AUTHOR=Calvanese Francesco , Jacquesson Timothée , Manet Romain , Vasiljevic Alexandre , Lasolle Hélène , Ducray Francois , Raverot Gerald , Jouanneau Emmanuel TITLE=Neoadjuvant B-RAF and MEK Inhibitor Targeted Therapy for Adult Papillary Craniopharyngiomas: A New Treatment Paradigm JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.882381 DOI=10.3389/fendo.2022.882381 ISSN=1664-2392 ABSTRACT=Background

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.

Method

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.

Result

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.

Conclusion

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.