{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:11:35Z","timestamp":1753891895677,"version":"3.41.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"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. Oncol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Nonfunctioning macroadenoma is a commonly diagnosed pituitary tumor. Resection is the favored treatment, with radiosurgery often utilized for residual or progressing disease. Long-term outcomes are established in the literature for single-fraction frame-based radiosurgery, but mature outcomes are lacking for fractionated frameless radiosurgery. We report our institution\u2019s 5-year efficacy and toxicity results for unfavorable nonfunctioning pituitary macroadenoma patients treated with 5-fraction robotic radiosurgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between 2010 and 2020, patients who completed 5-fraction robotic radiosurgery for the treatment of unfavorable nonfunctioning pituitary macroadenomas were included. A tumor was considered unfavorable if the gross tumor volume (GTV) was larger than 5 cc or if it closely approached a critical structure (optic apparatus, brainstem, or pituitary gland). Local control was calculated using the Kaplan\u2013Meier method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty predominantly female patients (60%), ages 21\u201377 (median: 53 years), were included in this study. All underwent primary resection at the time of diagnosis. The indication for radiosurgery was tumor progression (<jats:italic>n<\/jats:italic> = 14, 70%) or residual tumor after subtotal resection (<jats:italic>n<\/jats:italic> = 6, 30%). Eighty-five percent of patients treated with radiosurgery (<jats:italic>n<\/jats:italic> = 17) had cavernous sinus involvement. Median GTV was 3.4 cm<jats:sup>3<\/jats:sup> (range: 0.3\u201320.8 cm<jats:sup>3<\/jats:sup>), and 40% of the tumors had suprasellar extension. A mean dose of 28.8 Gy (range: 25\u201330 Gy) was delivered to a median isodose line of 80% (range: 75%\u201389%). The median optic chiasm maximum point dose was 21.8 Gy (range: 12.0\u201325.0 Gy). Acute toxicity was minimal with eight patients (40%) developing short-lived headaches and one patient (5%) developing a brief ipsilateral sixth nerve palsy. There was no late radiation-induced neurologic or optic dysfunction identified in this cohort. At a median follow-up of 5 years, local control was 94%. There was one in-field failure pathologically confirmed following surgery for pituitary hemorrhage and two radiographically confirmed out-of-field failures in patients with larger tumors (&amp;gt;20 cc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The treatment of unfavorable nonfunctioning pituitary macroadenoma with 5-fraction robotic radiosurgery provides excellent local control to date, with acceptable toxicity. However, tumors with GTVs greater than 20 cc may still require conventionally fractionated treatment with a margin to optimize local control.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1519445","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:28:54Z","timestamp":1738646934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fractionated robotic radiosurgery for unfavorable nonfunctioning pituitary macroadenoma: 5-year outcomes from a single institution protocol"],"prefix":"10.3389","volume":"15","author":[{"given":"Akrita","family":"Bhatnagar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica Pernia","family":"Marin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan 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