Horm Metab Res 2019; 51(12): 755-764
DOI: 10.1055/a-1060-1883
Review
© Georg Thieme Verlag KG Stuttgart · New York

Management of Aggressive Pituitary Tumors – A 2019 Update

Stephan Petersenn
1   ENDOC, Center for Endocrine Tumors, Hamburg, Germany
› Author Affiliations
Further Information

Publication History

received 03 November 2019

accepted 05 November 2019

Publication Date:
11 December 2019 (online)

Abstract

With a prevalence of 80–100/100000, pituitary adenomas are more frequent than thought. The rare aggressive pituitary adenoma presents a special challenge, due to the heterogenous presentation of the disease. The prognosis of aggressive pituitary adenomas has been improved due to recent studies demonstrating some efficacy of chemotherapy with temozolomide. However, there is very limited data on second-line therapies in patients with treatment failure. This review presents an update on the diagnostic and therapeutic management of aggressive pituitary tumors. Patients should be treated by a team consisting of an expert endocrinologist, neurosurgeon, radiation oncologist, and pathologist, and according to the recently published ESE guideline.

 
  • References

  • 1 Lloyd RV, Osamura RY, Klöppel G. et al. World Health Organization Classification of Tumours of Endocrine Organs. World Health Organization. 4th edition Lyons: IARC; 2017
  • 2 Raverot G, Burman P, McCormack A. et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol 2018; 178: G1-G24
  • 3 Saeger W, Ludecke DK, Buchfelder M. et al. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 2007; 156: 203-216
  • 4 DeLellis RA, Lloyd RV, Heitz PU. et al. World Health Organization Classification of Tumours of Endocrine Organs. World Health Organization. 3rd edition Lyons: IARC; 2004
  • 5 Trouillas J, Roy P, Sturm N. et al. A new prognostic clinicopathological classification of pituitary adenomas: A multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 2013; 126: 123-135
  • 6 Knosp E, Steiner E, Kitz K. et al. Pituitary adenomas with invasion of the cavernous sinus space: A magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993; 33: 610-617. Discussion 617
  • 7 Nachtigall LB, Karavitaki N, Kiseljak-Vassiliades K. et al. Physicians’ awareness of gadolinium retention and MRI timing practices in the longitudinal management of pituitary tumors: A “Pituitary Society” survey. Pituitary 2019; 22: 37-45
  • 8 Casanueva FF, Barkan AL, Buchfelder M. et al. Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement. Pituitary 2017; 20: 489-498
  • 9 Saeger W, Honegger J, Theodoropoulou M. et al. Clinical impact of the current WHO classification of pituitary adenomas. Endocr Pathol 2016; 27: 104-114
  • 10 Saeger W, Petersenn S, Schofl C. et al. Emerging histopathological and genetic parameters of pituitary adenomas: Clinical impact and recommendation for future WHO classification. Endocr Pathol 2016; 27: 115-122
  • 11 Miermeister CP, Petersenn S, Buchfelder M. et al. Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun 2015; 3: 50
  • 12 Buchy M, Lapras V, Rabilloud M. et al. Predicting early post-operative remission in pituitary adenomas: evaluation of the modified knosp classification. Pituitary 2019; 22: 467-475
  • 13 Heaney A. Management of aggressive pituitary adenomas and pituitary carcinomas. J Neurooncol 2014; 117: 459-468
  • 14 Barnett GH, Linskey ME, Adler JR. et al. Stereotactic radiosurgery – an organized neurosurgery-sanctioned definition. J Neurosurg 2007; 106: 1-5
  • 15 Ding D, Starke RM, Sheehan JP. Treatment paradigms for pituitary adenomas: Defining the roles of radiosurgery and radiation therapy. J Neurooncol 2014; 117: 445-457
