Abstract
The role of pituitary radiotherapy (RT) in the management of clinically non-functioning pituitary tumors (NFTs) remains controversial. Observational studies suggest that RT is effective in preventing the regrowth of NFT remnants following initial surgical debulking. However, not all tumor remnants will regrow in the absence of pituitary RT. Furthermore there are concerns relating to potential complications of pituitary RT, particularly hypopituitarism and its associated excess mortality. In the absence of any clear consensus guidelines relating to the application of pituitary RT in this setting, the following text sets out to review the evidence base for the efficacy of RT in preventing NFT regrowth and attempts to balance this against the potentially deleterious consequences of pituitary RT. A pragmatic approach is adopted with a view to offering clinically relevant guidance for managing patients with post-operative NFT remnants.
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References
Beclere J. The radiotherapeutic treatment of tumours of the hypophysis, gigantism and acromegaly. Archives of the Roentgen Ray 1909;III:114.
Grant F. Surgical experience with tumours of the pituitary gland. JAMA 1948;136:668-672.
Emmanuel I. Symposium on pituitary tumours: (3) Historical aspects of radiotherapy, present treatment technique, and results. Clin Radiol 1966;17:154-160.
Ray R, Patterson R. Surgical experience with chromophobe adenomas of the pituitary gland. J Neurosurg 1971;34:726-729.
Sheline G. Treatment of nonfunctioning adenomas of the pituitary. Am J Roentgenology 1974;120:553-561.
Ciric I, Mikhael M, Stafford T, Lawson L, Garces R. Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results. J Neurosurg 1983;59:395-401.
Ebersold M, Quasi L, Laws J, Sceithauer B, Randall R. Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 1986;64:713-719.
Chun M, Masko G, Hetelekidis S. Radiotherapy in the treatment of pituitary adenomas. Int J Rad Oncol Biol Phys 1988;15:305-309.
McCollough WM, Marcus R, Jr., Rhoton A, Jr., Ballinger WE, Million RR. Long-term follow-up of radiotherapy for pituitary adenoma The absence of late recurrence after greater than or equal to 4500 cGy. Int J Rad Oncol Biol Phys 1991;21:607-614.
Bradley K, Adams C, Potter C, Wheeler D, Anslow P, Burke C. An audit of selected patients with non-functioning pituitary adenoma treated by transsphenoidal surgery without irradiation. Clin Endocrinol 1994;41:655-659.
Turner HE, Stratton IM, Byrne JV, Adams CBT, Wass JAH. Audit of selected patients with nonfunctioning pituitary adenoms treated without irradiation-a follow-up study. Clin Endocrinol 1999;51:281-284.
Gittoes NJ, Bates AS, Tse W, et al. Radiotherapy for nonfunctioning pituitary tumours. Clin Endocrinol 1998;48:331-337.
Greenman Y, Ouaknine G, Veshchev I, Reider G, II, Segev Y, Stern N. Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: Markers of tumour quiescence and regrowth. Clin Endocrinol (Oxf) 2003;58:763-769.
Snyder PJ. Clinically nonfunctioning pituitary adenomas. Endocrinol Metab Clin North Am 1993;22:163-175.
Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989;70:145-160.
Tsang RW, Brierley JD, Panzarella T, Gospodarowicz MK, Sutcliffe SB, Simpson WJ. Radiation therapy for pituitary adenoma: Treatment outcome and prognostic factors. Int J Rad Oncol Biol Phys 1994;30:557-565.
Nelson P, Goodman M, Flickenger J, Richardson D, Robinson A. Endocrine function in patients with large pituitary tumours treated with operative decompression and radiation therapy. Neurosurg 1989;24:398-400.
Snyder P, Fowble B, Schatz N, Savino P, Gennarelli T. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986;81:457-462.
Brada M, Rajan B, Traish D, et al. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol 1993;38:571-578.
Al-Mefty O, Kersh J, Routh A, Smith R. The long-term side effects of radiation therapy for benign brain tumours in adults. J Neurosur 1990;73:502-512.
Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990;336:285-288.
Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996;81:1169-1172.
Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism [see comments]. Clin Endocrinol 1997;46:75-81.
Bates AS, Bullivant B, Sheppard MC, Stewart PM. Life expectancy following surgery for pituitary tumours. Clin Endocrinol 1999;50:315-319.
Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. Lancet 2001;357:425-431.
Erfurth EM, Bulow B, Hagmar LE. Is vascular mortality increased in hypopituitarism? Pituitary 2000;3:77-81.
Erfurth EM, Bulow B, Svahn-Tapper G, et al. Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. J Clin Endocrinol Metab 2002;87:4892-4899.
Jones A. Radiation oncogenesis in relation to the treatment of pituitarytumours. [Review]. Clin Endocrinol 1991;35:379-397.
Brada M, Ford D, Ashley S, et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br Med J 1992;304:1343-1346.
Bliss P, Kerr GR, Gregor A. Incidence of second brain tumours after pituitary irradiation in Edinburgh 1962-1990. Clinical Oncology (Royal College of Radiologists) 1994;6:361-363.
Tsang RW, Laperriere NJ, Simpson WJ, Brierley J, Panzarella T, Smyth HS. Glioma arising after radiation therapy for pituitary adenoma A report of four patients and estimation of risk. Cancer 1993;72:2227-2233.
Popovic V, Damjanovic S, Micic D, et al. Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group. Clin Endocrinol 1998;49:441-445.
Jones A. Complications of radiotherapy for acromegaly. In: Wass J, <nt>ed.</nt> Treating Acromegaly. Journal of Endocrinology, Bristol 1994:115-125.
