Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer

Elgin Hoffmann, Frank Paulsen, Philipp Schaedle, Daniel Zips, Cihan Gani, Hans-Georg Rammensee, Cécile Gouttefangeas, Franziska Eckert, Elgin Hoffmann, Frank Paulsen, Philipp Schaedle, Daniel Zips, Cihan Gani, Hans-Georg Rammensee, Cécile Gouttefangeas, Franziska Eckert

Abstract

Purpose: The influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters.

Patients and methods: For 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow.

Results: Most significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8+ subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8+ effector T cells correlated with V20 of blood vessels and bone volumes.

Conclusions: Patient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects.

Trial registration number: NCT01376674, 20.06.2011.

Keywords: DVH; IMRT; Immune status; Localized; Prostate cancer; T cells.

Conflict of interest statement

E. Hoffmann: Research and educational grants from Elekta, Philips, Siemens, and Sennewald. F. Paulsen: Research and educational grants from Elekta, Philips, Siemens, and Sennewald. P. Schaedle: No conflict of interest. D. Zips: Research and educational grants by Elekta, Philips, Siemens, Sennewald, Kaikuu, and TheraPanacea C. Gani: Research and educational grants, sponsoring for symposia by Elekta, Philips, Siemens, Sennewald, Kaikuu, and TheraPanacea. H.-G. Rammensee: No conflict of interest. C. Gouttefangeas: No conflict of interest. F. Eckert: Research and educational grants from Elekta, Philips, Siemens, and Sennewald. Speaker’s honoraria by Sennewald.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
To compare immune cell changes with radiation planning parameters, the ratio of immune cell subsets and proliferative fractions within each of these cell subsets is displayed for time point B (4 weeks into radiotherapy), time point C (end of radiotherapy) and time point D (3 months after end of radiotherapy) compared to baseline levels (time point A). Significant changes have been observed for proliferation of most cell subsets at time point B, most subsets at time point C, and only a few long-lasting effects at time point D. The red line indicates a ratio of 1 and thus no change compared to baseline frequencies. * indicates significant changes with one sample t-test compared to a ratio of 1
Fig. 2
Fig. 2
Correlation of patient age at time of radiotherapy and CD8+ effector cells as well as CD8+ memory cells is shown for all time points in the subgroup of patients treated with radiotherapy to the prostate. Patient age correlated positively with CD8+ effector cells and negatively with CD8+ memory cells at early and late time points (B/A and D/A, respectively)
Fig. 3
Fig. 3
Volumes contoured in addition to standard radiotherapy target volume (turquoise) and organs at risk such as bladder (yellow) and rectum (brown) are pelvic bone marrow (PBM union) comprising iliac bone marrow (red), lumbosacral spine (yellow) and lower pelvic bone marrow (light blue) as well as arteries (orange) and veins (dark blue) combined as vessels are shown
Fig. 4
Fig. 4
Dose-volume histograms of PBM union and vessels (upper panels) are shown for two patients comparing radiotherapy to the prostate only and radiotherapy including pelvic node irradiation. Correlations of CTV and V20 of vessels and PBM are shown for all patients. The clinical target volume (CTV) used for radiation planning and dose parameters for PBM and vessels showed no to moderate correlation to each other. Thus, the volume of CTV is not an adequate surrogate parameter for the dose to PBM and vessels (V20). V20 for PBM and V20 for vessels showed a moderate correlation
Fig. 5
Fig. 5
Changes of T cells and T cell proliferation are shown for time points B/A, C/A and D/A in the primary analysis of patients receiving radiotherapy to prostate only. T cells negatively correlated with CTV volume when comparing time points B and D, but not C, to A. T cell proliferation was positively correlated with CTV volume for ratio D/A, while having the lowest total ratio at this time point
Fig. 6
Fig. 6
Ratios of Treg cells as well as CD8+ effector cells are shown in correlation with V20 (blood vessels) and V20 (PBM union) for time points B/A, C/A and D/A. Treg cells correlated positively with V20 (blood vessels) as well as V20 (PBM) at time point B/A in the primary analysis. At the same time, CD8+ effector cell ratios showed a negative correlation with V20 (blood vessels) as well as V20 (PBM). No such correlation was found with the ratios at time points C/A or D/A

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