RADIATION ONCOLOGISTS VIEW

2.  pituitary gland is a midline structure
 measuring approximately 15 mm in AP and 12 mm
in the SI axis.
 The pituitary gland occupies a cavity of the
sphenoid bone, called the sella turcica
 The diaphragm sellae, an extension of the dura,
separates the pituitary gland from the structures
lying above it

5.  The diaphragm sellae is traversed by the pituitary
stalk
 connects the median eminence of the pituitary to
the hypothalamus.
 The posterior border of the sella is formed by the
dorsum sellae
 thin structure with two prominences: the posterior
clinoids.
 The tuberculum sellae lies anteriorly in the floor of
the sella turcica, and projects laterally as the
anterior clinoid processes.
 Lateral to the sella are the cavernous sinuses

6.  The pituitary gland has two components of distinct
embryologic origins.
 The anterior and intermediate lobes of the pituitary
gland arise from Rathke's pouch
 an evagination of ectodermal tissue from the roof
of the oral cavity

7.  The posterior lobe (or neurohypophysis) and stalk
arise from a down-pocketing of the third ventricle.
 The posterior lobe contains terminal axons from
neurons originating in the hypothalamus.
 Secretory granules are synthesized in the
supraoptic and paraventricular nuclei and
transported along the stalk to the posterior lobe
 where they are released as the posterior pituitary
hormones oxytocin and vasopressin

8.  Secretion of anterior pituitary hormones is
controlled by hypothalamic hormones carried by
the hypothalamic-hypophyseal portal system
 corticotropin-releasing hormone
 thyrotropin-releasing hormone
 GH-releasing hormone
 GH-inhibiting hormone or somatostatin
 FSH-releasing hormone
 LH-releasing hormone
 prolactin-releasing hormone
 prolactin-inhibiting hormone

9.  ANTERIOR PITUITARY HORMONES
 Adrenocorticotropic hormone (ACTH)
 thyroid-stimulating hormone (TSH)
 growth hormone (GH)
 follicle-stimulating hormone (FSH)
 luteinizing hormone (LH)
 prolactin

10.  10% of the healthy adult population has pituitary
abnormalities detectable by MRI
 Pituitary neoplasms account for 10% to 15% of
diagnosed primary intracranial neoplasms
 Approximately 70% are endocrinologically active
 The incidence of macroadenomas is similar
between males and females

11.  clinical manifestations of microadenomas are more
frequent in women.
 Seventy percent of adenomas present between the
ages of 30 and 50

12.  The etiology of most pituitary adenomas is
unknown.
 A genetic predisposition
 25% of patients with MEN type-1
 the Carney complex -inherited condition with
spotty skin pigmentation, myxomas, endocrine
overactivity, and schwannomas
 isolated familial somatotropinomas (IFS) -
occurrence of two or more cases of acromegaly in a
family in the absence of MEN or the Carney
complex

13.  Most of the pituitary adenomas arise from the
anterior lobe, are benign in nature.
 Pituitary adenoma can be categorized
 secretory or nonsecretory tumors (ratio of 2:1)
 Tumors that hypersecrets- prolactin,
corticosteroids, and GH account for 50, 25, and
20%

14.  Depending on size (Jules Hardy classification)
 microadenomas (tumor diameter less than or
equal to 10 mm)
 macroadenomas (tumor diameter greater than
10 mm).
 Corticotroph and lactotroph adenomas tend to
be microadenomas
 other functional and the nonfunctioning
adenomas are usually macroadenomas at
diagnosis

15.  Clinical feature
 local tumor extension (mass effect and
neuro-ophthalmic manifestation)
 hormonal dysfunction (endocrine
syndromes)

16.  Due to local extension
 Common symptoms: headache, extraocular palsies,
and visual symptoms
 Extension laterally into the cavernous sinuses
 cause diplopia, opthalmoplegia, ptosis, diminished
corneal sensation, or facial paresthesias in the
upper face

17.  If extension occurs superiorly the optic chiasm
 bitemporal hemianopic and superior temporal deficits,
homonymous hemianopsia, central scotoma, and
inferior temporal field defects
 inferior growth causes extension into the sphenoid
sinus
 Hypopituitarism - compression of the native pituitary
gland and resulting hyposecretion of pituitary hormones
 Large tumors that are allowed to grow unabated can
ultimately extend into the temporal lobe, third ventricle,
and posterior fossa.

