The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study

View More View Less
  • 1 Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia;
  • 2 Departments of Neurosurgery and Surgery, Chi-Mei Medical Center, Tainan;
  • 3 Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan;
  • 4 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei;
  • 5 School of Medicine, National Yang-Ming University, Taipei, Taiwan;
  • 6 Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo;
  • 7 Department of Neurosurgery, Benha University, Qalubya, Egypt;
  • 8 Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague;
  • 9 Department of Endocrinology and Metabolism, 3rd Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic;
  • 10 Department of Neurological Surgery, University of Pittsburgh, Pennsylvania;
  • 11 Radiosurgery Unit, Hospital Ruber Internacional, Madrid, Spain;
  • 12 Department of Neurosurgery, NYU Langone Health System, New York, New York;
  • 13 Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan;
  • 14 Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio;
  • 15 Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania;
  • 16 Departments of Neurosurgery and
  • 17 Clinical Oncology, Ain Shams University, Cairo; and
  • 18 Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

OBJECTIVE

The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas.

METHODS

This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients’ clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

RESULTS

The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

CONCLUSIONS

In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.

ABBREVIATIONS ACTH = adrenocorticotropic hormone; EBRT = external beam radiotherapy; GH = growth hormone; IRRF = International Radiosurgery Research Foundation; PRL = prolactin; SRS = stereotactic radiosurgery; TSH = thyroxine-stimulating hormone.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Correspondence Jason Sheehan: University of Virginia, Charlottesville, VA. jsheehan@virginia.edu.

INCLUDE WHEN CITING Published online August 2, 2019; DOI: 10.3171/2019.4.JNS183443.

Disclosures Dr. Grills owns stock in and serves on the board of directors for Greater Michigan Gamma Knife and receives funding from Elekta through her institution for non–study-related research. Dr. Lunsford owns stock in Elekta AB and is a consultant for Insightec, DSMB. Dr. Liscak is a consultant for Elekta AB. Dr. Zacharia is a consultant for Medtronic Inc. and serves on the Speakers Bureau for NICO Corp.

  • 1

    Amar AP, Couldwell WT, Chen JC, Weiss MH: Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery. J Neurosurg 97:307314, 2002

    • Search Google Scholar
    • Export Citation
  • 2

    Berinder K, Stackenäs I, Akre O, Hirschberg AL, Hulting AL: Hyperprolactinaemia in 271 women: up to three decades of clinical follow-up. Clin Endocrinol (Oxf) 63:450455, 2005

    • Search Google Scholar
    • Export Citation
  • 3

    Biswas M, Smith J, Jadon D, McEwan P, Rees DA, Evans LM, : Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol (Oxf) 63:2631, 2005

    • Search Google Scholar
    • Export Citation
  • 4

    Brue T, Pellegrini I, Priou A, Morange I, Jaquet P: Prolactinomas and resistance to dopamine agonists. Horm Res 38:8489, 1992

  • 5

    Buchfelder M, Schlaffer S: Surgical treatment of pituitary tumours. Best Pract Res Clin Endocrinol Metab 23:677692, 2009

  • 6

    Cohen-Inbar O, Xu Z, Schlesinger D, Vance ML, Sheehan JP: Gamma Knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary 18:820830, 2015

    • Search Google Scholar
    • Export Citation
  • 7

    Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G: Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 349:20232033, 2003

    • Search Google Scholar
    • Export Citation
  • 8

    Darzy KH, Shalet SM: Radiation-induced growth hormone deficiency. Horm Res 59 (Suppl 1):111, 2003

  • 9

    Dekkers OM, Lagro J, Burman P, Jørgensen JO, Romijn JA, Pereira AM: Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 95:4351, 2010

    • Search Google Scholar
    • Export Citation
  • 10

    Delgrange E, Daems T, Verhelst J, Abs R, Maiter D: Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. Eur J Endocrinol 160:747752, 2009

    • Search Google Scholar
    • Export Citation
  • 11

    Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, : Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 86:52565261, 2001

    • Search Google Scholar
    • Export Citation
  • 12

    Ding D, Mehta GU, Patibandla MR, Lee CC, Liscak R, Kano H, : Stereotactic radiosurgery for acromegaly: an international multicenter retrospective cohort study. Neurosurgery 84:717725, 2019

    • Search Google Scholar
    • Export Citation
  • 13

    dos Santos Nunes V, El Dib R, Boguszewski CL, Nogueira CR: Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis. Pituitary 14:259265, 2011

    • Search Google Scholar
    • Export Citation
  • 14

    Feigl GC, Bonelli CM, Berghold A, Mokry M: Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function. J Neurosurg 97 (5 Suppl):415421, 2002

    • Search Google Scholar
    • Export Citation
  • 15

    Gillam MP, Molitch ME, Lombardi G, Colao A: Advances in the treatment of prolactinomas. Endocr Rev 27:485534, 2006

  • 16

    Hofstetter CP, Shin BJ, Mubita L, Huang C, Anand VK, Boockvar JA, : Endoscopic endonasal transsphenoidal surgery for functional pituitary adenomas. Neurosurg Focus 30(4):E10, 2011

    • Search Google Scholar
    • Export Citation
  • 17

    Ikeda H, Watanabe K, Tominaga T, Yoshimoto T: Transsphenoidal microsurgical results of female patients with prolactinomas. Clin Neurol Neurosurg 115:16211625, 2013

    • Search Google Scholar
    • Export Citation
  • 18

    Izawa M, Hayashi M, Nakaya K, Satoh H, Ochiai T, Hori T, : Gamma knife radiosurgery for pituitary adenomas. J Neurosurg 93 (Suppl 3):1922, 2000

