{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:46:21Z","timestamp":1792025181022,"version":"4.4.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Surgical and clinical management of craniopharyngiomas is associated with high long-term morbidity especially in the case of hypothalamic involvement. Improvements in knowledge of craniopharyngioma molecular biology may offer the possibility of safe and effective medical neoadjuvant treatments in a subset of patients harboring papillary subtype tumors with a BRAFV600E mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We report herein two cases of tubero-infundibular and ventricular Papillary Craniopharyngiomas in which BRAF\/MEK inhibitor combined therapy was used as adjuvant (Case 1) or neoadjuvant (Case 2) treatment, with a 90% reduction in tumor volume observed after only 5 months. In Case 2 the only surgical procedure used was a minimal invasive biopsy by the trans-ventricular neuroendoscopic approach. As a consequence, targeted therapy was administered in purely neoadjuvant fashion. After shrinkage of the tumor, both patients underwent fractionated radiotherapy on the small tumor remnant to achieve long-term tumor control. A review of a previously reported case has also been performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>This approach led to tumor control with minimal long-term morbidity in both cases. No side effects or complications were reported after medical treatment and adjuvant radiotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our experience and a review of the literature argue for a change in the current treatment paradigm for Craniopharyngiomas (CPs). In giant and invasive tumors, confirmation of BRAFV600E mutated PCPs by biopsy and BRAF\/MEK inhibitor therapy before proposing other treatments may be useful to improve long term outcomes for patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.882381","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T03:33:40Z","timestamp":1654745620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Neoadjuvant B-RAF and MEK Inhibitor Targeted Therapy for Adult Papillary Craniopharyngiomas: A New Treatment Paradigm"],"prefix":"10.3389","volume":"13","author":[{"given":"Francesco","family":"Calvanese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoth\u00e9e","family":"Jacquesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Manet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Vasiljevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Lasolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Ducray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Raverot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jouanneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41572-019-0125-9","article-title":"Craniopharyngioma","volume":"5","author":"M\u00fcller","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1159\/000506904","article-title":"Biological Behaviour of Craniopharyngiomas","volume":"110","author":"Martinez-Barbera","year":"2020","journal-title":"Neuroendocrinology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3171\/2016.9.FOCUS16325","article-title":"Diagnosis and Management of Craniopharyngiomas in the Era of Genomics and Targeted Therapy","volume":"41","author":"Martinez-Gutierrez","year":"2016","journal-title":"Neurosurg Focus"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2020.05.171","article-title":"Surgical Anatomy Applied to the Resection of Craniopharyngiomas: Anatomic Compartments and Surgical Classifications","volume":"142","author":"Almeida","year":"2020","journal-title":"World Neurosurg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2217\/fon.15.233","article-title":"Is There a Role for Targeted Medical Therapies in Patients With Craniopharyngiomas","volume":"11","author":"Tritos","year":"2015","journal-title":"Future Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.wneu.2020.05.172","article-title":"Craniopharyngiomas: Challenges and Controversies","volume":"142","author":"Asha","year":"2020","journal-title":"World Neurosurg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyy569","article-title":"A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas","volume":"85","author":"Fujio","year":"2019","journal-title":"Neurosurgery"},{"key":"B8","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s00701-004-0295-3","article-title":"Intraventricular Craniopharyngiomas: Topographical Classification and Surgical Approach Selection Based on an Extensive Overview","volume":"146","author":"Pascual","year":"2004","journal-title":"Acta Neurochir (Wien)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-018-1010-9","article-title":"Craniopharyngioma Adherence: A Reappraisal of the Evidence","volume":"43","author":"Prieto","year":"2020","journal-title":"Neurosurg Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e803","DOI":"10.1016\/j.wneu.2019.06.037","article-title":"Is Gross Total Resection Reasonable in Adults With Craniopharyngiomas With Hypothalamic Involvement","volume":"129","author":"Apra","year":"2019","journal-title":"World Neurosurg"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2013.07.005","article-title":"Radiotherapy in Craniopharyngiomas","volume":"25","author":"Iannalfi","year":"2013","journal-title":"Clin Oncol (R Coll Radiol)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3171\/2013.1.JNS111722","article-title":"Displacement of Mammillary Bodies by Craniopharyngiomas Involving the Third Ventricle: Surgical-MRI Correlation and Use in Topographical Diagnosis","volume":"119","author":"Pascual","year":"2013","journal-title":"J Neurosurg"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-011-1149-4","article-title":"Infundibulo-Tuberal or Not Strictly Intraventricular Craniopharyngioma: Evidence for a Major Topographical Category","volume":"153","author":"Pascual","year":"2011","journal-title":"Acta Neurochir (Wien)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.09.053","article-title":"Craniopharyngiomas Primarily Involving the Hypothalamus: A Model of Neurosurgical Lesions to Elucidate the Neurobiological Basis of Psychiatric Disorders","volume":"120","author":"Pascual","year":"2018","journal-title":"World Neurosurg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.21037\/cco-20-168","article-title":"A Narrative Review of Targeted Therapy in Meningioma, Pituitary Adenoma, and Craniopharyngioma of the Skull Base","volume":"9","author":"Martinez","year":"2020","journal-title":"Chin Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-01299","article-title":"The Medical Therapy of Craniopharyngiomas: The Way Ahead","volume":"104","author":"Alexandraki","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-015-0663-4","article-title":"Pronounced Response of Papillary Craniopharyngioma to Treatment With Vemurafenib, a BRAF