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Original article

Vol. 151 No. 2526 (2021)

Gamma Knife surgery for recurrent or persistent Cushing disease: long-term results and evaluation of biological effective dose in a series of 26 patients

DOI
https://doi.org/10.4414/smw.2021.20520
Cite this as:
Swiss Med Wkly. 2021;151:w20520
Published
21.06.2021

Summary

INTRODUCTION

Here we report long-term results after stereotactic radiosurgery (SRS) with Gamma Knife (GKRS) for Cushing disease. We further evaluated the potential role of the biological effective dose (BED) in the cure of this disease.

METHODS

A retrospective review of a prospectively collected database (n = 26) was undertaken at Lille University Hospital, France. The mean follow-up period was 66 months (median 80, range 19–108). The mean marginal prescribed dose was 28.5 Gy (median 27.5, range 24–35) and the mean BED was 208.5 Gy2.47 (median 228.1, range 160–248). We divided patients with endocrine remission into a high BED group (160–228 Gy2.47, n = 6) and a low BED group (228–248 Gy2.47, n = 12).

RESULTS

Eighteen (69.2%) patients had endocrine remission in the absence of any pharmacological therapy after a mean of 36 months (median 24, range 6–98). The actuarial probability of endocrine remission was 59% at 3 years and 77.6% at 7 years, which remained stable up to 10 years. There was a tendency to a higher overall probability of biological remission associated with higher BED values (77% versus 66% at last follow-up), although this did not reach statistical significance. Of note, the numbers of patients reflecting this actuarial probability at 12, 24, 36, 51 and 96 months were 21, 15, 11, 7 and 3, respectively. Tumour control was achieved in all cases (mean decrease in size for patients experiencing one was 29.4%, range 0–100%). Seven patients developed new pituitary insufficiency after GKRS.

CONCLUSONS

Gamma Knife radiosurgery offers high rates of tumour control and endocrine remission on a long-term basis for ACTH-secreting pituitary adenomas. In this small series, higher BED values appeared to be associated with better endocrine remission rates. Owing to the limited sample size, such results should be validated in a larger cohort.