22.  Pituitary apoplexy,-acute infarction and
hemorrhage of a pituitary adenoma.
 Apoplexy usually occurs in macroadenomas
 C/F- severe headache, altered consciousness,
opthalmoplegia, and visual deficits including
blindness.
 Imaging studies usually reveal intratumoral
hemorrhage (sometimes ischemic changes).

23.  These patients present with severe hypopituitarism
 require urgent medical care for administration of
stress doses of steroids, fluid administration, and
pain control.
 Urgent surgery is also generally warranted to avoid
potential permanent sequelae.

24.  PATHOLOGY
 With classic fixation, staining, and light
microscopy
 pituitary tumors are designated as
 Chromophobic
 Basophilic
 acidophilic

25.  Acidophilic tumors were thought to be
associated with acromegaly
 basophilic tumors with Cushing's disease
 chromophobic tumors with nonfunctional
 But these properties may not correlate with
clinical or immunohistochemical findings

26.  Newer methods of fixation and staining, electron
microscopy, and immunohistochemical procedures
can identify cells secreting GH, ACTH, TSH, and
prolactin
 Hormonally inactive adenomas referred to as null
cell adenomas
 now often pathologically classified as members of
the gonadotroph family.

30.  MRI gadolinium enhancement test of
choice
 High degree of sensitivity for micro & macro
adenoma
 Micro- hypointense
 Macro- isodense in unenhanced T 1 wtd
image
 Macro adenoma – compression of adj
pituitary & may distort stalk, larger –
extrasellar extn

36.  Goals
 remove or control tumor masses
 control hypersecretion
 correct endocrine deficiencies
 while minimizing the risk of hypopituitarism
or injury to adjacent structure

37.  MANAGEMENT OPTIONS
 OBSERVATION
 MEDICAL THERAPY
 SURGERY
 RADIOTHERAPY

38.  Observation -an option for nonsecreting
microadenomas
 small asymptomatic prolactinomas
 imaging must be performed at least yearly
for the duration of the patient's life

39.  When you will intervene?
 Tumor growth on imaging
 symptoms of hypersecretion
 development of visual field deficits

40.  Comorbidities associated with alterations in
hormonal levels including
 Hypertension
 Osteopenia
 Diabetes
 electrolyte imbalance
 Dyslipidemia

41.  increased mortality rates seen in acromegaly
 Excess circulating levels of GH and IGF-I
 multiple metabolic disturbances, cardiovascular
and respiratory comorbidities
 Goals of treatment-
 The reduction of circulating hormone levels
 reversal of mass effect

42.  Surgical intervention alone provides the
most rapid means of achieving both goals
 Transsphenoidal microsurgery-The
standard surgery for most tumors
 particularly effective in selective removal of
microadenomas
 but it also is used for adenomas that extend
outside the sella.

44.  Mortality rate of approximately 0.5%
 Major complications
 Meningitis
 Cerebrospinal fluid leak
 Hemorrhage
 Stroke
 Visual loss
 Approximately 1.5% of the procedures.

45.  Contraindications
 sphenoid sinusitis
 ectatic midline carotid arteries
 significant lateral suprasellar extent
 A transcranial approach is preferred in
such situations

46.  adjuvant therapies for patients with residual
tumor
 persistently elevated GH levels after surgery
 radical alternatives for medically inoperable
patients
 the most significant predictive factors
 tumor size and pretreatment GH levels.

47.  GH levels decrease over a period of several
years
 A 50% reduction in serum GH is expected
after approximately 2 years
 by 10 years after radiation therapy, 60% to
100% of patients have GH levels <10 ng/mL

48.  following failure of local therapies
 while awaiting the typically slow response
to radiation.

