Pituitary Disorders
Fractionated Stereotactic Radiotherapy as an Adjuvant Therapy for Pituitary Adenomas
Camilla Schalin-Jäntti Senior Endocrinologist, Division of Endocrinology, Department of Medicine, Helsinki University Hospital
Abstract
Pituitary adenomas characterised by excessive growth or hormonal overproduction despite surgical and medical interventions are a treatment challenge. This article discusses fractionated stereotactic radiotherapy (FSRT) as an adjuvant treatment for pituitary adenomas. Previously, management largely depended on conventional radiotherapy (RT). RT is effective but induces irradiation of surrounding healthy tissues, which has raised safety concerns. With the introduction of modern high-precision stereotactic techniques, irradiation of surrounding tissues can be avoided. The dose can be delivered in one (stereotactic radiosurgery) or several fractions (FSRT). While the use of radiosurgery is restricted to smaller tumours located away from the optic chiasm and nerves, there are no such restrictions for FSRT. FSRT provides an efficient and safe option for pituitary adenomas refractory to conventional treatments. The results seem to be at least as good as those achieved with RS but no direct comparison of these two techniques is yet available.
Keywords Pituitary adenoma, acromegaly, giant prolactinoma, Cushing’s disease, radiotherapy (RT), fractionated steroetactic radiotherapy (FSRT)
Disclosure: The author has no conflicts of interest to declare. Received: 11 August 2010 Accepted: 17 September 2010 Citation: European Endocrinology, 2010;6(2):42–4 Correspondence: Camilla Schalin-Jäntti, Division of Endocrinology, Department of Medicine, University of Helsinki, PO Box 340, FIN-00290 Helsinki, Finland. E:
camilla.schalin-jantti@
hus.fi
Surgery is first-line therapy for functioning pituitary adenomas (FPAs) and non-functioning pituitary macroadenomas (NFPAs) apart from prolactinomas. About 30% of NFPAs recur within five to 10 years1
and up
to 60% of FPAs are still biochemically active after surgery.2–4 Somatostatin analogues and/or the growth hormone (GH)-receptor antagonist pegvisomant are often needed to achieve disease control in acromegaly. Pegvisomant is highly effective but does not control tumour growth. Currently, for residual Cushing’s disease, medical treatment can only partly control excess cortisol. Dopamine agonists are first-line therapy for prolactinomas as they efficiently control both tumour size and hypersecretion. Operative treatment of large macroprolactinomas is frequently associated with complications.5,6
Pituitary adenomas that grow or are hormonally active despite surgical and medical interventions are a treatment challenge. If possible, which often is the case when located within the sella, recurrent or residual tumours are re-operated on. Management has otherwise largely depended on conventional radiotherapy (RT). With RT, long-term tumour control is excellent, while the effects on hormonal overproduction are less consistent and may take several years to become apparent.7–10
RT induces irradiation of surrounding healthy tissues, which is a safety concern. Hypopituitarism is seen in up to 50%10,11
of patients
and there is increased risk of optic nerve damage, blindness, cerebrovascular disease, secondary brain tumours and dementia.12–14 It has been indicated that excess mortality in acromegaly could be related not only to poor disease control but also to RT.15,16
42
This has resulted in renewed interest in RT as a treatment option for pituitary adenomas. Localised irradiation is achieved by shaping the radiation beams to conform to the tumour shape, which spares more surrounding healthy tissues.10
With the development of modern high-precision (i.e. stereotactic) techniques, irradiation of surrounding healthy tissues can be avoided.9,10
Immobilisation, imaging and treatment delivery is improved compared to conventional RT.
Stereotactic irradiation can be given in one single fraction, called radiosurgery (RS), using a multiheaded cobalt unit (gamma knife RS) or a linear accelerator (Linac RS). Alternatively, it can be given in several fractions using a linear accelerator, called fractionated stereotactic radiotherapy (FSRT).10
The use of RS is restricted to smaller tumours
located away from the optic chiasm and nerves, in contrast to FSRT. The use of FSRT as adjuvant therapy for different pituitary adenomas in terms of possible adverse effects and efficacy is discussed in this article.
Effects of Fractionated Stereotactic Radiotherapy Acute and Late Adverse Effects
Only mild grade I acute adverse effects have been described with the use of FSRT. These may occur in up to 67% of patients.17
They include
headache, transient local hair loss at the beam entrance site, taste/smell sensation, tiredness, eye-irritation, visual sensation, nausea and allergy to the fixation mask.17,18
No clinically apparent late
adverse effects associated with conventional RT – such as neurocognitive dysfunction, cerebrovascular morbidity, mortality or secondary brain tumours – have so far been reported after FSRT.17,18 date, there are only a few studies that have systematically investigated
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