  • 16 Brochier S, Galland F, Kujas M. et al. Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: A study of 142 patients. Eur J Endocrinol 2010; 163: 193-200
  • 17 Chang EF, Zada G, Kim S. et al. Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. J Neurosurg 2008; 108: 736-745
  • 18 Greenman Y, Ouaknine G, Veshchev I. et al. Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: Markers of tumour quiescence and regrowth. Clin Endocrinol (Oxf) 2003; 58: 763-769
  • 19 Noh TW, Jeong HJ, Lee MK. et al. Predicting recurrence of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 2009; 94: 4406-4413
  • 20 Widhalm G, Wolfsberger S, Preusser M. et al. Residual nonfunctioning pituitary adenomas: Prognostic value of MIB-1 labeling index for tumor progression. J Neurosurg 2009; 111: 563-571
  • 21 Edwards AA, Swords FM, Plowman PN. Focal radiation therapy for patients with persistent/recurrent pituitary adenoma, despite previous radiotherapy. Pituitary 2009; 12: 30-34
  • 22 Gittoes NJ. Radiotherapy for non-functioning pituitary tumors–when and under what circumstances?. Pituitary 2003; 6: 103-108
  • 23 Fadul CE, Kominsky AL, Meyer LP. et al. Long-term response of pituitary carcinoma to temozolomide. Report of two cases. J Neurosurg 2006; 105: 621-626
  • 24 Lim S, Shahinian H, Maya MM. et al. Temozolomide: a novel treatment for pituitary carcinoma. Lancet Oncol 2006; 7: 518-520
  • 25 Syro LV, Uribe H, Penagos LC. et al. Antitumour effects of temozolomide in a man with a large, invasive prolactin-producing pituitary neoplasm. Clin Endocrinol (Oxf) 2006; 65: 552-553
  • 26 Ji Y, Vogel RI, Lou E. Temozolomide treatment of pituitary carcinomas and atypical adenomas: Systematic review of case reports. Neuro-Oncol Pract 2016; 3: 188-195
  • 27 Losa M, Mazza E, Terreni MR. et al. Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: Experience in six cases. Eur J Endocrinol 2010; 163: 843-851
  • 28 Bush ZM, Longtine JA, Cunningham T. et al. Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab 2010; 95: E280-E290
  • 29 Raverot G, Sturm N, de Fraipont F. et al. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: A French Multicenter Experience. J Clin Endocrinol Metab 2010; 95: 4592-4599
  • 30 Hirohata T, Asano K, Ogawa Y. et al. DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors. J Clin Endocrinol Metab 2013; 98: 1130-1136
  • 31 Bengtsson D, Schroder HD, Andersen M. et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab 2015; 100: 1689-1698
  • 32 Ceccato F, Lombardi G, Manara R. et al. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: Expertise at a tertiary care center. J Neurooncol 2015; 122: 189-196
  • 33 Bruno OD, Juárez-Allen L, Christiansen SB. et al. Temozolomide therapy for aggressive pituitary tumors: Results in a small series of patients from Argentina. Int J Endocrinol 2015; 1-8
  • 34 Losa M, Bogazzi F, Cannavo S. et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neuro-Oncol 2016; 126: 519-525
  • 35 Lasolle H, Cortet C, Castinetti F. et al. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol 2017; 176: 769-777
  • 36 Jordan JT, Miller JJ, Cushing T. et al. Temozolomide therapy for aggressive functioning pituitary adenomas refractory to surgery and radiation: a case series. Neurooncol Pract 2018; 5: 64-68
  • 37 McCormack A, Dekkers OM, Petersenn S. et al. Treatment of aggressive pituitary tumours and carcinomas: Results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol 2018; 178: 265-276
  • 38 Heaney AP. Clinical review: Pituitary carcinoma: Difficult diagnosis and treatment. J Clin Endocrinol Metab 2011; 96: 3649-3660
  • 39 Kaltsas GA, Mukherjee JJ, Plowman PN. et al. The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors. J Clin Endocrinol Metab 1998; 83: 4233-4238
