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Radiotherapy for craniopharyngioma

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Pituitary (2013) 16:26–33
DOI 10.1007/s11102-012-0429-1
Radiotherapy for craniopharyngioma
Ajay Aggarwal • Naomi Fersht • Michael Brada
Published online: 5 September 2012
Ó Springer Science+Business Media, LLC 2012
Abstract Radiotherapy remains the mainstay of multi-
disciplinary management of patients with incompletely
resected and recurrent craniopharyngioma. Advances in
imaging and radiotherapy technology offer new alterna-
tives with the principal aim of improving the accuracy of
treatment and reducing the volume of normal brain
receiving significant radiation doses. We review the
available technologies, their technical advantages and dis-
advantages and the published clinical results. Fractionated
high precision conformal radiotherapy with image guid-
ance remains the gold standard; the results of single frac-
tion treatment are disappointing and hypofractionation
should be used with caution as long term results are not
available. There is insufficient data on the use of protons to
assess the comparative efficacy and toxicity. The precision
of treatment delivery needs to be coupled with experienced
infrastructure and more intensive quality assurance to
ensure best treatment outcome and this should be carried
out within multidisciplinary teams experienced in the
management of craniopharyngioma. The advantages of the
combined skills and expertise of the team members may
outweigh the largely undefined clinical gain from novel
radiotherapy technologies.
Keywords Craniopharyngioma
Radiotherapy

Radiosurgery
Stereotactic radiotherapy
IMRT
A. Aggarwal
N. Fersht
M. Brada
University College London Hospitals, London, UK
M. Brada (&)
Leaders in Oncology Care, 95 Harley Street,
London W1G 6AF, UK
e-mail: mbrada@theloc.com
123
Introduction
Radiotherapy is an integral component of management of
children and adults with craniopharyngioma. The principal
aim has been and remains the achievement of long term
disease control in patients with residual or recurrent
tumours where complete surgical removal is considered
inappropriate due to unacceptable morbidity. We review
the current evidence advocating its use particularly in the
light of advances in surgery and technical advances in
radiotherapy delivery.
Rationale for radiotherapy
The rationale for radiotherapy has been the recognition of
significant morbidity [1–5] and mortality following radical
compared with conservative surgery [1, 2, 6], combined
with the excellent local control achieved with the combi-
nation of partial surgical excision and radiotherapy com-
pared to attempts at complete excision alone [7–11]. In
addition, the use of radiotherapy following incomplete
removal of craniopharyngioma largely avoids the need for
repeat surgery which has been associated with further
morbidity and mortality [2, 3].
The 10 year tumour control rates reported in single arm,
often retrospective, studies (75–90 %) [7–12] were supe-
rior to the results following incomplete excision alone
(30–50 %) [6, 7, 13, 14] and have led to radiotherapy being
considered the standard of care for patients with residual
and recurrent disease. While the results were based on
conventional fractionated external beam radiotherapy, the
tumour control rates with newer higher precision tech-
niques such as fractionated stereotactic conformal radio-
therapy have remained excellent with 5 year local control
Pituitary (2013) 16:26–33 27

rates of [90 % [15], with 100 % 10 year local control in

one study [16].
There are no prospective randomised studies comparing
the various treatment approaches to provide high level
evidence for the choice of treatment.
In a changing world with advances in imaging and
significant progress in radiotherapy and surgery the debate
about the correct choice of treatment continues. In a rela-
tively rare condition such as craniopharyngioma, where
randomised studies are difficult, if not impossible, to rea-
lise there is a need for careful observational studies
examining all the aspect of the condition and its treatment.
With increased specialisation there is a risk that the per-
ception of overwhelming technological advance in an
individual field hijacks the management pathway. The
reality remains that advances, while real, have an impact
not always supported by high level clinical evidence and
any planned change in management policy should be
accompanied by an informed debate between all the spe-
Fig. 1 Example of dose distribution of 3D conformal therapy of
cialists involved in the care of craniopharyngioma patients.
craniopharyngioma
In this spirit, we present the current evidence for radio-
therapy reviewing both conventional and novel treatment
approaches to provide the basis for evaluating the different GTV plus a margin define the PTV where the high radia-
approaches. tion dose is aimed.
