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Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
Pituitary Adenomas
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Pituitary Adenomas

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  • 1. Pituitary Adenomas Chien Wei OMS IV September 14, 2006
  • 2. Overview <ul><li>Background </li></ul><ul><li>Clinical Presentation </li></ul><ul><li>Classification </li></ul><ul><li>Is it beneficial to give RT after transsphenoidal resection </li></ul><ul><li>How much time post-RT should pt. be followed? </li></ul><ul><li>Is there benefit to GKS? </li></ul><ul><li>General Management </li></ul><ul><li>Complications </li></ul>
  • 3. Anatomy <ul><li>60 mg midline structure in sella turcica </li></ul><ul><li>Bordered by diaphragma sellae, tuberculum sellae, dorsum sellae, lateral sinuses, and sphenoid sinuses </li></ul><ul><li>Anterior and posterior lobes </li></ul>
  • 4.  
  • 5.  
  • 6. Function <ul><li>Anterior Lobe: </li></ul><ul><ul><li>FSH </li></ul></ul><ul><ul><li>LH </li></ul></ul><ul><ul><li>ACTH </li></ul></ul><ul><ul><li>TSH </li></ul></ul><ul><ul><li>Prolactin </li></ul></ul><ul><ul><li>GH </li></ul></ul><ul><li>Posterior Lobe: </li></ul><ul><ul><li>ADH </li></ul></ul><ul><ul><li>Oxytocin </li></ul></ul>
  • 7. Epidemiology <ul><li>Etiology is unknown </li></ul><ul><li>Not associated with environmental factors </li></ul><ul><li>10-15% of all primary brain tumors </li></ul><ul><li>20-25% of pituitary glands at autopsy found to have adenomas </li></ul><ul><li>70% of adenomas are endocrinogically secreting </li></ul><ul><li>25% of those with MEN-I develop pituitary adenomas </li></ul>
  • 8. Natural History <ul><li>Pituitary adenomas have long natural history </li></ul><ul><li>Vary in size and direction of spread </li></ul><ul><li>Microadenomas < 10 mm – may cause focal bulging </li></ul><ul><li>Macroadenomas > 10 mm – cause problems due to mass effect </li></ul>
  • 9. Clinical Presentation <ul><li>Most common are endocrine abnormalities – hyper-/hyposecretion of ant. pituitary hormones </li></ul><ul><li>HA </li></ul><ul><li>Vision changes – bitemporal hemianopsia and superior </li></ul><ul><li>temporal defects </li></ul>
  • 10. Endocrine-Active Pituitary Adenomas <ul><li>Prolactin – Amenorrhea, galactorrhea, impotence </li></ul><ul><li>Growth hormone – Gigantism and acromegaly </li></ul><ul><li>Corticotropin – Cushing’s disease, Nelson’s syndrome post adrenalectomy </li></ul><ul><li>TSH - Hyperthyroidism </li></ul>
  • 11. Non-functioning Adenomas <ul><li>25-30 % of patients do not have classical hypersecretory syndromes </li></ul><ul><li>May grow to a large size before they are detected </li></ul><ul><li>Present due to mass effect </li></ul><ul><ul><li>Visual deficits </li></ul></ul><ul><ul><li>HA </li></ul></ul><ul><ul><li>Hormone deficiency </li></ul></ul>
  • 12. Evaluation <ul><li>MRI </li></ul><ul><li>Visual field assessment </li></ul><ul><li>Endocrine evaluation </li></ul><ul><ul><li>Tests of normal gonadal, thyroid, and adrenal function </li></ul></ul><ul><ul><li>Radioimmunoassays – for hormone levels </li></ul></ul>
  • 13. Classifying <ul><li>Imaging/surgical classification </li></ul><ul><li>Clinical/endocrine – functional vs. nonfunctional </li></ul><ul><li>Pathological classification </li></ul><ul><li>WHO classification – reconciles the three systems above </li></ul>
  • 14. Classification <ul><li>Microadenomas – Grades 0 and I </li></ul><ul><li>Macroadenomas – Grades II to IV </li></ul><ul><li>Grade 0: Intrapituitary microadenoma with normal sellar appearance </li></ul><ul><li>Grade I: Nml-sized sella with asymmetric floor </li></ul><ul><li>Grade II: Enlarged sella with an intact floor </li></ul><ul><li>Grade III: Localized erosion of sellar floor </li></ul><ul><li>Grade IV: Diffuse destruction of floor </li></ul>
  • 15. Classification <ul><li>Type A: Tumor bulges into the chiasmatic cistern </li></ul><ul><li>Type B: Tumor reaches the floor of the 3 rd ventricle </li></ul><ul><li>Type C: Tumor is more voluminous with extension into the 3 rd ventricle up to the foramen of Monro </li></ul><ul><li>Type D: Tumor extends into temporal or frontal fossa </li></ul>
  • 16. Pathologic Classification <ul><li>Benign or malignant </li></ul><ul><li>Chromophobic – Non-functioning </li></ul><ul><li>Basophilic – Cushing’s </li></ul><ul><li>Acidophilic - Acromegaly </li></ul><ul><li>Mixed </li></ul>