    • Search Google Scholar
    • Export Citation
  • 19

    Kharlip J, Salvatori R, Yenokyan G, Wand GS: Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J Clin Endocrinol Metab 94:24282436, 2009

    • Search Google Scholar
    • Export Citation
  • 20

    Kleinberg DL, Noel GL, Frantz AG: Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. N Engl J Med 296:589600, 1977

    • Search Google Scholar
    • Export Citation
  • 21

    Klibanski A, Greenspan SL: Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N Engl J Med 315:542546, 1986

  • 22

    Kong DS, Lee JI, Lim DH, Kim KW, Shin HJ, Nam DH, : The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution. Cancer 110:854860, 2007

    • Search Google Scholar
    • Export Citation
  • 23

    Kovacs K, Horvath E: Tumors of the pituitary gland, in Atlas of Tumor Pathology (Second Series, Fascicle 21). Washington, DC: Armed Forces Institute of Pathology, 1986

    • Search Google Scholar
    • Export Citation
  • 24

    Landolt AM, Lomax N: Gamma knife radiosurgery for prolactinomas. J Neurosurg 93 (Suppl 3):1418, 2000

  • 25

    Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML: Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 70:145160, 1989

    • Search Google Scholar
    • Export Citation
  • 26

    Melmed S (ed): The Pituitary. London: Elsevier Science, 2016

  • 27

    Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, : Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:273288, 2011

    • Search Google Scholar
    • Export Citation
  • 28

    Molitch ME: Management of medically refractory prolactinoma. J Neurooncol 117:421428, 2014

  • 29

    Morange I, Barlier A, Pellegrini I, Brue T, Enjalbert A, Jaquet P: Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. Eur J Endocrinol 135:413420, 1996

    • Search Google Scholar
    • Export Citation
  • 30

    Oh MC, Aghi MK: Dopamine agonist-resistant prolactinomas. J Neurosurg 114:13691379, 2011

  • 31

    Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, : Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab 93:47214727, 2008

    • Search Google Scholar
    • Export Citation
  • 32

    Pan L, Zhang N, Wang EM, Wang BJ, Dai JZ, Cai PW: Gamma knife radiosurgery as a primary treatment for prolactinomas. J Neurosurg 93 (Suppl 3):1013, 2000

    • Search Google Scholar
    • Export Citation
  • 33

    Petrovich Z, Yu C, Giannotta SL, Zee CS, Apuzzo ML: Gamma knife radiosurgery for pituitary adenoma: early results. Neurosurgery 53:5161, 2003

    • Search Google Scholar
    • Export Citation
  • 34

    Pollock BE, Brown PD, Nippoldt TB, Young WF Jr: Pituitary tumor type affects the chance of biochemical remission after radiosurgery of hormone-secreting pituitary adenomas. Neurosurgery 62:12711278, 2008

    • Search Google Scholar
    • Export Citation
  • 35

    Pollock BE, Nippoldt TB, Stafford SL, Foote RL, Abboud CF: Results of stereotactic radiosurgery in patients with hormone-producing pituitary adenomas: factors associated with endocrine normalization. J Neurosurg 97:525530, 2002

    • Search Google Scholar
    • Export Citation
  • 36

    Pouratian N, Sheehan J, Jagannathan J, Laws ER Jr, Steiner L, Vance ML: Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery 59:255266, 2006

    • Search Google Scholar
    • Export Citation
  • 37

    Roelfsema F, Biermasz NR, Pereira AM: Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary 15:7183, 2012

    • Search Google Scholar
    • Export Citation
  • 38

    Rush S, Donahue B, Cooper P, Lee C, Persky M, Newall J: Prolactin reduction after combined therapy for prolactin macroadenomas. Neurosurgery 28:502505, 1991

    • Search Google Scholar
    • Export Citation
  • 39

    Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E: Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 356:2938, 2007

    • Search Google Scholar
    • Export Citation
  • 40

    Sheehan JP, Pouratian N, Steiner L, Laws ER, Vance ML: Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes. J Neurosurg 114:303309, 2011

    • Search Google Scholar
    • Export Citation
  • 41

    Sheplan Olsen LJ, Robles Irizarry L, Chao ST, Weil RJ, Hamrahian AH, Hatipoglu B, : Radiotherapy for prolactin-secreting pituitary tumors. Pituitary 15:135145, 2012

    • Search Google Scholar
    • Export Citation
  • 42

    Shucart WA: Implications of very high serum prolactin levels associated with pituitary tumors. J Neurosurg 52:226228, 1980

  • 43

    Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA: Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 81:457462, 1986

    • Search Google Scholar
    • Export Citation
  • 44

    Vasilev V, Daly AF, Vroonen L, Zacharieva S, Beckers A: Resistant prolactinomas. J Endocrinol Invest 34:312316, 2011

  • 45

    Verhelst J, Abs R: Hyperprolactinemia: pathophysiology and management. Treat Endocrinol 2:2332, 2003

  • 46

    Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, : Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 84:25182522, 1999

    • Search Google Scholar
    • Export Citation
  • 47

    Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, : Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol 167:651662, 2012

    • Search Google Scholar
    • Export Citation
  • 48

    Wang AT, Mullan RJ, Lane MA, Hazem A, Prasad C, Gathaiya NW, : Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev 1:33, 2012

    • Search Google Scholar
    • Export Citation
  • 49

    Wilson PJ, Williams JR, Smee RI: Single-centre experience of stereotactic radiosurgery and fractionated stereotactic radiotherapy for prolactinomas with the linear accelerator. J Med Imaging Radiat Oncol 59:371378, 2015

    • Search Google Scholar
    • Export Citation
  • 50

    Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G: Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 356:3946, 2007

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 90 90 90
Full Text Views 38 38 38
PDF Downloads 30 30 30
EPUB Downloads 0 0 0