- Email: [email protected]
A Perspective on Craniopharyngioma
Perspectives Commentary on: Predictive Factors for Craniopharyngioma Recurrence: A Systematic Review and Illustrative Case Report of a Rapid Recurrence by Prieto et al. pp. 733-749.
Griffith R. Harsh, IV, M.D. Professor, Department of Neurosurgery Stanford Hospitals and Clinics
A Perspective on Craniopharyngioma Robert M. Lober and Griffith R. Harsh, IV
R
elatively rare, with an incidence of 0.1 cases per 100,000 person-years, and comprising 6.6% of sellar tumors (4), the craniopharyngioma remains a major therapeutic challenge to even the most experienced neurosurgeon. With improved neuroimaging, microneurosurgery, neuroendoscopy, and adjuvant therapies, the overall 10-year survival for craniopharyngioma is now close to 90% (6), in stark contrast to the 41% perioperative mortality during the first part of the last century (17). We know that most patients will survive their disease and attempts to treat it, but we have difficulty in predicting which patients might remain virtually symptom-free for decades without treatment, which ones might be severely debilitated despite our best efforts, and which ones can be safely cured with surgery alone. Because morbidity from visual loss and hypothalamic function remains high, the surgical management of craniopharyngioma remains controversial. After the advent of steroid replacement therapy in the 1950s, Matson and Crigler at Boston Children’s Hospital adopted the philosophy of attempting gross total resection for every patient with the belief that anything less was inevitably followed by recurrence (13). Meanwhile, their contemporaries at Jefferson Medical Center subscribed to a different approach: biopsy and cyst decompression followed by radiotherapy, which were curative in most patients (12). These two camps became increasingly distinct as surgical techniques improved with the use of the operating microscope in the late 1960s and early 1970s. Hoffman et al. (9) at the Hospital for Sick Children in Toronto followed Matson and Crigler in attempting gross total resection whenever possible to avoid radiotherapy (a source of cognitive dysfunction, delayed vascular compromise, and secondary malignancy). In their series of 48 patients, complete excision in 17 patients resulted in no recurrence and 12% mortality; subtotal resection in 15 patients resulted in 53%
Key words 䡲 Craniopharyngioma 䡲 Gliosis 䡲 Ki-67 䡲 P53 䡲 Recurrence 䡲 Regrowth
WORLD NEUROSURGERY 79 [5/6]: 645-646, MAY/JUNE 2013
recurrence and 13% mortality; and cyst aspiration in 16 patients resulted in 100% recurrence and 63% mortality. Radiotherapy followed subtotal resection in six patients (one prophylactically and five upon recurrence), and followed cyst aspiration in 10 patients (two prophylactically and eight upon recurrence). In contrast, Richmond et al. (15) at the University of California, San Francisco concluded that biopsy and/or cyst drainage followed by radiotherapy produced outcomes similar to those of aggressive treatment. In their series of 32 patients, five-year survival was 88% after gross total resection or subtotal resection with radiotherapy, and 100% after biopsy or cyst aspiration with radiotherapy. Bartlett’s contention that complete excision is essentially impossible (1) was supported by his postmortem examinations and the high recurrence rate in almost every major surgical series in the era of computed tomography and magnetic resonance imaging. Tumors often adhere to the hypothalamus, optic chiasm, or major vessels at the base of the brain (3). Pathologic studies have identified microscopic “pegs” of tumor that is left embedded in gliotic hypothalamic tissue (15); these are the origins of tumor regrowth. In a recent large series representative of many previous reports, gross total resection was achieved in all intrasellar tumors but in only approximately 80% of suprasellar tumors and 64% of “giant” tumors (2). The tumor recurrence rate was approximately 8% after gross total resection and 50% after less than gross total resection. Recently, the authors of a retrospective review of 171 patients of the Craniopharyngioma Study Group in France showed that hydrocephalus at presentation was a significant predictor of tumor recurrence, even after they adjusted for incomplete resection (8). This surprising finding, not previously seen in smaller studies (7, 11, 16), corroborated the results of another recent multivariate analysis of 86 children (5). This finding suggests that
Department of Neurosurgery, Stanford Hospitals and Clinics, Stanford, California, USA To whom correspondence should be addressed: Griffith R. Harsh, IV, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2013) 79, 5/6:645-646. http://dx.doi.org/10.1016/j.wneu.2012.10.064
