| 1. |
- Mavroidis, Panayiotis, et al.
(author)
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Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models
- 2014
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 88:1, s. 216-223
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Journal article (peer-reviewed)abstract
- Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P (+)), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 x 20 Gy, 98.6% in 2 x 14 Gy, 97.5% in 3 x 11 Gy, and 97.8% in 4 x 9.5 Gy. The corresponding P+ values were 88.8% in 1 x 20 Gy, 83.9% in 2 x 14 Gy, 86.0% in 3 x 11 Gy, and 82.3% in 4 x 9.5 Gy. With use of the fractionation scheme 4 x 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 x 19.68 Gy, 2 x 13.75 Gy, and 3 x 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 x 19.16 Gy with a P+ of 91.8%, 2 x 13.2 Gy with a P+ of 89.6%, 3 x 10.6 Gy with a P+ of 88.4%, and 4 x 9.02 Gy with a P+ of 86.9%. Conclusions: Among the fractionation schemes 1 (+) 20 Gy, 2 (+) 14 Gy, 3 x 11 Gy, and 4 x 9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 x 9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.
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| 2. |
- Nielsen, Steffen, et al.
(author)
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Comparison of Coding Transcriptomes in Fibroblasts Irradiated With Low and High LET Proton Beams and Cobalt-60 Photons
- 2019
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 103:5, s. 1203-1211
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Journal article (peer-reviewed)abstract
- Purpose: To identify differential cellular responses after proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type. Methods and Materials: A panel of primary dermal fibroblast cultures was irradiated with low and higher linear energy transfer (LET) proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions of 3.5 Gy (relative biological effectiveness) using a relative biological effectiveness of 1.1 for proton doses. Cells were harvested 2 hours after the final fraction was delivered, and RNA was purified. RNA sequencing was performed using Illumina NextSeq 500 with high-output kit. The edgeR package in R was used for differential gene expression analysis. Results: Pairwise comparisons of the transcriptomes in the 3 treatment groups showed that there were 84 and 56 differentially expressed genes in the low LET group compared with the Cobalt-60 group and the higher LET group, respectively. The higher LET proton group and the Cobalt-60 group had the most distinct transcriptome profiles, with 725 differentially regulated genes. Differentially regulated canonical pathways and various regulatory factors involved in regulation of biological mechanisms such as inflammation, carcinogenesis, and cell cycle control were identified. Conclusions: Inflammatory regulators associated with the development of normal tissue complications and malignant transformation factors seem to be differentially regulated by higher LET proton and Cobalt-60 photon irradiation. The reported transcriptome differences could therefore influence the progression of adverse effects and the risk of developing secondary cancers.
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| 3. |
- Traneus, Erik, et al.
(author)
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Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy Transfer and Relative Biological Effectiveness in Critical Structures
- 2019
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 103:3, s. 747-757
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Journal article (peer-reviewed)abstract
- Purpose: We propose the use of proton track-end objectives in intensity modulated proton therapy (IMPT) optimization to reduce the linear energy transfer (LET) and the relative biological effectiveness (RBE) in critical structures. Methods and Materials: IMPT plans were generated for 3 intracranial patient cases (1.8 Gy (RBE) in 30 fractions) and 3 head-and-neck patient cases (2 Gy (RBE) in 35 fractions), assuming a constant RBE of 1.1. Two plans were generated for each patient: (1) physical dose objectives only (DOSEopt) and (2) same dose objectives as the DOSEopt plan, with additional proton track-end objectives (TEopt). The track-end objectives penalized protons stopping in the risk volume of choice. Dose evaluations were made using a RBE of 1.1 and the LET-dependent Wedenberg RBE model, together with estimates of normal tissue complication probabilities (NTCPs). In addition, the distributions of proton track-ends and dose-average LET (LETd) were analyzed. Results: The TEopt plans reduced the mean LETd in the critical structures studied by an average of 37% and increased the mean LETd in the primary clinical target volume (CTV) by an average of 23%. This was achieved through a redistribution of the proton track-ends, concurrently keeping the physical dose distribution virtually unchanged compared to the DOSEopt plans. This resulted in substantial RBE-weighted dose (DRBE) reductions, allowing the TEopt plans to meet all clinical goals for both RBE models and reduce the NTCPs by 0 to 19 percentage points compared to the DOSEopt plans, assuming the Wedenberg RBE model. The DOSEopt plans met all clinical goals assuming a RBE of 1.1 but failed 10 of 19 normal tissue goals assuming the Wedenberg RBE model. Conclusions: Proton track-end objectives allow for LETd reductions in critical structures without compromising the physical target dose. This approach permits the lowering of DRBE and NTCP in critical structures, independent of the variable RBE model used, and it could be introduced in clinical practice without changing current protocols based on the constant RBE of 1.1.
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