{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:25:22Z","timestamp":1781576722711,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single\u2010patient\u2010level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single\u2010patient\u2010level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (<jats:italic>n<\/jats:italic>\u2009=\u200964 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (<jats:italic>n<\/jats:italic>\u2009=\u200943) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II\/III (4.7%), papillary tumor of pineal region WHO II\/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (<jats:italic>n<\/jats:italic>\u2009=\u200933) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low\u2010grade glioma (6%), high\u2010grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2\u2009\u00b1\u20094 cc. All patients received GKSR with a mean marginal dose of 14.7\u2009\u00b1\u20092.1\u2009Gy (50% isodose). At a median 36\u2010month follow\u2010up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high\u2010grade gliomas (8mo). The 3\u2010year\u00a0OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low\u2010grade pineal lesions, 66% for high\u2010grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3\u2010year\u00a0progression\u2010free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low\u2010grade pineal, 66% for high\u2010grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, <jats:italic>p<\/jats:italic>\u2009=\u2009.02), while GCTs and HGG histology well predicted PD (OR: 13, <jats:italic>p<\/jats:italic>\u2009=\u2009.04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.<\/jats:p>","DOI":"10.1111\/jpi.12910","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:17:06Z","timestamp":1694697426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-1764","authenticated-orcid":false,"given":"Filippo","family":"Gagliardi","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute Vita\u2010Salute University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierfrancesco","family":"De Domenico","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute Vita\u2010Salute University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Garbin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute Vita\u2010Salute University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Snider","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute Vita\u2010Salute University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mortini","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute Vita\u2010Salute University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0b013e3181f895a4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.10.28"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2011.05.006"},{"issue":"3","key":"e_1_2_8_5_1","first-page":"239","article-title":"Pathology of pineal region tumors","volume":"54","author":"Hirato J","year":"2001","journal-title":"JNO"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00296564"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-3019(03)00080-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuchi.2014.02.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.129430"},{"issue":"1","key":"e_1_2_8_10_1","first-page":"221","article-title":"Surgical strategies for treating patients with pineal region tumors","volume":"69","author":"Bruce JN","year":"2004","journal-title":"JNO"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3171\/2017.7.JNS17260"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2011.05.002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1054\/jocn.1999.0164"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuchi.2013.11.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000129479.70696.D2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.05.080"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-200210000-00006"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000070417"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3171\/FOC-07\/12\/E12"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.06.189"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000210057"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2015.58.4.334"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-005-0626-z"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282X20130217"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_8_26_1","unstructured":"National Heart Lung and Blood Institute.Quality assessment tool for case series studies. 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