The role of radiation in
the management of
acromegaly
Current concepts and
controversies
Axial and Coronal MRI
Radiological Anatomy
 Coronal
section showing optic chiasm
MRI Anatomy
Functional imaging withGallium
Dotatate
Coronal section demonstrating
proximity to optic chiasm
Stem Cell regions
Management of Acromegaly
 Surgery
 Radiation
therapy
 Medical Therapy
Surgery
 Generally
first line therapy
 Indicated for active acromegaly, visual
loss, pituitary tumour apoplexy, mass
effect and treatment of progressive or
refractory disease
 Transsphenoidal
 Endoscopic transsphenoidal
 Craniotomy
Surgical Results
 Goal
of management is restoration of a
normal GH secretion profile and
normalisation of IGF-1
 70-88% long term control in
microadenomas
 50-61% long term control in
macroadenomas
 Recurrence more likely with invasive
tumours
Surgical complications
 Low
mortality <0.5%
 CSF leak and meningitis
 Vascular injury <1%
 Sinusitis
 Diabetes insipidus ; transient 3%
pemanent <2%
 Visual loss in 5%
 New hypopituitarism in 10-20%
Multimodality therapy

Indicated in residual or recurrent adenomas
 75% are macroadenomas at diagnosis and often
invade surrounding structures such as bone or
dura rendering complete safe resection
unfeasible
 Between 10-50% will have persistent elevations
of IGF-1 and GH
 Up to 20% can recur in spite of normalisation of
hormone levels
Multimodality Therapy

Following incomplete resection or recurrence
radiation therapy and medical therapy either in a
combined or sequential fashion can be used
 The aim is to achieve normalisation of GH and
IGF-1 levels
 Therapy is best considered in a multi-disciplinary
team evluating the most effective and least risky
therapy for each patient on an individual basis
Stereotactic Radiation

From the Greek stereos solid, taxis form or order
 3 dimensional localisation of objects with
Cartesian coordinates
 Two major divisions, Radiosurgery ; the delivery
of a single large dose and Radiotherapy ; the
delivery of multiple smaller doses
 Benefits must always be balanced against
inherent risks of new hypopituitarism, visual loss
and cranial nerve deficits
Conventional External beam
Radiotherapy(EBRT)
 Old
technology
 Has been used since the 1920’s, not much
planning involved and large volumes of
normal tissues irradiated
EBRT
EBRT

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Widely varying reported rates of effectiveness 574% hormonal remission, variation probably due
to levels defining remission
Functional response can take 5-15 years to
manifest
50-80% risk of new hypopituitarism
Increased stroke risk
EBRT use has thus significantly dropped in the
last decade
Complications of EBRT

Low risk of radiation cerebral damage at doses<50 Gy at
2Gy/#, radionecrosis <1%
 Optic neuropathy at this dose schedule occurs at
approximately 1-5%
 New hypopituitarism in up to 60%
 Increased incidence of stroke has been demonstrated
with a 1.6 fold excess
 Radiation induced second tumours in 2% at 10 years
and 2.4% at 20 years
 Possible mild cognitive impairment with older techniques
Stereotactic Radiosurgery
 Gamma
Knife
 Cyber Knife
 Linac Based
 Can
be frame based
 Recent use of Image guided Radiotherapy
IGRT with on-line cone beam CT scan in a
linear accelerator(Linac)
Frame for Gamma Knife
Gamma Knife
Cyber Knife
Radiosurgery
 Single
dose to a mean marginal dose of
14-34 Gy
 Can only be used if the adenoma is at
least 3-5mm away from the optic chiasm
or optic nerves
 Tolerance dose of optic chiasm is 8Gy
after which there is a significant risk of
blindness in both eyes
Coronal section on Gamma Plan
Gamma Plan
Radiosurgery