  • 17. WHO Classification <ul><li>Five-tiered system </li></ul><ul><ul><li>Clinical presentation and secretory activity </li></ul></ul><ul><ul><li>Size and invasiveness (e.g. Hardy) </li></ul></ul><ul><ul><li>Histology (typical vs. atypical) </li></ul></ul><ul><ul><li>Immunohistologic profile </li></ul></ul><ul><ul><li>Ultrasturctural subtype </li></ul></ul>
  • 18. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas <ul><li>Retrospective study of 411 patients treated with EBRT for pituitary adenomas </li></ul><ul><li>Goal is to assess both long-term efficacy and toxicity of conservative surgery and RT in the management of pituitary adenomas </li></ul>M. Brada et al, Clinical Endocrinology (1993) 38, 571-578
  • 19. Method <ul><li>252 of 411 pts with non-functioning pituitary adenomas </li></ul><ul><li>131 of 411 pts had functional pituitary adenomas (62 acromegaly, 60 prolactinomas, 7 Cushing’s, 1 TSH, 1 Gn secreting) </li></ul><ul><li>338 had surgical intervention; 11 with complete resection </li></ul><ul><li>187 transfrontal approach, 24 trans-sphenoidal approach, 35 had no surgery </li></ul><ul><li>Median f/u of 10.5 yrs </li></ul>M. Brada et al, Clinical Endocrinology (1993) 38, 571-578
  • 20. Radiation Therapy <ul><li>Post-op RT to prescribed dose of 45-50 Gy in 25-30 fxs delivered at ≤ 1.8Gy/fx </li></ul><ul><li>Three-field technique aimed at a target volume encompassing the tumor and a 1-2cm margin </li></ul><ul><li>Patient treated in supine position </li></ul>M. Brada et al, Clinical Endocrinology (1993) 38, 571-578
  • 21. Results M. Brada et al, Clinical Endocrinology (1993) 38, 571-578 88% 20 94% 10 96% 5 Progression free survival Years after RT
  • 22. Results <ul><li>Extent of surgical resection did not correlate with outcome </li></ul><ul><li>Relative risk of death compared with normal population was 1.76 (p<0.001) </li></ul><ul><li>No prognostic factors for survival were identified </li></ul><ul><li>Morbidity of RT was low </li></ul><ul><li>1.5% of pts had assumed radiation induced visual deterioration </li></ul><ul><li>Cumulative risk for 2 nd brain tumor at 20 yrs was 1.9% </li></ul>M. Brada et al, Clinical Endocrinology (1993) 38, 571-578
  • 23. Conclusions <ul><li>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 </li></ul>M. Brada et al, Clinical Endocrinology (1993) 38, 571-578
  • 24. Results of surgery and irradiation or irradiation alone for pituitary adenomas <ul><li>Retrospective review of all patients with pituitary adenoma treated with RT alone, surgery and RT, or RT following surgical failure </li></ul>Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 25. Methods <ul><li>212 patients with pituitary adenoma underwent treatment between 1954 and 1982 </li></ul><ul><li>Median f/u was 11.9 yrs </li></ul><ul><li>Radiologic evaluation consisted of skull films, angiography, pneumoenchephalography, ventriculgraphy, CT and MRI </li></ul><ul><li>73% had transfrontal approach </li></ul>Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 26. Radiation Therapy Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988) 175 18-25 MV X-rays 13 4 MV X-rays 8 Cobalt 60 12 Orthovoltage X-rays Number of Patients RT
  • 27. Radiation Therapy <ul><li>Most patients treated with parallel-opposed portals </li></ul><ul><li>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 </li></ul><ul><li>Median dose for all patients is 4967 cGy </li></ul><ul><li>Pts receiving EBRT only had a mean dose of 3989 cGy; post-op EBRT 4493 cGy, and 4553 for EBRT salvage of surgical failures </li></ul>Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 28. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 29. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 30. Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 31. Conclusion <ul><li>Overall survival after treatment for all patients is not significantly different from an age, sex, and race matched population </li></ul><ul><li>Patients receiving surgery and post-op RT had a greater control of local disease </li></ul><ul><li>EBRT salvage of surgical failures is possible </li></ul><ul><li>EBRT treatment results in a low complication rate </li></ul>Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)
