Elsevier

World Neurosurgery

Volume 142, October 2020, Pages 601-610
World Neurosurgery

From the Annals of The University of Toronto, The Division of Neurosurgery
Creative and Innovative Methods and Techniques for the Challenges in the Management of Adult Craniopharyngioma

https://doi.org/10.1016/j.wneu.2020.05.173Get rights and content

Craniopharyngioma remains a major challenge in daily clinical practice. The pathobiology of the tumor is still elusive, and there are no consensus or treatment guidelines on the optimal management strategy for this relatively rare tumor. However, recent technical and scientific advances, including genomic and radiomic profiling, innovation in surgical approaches, more precise radiotherapy protocols, targeted therapy, and restoration of lost functions all have the potential to significantly improve the outcome of patients with craniopharyngioma in the near future. Although many of these innovative tools in the new armamentarium of the clinician are still in their infancy, they could reduce craniopharyngioma-related morbidity and mortality and improve the patients' quality of life. In this article, we discuss these creative and innovative approaches that may offer solutions to the obstacles faced in treating craniopharyngioma and future possibilities in improving the care of these patients.

Introduction

Craniopharyngioma is a rare brain tumor that can occur at the floor of the third ventricle, along the pituitary stalk, or in the sella turcica. The overall incidence in the United States is reported to be 0.13 per 100,000 person years.1 Although craniopharyngioma is a benign tumor histologically, its management poses significant challenges,2 as described in detail in the companion article on challenges and controversies. This situation is primarily because of its location close to visual, endocrine, pituitary stalk and gland, hypothalamic, and vascular structures.

Although long-term survival is high (>90% at 10 years), significant morbidity and poor quality of life are associated with both the tumor and its treatment. Although surgery remains the primary form of treatment, attempts at total removal are often difficult (<50% rates of GTR3,4 in some series) and can result in both short-term and long-term sequelae. Likewise, reported recurrence rates remain high (10-year control rate, 30%–50% after incomplete resection).5

In this article, we discuss possible solutions to the obstacles in treating craniopharyngioma and future possibilities for improving the care of these patients (Table 1).

Section snippets

Cerebrospinal Fluid/Blood Liquid Biopsy

The use of liquid biopsy for central nervous system tumors is rapidly expanding.6 In general, it has been described mainly in 2 types of fluids: blood and cerebrospinal fluid (CSF). Blood-based biomarkers include circulating tumor cells, nucleic acids (cell-free circulating tumor DNA and microRNA) and exosomes.7 Moreover, CSF-based liquid biopsy may have a superior yield compared with other fluids.8,9

In craniopharyngioma, which has a signature mutation in most cases (>90%),10 liquid biopsy

Operative Technological Innovation

In the last few decades, the main innovation in the surgical treatment of craniopharyngiomas has been the introduction of the endoscopic endonasal approach (EEA). Recently, several studies have confirmed the advantages of this technique for the management of craniopharyngiomas, in terms of extent of resection, functional sequelae, and complication rate.35, 36, 37, 38, 39

Furthermore, other technological advances could also rapidly change the field. New-generation endonasal transsphenoidal

Endocrinologic Treatment

Endocrinologic morbidity may develop during tumor growth or after surgical intervention or radiation therapy in patients with craniopharyngioma. Hypopituitarism and hypothalamic insufficiency can be lifelong morbidities. Hormone replacement is the standard therapy. Damage of the homeostatic function located in the hypothalamus causes impaired control of satiety and hunger, sleep disorders, and dysregulation of temperature.78

Hypothalamic Obesity

One of the most devastating sequelae is hypothalamic obesity, as

Preventive Medicine

Single-nucleotide polymorphisms (SNPs) of the germline genome are known be associated with a plethora of individual characteristics based on extensive data from genome-wide association studies.105 Many types of diseases, including brain tumors such as glioma and meningioma, have been found to be related to SNPs.106, 107, 108, 109 They were also shown to be associated with treatment response and prognosis in glioblastoma110 and medulloblastoma.111 No particular SNP has yet been found to be

Restoration/Regeneration Medicine

As discussed earlier, resection of tumors can result in high morbidity, and optic pathways and endocrinologic and visual functions are often most affected. Natural recovery is unlikely, because of limited self-renewal capacity in adult cells. However, the development of regenerative medicine may offer new treatments in the future.

Stem cell therapy is still in the stage of clinical trials, but it has already been tested for the treatment of demyelinating diseases/spinal cord injury, amyotrophic

Conclusions

Despite modern technological and medical advances, craniopharyngioma remains a considerable challenge for neurosurgeons, radiation oncologists, and endocrinologists in terms of tumor resection, planning the optimal radiation coverage, and endocrinologic management. Craniopharyngioma is one of the tumor types that are at the center of a treatment revolution, including advances in surgical techniques, surgical tools, diagnostic imaging, genomic analyses, gene-based treatments, and regeneration of

Acknowledgments

We acknowledge the contribution of Anne Stanford, E.L.S., who provided professional editing services.

References (125)

  • E.A.C. Pereira et al.

    Cerebrospinal fluid leaks after transsphenoidal surgery–effect of a polyethylene glycol hydrogel dural sealant

    J Clin Neurosci

    (2017)
  • J.P. Thawani et al.

    Resident simulation training in endoscopic endonasal surgery utilizing haptic feedback technology

    J Clin Neurosci

    (2016)
  • M. de Notaris et al.

