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The endoscopic endonasal approach has improved outcomes, but in cases of optic pathways or hypothalamic involvement, complete resection is impossible without significant functional deficits. Subtotal resection followed by radiation therapy has been achieving comparable rates of tumor control to gross total resection alone. Proton therapy (PRT) achieves comparable oncological outcomes to photon therapy, but with better functional outcomes thanks to its capability of sparing surrounding healthy tissues. Herein we summarize the most recent evidence on the use of PRT for craniopharyngiomas and provides paradigmatic, challenging case scenarios managed with a combination of surgery and PRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eight patients who were treated with PRT for craniopharyngiomas between January 2016 and September 2023 are presented. Patients underwent thorough endocrinological, clinical, cognitive, and radiological evaluation before and after treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All patients underwent at least one surgical procedure. One patient was treated with primary PRT. Five patients presented with visual impairment before treatment. All 8 cases had some degree of endocrinological dysfunction before PRT. Four patients presented signs of hypothalamic dysfunction. Seven patients received a conventional cycle of treatment (54 GyRBE total, 1.8 GyRBE\/fraction, 30 fractions), but one patient received 52.5 GyRBE in 29 fractions with caution due to pre-treatment bitemporal hemianopia and old age. One patient\u2019s visual acuity worsened within grade 2 (according to CTCAE v5.0), while all the others improved or remained stable after treatment. Endocrinological status improved in one case and remained stable in the others. Hypothalamic dysfunction worsened in two patients and improved in two. In one case, a complete response was achieved, in one the tumor remained stable, and the remaining six achieved a partial response with reduction\u2009\u2265\u200950%. A case with brain multifocal dissemination was successfully treated with surgery and systemic therapy, and concomitant asymptomatic early radio-induced contrast enhancement was observed. Median follow-up spanned 58.5 months (range: 24\u201372).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PRT appears as a safe and feasible option for the management of craniopharyngiomas, especially for children and in cases of adherence to the optic pathways or hypothalamus, and generally in various challenging case scenarios. From a modern neuro-oncological perspective, multimodal function-sparing management should be favored over aggressive surgery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10143-026-04258-1","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:34:28Z","timestamp":1774938868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined surgery and proton radiotherapy in the management of craniopharyngiomas: an update with paradigmatic and challenging case scenarios"],"prefix":"10.1007","volume":"49","author":[{"given":"Federico","family":"Valeri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Zoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Tengattini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Pasquini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Salierno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Carretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Babaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Agosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Mattogno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Maria","family":"Fontanella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liverana","family":"Lauretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Mazzatenta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Doglietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Iannalfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"issue":"8\u20139","key":"4258_CR1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1007\/s00381-005-1190-9","volume":"21","author":"VC Prabhu","year":"2005","unstructured":"Prabhu VC, Brown HG (2005) The pathogenesis of craniopharyngiomas. 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