The principle of 3DCRT is to deliver the same dose
(dose homogeneity to within 7 % of the maximum dose) to
Radiotherapy techniques the whole extent of the tumour (craniopharyngioma) and
this is achieved with 3–4 radiation beams equally spaced in
3-Dimensional (3D) conformal radiotherapy (3DCRT) 3D and shaped using multileaf collimators (MLC’s). The
process of computer planning defines the position of the
The last decade has seen transition from 2D to 3D radio- beams to achieve dose homogeneity within the PTV and
therapy and 3D conformal external beam radiotherapy is the allows for optimum avoidance of surrounding critical
standard treatment for most clinical situations where it is normal structures. An example of dose distribution in a
given with radical intent, such as the treatment of cranio- single plane is shown in Fig. 1.
pharyngioma. It is delivered with photons using a linear
accelerator and for accurate conformal treatment delivery Advances in radiotherapy
(conforming to the shape of the tumour) requires precise
immobilisation, accurate tumour localisation with the best Technical advances in radiotherapy are largely in the form
available imaging and computerised 3D treatment planning. of refinement of the various stages of treatment preparation
Standard immobilisation for the treatment of cranio- and delivery. The relocation accuracy is improved with a
pharyngioma is the use of an individually moulded ther- more restrictive immobilisation system and ranges from
moplastic mask with a relocation accuracy of 2–4 mm. better fitting masks to frame fixation, which can be either
Accurate tumour localisation requires a high quality relocatable or fixed. With better immobilisation the GTV-
enhanced MRI scan co-registered with a CT planning scan PTV margin can be reduced with less normal tissue treated
performed in the treatment position in the mask. The extent to high radiation doses. The use of fractionated treatment
of visible residual craniopharyngioma and presumed demands relocatable fixation devices, with fixed frames
microscopic extension are delineated defining the gross only applicable for single fraction treatment.
tumour volume (GTV). An additional 3–5 mm 3D margin The optimum immobilisation system tends to be specific
is added to take into account relocation accuracy in the to each department and can be either in the form of a
mask and technical uncertainties in target localisation, relocatable frame or less firm mask immobilisation com-
computer planning and treatment delivery [defined as bined with daily on treatment imaging to ensure accuracy
planning target volume, (PTV)]. The margin is specific for [the technique of imaging is described as image guided
each department, based on departmental measurements. radiotherapy (IGRT)].

123
28
The term stereotactic, borrowed from neurosurgical
target localisation developed some decades ago, has been
used largely for frame based high precision treatment
where the target was defined using 3D coordinate system,
largely superseded by modern 3D imaging. While the term
stereotactic remains, the coordinate system is not fre-
quently employed and the meaning tends to refer to high
precision treatment.
It has been assumed that employing more radiation beams
arranged in space achieves more focussed radiation with
better sparing of surrounding normal tissue. This concept,
tested using 3D dose distribution [dose volume histograms,
(DVH)] is only partially correct as for volumes beyond
1.5–2 cm in diameter there is no evidence that increasing the
number of spatially separated beams beyond 4–6 improves
the dose distribution in the target or normal tissues [17].
The use of modulation of intensity of radiation using
MLC and more complex computerised treatment planning
[described as intensity modulated radiotherapy, (IMRT)]
allows for more individualised beam shaping particularly
for avoidance of normal structures within concave target
volumes. While it is possible to avoid some normal
structures using IMRT compared to 3DCRT, this is usually
at the cost of putting the dose elsewhere in the normal
tissues and currently there is no clear evidence that the use
of IMRT leads to better dose distribution for the treatment
of craniopharyngiomas.
The use of beam shaping and IMRT has been refined so
that both the shape of the radiation beam and the beam
modulation can be carried out while the beam is moving in
a circle around the target and this is described as arcing
IMRT. It does not offer better dose distribution but is a
faster means of delivering complex 3DCRT or IMRT.
Commercially it goes under the name of RapidArcÒ or
VMATÒ when using standard linear accelerator or as
Tomotherapy using a dedicated linear accelerator only
treating with arcs.
Multiheaded cobalt unit
Radiation can be delivered with multiple cobalt sources
arranged in a hemisphere focussed through a static colli-
mator system onto a target (gamma knife). The individual
high dose volumes range from 8 to 18 mm diameter (defined
as 50 % of maximum dose) and for most clinical situations
multiple small volumes have to be treated with a multiple
isocentre technique. The dose distribution is similarly plan-
ned using a computerised planning system although its aims
are different to linear accelerator planning where within
the target the dose is inhomogeneous (by a factor of 2) and
the prescribed dose is to a 50 % of the maximum tumour
dose.
