Skip to main content
SpringerLink
Log in

Targeted therapy in BRAF mutated aggressive papillary craniopharyngioma: a case report and overview of the literature

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Papillary craniopharyngiomas harbor the BRAF V600E mutation, which paves the way for using BRAF inhibitor molecules to treat tumors refractory to standard therapies. Single case reports confirmed the efficacy of targeted therapy. However, most reports were limited by the short follow-up. We describe the long-term course of a patient treated with dual-agent BRAF and MEK inhibitors and review the available literature.

Case report

A 75-year-old male patient had recurrence of a papillary craniopharyngioma after transsphenoidal surgery and Gamma Knife radiosurgery. Review of the pathologic specimen confirmed the presence of the BRAF V600E mutation. Because of the few therapeutic options, we decided to initiate BRAF/MEK inhibitor combined therapy for six months. Rapid reduction of the tumor occurred, but three months after quitting combined medical therapy the tumor recurred. BRAF/MEK inhibitor therapy was resumed and the tumor again showed a marked reduction. The second course was maintained for 20 months and the tumor showed another recurrence within three months, which, again, responded to a third course of targeted therapy.

Conclusions

Our study confirms the excellent response of papillary craniopharyngioma to combined BRAF and MEK inhibitors. However, rapid tumor recurrence is the rule when medical therapy is stopped. Resistance to a second and third course of targeted therapy did not occur, suggesting that tumor mutations affecting the response to drugs seems an uncommon event in papillary craniopharyngioma. The exact role of targeted therapy in the treatment algorithm of papillary craniopharyngiomas has still to be refined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Karavitaki N, Cudlip S, Adams CB, Wass JA (2006) Craniopharyngiomas. Endocr Rev 27(4):371–397. https://doi.org/10.1210/er.2006-0002

    Article  PubMed  Google Scholar 

  2. Mortini P, Losa M, Pozzobon G, Barzaghi R, Riva M, Acerno S, Angius D, Weber G, Chiumello G, Giovanelli M (2011) Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series. J Neurosurg 114(5):1350–1359. https://doi.org/10.3171/2010.11.JNS10670

    Article  PubMed  Google Scholar 

  3. Petito CK, De Girolami U, Earle K (1976) Craniopharyngiomas. A clinical and pathological review. Cancer 37(4):1944–1952. https://doi.org/10.1002/1097-0142(197604)37. (4<1944::aid-cncr2820370446>3.0.co;2-#)

    Article  CAS  PubMed  Google Scholar 

  4. Fernandez-Miranda JC, Gardner PA, Snyderman CH, Devaney KO, Strojan P, Suarez C, Genden EM, Rinaldo A, Ferlito A (2012) Craniopharyngioma: a pathologic, clinical, and surgical review. Head Neck 34(7):1036–1044. https://doi.org/10.1002/hed.21771

    Article  PubMed  Google Scholar 

  5. Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC (1994) Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery 35(6):1001–1010. https://doi.org/10.1227/00006123-199412000-00001. (discussion 1010-1011)

    Article  CAS  PubMed  Google Scholar 

  6. Mortini P, Gagliardi F, Boari N, Losa M (2013) Surgical strategies and modern therapeutic options in the treatment of craniopharyngiomas. Crit Rev Oncol Hematol 88(3):514–529. https://doi.org/10.1016/j.critrevonc.2013.07.013

    Article  PubMed  Google Scholar 

  7. Bülow B, Attewell R, Hagmar L, Malmström P, Nordström CH, Erfurth EM (1998) Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence. J Clin Endocrinol Metab 83(11):3897–3904. https://doi.org/10.1210/jcem.83.11.5240

    Article  PubMed  Google Scholar 

  8. Losa M, Pieri V, Bailo M, Gagliardi F, Barzaghi LR, Gioia L, Del Vecchio A, Bolognesi A, Mortini P (2018) Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma. Pituitary 21(5):499–506. https://doi.org/10.1007/s11102-018-0903-5

