| 31. |
- Daşu, Alexandru, et al.
(författare)
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In response to Dr. Karger et al.
- 2008
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 70:5, s. 1614-1615
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Daşu, Alexandru, et al.
(författare)
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Secondary malignancies from prostate cancer radiation treatment : a risk analysis of the influence of target margins and fractionation patterns
- 2011
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 79:3, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study explores the implications for cancer induction of treatment details such as fractionation, planning target volume (PTV) definition, and interpatient variations, which are relevant for the radiation treatment of prostate carcinomas.METHODS AND MATERIALS: Treatment planning data from 100 patients have been analyzed with a risk model based on the United Nations Scientific Committee on the Effects of Atomic Radiation competition model. The risk model can account for dose heterogeneity and fractionation effects characteristic for modern radiotherapy. Biologically relevant parameters from clinical and experimental data have been used with the model.RESULTS: The results suggested that changes in prescribed dose could lead to a modification of the risks for individual organs surrounding the clinical target volume (CTV) but that the total risk appears to be less affected by changes in the target dose. Larger differences are observed for modifications of the margins between the CTV and the PTV because these have direct impact onto the dose level and dose heterogeneity in the healthy tissues surrounding the CTV. Interpatient anatomic variations also have to be taken into consideration for studies of the risk for cancer induction from radiotherapy.CONCLUSIONS: The results have shown the complex interplay between the risk for secondary malignancies, the details of the treatment delivery, and the patient heterogeneity that may influence comparisons between the long-term effects of various treatment techniques. Nevertheless, absolute risk levels seem very small and comparable to mortality risks from surgical interventions, thus supporting the robustness of radiation therapy as a successful treatment modality for prostate carcinomas.
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| 33. |
- Dasu, Alexandru, et al.
(författare)
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What is the Clinically Relevant Relative Biologic Effectiveness? A Warning for Fractionated Treatments With High Linear Energy Transfer Radiation
- 2008
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 70:3, s. 867-874
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the clinically relevant relative biologic effectiveness (RBE) of fractionated treatments with high linear energy transfer (LET) radiation and to identify the important factors that might influence the transfer of tolerance and curative levels from low LET radiation. These are important questions in the light of the growing interest for the therapeutic use of radiation with higher LET than electrons or photons.METHODS AND MATERIALS: The RBE of various fractionated schedules was analyzed with theoretical models for radiation effect, and the resulting predictions were compared with the published clinical and experimental data regarding fractionated irradiation with high LET radiation.RESULTS: The clinically relevant RBE increased for greater doses per fraction, in contrast to the predictions from single-dose experiments. Furthermore, the RBE for late-reacting tissues appeared to modify more quickly than that for early-reacting tissues. These aspects have quite important clinical implications, because the increased biologic effectiveness reported for this type of radiation would otherwise support the use of hypofractionation. Thus, the differential between acute and late-reacting tissues could put the late-reacting normal tissues at more risk from high LET irradiation; however, at the same time, it could increase the therapeutic window for slow-growing tumors.CONCLUSIONS: The modification of the RBE with the dose per fraction must be carefully taken into consideration when devising fractionated treatments with high LET radiation. Neglecting to do so might result in an avalanche of complications that could obscure the potential advantages of the therapeutic use of this type of radiation.
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| 34. |
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| 35. |
- Dewyngaert, J. Keith, et al.
(författare)
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Procedure for unmasking localization information from ProstaScint scans for prostate radiation therapy treatment planning
- 2004
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 60:2, s. 654-662
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To demonstrate a method to extract the meaningful biologic information from In-111-radiolabeled capromab pendetide (ProstaScint) SPECT scans for use in radiation therapy treatment planning by removing that component of the In-111 SPECT images associated with normal structures. Methods and Materials: We examined 20 of more than 80 patients who underwent simultaneous Tc-99m/In-111 SPECT scans, which were subsequently registered to the corresponding CT/MRI scans. A thresholding algorithm was used to identify Tc-99m uptake associated with blood vessels and CT electron density associated with bone marrow. Corresponding voxels were removed from the In-111 image set. Results: No single threshold value was found to be associated with the Tc-99m uptake that corresponded to the blood vessels. Intensity values were normalized to a global maximum and, as such, were dependent upon the quantity of Tc-99m pooled in the bladder. The reduced ProstaScint volume sets were segmented by use of a thresholding feature of the planning system and superimposed on the CT/MRI scans. Conclusions: ProstaScint images are now closer to becoming a biologically and therapeutically useful and accurate image set. After known sources of normal intensity are stripped away, the remaining areas that demonstrate uptake may be segmented and superimposed on the treatment-planning CT/MRI volume.