49.  Agents used
 somatostatin analogs (octreotide and
lanreotide)
 reduce GH and IGF-I levels in 50% to 60% of
patients who have failed surgery
 Tumor shrinkage occurs in 30% to 45% of
patients
 A/E-transient abdominal cramps
 malabsorptive diarrhea,
 nausea of mild-to-moderate intensity
 Gallbladder sludge or stones may develop in
15%

50.  dopamine agonists
 GH receptor antagonist- Pegvisomant, a
genetically engineered GH receptor
antagonist
 effective in reducing serum IGF-I
concentrations
 Daily injections of pegvisomant resulted in
normalization of IGF-I in 89% of patients
 A/E-diarrhea, nausea, flu syndrome, and
abnormal liver function tests

52.  Observation
 Surgery
 Medical therapy
 radiotherapy

53.  A dopamine agonist-
 Bromocriptine and cabergoline
 Bromocriptine results in rapid normalization
of prolactin levels in 80% to 90% of patients
 Bromocriptine can also reduce tumor size in
about 80% of cases, although size reduction
can be modest

54.  Long-term therapy appears to be required
 The dose may be reduced considerably once
a response is obtained
 Complete discontinuation of bromocriptine
results in recurrent hyperprolactinemia in
80% to 90% of patients
 A/E -transient nausea and vomiting
 Orthostatic hypotension may also occur at
the initiation of therapy

55.  Cabergoline is as effective as bromocriptine
in lowering prolactin levels and reducing
tumor size
 And has a better toxicity profile
 Biochemical recurrence rates 2 to 5 years
after withdrawal were 31% in
microprolactinomas
 36% in macroprolactinomas

56.  Transsphenoidal Resection
 Indication-
 rapidly progressive vision loss
 increase in adenoma size despite dopamine
agonists,
 intolerance or inadequate hormonal
response to medical therapy

57.  About 74% of microprolactinomas 32% of
macroadenomas, prolactin levels normalize
1 to 12 weeks postsurgery
 20% of patients present a biochemical
recurrence within 1 year
 Patients with large tumors (>2 cm in
diameter)
 prolactin levels above 20 ng/mL typically
fare worse

58.  mean prolactin levels after radiation ranged
from 25% to 50% of the pretreatment level
 with few patients achieving normal values
 The mean time required to reach normal
prolactin levels was 7.3 years

59.  Patients receiving dopamine agonists at the
time of radiosurgical treatment had a
significantly worse outcome
 A 2-month break between medical therapy
and radiotherapy was suggested

61.  Surgical Management-
 Selective transsphenoidal removal of the
ACTH-secreting adenoma remains the standard
of care
 Hormonal cure rates range from 57% to 90
 highest success rates seen in patients
harboring well-defined microadenomas
 Recurrence rates after achieving surgical
remission range from 2% to 25%

62.  Bilateral adrenalectomy is reserved for patients who
have failed other treatment modalities
 The procedure can performed laparoscopically
 induces a predictable and rapid hormonal response
 patients subsequently require lifelong treatment
with glucocorticoids and mineralocorticoids
 Bilateral adrenalectomy can also result in Nelson's
syndrome:
 local progression of the pituitary tumor with
characteristic skin pigmentation resulting from the
high concentrations of corticotropin.

63.  adjuvant or definitive radiotherapy with
doses of 35 to 50 Gy have provided
hormonal control rates of 50% to 100%
 most remissions achieved in the first 2
years
 Radiosurgery has been mainly used as
salvage therapy after failed or incomplete
transsphenoidal surgery

64.  Forty-nine percent of patients normalized
their cortisol level at a median of 7.5
months following radiosurgery (Devin et al)
 a trend for late recurrences in up to 20% of
patients treated with radiosurgery

65.  reserved for patients who fail either surgery
or radiotherapy
 lifelong and associated with important side
effects
 agents that modulate pituitary ACTH
release-cyproheptadine, bromocriptine,
somatostatin, and valproic acid provide
poor response rates with only modest
effect.