www.WORLDNEUROSURGERY.org
645
PERSPECTIVES
tumor location, including its effect on the third ventricle and possible invasion of the hypothalamus, may be more important than therapeutic strategy in predicting recurrence. To this day, the field remains polarized, with advocates of each approach reporting similar rates of progression-free and overall survival. Some neurosurgeons, however, have adopted a more flexible strategy, attempting gross total resection only when the risk of hypothalamic injury is low or in cases of solid tumors (10). Whether adjuvant therapy should be given soon after surgery or at recurrence is also controversial. Adjuvant options include external beam irradiation, intracystic irradiation or chemotherapy, stereotactic radiosurgery or fractionated radiotherapy, and systemic chemotherapy (10). There are no prospective, randomized studies for craniopharyngioma, and all reports are biased by patient selection, physician specialty and surgical philosophy. Having observed a rapid recurrence in one of their own patients, Prieto et al. (14) in Madrid, Spain, sought therapeutic variables or morphologic, histologic, or molecular markers independently predictive of recurrence. This was difficult because most studies have focused on the extent of tumor resection (with varying definitions) and postoperative radiotherapy. Moreover, recurrence is inconsistently defined as growth of residual tumor, asymptomatic radiographic findings on a surveillance scan, or even symptomatic enlargement of an irradiated cyst that might subsequently regress. With these recognized limitations, the Madrid group found that, in most studies, extent of resection correlated with risk of recurrence, with aggregate rates of 23% and 63% after gross total and subtotal resection, respectively, and of 20% after
REFERENCES 1. Bartlett JR: Craniopharyngiomas—a summary of 85 cases. J Neurol Neurosurg Psychiat 34:37-41, 1971. 2. Caldarelli M, Massimi L, Tamburrini G, Cappa M, Di Rocco C: Long-term results of the surgical treatment of craniopharyngioma: the experience at the Policlinico Gemelli, Catholic University, Rome. Childs Nerv Syst 21:747-757, 2005. 3. Carmel PW, Antunes JL, Chang CH: Craniopharyngiomas in children. Neurosurgery 11:382-389, 1982. 4. Central Brain Tumor Registry of the United States: Primary Brain Tumors in the United States, 19972001: Statistical Report. Hinsdale IL: Central Brain Tumor Registry of the United States; 2004 5. Elliott RE, Hsieh K, Hochman T, Belitskaya-Levy I, Wisoff J, Wisoff JH: Efficacy and safety of radical resection of primary recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatrics 5:30-48, 2010. 6. Elliott RE, Jane JA Jr, Wisoff JH: Surgical management of craniopharyngiomas in children: metaanalysis and comparison of transcranial and transsphenoidal approaches. Neurosurgery 69:630-643, 2011.
646
www.SCIENCEDIRECT.com
subtotal resection with radiotherapy (14). Large size (⬎3 cm), involvement of the third ventricle, and adherence to neurovascular structures were associated with recurrence, but these findings were difficult to separate from the contribution of extent of resection. The authors found no differences in outcome between adamantinomatous and squamous papillary subtypes in the reviewed literature and no consensus about an association with either proliferation index (Ki-67) or p53 mutation. Bartlett recognized more than 40 years ago (1) what Prieto et al. continue to find in the current literature: that the great variability in the behavior of craniopharyngiomas confounds the prediction of both the natural history and response to therapy of any individual tumor. Currently, we can agree that: (1) some (particularly predominantly intrasellar) tumors can be safely removed, (2) complete resection of tumors not invading the hypothalamus permits eschewing irradiation unless recurrence is seen, and (3) craniopharyngioma remnants not treated with radiation will regrow. Thus, many clinicians, influenced by one school or the other, continue to treat every patient uniformly. Prieto et al. appropriately seek prognostic indicators that might guide the aggressiveness of our approach to each patient individually, but they find little definitive evidence. Although freedom from recurrence does correlate with extent of resection, we cannot conclude that more extensive subtotal resection leads to better outcomes than less extensive subtotal resection followed by irradiation, nor do we know that increased freedom from recurrence after complete removal of a supradiaphragmatic tumor leads to longer survival or better functional outcomes than does subtotal resection followed by irradiation.
