Radiation treatment strategies for acromegaly.

The high morbidity and mortality associated with acromegaly can be addressed with multiple treatment modalities, including surgery, medicines, and radiation therapy. Radiation was initially delivered through conventional fractionated radiotherapy, which targets a wide area over many treatment sessions and has been shown to induce remission in 50%–60% of patients with acromegaly. However, conventional fractionated radiotherapy takes several years to achieve remission in patients with acromegaly and carries a risk of hypopituitarism that may limit its use. Stereotactic radiosurgery, of which there are several forms, including Gamma Knife surgery, CyberKnife therapy, and proton beam therapy, offers slightly attenuated efficacy but achieves remission in less time and provides more precise targeting of the adenoma with better control of the dose of radiation received by adjacent structures such as the pituitary stalk, pituitary gland, optic chiasm, and cranial nerves in the cavernous sinus. Of the forms of stereotactic radiosurgery, Gamma Knife surgery is the most widely used and, because of its long-term follow-up in clinical studies, is the most likely to compete with medical therapy for first-line adjuvant use after resection. In this review, the authors outline the major modes of radiation therapies in clinical use today, and they critically assess the feasibility of these modalities for acromegaly treatment. Acromegaly is a multisystem disorder that demands highly specialized treatment protocols including neurosurgical and endocrinological intervention. As more efficient forms of pituitary radiation develop, acromegaly treatment options may continue to change with radiation therapies playing a more prominent role.

[1]  M. Weiss Radiosurgery for pituitary adenomas. , 2011, Journal of neurosurgery.

[2]  J. Régis,et al.  Role of stereotactic radiosurgery in the management of pituitary adenomas , 2010, Nature Reviews Endocrinology.

[3]  C. Ronchi,et al.  Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10‐year follow‐up study , 2009, Clinical endocrinology.

[4]  A. Grossman,et al.  Gamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumours not controlled despite conventional radiotherapy. , 2009, European journal of endocrinology.

[5]  M. Connock,et al.  Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation , 2009, BMC endocrine disorders.

[6]  P. Chanson,et al.  Long-term results of stereotactic radiosurgery in secretory pituitary adenomas. , 2009, The Journal of clinical endocrinology and metabolism.

[7]  Steven D Chang,et al.  Non-surgical management of hormone-secreting pituitary tumors , 2009, Journal of Clinical Neuroscience.

[8]  M. Aghi,et al.  Recent advances in the treatment of acromegaly , 2009, Current opinion in endocrinology, diabetes, and obesity.

[9]  C. O'connell,et al.  Outcome of Stereotactic Radiotherapy for Patients with Uncontrolled Acromegaly , 2009, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[10]  J. Romijn,et al.  Cost–effectiveness of lanreotide Autogel® in treatment algorithms of acromegaly , 2009, Expert review of pharmacoeconomics & outcomes research.

[11]  S. Yang,et al.  Outcomes and cost-effectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors , 2009, Journal of Clinical Neuroscience.

[12]  P. Chanson,et al.  Guidelines for acromegaly management: an update. , 2009, The Journal of clinical endocrinology and metabolism.

[13]  W. Joo,et al.  Stereotactic Radiosurgery with the CyberKnife for Pituitary Adenomas. , 2009, Journal of Korean Neurosurgical Society.

[14]  T. Brue ACROSTUDY: Status Update on 469 Patients , 2009, Hormone Research in Paediatrics.

[15]  Tatsuya Kobayashi Long-term results of stereotactic gamma knife radiosurgery for pituitary adenomas. Specific strategies for different types of adenoma. , 2009, Progress in neurological surgery.

[16]  J. Loeffler,et al.  Does radiosurgery have a role in the treatment of acromegaly? , 2008, Nature Clinical Practice Endocrinology &Metabolism.

[17]  A. Franzin,et al.  The role of stereotactic radiotherapy in patients with growth hormone-secreting pituitary adenoma. , 2008, The Journal of clinical endocrinology and metabolism.

[18]  N. Pouratian,et al.  GAMMA KNIFE RADIOSURGERY FOR ACROMEGALY: OUTCOMES AFTER FAILED TRANSSPHENOIDAL SURGERY , 2008, Neurosurgery.

[19]  J. Vandenbroucke,et al.  Mortality in acromegaly: a metaanalysis. , 2008, The Journal of clinical endocrinology and metabolism.

[20]  S. Grottoli,et al.  Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal. , 2008, European Journal of Endocrinology.

[21]  E. Laws Surgery for acromegaly: Evolution of the techniques and outcomes , 2008, Reviews in Endocrine and Metabolic Disorders.

[22]  I. Gibbs,et al.  CyberKnife® Robotic Radiosurgery system for tumor treatment , 2007, Expert review of anticancer therapy.

[23]  J. Petit,et al.  Proton stereotactic radiosurgery in management of persistent acromegaly. , 2007, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[24]  P. Brown,et al.  Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission. , 2007, Journal of neurosurgery.

[25]  F. Thorsen,et al.  Gamma knife stereotactic radiosurgery for acromegaly. , 2007, European journal of endocrinology.