    Article  PubMed  Google Scholar 

  9. Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, Lawrence MS, Rodriguez FJ, Bernardo LA, Schubert L, Sunkavalli A, Shillingford N, Calicchio ML, Lidov HG, Taha H, Martinez-Lage M, Santi M, Storm PB, Lee JY, Palmer JN, Adappa ND, Scott RM, Dunn IF, Laws ER Jr, Stewart C, Ligon KL, Hoang MP, Van Hummelen P, Hahn WC, Louis DN, Resnick AC, Kieran MW, Getz G, Santagata S (2014) Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 46(2):161–165. https://doi.org/10.1038/ng.2868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alexandraki KI, Kaltsas GA, Karavitaki N, Grossman AB (2019) The medical therapy of craniopharyngiomas: the way ahead. J Clin Endocrinol Metab 104(12):5751–5764. https://doi.org/10.1210/jc.2019-01299

    Article  PubMed  Google Scholar 

  11. Brastianos PK, Shankar GM, Gill CM, Taylor-Weiner A, Nayyar N, Panka DJ, Sullivan RJ, Frederick DT, Abedalthagafi M, Jones PS, Dunn IF, Nahed BV, Romero JM, Louis DN, Getz G, Cahill DP, Santagata S, Curry WT Jr, Barker FG 2nd (2015) Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst 108(2):djv310. https://doi.org/10.1093/jnci/djv310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Aylwin SJ, Bodi I, Beaney R (2016) Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary 19(5):544–546. https://doi.org/10.1007/s11102-015-0663-4

    Article  PubMed  Google Scholar 

  13. Roque A, Odia Y (2017) BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol 6(2):95–99. https://doi.org/10.2217/cns-2016-0034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rostami E, Witt Nyström P, Libard S, Wikström J, Casar-Borota O, Gudjonsson O (2017) Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant -targeted therapy. Acta Neurochir (Wien) 159(11):2217–2221. https://doi.org/10.1007/s00701-017-3311-0

    Article  PubMed  Google Scholar 

  15. Himes BT, Ruff MW, Van Gompel JJ, Park SS, Galanis E, Kaufmann TJ, Uhm JH (2018) Recurrent papillary craniopharyngioma withBRAF V600E mutation treated with dabrafenib: case report. J Neurosurg. https://doi.org/10.3171/2017.11.JNS172373

    Article  PubMed  Google Scholar 

  16. Juratli TA, Jones PS, Wang N, Subramanian M, Aylwin SJB, Odia Y, Rostami E, Gudjonsson O, Shaw BL, Cahill DP, Galanis E, Barker FG 2nd, Santagata S, Brastianos PK (2019) Targeted treatment of papillary craniopharyngiomas harboring BRAF V600E mutations. Cancer 125(17):2910–2914. https://doi.org/10.1002/cncr.32197

    Article  PubMed  Google Scholar 

  17. Rao M, Bhattacharjee M, Shepard S, Hsu S (2019) Newly diagnosed papillary craniopharyngioma with BRAF V600E mutation treated with single-agent selective BRAF inhibitor dabrafenib: a case report. Oncotarget 10(57):6038–6042. https://doi.org/10.18632/oncotarget.27203

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bernstein A, Mrowczynski OD, Greene A, Ryan S, Chung C, Zacharia BE, Glantz M (2019) Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity. J Neurosurg 144(6):1704–1709. https://doi.org/10.3171/2019.8.JNS19643

    Article  Google Scholar 

  19. Di Stefano AL, Guyon D, Sejean K, Feuvret L, Villa C, Berzero G, Desforges Bullet V, Halimi E, Boulin A, Baussart B, Gaillard S (2020) Medical debulking with BRAF/MEK inhibitors in aggressive BRAF-mutant craniopharyngioma. Neurooncol Adv 2(1):vdaa141. https://doi.org/10.1093/noajnl/vdaa141

