Clinical Endocrinology (2014)
doi: 10.1111/cen.12568
CLINICAL QUESTION
Intracystic interferon therapy in childhood craniopharyngioma: who, when and how? Simon Bailey* and Jeannette Parkes† *Great North Childrens Hospital, Newcastle upon Tyne, UK and †Department of Radiation Oncology, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa
Summary A 13-year-old male presents with fluctuating visual disturbance and headaches. Imaging reveals a significant predominantly cystic suprasellar tumour, typical of a craniopharyngioma. The patient has growth hormone deficiency but the rest of the hypothalamic/pituitary axis is intact. What are the options for therapy in 2014? Specifically, is there a role for local treatment with interferon injected into the cyst cavity? The aim of management in children with craniopharyngiomas is to reduce the impact of the tumour as much as possible, while minimising the morbidity associated with treatment. There are a number of therapeutic options available: surgery, radiotherapy and the insertion of therapeutic agents directly into the tumour cyst. The role of intracystic therapy in the form of interferon is discussed; including when to use this therapeutic option and practical details of its use. (Received 25 April 2014; returned for revision 7 June 2014; finally revised 19 July 2014; accepted 21 July 2014)
Background of treatment options Craniopharyngiomas account for 5–10% of childhood brain tumours. They are frequently cystic but also contain solid tumour elements which are often calcified.1–3 The commonest presenting features relate to either raised intracranial pressure, endocrine abnormalities or visual field deficits. Endocrine abnormalities can involve some or all components of the hypothalamic/pituitary axis. The direct mortality rate for this tumour is low (60% of the tumour should be cystic). Other characteristics in addition to that above which should make one consider intracystic therapy include young patients with a predominantly cystic tumour, those patients with a cystic tumour and minimal
Table 1. Characteristics of craniopharyngiomas and appropriate therapies Characteristic
Surgery
Radiotherapy
Intracystic therapy
Predominantly cystic tumour >60% cyst Predominantly solid component Minimal hormonal deficits Panhypopituitarism Recurrence after surgery and radiotherapy Recurrence after surgery
+
+
+++
++
++
+
+
+++
+++ +
+++
+ +++ (if predominantly cystic)
+
+++
+++ (if predominantly cystic)
hormonal deficits or those who develop a recurrent cyst post radiotherapy or surgery. In some countries, hormone replacement and especially growth hormone is not readily available and in such cases preservation of a functioning growth hormone axis until after puberty may be an important consideration when choosing treatment options in those with cystic craniopharyngiomas. The cyst should measure a minimum of 2 cm in depth in order to allow the catheter tip of the Rickham or Ommaya reservoir to be completely enclosed by the cyst. Providing there is an initial response, intracystic therapy may be repeated. Up to nine courses have been used although a median of 2–4 is usual.2,19–21 At presentation, it must be ensured that any significant hydrocephalus is treated. The insertion of a reservoir with consequent cyst decompression may alleviate hydrocephalus. Occasionally, simple cyst decompression will be sufficient treatment on its own, but the majority of cysts will re-accumulate without further treatment. If the cyst has been decompressed, intracystic therapy should not be commenced until there is re-accumulation of the cyst, or in the case of recurrence. Intracystic therapy is unlikely to affect the solid portion of the tumour, but this may not progress or may only require further therapy at a later date (usually in the form of Radiotherapy and/or surgery). In terms of long-term outcome, it is preferable to delay radiotherapy/surgery until after puberty, if possible.2 Intracystic therapy is particularly attractive for those patients with minimal existing hormonal deficits and who fulfil the criteria mentioned above. Interferon a appears to be at least as effective as bleomycin and intracystic radioactive compounds, but has the advantage that any leak developing around the catheter has less potential for damage of the surrounding normal brain.