Stable or reduced tumour volume is achieved in
97% of patients
 Normalisation of IGF-1 and GH levels is
achieved in17-96%, this variation is probably
due to varying doses, length of follow up and
thresholds for defining remission
 A large meta-analysis demonstrated remission in
approximately 50% , overall control +/- medical
therapy was 73%
 Median time to remission was 29.8 months
Radiosurgery
 The
smaller the adenoma and the lower
the IGF-1 and GH levels the more likely
remission is to be attained
 Prior or concurrent use of Octreotide may
decrease the effectiveness of radiosurgery
 People treated with radiosurgery require
close follow up due to the long latency of
remission, risks of late relapse and
potential late side effects
Complications of Radiosurgery
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New hypopituiarism, 2-47%
Visual disturbances, 1-11%
Cranial nerve damage, rare
Temporal lobe epilepsy
Radiation Necrosis
Carotid artery stenosis
The larger the volume of tumour and the closer it
is to the optic nerves the greater the risk of
complications
Fractionated Stereotactic
Radiotherapy (f-SRT)

In recent years the advent of frameless, high precision
reproducibly accurate systems with <1mm variation
using image guidance(IGRT) has allowed far more
localised radiation delivery
 This reduces the volume of normal tissue irradiated
 A recent study delivering 54Gy in 27-30 treatments
demonstrated stable or reduced volume in 91%
 50% achieved biochemical control within 30 months of
those 30%had complete remission and came off all
medical therapy, none of this group showed late relapse
Comparison of frame based with
Image guided Radiotherapy
Immobilisation using a bite block
and a thermoplastic mask
Bite block
Thermoplastic Mask alone
Schematic Dose distribution
f-SRT

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In those who had one or more functional
pituitary axes prior to f-SRT 29% developed
further hypopituitarism at 48 months
In people who had hypopituitarism prior to
therapy 21% developed a defficiency in a new
axis
Overall 50% demonstrated biochemical control
91% demonstrated tumour control at a median
of 34 months
55% showed tumour regression
f-SRT

Low rates of toxicity have been demonstrated with high
rates of durable control
 Recent studies have shown 5 year tumour control rates
of 100% and hormonal control rates of 80%
 Optic neuropathy occurs in 1-5% of cases
 Overall hypopituitarism rates vary from 15-37%
 No cases of CVA have been recorded although this may
be due to the fact that f-SRT has not been used for long
and stroke is a late effect
 Possibly less cognitive impairment than EBRT , requires
validation
Advanced techniques in f-SRT

IMRT( Intensity modulated radiation therapy)
shapes and modulates the beam to allow far
higher target conformity whilst minimising
radiation dose to adjacent normal tissue
especially sensitive structures. This may take1012 minutes to deliver
 VMAT(volumetric Modulated Arc Therapy) is a
more refined form of IMRT capable of greater
conformality and sparing of critical structures in
certain settings. Treatment takes 70 seconds
Advanced f-SRT

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Image guided radiation therapy(IGRT)
This may be combined with IMRT or VMAT
Micro Multileaf Collimators (mMLC) available
from a number of vendors; Elekta particularly
the Agility or the Apex collimator, Brain Lab
including Novalis , Varian particularly True Beam
 May also be delivered by cone collimation
available from a number of vendors including the
aforementioned and Radionics. These are not
capable of beam modulation as are the mMLC
devices and may not be able to spare adjacent
structures as well particularly if they are close by
Micro Multi Leaf Collimator m-MLC
Conclusion

Radiotherapy is very effective in the
management of recurrent or persistent active
acromegaly following surgery
 Conventional EBRT achieves biochemical
remission in 50-60% with a reasonable risk of
complications
 Stereotactic Therapy SRS or f-SRT provide
comparable high rates of tumour control and
hormonal remission with low morbidity risks.
 Possibly reduce late toxicities to normal tissue
Conclusion

Tumour characteristics particularly size,
proximity to optic chiasm or cavernous sinus and
dural involvement are particularly important in
deciding between SRS and f-SRT.
 For small tumours >3mm away from the chiasm
SRS is a convenient option
 For larger tumours close to critical structures
f-SRT is an option with equivalent control rates
but lower morbidity
 Research into other fractionation schedules
involving a smaller number of higher dose
fractions (HIGRT) is ongoing