Lack of delayed neurocognitive side effects of Gamma Knife radiosurgery in acromegaly: the Later-Ac study

in European Journal of Endocrinology
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  • 1 Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Marseille, France
  • | 2 Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
  • | 3 Service d’Endocrinologie, Hôpital Larrey, Toulouse, France
  • | 4 Service d’Endocrinologie, CHU de Montpellier, Montpellier, France
  • | 5 Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse and Université Paris-Saclay, Univ. Paris-Sud, Inserm, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Le Kremlin-Bicêtre, France
  • | 6 Department of Neurosurgery, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Timone, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
  • | 7 Santé publique, Faculté de Médecine de Marseille, Marseille, France
  • | 8 Department of Functional Neurosurgery, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Timone, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France

Correspondence should be addressed to F Castinetti; Email: frederic.castinetti@ap-hm.fr

(J Regis and T Brue contributed equally as senior authors)

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Introduction

Persistent growth hormone hypersecretion can be observed in roughly 50% of patients operated for somatotroph adenomas, requiring additional treatments. Despite its proven antisecretory efficacy, the use of Gamma Knife radiosurgery (GK) is limited probably due to the lack of data on long-term side effects, including potential cognitive consequences.

Methods

The LATe Effects of Radiosurgery in Acromegaly study was a cross-sectional exposed/unexposed non-randomized study. The primary objective was to determine the long-term neurocognitive effects of GK focusing on memory, executive functions, and calculation ability. Exposed patients had been treated by GK for acromegaly at least 5 years before inclusion. Unexposed patients (paired for age) had to be cured or controlled at last follow-up without any radiation technique. Patients of both groups were cured or controlled at the last follow-up.

Results

Sixty-four patients were evaluated (27 exposed and 37 unexposed). Mean follow-up after GK was 13 ± 6 years (including 24 patients followed for at least 10 years). While up to 23.8% of the patients of the whole cohort presented at least one abnormal cognitive test, we did not observe any significant difference in neurocognitive function between both groups. During the follow-up, 11 patients presented at least one new pituitary deficiency (P  = 0.009 for thyroid-stimulating hormone deficiency with a higher rate in exposed patients), two presented a stroke (1 in each group), and one presented a meningioma (12 years after GK).

Conclusions

While GK exposes patients to a well-known risk of pituitary deficiency, it does not seem to induce long-term cognitive consequences in patients treated for acromegaly.

 

     European Society of Endocrinology

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  • 1

    Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA & Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2014 99 39333951. (https://doi.org/10.1210/jc.2014-2700)

    • Search Google Scholar
    • Export Citation
  • 2

    Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH, Strasburger CJ, Luger A, Clemmons DR, Giustina A. A consensus statement on acromegaly therapeutic outcomes. Nature Reviews: Endocrinology 2018 14 552561. (https://doi.org/10.1038/s41574-018-0058-5)

    • Search Google Scholar
    • Export Citation
  • 3

    Maione L, Brue T, Beckers A, Delemer B, Petrossians P, Borson-Chazot F, Chabre O, François P, Bertherat J & Cortet-Rudelli C et al.Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry. European Journal of Endocrinology 2017 176 645655. (https://doi.org/10.1530/EJE-16-1064)

    • Search Google Scholar
    • Export Citation
  • 4

    Castinetti F, Nagai M, Morange I, Dufour H, Caron P, Chanson P, Cortet-Rudelli C, Kuhn JM, Conte-Devolx B & Regis J et al.Long-term results of stereotactic radiosurgery in secretory pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 2009 94 34003407. (https://doi.org/10.1210/jc.2008-2772)

    • Search Google Scholar
    • Export Citation
  • 5

    Vik-Mo EO, Oksnes M, Pedersen PH, Wentzel-Larsen T, Rødahl E, Thorsen F, Schreiner T, Aanderud S, Lund-Johansen M. Gamma knife stereotactic radiosurgery for acromegaly. European Journal of Endocrinology 2007 157 255263. (https://doi.org/10.1530/EJE-07-0189)

    • Search Google Scholar
    • Export Citation
  • 6

    Ronchi CL, Attanasio R, Verrua E, Cozzi R, Ferrante E, Loli P, Montefusco L, Motti E, Ferrari DI & Giugni E et al. Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10-year follow-up study. Clinical Endocrinology 2009 71 846852. (https://doi.org/10.1111/j.1365-2265.2009.03589.x)

    • Search Google Scholar
    • Export Citation
  • 7

    Ding D, Mehta GU, Patibandla MR, Lee CC, Liscak R, Kano H, Pai FY, Kosak M, Sisterson ND & Martinez-Alvarez R et al.Stereotactic radiosurgery for acromegaly: an International Multicenter Retrospective Cohort Study. Neurosurgery 2019 84 717725. (https://doi.org/10.1093/neuros/nyy178)