How to deliver intracystic therapy If intracystic therapy is undertaken, the first step is the insertion of an intracystic reservoir such as a Rickham or Ommaya reservoir. These may be inserted in three main ways: 1) insertion under direct vision, 2) insertion under stereotactic control or
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
Intracystic interferon therapy 3
Fig. 1 Details of administration of intracystic interferon a (Adapted from Bartels et al2). © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
4 S. Bailey and J. Parkes using an endoscope or 3) free hand insertion via a burr hole. The complication rates are similar22,23 but endoscopic insertion is believed to offer the safest route and the best opportunity to break down any cyst septations. However occasionally due to the thickness of the cyst wall, it may be technically difficult to insert the catheter using this method and insertion under direct vision may be necessary. It is important that the neurosurgeon is experienced and comfortable with the technique to be used. The majority of the catheters used with reservoirs have side holes up to a level of 2 cm from the tip, and all these perforations should be located within the cyst cavity to ensure that there is no subsequent leak. The catheter needs to be in place for a minimum of 5 days, but preferably 2 weeks after insertion, to allow a seal to form around it. It is advisable to perform a MRI scan to check the position of the catheter and cyst size, a single T2 sagittal sequence may be sufficient (Fig. 2). A leak test should then be performed (see Fig. 1 for details and Fig. 2 for example). Prior to commencing Interferon a, the patient should have blood electrolytes, a full blood and a complete endocrinological
(a)
(c)
workup with replacement therapy as deemed appropriate. A complete opthalmological assessment to document any visual deficits (including fields, acuity and eye movements) should be done. The recommended treatment course for intracystic interferon a is three times a week (usually Monday, Wednesday, Friday) for a total of 4 weeks (12 doses). The details of administration are found in Fig. 1. If the fluid is clear, this may suggest that the cyst has collapsed and the catheter tip is within a CSF space (usually the third ventricle) and if that is the case then interferon should not be given. An MRI scan should be performed after each 4 week course or earlier if the fluid has become clear. If there is a complete response then no further courses may be necessary. If there is a partial response, then a further course should be given. In cases where there is no response then alternative therapy should be considered. When there is a complete response (with a minimum of two courses) or there ceases to be any further response, the therapy should be stopped. Follow-up MRI scans should be performed every 3–4 months in the first year after completion
(b)
(d)
Fig. 2 (a) Coronal T1 MRI scan with contrast showing a large cystic craniopharyngioma. (b) Leak test showing an intact cyst with no leak. (c) Leak test showing a leak into the 4th ventricle (via the third ventricle) as well as contrast within the cystic portion of a child with carniopharyngioma. (d) Leak test showing cyst with local and ventricular leak. © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
Intracystic interferon therapy 5 of therapy. Beyond the first year, scanning frequency should be based on institutional guidelines.
What are the potential pitfalls and side effects? 1 Poor patient selection is the major pitfall in the use of intracystic therapy. It is essential that the decision to use this therapy is carefully discussed in a multi-disciplinary team (MDT) setting. This includes, neurosurgeons, endocrinologists, radiation oncologists and in the case of children, paediatric oncologists. The patients and their families need to have the proposed intracystic treatment carefully described to them, with the rationale behind its use in their particular circumstances. 2 Catheter leakage or some of the catheter perforations being outside the cyst is a major potential problem. This will be seen on the leak test but if clear fluid, instead of proteinaceous cyst fluid, is aspirated prior to therapy being started then it is likely that the catheter is not completely enclosed by the cyst. The fluid aspirate may thin as treatment progresses. 3 Side effects of interferon are usually predictable and self limiting; predominantly arthralgia, fatigue, fevers and occasionally new endocrine deficits.2,19–21 These tend to reduce as the course of treatment continues and it is very rare that treatment needs to be suspended for them. Simple antipyretics and analgesics are usually all that is required. The patient and their family should be warned of the potential side effects and given antipyretics to take home. It is also important that they have a robust mechanism for contacting members of the treating team at all times.
Will further therapy be needed? Craniopharyngioma is considered a chronic disease and multiple treatment modalities may be required at different times. If intracystic therapy has been used and proven to be effective, then this may be repeated. An alternative form of intracystic therapy such as bleomycin or colloidal radioactive compounds may also be considered. In the case of mixed solid/cystic or complex cystic tumours, it is likely that other therapeutic options such as primary surgery and/or external beam radiotherapy (photons, protons or radiosurgery) will be considered. The timing and choice of these therapeutic options remains one of the biggest challenges in the management of these tumours.1,3 Mortality rates may be low for these tumours, but morbidity is high and the further impact of treatment on quality of life remains a major hurdle.
