Evaluation and comparison of second-check monitor unit calculation software with Pinnacle3 treatment planning system.

The purpose of this study was to evaluate and compare the accuracy of dose calculations in second check softwares (Diamond, IMSure, MuCheck, and RadCalc) against the Phillips Pinnacle3 treatment planning system. Eighteen previously treated patients' treatment planning files consisting of a total of 204 beams were exported from the Pinnacle3 TPS to each of the four second check software. Of these beams, 145 of the beams used were IMRT plans while 59 were VMAT arcs. The values were represented as a percent difference between primary and secondary calculations and used for statistical analysis. Box plots, Pearson Correlation, and Bland-Altman analysis were performed in MedCalc. The mean percent difference in calculated dose for Diamond, IMSure, MuCheck, and RadCalc from Pinnacle3 were -0.67%, 0.31%, 1.51% and -0.36%, respectively. The corresponding variances were calculated to be 0.07%, 0.13%, 0.08%, and 0.03%; and the largest percent differences were -7.9%, 9.70%, 9.39%, and 5.45%. The dose differences of each of the second check software in this study can vary considerably and VMAT plans have larger differences than IMRT. Among the four second check softwares, RadCalc values has shown a high agreement on average with low variation, and had the smallest percent range from Pinnacle3 values. The closest in average percent difference from the Pinnacle3data was the IMSure software, but suffered from significantly larger variance and percent range. The values reported by Diamond and MuCheck had significantly high percent differences with TPS values.

Arachnoid cysts: the role of the BLADE technique.

BACKGROUND: This study aims at demonstrating the ability of BLADE sequences to reduce or even eliminate all the image artifacts as well as verifying the significance of using this technique in certain pathological conditions. MATERIAL AND METHODS: This study involved fourteen consecutive patients (5 females, 9 males), who routinely underwent magnetic resonance imaging (MRI) brain examination, between 2010-2014. The applied routine protocol for brain MRI examination included the following sequences: i) T2-weighted (W) fluid-attenuated inversion recovery (FLAIR) axial; ii) T2-W turbo spin echo (TSE) axial; iii) T2*-W axial, iv) T1-W TSE sagittal; v) Diffusion-weighted (DWI) axial; vi) T1-W TSE axial; vii) T1-W TSE axial+contrast. Additionally, the T2-W FLAIR BLADE sequence was added to the protocol in cases of cystic tumors. Two radiologists independently evaluated all the images at two separate settings, which were performed 3 weeks apart. The presence of image artifacts such as motion, flow, chemical shift and Gibbs ringing artifacts, were also evaluated by the radiologists. In the measurements of the cysts, the extent of the divergence by the two MRI techniques (conventional and BLADE) was used by the two radiologists to evaluate the accuracy of the two techniques to determine the size of the cysts. RESULTS: BLADE sequences were found to be more reliable than the conventional ones regarding the estimation of the cyst size. The qualitative analysis showed that the T2 FLAIR BLADE sequences were superior to the conventional T2 FLAIR with statistical significance (p <0.001) in the following fields: i) overall image quality, ii) cerebrospinal fluid (CSF) nulling; iii) contrast between pathology and its surrounding; iv) borders of the pathology; v) motion artifacts; vi) flow artifacts; vii) chemical shift artifacts and viii) Gibbs ringing artifacts. CONCLUSIONS: BLADE sequence was found to decrease both flow artifacts in the temporal lobes and motion artifacts from the orbits. Additionally, it was shown to improve flow artifacts and image quality in cystic pathologies such as arachnoid cysts. Hippokratia 2016, 20(3): 244-248.

Radiobiological evaluation of intensity modulated radiation therapy treatments of patients with head and neck cancer: A dual-institutional study.

In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) models were used in the Histogram Analysis in Radiation Therapy (HART) analysis. In this study, 33 patients with oropharyngeal primaries in the head and neck region were used to establish the correlation between NTCP values of (a) bilateral parotids with clinically observed rates of xerostomia, (b) esophagus with dysphagia, and (c) larynx with dysphagia. The results of the study indicated a strong correlation between the severity of xerostomia and dysphagia with Lyman NTCP of bilateral parotids and esophagus, respectively, but not with the larynx. In patients without complications, NTCP values of these organs were negligible. Using appropriate radiobiological models, the presence of a moderate to strong correlation between the severities of complications with NTCP of selected OARs suggested that the clinical outcome could be estimated prior to treatment.

Pediatric Cranio-spinal Axis Irradiation: Comparison of Radiation-induced Secondary Malignancy Estimations Based on Three Methods of Analysis for Three Different Treatment Modalities.

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.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: feasibility study.

PURPOSE: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. METHODS: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. RESULTS: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D10 or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. CONCLUSIONS: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.