7. Fisher PG, Jenab J, Goldthwaite PT, Tihan T, Wharam MD, Foer DR, Burger PC: Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 14:558-563, 1998. 8. Gautier A, Godbout A, Grosheny C, Tejedor I, Coudert M, Courtillot C, Jublanc C, De Kerdanet M, Poirier JY, Riffaud L, Sainte-Rose C, Van Effenterre R, Brassier G, Bonnet F, Touraine P; Craniopharyngioma Study Group: Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients. J Clin Endocrinol Metab 97:1258-1267, 2012. 9. Hoffman HJ, Hendrick EB, Humphreys RP, Buncic JR, Armstrong DL, Jenkin RDT: Management of craniopharyngioma in children. J Neurosurg 47:218227, 1977. 10. Karavatiki N, Cudlip S, Adams CBT, Wass JAH: Craniopharyngiomas. Endocr Rev 27:371-397, 2006. 11. Kim SK, Wang KC, Shin SH, Choe G, Chi JG, Cho BK: Radical excision of pediatric craniopharyngioma: recurrence pattern and prognostic factors. Childs Nerv Syst 17:531-536, 2001. 12. Kramer S, Southard M, Mansfield CM: Radiotherapy in the management of craniopharyngiomas: further experiences and late results. Am J Roentgenol Radium Ther Nucl Med 103:44-52, 1968.
13. Matson DD, Crigler JF: Management of craniopharyngioma in childhood. J Neurosurg 30:377-390, 1969. 14. Prieto R, Pascual JM, Subhi-Issa I, Jorquera M, Yus M, Martinez R: Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence. World Neurosurg 79:733-749, 2013. 15. Richmond IL, Wara WM, Wilson CB: Role of radiation therapy in the management of craniopharyngiomas in children. Neurosurgery 6:513-517, 1980. 16. Tomita T, Bowman RB: Craniopharyngiomas in children: surgical experience at Children’s Memorial Hospital. Child’s Nerv Syst 21:729-746, 2005. 17. Tytus JS, Seltzer HS, Kahn EA: Cortisone as an aid in the surgical treatment of craniopharyngiomas. J Neurosurg 12:555-564, 1955. Citation: World Neurosurg. (2013) 79, 5/6:645-646. http://dx.doi.org/10.1016/j.wneu.2012.10.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2013 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2012.10.064
Griffith R. Harsh, IV, M.D. Professor, Department of Neurosurgery Stanford Hospitals and Clinics
A Perspective on Craniopharyngioma Robert M. Lober and Griffith R. Harsh, IV
R
elatively rare, with an incidence of 0.1 cases per 100,000 person-years, and comprising 6.6% of sellar tumors (4), the craniopharyngioma remains a major therapeutic challenge to even the most experienced neurosurgeon. With improved neuroimaging, microneurosurgery, neuroendoscopy, and adjuvant therapies, the overall 10-year survival for craniopharyngioma is now close to 90% (6), in stark contrast to the 41% perioperative mortality during the first part of the last century (17). We know that most patients will survive their disease and attempts to treat it, but we have difficulty in predicting which patients might remain virtually symptom-free for decades without treatment, which ones might be severely debilitated despite our best efforts, and which ones can be safely cured with surgery alone. Because morbidity from visual loss and hypothalamic function remains high, the surgical management of craniopharyngioma remains controversial. After the advent of steroid replacement therapy in the 1950s, Matson and Crigler at Boston Children’s Hospital adopted the philosophy of attempting gross total resection for every patient with the belief that anything less was inevitably followed by recurrence (13). Meanwhile, their contemporaries at Jefferson Medical Center subscribed to a different approach: biopsy and cyst decompression followed by radiotherapy, which were curative in most patients (12). These two camps became increasingly distinct as surgical techniques improved with the use of the operating microscope in the late 1960s and early 1970s. Hoffman et al. (9) at the Hospital for Sick Children in Toronto followed Matson and Crigler in attempting gross total resection whenever possible to avoid radiotherapy (a source of cognitive dysfunction, delayed vascular compromise, and secondary malignancy). In their series of 48 patients, complete excision in 17 patients resulted in no recurrence and 12% mortality; subtotal resection in 15 patients resulted in 53%
Key words 䡲 Craniopharyngioma 䡲 Gliosis 䡲 Ki-67 䡲 P53 䡲 Recurrence 䡲 Regrowth
WORLD NEUROSURGERY 79 [5/6]: 645-646, MAY/JUNE 2013
