| 1. |
- Alcorn, Sara R., et al.
(författare)
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Low-Dose Image-Guided Pediatric CNS Radiation Therapy : Final Analysis From a Prospective Low-Dose Cone-Beam CT Protocol From a Multinational Pediatrics Consortium
- 2020
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE PUBLICATIONS INC. - 1533-0346 .- 1533-0338. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium.Methods: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients <= 21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling.Results: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization.Conclusions: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.
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| 2. |
- Andisheh, B., et al.
(författare)
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A Comparative Analysis of Radiobiological Models for Cell Surviving Fractions at High Doses
- 2013
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 12:2, s. 183-192
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Tidskriftsartikel (refereegranskat)abstract
- For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed for improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the Kavanagh-Newman (KN) and several generalizations of the LQ model, e.g. the Linear-Quadratic-Linear (LQL) model and the Pade Linear Quadratic (PLQ) model. The purpose of the present study is to compare a number of models in order to find the best option(s) which could successfully be used as a fractionation correction method in SRT. In this work, six independent experimental data sets were used: CHOAA8 (Chinese hamster fibroblast), H460 (non-small cell lung cancer, NSLC), NCI-H841 (small cell lung cancer, SCLC), CP3 and DU145 (human prostate carcinoma cell lines) and U1690 (SCLC). By detailed comparisons with these measurements, the performance of nine different radiobiological models was examined for the entire dose range, including high doses beyond the shoulder of the survival curves. Using the computed and measured cell surviving fractions, comparison of the goodness-of-fit for all the models was performed by means of the reduced e-test with a 95% confidence interval. The obtained results indicate that models with dose-independent final slopes and extrapolation numbers generally represent better choices for SRT. This is especially important at high doses where the final slope and extrapolation numbers are presently found to play a major role. The PLQ, USC and LQL models have the least number of shortcomings at all doses. The extrapolation numbers and final slopes of these models do not depend on dose. Their asymptotes for the cell surviving fractions are exponentials at low as well as high doses, and this is in agreement with the behaviour of the corresponding experimental data. This is an important improvement over the LQ model which predicts a Gaussian at high doses. Overall and for the highlighted reasons, it was concluded that the PLQ, USC and LQL models are theoretically well-founded. They could prove useful compared to the other proposed radiobiological models in clinical applications for obtaining uniformly accurate cell surviving fractions encountered in stereotactic high-dose radiotherapy as well as at medium and low doses.
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| 3. |
- Andisheh, Bahram, et al.
(författare)
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Improving the therapeutic ratio in stereotactic radiosurgery : optimizing treatment protocols based on kinetics of repair of sublethal radiation damage
- 2013
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 12:4, s. 349-361
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Tidskriftsartikel (refereegranskat)abstract
- Sublethal damage after radiation exposure may become lethal or be repaired according to repair kinetics. This is a well-established concept in conventional radiotherapy. It also plays an important role in single-dose stereotactic radiotherapy treatments, often called stereotactic radiosurgery, when duration of treatment is extended due to source decay or treatment planning protocol. The purpose of this study is to look into the radiobiological characteristics of normal brain tissue and treatment protocols and find a way to optimize the time course of these protocols. The general problem is nonlinear and can be solved numerically. For numerical optimization of the time course of radiation protocol, a biexponential repair model with slow and fast components was considered. With the clinically imposed constraints of a fixed total dose and total treatment time, three parameters for each fraction (dose-rate, fraction duration, time of each fraction) were simultaneously optimized. A biological optimization can be performed by maximizing the therapeutic difference between tumor control probability and normal tissue complication probability. Specifically, for gamma knife radiosurgery, this approach can be implemented for normal brain tissue or tumor voxels separately in a treatment plan. Differences in repair kinetics of normal tissue and tumors can be used to find clinically optimized protocols. Thus, in addition to considering the physical dose in tumor and normal tissue, we also account for repair of sublethal damage in both these tissues.
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| 4. |
- Belkic, D, et al.
