Use of radiobiological modeling in treatment plan evaluation and optimization of prostate cancer radiotherapy

There are many tools available that are used to evaluate a radiotherapy treatment plan, such as isodose distribution charts, dose volume histograms (DVH), maximum, minimum and mean doses of the dose distributions as well as DVH point dose constraints. All the already mentioned evaluation tools are dosimetric only without taking into account the radiobiological characteristics of tumors or OARs. It has been demonstrated that although competing treatment plans might have similar mean, maximum or minimum doses they may have significantly different clinical outcomes (Mavroidis et al. 2001). For performing a more complete treatment plan evaluation and comparison the complication-free tumor control probability (P+) and the biologically effective uniform dose (D ) have been proposed (Källman et al. 1992a, Mavroidis et al. 2000). The D concept denotes that any two dose distributions within a target or OAR are equivalent if they produce the same probability for tumor control or normal tissue complication, respectively (Mavroidis et al. 2001)..

Clinical implementation of radiobiological measures in treatment planning. Why has it taken so long?

This article is an editorial, and it doesn't include an abstract. Full text of this article is available in HTML and PDF.Cite this article as:Mavroidis P. Clinical implementation of radiobiological measures in treatment planning. Why has it taken so long? Int J Cancer Ther Oncol 2013;1(1):01019.DOI: 10.14319/ijcto.0101.9-------------------------------

Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours

<p>Abstract</p> <p>Purpose</p> <p>To quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark.</p> <p>Methods</p> <p>Seven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour.</p> <p>Results</p> <p>The average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively.</p> <p>Conclusions</p> <p>A significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.</p

Investigation of error detection capabilities of phantom, EPID and MLC log file based IMRT QA methods

A patient specific quality assurance (QA) should detect errors that originate anywhere in the treatment planning process. However, the increasing complexity of treatment plans has increased the need for improvements in the accuracy of the patient specific pretreatment verification process. This has led to the utilization of higher resolution QA methods such as the electronic portal imaging device (EPID) as well as MLC log files and it is important to know the types of errors that can be detected with these methods. In this study, we will compare the ability of three QA methods (Delta 4 ®, MU-EPID, Dynalog QA) to detect specific errors. Multileaf collimator (MLC) errors, gantry angle, and dose errors were introduced into five volumetric modulated arc therapy (VMAT) plans for a total of 30 plans containing errors. The original plans (without errors) were measured five times with each method to set a threshold for detectability using two standard deviations from the mean and receiver operating characteristic (ROC) derived limits. Gamma passing percentages as well as percentage error of planning target volume (PTV) were used for passing determination. When applying the standard 95% pass rate at 3%/3 mm gamma analysis errors were detected at a rate of 47, 70, and 27% for the Delta 4 , MU-EPID and Dynalog QA respectively. When using thresholds set at 2 standard deviations from our base line measurements errors were detected at a rate of 60, 30, and 47% for the Delta 4 , MU-EPID and Dynalog QA respectively. When using ROC derived thresholds errors were detected at a rate of 60, 27, and 47% for the Delta 4 , MU-EPID and Dynalog QA respectively. When using dose to the PTV and the Dynalog method 11 of the 15 small MLC errors were detected while none were caught using gamma analysis. A combination of the EPID and Dynalog QA methods (scaling Dynalog doses using EPID images) matches the detection capabilities of the Delta 4 by adding additional comparison metrics. These additional metrics are vital in relating the QA measurement to the dose received by the patient which is ultimately what is being confirmed