Summary Intracystic interferon therapy for craniopharyngioma is an effective treatment option for a subset of patients with craniopharyngioma and may decrease the treatment-related morbidity associated with this chronic tumour, resulting in improved quality of life. It is important that patients chosen for this treatment option are carefully selected and discussed within the MDT setting prior to embarking on this therapeutic option. © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
References 1 Muller, H.L. (2010a) Childhood craniopharyngioma–current concepts in diagnosis, therapy and follow-up. Nature Reviews. Endocrinology, 6, 609–618. 2 Bartels, U., Laperriere, N., Bouffet, E. et al. (2012) Intracystic therapies for cystic craniopharyngioma in childhood. Frontiers in Endocrinology (Lausanne), 3, 39. 3 Muller, H.L. (2014) Craniopharyngioma. Endocrine Reviews, 35, 513–543. 4 Hukin, J., Steinbok, P., Lafay-Cousin, L. et al. (2007) Intracystic bleomycin therapy for craniopharyngioma in children: the Canadian experience. Cancer, 109, 2124–2131. 5 Muller, H.L. (2010b) Increased daytime sleepiness in patients with childhood craniopharyngioma and hypothalamic tumor involvement: review of the literature and perspectives. International Journal of Endocrinology, 2010, 519607. 6 Jane, J.A.J., Kiehna, E., Payne, S.C. et al. (2010) Early outcomes of endoscopic transsphenoidal surgery for adult craniopharyngiomas. Neurosurgical Focus, 28, E9. 7 Thompson, D., Phipps, K. & Hayward, R. (2005) Craniopharyngioma in childhood: our evidence-based approach to management. Childs Nervous System, 21, 660–668. 8 Kalapurakal, J.A. (2005) Radiation therapy in the management of pediatric craniopharyngiomas–a review. Childs Nervous System, 21, 808–816. 9 Merchant, T.E., Kiehna, E.N., Sanford, R.A. et al. (2002) Craniopharyngioma: the St. Jude Children’s Research Hospital experience 1984–2001. International Journal of Radiation Oncology Biology Physics, 53, 533–542. 10 Barriger, R.B., Chang, A., Lo, S.S. et al. (2011) Phosphorus-32 therapy for cystic craniopharyngiomas. Radiotherapy and Oncology, 98, 207–212. 11 Blackburn, T.P., Doughty, D. & Plowman, P.N. (1999) Stereotactic intracavitary therapy of recurrent cystic craniopharyngioma by instillation of 90yttrium. British Journal of Neurosurgery, 13, 359–365. 12 Derrey, S., Blond, S., Reyns, N. et al. (2008) Management of cystic craniopharyngiomas with stereotactic endocavitary irradiation using colloidal 186Re: a retrospective study of 48 consecutive patients. Neurosurgery, 63, 1045–1052; discussion 1052–3. 13 Julow, J.V. (2013) Intracystic irradiation for craniopharyngiomas. Pituitary, 16, 34–45. 14 Julow, J., Backlund, E.O., Lanyi, F. et al. (2007) Long-term results and late complications after intracavitary yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas. Neurosurgery, 61, 288–295; discussion 295–6. 15 Mottolese, C., Szathmari, A., Berlier, P. et al. (2005) Craniopharyngiomas: our experience in Lyon. Childs Nervous System, 21, 790–798. 16 Lafay-Cousin, L., Bartels, U., Raybaud, C. et al. (2007) Neuroradiological findings of bleomycin leakage in cystic craniopharyngioma. Report of three cases. Journal of Neurosurgery, 107, 318–323. 17 Mottolese, C., Stan, H., Hermier, M. et al. (2001) Intracystic chemotherapy with bleomycin in the treatment of craniopharyngiomas. Childs Nervous System, 17, 724–730. 18 Jakacki, R.I., Cohen, B.H., Jamison, C. et al. (2000) Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas. Journal of Neurosurgery, 92, 255–260. 19 Ierardi, D.F., Fernandes, M.J., Silva, I.R. et al. (2007) Apoptosis in alpha interferon (IFN-alpha) intratumoral chemotherapy for
6 S. Bailey and J. Parkes cystic craniopharyngiomas. Childs Nervous System, 23, 1041– 1046. 20 Cavalheiro, S., Dastoli, P.A., Silva, N.S. et al. (2005) Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma. Childs Nervous System, 21, 719–724. 21 Cavalheiro, S., Di Rocco, C., Valenzuela, S. et al. (2010) Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases. Neurosurgical Focus, 28, E12.
22 Zanon, N., Cavalheiro, S. & da Silva, M.C. (2008) Does the choice of surgical approach to insert an intratumoral catheter influence the results of intratumoral cystic treatment? Surgical Neurology, 70, 66–69; discussion 69. 23 Pettorini, B.L., Tamburrini, G., Massimi, L. et al. (2009) Endoscopic transventricular positioning of intracystic catheter for treatment of craniopharyngioma. Technical note. Journal of Neurosurgery and Pediatrics, 4, 245–248.