(författare)
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Proof-of-the-Concept Study on Mathematically Optimized Magnetic Resonance Spectroscopy for Breast Cancer Diagnostics
- 2015
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Ingår i: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 14:3, s. 277-297
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance (MR)-based modalities aid breast cancer detection without exposure to ionizing radiation. Magnetic resonance imaging is very sensitive but costly and insufficiently specific. Molecular imaging through magnetic resonance spectroscopy (MRS) can provide information about key metabolites. Here, the measured/encoded time signals cannot be interpreted directly, necessitating mathematics for mapping to the more manageable frequency domain. Conventional applications of MRS are hampered by data analysis via the fast Fourier transform (FFT) and postprocessing by fitting techniques. Most in vivo MRS studies on breast cancer rely upon estimations of total choline (tCHO). These have yielded only incremental improvements in diagnostic accuracy. In vitro studies reveal richer metabolic information for identifying breast cancer, particularly in closely overlapping components of tCHO. Among these are phosphocholine (PC), a marker of malignant transformation of the breast. The FFT cannot assess these congested spectral components. This can be done by the fast Padé transform (FPT), a high-resolution, quantification-equipped method, which we presently apply to noisy MRS time signals consistent with those encoded in breast cancer. The FPT unequivocally and robustly extracted the concentrations of all physical metabolites, including PC. In sharp contrast, the FFT produced a rough envelope spectrum with a few distorted peaks and key metabolites absent altogether. As such, the FFT has poor resolution for these typical MRS time signals from breast cancer. Hence, based on Fourier-estimated envelope spectra, tCHO estimates are unreliable. Using even truncated time signals, the FPT clearly distinguishes noise from true metabolites whose concentrations are accurately extracted. The high resolution of the FPT translates directly into shortened examination time of the patient. These capabilities strongly suggest that by applying the FPT to time signals encoded in vivo from the breast, MRS will, at last, fulfill its potential to become a clinically reliable, cost-effective method for breast cancer detection, including screening/surveillance.
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| 5. |
- Belkic, D, et al.
(författare)
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Strategic steps for advanced molecular imaging with magnetic resonance-based diagnostic modalities
- 2015
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Ingår i: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 14:1, s. 119-142
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Tidskriftsartikel (refereegranskat)abstract
- With the rapidly-expanding sophistication in our understanding of cancer cell biology, molecular imaging offers a critical bridge to oncology. Molecular imaging through magnetic resonance spectroscopy (MRS) can provide information about many metabolites at the same time. Since MRS entails no ionizing radiation, repeated monitoring, including screening can be performed. However, MRS via the fast Fourier transform (FFT) has poor resolution and signal-to-noise ratio (SNR). Moreover, subjective and non-unique (ambiguous) fittings of FFT spectra cannot provide reliable quantification of clinical usefulness. In sharp contrast, objective and unique (unambiguous) signal processing by the fast Padé transform (FPT) can increase resolution and retrieve the true quantitative metabolic information. To illustrate, we apply the FPT to in vitro MRS data as encoded from malignant ovarian cyst fluid and perform detailed analysis. This problem area is particularly in need of timely diagnostics by more advanced modalities, such as high-resolution MRS, since conventional methods usually detect ovarian cancers at late stages with poor prognosis, whereas at an early stage the prognosis is excellent. The reliability and robustness of the FPT is assessed for time signals contaminated with varying noise levels. In the presence of higher background noise, all physical metabolites were unequivocally identified and their concentrations precisely extracted, using small fractions of the total signal length. Via the “signal-noise separation” concept alongside the “stability test”, all non-physical information was binned, such that fully denoised spectra were generated. These results imply that a reformulation of data acquisition is needed, as guided by the FPT in MRS, since a small number of short transient time signals can provide high resolution and good SNR. This would enhance the diagnostic accuracy of MRS and shorten examination times, thereby improving efficiency and cost-effectiveness of this high throughput cancer diagnostic modality. Such advantages could be particularly important for more effective ovarian cancer detection, as well as more broadly for improved diagnostics and treatment within oncology.
