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Pituitary Adenomas

Pituitary Adenomas. Chien Wei OMS IV September 14, 2006. Overview. Background Clinical Presentation Classification Is it beneficial to give RT after transsphenoidal resection How much time post-RT should pt. be followed? Is there benefit to GKS? General Management Complications.

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Pituitary Adenomas

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  1. Pituitary Adenomas Chien Wei OMS IV September 14, 2006

  2. Overview • Background • Clinical Presentation • Classification • Is it beneficial to give RT after transsphenoidal resection • How much time post-RT should pt. be followed? • Is there benefit to GKS? • General Management • Complications

  3. Anatomy • 60 mg midline structure in sella turcica • Bordered by diaphragma sellae, tuberculum sellae, dorsum sellae, lateral sinuses, and sphenoid sinuses • Anterior and posterior lobes

  4. Function • Anterior Lobe: • FSH • LH • ACTH • TSH • Prolactin • GH • Posterior Lobe: • ADH • Oxytocin

  5. Epidemiology • Etiology is unknown • Not associated with environmental factors • 10-15% of all primary brain tumors • 20-25% of pituitary glands at autopsy found to have adenomas • 70% of adenomas are endocrinogically secreting • 25% of those with MEN-I develop pituitary adenomas

  6. Natural History • Pituitary adenomas have long natural history • Vary in size and direction of spread • Microadenomas < 10 mm – may cause focal bulging • Macroadenomas > 10 mm – cause problems due to mass effect

  7. Clinical Presentation • Most common are endocrine abnormalities – hyper-/hyposecretion of ant. pituitary hormones • HA • Vision changes – bitemporal hemianopsia and superior temporal defects

  8. Endocrine-Active Pituitary Adenomas • Prolactin – Amenorrhea, galactorrhea, impotence • Growth hormone – Gigantism and acromegaly • Corticotropin – Cushing’s disease, Nelson’s syndrome post adrenalectomy • TSH - Hyperthyroidism

  9. Non-functioning Adenomas • 25-30 % of patients do not have classical hypersecretory syndromes • May grow to a large size before they are detected • Present due to mass effect • Visual deficits • HA • Hormone deficiency

  10. Evaluation • MRI • Visual field assessment • Endocrine evaluation • Tests of normal gonadal, thyroid, and adrenal function • Radioimmunoassays – for hormone levels

  11. Classifying • Imaging/surgical classification • Clinical/endocrine – functional vs. nonfunctional • Pathological classification • WHO classification – reconciles the three systems above

  12. Classification • Microadenomas – Grades 0 and I • Macroadenomas – Grades II to IV • Grade 0: Intrapituitary microadenoma with normal sellar appearance • Grade I: Nml-sized sella with asymmetric floor • Grade II: Enlarged sella with an intact floor • Grade III: Localized erosion of sellar floor • Grade IV: Diffuse destruction of floor

  13. Classification • Type A: Tumor bulges into the chiasmatic cistern • Type B: Tumor reaches the floor of the 3rd ventricle • Type C: Tumor is more voluminous with extension into the 3rd ventricle up to the foramen of Monro • Type D: Tumor extends into temporal or frontal fossa

  14. Pathologic Classification • Benign or malignant • Chromophobic – Non-functioning • Basophilic – Cushing’s • Acidophilic - Acromegaly • Mixed

  15. WHO Classification • Five-tiered system • Clinical presentation and secretory activity • Size and invasiveness (e.g. Hardy) • Histology (typical vs. atypical) • Immunohistologic profile • Ultrasturctural subtype

  16. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas • Retrospective study of 411 patients treated with EBRT for pituitary adenomas • Goal is to assess both long-term efficacy and toxicity of conservative surgery and RT in the management of pituitary adenomas M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  17. Method • 252 of 411 pts with non-functioning pituitary adenomas • 131 of 411 pts had functional pituitary adenomas (62 acromegaly, 60 prolactinomas, 7 Cushing’s, 1 TSH, 1 Gn secreting) • 338 had surgical intervention; 11 with complete resection • 187 transfrontal approach, 24 trans-sphenoidal approach, 35 had no surgery • Median f/u of 10.5 yrs M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  18. Radiation Therapy • Post-op RT to prescribed dose of 45-50 Gy in 25-30 fxs delivered at ≤ 1.8Gy/fx • Three-field technique aimed at a target volume encompassing the tumor and a 1-2cm margin • Patient treated in supine position M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  19. Results M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  20. Results • Extent of surgical resection did not correlate with outcome • Relative risk of death compared with normal population was 1.76 (p<0.001) • No prognostic factors for survival were identified • Morbidity of RT was low • 1.5% of pts had assumed radiation induced visual deterioration • Cumulative risk for 2nd brain tumor at 20 yrs was 1.9% M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  21. Conclusions • High tumor control rate and low toxicity in nonfunctional pituitary adenomas suggests that limited surgical approach and post-surgical conventional fractionated EBRT should be the treatment of choice M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