66.  agents that inhibit steroidogenesis-
 Ketoconazole, mitotane, trilostane,
aminoglutethimide, and metyrapone
 with important side effects and limited
efficacy

68.  first directed toward relief of any mass
effect
 If the tumor cannot be resected completely,
decompression of the chiasm (if indicated)
 followed by radiation provides excellent
long-term results
 use of adjuvant radiotherapy significantly
reduces local recurrence

69.  risk factors for recurrence
 local invasion
 suprasellar extent
 residual tumor on postoperative imaging
 recurrences continue to occur 10 to 20
years following surgery- MRI-confirmed
complete resection

71.  Image-based treatment planning using a
three-dimensional technique is the standard of
care
 All diagnostic evidence, but particularly MRI
and CT, as well as clinical and surgical findings,
should be used to define the tumor volume.
 Registration of a contrast-enhanced MRI scan
with the treatment CT scan allows for optimum
definition of the tumor and the optic apparatus

72.  (GTV) is the pituitary adenoma, including any
extension into adjacent anatomic regions.
 (CTV) limited to a 5-mm margin around the
tumor is adequate
 With invasive tumors, such as those involving
the sphenoid sinus, cavernous sinus, or other
intracranial structures
 there is greater uncertainty that must be
considered in determining the volume to be
included.
 the entire contents of the sella and the entire
cavernous sinus are included in the CTV.

73.  Standard thermoplastic masks are
associated with setup variability of the
order of 3 to 4 mm.
 A total PTV margin of 5 mm is usually
reasonable

74.  For two-dimensional planning in which an
eye-sparing anterior or vertex beam will be
used, the patient is positioned supine with
neck flexed and the head at a 45-degree
angle
 OR
 patient is generally positioned with the
head and neck in a neutral position.

76.  Immobilization will generally be performed
with a thermoplastic mask
 For three-dimensional simulation, a
contrast-enhanced planning CT scan is
obtained.
 When possible, a thin- slice T1-weighted
contrast-enhanced MRI should be
registered to the planning CT scan.

78.  The volumes described are then defined on
the MRI but reviewed on the CT.
 Normal structures to be contoured include
the eyes (lenses), optic nerves, optic
chiasm, brainstem, and temporal lobes.

80.  Beam arrangements
 The use of two lateral opposed portals should
be avoided in order to decrease the dose to the
temporal lobes.
 A simple technique is to use three static
shaped beams: wedged opposed laterals and
an anterior or vertex beam that enters above
the eyes
 When complex treatment planning is available
 five noncoplanar beams present a good
solution.
 This allows custom beam shaping and optimal
normal structure sparing.

83.  The beams are hemispherically distributed,
avoiding entry or exit through the eyes
 Photons in the megavoltage range should
be used to spare surrounding structures,
most notably the temporal lobes.
 Six- to 10-MV photons are generally used.

85.  Pituitary adenomas show dose-response
rates that depend on tumor type
 Nonfunctioning tumors are usually
controlled with 45 to 50.4 Gy using daily
fractions of 1.8 Gy.
 Functioning tumors require slightly higher
doses, typically 50.4 to 54 Gy

86.  contraindicated if the optic chiasm is closer than 3
to 5 mm to the tumor
 After fixation of the appropriate stereotactic head
frame, a high-resolution imaging study is
obtained.
 the dose to the optic chiasm must be kept <8 to 9
Gy
 The dose prescribed will be 12 to 20 Gy for
nonfunctioning tumors
 15 to 30 Gy for functioning adenomas

87.  The acute complications
 Fatigue
 focal alopecia
 otitis

88.  Long term complications include
 Hypopituitarism (25-80% with conventional
RT and 5-40% radiosurgery)
 Impairment of vision (1-2%)
 Second malignancy -The cumulative risk of
second brain tumors (mainly meningiomas
and high-grade astrocytomas) was 2.4% at
20 years
 Brain necrosis < 1%

89.  Contrast-enhanced MRI is the imaging
modality of choice
 It should be obtained at least yearly
 Monitoring of hormonal response
 Both insulin growth factor-I (somatomedin-
C or IGF-I) and GH levels should be
followed in acromegaly

90.  In prolactin-secreting tumors-measurement
of plasma and urine steroids and plasma
ACTH levels.
 Periodic assessment of gonadal, thyroid,
and adrenal function is necessary.
 regular formal visual field testing should be
performed following radiotherapy.