  • 40 Brabander T, Teunissen JJM, Van Eijck CHJ. et al. Peptide receptor radionuclide therapy of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2016; 30: 103-114
  • 41 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 Trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376: 125-135
  • 42 Acosta-Gómez MJ, Muros MA, Llamas-Elvira JM. et al. The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours. Br J Radiol 2005; 78: 110-115
  • 43 Boni G, Ferdeghini M, Bellina CR. et al. [111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning pituitary adenomas. Q J Nucl Med 1995; 39: 90-93
  • 44 Borson-Chazot F, Houzard C, Ajzenberg C. et al. Somatostatin receptor imaging in somatotroph and non-functioning pituitary adenomas: Correlation with hormonal and visual responses to octreotide. Clin Endocrinol (Oxf) 1997; 47: 589-598
  • 45 Colao A, Lastoria S, Ferone D. et al. The pituitary uptake of (111)In-DTPA-D-Phe1-octreotide in the normal pituitary and in pituitary adenomas. J Endocrinol Invest 1999; 22: 176-183
  • 46 Duet M, Ajzenberg C, Benelhadj S. et al. Somatostatin receptor scintigraphy in pituitary adenomas: A somatostatin receptor density index can predict hormonal and tumoral efficacy of octreotide in vivo. J Nucl Med 1999; 40: 1252-1256
  • 47 Görges R, Cordes U, Engelbach M. et al. [Prediction of pharmacological effect of octreotide in acromegaly by means of 111In-pentetreotide scintigraphy and calculation of a pituitary uptake index]. Nuklearmedizin 1997; 36: 117-124
  • 48 Legovini P, De Menis E, Billeci D. et al. 111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients. J Endocrinol Invest 1997; 20: 424-428
  • 49 Oppizzi G, Cozzi R, Dallabonzana D. et al. Scintigraphic imaging of pituitary adenomas: An in vivo evaluation of somatostatin receptors. J Endocrinol Invest 1998; 21: 512-519
  • 50 Plöckinger U, Reichel M, Fett U. et al. Preoperative octreotide treatment of growth hormone-secreting and clinically nonfunctioning pituitary macroadenomas: Effect on tumor volume and lack of correlation with immunohistochemistry and somatostatin receptor scintigraphy. J Clin Endocrinol Metab 1994; 79: 1416-1423
  • 51 Rieger A, Rainov NG, Elfrich C. et al. Somatostatin receptor scintigraphy in patients with pituitary adenoma. Neurosurg Rev 1997; 20: 7-12
  • 52 Schmidt M, Scheidhauer K, Luyken C. et al. Somatostatin receptor imaging in intracranial tumours. Eur J Nucl Med 1998; 25: 675-686
  • 53 Tofani A, Cucchi R, Pompili A. et al. 111In-octreotide scintigraphy in pituitary adenomas. Q J Nucl Med 1995; 39: 94-97
  • 54 Boy C, Heusner TA, Poeppel TD. et al. 68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: Correlation of sst2 mRNA and SUVmax. Eur J Nucl Med Mol Imaging 2011; 38: 1224-1236
  • 55 Parghane RV, Agrawal K, Mittal BR. et al. 68Ga DOTATATE PET/CT in a rare coexistence of pituitary macroadenoma and multiple paragangliomas. Clin Nucl Med 2014; 39: 91-93
  • 56 d’Amico A, Stąpór-Fudzińska M, Tarnawski R. CyberKnife radiosurgery planning of a secreting pituitary adenoma performed with ⁶⁸Ga DOTATATE PET and MRI. Clin Nucl Med 2014; 39: 1043-1044
  • 57 Xiao J, Zhu Z, Zhong D. et al. Improvement in diagnosis of metastatic pituitary carcinoma by 68Ga DOTATATE PET/CT. Clin Nucl Med 2015; 40: e129-e131
  • 58 Garmes HM, Carvalheira JBC, Reis F. et al. Pituitary carcinoma: A case report and discussion of potential value of combined use of Ga-68 DOTATATE and F-18 FDG PET/CT scan to better choose therapy. Surg Neurol Int 2017; 8: 162
  • 59 Basu S, Ranade R, Hazarika S. 68Ga DOTATATE PET/CT of synchronous meningioma and prolactinoma. Clin Nucl Med 2016; 41: 230-231