Inhibitor","volume":"19","author":"Aylwin","year":"2016","journal-title":"Pituitary"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60898-4","article-title":"Dabrafenib and Trametinib Versus Dabrafenib and Placebo for Val600 BRAF-Mutant Melanoma: A Multicentre, Double-Blind, Phase 3 Randomised Controlled Trial","volume":"386","author":"Long","year":"2015","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/2019.8.JNS19643","article-title":"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","volume":"1","author":"Bernstein","year":"2019","journal-title":"J Neurosurg"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2868","article-title":"Exome Sequencing Identifies BRAF Mutations in Papillary Craniopharyngiomas","volume":"46","author":"Brastianos","year":"2014","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-021-01510-8","article-title":"Stereotactic Cysto-Ventricular Catheters in Craniopharyngiomas: An Effective Minimally Invasive Method to Improve Visual Impairment and Achieve Long-Term Cyst Volume Reduction","volume":"44","author":"Steiert","year":"2021","journal-title":"Neurosurg Rev"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/2017.11.JNS172373","article-title":"Recurrent Papillary Craniopharyngioma With BRAF V600E Mutation Treated With Dabrafenib: Case Report","volume":"1","author":"Himes","year":"2018","journal-title":"J Neurosurg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.7624","article-title":"Successful Use of BRAF\/MEK Inhibitors as a Neoadjuvant Approach in the Definitive Treatment of Papillary Craniopharyngioma","volume":"18","author":"Khaddour","year":"2020","journal-title":"J Natl Compr Canc Netw"},{"key":"B24","doi-asserted-by":"publisher","first-page":"djv310","DOI":"10.1093\/jnci\/djv310","article-title":"Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy","volume":"108","author":"Priscilla","year":"2016","journal-title":"JNCI: J Nat Cancer Institute"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27203","article-title":"Newly Diagnosed Papillary Craniopharyngioma With BRAF V600E Mutation Treated With Single-Agent Selective BRAF Inhibitor Dabrafenib: A Case Report","volume":"10","author":"Rao","year":"2019","journal-title":"Oncotarget"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-017-3311-0","article-title":"Recurrent Papillary Craniopharyngioma With BRAFV600E Mutation Treated With Neoadjuvant-Targeted Therapy","volume":"159","author":"Rostami","year":"2017","journal-title":"Acta Neurochir (Wien)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdaa141","article-title":"Medical Debulking With BRAF\/MEK Inhibitors in Aggressive BRAF-Mutant Craniopharyngioma","volume":"2","author":"Di Stefano","year":"2020","journal-title":"Neurooncol Adv"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32197","article-title":"Targeted Treatment of Papillary Craniopharyngiomas Harboring BRAF V600E Mutations","volume":"125","author":"Juratli","year":"2019","journal-title":"Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2217\/cns-2016-0034","article-title":"BRAF-V600E Mutant Papillary Craniopharyngioma Dramatically Responds to Combination BRAF and MEK Inhibitors","volume":"6","author":"Roque","year":"2017","journal-title":"CNS Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.2000","article-title":"Alliance A071601: Phase II Trial of BRAF\/MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas","volume":"39","author":"Brastianos","year":"2021","journal-title":"J Clin Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-018-0909-z","article-title":"BRAF V600E Mutant Papillary Craniopharyngiomas: A Single-Institutional Case Series","volume":"21","author":"La Corte","year":"2018","journal-title":"Pituitary"},{"key":"B32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.5414\/NP301268","article-title":"Craniopharyngiomas: A Clinicopathological and Molecular Study of 52 Cases - Experience in the Complejo Hospitalario De Toledo and Hospital Universitario 12 De Octubre (Madrid)","volume":"40","author":"Moreno-Torres","year":"2021","journal-title":"Clin Neuropathol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.11.004","article-title":"Neuroendoscopic Treatment of Cystic Craniopharyngiomas: A Case Series With Systematic Review of the Literature","volume":"110","author":"Lauretti","year":"2018","journal-title":"World Neurosurg"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000504512","article-title":"The Diagnosis and Treatment of Craniopharyngioma","volume":"110","author":"M\u00fcller","year":"2020","journal-title":"Neuroendocrinology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/2019.3.JNS181953","article-title":"Clinical Features and Operative Technique of Transinfundibular Craniopharyngioma","volume":"14","author":"Tang","year":"2019","journal-title":"J Neurosurg"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.07.217","article-title":"Ommaya Reservoir System for the Treatment of Cystic Craniopharyngiomas: Surgical Results in a Series of 11 Adult Patients and Review of the Literature","volume":"132","author":"Frio","year":"2019","journal-title":"World Neurosurg"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-020-09644-z","article-title":"Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma","volume":"32","author":"Fukuhara","year":"2021","journal-title":"Endocr Pathol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/neup.12408","article-title":"High-Resolution Melting and Immunohistochemical Analysis Efficiently Detects Mutually Exclusive Genetic Alterations of Adamantinomatous and Papillary Craniopharyngiomas","volume":"38","author":"Yoshimoto","year":"2018","journal-title":"Neuropathology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2016.01.001","article-title":"Comparison of Whole-Exome Sequencing of Matched Fresh and Formalin Fixed Paraffin Embedded Melanoma Tumours: Implications for Clinical Decision Making","volume":"48","author":"De Paoli-Iseppi","year":"2016","journal-title":"Pathology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab043","article-title":"Aggressive Childhood-Onset Papillary Craniopharyngioma Managed With Vemurafenib, a BRAF Inhibitor","volume":"5","author":"Chik","year":"2021","journal-title":"J Endocr Soc"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-018-3925-4","article-title":"Papillary Craniopharyngioma in a 4-Year-Old Girl With BRAF V600E Mutation: A Case Report and Review of the Literature","volume":"35","author":"Borrill","year":"2019","journal-title":"Childs Nerv Syst"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.882381\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T03:33:42Z","timestamp":1654745622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.882381\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":41,"alternative-id":["10.3389\/fendo.2022.882381"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.882381","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]},"article-number":"882381"}}