{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:18:16Z","timestamp":1789417096848,"version":"build-2803163510"},"reference-count":28,"publisher":"Bioscientifica","issue":"9","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:p>\n                    Adjuvant treatment with mitotane and chemotherapy is recommended for paediatric advanced and metastatic adrenocortical carcinoma (ACC). Yet, questions on the indication, dosage, and length of therapy are unanswered. Data from the German Paediatric Oncology Haematology-Malignant Endocrine Tumour studies were analysed retrospectively for patients receiving mitotane during first- and\/or second-line therapy. Forty-three patients were identified (median age: 7.5 years (range: 0.2\u201317.8); 29 female) with median follow-up of 2.2 years (range: 0.04\u201312.71). Three-year overall (OS) and progression-free survival (PFS) were 44.9% and 28.5%, respectively. Eleven of 43 patients received mitotane as neoadjuvant treatment, and 4\/11 tumours reached partial remission (PR). Twenty-seven of 43 patients received mitotane combined with chemotherapy in an adjuvant setting resulting in PR of measurable target lesions in 5\/13 patients. Metastatic disease (hazard ratio (HR): 3.2; 95% CI: 1.2\u201318.6;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.018), duration of mitotane treatment &lt;9 months (HR: 5.6; 95% CI: 1.9\u201316.9;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.002), and not achieving drug target range (TR) (HR: 28.5; 95% CI: 5.4\u2013150.3;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) significantly impacted as negative prognostic factors upon PFS and OS (metastatic disease: HR: 4.9; 95% CI: 1.6\u201315.5;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.006; duration of mitotane treatment: HR: 7.0: 95% CI 1.9\u201326.0;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004; TR not reached: HR: 13.5; 95% CI 3.6\u201350.3;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Cox regression determined the risk of event decreasing by 10.4% for each month of mitotane treatment (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015). Re-treatment with mitotane after first-line treatment proved ineffective. The duration of mitotane treatment and reaching mitotane TR significantly impacted survival. Improving the efficacy of mitotane, including appropriate indications, needs to be evaluated in prospective randomized trials.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0146","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T11:42:25Z","timestamp":1657107745000},"page":"545-555","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":11,"title":["Key factors for effective mitotane therapy in children with adrenocortical carcinoma"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-0503","authenticated-orcid":true,"given":"Michaela","family":"Kuhlen","sequence":"first","affiliation":[{"name":"Paediatric and Adolescent Medicine, Faculty of Medicine, University Medical Centre Augsburg, Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Mier","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kunstreich","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lienhard","family":"Lessel","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Schneider","sequence":"additional","affiliation":[{"name":"Clinic of Paediatrics, Klinikum Dortmund, University Witten\/Herdecke, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Brecht","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology, Department of Paediatrics, University Hospital Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis M","family":"Schewe","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Fr\u00fchwald","sequence":"additional","affiliation":[{"name":"Paediatric and Adolescent Medicine, Faculty of Medicine, University Medical Centre Augsburg, Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vorwerk","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Redlich","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, University Children\u2019s Hospital, Otto-von-Guericke-University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Pediatric Blood and Cancer","article-title":"Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: a report from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT","volume":"64","author":"Cecchetto","year":"2017","unstructured":"Cecchetto GGanarin ABien EVorwerk PBisogno GGodzinski JDall\u2019Igna PReguerre YSchneider DBrugieres L2017Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: a report from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). 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