Original ArticleCyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease
Introduction
Cushing disease (CD) refers to hypercortisolism resulting from an adrenocorticotropic hormone (ACTH)–producing pituitary adenoma and accounts for 70% of cases of Cushing syndrome.1, 2, 3 Approximately 40% of patients have a microadenoma or no visible tumor at presentation.4 The Endocrine Society Clinical Guidelines5 recommend surgery as initial treatment, but failure to achieve surgical remission is common (60% in macroadenomas),6 and patients with recurrent or residual disease often require additional treatment. Adjuvant therapeutic options in both adult and pediatric patients include repeat transsphenoidal (or open) surgery, radiotherapy, medical therapy, and bilateral adrenalectomy.7
Use of stereotactic radiosurgery (SRS) in recurrent or residual CD has increased, but experience is still limited.8, 9 Several small series of patients with CD treated with Gamma Knife (GK) (Elekta AB, Stockholm, Sweden) SRS have reported biochemical remission rates of 17%–87%.10, 11 GK SRS was complicated by hypopituitarism in approximately 30% of patients and optic neuropathy in selected cases.10, 12, 13 CyberKnife (CK) (Accuray Inc., Sunnyvale, California, USA) robotic SRS is a frameless image-guided stereotactic device that was first described by Adler et al.14 in 1997 and is increasingly incorporated into treatment regimens for recalcitrant pituitary tumors. CK appears to be an efficacious adjuvant treatment option in clinically nonfunctioning pituitary adenomas.5 Similar to other forms of SRS, CK may be associated with complications, including visual field deficits and hypopituitarism.13 At the present time, there are virtually no data on outcomes of patients with CD treated with CK. This study aims to review the outcomes and complication profile of the first cohort of patients treated with the CK at Stanford Health Care.
Section snippets
Patient Selection
Following institutional review board approval, a retrospective review of all patients with pituitary adenomas who underwent CK treatment between 2000 and 2016 at Stanford Health Care was performed. This article conforms to the STROBE (STrengthening the Reporting of OBservation studies in Epidemiology) guidelines. Patients met the study inclusion criteria if they had histologically confirmed diagnosis of an ACTH-staining pituitary adenoma, confirmed residual or recurrent tumor based on imaging
Patients
Inclusion criteria were met by 7 patients (2 men and 5 women) with active CD. Age range was 18–67 years (median 35.2 ± 18.7 years) (Table 1). At diagnosis, in addition to typical signs and symptoms of CD, 2 patients (28.5%) presented with visual impairment, and 4 patients (57.1%) presented with headaches. No patients presented with diabetes insipidus. Radiologic evaluation at diagnosis showed an intrasellar location of the tumor in 1 (14.2%) patient, suprasellar extension in 2 (28.6%) patients,
Discussion
In the treatment guidelines for CD, SRS is recommended as a therapeutic option for patients who have failed surgery and/or medical therapy.5 In our initial cohort of patients with CD, we found that CK resulted in biochemical remission in 78% at 5 years in patients who had persistent histologically confirmed CD following initial surgery. This study shows the value of CK as an adjunct treatment in such patients. Only 1 other study has reported the results of CK in 2 patients with CD.20 In this
Conclusions
We described the efficacy and complication profile of CK in the treatment of CD. Our study suggests that CK is a safe and effective treatment for CD, allowing excellent local control and remission of the disease in more than half of patients. The shorter time between surgery and CK appears to result in a higher rate of remission. In this small cohort of patients, biochemical control was achieved without visual complications and only rarely new pituitary deficiency.
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Cited by (20)
Updates in the outcomes of radiation therapy for Cushing's disease
2021, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :The visual defects rate varies from 0 to 1.4% in both CRT and FSRT series with CD patients [11,24]. Hypofractionated SRS (in 2–5 sessions) has been used with success for perioptic tumors, but experience with this method is limited [37]. Clinical case 2 - continued.
Management of Pituitary Adenomas Invading the Cavernous Sinus
2019, Neurosurgery Clinics of North AmericaCyberknife stereotactic treatment of pituitary adenomas: A single center experience using different irradiation schemes and modalities
2019, Interdisciplinary Neurosurgery: Advanced Techniques and Case ManagementCitation Excerpt :In our series of mixed PAs, we achieved a tumor growth control rate of 91.6%. This result is concordant with the current literature that reports an excellent and quite homogenous tumor growth control, ranging from 92.3% to 100% for CK treatment [7–10,12,17–22,26], and from 83.3% to 100% for GK-SRS [6]. It is note of worthy that the two patients showing tumor progression harbored aggressive PAs, bigger than the other ones and extensively invasive.
Therapeutic options after surgical failure in Cushing's disease: A critical review
2019, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :Remission rates of RT are therefore comparable to that of SRS, which is also true for the risk of new hypopituitarism. SRS using Cyberknife was used in seven patients with persistent or recurrent CD with sinus cavernosus invasion, reporting a remission rate 57% and no recurrence after a median follow-up of 4 years and 7 months (55 months) [21]. Recently, in 2017 and 2018 the group around Jason Sheehan from the International Gamma Knife Research Foundation published their results from a large, international and multicenter retrospective analysis for patients with CD treated with Gamma Knife.
Conflict of interest statement: This work was supported by National Institutes of Health Clinical and Translational Science Awards program REDCap grant UL1 TR001085.
Justin M. Moore and Elisa Sala co–first authors.