Improving the therapeutic ratio in stereotactic radiosurgery: optimizing treatment protocols based on kinetics of repair of sublethal radiation damage.

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.

Radiobiological evaluation of breast cancer radiotherapy accounting for the effects of patient positioning and breathing in dose delivery. A meta analysis.

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 (R1)), 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, (BEUD)concepts. For the Mastectomy case, the average P(+) values of the planned and delivered dose distributions are 93.8% for a (BEUD)(CTV) of 51.8 Gy and 85.0% for a (BEUD)(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(1) values are 0.9% and 7.4%. For the R- case, the average P(+) values are 89.4% for a (BEUD)(CTV) of 48.9 Gy and 88.6% for a (BEUD)(CTV) of 49.2 Gy and 85.5% for a (BEUD)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P(+) 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.

A comparative analysis of radiobiological models for cell surviving fractions at high doses.

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 χ (2)-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.

WE-G-BRCD-05: Evaluation of Localization Errors for CSA Delivery Using VMAT.

PURPOSE: To dosimetrically evaluate the effects of improper patient positioning in the junction area of a VMAT cranio-spinal axis irradiation technique consisting of one superior and one inferior arc. METHODS: Five (n=5) cranio-spinal axis irradiation patients were planned with 2 arcs: one superior and one inferior. The plans were then recalculated with inferior isocenter shifted, in order to mimic patient setup errors, eight times: lmm, 2mm, 5mm, and 10mm superiorly, and 1mm, 2mm, 5mm, and 10mm inferiorly. Plans were then compared to the original, non-shifted arc plan based on target metrics of conformity number and homogeneity index, as well as several normal structure mean doses. RESULTS: Percent differences were calculated in order to compare each of the eight shifted plans to the original arc plan without shifts, which would be the ideal setup of patient without error. The conformity number was on average 0.87%, 2.74%, 5.75%, and 9.10% lower for the 1mm, 2mm, 5mm, and 10mm inferiorly- shifted plans and 0.41%, 0.82%, 2.75%, and 5.99% lower for the respective superiorly-shifted plans. The homogeneity indices were, averaged among the five patients, 0.03%, 0.26%, 0.97%, and 2.84% for the inferior shifts and 0.23%, 1.17%, 6.31%, and 15.29% worse, or less homogenous for the superior shifts. Overall the mean doses to the organs at risk were less than 2% different for the 1mm, 2mm, and 5mm shifted plans. The 10mm shifted plans, however, showed percent differences from original plan of up to 5.6% on average. CONCLUSIONS: Setup errors when shifting isocenters should be minimized in order to provide the patient with the best treatment possible. Errors of 1 to 2mm can negatively affect patient treatment, most notably in the arc junction area, but are not as problematic as larger errors of 5 to 10mm.

SU-E-T-562: Reducing the Arc Span for CSA VMAT Delivery.

PURPOSE: To dosimetrically evaluate advantages and disadvantages of using multiple, shorter, sub-arcs versus full arc deliveries for treatment of cranio-spinal axis (CSA) irradiation. METHODS: Five (n=5) cranio-spinal axis irradiation patients were planned using 2 complete arcs, one superior and one inferior; with gantry rotations from 1 to 359 degrees. Due to supine patient setup, each original full arc was then replanned split into two sub arcs with gantry rotations from 1 to 100 and 260 to 359 degrees creating 4 smaller arcs. The PTV was normalized such that 95% received at least 23.4 Gy in 13 fractions. The PTV was evaluated based on conformity number and homogeneity index. The normal structures were evaluated based on maximum and mean doses. Beam on times and monitor units were compared. RESULTS: Averaged over all patients, conformity number was calculated to be approximately 0.86 and 0.82 for full arc and sub arc plans respectively. The homogeneity index was approximately 1.07 and 1.06 for full arc and sub arc plans. This indicates better target conformity but less homogeneous dose distribution for full arc plans as compared with sub arc plans. With the exception of the eyes, each normal structure evaluated had lower maximum doses with subarc plans. All normal structures, with the exception of the left kidney, had lower mean doses using sub arc deliveries. Beam on times were shorter on average for full arcs, but the monitor units were lower on average for sub arcs. CONCLUSIONS: Overall, CSA patients would benefit from the use of sub arc treatment deliveries versus full arc deliveries. Nearly all normal structure doses were lower for sub arcs, while the PTV was still adequately covered and beam on times and monitor units were similar.

SU-E-T-601: Dosimetric Evaluation of the Parameter Variation with Varying Calculation Grid Size in the IMRT Cases.