123
Pituitary (2013) 16:26–33
The use of fixed frame for treatment demands that
imaging, treatment planning and the treatment itself are
performed in 1 day and the treatment is given in a single
fraction (defined as radiosurgery).
There is no data to suggest that the normal tissue dose
distribution (DVH) for average size craniopharyngioma is
any different to that achieved with high precision 3D
conformal or stereotactic fractionated radiotherapy.
Robotic arm mounted linear accelerator
The miniaturisation of linear accelerator allowed for its
mounting on a high precision industrial robotic arm and
this is combined with real time kV imaging (IGRT) which
allows for adjustment of positioning of the beams in rela-
tion to the target. The machine is commercially known as
the cyberknife. Smaller size, low dose rate beams have to
be summated to create a dose distribution equivalent to that
achieved with other techniques. While the treatment is of
high precision (not dissimilar to that achieved with other
methods) there is no data to demonstrate superiority of
dose distribution (if anything the reported results in
meningioma show worse DVH) [18]. The long duration of
each treatment also necessitates the treatment to be given
in few large fractions (hypofractionated radiotherapy) with
poorly defined long term consequences.
Image guidance (IGRT)
A major advance in radiotherapy in the last decade has
been the introduction of imaging during the course of
treatment. It ensures that the right area targeted at the
beginning is treated accurately throughout the course of
treatment. This can be done using X-rays either mounted
separately in the treatment room (commercially known as
Novalis or ExacTrac) or directly on the linear accelerator
as orthogonal planar or CT imaging (CT scanner mounted
on the linear accelerator is called cone beam CT (CBCT)).
A significant proportion of craniopharyngiomas have a
cystic component which can enlarge during the course of
radiotherapy. It is important that the size of the cystic
component is assessed during the course of treatment either
with CBCT or with a separate MRI to ensure the whole of
the lesion is treated throughout the course of fractionated
treatment and this is particularly important with the use of
higher precision techniques where the small margins don’t
leave room for the potential expansion of the lesion.
Dose fractionation
Fractionated radiation is delivered in daily doses (fractions)
each in the region of 1.6–1.8 Gy per fraction. There is no
clear dose response data and the total dose given ranges
Pituitary (2013) 16:26–33
from 50 to 55 Gy. We employ a dose of 50 Gy in 28–30
fractions and this provides the benchmark in terms of
assessing long term efficacy and toxicity of treatment
particularly as the total dose is within the tolerance of the
surrounding neural structures with low risk of radiation
optic neuropathy (1–2 %) and no significant risk of radia-
tion necrosis. Fractionated treatment is therefore suitable
for craniopharyngiomas of any size and location. Currently
the dose fractionation used is the same for children and
adults and most of the technical and clinical outcome data
combine all age groups.
Large single fraction radiation is potentially damaging
to neural structures at doses of 10 Gy or more (8 Gy and
more in some studies). Craniopharyngiomas closely related
to the optic nerves and chiasm cannot therefore be safely
treated with single fraction radiosurgery to doses greater
than 10 Gy reaching the optic apparatus [19, 20]. The
potential solution by reducing the dose to the primary
tumour to spare the optic apparatus can lead to worse
tumour control [21]. Radiosurgery is therefore limited to
small residual lesions away from critical structures.
Proton beam therapy
The principal theoretical advantage of protons, heavy
charged particles with the same biological effect as pho-
tons, is the deposition of energy at a defined point along its
path (Bragg peak) with little radiation beyond that point.
Dosimetric evaluation of 3D conformal proton therapy in
paediatric craniopharyngiomas has shown a reduction in
the volume of whole brain irradiated to high and medium
doses though without improved target dose distribution
compared with best photon radiotherapy [22, 23].
Clinical outcome following radiotherapy
Conventional radiotherapy
The principal aim of radiotherapy is to control the growth
of residual craniopharyngioma after incomplete surgical
excision. Most of the long term data on tumour control and
survival come from 2D radiotherapy era where the addition
of radiotherapy was shown to be associated with improved
tumour control and survival compared to partial excision
alone [7–11]. The 10 year progression free survival (PFS)
and overall survival (OS) rates are in the region of
75–90 % [7–12]. This provides the baseline for comparison
with newer radiotherapy techniques.
