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. 2021 Jun 29;11:703893. doi: 10.3389/fonc.2021.703893

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Copyright © 2021 Daniello, Elshiaty, Bozorgmehr, Kuon, Kazdal, Schindler, Shah, Volckmar, Lusky, Diekmann, Liersch, Faehling, Muley, Kriegsmann, Benesova, Stenzinger, Thomas and Christopoulos

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Steroid management of grades 1–4 irAEs. (A) Mean initial daily dose, mean average daily dose, and mean cumulative dose for steroid treatment in patients with grade 2–4 irAEs analyzed by one-way ANOVA. While no grade 1 irAE received steroid treatment, mean initial daily, mean average daily and cumulative steroid dose increased steadily from grades 2–4: for grade 2 irAE mean initial dose: 20.2 mg [standard error (SE): 2.9], cumulative dose: 1056.4 mg (SE: 300.3), mean daily dose: 12.9 mg (SE: 2.0); for grade 3 irAE: mean initial dose: 93.4 mg (SE: 9.7), cumulative dose: 1747.5 mg (SE: 186.3), mean daily dose: 51.5 mg (SE: 5.3); for grade 4 irAE mean initial dose: 96.4 mg (SE: 10.9), cumulative dose: 1823.5 mg (SE: 348.4), mean daily dose: 62.8 mg (SE: 8.0). ANOVA with post-hoc test for trend across grades: p < 0.001 (mean initial daily dose), p < 0.001 (mean average daily dose), p = 0.005 (cumulative dose). (B) Cumulative steroid dose and total duration of steroid treatment by affected organ: endocrine: 942 mg (SE: 536) over 31 days (SE: 16); lungs: 1,519 mg (SE: 248) over 41 days (SE: 6)); musculoskeletal: mean cumulative dose 1455 mg (SE: 442) over 128 days (SE: 33); colon: 1,371 mg (SE: 227) over 44 days (SE: 7); liver: 1,622 mg (SE: 339) over 33 days (SE: 5); skin: 237 mg (SE: 123) over 23 days (SE: 11); nervous system: 863 mg (SE: 427) over 21 days (SE: 9); cardiologic: 1,183 mg (SE: 684) over 39 days (SE: 31); kidney: 3,330 (SE: 2,394) over 86 days (SE: 9); pancreas: 1,413 mg (SE: 1035) over 53 days (SE: 5); blood: 940 mg (SE: na) over 20 days (SE: na). One-way ANOVA p = 0.002 for the cumulative dose across affected organs (with statistical significance in post-hoc testing for musculoskeletal irAE, please see Table 2 ), and p = 0.61 for the treatment duration. Abbreviations: irAEs, immune related adverse events; SE, standard error of the mean; n/a, not applicable.