Modelling the In Vivo and Ex Vivo DNA Damage Response after Internal Irradiation of Blood from Patients with Thyroid Cancer
Abstract
:1. Introduction
2. Results
2.1. Patient Data
2.2. Absorbed Doses to the Blood and Number of RIF
2.3. Modelling
2.4. Comparison with Ex Vivo Data
2.5. Correlations of Fit Parameters with Clinical Data
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Dosimetry
4.3. Evaluation of DSB Damage
4.4. Modelling the DNA Damage Response
4.5. Fitting Process
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient ID | Gender | Age (a) | Weight (kg) | Administered Activity (GBq) | Tumour Type | TNM Staging |
---|---|---|---|---|---|---|
IP1 | f | 44.7 | 85 | 3.55 | papillary | pT1a, pNx |
IP2 | f | 65.3 | 72 | 3.51 | papillary (follicular variant) | pT1b, Nx |
IP3 | f | 24.9 | 67 | 3.55 | papillary | pT2m, N1a (3/6) |
IP4 * | f | 28.6 | 78 | 3.57 | papillary | pT1b, pNx |
IP5 | f | 55.2 | 46 | 3.43 | papillary | pT1b, pNx |
IP6 * | f | 21.0 | 115 | 3.52 | follicular (encapsulated angio-invasive) | pT1b, Nx |
IP7 | f | 54.7 | 70 | 3.72 | papillary | pT2m, pNx |
IP8 | f | 48.8 | 60 | 3.65 | papillary | T2, Nx |
IP9 * | f | 45.1 | 108 | 3.50 | papillary | pT2(m), pN0 (0/1) |
IP10 | f | 44.6 | 77 | 3.56 | papillary | pT2, N0 (0/10) |
IP11 | m | 59.9 | 80 | 3.58 | papillary | pT1b, pN0 (0/12) |
IP12 | f | 26.2 | 85 | 3.56 | papillary | pT1b, pN0 (0/3) |
IP13 | m | 36.3 | 96 | 3.60 | papillary | pT2, pNx |
IP14 | f | 38.9 | 68 | 3.91 | papillary | pT1b, pN1b (3/22) |
IP15 * † | m | 54.7 | 94 | 3.52 | papillary | pT3a, pNx |
IP16 | f | 63.8 | 85 | 3.60 | follicular | pT2, pN0 (0/6) |
IP17 | m | 19.8 | 82 | 3.66 | papillary | pT1b, pN0 |
IP18 | f | 59.2 | 96 | 3.60 | papillary | pT2, pN1b (2/33) |
Nominal Time Point | Median Absorbed Dose to the Blood (mGy) | Median Absorbed Dose Rate (mGy h−1) | Median of the Average Number of RIF per Cell | Number of Patients with RIF-Data |
---|---|---|---|---|
0 (baseline) | 0 | 0 | 0 | 18 |
1 h | 14 (12–19) | 15.5 (8.1–20.0) | 0.37 (0.16–0.74) | 18 |
2 h | 29 (24–37) | 14.7 (12.3–18.3) | 0.61 (0.26–0.88) | 17 |
3 h | 43 (37–55) | 13.9 (10.2–16.7) | 0.48 (0.27–0.83) | 18 |
4 h | 57 (48–71) | 12.8 (8.7–15.3) | 0.66 (0.33–0.99) | 18 |
24 h | 200 (144–239) | 3.5 (2.5–5.4) | 0.41 (−0.07–0.81) | 18 |
48 h | 249 (192–323) | 1.1 (0.5–2.2) | 0.26 (−0.12–0.60) | 18 |
96 h | 278 (203–385) | 0.2 (0.0–1.9) | 0.15 (−0.09–0.34) | 12 |
168 h | 287 (205–419) | 0.1 (0.0–1.1) | 0.05 (−0.21–0.38) | 17 |
∞ | 299 (205–605) | -- | -- | -- |
Patient ID | c (mGy−1) | α | k1 (h−1) | k2 (h−1) | N0 | r2 | Number of Data Points | Group | Ex Vivo R (h−1) [17] |
---|---|---|---|---|---|---|---|---|---|
IP1 | 0.012 ± 0.001 | 0.931 ± 0.036 | 0.210 ± 0.038 | 0.018 ± 0.011 | 0.004 ± 0.015 | 0.99 | 9 | 1 | 0.19 ± 0.04 |