[26]  G. Cantore,et al.  Radiotherapy for nonfunctioning pituitary adenomas: from conventional to modern stereotactic radiation techniques , 2007, Neurosurgical Review.

[27]  O. Dekkers,et al.  Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. , 2007, The Journal of clinical endocrinology and metabolism.

[28]  M. Bronstein,et al.  Treatment of acromegaly: is there still a place for radiotherapy? , 2007, Pituitary.

[29]  Laurence Katznelson,et al.  Efficacy and safety of CyberKnife radiosurgery for acromegaly , 2007, Pituitary.

[30]  J. Régis,et al.  Radiotherapy and radiosurgery in acromegaly , 2007, Pituitary.

[31]  S. Scheib,et al.  Gamma Knife surgery after fractionated radiotherapy for acromegaly. , 2006, Journal of neurosurgery.

[32]  Y. Iwadate,et al.  Gamma Knife surgery for metastatic brain tumors without prophylactic whole-brain radiotherapy: results in 1000 consecutive cases. , 2006, Journal of neurosurgery.

[33]  J. Monson Is There Still a Role for Radiotherapy in Acromegaly? , 2006, Neuroendocrinology.

[34]  J. Vymazal,et al.  Gamma knife radiosurgery for acromegaly – long‐term experience , 2006, Clinical endocrinology.

[35]  Wen-Yuan Lee,et al.  Socioeconomic Costs of Open Surgery and Gamma Knife Radiosurgery for Benign Cranial Base Tumors , 2006, Neurosurgery.

[36]  M. Carson,et al.  Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. , 2006, The Journal of clinical endocrinology and metabolism.

[37]  N. Pouratian,et al.  Stereotactic radiosurgery for pituitary adenomas: a review of the literature and our experience. , 2006, Frontiers of hormone research.

[38]  C. Ersoy,et al.  Outcome of Surgery for Acromegaly Performed by Different Surgeons: Importance of Surgical Experience , 2005, Pituitary.

[39]  P. Chanson,et al.  Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. , 2005, The Journal of clinical endocrinology and metabolism.

[40]  E. Uhl,et al.  Gamma-knife surgery is effective in normalising plasma insulin-like growth factor I in patients with acromegaly. , 2005, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[41]  Michiyasu Suzuki,et al.  Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas. , 2005, Minimally invasive neurosurgery : MIN.

[42]  R. Fahlbusch,et al.  The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'. , 2005, European journal of endocrinology.

[43]  V. Esposito,et al.  The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas , 2005, Clinical endocrinology.

[44]  N. Oyesiku Multimodality treatment of pituitary adenomas. , 2005, Clinical neurosurgery.

[45]  B. Lutz,et al.  The choice of treatment after incomplete adenomectomy in acromegaly: Proton- versus highvoltage radiation , 2005, Acta Neurochirurgica.

[46]  R. Fahlbusch,et al.  Diagnosis and treatment of pituitary tumors , 2004, Current opinion in neurology.

[47]  M. Mayberg,et al.  Gamma Knife Radiosurgery in the Management of Patients with Acromegaly: A Review , 2001, Pituitary.

[48]  G. Noren,et al.  Role of Gamma Knife Radiosurgery in Acromegaly , 1999, Pituitary.

[49]  M. Vance,et al.  Current Status and Future Opportunities for Controlling Acromegaly , 2004, Pituitary.

[50]  B. Wowra,et al.  Gamma-knife irradiation is effective in normalising plasma insulin-like growth factor I in patients with acromegaly , 2003 .

[51]  Jong-Hee Chang,et al.  Radiological and hormonal responses of functioning pituitary adenomas after gamma knife radiosurgery. , 2003, Yonsei medical journal.

[52]  P. Freda How effective are current therapies for acromegaly? , 2003, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[53]  E. Motti,et al.  Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. , 2003, Journal of Clinical Endocrinology and Metabolism.

[54]  E. Laws,et al.  Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach. , 2003, Neurosurgical focus.

[55]  W. Couldwell,et al.  Assessment of long-term remission of acromegaly following surgery. , 2003, Journal of neurosurgery.

[56]  Z. Merza Modern treatment of acromegaly , 2003, Postgraduate medical journal.

[57]  J. Wass Radiotherapy in acromegaly: a protagonists viewpoint , 2003, Clinical endocrinology.

[58]  A. Barkan Radiotherapy in acromegaly: the argument against , 2003, Clinical endocrinology.

[59]  S. Cannavò,et al.  Therapy for the syndromes of GH excess. , 2003, Journal of endocrinological investigation.

[60]  A. Berghold,et al.  Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function. , 2002, Journal of neurosurgery.

[61]  B. Norrving,et al.  Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. , 2002, The Journal of clinical endocrinology and metabolism.

[62]  R. Attanasio,et al.  Failure of radiotherapy in acromegaly. , 2001, European journal of endocrinology.

[63]  P. Epaminonda,et al.  Efficacy of radiotherapy in normalizing serum IGF‐I, acid‐labile subunit (ALS) and IGFBP‐3 levels in acromegaly , 2001, Clinical endocrinology.

