Skip to main content

Advertisement

SpringerLink
Log in

Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new technique with a need for long-term evaluation. The purpose of the study was to evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio 1.12, age 45 (5–65) years] with a pituitary adenoma of 24.5 (9–76) mm including 20 invasive tumors were treated by radiotherapy in fractionated stereotactic conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1 levels were 18 (±14.5) and 632.6 (±339) µg/L, respectively. Indications of FSRT were failure of surgery and drug treatments (n = 30) or contraindication/refusal of surgery (n = 4). Hormonal control was defined by normal age- and sex-adjusted IGF1. Remission was defined by hormonal control after withdrawal of drugs for a minimum of three consecutive months. Data were analyzed in SPSS software with a significance level at p < 0.05. After a mean follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found to be significantly associated to remission in a multivariate Cox regression were lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control was achieved in all patients. Acquired hypopituitarism after radiotherapy was the main side effect reported with a rate of 39 %. FSRT seems to be an effective and well tolerated third-line treatment of acromegaly, particularly adapted to macro adenomas treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. S. Melmed, F.F. Casanueva, A. Klibanski, M. Bronstein, P. Chanson, S.W. Lamberts, C.J. Strasburger, J.A. Wass, A. Giustina, A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16, 294–302 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. A. Mestron, S.M. Webb, R. Astorga, P. Benito, M. Catala, S. Gaztambide, J.M. Gomez, I. Halperin, T. Lucas-Morante, B. Moreno, G. Obiols, P.P. De, C. Paramo, A. Pico, E. Torres, C. Varela, J.A. Vazquez, J. Zamora, M. Albareda, M. Gilabert, Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish acromegaly registry (Registro Espanola de Acromegalia, REA). Eur. J. Endocrinol. 151, 439–446 (2004)

    Article  CAS  PubMed  Google Scholar 

  3. I.M. Holdaway, Excess mortality in acromegaly. Hormon. Res. 68, 166–172 (2007)

    Article  Google Scholar 

  4. O.M. Dekkers, N.R. Biermasz, A.M. Pereira, J.A. Romijn, J.P. Vandenbroucke, Mortality in acromegaly—a metaanalysis. JCEM 93, 61–67 (2008)

    CAS  PubMed  Google Scholar 

  5. P. Chanson, J. Bertherat, A. Beckers, H. Bihan, T. Brue, P. Caron, O. Chabre, M. Cogne, C. Cortet-Rudelli, B. Delemer, H. Dufour, R. Gaillard, M. Gueydan, I. Morange, J.C. Souberbielle, A. Tabarin, Club Français De L’hypophyse (French Pituitary Club), Société Française d’Endocrinologie (French Endocrinology Society), French Consensus on the management of acromegaly. Ann. Endocrinol. 70, 92–106 (2009)

    Article  CAS  Google Scholar 

  6. S. Melmed, A. Colao, A. Barkan, M. Molitch, A.B. Grossman, D. Kleinberg, D. Clemmons, P. Chanson, E. Laws, J. Schletche, M.L. Vance, K. Ho, A. Giustina, Guidelines for acromegaly management: an update. JCEM 94, 1509–1517 (2009)

    CAS  PubMed  Google Scholar 

  7. J.P. Monson, Is there still a role for radiotherapy in acromegaly? Neuroendocrinology 83, 269–273 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. S. Melmed, F. Casanueva, F. Cavagnini, P. Chanson, L.A. Frohman, R. Gaillard, E. Ghigo, K. Ho, P. Jaquet, D. Kleinberg, S. Lambers, E. Laws, G. Lombardi, M.C. Sheppard, M. Thorner, M.L. Vance, J.A. Wass, A. Giustina, Consensus statement: medical management of acromegaly. Eur. J. Endocrinol. 153, 737–740 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. P.J. Jenkins, P. Bates, M.N. Carson, P.M. Stewart, J.A. Wass, Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. JCEM 91, 1239–1245 (2006)

    CAS  PubMed  Google Scholar 

  10. F. Castinetti, J. Regis, H. Dufour, T. Brue, Role of stereotactic radiosurgery in the management of pituitary adenomas. Nat. Rev. Endocrinol. 6, 214–223 (2010)

    Article  PubMed  Google Scholar 

  11. D.S. Kong, J.I. Lee, H. Lim do, K.W. Kim, H.J. Shin, D.H. Nam, K. Park, J.H. Kim, The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution. Cancer 110, 854–860 (2007)

    Article  PubMed  Google Scholar 

  12. J. Jagannathan, J.P. Sheehan, N. Pouratian, E.R. Laws Jr, L. Steiner, M.L. Vance, Gamma knife radiosurgery for acromegaly: outcomes after failed transsphenoidal surgery. Neurosurgery 62, 1262–1270 (2008)

