Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tumour Biology Maps
2.2. TCP Model
2.3. Treatment Planning
2.3.1. Method 1: Uniform-Dose Planning
2.3.2. Method 2: Focal Tumour DE
2.3.3. Method 3: Focal Tumour + Hypoxia DE
2.3.4. Method 4: Biologically Targeted Radiotherapy Approach
2.4. Aim 1: Effect of Hypoxia on <TCP> of Dose-Based Planning Methods
2.5. Aim 2: Comparison of Normal Tissue Effects in Focal DE and Biologically Optimised Plans for Targeting Tumour Hypoxia
2.6. Sensitivity to Oxygen Enhancement Ratio (OER)
2.7. Statistical Analysis
3. Results
3.1. Effect of Hypoxia on <TCP> of Dose-Based Planning Methods
3.2. Comparison of Focal DE and Biologically Optimised Plans for Targeting Tumour Hypoxia
3.3. Sensitivity of Robust Biological Optimisation to OER
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient | Age (Years) | Prostate Volume (cm3) | PSA (ng/mL) | Gleason Score of the Dominant Nodule | Pathological StagSe |
---|---|---|---|---|---|
1 | 58 | 28.9 | 9 | 9 (5 + 4) | pT3b N0 |
2 | 64 | 30.6 | 6.1 | 7 (4 + 3) | pT3a |
3 | 68 | 28.1 | 11 | 7 (4 + 3) | pT3b N1 |
4 | 68 | 57.0 | 42 | 7 (4 + 3) | pT3a |
5 | 72 | 27.6 | 2.2 | 7 (4 + 3) | pT3a |
Patient | Total Cell Number in CTV | |
---|---|---|
Original (Normal + Clonogen) | Scaled (Clonogen) | |
1 | 2.07 × 108 | 7.27 × 106 |
2 | 1.65 × 108 | 5.79 × 106 |
3 | 4.46 × 108 | 1.57 × 107 |
4 | 1.14 × 109 | 4.00 × 107 |
5 | 2.85 × 108 | 1.00 × 107 |
Tumour Control Probability | ||
---|---|---|
TCP of voxel for sample | [1] | |
TCP of voxel i over population distribution | [2] | |
sample for hypoxic tissue | [3] | |
ratio for hypoxic tissue | [4] | |
TCP across whole target volume | [5] | |
Expectation value of target TCP in presence of geometric uncertainty | [6] | |
Expectation value of target TCP for sample in presence of geometric uncertainty | [7] | |
Normal Tissue Response | ||
Expectation value of EUD in presence of geometric uncertainty | [8] | |
Equivalent dose in 2 Gy fractions for voxel | [9] | |
Expectation value of NTCP in presence of geometric uncertainty | [10] | |
NTCP model parameter | [11] |
Symbol | Parameter | Value | Reference |
---|---|---|---|
Tumour dose-proportional radiosensitivity coefficient | Sampled from lognormal population distribution | N/A | |
Mean value of distribution | 0.15 Gy−1 | [12] | |
Standard deviation of distribution | 0.04 Gy−1 | [12] | |
Fractionation-correction parameter for tumour or OAR | 3.1 Gy (tumour) 5.4 Gy (rectum) 8.0 Gy (bladder) | [12] [16] [17,18] | |
Tumour clonogen density (voxel-specific) | Variable (population median 107 cells per whole prostate volume) | [12] | |
Voxel volume (resolution-dependent) | 2 × 2 × 2.5 mm3 | N/A | |
Number of treatment fractions | 5 | N/A | |
Dose per fraction per voxel | Variable | N/A | |
Overall treatment time | Approximated as days | N/A | |
Potential tumour doubling time | 42 days | [12] | |
Number of samples from population distribution | 36 | N/A | |
Weight factors normalising the distribution such that | Variable | N/A | |
Oxygen enhancement ratio | 1.4 (1.2–1.8) | [12] | |
Number of voxels comprising structure (prostate or OAR) | Variable | N/A | |
Effective systematic geometric error | Variable | [19,20,21] | |
Gaussian distribution of effective systematic error | Variable | N/A | |
EUD model scaling parameter | See Table 5 | N/A | |
OAR uniform dose which will lead to complications in 50% of the population | See Table 5 | N/A | |
NTCP model slope | See Table 5 | N/A |
Planning Method | VOI | Constraints |
---|---|---|
(1) Uniform-dose | CTV | V35Gy ≥ 99% |
PTV | V33.25Gy ≥ 99% | |
Rectum | V28Gy ≤ 15% V32Gy ≤ 20% | |
Bladder | V28Gy ≤ 15% V32Gy ≤ 20% | |
HOF | V28Gy ≤ 5% | |
(2) Focal DE to tumour * | GTV | V35Gy ≥ 99%; aimed up to 50 Gy ⁑ V52Gy ≤ 0.1cc |
(3) Focal DE to tumour and hypoxic volume * | GTV | V35Gy ≥ 99%; aimed up to 50 Gy ⁑ |
HTV | V35Gy ≥ 99%; aimed up to 60 Gy ⁑ V62Gy ≤ 0.1cc | |
(4) Biological optimisation | CTV | Maximise <TCP> V35Gy≥ 99% |
Rectum | Minimise <NTCP> TD50 = 78.4 Gy, m = 0.108, a = 6 | |
Bladder | Minimise <NTCP> TD50 = 80 Gy, m = 0.11, a = 6 | |
HOF | V28Gy ≤ 5% |
Uncertainties (mm) | Dose-Based Planning | Biological Optimisation | ||
---|---|---|---|---|
Mean | Margin | |||
AP | −0.86 | 3.6 | 9.0 | 5.3 |
LR | −0.03 | 2.6 | 6.5 | 4.6 |
SI | 0.21 | 3.2 | 8.0 | 5.0 |
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Her, E.J.; Haworth, A.; Sun, Y.; Williams, S.; Reynolds, H.M.; Kennedy, A.; Ebert, M.A. Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging. Cancers 2021, 13, 4897. https://doi.org/10.3390/cancers13194897
Her EJ, Haworth A, Sun Y, Williams S, Reynolds HM, Kennedy A, Ebert MA. Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging. Cancers. 2021; 13(19):4897. https://doi.org/10.3390/cancers13194897
Chicago/Turabian StyleHer, Emily J., Annette Haworth, Yu Sun, Scott Williams, Hayley M. Reynolds, Angel Kennedy, and Martin A. Ebert. 2021. "Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging" Cancers 13, no. 19: 4897. https://doi.org/10.3390/cancers13194897