[64]  Z. Ram,et al.  Transsphenoidal Surgery for Acromegaly: Endocrinological Follow-up of 98 Patients , 2001, Neurosurgery.

[65]  K. Wheatley,et al.  Association between premature mortality and hypopituitarism , 2001, The Lancet.

[66]  F. Roelfsema,et al.  Ten-year follow-up results of transsphenoidal microsurgery in acromegaly. , 2000, The Journal of clinical endocrinology and metabolism.

[67]  J. Bertherat,et al.  Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center. , 2000, The Journal of clinical endocrinology and metabolism.

[68]  E. Laws,et al.  Pituitary Surgery for the Management of Acromegaly , 2000, Hormone Research in Paediatrics.

[69]  T. Nakajima,et al.  The efficacy of conventional radiation therapy in the management of pituitary adenoma. , 2000, International journal of radiation oncology, biology, physics.

[70]  F. Roelfsema,et al.  Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly. , 2000, The Journal of clinical endocrinology and metabolism.

[71]  S. Wardlaw,et al.  Outcome of radiotherapy for acromegaly using normalization of insulin-like growth factor I to define cure. , 2000, The Journal of clinical endocrinology and metabolism.

[72]  S. Scheib,et al.  Octreotide may act as a radioprotective agent in acromegaly. , 2000, The Journal of clinical endocrinology and metabolism.

[73]  L. Pan,et al.  Radiosurgery for growth hormone-producing pituitary adenomas. , 2000, Journal of neurosurgery.

[74]  J. Sim,et al.  Gamma Knife Radiosurgery for Functioning Pituitary Microadenoma , 1999, Stereotactic and Functional Neurosurgery.

[75]  R. Huh,et al.  Gamma Knife Radiosurgery for Functioning Pituitary Adenomas , 1999, Stereotactic and Functional Neurosurgery.

[76]  K. Takakura,et al.  Gamma Knife Radiosurgery for Pituitary Adenomas , 1999, Stereotactic and Functional Neurosurgery.

[77]  J. Régis,et al.  Short-Term Endocrinological Results after Gamma Knife Surgery of Pituitary Adenomas , 1998, Stereotactic and Functional Neurosurgery.

[78]  B. Rhee,et al.  Four Years’ Experiences in the Treatment of Pituitary Adenomas with Gamma Knife Radiosurgery , 1998, Stereotactic and Functional Neurosurgery.

[79]  G. Bravo,et al.  Pituitary Tumors and Gamma Knife Surgery - Clinical Experience with More Than Two Years of Follow-Up , 1998, Stereotactic and Functional Neurosurgery.

[80]  R. Orlandi,et al.  Scintigraphic imaging of pituitary adenomas: An in vivo evaluation of somatostatin receptors , 1998, Journal of endocrinological investigation.

[81]  D. Torigian,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Octreotide as Primary Therapy for Acromegaly* , 2022 .

[82]  S. Scheib,et al.  Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. , 1998, Journal of neurosurgery.

[83]  J. Régis,et al.  Gamma-Knife Surgery for Secreting Pituitary Adenomas , 1998, Acta Neurochirurgica.

[84]  H. Sandler,et al.  Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. , 1997, The Journal of clinical endocrinology and metabolism.

[85]  Y. G. Park,et al.  Gamma knife surgery in pituitary microadenomas. , 1996, Yonsei medical journal.

[86]  D. Kondziolka,et al.  Stereotactic radiosurgery for pituitary adenomas: imaging, visual and endocrine results. , 1994, Acta neurochirurgica. Supplement.

[87]  U. Plöckinger,et al.  Octreotide long term treatment of acromegaly: effect of drug withdrawal on serum growth hormone/insulin-like growth factor-I concentrations and on serum gastrin/24-hour intragastric pH values. , 1993, The Journal of clinical endocrinology and metabolism.

[88]  J. Ganz,et al.  The effects of Gamma Knife surgery of pituitary adenomas on tumor growth and endocrinopathies. , 1993, Stereotactic and functional neurosurgery.

[89]  M. Phillips,et al.  Heavy-charged-particle radiosurgery of the pituitary gland: clinical results of 840 patients. , 1990, Stereotactic and functional neurosurgery.

[90]  M. Thorén,et al.  Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormone-producing pituitary tumors. , 1991, Neurosurgery.

[91]  J. Lyman,et al.  Delayed sequelae of pituitary irradiation. , 1984, Human pathology.

[92]  J. Arndt,et al.  Gamma irradiation effects on human growth hormone producing pituitary adenoma tissue. An analysis of morphology and hormone secretion in an in vitro model system. , 1982, Acta oto-laryngologica.

[93]  H. Quabbe [Treatment of acromegaly]. , 1982, Deutsche medizinische Wochenschrift.

[94]  R. Welbourn,et al.  Letter: Proton beam therapy for acromegaly. , 1975, British medical journal.

[95]  B. Kliman,et al.  Proton-Beam Therapy of Pituitary Disease , 1974 .

[96]  E HICKMAN,et al.  Pituitary tumors. , 1953, Journal of the National Medical Association.

[97]  L. Leksell The stereotaxic method and radiosurgery of the brain. , 1951, Acta chirurgica Scandinavica.