The side effects of irradiation are categorised according
to the time at which the clinical syndromes manifest into
acute toxicity which occurs during treatment, early delayed
toxicity which occurs within weeks of completion of
29
treatment and late toxicity which occurs months to years
following treatment. The risk of toxicity depends on the
total dose of radiation, the dose per fraction, the duration of
treatment and the volume of normal brain irradiated.
Acute and early delayed effects of conventional frac-
tionated radiotherapy to small volume sellar and suprasel-
lar structures are minimal with some tiredness and
temporary change in taste sensation. However 10–20 %
patients develop cystic enlargement of the craniopharyn-
gioma before, during and within some months of comple-
tion of radiotherapy leading to compression of the optic
apparatus and hydrocephalus [9]. This is a potentially life
threatening event and requires early recognition and sur-
gical intervention. Cystic enlargement does not represent
disease progression, as the outcome in terms of disease
control is the same as in patients without cystic enlarge-
ment. The acute effects of radiation also include transient
skin changes and small patches of hair loss at the entrance
and exit of radiation beam with subsequent full hair
regrowth.
The late side effects of irradiation can be broadly clas-
sified as structural and functional and as ‘‘very late effects’’
in the form of cerebrovascular disturbance and the devel-
opment of radiation induced second brain tumour.
Structural damage in the form of radiation necrosis
following properly executed fractionated radiotherapy to
conventional doses is almost unknown as the treatment is
within the recognised limits of radiation tolerance [5].
Functional damage in the form of radiation neuropathy
is also uncommon. Radiation optic neuropathy occurs in
1–2 % patients receiving doses to 50 Gy and this is mostly
confined to those with pre-radiotherapy visual impairment
[9, 11]. The risk is higher with doses of 55 Gy and above
[10, 24].
Pituitary dysfunction is the commonest late complica-
tion of conventional radiotherapy with 30–50 % of patients
developing new hormone deficiency requiring replacement
after a 5–10 year period [7–9]. However, the proportion of
patients with normal pituitary function after surgery is
small. Radiation does not cause diabetes insipidus. While
radiotherapy to large volumes of normal brain is associated
with neurocognitive dysfunction the frequency after small
volume irradiation is not well defined, particularly in a
situation where the disease itself and the surgical inter-
vention also have an effect [25–27]. Nevertheless, where
reported, a decline has been observed following radio-
therapy [9, 10].
Radiation therapy for pituitary adenoma is associated
with a 1–2 % risk of developing a second brain tumour at
20 years [28, 29]. While the risk of a second radiation
induced brain tumour is also likely to be increased fol-
lowing craniopharyngioma radiotherapy, the magnitude is
not fully defined. Irradiation of tumours in the sellar and
123
30
parasellar region, particularly pituitary adenomas, is asso-
ciated with an increased risk of cerebro-vascular accident
assumed to be in part due to radiation induced vascular
injury [30–32]. The precise risk is however not defined.
Conformal radiotherapy techniques
Modern conformal techniques of treatment using 3DCRT
have become the standard treatment of craniopharyngioma.
Better immobilisation, the routine use of MRI for target
delineation, the use of multiple shaped beams combined
with image verification (IGRT) achieve high treatment
accuracy with less dose delivered to normal tissues. This
can be further elaborated with intensity modulation either
as fixed field IMRT or as arcing IMRT. While providing
marginally better shaping of high doses to complex shaped
tumours it is unlikely the clinical results will be signifi-
cantly different to those achieved with conventional
radiotherapy. This is currently shown in early reports of the
use of IMRT and arcing IMRT.
Fractionated stereotactic radiotherapy
The reported outcomes following fractionated stereotactic
radiotherapy are similar to those reported following con-
ventional radiotherapy (Table 1) with 5 year PFS rates
over 90 % [15, 16] and up to 100 % 5-year survival [15].
The toxicity profile is also so far similar to that achieved
with conventional radiotherapy in terms of pituitary dys-
function (5–40 %), and visual deterioration presumed to be
radiation induced (\3 %) [33]. The results in terms of
cognitive function are not yet fully defined and the data is
not sufficiently mature to assess the risk of vasculopathy
and second tumour.
Single fraction radiosurgery
Radiosurgery has mostly been delivered with the gamma
knife. In the largest series [34] the reported 5 and 10 year
PFS rates are 61 and 54 % respectively and survival rates
at 5 and 10 years of over 90 %. Smaller series reported
PFS rates of 87 % at a median follow up 36 months [35].