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| 6. |
- Dey, Amit, et al.
(författare)
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Recent Advancements, Limitations, and Future Perspectives of the use of Personalized Medicine in Treatment of Colon Cancer
- 2023
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Ingår i: Technology in Cancer Research & Treatment. - : Sage Publications. - 1533-0346 .- 1533-0338. ; 22
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Forskningsöversikt (refereegranskat)abstract
- Due to the heterogeneity of colon cancer, surgery, chemotherapy, and radiation are ineffective in all cases. The genomic profile and biomarkers associated with the process are considered in personalized medicine, along with the patient's personal history. It is based on the response of the targeted therapies to specific genetic variations. The patient's genetic transcriptomic and epigenetic features are evaluated, and the best therapeutic approach and diagnostic testing are identified through personalized medicine. This review aims to summarize all the necessary, updated information on colon cancer related to personalized medicine. Personalized medicine is gaining prominence as generalized treatments are finding it challenging to contain colon cancer cases which currently rank fourth among global cancer incidence while being the fifth largest in total death cases worldwide. In personalized therapy, patients are grouped into specific categories, and the best therapeutic approach is chosen based on evaluating their molecular features. Various personalized strategies are currently being explored in the treatment of colon cancer involving immunotherapy, phytochemicals, and other biomarker-specific targeted therapies. However, significant challenges must be overcome to integrate personalized medicine into healthcare systems completely. We look at the various signaling pathways and genetic and epigenetic alterations associated with colon cancer to understand and identify biomarkers useful in targeted therapy. The current personalized therapies available in colon cancer treatment and the strategies being explored to improve the existing methods are discussed. This review highlights the advantages and limitations of personalized medicine in colon cancer therapy. The current scenario of personalized medicine in developed countries and the challenges faced in middle- and low-income countries are also summarized. Finally, we discuss the future perspectives of personalized medicine in colon cancer and how it could be integrated into the healthcare systems.
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| 7. |
- Ericsson-Szecsenyi, Rebecka, et al.
(författare)
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Robustness Assessment of Images From a 0.35T Scanner of an Integrated MRI-Linac : Characterization of Radiomics Features in Phantom and Patient Data
- 2022
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Ingår i: Technology in Cancer Research and Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Radiomics entails the extraction of quantitative imaging biomarkers (or radiomics features) hypothesized to provide additional pathophysiological and/or clinical information compared to qualitative visual observation and interpretation. This retrospective study explores the variability of radiomics features extracted from images acquired with the 0.35 T scanner of an integrated MRI-Linac. We hypothesized we would be able to identify features with high repeatability and reproducibility over various imaging conditions using phantom and patient imaging studies. We also compared findings from the literature relevant to our results. Methods: Eleven scans of a Magphan® RT phantom over 13 months and 11 scans of a ViewRay Daily QA phantom over 11 days constituted the phantom data. Patient datasets included 50 images from ten anonymized stereotactic body radiation therapy (SBRT) pancreatic cancer patients (50 Gy in 5 fractions). A True Fast Imaging with Steady-State Free Precession (TRUFI) pulse sequence was selected, using a voxel resolution of 1.5 mm × 1.5 mm × 1.5 mm and 1.5 mm × 1.5 mm × 3.0 mm for phantom and patient data, respectively. A total of 1087 shape-based, first, second, and higher order features were extracted followed by robustness analysis. Robustness was assessed with the Coefficient of Variation (CoV < 5%). Results: We identified 130 robust features across the datasets. Robust features were found within each category, except for 2 second-order sub-groups, namely, Gray Level Size Zone Matrix (GLSZM) and Neighborhood Gray Tone Difference Matrix (NGTDM). Additionally, several robust features agreed with findings from other stability assessments or predictive performance studies in the literature. Conclusion: We verified the stability of the 0.35 T scanner of an integrated MRI-Linac for longitudinal radiomics phantom studies and identified robust features over various imaging conditions. We conclude that phantom measurements can be used to identify robust radiomics features. More stability assessment research is warranted.
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| 8. |
- Henry, Thomas, et al.