IP2 | 0.023 ± 0.008 | 0.942 ± 0.031 | 0.389 ± 0.231 | 0.006 ± 0.007 | −0.005 ± 0.080 | 0.91 | 9 | 1 | 0.19 ± 0.01 |
IP3 | 0.023 ± 0.005 | 0.945 ± 0.020 | 0.324 ± 0.156 | 0.006 ± 0.005 | 0.015 ± 0.060 | 0.96 | 9 | 1 | 0.23 ± 0.15 |
IP4 | 0.071 ± 0.014 | 0.980 ± 0.006 | 1.330 ± 0.302 | 0.017 ± 0.008 | 0.003 ± 0.030 | 0.99 | 9 | 2 | 0.12 ± 0.03 |
IP5 | 0.028 ± 0.009 | 0.986 ± 0.017 | 0.499 ± 0.226 | 0.000 ± 0.011 | −0.020 ± 0.090 | 0.94 | 9 | 1 | 0.10 ± 0.08 |
IP6 | 0.109 ± 0.125 | 0.954 ± 0.050 | 3.028 ± 3.811 | 0.026 ± 0.010 | −0.009 ± 0.044 | 0.98 | 8 | 2 | 0.43 ± 0.32 |
IP7 | 0.024 ± 0.017 | 0.943 ± 0.057 | 0.554 ± 0.596 | 0.016 ± 0.028 | −0.103 ± 0.148 | 0.81 | 9 | 1 | 0.24 ± 0.13 |
IP9 | 0.047 ± 0.056 | 0.950 ± 0.091 | 1.479 ± 2.259 | 0.040 ± 0.097 | −0.029 ± 0.098 | 0.84 | 8 | 2 | 0.16 ± 0.03 |
IP13 | 0.044 ± 0.031 | 0.959 ± 0.027 | 1.262 ± 0.993 | 0.006 ± 0.005 | −0.004 ± 0.085 | 0.87 | 9 | 2 | 0.35 ± 0.04 |
IP14 | 0.047 ± 0.031 | 0.924 ± 0.056 | 1.140 ± 1.004 | 0.031 ± 0.024 | −0.042 ± 0.091 | 0.92 | 9 | 2 | 0.27 ± 0.08 |
IP15 | 0.019 ± 0.006 | 0.979 ± 0.061 | 0.193 ± 0.102 | 0.000 ± 0.030 | 0.018 ± 0.083 | 0.85 | 9 | 1 | 0.19 ± 0.08 |
IP16 | 0.021 ± 0.005 | 0.958 ± 0.011 | 0.451 ± 0.178 | 0.000 ± 0.003 | −0.003 ± 0.051 | 0.96 | 9 | 1 | 0.18 ± 0.03 |
IP17 | 0.051 ± 0.031 | 0.935 ± 0.045 | 1.393 ± 1.117 | 0.044 ± 0.030 | −0.049 ± 0.050 | 0.95 | 9 | 2 | 0.18 ± 0.11 |
IP18 | 0.020 ± 0.006 | 1.000 ± 0.020 | 0.217 ± 0.077 | not applicable | −0.033 ± 0.109 | 0.90 | 9 | 1 | 0.20 ± 0.11 |
Group | c (mGy−1) | α | k1 (h−1) | k2 (h−1) | N0 | r2 | Number of Data Points |
---|---|---|---|---|---|---|---|
1 | 0.022 ± 0.004 | 0.954 ± 0.015 | 0.362 ± 0.109 | 0.006 ± 0.005 | 0.000 ± 0.038 | 0.73 | 72 |
2 | 0.065 ± 0.024 | 0.962 ± 0.016 | 1.546 ± 0.669 | 0.027 ± 0.012 | 0.001 ± 0.035 | 0.81 | 52 |
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Schumann, S.; Scherthan, H.; Hartrampf, P.E.; Göring, L.; Buck, A.K.; Port, M.; Lassmann, M.; Eberlein, U. Modelling the In Vivo and Ex Vivo DNA Damage Response after Internal Irradiation of Blood from Patients with Thyroid Cancer. Int. J. Mol. Sci. 2024, 25, 5493. https://doi.org/10.3390/ijms25105493
Schumann S, Scherthan H, Hartrampf PE, Göring L, Buck AK, Port M, Lassmann M, Eberlein U. Modelling the In Vivo and Ex Vivo DNA Damage Response after Internal Irradiation of Blood from Patients with Thyroid Cancer. International Journal of Molecular Sciences. 2024; 25(10):5493. https://doi.org/10.3390/ijms25105493
Chicago/Turabian StyleSchumann, Sarah, Harry Scherthan, Philipp E. Hartrampf, Lukas Göring, Andreas K. Buck, Matthias Port, Michael Lassmann, and Uta Eberlein. 2024. "Modelling the In Vivo and Ex Vivo DNA Damage Response after Internal Irradiation of Blood from Patients with Thyroid Cancer" International Journal of Molecular Sciences 25, no. 10: 5493. https://doi.org/10.3390/ijms25105493