Visual problems were initially reported in 38 % and
endocrinological deficiencies in 19 % of patients [21].
Single radiation doses above 8–10 Gy to the optic chiasm
are associated with up to 25 % risk of optic neuropathy and
this limits the technique to lesions away from the optic
chiasm [20]. The alternative solution of reducing dose to
the primary tumour to limit the risk of radiation neuropathy
results in unsatisfactory tumour control rates [21]. More
recent case series which confine the treatment to smaller
123
Pituitary (2013) 16:26–33
lesions report minimal morbidity [34–37] and rates of
visual deterioration of 3 % [35]. The reported results so far
(Table 1) demonstrate significantly worse outcome in
terms of tumour control and this is of particular concern as
the treatment is only suitable for small lesions away from
critical structures. On the basis of the published data single,
fraction radiosurgery is an inappropriate treatment for this
group of patients.
Robotic mounted linac (cyberknife) has been used
to deliver hypofractionated stereotactic radiotherapy
(Table 1). This uses an untested fractionation with the
treatment delivered in 3–5 fractions and the currently short
follow up does not allow for a reliable assessment of
efficacy and toxicity [38, 39].
Proton therapy
Early results of small case series of proton therapy report
similar results to those achieved with fractionated 3DCRT
and stereotactic radiotherapy, with 5 year PFS rates over
90 % [40]. The potential advantage of lower doses to
normal tissues beyond the irradiated target [22] have not
yet been translated to lower reported toxicity. Currently it
is the potential itself which drives the implementation of
proton radiotherapy particularly in young children where
any magnitude of avoidance of normal tissue irradiation is
considered of importance.
Practical management issues
This article deals primarily with the technology of
radiotherapy. The evolving clinical issues relate to the
timing of treatment and the management of children and
adults. Historically all patients were offered postoperative
radiotherapy to reduce the risk of recurrence following
apparent complete macroscopic excision and to achieve
control of residual craniopharyngioma following conser-
vative surgery. Especially because progressive cranio-
pharyngioma is of threat to function and is an important
determinant of survival. With modern MRI imaging it is
possible to adopt an initial policy of surveillance where
complete or other radical excision has been performed
and where there are few immediate risks from some
degree of tumour progression. This allows for a delay in
radiotherapy which is of particular value in children.
However, it is important that the clear objective of such a
policy is a delay in offering radiation and this is carried
out before the need for further surgery. Need for repeat
surgery would be considered a failure of the surveillance
policy, as the aim of irradiation is to avoid the risks
associated with surgical intervention.
Pituitary (2013) 16:26–33 31

Table 1 Published results of different techniques of irradiation for craniopharyngioma

Author Study Years Patients Treatment Follow-up Dose Mean Control (%) Complications (%)
country (n) months (Gy) tumour
size
(cm3)

Xu et al. [41] USA 2010 37 GK 50 14.5 1.6 67 % at 5 years 2 % endocrine

Niranjan USA 2009 46 GK 62 13 1 68 % at 5 years 2 % endocrine
et al. [42]
Kobayashi Japan 2009 98 GK 65 11.6 3.5 61 and 54 % at 5 6 % visual and
et al. [34] and 10 years endocrine
Yomo et al. Japan 2009 18 GK 24 11.5 1.8 (94 %)a 0
[43]
Amendola USA 2003 14 GK 39 14 3.7 (86 %)a 0
et al. [36]
Ulfarsson Sweden 2002 21 GK 3.5 years 3–25 7.8 (36 %)a 38 % visual/19 %
et al. [21] endocrine
Chiou et al. USA 2001 10 GK 66.5 16.4 1.7 (58 %)a 10 % visual/30 %
[37] cyst enlargement
Chung et al. Taiwan 2000 31 GK 36 9.5–16 9 (87 %)a 3 % visual
[35]
Mokry [44] Austria 1999 23 GK 24 8–9.7 7 (74 %)a 0
a
Prasad et al. USA 1995 9 GK NA 13 10 (63 %) NA
[45]
Iwata et al. Japan 2011 40 CK 40 13–25 2 85 % at 3 years 2.5 % endocrine/20 %
[39] cyst enlargement
Miyazaki Japan 2009 13 CK 12 22.7 NA (84 %)a 15 % cyst enlargement
et al. [46]
Lee et al. [38] USA 2008 11 CK 15.4 21.6 6 (91 %)a 9 % cyst enlagement
Giller et al. USA 2005 3 CK 18 42 1.14 (100 %)a NA
[47]
Kaneska et al. Japan 2011 16 FSRT 52 30 1.8 82.4 % at 3 years 0
[48]
Combs et al. Germany 2007 40 FSRT 22 52.2 13.3 100 % at 10 years 5 % endocrine/10 %
[16] cyst enlargement
Minniti et al. UK 2007 39 FSRT 40 50 10.2 92 % at 5 years 42 % endocrine/3 %
[15] visual/30 % cyst
enlargement
Schulz-Ertner Germany 2002 26 FSRT 43 52.2 5.2 100 % at 10 years 17 % endocrine/4 %
et al. [33] cyst enlargement
Selch et al. US 2002 16 FSRT 22 55 7.7 75 % at 3 years NA
[49]
GK gamma knife radiosurgery (multiheaded cobalt unit), CK cyberknife (robotic mounted linac), FSRT fractionated stereotactic radiotherapy
a
% control rate given without time and not in actuarial manner

Conclusion induced toxicity, this potential advantage has not been

Despite improvements in surgery, radiotherapy remains
part of multidisciplinary management of patients with
incompletely resected and recurrent craniopharyngiomas
with good long term disease control and limited toxicity.