recurrence and 13% mortality; and cyst aspiration in 16 patients resulted in 100% recurrence and 63% mortality. Radiotherapy followed subtotal resection in six patients (one prophylactically and five upon recurrence), and followed cyst aspiration in 10 patients (two prophylactically and eight upon recurrence). In contrast, Richmond et al. (15) at the University of California, San Francisco concluded that biopsy and/or cyst drainage followed by radiotherapy produced outcomes similar to those of aggressive treatment. In their series of 32 patients, five-year survival was 88% after gross total resection or subtotal resection with radiotherapy, and 100% after biopsy or cyst aspiration with radiotherapy. Bartlett’s contention that complete excision is essentially impossible (1) was supported by his postmortem examinations and the high recurrence rate in almost every major surgical series in the era of computed tomography and magnetic resonance imaging. Tumors often adhere to the hypothalamus, optic chiasm, or major vessels at the base of the brain (3). Pathologic studies have identified microscopic “pegs” of tumor that is left embedded in gliotic hypothalamic tissue (15); these are the origins of tumor regrowth. In a recent large series representative of many previous reports, gross total resection was achieved in all intrasellar tumors but in only approximately 80% of suprasellar tumors and 64% of “giant” tumors (2). The tumor recurrence rate was approximately 8% after gross total resection and 50% after less than gross total resection. Recently, the authors of a retrospective review of 171 patients of the Craniopharyngioma Study Group in France showed that hydrocephalus at presentation was a significant predictor of tumor recurrence, even after they adjusted for incomplete resection (8). This surprising finding, not previously seen in smaller studies (7, 11, 16), corroborated the results of another recent multivariate analysis of 86 children (5). This finding suggests that
Department of Neurosurgery, Stanford Hospitals and Clinics, Stanford, California, USA To whom correspondence should be addressed: Griffith R. Harsh, IV, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2013) 79, 5/6:645-646. http://dx.doi.org/10.1016/j.wneu.2012.10.064
www.WORLDNEUROSURGERY.org
645
PERSPECTIVES
tumor location, including its effect on the third ventricle and possible invasion of the hypothalamus, may be more important than therapeutic strategy in predicting recurrence. To this day, the field remains polarized, with advocates of each approach reporting similar rates of progression-free and overall survival. Some neurosurgeons, however, have adopted a more flexible strategy, attempting gross total resection only when the risk of hypothalamic injury is low or in cases of solid tumors (10). Whether adjuvant therapy should be given soon after surgery or at recurrence is also controversial. Adjuvant options include external beam irradiation, intracystic irradiation or chemotherapy, stereotactic radiosurgery or fractionated radiotherapy, and systemic chemotherapy (10). There are no prospective, randomized studies for craniopharyngioma, and all reports are biased by patient selection, physician specialty and surgical philosophy. Having observed a rapid recurrence in one of their own patients, Prieto et al. (14) in Madrid, Spain, sought therapeutic variables or morphologic, histologic, or molecular markers independently predictive of recurrence. This was difficult because most studies have focused on the extent of tumor resection (with varying definitions) and postoperative radiotherapy. Moreover, recurrence is inconsistently defined as growth of residual tumor, asymptomatic radiographic findings on a surveillance scan, or even symptomatic enlargement of an irradiated cyst that might subsequently regress. With these recognized limitations, the Madrid group found that, in most studies, extent of resection correlated with risk of recurrence, with aggregate rates of 23% and 63% after gross total and subtotal resection, respectively, and of 20% after
REFERENCES 1. Bartlett JR: Craniopharyngiomas—a summary of 85 cases. J Neurol Neurosurg Psychiat 34:37-41, 1971. 2. Caldarelli M, Massimi L, Tamburrini G, Cappa M, Di Rocco C: Long-term results of the surgical treatment of craniopharyngioma: the experience at the Policlinico Gemelli, Catholic University, Rome. Childs Nerv Syst 21:747-757, 2005. 3. Carmel PW, Antunes JL, Chang CH: Craniopharyngiomas in children. Neurosurgery 11:382-389, 1982. 4. Central Brain Tumor Registry of the United States: Primary Brain Tumors in the United States, 19972001: Statistical Report. Hinsdale IL: Central Brain Tumor Registry of the United States; 2004 5. Elliott RE, Hsieh K, Hochman T, Belitskaya-Levy I, Wisoff J, Wisoff JH: Efficacy and safety of radical resection of primary recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatrics 5:30-48, 2010. 6. Elliott RE, Jane JA Jr, Wisoff JH: Surgical management of craniopharyngiomas in children: metaanalysis and comparison of transcranial and transsphenoidal approaches. Neurosurgery 69:630-643, 2011.