    Article  PubMed  Google Scholar 

  13. S.A. Imran, I.G. Fleetwood, C.M. O’Connell, T. Ransom, L.A. Mulroy, E. Ur, D.B. Clarke, Outcome of stereotactic radiotherapy for patients with uncontrolled acromegaly. Can. J. Neurol. Sci. 36, 468–474 (2009)

    Article  PubMed  Google Scholar 

  14. G. Minniti, M.-L. Jaffrain-Rea, M. Osti, V. Esposito, A. Santoro, F. Solda, P. Gargiulo, G. Tamburrano, R.M. Enrici, The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas. Clin. Endocrinol. 62, 210–216 (2005)

    Article  Google Scholar 

  15. C. Schöfl, H. Franz, M. Grussendorf, J. Honegger, C. Jaursch-Hancke, B. Mayr, J. Schopohl, Long-term outcome in patients with acromegaly: analysis of 1344 patients from the German Acromegaly Register. Eur. J. Endocrinol. 168, 39–47 (2013)

    Article  PubMed  Google Scholar 

  16. B.K. Roberts, D.L. Ouyang, S.P. Lad, S.D. Chang, G.R. Harch IV, J.R. Adler Jr, G.S. Soltys, I.C. Gibbs, I. Katznelson, Efficacy and safety of Cyberknife radiosurgery for acromegaly. Pituitary 10, 19–25 (2007)

    Article  CAS  PubMed  Google Scholar 

  17. L. Steiner, C. Lindquist, M. Steiner, Radiosurgery, in Advances and technical standards in neurosurgery, ed. by L. Symon, et al. (Springer, New York, 1992), pp. 18–102

    Google Scholar 

  18. S.L. Stafford, B.E. Pollock, J.A. Leavitt, R.L. Foote, P.D. Brown, M.J. Link, D.A. Gorman, P.J. Schomberg, A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 55, 1177–1181 (2003)

    Article  PubMed  Google Scholar 

  19. M.T. Selch, A. Gorgulho, S.P. Lee, C. Mattozo, T.D. Solberg, N. Agazaryan, A.A.F. De Salles, Stereotactic radiotherapy for the treatment of pituitary adenomas. Minim. Invasive. Neurosurg. 49, 150–155 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. G. Minniti, C. Scaringi, D. Amelio, R. Maurizi Enrici, Stereotactic irradiation of GH-secreting pituitary adenomas. Int. J. Endocrinol. (2012). doi:10.1155/2012/482861

    PubMed Central  PubMed  Google Scholar 

  21. G. Minniti, D.C. Gilbert, M. Brada, Modern techniques for pituitary radiotherapy. Rev. Endocr. Metab. Dis. 10, 135–144 (2009)

    Article  CAS  Google Scholar 

  22. C.C. Lee, M.L. Vance, Z. Xu, C.P. Yen, D. Schlesinger, B. Dodson, J. Sheehan, Stereotactic radiosurgery for acromegaly. JCEM 99, 1273–1281 (2014)

    CAS  PubMed  Google Scholar 

  23. R. Attanasio, P. Epaminonda, E. Motti, E. Giugni, L. Ventrella, R. Cozzi, M. Farabola, P. Loli, P. Beck-Peccoz, M. Arosio, Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. JCEM 88, 3105–3112 (2003)

    CAS  PubMed  Google Scholar 

  24. F. Castinetti, D. Taeib, J.M. Kuhn, P. Chanson, M. Tamura, P. Jaquet, B. Conte-Devolx, J. Régis, H. Dufour, T. Brue, Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. JCEM 90, 4483–4488 (2005)

    CAS  PubMed  Google Scholar 

  25. F. Castinetti, M. Nagai, I. Morange, H. Dufour, P. Caron, P. Chanson, C. Cortet-Rudelli, J.M. Kuhn, B. Conte-Devolx, J. Regis, T. Brue, Long-term results of stereotactic radiosurgery in secretory pituitary adenomas. JCEM 94, 3400–3407 (2009)

    CAS  PubMed  Google Scholar 

  26. A. Colao, R.S. Auriemma, R. Pivonello, M. Galdiero, G. Lombardi, Medical consequences of acromegaly: what are the effects of biochemical control? Rev Endocr. Metab. Disord. 9, 21–31 (2008)

    Article  CAS  PubMed  Google Scholar 

  27. R. Trepp, R. Everts, C. Stettler, S. Fischli, S. Allemann, S.M. Webb, E.R. Christ, Assessment of quality of life in patients with uncontrolled versus controlled acromegaly using the acromegaly quality of life questionnaire. Clin. Endocrinol. 63, 103–110 (2005)