(författare)
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Proton Grid Therapy : A Proof-of-Concept Study
- 2017
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 16:6, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we studied the possibility of merging proton therapy with grid therapy. We hypothesized that patients with larger targets containing solid tumor growth could benefit from being treated with this method, proton grid therapy. We performed treatment planning for 2 patients with abdominal cancer with the suggested proton grid therapy technique. The proton beam arrays were cross-fired over the target volume. Circular or rectangular beam element shapes (building up the beam grids) were evaluated in the planning. An optimization was performed to calculate the fluence from each beam grid element. The optimization objectives were set to create a homogeneous dose inside the target volume with the constraint of maintaining the grid structure of the dose distribution in the surrounding tissue. The proton beam elements constituting the grid remained narrow and parallel down to large depths in the tissue. The calculation results showed that it is possible to produce target doses ranging between 100% and 130% of the prescribed dose by cross-firing beam grids, incident from 4 directions. A sensitivity test showed that a small rotation or translation of one of the used grids, due to setup errors, had only a limited influence on the dose distribution produced in the target, if 4 beam arrays were used for the irradiation. Proton grid therapy is technically feasible at proton therapy centers equipped with spot scanning systems using existing tools. By cross-firing the proton beam grids, a low tissue dose in between the paths of the elemental beams can be maintained down to the vicinity of a deep-seated target. With proton grid therapy, it is possible to produce a dose distribution inside the target volume of similar uniformity as can be created with current clinical methods.
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| 9. |
- Mavroidis, Panayiotis, et al.
(författare)
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Comparison of the helical tomotherapy and MLC-based IMRT radiation modalities in treating brain and cranio-spinal tumors.
- 2009
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 8:1, s. 3-14
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Tidskriftsartikel (refereegranskat)abstract
- The investigation of the clinical efficacy and effectiveness of Intensity Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical Tomotherapy (HT) has been an issue of increasing interest over the past few years. In order to assess the suitability of a treatment plan, dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and standard deviation of the dose distribution are typically used. Nevertheless, the radiobiological parameters of the different tumors and normal tissues are often not taken into account. The use of the biologically effective uniform dose (D=) together with the complication-free tumor control probability (P(+)) were applied to evaluate the two radiation modalities. Two different clinical cases of brain and cranio-spinal axis cancers have been investigated by developing a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the MLC-based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the P(+) index and the D(=) concept as the common prescription point, the different treatment plans were compared based on radiobiological measures. The tissue response probabilities were plotted against D(=) for a range of prescription doses. The applied plan evaluation method shows that in the brain cancer, the HT treatment gives slightly better results than the MLC-based IMRT in terms of optimum expected clinical outcome (P(+) of 66.1% and 63.5% for a D(=) to the PTV of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT plan is significantly better compared to the MLC-based IMRT plan over the clinically useful dose prescription range (P(+) of 84.1% and 28.3% for a D(=) to the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for complications could be allowed, the complication-free tumor control could be increased by almost 30% compared to the initial dose prescription. In comparison to MLC based-IMRT, HT can better encompass the often large PTV while minimizing the volume of the OARs receiving high dose. A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumors and normal tissues. The use of P - (D=) diagrams can complement the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.
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| 10. |
- Mavroidis, P, et al.
(författare)
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Radiobiological and dosimetric analysis of daily megavoltage CT registration on adaptive radiotherapy with Helical Tomotherapy
- 2011
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Ingår i: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 10:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose ([Formula: see text]) and the complication-free tumor control probability ( P+). A new module of the Tomotherapy software (TomoTherapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P+ and [Formula: see text] concepts and plotting the tissue response probabilities vs. [Formula: see text] a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P+ are 48.5% and 48.9% for a [Formula: see text] of 53.3 Gy. The respective total control probabilities, PB are 56.3% and 56.5%, whereas the corresponding total complication probabilities, PI are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P+ values are 53.7% and 45.7% for a [Formula: see text] of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding PI values are ~0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P+ values are 10.9% for a [Formula: see text] of 75.2 Gy and 11.9% for a [Formula: see text] of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding PI values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within ±2% in terms of P+. In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.
