Journal of Neuro-Oncology

, Volume 145, Issue 2, pp 301–307 | Cite as

Safety and efficacy of repeat radiosurgery for acromegaly: an International Multi-Institutional Study

  • Clayton E. Alonso
  • Adomas Bunevicius
  • Daniel M. Trifiletti
  • James Larner
  • Cheng-Chia Lee
  • Fu-Yuan Pai
  • Roman Liscak
  • Mikulas Kosak
  • Hideyuki Kano
  • Nathaniel D. Sisterson
  • David Mathieu
  • L. Dade Lunsford
  • Jason P. SheehanEmail author
Clinical Study



Surgical resection is the first line treatment for growth hormone (GH) secreting tumors. Stereotactic radiosurgery (SRS) is recommended for patients who do not achieve endocrine remission after resection. The purpose of this study was to evaluate safety and efficacy of repeat radiosurgery for acromegaly.


Three hundred and ninety-eight patients with acromegaly treated with the Gamma Knife radiosurgery (Elekta AB, Stockholm) were identified from the International Gamma Knife Research Foundation database. Among these, 21 patients underwent repeated SRS with sufficient endocrine follow-up and 18 patients had sufficient imaging follow-up. Tumor control was defined as lack of adenoma progression on imaging. Endocrine remission was defined as a normal IGF-1 concentration while off medical therapy.


Median time from initial SRS to repeat SRS was 5.0 years. The median imaging and endocrine follow-up duration after repeat SRS was 3.4 and 3.8 years, respectively. The median initial marginal dose was 17 Gy, and the median repeat marginal dose was 23 Gy. Of the 18 patients with adequate imaging follow up, 15 (83.3%) patients had tumor control and of 21 patients with endocrine follow-up, 9 (42.9%) patients had endocrine remission at last follow-up visit. Four patients (19.0%) developed new deficits after repeat radiosurgery. Of these, 3 patients had neurologic deficits and 1 patient had endocrine deficit.


Repeat radiosurgery for persistent acromegaly offers a reasonable benefit to risk profile for this challenging patient cohort. Further studies are needed to identify patients best suited for this type of approach.


Gamma Knife radiosurgery Acromegaly Radiosurgery Stereotactic radiosurgery Pituitary adenoma 


Compliance with ethical standards

Conflict of interest

L.D.L. reports stock ownership in Elekta AB.