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
doi: 10.1111/cen.12568
CLINICAL QUESTION
Intracystic interferon therapy in childhood craniopharyngioma: who, when and how? Simon Bailey* and Jeannette Parkes† *Great North Childrens Hospital, Newcastle upon Tyne, UK and †Department of Radiation Oncology, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa
Summary A 13-year-old male presents with fluctuating visual disturbance and headaches. Imaging reveals a significant predominantly cystic suprasellar tumour, typical of a craniopharyngioma. The patient has growth hormone deficiency but the rest of the hypothalamic/pituitary axis is intact. What are the options for therapy in 2014? Specifically, is there a role for local treatment with interferon injected into the cyst cavity? The aim of management in children with craniopharyngiomas is to reduce the impact of the tumour as much as possible, while minimising the morbidity associated with treatment. There are a number of therapeutic options available: surgery, radiotherapy and the insertion of therapeutic agents directly into the tumour cyst. The role of intracystic therapy in the form of interferon is discussed; including when to use this therapeutic option and practical details of its use. (Received 25 April 2014; returned for revision 7 June 2014; finally revised 19 July 2014; accepted 21 July 2014)
Background of treatment options Craniopharyngiomas account for 5–10% of childhood brain tumours. They are frequently cystic but also contain solid tumour elements which are often calcified.1–3 The commonest presenting features relate to either raised intracranial pressure, endocrine abnormalities or visual field deficits. Endocrine abnormalities can involve some or all components of the hypothalamic/pituitary axis. The direct mortality rate for this tumour is low (60% of the tumour should be cystic). Other characteristics in addition to that above which should make one consider intracystic therapy include young patients with a predominantly cystic tumour, those patients with a cystic tumour and minimal
Table 1. Characteristics of craniopharyngiomas and appropriate therapies Characteristic
Surgery
Radiotherapy
Intracystic therapy
Predominantly cystic tumour >60% cyst Predominantly solid component Minimal hormonal deficits Panhypopituitarism Recurrence after surgery and radiotherapy Recurrence after surgery
+
+
+++
++
++
+
+
+++
+++ +
+++
+ +++ (if predominantly cystic)
+
+++
+++ (if predominantly cystic)
hormonal deficits or those who develop a recurrent cyst post radiotherapy or surgery. In some countries, hormone replacement and especially growth hormone is not readily available and in such cases preservation of a functioning growth hormone axis until after puberty may be an important consideration when choosing treatment options in those with cystic craniopharyngiomas. The cyst should measure a minimum of 2 cm in depth in order to allow the catheter tip of the Rickham or Ommaya reservoir to be completely enclosed by the cyst. Providing there is an initial response, intracystic therapy may be repeated. Up to nine courses have been used although a median of 2–4 is usual.2,19–21 At presentation, it must be ensured that any significant hydrocephalus is treated. The insertion of a reservoir with consequent cyst decompression may alleviate hydrocephalus. Occasionally, simple cyst decompression will be sufficient treatment on its own, but the majority of cysts will re-accumulate without further treatment. If the cyst has been decompressed, intracystic therapy should not be commenced until there is re-accumulation of the cyst, or in the case of recurrence. Intracystic therapy is unlikely to affect the solid portion of the tumour, but this may not progress or may only require further therapy at a later date (usually in the form of Radiotherapy and/or surgery). In terms of long-term outcome, it is preferable to delay radiotherapy/surgery until after puberty, if possible.2 Intracystic therapy is particularly attractive for those patients with minimal existing hormonal deficits and who fulfil the criteria mentioned above. Interferon a appears to be at least as effective as bleomycin and intracystic radioactive compounds, but has the advantage that any leak developing around the catheter has less potential for damage of the surrounding normal brain.
