that typically arises from the anterior pituitary gland and comprises ~15% of all primary intracranial tumors (1). Although the majority of PA cases are benign, they can occasionally be either invasive, inoperable or non-responsive (2). PA has the potential of causing serious complications long-term due to its compressive effect on the local cranial structure. In addition, functional PA tumors cause hormone hypersecretion, which can have serious clinical implications if left untreated (3). Complications associated with compression and hormonal hypersecretion include blindness, diabetes insipidus, pituitary hormonal deficiency, Cushing syndrome, acromegaly, secondary hyperthyroidism and infertility (4). Recent epidemiological data showed a markedly increasing trend in the prevalence of PA (5). This may be due to recent advancements in diagnostic modalities and incidental finding during imaging (6). PA can be categorized using a number of methods, namely based on size [micro (<1 cm) or macro (>1 cm)] and functionality (secretory or non-secretory) (7).

Several therapeutic options [medical, surgical and radiation therapy (RT)] are available for treating PA (8). However, the type of therapeutic intervention used depends on the size and functional status of the tumor (9). Except prolactinoma which is treated medically with dopamine agonist (cabergoline, bromocriptine), surgical intervention is normally the treatment of choice for all PA (10). In addition, tumor recurrence frequently occurs even after surgery as complete resection is difficult to achieve due to its invasion in local structures such as cavernous sinus, nasopharynx and orbital extension (11,12). Therefore, RT is now being proposed as a viable therapeutic option for postoperative remnant growth or tumor recurrence (13). Conventionally, RT is delivered in multiple fractions with high radiation exposure (45-50, 1.8-2 Gy per fraction) to the PA tumors (14). RT has demonstrated potency in inhibiting PA tumor growth (15). However, RT is also associated with a number of serious side effects, such as hypopituitarism, optic nerve neuropathy, occasionally cerebrovascular events and even second primary brain tumors (15,16).

Therefore, the aim of the present retrospective study was to evaluate the rate of tumor control and the incidence of RT side effects in patients with pituitary macroadenomas.

Pituitary macroadenoma is not acquiescent to complete resection due to its invasive characteristics in the local structure (12,17). Therefore, the majority of patients with incompletely resected tumors are recommended for RT (18). The aim of the present study was to examine the efficacy and toxicity of RT for pituitary macroadenoma. This was achieved by studying the degree of local tumor control, hormonal control rate and complications following RT.

All patients included in the present study had pituitary macroadenoma. Specifically, 59 patients (78.7%) needed RT post-surgery for recurrent/residual tumors, whilst 16 patients (21.3%) received RT without surgery either due to being unresponsive to medical therapy dopamine agonist in case of prolactin secreting PA or not fit for surgery due to comorbidities in case of non-functional PA. Furthermore, local tumor control was achieved in the majority of patients (92% at 6.68 years median follow up) with both functional and nonfunctional tumors. These results are consistent with those previously reported by Langsenlehner et al (19), where the overall local tumor control rate for both functional and non-functional tumors was 95.4% after 15 years.

The effectiveness of RT has been frequently reported to alleviate pathological hormone hypersecretion (19). In the present study, normalization of increased hormone levels after RT was attained in 7 (28%) patients. By contrast, the biochemical remission rate achieved in the present study was lower compared with that reported in previous studies (20,21). This may be due to the shorter median follow up time of 6.68 years. Additionally, the lack of anti-hormonal medication after RT due to financial constraints may be another underlying cause. It has been previously found that for patients undergoing conventional external RT the time required for the raised hormone levels to return to normal is relatively long (median follow up of 5-8 years), thereby necessitating additional antihormonal therapy (20,22).

With regards to toxicity, the most frequently encountered late complication following RT in patients with pituitary macroadenoma is hypopituitarism (23). Pan-hypopituitarism following RT is a gradual process (24). In the present study, panhypopituitarism following RT was observed in 29 (38.7%) patients. These results are in accordance with those previously reported (20,23,25). Only 7 (9.3%) patients developed visual acuity deterioration, which is consistent with the data reported by Wilson et al (26). Furthermore, other complications, such as optic neuropathy, stroke, diabetes insipidus, brain atrophy, cognitive decline and fits, were also observed. Therefore, these data suggested that RT is a relatively safe modality. However, the risk of these complications, except for hypopituitarism, can be reduced further with development of novel stereotactic RT techniques, including stereotactic radiosurgery and fractionated stereotactic RT (15,27). This is because they can deliver high doses of RT to the tumor more precisely with lesser exposure to the adjacent structures (14,26). The present study has the limitation of only assessing complications associated with EBRT, since stereotactic RT was not available in the Centre in the present study.

To conclude, data from the present study showed that local tumor control in non-functional and functional pituitary macroadenoma can be managed well with RT. However, the biochemical control in functional pituitary macroadenoma was not as effective as local tumor control. To optimize the outcome in biochemical control, other treatment modalities may be considered alongside RT.