  • 60 Gauthé M, Sarfati J, Bourcigaux N. et al. Pituitary adenoma recurrence suspected on central hyperthyroidism despite empty sella and confirmed by 68Ga-DOTA-TOC PET/CT. Clin Nucl Med 2017; 42: 454-455
  • 61 Kim S, Dillon WP, Hope TA. et al. Ectopic thyroid-stimulating hormone-secreting pituitary adenoma of the nasopharynx diagnosed by 68Ga-DOTA-TATE PET/CT. World Neurosurg 2019; 125: 400-404
  • 62 Zhao X, Xiao J, Xing B. et al. Comparison of (68)Ga DOTATATE to 18F-FDG uptake is useful in the differentiation of residual or recurrent pituitary adenoma from the remaining pituitary tissue after transsphenoidal adenomectomy. Clin Nucl Med 2014; 39: 605-608
  • 63 Wang H, Hou B, Lu L. et al. PET/MRI in the diagnosis of hormone-producing pituitary microadenoma: A prospective pilot study. J Nucl Med 2018; 59: 523-528
  • 64 Baldari S, Ferraù F, Alafaci C. et al. First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary 2012; (15) S57-S60
  • 65 Kumar Gupta S, Singla S, Damle NA. et al. Diagnosis of Men-I Syndrome on (68)Ga-DOTANOC PET-CT and role of peptide receptor radionuclide therapy with (177)Lu-DOTATATE. Int J Endocrinol Metab 2012; 10: 629-633
  • 66 Kovacs GL, Goth M, Rotondo F. et al. ACTH-secreting Crooke cell carcinoma of the pituitary. Eur J Clin Invest 2013; 43: 20-26
  • 67 Komor J, Reubi JC, Christ ER. Peptide receptor radionuclide therapy in a patient with disabling non-functioning pituitary adenoma. Pituitary 2014; 17: 227-231
  • 68 Maclean J, Aldridge M, Bomanji J. et al. Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: Variable clinical response in preliminary evaluation. Pituitary 2014; 17: 530-538
  • 69 Novruzov F, Aliyev JA, Jaunmuktane Z. et al. The use of (68)Ga DOTATATE PET/CT for diagnostic assessment and monitoring of (177)Lu DOTATATE therapy in pituitary carcinoma. Clin Nucl Med 2015; 40: 47-49
  • 70 Waligorska-Stachura J, Gut P, Sawicka-Gutaj N. et al. Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: Case report. J Neurosurg 2016; 125: 346-349
  • 71 Giuffrida G, Ferraù F, Laudicella R. et al. Peptide receptor radionuclide therapy for aggressive pituitary tumors: A monocentric experience. Endocr Connect 2019; 8: 528-535
  • 72 Ortiz LD, Syro LV, Scheithauer BW. et al. Anti-VEGF therapy in pituitary carcinoma. Pituitary 2012; 15: 445-449
  • 73 Touma W, Hoostal S, Peterson RA. et al. Successful treatment of pituitary carcinoma with concurrent radiation, temozolomide, and bevacizumab after resection. J Clin Neurosci 2017; 41: 75-77
  • 74 Rotman LE, Vaughan TB, Hackney JR. et al. Long-term survival after transformation of an adrenocorticotropic hormone-secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma. World Neurosurg 2019; 122: 417-423
  • 75 Dutta P, Reddy KS, Rai A. et al. Surgery, octreotide, temozolomide, bevacizumab, radiotherapy, and pegvisomant treatment of an AIP Mutation-Positive Child. J Clin Endocrinol Metab 2019; 104: 3539-3544
  • 76 Jouanneau E, Wierinckx A, Ducray F. et al. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary 2012; 15: 37-43
  • 77 Donovan LE, Arnal AV, Wang SH. et al. Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy. CNS Oncol 2016; 5: 203-209
  • 78 Zhang D, Way JS, Zhang X. et al. Effect of everolimus in treatment of aggressive prolactin-secreting pituitary adenomas. J Clin Endocrinol Metab 2019; 104: 1929-1936
  • 79 Cooper O, Mamelak A, Bannykh S. et al. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors. Endocrine 2014; 46: 318-327
  • 80 Lin AL, Jonsson P, Tabar V. et al. Marked response of a hypermutated acth-secreting pituitary carcinoma to ipilimumab and nivolumab. J Clin Endocrinol Metab 2018; 103: 3925-3930