How to deliver intracystic therapy If intracystic therapy is undertaken, the first step is the insertion of an intracystic reservoir such as a Rickham or Ommaya reservoir. These may be inserted in three main ways: 1) insertion under direct vision, 2) insertion under stereotactic control or
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
Intracystic interferon therapy 3
Fig. 1 Details of administration of intracystic interferon a (Adapted from Bartels et al2). © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
4 S. Bailey and J. Parkes using an endoscope or 3) free hand insertion via a burr hole. The complication rates are similar22,23 but endoscopic insertion is believed to offer the safest route and the best opportunity to break down any cyst septations. However occasionally due to the thickness of the cyst wall, it may be technically difficult to insert the catheter using this method and insertion under direct vision may be necessary. It is important that the neurosurgeon is experienced and comfortable with the technique to be used. The majority of the catheters used with reservoirs have side holes up to a level of 2 cm from the tip, and all these perforations should be located within the cyst cavity to ensure that there is no subsequent leak. The catheter needs to be in place for a minimum of 5 days, but preferably 2 weeks after insertion, to allow a seal to form around it. It is advisable to perform a MRI scan to check the position of the catheter and cyst size, a single T2 sagittal sequence may be sufficient (Fig. 2). A leak test should then be performed (see Fig. 1 for details and Fig. 2 for example). Prior to commencing Interferon a, the patient should have blood electrolytes, a full blood and a complete endocrinological
(a)
(c)
workup with replacement therapy as deemed appropriate. A complete opthalmological assessment to document any visual deficits (including fields, acuity and eye movements) should be done. The recommended treatment course for intracystic interferon a is three times a week (usually Monday, Wednesday, Friday) for a total of 4 weeks (12 doses). The details of administration are found in Fig. 1. If the fluid is clear, this may suggest that the cyst has collapsed and the catheter tip is within a CSF space (usually the third ventricle) and if that is the case then interferon should not be given. An MRI scan should be performed after each 4 week course or earlier if the fluid has become clear. If there is a complete response then no further courses may be necessary. If there is a partial response, then a further course should be given. In cases where there is no response then alternative therapy should be considered. When there is a complete response (with a minimum of two courses) or there ceases to be any further response, the therapy should be stopped. Follow-up MRI scans should be performed every 3–4 months in the first year after completion
(b)
(d)
Fig. 2 (a) Coronal T1 MRI scan with contrast showing a large cystic craniopharyngioma. (b) Leak test showing an intact cyst with no leak. (c) Leak test showing a leak into the 4th ventricle (via the third ventricle) as well as contrast within the cystic portion of a child with carniopharyngioma. (d) Leak test showing cyst with local and ventricular leak. © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
Intracystic interferon therapy 5 of therapy. Beyond the first year, scanning frequency should be based on institutional guidelines.
What are the potential pitfalls and side effects? 1 Poor patient selection is the major pitfall in the use of intracystic therapy. It is essential that the decision to use this therapy is carefully discussed in a multi-disciplinary team (MDT) setting. This includes, neurosurgeons, endocrinologists, radiation oncologists and in the case of children, paediatric oncologists. The patients and their families need to have the proposed intracystic treatment carefully described to them, with the rationale behind its use in their particular circumstances. 2 Catheter leakage or some of the catheter perforations being outside the cyst is a major potential problem. This will be seen on the leak test but if clear fluid, instead of proteinaceous cyst fluid, is aspirated prior to therapy being started then it is likely that the catheter is not completely enclosed by the cyst. The fluid aspirate may thin as treatment progresses. 3 Side effects of interferon are usually predictable and self limiting; predominantly arthralgia, fatigue, fevers and occasionally new endocrine deficits.2,19–21 These tend to reduce as the course of treatment continues and it is very rare that treatment needs to be suspended for them. Simple antipyretics and analgesics are usually all that is required. The patient and their family should be warned of the potential side effects and given antipyretics to take home. It is also important that they have a robust mechanism for contacting members of the treating team at all times.
Will further therapy be needed? Craniopharyngioma is considered a chronic disease and multiple treatment modalities may be required at different times. If intracystic therapy has been used and proven to be effective, then this may be repeated. An alternative form of intracystic therapy such as bleomycin or colloidal radioactive compounds may also be considered. In the case of mixed solid/cystic or complex cystic tumours, it is likely that other therapeutic options such as primary surgery and/or external beam radiotherapy (photons, protons or radiosurgery) will be considered. The timing and choice of these therapeutic options remains one of the biggest challenges in the management of these tumours.1,3 Mortality rates may be low for these tumours, but morbidity is high and the further impact of treatment on quality of life remains a major hurdle.