References

  1. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367(9522):1605–17. doi:.https://doi.org/10.1016/S0140-6736(06)68699-6
  2. Pivonello R, De Leo M, Cozzolino A, Colao A. The Treatment of Cushing’s Disease. Endocr Rev. 2015;36(4):385–486. doi:.https://doi.org/10.1210/er.2013-1048
  3. Steffensen C, Bak AM, Zøylner Rubeck KZ, Jørgensen JO. Epidemiology of Cushing’s syndrome. Neuroendocrinology. 2010;92(Suppl 1):1–5. doi:.https://doi.org/10.1159/000314297
  4. Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, et al. Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab. 2004;89(12):6348–57. doi:.https://doi.org/10.1210/jc.2003-032180
  5. Patil CG, Prevedello DM, Lad SP, Vance ML, Thorner MO, Katznelson L, et al. Late recurrences of Cushing’s disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab. 2008;93(2):358–62. doi:.https://doi.org/10.1210/jc.2007-2013
  6. Beauregard C, Dickstein G, Lacroix A. Classic and recent etiologies of Cushing’s syndrome: diagnosis and therapy. Treat Endocrinol. 2002;1(2):79–94. doi:.https://doi.org/10.2165/00024677-200201020-00002
  7. Ciric I, Zhao JC, Du H, Findling JW, Molitch ME, Weiss RE, et al. Transsphenoidal surgery for Cushing disease: experience with 136 patients. Neurosurgery. 2012;70(1):70–80, discussion 80–1. doi:.https://doi.org/10.1227/NEU.0b013e31822dda2c
  8. Porterfield JR, Thompson GB, Young WF, Jr, Chow JT, Fryrear RS, van Heerden JA, et al. Surgery for Cushing’s syndrome: an historical review and recent ten-year experience. World J Surg. 2008;32(5):659–77. doi:.https://doi.org/10.1007/s00268-007-9387-6
  9. Castinetti F, Brue T. Radiothérapie et radiochirurgie des adénomes hypophysaires [Radiotherapy and radiosurgery of pituitary adenomas]. Presse Med. 2009;38(1):133–9. Article in French. doi:.https://doi.org/10.1016/j.lpm.2008.09.012
  10. Castinetti F, Morange I, Dufour H, Regis J, Brue T. Radiotherapy and radiosurgery in acromegaly. Pituitary. 2009;12(1):3–10. doi:.https://doi.org/10.1007/s11102-007-0078-y
  11. Castinetti F, Brue T. Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat? Discov Med. 2010;10(51):107–11.
  12. Tritos NA, Biller BM, Swearingen B. Management of Cushing disease. Nat Rev Endocrinol. 2011;7(5):279–89. doi:.https://doi.org/10.1038/nrendo.2011.12
  13. Tritos NA, Biller BMK. Medical Management of Cushing Disease. Neurosurg Clin N Am. 2019;30(4):499–508. doi:.https://doi.org/10.1016/j.nec.2019.05.007
  14. Hughes JD, Young WF, Jr, Chang AY, Link MJ, Garces YI, Laack NN, et al. Radiosurgical Management of Patients With Persistent or Recurrent Cushing Disease After Prior Transsphenoidal Surgery: A Management Algorithm Based on a 25-Year Experience. Neurosurgery. 2020;86(4):557–64. doi:.https://doi.org/10.1093/neuros/nyz159
  15. Mehta GU, Ding D, Patibandla MR, Kano H, Sisterson N, Su YH, et al. Stereotactic Radiosurgery for Cushing Disease: Results of an International, Multicenter Study. J Clin Endocrinol Metab. 2017;102(11):4284–91. doi:.https://doi.org/10.1210/jc.2017-01385
  16. Pollock BE, Young WF, Jr. Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy. Int J Radiat Oncol Biol Phys. 2002;54(3):839–41. doi:.https://doi.org/10.1016/S0360-3016(02)02975-9
  17. Shepard MJ, Mehta GU, Xu Z, Kano H, Sisterson N, Su YH, et al. Technique of Whole-Sellar Stereotactic Radiosurgery for Cushing Disease: Results from a Multicenter, International Cohort Study. World Neurosurg. 2018;116:e670–9. doi:.https://doi.org/10.1016/j.wneu.2018.05.067
  18. Minniti G, Clarke E, Scaringi C, Enrici RM. Stereotactic radiotherapy and radiosurgery for non-functioning and secreting pituitary adenomas. Rep Pract Oncol Radiother. 2016;21(4):370–8. doi:.https://doi.org/10.1016/j.rpor.2014.09.004
  19. Jones B, Hopewell JW. Modelling the influence of treatment time on the biological effectiveness of single radiosurgery treatments: derivation of “protective” dose modification factors. Br J Radiol. 2019;92(1093):20180111.
  20. Jones B, Dale RG, Deehan C, Hopkins KI, Morgan DA. The role of biologically effective dose (BED) in clinical oncology. Clin Oncol (R Coll Radiol). 2001;13(2):71–81.
  21. Millar WT, Hopewell JW, Paddick I, Lindquist C, Nordströn H, Lidberg P, et al. The role of the concept of biologically effective dose (BED) in treatment planning in radiosurgery. Phys Med. 2015;31(6):627–33. doi:.https://doi.org/10.1016/j.ejmp.2015.04.008
  22. Tuleasca C, Paddick I, Hopewell JW, Jones B, Millar WT, Hamdi H, et al. Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose. World Neurosurg. 2020;134:e204–13. doi:.https://doi.org/10.1016/j.wneu.2019.10.021
  23. Balossier A, Tuleasca C, Cortet-Rudelli C, Soto-Ares G, Levivier M, Assaker R, et al. Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases. Horumon To Rinsho. 2021;94(3):424–33. doi:.https://doi.org/10.1111/cen.14346