  • 32. Gamma-Knife Radiosurgery
  • 33. Gamma knife radiosurgery for pituitary adenomas <ul><li>Retrospective review of 79 pts treated with GKS for pituitary adenomas </li></ul><ul><li>Purpose: To look at the clinical results of GKS and both its efficacy and safety in treatment of pituitary adenomas </li></ul>Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000
  • 34. Methods <ul><li>79 of 108 pts treated between 1993 to 1999 with GKS whom f/u exceeded 6 mo. </li></ul><ul><li>56 FAs ( 29 acromegaly, 15 prolactinomas, 12 Cushing’s) and 23 NFAs </li></ul><ul><li>Mean age 50.2 yrs (26 y/o – 82 y/o) </li></ul><ul><li>49 female and 30 male </li></ul><ul><li>Mean tumor vol. 7.1 cm3 </li></ul>Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000
  • 35. Radiosurgical Treatment <ul><li>40 pts (24 FAs and 16 NFAs) underwent pre-GKS surgical resection </li></ul><ul><li>Mean margin dose – 22.5 Gy (FA 24.2 Gy, NFA 19.5) </li></ul><ul><li>Highest possible isodose (50-70%) used </li></ul><ul><li>Mean f/u period of 26.4 months </li></ul><ul><li>Tumor control= decreasing or unchanged tumor vol. </li></ul><ul><li>Endocrinologic improvement=fall in elev. hormone level </li></ul>Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000
  • 36. Results <ul><li>Tumor control – 93.6% (NFA 95.6%, FA 92.8%) </li></ul><ul><li>Tumor shrinkage – 24.1% (NFA 26.1%, FA 23.2%) </li></ul><ul><li>Endocrinological improvement – 80.3% </li></ul><ul><li>Endocrinological normalization – 30.3% </li></ul><ul><li>5/6 pts with preexisting visual field showed improvement </li></ul><ul><li>3 pts. developed complications </li></ul>Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000
  • 37. Conclusion <ul><li>Tumor growth control results achieved with GKS is similar to those for fractionated RT </li></ul><ul><li>GKS may produce better results than conventional RT in tx of pituitary adenoma produced endocrinopathies </li></ul><ul><li>GKS seems to be safer than fractionated RT in terms of complications </li></ul>Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000
  • 38. Pituitary Adenoma: The efficacy of RT as the sole treatment <ul><li>Retrospective study of 29 patients with nonfunctional or prolactin secreting macroadenomas </li></ul><ul><li>Tumor dose – 4500 cGy in 4-5 wks </li></ul><ul><li>Tumor controlled in 93% of pts </li></ul><ul><li>Conclusion: RT is effective for improving vision and can normalize hyperprolactinemia </li></ul><ul><li>Doses need not exceed 4500 cGy in 25 fxs </li></ul>Rush SC, Newall J., Int J Radiat Oncol Biol Phys 1989; 17:165
  • 39. General Management <ul><li>Pituitary adenoma management is complex and is dictated by size, symptoms, and character of tumor </li></ul><ul><li>Treatment options require multiple modalities, including: Surgery, RT, SRS, and medical management </li></ul>
  • 40. General Management <ul><li>Multidisciplinary approach </li></ul><ul><li>Goals: </li></ul><ul><ul><li>Define tumor extent </li></ul></ul><ul><ul><li>Evaluate hormone activity </li></ul></ul><ul><ul><li>Remove tumor mass </li></ul></ul><ul><ul><li>Control hypersecretion </li></ul></ul><ul><ul><li>Correct endocrine deficiencies </li></ul></ul>
  • 41. General Management <ul><li>Microadenomas: transsphenoidal surgery or RT </li></ul><ul><li>Macoradenomas: initial surgery with post-op RT </li></ul><ul><li>Medical Management </li></ul><ul><ul><li>Bromocriptine </li></ul></ul><ul><ul><li>Somatostatin </li></ul></ul>
  • 42. Pre-treatment MRI Close to Chiasm? yes no Surgery EBRT SRS/gamma-knife Visual field testing Deficit yes no Surgery Surgery EBRT Treatment Algorithm
  • 43. Appropriate for GKS
  • 44. Contraindication for GKS
  • 45. RT Dosing Guidelines 33-95% 90-95% 25-30 Gy to margin 45-54 Gy Functioning tumors NA 95% 12-24 Gy to margin 45-50.4 Gy Nonfunctioning tumors Biochemical Control Local Tumor Control Radio-surgery (optic chiasm dose < 9 Gy) EBRT (1.8Gy/fx)
  • 46. Complications <ul><li>Hypopituitarism </li></ul><ul><li>Vision loss </li></ul><ul><li>Carcinogenic </li></ul><ul><li>Radiation necrosis </li></ul><ul><li>Cerebral Infarction </li></ul>
  • 47. Future Directions <ul><li>Profiles of toxicity in the 2-D vs. 3-D era </li></ul>
  • 48. Thank You <ul><li>Faculty </li></ul><ul><li>Residents </li></ul>

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