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. 2020 Feb 3;10:1653. doi: 10.1038/s41598-020-58569-4

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Comparison of growth responses after isoeffective treatments having the same 2D clonogenic survival fraction, delivered by either RT, HT or a combination thereof. (A) Clonogenic survival (mean values and standard deviations of at least three repeat experiments ( $n \geq 3$ )) of HCT116 and CAL27 cells as a function of radiation or thermal dose. BEQD levels seen for 10 Gy RT are indicated as horizontal boxes. (B) Growth curves for HCT116-300 and CAL27 spheroids. Mean values and standard errors of at least three independent experiments are shown. (C) Cell viability measured by Cell-Titer-Glo3D 21 days after treatment of the samples shown in B. *p < 0.01, **p < 0.05. (D) Spatial distribution of PI staining within representative examples of treated HCT116-4000 spheroids. The x-axis indicates the distance in pixels from the spheroid centre of mass.