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Journal of Neuro-Oncology

, Volume 138, Issue 3, pp 519–525 | Cite as

Repeat stereotactic radiosurgery for Cushing’s disease: outcomes of an international, multicenter study

  • Gautam U. Mehta
  • Dale Ding
  • Amitabh Gupta
  • Hideyuki Kano
  • Nathaniel D. Sisterson
  • Nuria Martinez-Moreno
  • Michal Kršek
  • Huai-Che Yang
  • Cheng-Chia Lee
  • Roman Liščák
  • Roberto Martinez-Alvarez
  • L. Dade Lunsford
  • Mary Lee Vance
  • Jason P. SheehanEmail author
Clinical Study

Abstract

Stereotactic radiosurgery (SRS) is frequently used for Cushing’s disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3–9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4–19.1 years). Median margin dose was 20 Gy (range 10.8–35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2–64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

Keywords

Adrenocorticotropic hormone Cushing’s disease Gamma knife Pituitary adenoma Radiosurgery 

Notes

Acknowledgements

We appreciate the assistance of Ms. Linda Baxendell with coordination of data for the International Gamma Knife Research Consortium.

Compliance with ethical standards

Conflict of interest

Dr. Lunsford reports stock ownership in Elekta AB.

References

  1. 1.
    Clayton RN, Raskauskiene D, Reulen RC, Jones PW (2011) Mortality and morbidity in Cushing’s disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab 96:632–642CrossRefPubMedGoogle Scholar
  2. 2.
    Lonser RR, Wind JJ, Nieman LK et al (2013) Outcome of surgical treatment of 200 children with Cushing’s disease. J Clin Endocrinol Metab 98:892–901CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hofmann BM, Hlavac M, Martinez R et al (2008) Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg 108:9–18CrossRefPubMedGoogle Scholar
  4. 4.
    Semple PL, Vance ML, Findling J, Laws ER (2000) Transsphenoidal surgery for Cushing’s disease: outcome in patients with a normal magnetic resonance imaging scan. Neurosurgery 46:553-8-9CrossRefGoogle Scholar
  5. 5.
    Ciric I, Zhao JC, Du H et al (2012) Transsphenoidal surgery for cushing disease: experience with 136 patients. Neurosurgery 70:70–80CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Nieman LK, Biller BMK, Findling JW et al (2015) Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 100:2807–2831CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mehta GU, Lonser RR (2017) Management of hormone-secreting pituitary adenomas. Neuro Oncol 19:762–773PubMedGoogle Scholar
  8. 8.
    Nagesser SK, van Seters AP, Kievit J et al (2000) Long-term results of total adrenalectomy for Cushing’s disease. World J Surg 24:108–113CrossRefPubMedGoogle Scholar
  9. 9.
    Assie G, Bahurel H, Coste J et al (2006) Corticotroph tumor progression after adrenalectomy in Cushing’s disease: a reappraisal of nelson’s syndrome. J Clin Endocrinol Metab 92:172–179CrossRefPubMedGoogle Scholar
  10. 10.
    Estrada J, Boronat M, Mielgo M et al (1997) The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing’s disease. N Engl J Med 336:172–177CrossRefPubMedGoogle Scholar
  11. 11.
    Mehta GU, Ding D, Patibandla MR et al (2017) Stereotactic radiosurgery for Cushing disease: results of an international, multicenter study. J Clin Endocrinol Metab 102:4284–4291.  https://doi.org/10.1210/jc.2017-01385 CrossRefPubMedGoogle Scholar
  12. 12.
    Marks LB, Yorke ED, Jackson A et al (2010) Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 76:S10-9CrossRefPubMedGoogle Scholar
  13. 13.
    Snell JW, Sheehan J, Stroila M, Steiner L (2006) Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. J Neurosurg 104:157–162CrossRefPubMedGoogle Scholar
  14. 14.
    Peduzzi P, Concato J, Feinstein AR, Holford TR (1995) Importance of events per independent variable in proportional hazards regression analysis II. Accuracy and precision of regression estimates. J Clin Epidemiol 48:1503–1510CrossRefPubMedGoogle Scholar
  15. 15.
    Lonser RR, Nieman L, Oldfield EH (2017) Cushing’s disease: pathobiology, diagnosis, and management. J Neurosurg 126:404–417CrossRefPubMedGoogle Scholar
  16. 16.
    Ram Z, Nieman LK, Cutler GB et al (1994) Early repeat surgery for persistent Cushing’s disease. J Neurosurg 80:37–45CrossRefPubMedGoogle Scholar
  17. 17.
    Castinetti F, Guignat L, Giraud P et al (2014) Ketoconazole in cushing’s disease: is it worth a try. J Clin Endocrinol Metab 99:1623–1630CrossRefPubMedGoogle Scholar
  18. 18.
    Daniel E, Aylwin S, Mustafa O et al (2015) Effectiveness of metyrapone in treating Cushing’s syndrome: a retrospective multicenter study in 195 patients. J Clin Endocrinol Metab 100:4146–4154CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Colao A, Petersenn S, Newell-Price J et al (2012) A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366:914–924CrossRefPubMedGoogle Scholar
  20. 20.
    Cifarelli CP, Schlesinger DJ, Sheehan JP (2012) Cranial nerve dysfunction following Gamma Knife surgery for pituitary adenomas: long-term incidence and risk factors. J Neurosurg 116:1304–1310CrossRefPubMedGoogle Scholar
  21. 21.
    Lee C-C, Vance ML, Xu Z et al (2014) Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab 99:1273–1281CrossRefPubMedGoogle Scholar
  22. 22.
    Lee CC, Chen CJ, Yen CP et al (2014) Whole-sellar stereotactic radiosurgery for functioning pituitary adenomas. Neurosurgery 75:227–237CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gautam U. Mehta
    • 1
    • 2
  • Dale Ding
    • 1
    • 3
  • Amitabh Gupta
    • 1
  • Hideyuki Kano
    • 4
  • Nathaniel D. Sisterson
    • 4
  • Nuria Martinez-Moreno
    • 5
  • Michal Kršek
    • 6
  • Huai-Che Yang
    • 7
  • Cheng-Chia Lee
    • 7
  • Roman Liščák
    • 8
  • Roberto Martinez-Alvarez
    • 5
  • L. Dade Lunsford
    • 4
  • Mary Lee Vance
    • 9
  • Jason P. Sheehan
    • 1
    Email author
  1. 1.Department of NeurosurgeryUniversity of Virginia Medical CenterCharlottesvilleUSA
  2. 2.Department of NeurosurgeryM.D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of NeurosurgeryBarrow Neurological InstitutePhoenixUSA
  4. 4.Department of Neurological SurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA
  5. 5.Department of Functional Neurosurgery and RadiosurgeryRuber International HospitalMadridSpain
  6. 6.Second Department of Medicine, Third Faculty of Medicine of the Charles UniversityFaculty Hospital Kralovske VinohradyPragueCzech Republic
  7. 7.Department of Neurosurgery, Neurological InstituteTaipei Veterans General HospitalTaipeiTaiwan, Republic of China
  8. 8.Department of Stereotactic and Radiation NeurosurgeryNa Homolce HospitalPragueCzech Republic
  9. 9.Department of MedicineUniversity of Virginia Health SystemCharlottesvilleUSA

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