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| 11. |
- Mavroidis, Panayiotis, et al.
(författare)
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Radiobiological and Dosimetric Analysis of Daily Megavoltage CT Registration on Adaptive Radiotherapy with Helical Tomotherapy
- 2011
-
Ingår i: Technology in Cancer Research & Treatment. - 1533-0346 .- 1533-0338. ; 10:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (<(D)double over bar>) and the complication-free tumor control probability (P.). A new module of the Tomotherapy software (Tomo Therapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P, and <(D)double over bar> concepts and plotting the tissue response probabilities vs. <(D)double over bar> a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P. are 48.5% and 48.9% for a <(D)double over bar>(ITV) of 53.3 Gy. The respective total control probabilities, P(B) are 56.3% and 56.5%, whereas the corresponding total complication probabilities, P(I) are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 53.7% and 45.7% for a <(D)double over bar>(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding P, values are similar to 0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 10.9% for a <(D)double over bar>(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding P, values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within +/- 2% in terms of P(+). In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.
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| 12. |
- Mavroidis, P, et al.
(författare)
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Toolkit for determination of dose-response relations, validation of radiobiological parameters and treatment plan optimization based on radiobiological measures
- 2010
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Ingår i: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 9:5, s. 523-537
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Tidskriftsartikel (refereegranskat)abstract
- Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques. One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P+. The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head & neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head & neck cancer treatment plans. The results of the radiobiological evaluation are compared against dosimetric criteria. The presented toolkit appears to be very convenient and efficient for clinical implementation of radiobiological modeling. It can also be used for the development of a clinical data and health information database for assisting the performance of epidemiological studies and the collaboration between different institutions within research and clinical frameworks.
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| 13. |
- Myers, P. A., et al.
(författare)
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Pediatric Cranio-spinal Axis Irradiation : Comparison of Radiation-induced Secondary Malignancy Estimations Based on Three Methods of Analysis for Three Different Treatment Modalities
- 2015
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 14:2, s. 169-180
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four (n = 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.
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| 14. |
- Persson, Bertil R.R., et al.
(författare)
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A Model for Evaluating Therapeutic Response of Combined Cancer Treatment Modalities : Applied to Treatment of Subcutaneously Implanted Brain Tumors (N32 and N29) in Fischer Rats with Pulsed Electric Fields (PEF) and 60Co-gamma Radiation (RT)
- 2003
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Ingår i: Technology in Cancer Research and Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 2:5, s. 459-470
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t1/e = 1 ms were first applied to the tumors. Then within 5 min radiation therapy with 60Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively, Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV 0 · exp[TGR · t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogene-therapy.
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| 15. |
- Roland, Teboh, et al.
(författare)
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Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy : A Dosimetric and Radiobiological Analysis
- 2010
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 9:2, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V-20; (b) Radiobiologically by calculating the biological effective uniform dose ((sic)) for the target and organs at risk (OAR) and the complication free tumor control probability (P+). As a reference for the comparative study, we included a 40 Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V-20 and MLD were respectively (13.1 +/- 6.9) % and (11.4 +/- 5.6) % for the MPP modality, whereas for the SPP modality they were (9.4 +/- 6.2) % and (7.2 +/- 4.7) %. On the other hand, the CGI was observed to improve by 15.3 +/- 13.2 and 9.6 +/- 10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P+ improved on average by (6.7 +/- 4.9) % and (4.1 +/- 3.6) % for the MPP and SPP modalities, respectively while the (sic) computed for the OAR decreased on average by (6.2 +/- 3.6) % and (3.8 +/- 3.5) % for the MPP and SPP tracking modalities, respectively. The (sic) calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.
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| 16. |
- Su, F-C, et al.
(författare)
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Assessing four-dimensional radiotherapy planning and respiratory motion-induced dose difference based on biologically effective uniform dose.