  24. Tuleasca C, Peciu-Florianu I, Leroy HA, Vermandel M, Faouzi M, Reyns N. Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases. J Neurosurg. 2020. Online ahead of print. doi:.https://doi.org/10.3171/2020.4.JNS201250
  25. Messerer M, Daniel RT, Cossu G. No doubt: the invasion of the cavernous sinus is the limiting factor for complete resection in pituitary adenomas. Acta Neurochir (Wien). 2019;161(4):717–8. doi:.https://doi.org/10.1007/s00701-018-03784-2
  26. Pollock BE, Link MJ, Leavitt JA, Stafford SL. Dose-volume analysis of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Neurosurgery. 2014;75(4):456–60, discussion 460. doi:.https://doi.org/10.1227/NEU.0000000000000457
  27. Mampalam TJ, Tyrrell JB, Wilson CB. Transsphenoidal microsurgery for Cushing disease. A report of 216 cases. Ann Intern Med. 1988;109(6):487–93. doi:.https://doi.org/10.7326/0003-4819-109-6-487
  28. Sheehan JM, Lopes MB, Sheehan JP, Ellegala D, Webb KM, Laws ER, Jr. Results of transsphenoidal surgery for Cushing’s disease in patients with no histologically confirmed tumor. Neurosurgery. 2000;47(1):33–6, discussion 37–9.
  29. Alexandraki KI, Kaltsas GA, Isidori AM, Storr HL, Afshar F, Sabin I, et al. Long-term remission and recurrence rates in Cushing’s disease: predictive factors in a single-centre study. Eur J Endocrinol. 2013;168(4):639–48. doi:.https://doi.org/10.1530/EJE-12-0921
  30. Hassan-Smith ZK, Sherlock M, Reulen RC, Arlt W, Ayuk J, Toogood AA, et al. Outcome of Cushing’s disease following transsphenoidal surgery in a single center over 20 years. J Clin Endocrinol Metab. 2012;97(4):1194–201. doi:.https://doi.org/10.1210/jc.2011-2957
  31. Chandler WF, Schteingart DE, Lloyd RV, McKeever PE, Ibarra-Perez G. Surgical treatment of Cushing’s disease. J Neurosurg. 1987;66(2):204–12. doi:.https://doi.org/10.3171/jns.1987.66.2.0204
  32. Patil CG, Veeravagu A, Prevedello DM, Katznelson L, Vance ML, Laws ER, Jr. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery. 2008;63(2):266–70, discussion 270–1. doi:.https://doi.org/10.1227/01.NEU.0000313117.35824.9F
  33. Friedman RB, Oldfield EH, Nieman LK, Chrousos GP, Doppman JL, Cutler GB, Jr, et al. Repeat transsphenoidal surgery for Cushing’s disease. J Neurosurg. 1989;71(4):520–7. doi:.https://doi.org/10.3171/jns.1989.71.4.0520
  34. Plotz CM, Knowlton AI, Ragan C. The natural history of Cushing’s syndrome. Am J Med. 1952;13(5):597–614. doi:.https://doi.org/10.1016/0002-9343(52)90027-2
  35. Castinetti F, Nagai M, Morange I, Dufour H, Caron P, Chanson P, et al. Long-term results of stereotactic radiosurgery in secretory pituitary adenomas. J Clin Endocrinol Metab. 2009;94(9):3400–7. doi:.https://doi.org/10.1210/jc.2008-2772
  36. Cordeiro D, Xu Z, Mehta GU, Ding D, Vance ML, Kano H, et al. Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study. J Neurosurg. 2018. Online ahead of print. doi:.https://doi.org/10.3171/2018.5.JNS18509
  37. Jagannathan J, Yen CP, Pouratian N, Laws ER, Sheehan JP. Stereotactic radiosurgery for pituitary adenomas: a comprehensive review of indications, techniques and long-term results using the Gamma Knife. J Neurooncol. 2009;92(3):345–56. doi:.https://doi.org/10.1007/s11060-009-9832-5
  38. Lee CC, Chen CJ, Yen CP, Xu Z, Schlesinger D, Fezeu F, et al. Whole-sellar stereotactic radiosurgery for functioning pituitary adenomas. Neurosurgery. 2014;75(3):227–37, discussion 237. doi:.https://doi.org/10.1227/NEU.0000000000000425
  39. Gupta A, Xu Z, Kano H, Sisterson N, Su YH, Krsek M, et al. Upfront Gamma Knife radiosurgery for Cushing’s disease and acromegaly: a multicenter, international study. J Neurosurg. 2019;131(2):532–8. doi:.https://doi.org/10.3171/2018.3.JNS18110
  40. Taylor DG, Janssen A, Ding D, Xu Z, Mehta GU, Liscak R, et al. Whole Sella vs Targeted Stereotactic Radiosurgery for Acromegaly: A Multicenter Matched Cohort Study. Neurosurgery. 2020;86(5):656–64. doi:.https://doi.org/10.1093/neuros/nyz245
  41. Leavitt JA, Stafford SL, Link MJ, Pollock BE. Long-term evaluation of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2013;87(3):524–7. doi:.https://doi.org/10.1016/j.ijrobp.2013.06.2047
  42. Tuleasca C, Leroy HA, Régis J, Levivier M. Gamma Knife radiosurgery for cervical spine lesions: expanding the indications in the new era of Icon. Acta Neurochir (Wien). 2016;158(11):2235–6. doi:.https://doi.org/10.1007/s00701-016-2962-6
  43. Fowler JF. 21 years of biologically effective dose. Br J Radiol. 2010;83(991):554–68. doi:.https://doi.org/10.1259/bjr/31372149
  44. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med. 1998;339(20):1426–33. doi:.https://doi.org/10.1056/NEJM199811123392003

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