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| 36. |
- Edvardsen, Hege, et al.
(författare)
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SNP in TXNRD2 Associated With Radiation-Induced Fibrosis : A Study of Genetic Variation in Reactive Oxygen Species Metabolism and Signaling.
- 2013
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 86:4, s. 791-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of the study was to identify noninvasive markers of treatment-induced side effects. Reactive oxygen species (ROS) are generated after irradiation, and genetic variation in genes related to ROS metabolism might influence the level of radiation-induced adverse effects (AEs).METHODS AND MATERIALS: 92 breast cancer (BC) survivors previously treated with hypofractionated radiation therapy were assessed for the AEs subcutaneous atrophy and fibrosis, costal fractures, lung fibrosis, pleural thickening, and telangiectasias (median follow-up time 17.1 years). Single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed for association to AE grade. SNPs associated with subcutaneous fibrosis were validated in an independent BC survivor material (n=283). The influence of the studied genetic variation on messenger ribonucleic acid (mRNA) expression level of 18 genes previously associated with fibrosis was assessed in fibroblast cell lines from BC patients.RESULTS: Subcutaneous fibrosis and atrophy had the highest correlation (r=0.76) of all assessed AEs. The nonsynonymous SNP rs1139793 in TXNRD2 was associated with grade of subcutaneous fibrosis, the reference T-allele being more prevalent in the group experiencing severe levels of fibrosis. This was confirmed in another sample cohort of 283 BC survivors, and rs1139793 was found significantly associated with mRNA expression level of TXNRD2 in blood. Genetic variation in 24 ROS-related genes, including EGFR, CENPE, APEX1, and GSTP1, was associated with mRNA expression of 14 genes previously linked to fibrosis (P≤.005).CONCLUSION: Development of subcutaneous fibrosis can be associated with genetic variation in the mitochondrial enzyme TXNRD2, critically involved in removal of ROS, and maintenance of the intracellular redox balance.
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| 37. |
- Egevad, L, et al.
(författare)
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In Regard to Zietman et al
- 2016
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 96:5, s. 1126-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
- 2006
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 66:4, s. 1228-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.
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| 39. |
- Eriksson, Mina, et al.
(författare)
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Analysis of Chromatin Opening in Heterochromatic Non-Small Cell Lung Cancer Tumor-Initiating Cells in Relation to DNA-Damaging Antitumor Treatment
- 2018
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 100:1, s. 174-187
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We previously reported that sphere-forming non-small cell lung cancer (NSCLC) tumor-initiating cells (TICs) have an altered activation of DNA damage response-and repair proteins and are refractory to DNA-damaging treatments. We analyzed whether chromatin organization plays a role in the observed refractoriness.Methods and Materials: Bulk cells and TICs from the NSCLC H23 and H1299 cell lines were examined using cell viability, clonogenic survival, Western blot, short interfering RNA analysis, and micronucleus assay.Results: NSCLC TICs displayed elevated heterochromatin markers trimethylated lysine 9 of histone H3 and heterochromatin protein 1 gamma relative to bulk cells and reduced cell viability upon histone deacetylase inhibition (HDACi). Vorinostat and trichostatin A increased the euchromatin markers acetylated lysine 9/14 of histone H3 and lysine 8 of histone H4, and HDACi pretreatment increased the phosphorylation of the DNA damage response proteins ataxia telangiectasia mutated and DNA-dependent protein kinase, catalytic subunit, upon irradiation in TICs. HDACi sensitized TICs to cisplatin and to some extent to ionizing irradiation. The protectiveness of a dense chromatin structure was indicated by an enhanced frequency of micronuclei in TICs following irradiation, after knockdown of heterochromatin protein 1 gamma.Conclusions: Although confirmatory studies in additional NSCLC model systems and with respect to analyses of other DNA damage response proteins are needed, our data point toward a heterochromatic structure of NSCLC TICs, such that HDACi can sensitize TICs to DNA damage.
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| 40. |
- Fager, Marcus, et al.
(författare)
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Linear energy transfer painting with proton therapy : a means of reducing radiation doses with equivalent clinical effectiveness
- 2015
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 91:5, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LETd) while keeping the radiobiologically weighted dose (DRBE) to the target the same.Methods and Materials: The target is painted with LETd by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LETd within the target increases with increasing number of fields, D decreases to maintain the DRBE the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]).Results: The LETd increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LETd led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP.Conclusions: LETd painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.
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