PURPOSE: The aim of this study is to compare the plan results that are obtained by using different calculation grid sizes ranging from 0.15 to 0.50 cm, and the same dose calculation algorithm (Superposition), in Intensity Modulated Radiotherapy (IMRT) for different treatment sites. Results are then used to study the suitability of dose grid size with respect to site. METHODS: For each of the calculation grid sizes, three different sites; namely, Lung, Prostate, and Head and Neck were analyzed. Treatment plans were created using 6MV photon beam quality and IMRT technique on the CMS XiO (Computerized Medical System, St.Louis, MO) treatment planning system. Dose volume histograms were generated for each of the cases and statistical analysis performed included mean relative difference and Homogeneity Index for target structures. Comparison was done first by using 0.30 cm calculation grid as a golden standard and keeping the same number of monitor units (MUs) per beam for each grid size, then the second part involved renormalizing plans to have the same target coverage (100% of the prescription dose covering at least 95% of the target volume) for each grid size used. Future study plans include treatment plans delivery on Varian 21 EX linear accelerator with Millennium (120) MLC and their verification with the Sun Nuclear Mapcheck 2D array. To increase the diode array resolution, 2D array will be shifted in 1 mm increments in x and y direction. Measured fields will be merged using Sun Nuclear Files Combined function and compared with intensity maps exported from the CMS XiO treatment planning system calculated with minimum segment size of 1 cm. RESULTS: The maximum percentage of variation recorded between calculation grid sizes used was in the case of the Head and Neck treatments. For the lung and prostate cases there was little variation in the results based on the calculation grid size chosen, specifically between 0.30, 0.20 and 0.15 cm. However head and neck and prostate cases with nodal involvement showed significant variation in the dosimetric results based on the grid size chosen. Overall results vary from case to case and also depend on the plan complexity. For larger treatment areas calculating with the grid size smaller than 0.30 cm may be impossible as time needed for calculation rises exponentially with the field size involved. CONCLUSIONS: IMRT places a higher requirement on dose grid resolution than conventional radiation therapy. While 0.30-0.40 cm grid was assumed adequate for conformal treatment planning, smaller dose grid is required at least in the areas of high dose. In the cases where steep dose gradients exist smaller grid size should be used while calculating and evaluating treatment plans, as the choice of the calculation grid size may in certain cases even influence clinical results.

SU-E-T-465: Exploring the Dosimetric and Tumor Control Consequences of Prostate Seed Loss and Migration.

PURPOSE: Once implanted, prostate brachytherapy seeds are vulnerable to loss and movement. A general estimation of these effects may be useful for making patient care decisions when seeds are lost after the post-implant scan. The goal of this work was to explore the dosimetric and radiobiological effects of the types of seed loss and migration common in prostate brachytherapy. METHODS: This study evaluates five patients. For each, three treatment plans were created using Iodine-125, Palladium-103 and Cesium-131. The three seeds closest to the urethra were identified and modeled as seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in-house software to perform the dosimetric and radiobiological evaluation. The radiobiological evaluation was based on the linear-quadratic model. Seed loss was simulated by removing 1, 2 or 3 seeds near the urethra 0, 2 or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21 or 28 days after the implant. RESULTS: Loss of 1, 2 or 3 seeds through the urethra resulted in D90 reduction of 2%, 5% and 7% loss respectively. Due to delayed loss of peripheral seeds, effects were less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal. CONCLUSIONS: The goal of this work was to explore the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction of D90 coverage. However, the dose reduction was not seen to significantly reduce tumor control probability.

SU-E-T-458: Radiobiological Comparison of Single and Dual-Isotope Prostate Seed Implants.

PURPOSE: Several isotopes are available for low dose-rate brachytherapy of the prostate. Currently, most implants use a single isotope. However, the use of dual-isotope implants may yield an advantageous combination of characteristics such as half-life and relative biological effectiveness. However, the use of dual-isotope implants complicates treatment planning and quality assurance. Do the benefits of dual-isotope implants outweigh the added difficulty? The goal of this work was to use a linear-quadratic model to compare single and dual-isotope implants. METHODS: Ten patients were evaluated in this study. For each patient, six treatment plans were created with single or dual-isotope combinations of 1251, 103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were contoured by a physician. The biologically effective dose was used to determine the tumor control probability and normal tissue complication probabilities for each plan. Each plan was evaluated using favorable, intermediate and unfavorable radiobiological parameters. The results of the radiobiological analysis were used to compare the single and dual-isotope treatment plans. RESULTS: Iodine-125 only implants were seen to be most affected by changes in tumor aggressiveness. Significant differences in organ response probabilities were seen at common dose levels. It was recognized that these differences were likely a result of suboptimal initial seed strengths. After adjusting the initial seed strength to maximize complication-free tumor control the differences between isotope combinations were minimal. This result was true even for unfavorable tumors. CONCLUSIONS: The objective of this work was to perform a radiobiologically based comparison of single and dual-isotope prostate seed implant plans. For all isotope combinations, the plans were improved by varying the initial seed strength. For the minimally-optimized treatment plans, no substantial differences in predicted treatment outcomes were seen among the different isotope combinations.