- 2009
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 8:3, s. 187-200
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Tidskriftsartikel (refereegranskat)abstract
- Four-dimensional (4D) radiotherapy is considered as a feasible and ideal solution to accommodate intra-fractional respiratory motion during conformal radiation therapy. With explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy, 4D treatment planning in principle provides better dose conformity. However, the clinical benefits of developing 4D treatment plans in terms of tumor control rate and normal tissue complication probability as compared to other treatment plans based on CT images of a fixed respiratory phase remains mostly unproven. The aim of our study is to comprehensively evaluate 4D treatment planning for nine lung tumor cases with both physical and biological measures using biologically effective uniform dose (D =) together with complication-free tumor control probability, P+. Based on the examined lung cancer patients and PTV margin applied, we found similar but not identical curves of DVH, and slightly different mean doses in tumor (up to 1.5%) and normal tissue in all cases when comparing 4D, P0%, and P50% plans. When it comes to biological evaluations, we did not observe definitively PTV size dependence in P+ among these nine lung cancer patients with various sizes of PTV. Moreover, it is not necessary that 4D plans would have better target coverage or higher P+ as compared to a fixed phase IMRT plan. However, on the contrary to significant deviations in P+ (up to 14.7%) observed if delivering the IMRT plan made at end-inhalation incorrectly at end-exhalation phase, we estimated the overall P+, PB, and PI for 4D composite plans that have accounted for intra-fractional respiratory motion.
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| 17. |
- Tzikas, A, et al.
(författare)
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Investigating the clinical aspects of using CT vs. CT-MRI images during organ delineation and treatment planning in prostate cancer radiotherapy
- 2011
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Ingår i: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 10:3, s. 231-242
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Tidskriftsartikel (refereegranskat)abstract
- In order to apply highly conformal dose distributions, which are characterized by steep dose fall-offs, it is necessary to know the exact target location and extension. This study aims at evaluating the impact of using combined CT-MRI images in organ delineation compared to using CT images alone, on the clinical results. For 10 prostate cancer patients, the respective CT and MRI images at treatment position were acquired. The CTV was delineated using the CT and MRI images, separately, whereas bladder and rectum were delineated using the CT images alone. Based on the CT and MRI images, two CTVs were produced for each patient. The mutual information algorithm was used in the fusion of the two image sets. In this way, the structures drawn on the MRI images were transferred to the CT images in order to produce the treatment plans. For each set of structures of each patient, IMRT and 3D-CRT treatment plans were produced. The individual treatment plans were compared using the biologically effective uniform dose ([Formula: see text]) and the complication-free tumor control probability ( P+) concepts together with the DVHs of the targets and organs at risk and common dosimetric criteria. For the IMRT treatment, at the optimum dose level of the average CT and CT-MRI delineated CTV dose distributions, the P+ values are 74.7% in both cases for a [Formula: see text] of 91.5 Gy and 92.1 Gy, respectively. The respective average total control probabilities, PB are 90.0% and 90.2%, whereas the corresponding average total complication probabilities, PI are 15.3% and 15.4%. Similarly, for the 3D-CRT treatment, the average P+ values are 42.5% and 46.7%, respectively for a [Formula: see text] of 86.4 Gy and 86.7 Gy, respectively. The respective average PB values are 80.0% and 80.6%, whereas the corresponding average PI values are 37.4% and 33.8%, respectively. For both radiation modalities, the improvement mainly stems from the better sparing of rectum. According to these results, the expected clinical effectiveness of IMRT can be increased by a maximum Δ P+ of around 0.9%, whereas of 3D-CRT by about 4.2% when combined CT-MRI delineation is performed instead of using CT images alone. It is apparent that in both IMRT and 3D-CRT radiation modalities, the better knowledge of the CTV extension improved the produced dose distribution. It is shown that the CTV is irradiated more effectively, while the complication probabilities of bladder and rectum, which is the principal organs at risk, are lower in the CT-MRI based treatment plans.
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| 18. |
- Tzikas, A., et al.