646
www.SCIENCEDIRECT.com
subtotal resection with radiotherapy (14). Large size (⬎3 cm), involvement of the third ventricle, and adherence to neurovascular structures were associated with recurrence, but these findings were difficult to separate from the contribution of extent of resection. The authors found no differences in outcome between adamantinomatous and squamous papillary subtypes in the reviewed literature and no consensus about an association with either proliferation index (Ki-67) or p53 mutation. Bartlett recognized more than 40 years ago (1) what Prieto et al. continue to find in the current literature: that the great variability in the behavior of craniopharyngiomas confounds the prediction of both the natural history and response to therapy of any individual tumor. Currently, we can agree that: (1) some (particularly predominantly intrasellar) tumors can be safely removed, (2) complete resection of tumors not invading the hypothalamus permits eschewing irradiation unless recurrence is seen, and (3) craniopharyngioma remnants not treated with radiation will regrow. Thus, many clinicians, influenced by one school or the other, continue to treat every patient uniformly. Prieto et al. appropriately seek prognostic indicators that might guide the aggressiveness of our approach to each patient individually, but they find little definitive evidence. Although freedom from recurrence does correlate with extent of resection, we cannot conclude that more extensive subtotal resection leads to better outcomes than less extensive subtotal resection followed by irradiation, nor do we know that increased freedom from recurrence after complete removal of a supradiaphragmatic tumor leads to longer survival or better functional outcomes than does subtotal resection followed by irradiation.
7. Fisher PG, Jenab J, Goldthwaite PT, Tihan T, Wharam MD, Foer DR, Burger PC: Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 14:558-563, 1998. 8. Gautier A, Godbout A, Grosheny C, Tejedor I, Coudert M, Courtillot C, Jublanc C, De Kerdanet M, Poirier JY, Riffaud L, Sainte-Rose C, Van Effenterre R, Brassier G, Bonnet F, Touraine P; Craniopharyngioma Study Group: Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients. J Clin Endocrinol Metab 97:1258-1267, 2012. 9. Hoffman HJ, Hendrick EB, Humphreys RP, Buncic JR, Armstrong DL, Jenkin RDT: Management of craniopharyngioma in children. J Neurosurg 47:218227, 1977. 10. Karavatiki N, Cudlip S, Adams CBT, Wass JAH: Craniopharyngiomas. Endocr Rev 27:371-397, 2006. 11. Kim SK, Wang KC, Shin SH, Choe G, Chi JG, Cho BK: Radical excision of pediatric craniopharyngioma: recurrence pattern and prognostic factors. Childs Nerv Syst 17:531-536, 2001. 12. Kramer S, Southard M, Mansfield CM: Radiotherapy in the management of craniopharyngiomas: further experiences and late results. Am J Roentgenol Radium Ther Nucl Med 103:44-52, 1968.
13. Matson DD, Crigler JF: Management of craniopharyngioma in childhood. J Neurosurg 30:377-390, 1969. 14. Prieto R, Pascual JM, Subhi-Issa I, Jorquera M, Yus M, Martinez R: Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence. World Neurosurg 79:733-749, 2013. 15. Richmond IL, Wara WM, Wilson CB: Role of radiation therapy in the management of craniopharyngiomas in children. Neurosurgery 6:513-517, 1980. 16. Tomita T, Bowman RB: Craniopharyngiomas in children: surgical experience at Children’s Memorial Hospital. Child’s Nerv Syst 21:729-746, 2005. 17. Tytus JS, Seltzer HS, Kahn EA: Cortisone as an aid in the surgical treatment of craniopharyngiomas. J Neurosurg 12:555-564, 1955. Citation: World Neurosurg. (2013) 79, 5/6:645-646. http://dx.doi.org/10.1016/j.wneu.2012.10.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2013 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2012.10.064