**5. Conclusions**

Central necrosis of tumours on [18F]FDG PET significantly impacts radiomic feature values. Almost two-third of the features were affected, demonstrating that the influence of whether or not to include regions of central necrosis in the delineation of the tumour on the radiomic feature values is significant. However, no significant difference in the predictive performance of both delineation methods was observed. In order to advance reproducibility of radiomic research, radiomic studies should report on whether or not central necrosis was (manually) included during delineation.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/2075-4 418/11/7/1296/s1, Supplementary File S1: Image Biomarker Standardisation Initiative Reporting Guidelines, Supplementary Table S1: Features affected by the choice of delineation method (VOIvital-tumour vs. VOIgross-tumour) for the different cohorts and subgroups based on NTF and SUVmax.

**Author Contributions:** Conceptualisation, W.A.N., D.V., C.H.S., L.-F.d.G.-O. and F.H.P.v.V.; methodology, W.A.N., D.V., L.-F.d.G.-O. and F.H.P.v.V.; software, W.A.N. and F.H.P.v.V.; validation, W.A.N., D.V., L.-F.d.G.-O. and F.H.P.v.V.; formal analysis, W.A.N. and C.D.Y.M.; investigation, W.A.N. and C.D.Y.M.; resources, D.V., E.H.A., A.v.B., H.J.L.M.T., J.B., T.W.H.M. and L.-F.d.G.-O.; data curation, W.A.N., D.V., L.-F.d.G.-O. and F.H.P.v.V.; writing—original draft preparation, W.A.N.; writing— Review and Editing, D.V., C.D.Y.M., C.H.S., E.H.A., A.v.B., H.J.L.M.T., J.B., T.W.H.M., L.-F.d.G.-O. and F.H.P.v.V.; visualisation, W.A.N.; supervision, D.V., L.-F.d.G.-O. and F.H.P.v.V.; project administration, D.V., L.-F.d.G.-O. and F.H.P.v.V.; funding acquisition, L.-F.d.G.-O. and F.H.P.v.V. All authors have read and agreed to the published version of the manuscript.

**Funding:** Dennis Vriens was supported in part by the Netherlands Organisation for Health Research and Development (ZonMw) stipends for a Clinical Research Fellowship (AGIKO) (project no. 92003552) for design and data collection of the original clinical NSCLC study. The costs of the additional dynamic PET scans were covered by the Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen. The PPGL study [19] was supported by the European Union Seventh Framework Programme (FP7/2007–2013) under gran<sup>t</sup> agreemen<sup>t</sup> 259735 (ENSAT CANCER). No additional funding was received for this study.

**Institutional Review Board Statement:** The studies were conducted according to the guidelines of the Declaration of Helsinki. The NSCLC study has been reviewed and approved by the Commission on Medical Research Involving Human Subjects Region Arnhem-Nijmegen, the Netherlands (protocol code: NL24886.091.08, date of approval: 8 December 2008). The PPGL retrospective database study has been reviewed and approved by the Commission on Medical Research Involving Human Subjects Region Arnhem-Nijmegen, the Netherlands (protocol code: 2018-4655, date of approval: 10 December 2018).

**Informed Consent Statement:** All NSCLC patients signed an informed consent form. For the PPGL study, informed consent was waived due to the retrospective nature of the study. Patients that objected to the use of their anonymised data were excluded.

**Data Availability Statement:** The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

**Acknowledgments:** The authors want to thank the PET/CT technologists from the Radboud University Medical Center for their assistance with the PET/CT scans.

**Conflicts of Interest:** The authors have declared that no competing interests exist.
