1. Chien Wei OMS IV September 14, 2006
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

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

7. 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

8. 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

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

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

11. 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

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

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

14. 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

15. 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

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

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

18. 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,

19. 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,

20. Radiation Therapy
Post-op RT to prescribed dose of Gy in 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,

21. Results Years after RT Progression free survival 5 96% 10 94% 20 88%
M. Brada et al, Clinical Endocrinology (1993) 38,

22. 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,

23. 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,

24. 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: (1988)

25. 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: (1988)

26. Radiation Therapy RT Number of Patients Orthovoltage X-rays 12
Cobalt 60 8
4 MV X-rays 13
18-25 MV X-rays
175
Grigsby et al, J of Neuro-Oncology 6: (1988)

27. 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: (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
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: (1988)

32. Gamma-Knife Radiosurgery

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

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

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

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

43. Appropriate for GKS

44. Contraindication for GKS

45. (optic chiasm dose < 9 Gy)
RT Dosing Guidelines
EBRT
(1.8Gy/fx)
Radio-surgery
(optic chiasm dose < 9 Gy)
Local
Tumor
Control
Biochemical Control
Nonfunctioning tumors Gy
12-24 Gy to margin
95% NA
Functioning tumors
45-54 Gy
25-30 Gy to margin
90-95%
33-95%

46. Complications Hypopituitarism Vision loss Carcinogenic
Radiation necrosis
Cerebral Infarction

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

48. Thank You
Faculty
Residents