Advances in fractionated radiotherapy where treatment can
be given with greater precision, allow for reduction of the
volume of normal brain structures receiving high radiation
doses. While the aim is the reduction in late radiation
demonstrated in prospective studies. This is in part due to
the low risk of late events with previous treatment and due
to the length of follow up required to assess these. The use
of high precision techniques has a potential downside. It
relies on complex technology and on the accuracy of
imaging and co-registration of images with the radiother-
apy planning system and demands a high degree of skill in
image interpretation particularly in the light of major
advances in modern imaging. It also requires more

123
32
intensive quality assurance particularly with on treatment
imaging to ensure the whole of a potentially enlarging
cystic craniopharyngioma is treated to full doses through-
out the whole course of treatment.
While there is considerable temptation to use radiosur-
gical tools such as the gamma knife which is currently only
used for single fraction treatment and the cyberknife using
hypofractionated regimens, the clinical results of radio-
surgery are disappointing with worse tumour control out-
come without lower toxicity. The use of hypofractionation
is also not evidence based and the long term results are not
available. Judged by poor outcome of hypofractionation in
acoustic neuroma [50], this technique should be used with
considerable caution, if at all.
Conflict of interest The authors declare they do not have financial
interest in the organisations sponsoring this work.
References
1. Yasargil MG, Curcic M, Kis M et al (1990) Total removal of
craniopharyngiomas, approaches and long-term results in 144
patients. J Neurosurg 73:3–11
2. Fahlbusch R, Honneger J, Paulus W et al (1999) Surgical treat-
ment of craniopharyngiomas: experience with 168 patients.
J Neurosurg 90:237–250
3. Hoffman HJ, De Silva M, Humphreys RP et al (1992) Aggressive
surgical management of craniopharyngiomas in children. J Neu-
rosurg 76:5–47
4. Schoenfeld A, Pekmezci M, Barnes MJ (2012) The superiority of
conservative resection and adjuvant radiation for craniopharyn-
giomas. J Neurooncol (Epub)
5. Minniti G, Esposito V, Amichetti M et al (2009) The role of
fractionated radiotherapy and radiosurgery in the management
of patients with craniopharyngioma. Neurosurg Rev 32:125–
132
6. Van Effenterre R, Boch AL (2002) Craniopharyngioma in adults
and children: a study of 122 surgical cases. J Neurosurg
97:492–499
7. Hetelkedis S, Barnes PD, Tao ML et al (1993) 20 Year experi-
ence in childhood craniopharyngioma. Int J Radiat Oncol Biol
Phys 27:189–195
8. Habrand JL, Ganry O, Couanet D et al (1999) The role of radi-
ation therapy in the management of craniopharyngioma: a
25 year experience and review of the literature. Int J Radiat
Oncol Biol Phys 44:255–263
9. Rajan B, Ashley S, Gorman C et al (1993) Craniopharyngioma:
long term results following limited surgery and radiotherapy.
