{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:38:37Z","timestamp":1780457917413,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hastings Center Report"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Pediatrics often faces ethical challenges when families request unproven therapies. We respond to a clinical case described in \u201cA Parental Request for an Unproven Treatment for a Rare Pediatric Cancer: Sound Reasons for Not Going Off\u2010Label,\u201d by Margot Hedlin and Louis Voigt, in the same issue of this journal. The case concerns Natalie, a three\u2010year\u2010old in remission from ependymoma, whose parents requested metformin to prevent recurrence. Although Natalie's neuro\u2010oncologist opposed the use of the drug, its favorable safety profile, pediatric Food and Drug Administration approval for other indications, emerging evidence in cancer research, and endorsement by a specialist support careful consideration. Off\u2010label prescribing is common in pediatric oncology due to issues presented by rare diseases and due to the limitations of clinical trials. With informed consent, monitoring, and interdisciplinary input about the patient's care, prescribing metformin may be ethically justifiable despite uncertain efficacy. This case illustrates the balance between evidence\u2010based practice, patient\u2010 and family\u2010centered care, and the realities of pediatric cancer treatment<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/hast.70044","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:58:36Z","timestamp":1773723516000},"page":"16-18","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Case for Prescribing Metformin Off\u2010Label for a Child in Remission from Ependymoma"],"prefix":"10.1002","volume":"56","author":[{"given":"Emily S.","family":"Hahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Hedlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/hast.5025"},{"key":"e_1_2_3_2_1","unstructured":"The name of the patient and other identifying details have been changed to preserve the privacy and confidentiality of the patient."},{"key":"e_1_2_3_3_1","unstructured":"These results were found December 2025 using the search terms \u201cCancer Metformin\u201d on the National Center for Biotechnology Information'sClinicalTrials.govsite; seehttps:\/\/clinicaltrials.gov\/search?cond=Cancer&intr=Metformin."},{"key":"e_1_2_3_4_1","unstructured":"The trial mentioned as forthcoming is Target Validation and Efficacy of Metformin in Patients with Posterior Fossa Group A (PFA) Ependymoma (PNOC041); seehttps:\/\/clinicaltrials.gov\/study\/NCT07226453 accessed December 2025."},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.4696"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1072879"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-018-4015-3"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-4060"},{"key":"e_1_2_3_9_1","doi-asserted-by":"crossref","unstructured":"E. M.Speeret al. \u201cThe State and Future of Pediatric Research\u2014an Introductory Overview \u201dPediatric Research(2023): doi:10.1038\/s41390-022-02439.","DOI":"10.1038\/s41390-022-02439-4"},{"key":"e_1_2_3_10_1","first-page":"7","volume-title":"Pediatric Self-Assessment Program: Research and Study Design in Pediatrics","author":"Podany A.","year":"2017"},{"key":"e_1_2_3_11_1","volume-title":"Cancer Facts & Figures: 2024","author":"Society American Cancer","year":"2024"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3349"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.02.011"},{"key":"e_1_2_3_14_1","unstructured":"Limet al. \u201cOff-Label Prescribing of Targeted Anticancer Therapy at a Large Pediatric Cancer Center.\u201d"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy131"},{"key":"e_1_2_3_16_1","unstructured":"Best Pharmaceuticals for Children Act Pub. L. No. 107-109(2002)."},{"key":"e_1_2_3_17_1","doi-asserted-by":"crossref","unstructured":"Pediatric Research Equity Act of 2003 Pub. L. No. 108-155 117 Stat. 1936(2003).","DOI":"10.1016\/S0169-328X(03)00361-9"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28871"},{"key":"e_1_2_3_19_1","unstructured":"[American Academy of Pediatrics] Committee on Drugs Nevilleet el. \u201cOff-Label Use of Drugs in Children.\u201d The quotation is from the abstract."},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/jop.18.00115"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-4018"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-1394c"}],"container-title":["Hastings Center Report"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hast.70044","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hast.70044","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hast.70044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:47:00Z","timestamp":1780408020000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hast.70044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/hast.70044"],"URL":"https:\/\/doi.org\/10.1002\/hast.70044","archive":["Portico"],"relation":{},"ISSN":["0093-0334","1552-146X"],"issn-type":[{"value":"0093-0334","type":"print"},{"value":"1552-146X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2026-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}