    Anatomic skull base education using advanced neuroimaging techniques

    World Neurosurg

    (2013)
  • R. Valentine et al.

    Simulation training for vascular emergencies in endoscopic sinus and skull base surgery

    Otolaryngol Clin North Am

    (2016)
  • P. Wolf et al.

    Hormone substitution after gastric bypass surgery in patients with hypopituitarism secondary to craniopharyngioma

    Endocr Pract

    (2016)
  • W. Ni et al.

    Interventions for the treatment of craniopharyngioma-related hypothalamic obesity: a systematic review

    World Neurosurg

    (2018)
  • R.M. Lober et al.

    A perspective on craniopharyngioma

    World Neurosurg

    (2013)
  • J.J. Grob et al.

    Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial

    Lancet Oncol

    (2015)
  • G.R. Bunin et al.

    The descriptive epidemiology of craniopharyngioma

    J Neurosurg

    (1998)
  • M. Wijnen et al.

    Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study

    Eur J Endocrinol

    (2018)
  • N. Karavitaki et al.

    Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up

    Clin Endocrinol (Oxf)

    (2005)
  • A. Aggarwal et al.

    Radiotherapy for craniopharyngioma

    Pituitary

    (2013)
  • I.D. Connolly et al.

    The “liquid biopsy”: the role of circulating DNA and RNA in central nervous system tumors

    Curr Neurol Neurosci Rep

    (2016)
  • M. Fontanilles et al.

    Liquid biopsy in primary brain tumors: looking for stardust!

    Curr Neurol Neurosci Rep

    (2018)
  • Y. Wang et al.

    Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

    Proc Natl Acad Sci U S A

    (2015)
  • W. Pan et al.

    Brain tumor mutations detected in cerebral spinal fluid

    Clin Chem

    (2015)
  • P.K. Brastianos et al.

    Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas

    Nat Genet

    (2014)
  • J.R. Apps et al.

    Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

    Neurosurg Focus

    (2016)
  • P. Momtaz et al.

    Quantification of tumor-derived cell free DNA(cfDNA) by digital PCR (DigPCR) in cerebrospinal fluid of patients with BRAFV600 mutated malignancies

    Oncotarget

    (2016)
  • J.C. Martinez-Gutierrez et al.

    Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy

    Neurosurg Focus

    (2016)
  • E.R. Smith et al.

    A recurrent craniopharyngioma illustrates the potential usefulness of urinary matrix metalloproteinases as noninvasive biomarkers

    Neurosurgery

    (2007)
  • X. Chen et al.

    Noninvasive molecular diagnosis of craniopharyngioma with MRI-based radiomics approach

    BMC Neurol

    (2019)
  • I.H. Lee et al.

    Craniopharyngiomas: radiological differentiation of two types

    J Korean Neurosurg Soc

    (2016)
  • Q. Yue et al.

    Prediction of BRAF mutation status of craniopharyngioma using magnetic resonance imaging features

    J Neurosurg

    (2018)
  • F. Wang et al.

    Predicting pituitary stalk position by in vivo visualization of the hypothalamo-hypophyseal tract in craniopharyngioma using diffusion tensor imaging tractography

    Neurosurg Rev

    (2018)
  • P.K. Brastianos et al.

    Endocrine tumors: BRAF V600E mutations in papillary craniopharyngioma

    Eur J Endocrinol

    (2016)
  • K. Yoshimoto et al.

    High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas

    Neuropathology

    (2018)
  • G. Marucci et al.

    Targeted BRAF and CTNNB1 next-generation sequencing allows proper classification of nonadenomatous lesions of the sellar region in samples with limiting amounts of lesional cells

    Pituitary

    (2015)
  • S.B. Omay et al.

    Do craniopharyngioma molecular signatures correlate with clinical characteristics?

    J Neurosurg

    (2018)
  • P.K. Brastianos et al.

    Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy

    J Natl Cancer Inst

    (2016)
  • J. Samis et al.

    Extensive miRNA expression analysis in craniopharyngiomas

    Childs Nerv Syst

    (2016)
  • A. Hölsken et al.

    Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles

    Acta Neuropathol Commun

    (2016)
  • C.H. Moon et al.

    Visual prognostic value of optical coherence tomography and photopic negative response in chiasmal compression

    Investig Opthalmology Vis Sci

    (2011)
  • M.F. Jacobsen et al.

    Predictors of visual outcome in patients operated for craniopharyngioma–a Danish national study

    Acta Ophthalmol

    (2018)
  • R. Prieto et al.

    Craniopharyngioma adherence: a reappraisal of the evidence

    Neurosurg Rev

    (2020)
  • L.M. Cavallo et al.

    The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients

    J Neurosurg

    (2014)
  • O. Ozgural et al.

    Single-center surgical experience of the treatment of craniopharyngiomas with emphasis on the operative approach: endoscopic endonasal and open microscopic transcranial approaches

    J Craniofac Surg

    (2018)
  • J. Mou et al.

    Endoscopic endonasal surgery for craniopharyngiomas: a series of 60 patients

    World Neurosurg

    (2019)
  • I. Radovanovic et al.

    Expanded endonasal endoscopic surgery in suprasellar craniopharyngiomas: a retrospective analysis of 43 surgeries including recurrent cases

    Oper Neurosurg

    (2019)
  • S. Dhandapani et al.

    Endonasal endoscopic reoperation for residual or recurrent craniopharyngiomas

    J Neurosurg

    (2017)
  • Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

    Hirokazu Takami and Carlos Velásquez are co–first authors.

    View full text