{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:05:22Z","timestamp":1793397922238,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>After temozolomide failure, no evidence-based treatment is available for pituitary carcinomas (PCs) and aggressive pituitary tumors (APTs). To date, only 12 cases treated with immune-checkpoint inhibitors (ICIs) have been published, showing encouraging efficacy. Predictive factors of response are lacking. Here, we aimed to assess the real-life efficacy and predictors of response to ICIs in PCs and APTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>This study is a multicentric, retrospective, observational cohort study, including all PCs and APTs treated with ICIs in France up to March 2022. PD-L1 immunohistochemistry and CD8+ T cell infiltration were evaluated centrally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six PCs (four corticotroph and two lactotroph) and nine APTs (five corticotroph and four lactotroph) were included. The real-life efficacy of ICIs was lower than previously published data. Three corticotroph tumors (33.3%) showed partial response, one (11.1%) stable disease, while five (55.6%) progressed. One lactotroph tumor (16.7%) showed partial response, one (16.7%) stable disease, while four (66.7%) progressed. PCs responded far better than APTs, with 4\/6 PCs showing partial response compared to 0\/9 APTs. Corticotroph tumors responded slightly better than lactotroph tumors. In the four responsive corticotroph tumors, PD-L1 staining was negative and CD8+ T cell infiltration attained a maximum of 1% in the tumor center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Confirmation of the presence or absence of metastases is necessary before starting ICIs. After temozolomide failure, ICIs appear as a good therapeutic option for PCs, especially for corticotroph carcinomas. Negative PD-L1 staining and very low CD8+ T cell infiltration in the tumor center should not preclude ICI administration in corticotroph carcinomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance statement<\/jats:title>\n                    <jats:p>This is the first study to assess the real-life efficacy of ICIs in pituitary carcinomas (PCs) and aggressive pituitary tumors. We also assessed potential predictors of response and are the first to assess the predictive value of CD8+ cell infiltration. We identified the tumor type as a major predictor, ICIs proving far more effective in treating PCs. Our study provides evidence that ICIs are a good option after temozolomide failure for PCs (four of six responded), especially for corticotroph carcinomas (three of four responded). We also provide evidence that negative PD-L1 staining and very low CD8+ cell infiltration in the tumor center should not preclude ICI administration in corticotroph carcinomas. Moreover, our findings point toward the need to systematically perform extension workup before starting ICIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-22-0647","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T06:32:00Z","timestamp":1663309920000},"page":"685-696","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":54,"title":["Real-life efficacy and predictors of response to immunotherapy in pituitary tumors: a cohort study"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7248-7258","authenticated-orcid":false,"given":"Mirela Diana","family":"Ilie","sequence":"first","affiliation":[{"name":"Inserm U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Cancer Research Center of Lyon , Lyon, France"},{"name":"Endocrinology Department, \u2018C.I. Parhon\u2019 National Institute of Endocrinology , Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Villa","sequence":"additional","affiliation":[{"name":"Neuropathology Department, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, AP-HP-Sorbonne University , Paris, France"},{"name":"Inserm U1016, CNRS UMR8104, Cochin Institute , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-0030","authenticated-orcid":false,"given":"Thomas","family":"Cuny","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Conception University Hospital, AP-HM , Marseille, France"},{"name":"Inserm U1251, Marseille Medical Genetics, Aix Marseille University , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Cortet","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Lille University Hospital , Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Assie","sequence":"additional","affiliation":[{"name":"Inserm U1016, CNRS UMR8104, Cochin Institute , Paris, France"},{"name":"Endocrinology Department, Cochin University Hospital, AP-HP , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0735-8278","authenticated-orcid":false,"given":"Bertrand","family":"Baussart","sequence":"additional","affiliation":[{"name":"Inserm U1016, CNRS UMR8104, Cochin Institute , Paris, France"},{"name":"Neurosurgery Department, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, AP-HP , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Cancel","sequence":"additional","affiliation":[{"name":"Oncology Department, Tours University Hospital , Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Chanson","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Reproduction Disorders, Bic\u00eatre