    Article  Google Scholar 

  28. G. T’Sjoen, M. Bex, D. Maiter, B. Velkeniers, R. Abs, Health-related quality of life in acromegalic subjects: data from AcroBel, the Belgian registry on acromegaly. Eur. J. Endocrinol. 157, 411–417 (2007)

    Article  PubMed  Google Scholar 

  29. R. Kauppinen-Makelin, T. Sane, A. Reunanen, M.J. Valimaki, L. Niskanen, H. Markkanen, E. Loyttyniemi, T. Ebeling, P. Jaatinen, H. Laine, A nationwide survey of mortality in acromegaly. JCEM 90, 4081–4086 (2005)

    PubMed  Google Scholar 

  30. P. Colin, N. Jovenin, B. Delemer, J. Caron, H. Grulet, A.C. Hecart, C. Lukas, A. Bazin, M.H. Bernard, B. Sherpereel, P. Peruzzi, I. Nakib, C. Redon, P. Rousseaux, Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients. Int. J. Radiat. Oncol. Biol. Phys. 62, 333–341 (2005)

    Article  PubMed  Google Scholar 

  31. S. Roug, A.K. Rassmussen, M. Juhler, M. Kosteljanetz, L. Poulsgaard, H. Heebøll, H. Roed, U. Feldt-Rasmussen, Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit. Eur. J. Endocrinol. 162, 468–474 (2010)

    Article  Google Scholar 

  32. G. Minniti, D. Traish, S. Ashley, A. Gonsalves, M. Brada, Fractionated stereotactic conformal radiotherapy for secreting and non-secreting pituitary adenoma. Clin. Endocrinol. 64, 542–548 (2006)

    Article  CAS  Google Scholar 

  33. S. Milker-Zabel, A. Zabel, P. Huber, W. Schlegel, M. Wannenmacher, J. Debus, Stereotactic conformal radiotherapy in patients with growth hormone-secreting pituitary adenoma. Int. J. Rad. Oncol. Biol. Phys. 59, 1088–1096 (2004)

    Article  Google Scholar 

  34. B.E. Pollock, J.T. Jacob, P.D. Brown, T.B. Nippoldt, Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission. J. Neurosurg. 106, 833–838 (2007)

    Article  CAS  PubMed  Google Scholar 

  35. S.J. Neggers, A.J. Van der Lely, Somatostatin analog and pegvisomant combination therapy for acromegaly. Nat. Rev. Endocrinol 5, 546–552 (2009)

    Article  CAS  PubMed  Google Scholar 

  36. I. Hodish, A. Barkan, Long-term effects of pegvisomant in patients with acromegaly. Nat. Clin. Pract. Endocrinol. Metab. 4, 324–332 (2008)

    CAS  PubMed  Google Scholar 

  37. K.H. Darzy, S.M. Shalet, Hypopituitarism following radiotherapy. Pituitary 12, 40–50 (2009)

    Article  PubMed  Google Scholar 

  38. G. Minniti, D. Traish, S. Ashley, A. Gonsalves, M. Brada, Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. JCEM 90, 800–804 (2005)

    CAS  PubMed  Google Scholar 

  39. M. Brada, D. Ford, S. Ashley, J.M. Bliss, S. Crowley, M. Mason, B. Rajan, D. Traish, Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma. BMJ 304, 1343–1346 (1992)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes, and Nutrition, University Hospital of Reims, 51092, Reims, France

    Alpha M. Diallo, Bénédicte Decoudier, Florence Bertoin & Brigitte Delemer

  2. Center of Radiotherapy, Institute of Cancer Courlancy Reims, 51100, Reims, France

    Philippe Colin

  3. Department of Neurosurgery, University Hospital of Reims, 51092, Reims, France

    Claude F. Litre & Pascal Rousseaux

  4. Depatment of Endocrinology and Metabolism, University Hospital of Donka, Conakry, Guinea

    Mamadou M. Diallo

  5. Department of Radiology, University Hospital of Reims, 51092, Reims, France

    Brigitte Higel

  6. Department of Anatomy and Pathology, University Hospital of Reims, 51092, Reims, France

    Martine Patey

Authors
  1. Alpha M. Diallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philippe Colin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claude F. Litre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mamadou M. Diallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bénédicte Decoudier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Florence Bertoin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brigitte Higel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martine Patey
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pascal Rousseaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Brigitte Delemer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brigitte Delemer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diallo, A.M., Colin, P., Litre, C.F. et al. Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly. Endocrine 50, 741–748 (2015). https://doi.org/10.1007/s12020-015-0610-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0610-1

Keywords

Search

Navigation