Sassolas G, Trouillas J, Treluyer C, Perrin G. Management of nonfunctioning pituitary adenomas. [Review]. Acta Endocrinologica 1993;1:21-26.
Tachibana O, Yamaguchi N, Yamashima T, Yamashita J. Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, Tl-weighted magnetic resonance imaging: Case report. Neurosurg 1990;27:640-643.
Kline LB, Kim JY, Ceballos R. Radiation optic neuropathy. Ophthalmology 1985;92:1118-1126.
Atkinson AB, Allen IV, Gordon DS, et al. Progressive visual failure in acromegaly following external pituitary irradiation. Clin Endocrinol (Oxf) 1979;10:469-479.
Grattan-Smith PJ, Morris JG, Langlands AO. Delayed radiation necrosis of the central nervous system in patients irradiated for pituitary tumours. Journal of Neurology, Neurosurgery & Psychiatry 1992;55:949-955.
Flickinger J, Nelson P, Martinez A, Deutsch M, Taylor F. Radiotherapy of nonfunctional adenomas of the pituitary gland. Cancer 1989;63:2409-2414.
Zierhut D, Flentje M, Adolph J, Erdmann J, Raue F, Wannenmacher M. External radiotherapy of pituitary adenomas. Int J Rad Oncol Biol Phys 1995;33:307-314.
Rush S, Cooper PR. Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas. Int J Rad Oncol Biol Phys 1997;37:1031-1034.
Fisher BJ, Gaspar LE, Noone B. Radiation therapy of pituitary adenoma: Delayed sequelae. Radiology 1993;187:843-846.
McCord MW, Buatti JM, Fennell EM, et al. Radiotherapy for pituitary adenoma: Long-term outcome and sequelae. Int J Rad Oncol Biol Phys 1997;39:437-444.
Breen P, Flickinger JC, Kondziolka D, Martinez AJ. Radiotherapyfor nonfunctionalpituitary adenoma: Analysis of long-term tumor control. J Neurosurg 1998;89:933-938.
Rosen T, Wiren L, Wilhelmsen L, Wildund I, Bengtsson BA. Decreased psychological well-being in adult patients with growth hormone deficiency. Clin Endocrinot 1994;40:111-116.
Peace KA, Orme SM, Padayatty SJ, Godfrey HP, Belchetz PE. Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication. Clin Endocrinol 1998;49:391-396.
Peace KA, Orme SM, Sebastian JP, et al. The effect of treatmentvariables on mood and social adjustment in adult patients with pituitary disease. Clin Endocrinol (Oxf) 1997;46:445-450.
Lillehei KO, Kirschman DL, Kleinschmidt-DeMasters BK, Ridgway EC. Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas. Neurosurg 1998;43:432-438; discussion 438-439.
Grigsby P, Stokes S, Marls J, Simpson J. Prognostic factors and results of radiotherapy alone in the management of pituitary adenoma. Int J Rad Oncol Biol Phys 1988;15:1103-1110.
Giannattasio G, Bassetti M. Human pituitary adenomas. Recent advances in morphological studies. [Review] [158 refs]. J Endocrinol Invest 1990;13:435-454.
Levy A, Hall L, Yeudall WA, Lightman SL. p53 gene mutations in pituitary adenomas: Rare events. Clin Endocrinol 1994;41:809-814.
Knosp E, Kitz K, Perneczky A. Proliferation activity in pituitary adenomas: Measurement by monoclonal antibody Ki-67. Neurosurg 1989;25:927-930.
Hsu DW, Hakim F, Biller BMK. Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg 1993;78:753-761.
Bates A, Farrell W, Bicknell E, et al. Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker. J Clin Endocrinol Metab 1997;82:818-824.
Gittoes NJ, McCabe CJ, Sheppard MC, Franklyn JA. Retinoid X receptor gamma mRNA expression is reduced in recurrent non-functioning pituitary adenomas [letter]. Clin Endocrinol 1998;48:527.
Zhang X, Horwitz GA, Heaney AP, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 1999;84:761-777.
Jackson IM, Noren G. Gamma knife radiosurgery for pituitary tumours. Best Practice & Research Clinical Endocrinology & Metabolism 1999;13:461-469.
Jackson IM, Noren G. Role of gamma knife therapy in the management of pituitary tumors. Endocrinol Metab Clin N Am 1999;28:133-142.
Thoren M, Rahn T, Guo WY, Werner S. Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormone-producing pituitary tumors. Neurosurg 1991;29:663-668.
Degerblad M, Rahn T, Bergstrand G, Thoren M. Long-term results of stereotactic radiosurgery to the pituitary gland in Cushing's disease. Acta Endocrinologica1 986;112:310-314.
Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg 2002;97:408-414.
Wowra B, Stummer W. Efficacy of gamma knife radiosurgery for nonfunctioning pituitary adenomas: A quantitative follow up with magnetic resonance imaging-based volumetric analysis. J Neurosurg 2002;97:429-432.
Fahlbusch R, Ganslandt O, Buchfelder M, Schott W, Nimsky C. Intraoperative magnetic resonance imaging during transsphenoidal surgery. J Neurosurg 2001;95:381-390.
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Gittoes, N.J. Radiotherapy for Non-Functioning Pituitary Tumors—When and Under What Circumstances?. Pituitary 6, 103–108 (2003). https://doi.org/10.1023/B:PITU.0000004801.95086.e2
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DOI: https://doi.org/10.1023/B:PITU.0000004801.95086.e2