  1. 1.
    Biller BM, Swearingen B, Zervas NT, Klibanski A (1997) A decade of the Massachusetts General Hospital Neuroendocrine Clinical Center. J Clin Endocrinol Metab 82:1668–1674. CrossRefPubMedGoogle Scholar
  2. 2.
    Shimon I, Melmed S (1998) Management of pituitary tumors. Ann Intern Med 129:472–483. CrossRefPubMedGoogle Scholar
  3. 3.
    Rajasoorya C, Holdaway IM, Wrightson P et al (1994) Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 41:95–102CrossRefGoogle Scholar
  4. 4.
    Giustina A, Chanson P, Bronstein MD et al (2010) A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95:3141–3148. CrossRefPubMedGoogle Scholar
  5. 5.
    Racine MS, Barkan AL (2002) Medical management of growth hormone-secreting pituitary adenomas. Pituitary 5:67–76CrossRefGoogle Scholar
  6. 6.
    Ben-Shlomo A, Melmed S (2008) Acromegaly. Endocrinol Metab Clin North Am 37:101–122, viii. CrossRefGoogle Scholar
  7. 7.
    Donangelo I, Melmed S (2005) Treatment of acromegaly: future. Endocrine 28:123–128. CrossRefPubMedGoogle Scholar
  8. 8.
    Giustina A, Barkan A, Casanueva FF et al (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526–529. CrossRefPubMedGoogle Scholar
  9. 9.
    Katznelson L, Atkinson JLD, Cook DM et al (2011) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly—2011 update. Endocr Pract 17(Suppl 4):1–44CrossRefGoogle Scholar
  10. 10.
    Phan K, Xu J, Reddy R et al (2017) Endoscopic endonasal versus microsurgical transsphenoidal approach for growth hormone-secreting pituitary adenomas-systematic review and meta-analysis. World Neurosurg 97:398–406. CrossRefPubMedGoogle Scholar
  11. 11.
    Katznelson L, Laws ER, Melmed S et al (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99:3933–3951. CrossRefPubMedGoogle Scholar
  12. 12.
    Wilson TJ, McKean EL, Barkan AL et al (2013) Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications. Pituitary 16:459–464. CrossRefPubMedGoogle Scholar
  13. 13.
    Yamada S, Fukuhara N, Oyama K et al (2010) Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly. Neurosurgery 67:949–956. CrossRefPubMedGoogle Scholar
  14. 14.
    Ding D, Mehta GU, Patibandla MR et al (2019) Stereotactic radiosurgery for acromegaly: an International Multicenter Retrospective Cohort Study. Neurosurgery 84:717–725. CrossRefPubMedGoogle Scholar
  15. 15.
    Lee C-C, Vance ML, Xu Z et al (2014) Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab 99:1273–1281. CrossRefPubMedGoogle Scholar
  16. 16.
    Sheehan JP, Pouratian N, Steiner L et al (2011) Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes. J Neurosurg 114:303–309. CrossRefPubMedGoogle Scholar
  17. 17.
    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. Technical note. J Neurosurg 104:157–162. CrossRefPubMedGoogle Scholar
  18. 18.
    Mehta GU, Lonser RR (2017) Management of hormone-secreting pituitary adenomas. Neuro-oncology 19:762–773. CrossRefPubMedGoogle Scholar
  19. 19.
    Grasso LFS, Auriemma RS, Pivonello R, Colao A (2015) Adverse events associated with somatostatin analogs in acromegaly. Expert Opin Drug Saf 14:1213–1226. CrossRefPubMedGoogle Scholar
  20. 20.
    Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ (1996) Octreotide. N Engl J Med 334:246–254. CrossRefPubMedGoogle Scholar
  21. 21.
    van der Lely AJ, Biller BMK, Brue T et al (2012) Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 97:1589–1597. CrossRefPubMedGoogle Scholar
  22. 22.
    Kirkpatrick JP, Soltys SG, Lo SS, et al (2017) The radiosurgery fractionation quandary: single fraction or hypofractionation? Neuro-oncology 19:ii38–ii49. 10.1093/neuonc/now301CrossRefGoogle Scholar
  23. 23.
    Mehta GU, Ding D, Gupta A et al (2018) Repeat stereotactic radiosurgery for Cushing’s disease: outcomes of an International, Multicenter Study. J Neurooncol 138:519–525. CrossRefPubMedGoogle Scholar
  24. 24.
    Herman JM, Petit JH, Amin P et al (2004) Repeat gamma knife radiosurgery for refractory or recurrent trigeminal neuralgia: treatment outcomes and quality-of-life assessment. Int J Radiat Oncol Biol Phys 59:112–116. CrossRefPubMedGoogle Scholar
  25. 25.
    Kano H, Kondziolka D, Flickinger JC et al (2012) Stereotactic radiosurgery for arteriovenous malformations, part 3: outcome predictors and risks after repeat radiosurgery. J Neurosurg 116:21–32. CrossRefPubMedGoogle Scholar
  26. 26.
    Kano H, Kondziolka D, Niranjan A et al (2010) Repeat stereotactic radiosurgery for acoustic neuromas. Int J Radiat Oncol Biol Phys 76:520–527. CrossRefPubMedGoogle Scholar
  27. 27.
    Ding D, Starke RM, Sheehan JP (2014) Treatment paradigms for pituitary adenomas: defining the roles of radiosurgery and radiation therapy. J Neurooncol 117:445–457. CrossRefPubMedGoogle Scholar
  28. 28.
    Xu Z, Lee Vance M, Schlesinger D, Sheehan JP (2013) Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery 72(630–637):636–637. CrossRefGoogle Scholar
  29. 29.
    Kondziolka D, Shin SM, Brunswick A et al (2015) The biology of radiosurgery and its clinical applications for brain tumors. Neuro-oncology 17:29–44. CrossRefPubMedGoogle Scholar
  30. 30.
    Sheehan JP, Kavanagh BD, Asher A, Harbaugh RE (2016) Inception of a national multidisciplinary registry for stereotactic radiosurgery. J Neurosurg 124:155–162. CrossRefPubMedGoogle Scholar
  31. 31.
    Liao H-I, Wang C-C, Wei K-C et al (2014) Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus. J Clin Neurosci 21:111–115. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Clayton E. Alonso
    • 1
  • Adomas Bunevicius
    • 2
  • Daniel M. Trifiletti
    • 3
  • James Larner
    • 1
  • Cheng-Chia Lee
    • 4
  • Fu-Yuan Pai
    • 4
  • Roman Liscak
    • 5
  • Mikulas Kosak
    • 6
  • Hideyuki Kano
    • 7
  • Nathaniel D. Sisterson
    • 7
  • David Mathieu
    • 8
  • L. Dade Lunsford
    • 7
  • Jason P. Sheehan
    • 9
    Email author
  1. 1.Department of Radiation OncologyUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of NeurosurgeryUniversity of VirginiaCharlottesvilleUSA
  3. 3.Department of Radiation OncologyMayo ClinicJacksonvilleUSA
  4. 4.School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  5. 5.Department of Stereotactic and Radiation NeurosurgeryNa Homolce HospitalPragueCzech Republic
  6. 6.3rd Department of Medicine, First Faculty of MedicineCharles UniversityPragueCzech Republic
  7. 7.Department of Neurological SurgeryUniversity of PittsburghPittsburghUSA
  8. 8.Division of Neurosurgery, Centre de Recherche du CHUSUniversity of SherbrookeSherbrookeCanada
  9. 9.University of VirginiaCharlottesvilleUSA

Personalised recommendations