    • Search Google Scholar
    • Export Citation
  • 8

    Jenkins PJ, Bates P, Carson MN, Stewart PM, Wass JA. Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. Journal of Clinical Endocrinology and Metabolism 2006 91 12391245. (https://doi.org/10.1210/jc.2005-1616)

    • Search Google Scholar
    • Export Citation
  • 9

    Castinetti F, Régis J, Dufour H, Brue T. Role of stereotactic radiosurgery in the management of pituitary adenomas. Nature Reviews: Endocrinology 2010 6 214223. (https://doi.org/10.1038/nrendo.2010.4)

    • Search Google Scholar
    • Export Citation
  • 10

    Cordeiro D, Xu Z, Mehta GU, Ding D, Vance ML, Kano H, Sisterson N, Yang HC, Kondziolka D & Lunsford LD et al. Hypopituitarism after gamma knife radiosurgery for pituitary adenomas: a multicenter, international study. Journal of Neurosurgery 2019 131 11881196. (https://doi.org/10.3171/2018.5.JNS18509)

    • Search Google Scholar
    • Export Citation
  • 11

    Stafford SL, Pollock BE, Leavitt JA, Foote RL, Brown PD, Link MJ, Gorman DA, Schomberg PJ. A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery. International Journal of Radiation Oncology, Biology, Physics 2003 55 11771181. (https://doi.org/10.1016/s0360-3016(0204380-8)

    • Search Google Scholar
    • Export Citation
  • 12

    Burman P, van Beek AP, Biller BMK, Camacho-Hübner C, Mattsson AF. Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary/sellar lesions. Journal of Clinical Endocrinology and Metabolism 2017 102 10511058. (https://doi.org/10.1210/jc.2016-3402)

    • Search Google Scholar
    • Export Citation
  • 13

    Ayuk J Does pituitary radiotherapy increase the risk of stroke and, if so, what preventative actions should be taken? Clinical Endocrinology 2012 76 328331. (https://doi.org/10.1111/j.1365-2265.2011.04300.x)

    • Search Google Scholar
    • Export Citation
  • 14

    Tooze A, Gittoes NJ, Jones CA, Toogood AA. Neurocognitive consequences of surgery and radiotherapy for tumours of the pituitary. Clinical Endocrinology 2009 70 503511. (https://doi.org/10.1111/j.1365-2265.2008.03464.x)

    • Search Google Scholar
    • Export Citation
  • 15

    Tooze A, Sheehan JP. Neurocognitive changes in pituitary adenoma patients after gamma Knife radiosurgery. Journal of Neurosurgery 2018 129 5562. (https://doi.org/10.3171/2018.7.GKS181595)

    • Search Google Scholar
    • Export Citation
  • 16

    Reuter F, Baumstarck-Barrau K, Loundou A, Pelletier J, Auquier P. Paced Auditory Serial Addition Test: données normatives dans une population Française. Revue Neurologique 2010 166 944947. (https://doi.org/10.1016/j.neurol.2010.01.018)

    • Search Google Scholar
    • Export Citation
  • 17

    Godefroy O Groupe de Reflexion pour l’Evaluation des Fonctions EXécutives (GREFEX). Fonctions exécutives et pathologies neurologiques et psychiatriques. Evaluation en pratique clinique. Solal, 2008.

    • Search Google Scholar
    • Export Citation
  • 18

    Van der Linden M, Coyette F, Poitrenaud J, Kalafat M, Calicis F, Wyns C, Adam S & GREMEM. L’épreuve de rappel libre, rappel indicé à 16 items. In L’évaluation des troubles de la mémoire Présentation de quatre tests de mémoire épisodique et étalonnage. Solal, 2004.

    • Search Google Scholar
    • Export Citation
  • 19

    Leplège A, Ecosse E, Verdier A, Perneger TV. The French SF-36 Health Survey: translation, cultural adaptation and preliminary psychometric evaluation. Journal of Clinical Epidemiology 1998 51 10131023. (https://doi.org/10.1016/s0895-4356(9800093-6)

    • Search Google Scholar
    • Export Citation
  • 20

    Badia X, Webb SM, Prieto L, Lara N. Acromegaly quality of life questionnaire (AcroQoL). Health and Quality of Life Outcomes 2004 2 13. (https://doi.org/10.1186/1477-7525-2-13)

    • Search Google Scholar
    • Export Citation
  • 21

    Kos D, Kerckhofs E, Carrea I, Verza R, Ramos M, Jansa J. Evaluation of the modified fatigue impact scale in four different European countries. Multiple Sclerosis 2005 11 7680. (https://doi.org/10.1191/1352458505ms1117oa)