    Article  PubMed  PubMed Central  Google Scholar 

  20. Khaddour K, Chicoine MR, Huang J, Dahiya S, Ansstas G (2020) Successful use of BRAF/MEK inhibitors as a neoadjuvant approach in the definitive treatment of papillary craniopharyngioma. J Natl Compr Canc Netw 18(12):1590–1595. https://doi.org/10.6004/jnccn.2020.7624

    Article  CAS  PubMed  Google Scholar 

  21. Chik CL, van Landeghem FKH, Easaw JC, Mehta V (2021) Aggressive childhood-onset papillary craniopharyngioma managed with Vemurafenib, a BRAF inhibitor. J Endocr Soc 5(5):bvab043. https://doi.org/10.1210/jendso/bvab043

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fasano M, Della Corte CM, Caterino M, Pirozzi M, Rauso R, Troiani T, Martini G, Napolitano S, Morgillo F, Ciardiello F (2022) Dramatic therapeutic response to dabrafenib plus trametinib in BRAF V600E mutated papillary craniopharyngiomas: a case report and literature review. Front Med (Lausanne) 8:652005. https://doi.org/10.3389/fmed.2021.652005

    Article  PubMed  Google Scholar 

  23. Nussbaum PE, Nussbaum LA, Torok CM, Patel PD, Yesavage TA, Nussbaum ES (2022) Case report and literature review of BRAF-V600 inhibitors for treatment of papillary craniopharyngiomas: a potential treatment paradigm shift. J Clin Pharm Ther. https://doi.org/10.1111/jcpt.13600

    Article  PubMed  Google Scholar 

  24. Calvanese F, Jacquesson T, Manet R, Vasiljevic A, Lasolle H, Ducray F, Raverot G, Jouanneau E (2022) Neoadjuvant B-RAF and MEK inhibitor targeted therapy for adult papillary craniopharyngiomas: a new treatment paradigm. Front Endocrinol (Lausanne) 13:882381. https://doi.org/10.3389/fendo.2022.882381

    Article  PubMed  Google Scholar 

  25. Brastianos PK, Twohy E, Geyer S, Gerstner ER, Kaufmann TJ, Tabrizi S, Kabat B, Thierauf J, Ruff MW, Bota DA, Reardon DA, Cohen AL, De La Fuente MI, Lesser GJ, Campian J, Agarwalla PK, Kumthekar P, Mann B, Vora S, Knopp M, Iafrate AJ, Curry WT Jr, Cahill DP, Shih HA, Brown PD, Santagata S, Barker FG 2nd, Galanis E (2023) BRAF-MEK inhibition in newly diagnosed papillary craniopharyngiomas. N Engl J Med 389(2):118–126. https://doi.org/10.1056/NEJMoa2213329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Welsh SJ, Corrie PG (2015) Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol 7(2):122–136. https://doi.org/10.1177/1758834014566428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Heinzerling L, Eigentler TK, Fluck M, Hassel JC, Heller-Schenck D, Leipe J, Pauschinger M, Vogel A, Zimmer L, Gutzmer R (2019) Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open 4(3):e000491. https://doi.org/10.1136/esmoopen-2019-000491

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, IRCCS San Raffaele, Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy

    M. Losa, E. Pedone, G. Nocera & P. Mortini

  2. Dept. of Oncology, IRCCS San Raffaele, Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy

    E. Mazza, N. Liscia & M. Reni

Authors
  1. M. Losa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Mazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Pedone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Nocera
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Liscia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Reni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Mortini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Losa.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest. The authors have nothing to disclose.

Human participants and animals

The study protocol complies with the 1964 Declaration of Helsinki.

Informed consent

A signed informed consent for all the therapeutic procedures was obtained from the patient.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Losa, M., Mazza, E., Pedone, E. et al. Targeted therapy in BRAF mutated aggressive papillary craniopharyngioma: a case report and overview of the literature. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02382-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40618-024-02382-7

Keywords

Search

Navigation