  22. Results of surgery and irradiation or irradiation alone for pituitary adenomas • Retrospective review of all patients with pituitary adenoma treated with RT alone, surgery and RT, or RT following surgical failure Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  23. Methods • 212 patients with pituitary adenoma underwent treatment between 1954 and 1982 • Median f/u was 11.9 yrs • Radiologic evaluation consisted of skull films, angiography, pneumoenchephalography, ventriculgraphy, CT and MRI • 73% had transfrontal approach Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  24. Radiation Therapy Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  25. Radiation Therapy • Most patients treated with parallel-opposed portals • Mean field sizes: 32.1 cm2 for EBRT alone, 45.3 cm2 for surgery and EBRT, and 40.3 cm2 for EBRT for surgical failures • Median dose for all patients is 4967 cGy • Pts receiving EBRT only had a mean dose of 3989 cGy; post-op EBRT 4493 cGy, and 4553 for EBRT salvage of surgical failures Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  26. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  27. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  28. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  29. Conclusion • Overall survival after treatment for all patients is not significantly different from an age, sex, and race matched population • Patients receiving surgery and post-op RT had a greater control of local disease • EBRT salvage of surgical failures is possible • EBRT treatment results in a low complication rate Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

  30. Gamma-Knife Radiosurgery

  31. Gamma knife radiosurgery for pituitary adenomas • Retrospective review of 79 pts treated with GKS for pituitary adenomas • Purpose: To look at the clinical results of GKS and both its efficacy and safety in treatment of pituitary adenomas Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

  32. Methods • 79 of 108 pts treated between 1993 to 1999 with GKS whom f/u exceeded 6 mo. • 56 FAs ( 29 acromegaly, 15 prolactinomas, 12 Cushing’s) and 23 NFAs • Mean age 50.2 yrs (26 y/o – 82 y/o) • 49 female and 30 male • Mean tumor vol. 7.1 cm3 Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

  33. Radiosurgical Treatment • 40 pts (24 FAs and 16 NFAs) underwent pre-GKS surgical resection • Mean margin dose – 22.5 Gy (FA 24.2 Gy, NFA 19.5) • Highest possible isodose (50-70%) used • Mean f/u period of 26.4 months • Tumor control= decreasing or unchanged tumor vol. • Endocrinologic improvement=fall in elev. hormone level Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

  34. Results • Tumor control – 93.6% (NFA 95.6%, FA 92.8%) • Tumor shrinkage – 24.1% (NFA 26.1%, FA 23.2%) • Endocrinological improvement – 80.3% • Endocrinological normalization – 30.3% • 5/6 pts with preexisting visual field showed improvement • 3 pts. developed complications Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

  35. Conclusion • Tumor growth control results achieved with GKS is similar to those for fractionated RT • GKS may produce better results than conventional RT in tx of pituitary adenoma produced endocrinopathies • GKS seems to be safer than fractionated RT in terms of complications Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

  36. Pituitary Adenoma: The efficacy of RT as the sole treatment • Retrospective study of 29 patients with nonfunctional or prolactin secreting macroadenomas • Tumor dose – 4500 cGy in 4-5 wks • Tumor controlled in 93% of pts • Conclusion: RT is effective for improving vision and can normalize hyperprolactinemia • Doses need not exceed 4500 cGy in 25 fxs Rush SC, Newall J., Int J Radiat Oncol Biol Phys 1989; 17:165

  37. General Management • Pituitary adenoma management is complex and is dictated by size, symptoms, and character of tumor • Treatment options require multiple modalities, including: Surgery, RT, SRS, and medical management

  38. General Management • Multidisciplinary approach • Goals: • Define tumor extent • Evaluate hormone activity • Remove tumor mass • Control hypersecretion • Correct endocrine deficiencies

  39. General Management • Microadenomas: transsphenoidal surgery or RT • Macoradenomas: initial surgery with post-op RT • Medical Management • Bromocriptine • Somatostatin

  40. Treatment Algorithm Pre-treatment MRI Close to Chiasm? yes no Visual field testing Surgery EBRT SRS/gamma-knife Deficit no yes Surgery Surgery EBRT

  41. Appropriate for GKS

  42. Contraindication for GKS

  43. RT Dosing Guidelines

  44. Complications • Hypopituitarism • Vision loss • Carcinogenic • Radiation necrosis • Cerebral Infarction

  45. Future Directions • Profiles of toxicity in the 2-D vs. 3-D era

  46. Thank You • Faculty • Residents

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