, Volume 64, Issue 1, pp 31–37 | Cite as

Excess mortality after craniopharyngioma treatment: are we making progress?

  • Nidan QiaoEmail author
Mini Review



Craniopharyngioma is associated with an increased risk of mortality even after surgical, radiotherapeutic and hormone supplementations. Previous studies using different designs showed a possible trend of decreasing mortality in recent years. This review summarises studies reporting standardised mortality ratio (SMR) after craniopharyngioma treatment, as well as the bias and confounding in these studies to plan further researches.


PubMed and Embase was searched for manuscripts published before October 2018 using medical subject heading terms (“craniopharyngioma” or “hypopituitarism” and “mortality”).


Eight studies reported SMR after craniopharyngioma treatment, with a total of 2802 patients. The subgroup meta-analysis using random effects model was conducted to pool the SMR, which was 6.2 (95% CI 4.1–9.4) before 2010 and 2.9 (95% CI 2.2–3.8) after 2010 (subgroup test p < 0.01), respectively. Misclassification (one study) and selection bias (six studies) either inflated or deflated the result. The trend of increasing survival rate over the time was observed in studies without reporting SMR. Female patients, childhood-onset disease, hydrocephalus, tumour recurrence, body mass index and panhypopituitarism were identified as the important risk factors for excess mortality.


Though bias and confounding existed across studies, the decreasing SMR and increasing survival rate over the time was in favour of a real signal. It is necessary to launch studies to further investigate the morality and risk factors after multidisciplinary treatment of craniopharyngioma in a hospital-based manner, using the modern statistical method to adjust for bias and confounding.


Craniopharyngioma Mortality Survival Hypopituitarism 


Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.