Hospital, AP-HP , Le Kremlin-Bic\u00eatre, France"},{"name":"Paris-Saclay University, Inserm, \u2018Physiologie et Physiopathologie Endocriniennes\u2019 , Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Decoudier","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Reims University Hospital , Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Deluche","sequence":"additional","affiliation":[{"name":"Oncology Department, Limoges University Hospital , Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Luisa","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Neurology Department, Foch Hospital , Suresnes, France"},{"name":"Neurosurgery Unit, Livorno Hospital , Livorno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Drui","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Nantes University Hospital , Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-8919","authenticated-orcid":false,"given":"Stephan","family":"Gaillard","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, AP-HP , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Goichot","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Strasbourg University Hospital , Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Huillard","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Cochin University Hospital, AP-HP, Paris Cancer Institute CARPEM , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Joncour","sequence":"additional","affiliation":[{"name":"Oncology Department, Poitiers University Hospital , Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Larrieu-Ciron","sequence":"additional","affiliation":[{"name":"Oncology Department, IUCT-Oncopole , Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Libe","sequence":"additional","affiliation":[{"name":"Inserm U1016, CNRS UMR8104, Cochin Institute , Paris, France"},{"name":"Endocrinology Department, Cochin University Hospital, AP-HP , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Nars","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Strasbourg University Hospital , Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Vasiljevic","sequence":"additional","affiliation":[{"name":"Inserm U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Cancer Research Center of Lyon , Lyon, France"},{"name":"Pathology Department, Reference Center for Rare Pituitary Diseases HYPO, \u2018Groupement Hospitalier Est\u2019 Hospices Civils de Lyon , Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9517-338X","authenticated-orcid":false,"given":"G\u00e9rald","family":"Raverot","sequence":"additional","affiliation":[{"name":"Inserm U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Cancer Research Center of Lyon , Lyon, France"},{"name":"Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO, \u2018Groupement Hospitalier Est\u2019 Hospices Civils de Lyon , Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"2023010809172395900_bib1","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0796","article-title":"European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas","volume":"178","author":"Raverot","year":"2018","journal-title":"European Journal of Endocrinology"},{"key":"2023010809172395900_bib2","first-page":"671","article-title":"Aggressive pituitary tumours and pituitary carcinomas","volume":"17","author":"Raverot","year":"2021","journal-title":"Nature Reviews: Endocrinology"},{"key":"2023010809172395900_bib3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ecl.2020.05.008","article-title":"Aggressive pituitary adenomas and carcinomas","volume":"49","author":"Ilie","year":"2020","journal-title":"Endocrinology and Metabolism Clinics of North America"},{"key":"2023010809172395900_bib4","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1210\/jc.2018-01347","article-title":"Marked response of a hypermutated ACTH-secreting pituitary carcinoma to ipilimumab and nivolumab","volume":"103","author":"Lin","year":"2018","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809172395900_bib5","doi-asserted-by":"crossref","first-page":"bvab133","DOI":"10.1210\/jendso\/bvab133","article-title":"Synergism of checkpoint inhibitors and peptide receptor radionuclide therapy in the treatment of pituitary carcinoma","volume":"5","author":"Lin","year":"2021","journal-title":"Journal of the Endocrine Society"},{"key":"2023010809172395900_bib6","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3390\/jpm10030088","article-title":"Immunotherapy in corticotroph and lactotroph aggressive tumors and carcinomas: two case reports and a review of the literature","volume":"10","author":"Duhamel","year":"2020","journal-title":"Journal of Personalized Medicine"},{"key":"2023010809172395900_bib7","doi-asserted-by":"crossref","first-page":"K1","DOI":"10.1530\/EJE-20-0151","article-title":"Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: a new emerging treatment?","volume":"184","author":"Sol","year":"2020","journal-title":"European Journal of Endocrinology"},{"key":"2023010809172395900_bib8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/CAD.0000000000000856","article-title":"Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab","volume":"31","author":"Caccese","year":"2020","journal-title":"Anti-Cancer