Radiother Oncol 26:1–10
10. Regine WF, Mohiuddin M, Kramer S (1993) Long term results of
paediatric and adult craniopharyngiomas treated with combined
surgery and radiation. Radiother Oncol 27:13–21
11. Brada M, Thomas G (1993) Craniopharyngioma revisited. Int J
Radiat Oncol Biol Phys 27(2):471–475
12. Merchant TE, Kiehna EN, Sanford RA et al (2002) Craniopha-
ryngioma: the St Jude children’s research hospital experience
1984–2001. Int J Radiat Oncol Biol Phys 53:533–542
13. Stripp DC, Maity A, Janss AJ et al (2004) Surgery with or
without radiation therapy in the management of craniopharyn-
giomas in children and young adults. Int J Radiat Oncol Biol Phys
58:714–720
123
Pituitary (2013) 16:26–33
14. Lin LL, El Naqa I, Leonard JR et al (2008) Long term outcome in
children treated for craniopharyngioma with and without radio-
therapy. J Neurosurg Pediatr 1:126–130
15. Minniti G, Saran F, Traish D et al (2007) Fractionated stereo-
tactic conformal radiotherapy following conservative surgery in
the control of craniopharyngiomas. Radiother Oncol 82:90–95
16. Combs SE, Thilmann C, Huber PE et al (2007) Achievement
of long term control in patients with craniopharyngiomas
using high precision stereotactic radiotherapy. Cancer 109:
2308–2314
17. Perks J, Jalali R, Cosgrove V et al (1999) Optimisation of ste-
reotacticaly-guided conformal treatment planning of sellar and
parasellar tumours based on normal dose volume histograms. Int
J Radiat Oncol Biol Phys 45(2):507–513
18. Cozzi L, Clivio A, Bauman G et al (2006) Comparison of
advanced irradiation techniques with photons for benign intra-
cranial tumours. Radiather Oncol 80(2):268–273
19. Stafford SL, Pollock BE, Leavitt JA et al (2003) A study on the
radiation tolerance of the optic nerves and chiasm after stereo-
tactic radiosurgery. Int J Radiat Oncol Biol Phys 55:1177–1181
20. Leber KA, Bergloff J, Pendl G (1998) Dose response tolerance of
the visual pathways and cranial nerves of the cavernous sinus to
stereotactic radiosurgery. J Neurosurg 88:43–50
21. Ulfarsson E, Linquist C, Roberts M et al (2002) Gamma knife
radiosurgery for craniopharyngiomas: long term results in the first
Swedish patients. J Neurosurg 97(Suppl):613–622
22. Beltran C, Roca M, Merchant TE (2012) On the benefits of proton
therapy in paediatric craniopharyngioma. Int J Radiat Oncol Biol
Phys 82(2):281–287
23. Boehling NS, Grosshans DR, Bluett JB et al (2012) Dosimetric
comparison of three dimensional conformal proton radiotherapy,
intensity modulated proton therapy and intensity modulated
radiotherapy for treatment of craniopharyngiomas. Int J Radiat
Oncol Biol Phys 82(2):643–652
24. Varlotto JM, Flickinger JC, Kondziolka S et al (2002) External
beam irradiation of craniopharyngiomas: long term analysis of
tumour control and morbidity. Int J Radiat Oncol Biol Phys
54:492–499
25. Grattan Smith PJ, Morris JG, Shores EA et al (1992) Neuro-
psychological abnormalities in patients with pituitary tumours.