    • Search Google Scholar
    • Export Citation
  • 22

    Gaudry E, Vagg P, Spielberger CD. Validation of the state-trait distinction in anxiety research. Multivariate Behavioral Research 1975 10 331341. (https://doi.org/10.1207/s15327906mbr1003_6)

    • Search Google Scholar
    • Export Citation
  • 23

    Beck AT, Beck RW. Screening depressed patients in family practice. A rapid technic. Postgraduate Medicine 1972 52 8185. (https://doi.org/10.1080/00325481.1972.11713319)

    • Search Google Scholar
    • Export Citation
  • 24

    Pertichetti M, Serioli S, Belotti F, Mattavelli D, Schreiber A, Cappelli C, Padovani A, Gasparotti R, Nicolai P & Fontanella MM et al. Pituitary adenomas and neuropsychological status: a systematic literature review. Neurosurgical Review 2020 43 10651078. (https://doi.org/10.1007/s10143-019-01134-z)

    • Search Google Scholar
    • Export Citation
  • 25

    Yedinak CG, Fleseriu M. Self-perception of cognitive function among patients with active acromegaly, controlled acromegaly, and non-functional pituitary adenoma: a pilot study. Endocrine 2014 46 585593. (https://doi.org/10.1007/s12020-013-0106-9)

    • Search Google Scholar
    • Export Citation
  • 26

    Shan S, Fang L, Huang J, Chan RCK, Jia G, Wan W. Evidence of dysexecutive syndrome in patients with acromegaly. Pituitary 2017 20 661667. (https://doi.org/10.1007/s11102-017-0831-9)

    • Search Google Scholar
    • Export Citation
  • 27

    Tiemensma J, Biermasz NR, van der Mast RC, Wassenaar MJE, Middelkoop HAM, Pereira AM, Romijn JA. Increased psychopathology and maladaptive personality traits, but normal cognitive functioning, in patients after long-term cure of acromegaly. Journal of Clinical Endocrinology and Metabolism 2010 95 E392E402. (https://doi.org/10.1210/jc.2010-1253)

    • Search Google Scholar
    • Export Citation
  • 28

    Brummelman P, Koerts J, Dullaart RPF, van den Berg G, Tucha O, Wolffenbuttel BHR, Van Beek AP. Effects of previous growth hormone excess and current medical treatment for acromegaly on cognition. European Journal of Clinical Investigation 2012 42 13171324. (https://doi.org/10.1111/j.1365-2362.2012.02721.x)

    • Search Google Scholar
    • Export Citation
  • 29

    Brummelman P, Sattler MGA, Meiners LC, van den Berg G, van der Klauw MM, Elderson MF, Dullaart RP, Koerts J, Werumeus Buning J & Tucha O et al.Cognition and brain abnormalities on MRI in pituitary patients. European Journal of Radiology 2015 84 295300. (https://doi.org/10.1016/j.ejrad.2014.11.033)

    • Search Google Scholar
    • Export Citation
  • 30

    Lecumberri B, Estrada J, García-Uría J, Millán I, Pallardo LF, Caballero L, Lucas T. Neurocognitive long-term impact of two-field conventional radiotherapy in adult patients with operated pituitary adenomas. Pituitary 2015 18 782795. (https://doi.org/10.1007/s11102-015-0653-6)

    • Search Google Scholar
    • Export Citation
  • 31

    Crouzeix G, Morello R, Thariat J, Morera J, Joubert M, Reznik Y. Quality of life but not cognition is impacted by radiotherapy in patients with non-functioning pituitary adenoma. Hormone and Metabolic Research 2019 51 178185. (https://doi.org/10.1055/a-0850-9448)

    • Search Google Scholar
    • Export Citation
  • 32

    Kunzler LS, Naves LA, Casulari LA. Cognitive-behavioral therapy improves the quality of life of patients with acromegaly. Pituitary 2018 21 323333. (https://doi.org/10.1007/s11102-018-0887-1)

    • Search Google Scholar
    • Export Citation
  • 33

    Kreitschmann-Andermahr I, Buchfelder M, Kleist B, Kohlmann J, Menzel C, Buslei R, Kołtowska-Häggsträm M, Strasburger C, Siegel S. Predictors of quality of life in 165 patients with acromegaly: results from a single-center study. Endocrine Practice 2017 23 7988. (https://doi.org/10.4158/EP161373.OR)

    • Search Google Scholar
    • Export Citation
  • 34

    Lee CK, Lee SR, Cho JM, Yang KA, Kim SH. Therapeutic effect of gamma knife radiosurgery for multiple brain metastases. Journal of Korean Neurosurgical Society 2011 50 179184. (https://doi.org/10.3340/jkns.2011.50.3.179)

    • Search Google Scholar
    • Export Citation