Investigating the clinical aspects of using CT vs. CT-MRI images during organ delineation and treatment planning in prostate cancer radiotherapy.

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 () 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 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, P(I) 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 of 86.4 Gy and 86.7 Gy, respectively. The respective average P(B) values are 80.0% and 80.6%, whereas the corresponding average P(I) 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 ΔP(+) 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.

Radiobiological and dosimetric analysis of daily megavoltage CT registration on adaptive radiotherapy with Helical Tomotherapy.

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) 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 D concepts and plotting the tissue response probabilities vs. D 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(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(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective P(B) values are 53.7% and 45.8%, whereas the corresponding P(I) 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 D(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective P(B) values are 14.5% and 15.3%, whereas the corresponding P(I) 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.

Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy.

OBJECTIVES: The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. METHODS: Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P(+)) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. RESULTS: The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P(+) of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average ΔP(+) of 27.0% for a Δ effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average ΔP(+) of 23.8% for a Δ effective uniform dose of 11.6 Gy. CONCLUSION: 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 tumours and normal tissues. The use of P - effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.

Tradeoffs for assuming rigid target motion in Mlc-based real time target tracking radiotherapy: a dosimetric and radiobiological analysis.

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(2)0; (b) Radiobiologically by calculating the biological effective uniform dose (D) 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 4D 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 D 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 D 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.

Assessing four-dimensional radiotherapy planning and respiratory motion-induced dose difference based on biologically effective uniform dose.

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.

Comparison of the 3D-conformal, helical tomotherapy and multileaf collimators-based intensity modulated radiotherapy modalities using radiobiological measures.

PURPOSE: Intensity modulated radiotherapy (IMRT) using multileaf collimators (MLC) and helical tomotherapy (HT) have become increasingly popular over the past few years. However, their clinical efficacy and effectiveness continue to be investigated. In order to provide a more thorough evaluation and comparison of treatment plans, the utilization of the biologically effective uniform dose (D) together with the complication-free tumor control probability (P(+)) are examined. MATERIALS AND METHODS: In this study, a typical case of lung cancer was investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and a HT plan. The 3 different treatment plans were compared based on radiobiological measures by using the P(+) index and the D concept as the common prescription point of the plans and plotting the tissue response probabilities vs. D for a range of prescription doses. RESULTS: The applied plan evaluation method showed that in this lung cancer case the MLC-based IMRT plan was best over the clinically useful dose prescription range. The 3D-conformal, MLC-based IMRT and HT treatment plans gave a P(+) of 55.4%, 72.9% and 66.9%, for a D to the internal target volume (ITV) of 57.0 Gy, 66.9 Gy and 64.0 Gy, respectively. CONCLUSION: In comparison to 3D conformal radiotherapy, both MLC based-IMRT and HT can better encompass the often large ITV required while minimizing the volume of the organs at risk receiving high dose. Taking into account the dose-response relations of the irradiated tumors and normal tissues, a radiobiological treatment plan evaluation can be performed, which may provide a closer association of the delivered treatment with the clinical outcome.

Assessing the difference between planned and delivered intensity-modulated radiotherapy dose distributions based on radiobiological measures.

AIMS: Because of the highly conformal distributions that can be obtained with intensity-modulated radiotherapy (IMRT), any discrepancy between the intended and delivered distributions would probably affect the clinical outcome. Consequently, there is a need for a measure that would quantify those differences in terms of a change in the expected clinical outcome. MATERIALS AND METHODS: To evaluate such a measure, cancer of the cervix was used, where the bladder and rectum are proximal and partially overlapping with the internal target volume. A solid phantom simulating the pelvic anatomy was fabricated and a treatment plan was developed to deliver the prescribed dose to the phantom. The phantom was then irradiated with films positioned in several transverse planes. The racetrack microtron at 50 MV was used in the treatment planning and delivery processes. The dose distribution delivered was analysed based on the film measurements and compared against the treatment plan. The differences in the measurements were evaluated using both physical and biological criteria. Whereas the physical comparison of dose distributions can assess the geometric accuracy of delivery, it does not reflect the clinical effect of any measured dose discrepancies. RESULTS: It is shown how small inaccuracies in delivered dose can affect the treatment outcome in terms of complication-free tumour cure. CONCLUSIONS: With highly conformal IMRT, the accuracy of the patient set-up and treatment delivery are critical for the success of the treatment. A method is proposed to evaluate the precision of the delivered plan based on changes in complication and control rates as they relate to uncertainties in dose delivery.