Acta Neurol Scand 86(6):626–631
26. Peace KA, Orme SM, Sebastian JP et al (1997) The effect of
treatment variables on mood and social adjustment in adult patients
with pituitary disease. Clin Endocrinol (Oxf) 46(4):445–450
27. Van Beek AP, Van den Bergh AC, Van den Berg LM (2007)
Radiotherapy is not associated with reduced quality of life and
cognitive function in patients treated for non functioning pituitary
adenoma. Int J Radiat Oncol Biol Phys 68(4):986–991
28. Brada M, Ford D, Ashley S et al (1992) Risk of secondary brain
tumour after conservative surgery and radiotherapy for pituitary
adenoma. Br Med J 304(6838):1343–1346
29. Minniti G, Traish D, Ashley S et al (2005) Risk of second brain
tumour after conservative surgery and radiotherapy for pituitary
adenoma: update after an additional 10 years. J Clin Endocrinol
Metab 90(2):800–804
30. Brada M, Burchell L, Ashley S et al (1999) The incidence of
cerebrovascular accidents in patients with pituitary adenoma. Int
J Radiat Oncol Biol Phys 45(3):693–698
31. Brada M, Ashley S, Ford D et al (2002) Cerebrovascular mor-
tality in patients with pituitary adenoma. Clin Endocrinol (Oxf)
57(6):713–717
32. Erfurth EM, Bulow B, Hagmar LE (2000) Is vascular mortality
increased in hypopituitarism? Pituitary 3(2):77–81
33. Schulz-Ertner D, Frank C, Herfarth KK et al (2002) Fractionated
stereotactic radiotherapy for craniopharyngioma. Int J Radiat
Oncol Biol Phys 54:1114–1120
Pituitary (2013) 16:26–33
34. Kobayashi T, Kida Y, Mori Y et al (2005) Long-term results of
gamma knife surgery for treatment of craniopharyngioma in 98
consecutive cases. J Neurosurg Pediatr 103(suppl):482–488
35. Chung WY, Pan DH, Shiau CY et al (2000) Gamma knife radi-
osurgery for craniopharyngiomas. J Neurosurg 93(Suppl):47–56
36. Amendola BE, Wolf A, Coy SR et al (2003) Role of radiosurgery
in craniopharyngiomas: a preliminary report. Med Pediatr Oncol
41:123–127
37. Chiou SM, Lunsford LD, Niranjan A et al (2001) Stereotactic
radiosurgery for residual or recurrent craniopharyngioma after
surgery with or without radiation therapy. Neuro Oncol 3:159–166
38. Lee M, Kalani Y, Cheshier S et al (2008) Radiation therapy and
cyberknife radiosurgery in the management of craniopharyngio-
mas. Neurosurg Focus 24(5):E4
39. Iwata H, Tatewaki K, Inoue M et al (2012) Single and hypo-
fractionated stereotactic radiotherapy with cyberknife for crani-
opharyngioma. J Neurooncol 106(3):571–577
40. Fitzek MM, Linggood RM, Adams J et al (2006) Combined
proton photon irradiation for craniopharyngiom: long term results
of the early cohort of patients treated at Harvard Cyclotron lab-
oratory and Massachusetts General Hospital. Int J Radiat Oncol
Biol Phys 64:1348–1354
41. Xu Z, Yen CP, Schlesinger D et al (2011) Outcomes of gamma
knife surgery for craniopharyngioma. J Neurooncol 104(1):305–
313
42. Niranjan A, Kano H, Mathieu D et al (2010) Radiosurgery for
craniopharyngioma. Int J Radiat Oncol Biol Phys 78(1):64–71
43. Yomo S, Hayashi M, Chernov M et al (2009) Stereotactic radi-
osurgery of residual or recurrent craniopharyngioma: new
View publication stats
33
treatment concept using Leksell gamma knife model C with
automatic positioning system. Stereotact Funct Neurosurg
87(6):360–367
44. Mokry M (1999) Craniopharyngiomas: a six year experience with
gamma knife radiosurgery. Stereotact Funct Neurosurg 72(Suppl
1):140–149
45. Prasad D, Steiner M, Steiner L (1996) Gamma knife surgery for
craniopharyngioma. Acta Neurochir (Wien) 134(3–4):167–176
46. Miyazaki ST, Takusagawa Y, Fukushima et al. (2009) Multi-
session cyberknife radiosurgery in management of craniopha-
ryngioma. In: Presented at the eight annual cyberknife users’
meeting, Hollywood, Florida, February 7 (Abstract) www.
cksociety.org/CKSociety/document.docdownload.aspx?docid=65
47. Giller CA, Berger BD, Pistenmaa DA et al (2005) Robotically
guided radiosurgery for children. Pediatr Blood Cancer 45:304–
310
48. Kaneska N, Mikami R, Nakayama H et al (2012) Preliminary
results of fractionated radiotherapy after cyst drainage for cra-
niopharyngioma in adults. Int J Radiat Oncol Biol Phys 82(4):
1356–1360
49. Selch MT, DeSalles AA, Wade M et al (2002) Initial clinical
results of stereotactic radiotherapy for the treatment of cranio-
pharyngiomas. Technol Cancer Res Treat 1:51–59
50. Kapoor S, Batra S, Carson K, Shuck J, Kharkar S, Gandhi R et al
(2011) Long-term outcomes of vestibular schwannomas treated
with fractionated stereotactic radiotherapy: an institutional
experience. Int J Radiat Oncol Biol Phys 81(3):647–653
123