Summary Intracystic interferon therapy for craniopharyngioma is an effective treatment option for a subset of patients with craniopharyngioma and may decrease the treatment-related morbidity associated with this chronic tumour, resulting in improved quality of life. It is important that patients chosen for this treatment option are carefully selected and discussed within the MDT setting prior to embarking on this therapeutic option. © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
References 1 Muller, H.L. (2010a) Childhood craniopharyngioma–current concepts in diagnosis, therapy and follow-up. Nature Reviews. Endocrinology, 6, 609–618. 2 Bartels, U., Laperriere, N., Bouffet, E. et al. (2012) Intracystic therapies for cystic craniopharyngioma in childhood. Frontiers in Endocrinology (Lausanne), 3, 39. 3 Muller, H.L. (2014) Craniopharyngioma. Endocrine Reviews, 35, 513–543. 4 Hukin, J., Steinbok, P., Lafay-Cousin, L. et al. (2007) Intracystic bleomycin therapy for craniopharyngioma in children: the Canadian experience. Cancer, 109, 2124–2131. 5 Muller, H.L. (2010b) Increased daytime sleepiness in patients with childhood craniopharyngioma and hypothalamic tumor involvement: review of the literature and perspectives. International Journal of Endocrinology, 2010, 519607. 6 Jane, J.A.J., Kiehna, E., Payne, S.C. et al. (2010) Early outcomes of endoscopic transsphenoidal surgery for adult craniopharyngiomas. Neurosurgical Focus, 28, E9. 7 Thompson, D., Phipps, K. & Hayward, R. (2005) Craniopharyngioma in childhood: our evidence-based approach to management. Childs Nervous System, 21, 660–668. 8 Kalapurakal, J.A. (2005) Radiation therapy in the management of pediatric craniopharyngiomas–a review. Childs Nervous System, 21, 808–816. 9 Merchant, T.E., Kiehna, E.N., Sanford, R.A. et al. (2002) Craniopharyngioma: the St. Jude Children’s Research Hospital experience 1984–2001. International Journal of Radiation Oncology Biology Physics, 53, 533–542. 10 Barriger, R.B., Chang, A., Lo, S.S. et al. (2011) Phosphorus-32 therapy for cystic craniopharyngiomas. Radiotherapy and Oncology, 98, 207–212. 11 Blackburn, T.P., Doughty, D. & Plowman, P.N. (1999) Stereotactic intracavitary therapy of recurrent cystic craniopharyngioma by instillation of 90yttrium. British Journal of Neurosurgery, 13, 359–365. 12 Derrey, S., Blond, S., Reyns, N. et al. (2008) Management of cystic craniopharyngiomas with stereotactic endocavitary irradiation using colloidal 186Re: a retrospective study of 48 consecutive patients. Neurosurgery, 63, 1045–1052; discussion 1052–3. 13 Julow, J.V. (2013) Intracystic irradiation for craniopharyngiomas. Pituitary, 16, 34–45. 14 Julow, J., Backlund, E.O., Lanyi, F. et al. (2007) Long-term results and late complications after intracavitary yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas. Neurosurgery, 61, 288–295; discussion 295–6. 15 Mottolese, C., Szathmari, A., Berlier, P. et al. (2005) Craniopharyngiomas: our experience in Lyon. Childs Nervous System, 21, 790–798. 16 Lafay-Cousin, L., Bartels, U., Raybaud, C. et al. (2007) Neuroradiological findings of bleomycin leakage in cystic craniopharyngioma. Report of three cases. Journal of Neurosurgery, 107, 318–323. 17 Mottolese, C., Stan, H., Hermier, M. et al. (2001) Intracystic chemotherapy with bleomycin in the treatment of craniopharyngiomas. Childs Nervous System, 17, 724–730. 18 Jakacki, R.I., Cohen, B.H., Jamison, C. et al. (2000) Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas. Journal of Neurosurgery, 92, 255–260. 19 Ierardi, D.F., Fernandes, M.J., Silva, I.R. et al. (2007) Apoptosis in alpha interferon (IFN-alpha) intratumoral chemotherapy for
6 S. Bailey and J. Parkes cystic craniopharyngiomas. Childs Nervous System, 23, 1041– 1046. 20 Cavalheiro, S., Dastoli, P.A., Silva, N.S. et al. (2005) Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma. Childs Nervous System, 21, 719–724. 21 Cavalheiro, S., Di Rocco, C., Valenzuela, S. et al. (2010) Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases. Neurosurgical Focus, 28, E12.
22 Zanon, N., Cavalheiro, S. & da Silva, M.C. (2008) Does the choice of surgical approach to insert an intratumoral catheter influence the results of intratumoral cystic treatment? Surgical Neurology, 70, 66–69; discussion 69. 23 Pettorini, B.L., Tamburrini, G., Massimi, L. et al. (2009) Endoscopic transventricular positioning of intracystic catheter for treatment of craniopharyngioma. Technical note. Journal of Neurosurgery and Pediatrics, 4, 245–248.
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 0, 1–6