  1. 1.
    H.L. Müller, Diagnosis, treatment, clinical course, and prognosis of childhood-onset craniopharyngioma patients. Minerva Endocrinol. 42(4), 356–375 (2017). Google Scholar
  2. 2.
    P. Mortini, Craniopharyngiomas: a life-changing tumor. Endocrine 57(2), 191–192 (2017). Google Scholar
  3. 3.
    J.A. Jane, E.R. Laws, Craniopharyngioma. Pituitary 9(4), 323–326 (2006). (2017) 42(4):356–375
  4. 4.
    L.Z. Leng, J.P. Greenfield, M.M. Souweidane, V.K. Anand, T.H. Schwartz, Endoscopic, endonasal resection of craniopharyngiomas: analysis of outcome including extent of resection, cerebrospinal fluid leak, return to preoperative productivity, and body mass index. Neurosurgery 70(1), 110–23 (2012). discussion123–4Google Scholar
  5. 5.
    A. Aggarwal, N. Fersht, M. Brada, Radiotherapy for craniopharyngioma. Pituitary 16(1), 26–33 (2013). Google Scholar
  6. 6.
    C. Du, C.-Y. Feng, X.-R. Yuan et al. Microsurgical Management of Craniopharyngiomas via a Unilateral Subfrontal Approach: A Retrospective Study of 177 Continuous Cases. WNEU 90(C), 454–468 (2016). Google Scholar
  7. 7.
    R. Van Effenterre, A.-L. Boch, Craniopharyngioma in adults and children: a study of 122 surgical cases. J. Neurosurg. 97(1), 3–11 (2002). Google Scholar
  8. 8.
    C. van Bunderen, I. van Nieuwpoort, L. Arwert et al. Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch national registry of growth hormone treatment in adults. J. Clin. Endocrinol. Metab. 96(10), 3151–3159 (2011). Google Scholar
  9. 9.
    S.M. Webb, Clinical outcomes of childhood craniopharyngioma: can we do better? Endocrine 62(1), 1–2 (2018). Google Scholar
  10. 10.
    M. Koutourousiou, P.A. Gardner, J.C. Fernandez-Miranda, E.C. Tyler-Kabara, E.W. Wang, C.H. Snyderman, Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients. J. Neurosurg. 119(5), 1194–1207 (2013). Google Scholar
  11. 11.
    H. Nishioka, N. Fukuhara, M. Yamaguchi-Okada, S. Yamada, Endoscopic Endonasal Surgery for Purely Intrathird Ventricle Craniopharyngioma. WNEU 91(C), 266–271 (2016). Google Scholar
  12. 12.
    W.C. Jean, Multimodality, Multidirectional Resection of Craniopharyngioma: Versatility in Alternating the Principal and Auxiliary Surgical Corridors and Visualization Modalities. WNEU 102, 376–382 (2017). Google Scholar
  13. 13.
    M. Losa, V. Pieri, M. Bailo et al. Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma. Pituitary 21(5), 499–506 (2018). Google Scholar
  14. 14.
    T. Ajithkumar, A.-L. Mazhari, M. Stickan-Verfürth et al. Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre. Clin. Oncol. (R. Coll. Radiol.) 30(5), 307–316 (2018). Google Scholar
  15. 15.
    H.L. Müller, T.E. Merchant, S. Puget, J.-P. Martinez-Barbera, New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma. Nat. Publ. Group. 13(5), 299–312 (2017). Google Scholar
  16. 16.
    F. Bolfi, A.F. Neves, C.L. Boguszewski, V.S. Nunes-Nogueira, Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. Eur. J. Endocrinol. 179(1), 59–71 (2018). Google Scholar
  17. 17.
    B. Bülow, R. Attewell, L. Hagmar, P. Malmström, C.H. Nordström, E.M. Erfurth, Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence. J. Clin. Endocrinol. Metab. 83(11), 3897–3904 (1998). Google Scholar
  18. 18.
    J.W. Tomlinson, N. Holden, R.K. Hills et al. Association between premature mortality and hypopituitarism. Lancet 357(9254), 425–431 (2001). Google Scholar
  19. 19.
    A.M. Pereira, E.M. Schmid, P.J. Schutte et al. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma. Clin. Endocrinol. 62(2), 197–204 (2005). Google Scholar
  20. 20.
    R.K. Crowley, O.P. Hamnvik, E.P. O’Sullivan et al. Morbidity and Mortality in Craniopharyngioma Patients after Surgery. Clin. Endocrinol. 2010:no–no.
  21. 21.
    C.C. van Bunderen, I.C. van Nieuwpoort, L.I. Arwert et al. Does Growth Hormone Replacement Therapy Reduce Mortality in Adults with Growth Hormone Deficiency? Data from the Dutch National Registry of Growth Hormone Treatment in Adults. J. Clin. Endocrinol. Metab. 96(10), 3151–3159 (2011). Google Scholar
  22. 22.
    D.S. Olsson, E. Andersson, I.-L. Bryngelsson, A.G. Nilsson, G. Johannsson, Excess Mortality and Morbidity in Patients with Craniopharyngioma, Especially in Patients with Childhood Onset: A Population-Based Study in Sweden. J. Clin. Endocrinol. Metab. 100(2), 467–474 (2015). Google Scholar
  23. 23.
    K.C.J. Yuen, A.F. Mattsson, P. Burman et al. Relative risks of contributing factors to morbidity and mortality in adults with craniopharyngioma on growth hormone replacement. J. Clin. Endocrinol. Metab. 103(2), 768–777 (2017). Google Scholar
  24. 24.
    M. Wijnen, D.S. Olsson, M.M. van den Heuvel-Eibrink et al. Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study. Eur. J. Endocrinol. 178(1), 93–102 (2017). Google Scholar
  25. 25.
    J.R. Bartlett, Craniopharyngiomas--a summary of 85 cases. J. Neurol. Neurosurg. Psychiatr. 34(1), 37–41 (1971)Google Scholar