(författare)
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Investigating the Clinical Aspects of Using CT vs. CT-MRI Images During Organ Delineation and Treatment Planning in Prostate Cancer Radiotherapy
- 2011
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Ingår i: Technology in Cancer Research & Treatment. - 1533-0346 .- 1533-0338. ; 10:3, s. 231-242
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Tidskriftsartikel (refereegranskat)abstract
- In order to apply highly conformal dose distributions, which are characterized by steep dose fall-offs, it is necessary to know the exact target location and extension. This study aims at evaluating the impact of using combined CT-MRI images in organ delineation compared to using CT images alone, on the clinical results. For 10 prostate cancer patients, the respective CT and MRI images at treatment position were acquired. The CTV was delineated using the CT and MRI images, separately, whereas bladder and rectum were delineated using the CT images alone. Based on the CT and MRI images, two CTVs were produced for each patient. The mutual information algorithm was used in the fusion of the two image sets. In this way, the structures drawn on the MRI images were transferred to the CT images in order to produce the treatment plans. For each set of structures of each patient, IMRT and 3D-CRT treatment plans were produced. The individual treatment plans were compared using the biologically effective uniform dose (D) and the complication-free tumor control probability (R) concepts together with the DVHs of the targets and organs at risk and common dosimetric criteria. For the IMRT treatment, at the optimum dose level of the average CT and CT-MRI delineated CTV dose distributions, the P. values are 74.7% in both cases for a D(CTV) of 91.5 Gy and 92.1 Gy, respectively. The respective average total control probabilities, P(B) are 90.0% and 90.2%, whereas the corresponding average total complication probabilities, P, are 15.3% and 15.4%. Similarly, for the 3D-CRT treatment, the average P. values are 42.5% and 46.7%, respectively for a D(CTV) of 86.4 Gy and 86.7 Gy, respectively. The respective average PB values are 80.0% and 80.6%, whereas the corresponding average P values are 37.4% and 33.8%, respectively. For both radiation modalities, the improvement mainly stems from the better sparing of rectum. According to these results, the expected clinical effectiveness of IMRT can be increased by a maximum Delta P, of around 0.9%, whereas of 3D-CRT by about 4.2% when combined CT-MRI delineation is performed instead of using CT images alone. It is apparent that in both IMRT and 3D-CRT radiation modalities, the better knowledge of the CTV extension improved the produced dose distribution. It is shown that the CTV is irradiated more effectively, while the complication probabilities of bladder and rectum, which is the principal organs at risk, are lower in the CT-MRI based treatment plans.
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| 19. |
- Tzikas, Athanasios, et al.
(författare)
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Radiobiological Evaluation of Breast Cancer Radiotherapy Accounting for the Effects of Patient Positioning and Breathing in Dose Delivery. A Meta Analysis
- 2013
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 12:1, s. 31-44
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Tidskriftsartikel (refereegranskat)abstract
- In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R) and 5 resected with positive node involvement (R+)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P+ and the biologically effective uniform dose, E, concepts. For the Mastectomy case, the average P+ values of the planned and delivered dose distributions are 93.8% for a (sic)(CTV) of 51.8 Gy and 85.0% for a (sic)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P-B values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P-I values are 0.9% and 7.4%. For the R- case, the average P+ values are 89.4% for a (sic)(CTV) of 48.9 Gy and 88.6% for a (sic)(CTV) of 49.0 Gy, respectively. The respective PB values are 89.8% and 89.9%, whereas the corresponding PI values are 0.4% and 1.2%. For the R+ case, the average P+ values are 86.1% for a (sic)(CTV) of 49.2 Gy and 85.5% for a (sic)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P-I values are 4.1% and 4.6%. The combined effects of positioning uncertainties and breathing can introduce a significant deviation between the planned and delivered dose distributions in lung in breast cancer radiotherapy. The positioning and breathing uncertainties do not affect much the dose distribution to the CTV. The simulated delivered dose distributions show larger lung complication probabilities than the treatment plans. This means that in clinical practice the true expected complications are underestimated. Radiation pneumonitis of Grade 1-2 is more frequent and any radiotherapy optimization should use this as a more clinically relevant endpoint.
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