Drugs"},{"key":"2023010809172395900_bib9","doi-asserted-by":"crossref","first-page":"e001532","DOI":"10.1136\/jitc-2020-001532","article-title":"Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study","volume":"8","author":"Majd","year":"2020","journal-title":"Journal for ImmunoTherapy of Cancer"},{"key":"2023010809172395900_bib10","doi-asserted-by":"crossref","first-page":"576027","DOI":"10.3389\/fendo.2020.576027","article-title":"Case report: A case of pituitary carcinoma treated with sequential dual immunotherapy and vascular endothelial growth factor inhibition therapy","volume":"11","author":"Lamb","year":"2020","journal-title":"Frontiers in Endocrinology"},{"key":"2023010809172395900_bib11","doi-asserted-by":"crossref","DOI":"10.1111\/cen.14645","article-title":"Should pituitary carcinoma be treated using a NET-like approach? A case of complete remission of a metastatic malignant prolactinoma with multimodal therapy including immunotherapy","author":"Goichot","year":"2021","journal-title":"Clinical Endocrinology"},{"key":"2023010809172395900_bib12","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1227\/neu.0000000000002024","article-title":"Complete response of a patient with a mismatch repair deficient aggressive pituitary adenoma to immune checkpoint inhibitor therapy: a case report","volume":"91","author":"Shah","year":"2022","journal-title":"Neurosurgery"},{"key":"2023010809172395900_bib13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1530\/ERC-22-0037","article-title":"Immunotherapy in aggressive pituitary tumors and carcinomas: a systematic review","volume":"29","author":"Ilie","year":"2022","journal-title":"Endocrine-Related Cancer"},{"key":"2023010809172395900_bib14","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.3390\/cancers12041012","article-title":"Gonadotroph tumors show subtype differences that might have implications for therapy","volume":"12","author":"Ilie","year":"2020","journal-title":"Cancers"},{"key":"2023010809172395900_bib15","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/PAP.0000000000000162","article-title":"Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the International Immunooncology Biomarkers Working Group: part 1: assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research","volume":"24","author":"Hendry","year":"2017","journal-title":"Advances in Anatomic Pathology"},{"key":"2023010809172395900_bib16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"European Journal of Cancer"},{"key":"2023010809172395900_bib17","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/bjc.2011.274","article-title":"FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy","volume":"105","author":"Day","year":"2011","journal-title":"British Journal of Cancer"},{"key":"2023010809172395900_bib18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1530\/EJE-17-0933","article-title":"Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) Survey 2016","volume":"178","author":"McCormack","year":"2018","journal-title":"European Journal of Endocrinology"},{"key":"2023010809172395900_bib19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11154-020-09562-9","article-title":"Are aggressive pituitary tumors and carcinomas two sides of the same coin? Pathologists reply to clinician's questions","volume":"21","author":"Trouillas","year":"2020","journal-title":"Reviews in Endocrine and Metabolic Disorders"},{"key":"2023010809172395900_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/jcm8081107","article-title":"Emerging and novel treatments for pituitary tumors","volume":"8","author":"Ilie","year":"2019","journal-title":"Journal of Clinical Medicine"},{"key":"2023010809172395900_bib21","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s12022-021-09673-2","article-title":"PD-L1 is preferentially expressed in PIT-1 positive pituitary neuroendocrine tumours","volume":"32","author":"Turchini","year":"2021","journal-title":"Endocrine Pathology"},{"key":"2023010809172395900_bib22","doi-asserted-by":"crossref","first-page":"e154","DOI":"10.1111\/ajco.13365","article-title":"The adverse events associated with combination immunotherapy in cancers: challenges and chances","volume":"16","author":"Zhuo","year":"2020","journal-title":"Asia-Pacific Journal of Clinical Oncology"},{"key":"2023010809172395900_bib23","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.4158\/ACCR-2020-0100","article-title":"Caution advised using combination ketoconazole and PD-1 inhibitors","volume":"6","author":"Yang","year":"2020","journal-title":"AACE Clinical Case Reports"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/187\/5\/EJE-22-0647.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/187\/5\/EJE-22-0647.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/5\/685\/48515771\/eje-22-0647.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/5\/685\/48515771\/eje-22-0647.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T11:18:20Z","timestamp":1676373500000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/187\/5\/685\/6972066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1530\/eje-22-0647","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742324154.793597099","asserted-by":"object"}]},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,11]]},"published":{"date-parts":[[2022,10,17]]}}}