  26. 26.
    D.I. Sung, Suprasellar tumors in children: a review of clinical manifestations and managements. Cancer 50(7), 1420–1425 (1982)Google Scholar
  27. 27.
    W.F. Regine, M. Mohiuddin, S. Kramer, Long-term results of pediatric and adult craniopharyngiomas treated with combined surgery and radiation. Radiother. Oncol. 27(1), 13–21 (1993)Google Scholar
  28. 28.
    S. Hetelekidis, P.D. Barnes, M.L. Tao et al. 20-year experience in childhood craniopharyngioma. Radiat. Oncol. Biol. 27(2), 189–195 (1993)Google Scholar
  29. 29.
    B. Rajan, S. Ashley, C. Gorman et al. Craniopharyngioma--a long-term results following limited surgery and radiotherapy. Radiother. Oncol. 26(1), 1–10 (1993)Google Scholar
  30. 30.
    R.M. Scott, S. Hetelekidis, P.D. Barnes, L. Goumnerova, N.J. Tarbell, Surgery, radiation, and combination therapy in the treatment of childhood craniopharyngioma--a 20-year experience. Pediatr. Neurosurg. 21(Suppl 1), 75–81 (1994). Google Scholar
  31. 31.
    C.J. De Vile, D.B. Grant, B.E. Kendall et al. Management of childhood craniopharyngioma: can the morbidity of radical surgery be predicted? J. Neurosurg. 85(1), 73–81 (1996). Google Scholar
  32. 32.
    Y. Khafaga, D. Jenkin, I. Kanaan, M. Hassounah, M. Shabanah Al, A. Gray, Craniopharyngioma in children. Radiat. Oncol. Biol. 42(3), 601–606 (1998).Google Scholar
  33. 33.
    R. Fahlbusch, J. Honegger, W. Paulus, W. Huk, M. Buchfelder, Surgical treatment of craniopharyngiomas: experience with 168 patients. J. Neurosurg. 90(2), 237–250 (1999). Google Scholar
  34. 34.
    J.-L. Habrand, O. Ganry, D. Couanet et al. The role of radiation therapy in the management of craniopharyngioma: a 25-year experience and review of the literature. Radiat. Oncol. Biol. 44(2), 255–263 (1999)Google Scholar
  35. 35.
    J.A. Kalapurakal, S. Goldman, Y.C. Hsieh, T. Tomita, M.H. Marymont, Clinical outcome in children with craniopharyngioma treated with primary surgery and radiotherapy deferred until relapse. Med. Pediatr. Oncol. 40(4), 214–218 (2003). Google Scholar
  36. 36.
    D.C.H. Stripp, A. Maity, A.J. Janss et al. Surgery with or without radiation therapy in the management of craniopharyngiomas in children and young adults. Radiat. Oncol. Biol. 58(3), 714–720 (2004). Google Scholar
  37. 37.
    A. Poretti, M.A. Grotzer, K. Ribi, E. Schönle, E. Boltshauser, Outcome of craniopharyngioma in children: long-term complications and quality of life. Dev. Med. Child Neurol. 46(4), 220–229 (2004)Google Scholar
  38. 38.
    N. Karavitaki, C. Brufani, J.T. Warner et al. Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin. Endocrinol. 62(4), 397–409 (2005). Google Scholar
  39. 39.
    T. Tomita, R.M. Bowman, Craniopharyngiomas in children: surgical experience at Children’s Memorial Hospital. Childs Nerv. Syst. 21(8-9), 729–746 (2005). Google Scholar
  40. 40.
    L.S. Pemberton, M. Dougal, B. Magee, H.R. Gattamaneni, Experience of external beam radiotherapy given adjuvantly or at relapse following surgery for craniopharyngioma. Radiother. Oncol. 77(1), 99–104 (2005). Google Scholar
  41. 41.
    L.L. Lin, El.I. Naqa, J.R. Leonard et al. Long-term outcome in children treated for craniopharyngioma with and without radiotherapy. J. Neurosurg. Pediatr. 1(2), 126–130 (2008). Google Scholar
  42. 42.
    H.L. Müller, Childhood craniopharyngioma. Recent advances in diagnosis, treatment and follow-up. Horm. Res. 69(4), 193–202 (2008). Google Scholar
  43. 43.
    J. Visser, J. Hukin, M. Sargent, P. Steinbok, K. Goddard, C. Fryer, Late mortality in pediatric patients with craniopharyngioma. J. Neurooncol. 100(1), 105–111 (2010). Google Scholar
  44. 44.
    K.M. Winkfield, H.K. Tsai, X. Yao et al. Long-term clinical outcomes following treatment of childhood craniopharyngioma. Pediatr. Blood Cancer 56(7), 1120–1126 (2011). Google Scholar
  45. 45.
    P. Mortini, M. Losa, G. Pozzobon et al. Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series. J. Neurosurg. 114(5), 1350–1359 (2011). Google Scholar
  46. 46.
    L. Masson-Cote, G.L. Masucci, E.G. Atenafu et al. Long-term outcomes for adult craniopharyngioma following radiation therapy. Acta Oncol. 52(1), 153–158 (2013). Google Scholar
  47. 47.
    A.C. Lo, A.F. Howard, A. Nichol et al. Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int. J. Radiat. Oncol. Biol. Phys. 88(5), 1011–1018 (2014). Google Scholar
  48. 48.
    A.S. Sterkenburg, A. Hoffmann, U. Gebhardt, M. Warmuth-Metz, A.M.M. Daubenbüchel, H.L. Müller, Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro. Oncol. 17(7), 1029–1038 (2015). Google Scholar
  49. 49.
    M.A. Hernán, J.M. Robins, Per-Protocol Analyses of Pragmatic Trials. N. Engl. J. Med. 377(14), 1391–1398 (2017). Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryHuashan HospitalShanghaiChina
  2. 2.Harvard Medical SchoolBostonUSA

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