Deformable image and dose registration evaluation using two commercial programs

Purpose: To evaluate the daily dose delivered to the patients using daily imaging.Methods: Thirty (n = 30) patients that were previously treated in our clinic (10 prostate, 10 SBRT lung and 10 abdomen) were used in this study. The patients’ plans were optimized and calculated using the Pinnacle treatment planning system. The daily CBCT scans were retrieved and imported into the Velocity and RayStation software along with the corresponding planning CTs, structure sets and 3D dose distributions. In addition, the critical structures were contoured on each CBCT by the prescribing physician and were included in the evaluation of the daily delivered dose. After registering each CBCT scan to the planning CT using deformable registration, the dose volume histograms (DVH) for the organs at risk (OAR) and the respective planning target volumes (PTV) were calculated in Velocity and Raystation.Results: For the prostate patients, we observed daily volume changes for the bladder, rectum and sigmoid. The DVH analysis for those patients showed variation in the sparing of the critical structures while PTV coverage showed no significant changes. Similar results were observed for patients with abdominal targets. In contrast, in SBRT lung patients, the DVH for the critical structures and the PTV were comparable to those from the initial treatment plan. By using daily CBCT dose reconstruction, we proved PTV coverage for prostate and abdominal targets is adequate. However, there is significant dosimetric change for the OAR. These changes were random with no apparent trending. For lung SBRT patients, the delivered daily dose for both PTV and OAR is comparable to the planned dose with no significant differences.Conclusion: Daily tracking of the delivered dose is feasible. The doses can be evaluated only if the OARs have been segmented taken into account any daily anatomical changes and not by deformation of the structures along.-------------------Cite this article as: Tuohy R, Bosse C, Mavroidis P, Shi Z, Crownover R, Papanikolaou N, Stathakis S. Deformable image and dose registration evaluation using two commercial programs. Int J Cancer Ther Oncol 2014; 2(2):020242. DOI: 10.14319/ijcto.0202.4

Dosimetric and radiobiological comparison for quality assurance of IMRT and VMAT plans

INTRODUCTION: The gamma analysis used for quality assurance of a complex radiotherapy plan examines the dosimetric equivalence between planned and measured dose distributions within some tolerance. This study explores whether the dosimetric difference is correlated with any radiobiological difference between delivered and planned dose. METHODS: VMAT or IMRT plans optimized for 14 cancer patients were calculated and delivered to a QA device. Measured dose was compared against planned dose using 2-D gamma analysis. Dose volume histograms (for various patient structures) obtained by interpolating measured data were compared against the planned ones using a 3-D gamma analysis. Dose volume histograms were used in the Poisson model to calculate tumor control probability for the treatment targets and in the Sigmoid dose-response model to calculate normal tissue complication probability for the organs at risk. RESULTS: Differences in measured and planned dosimetric data for the patient plans passing at ≥94.9% rate at 3%/3 mm criteria are not statistically significant. Average ± standard deviation tumor control probabilities based on measured and planned data are 65.8±4.0% and 67.8±4.1% for head and neck, and 71.9±2.7% and 73.3±3.1% for lung plans, respectively. The differences in tumor control probabilities obtained from measured and planned dose are statistically insignificant. However, the differences in normal tissue complication probabilities for larynx, lungs-GTV, heart, and cord are statistically significant for the patient plans meeting ≥94.9% passing criterion at 3%/3 mm. CONCLUSION: A ≥90% gamma passing criterion at 3%/3 mm cannot assure the radiobiological equivalence between planned and delivered dose. These results agree with the published literature demonstrating the inadequacy of the criterion for dosimetric QA and suggest for a tighter tolerance

On the evaluation of patient specific IMRT QA using EPID, dynalog files and patient anatomy

Purpose: This research, investigates the viability of using the Electronic portal imaging device (EPID) coupled with the treatment planning system (TPS), to calculate the doses delivered and verify agreement with the treatment plan. The results of QA analysis using the EPID, Delta4 and fluence calculations using the multi-leaf collimator (MLC) dynalog files on 10 IMRT patients are presented in this study.Methods: EPID Fluence Images in integrated mode and Dynalog files for each field were acquired for 10 IMRT (6MV) patients and processed through an in house MatLab program to create an opening density matrix (ODM) which was used as the input fluence for dose calculation with the TPS (Pinnacle3, Philips). The EPID used in this study was the aSi1000 Varian on a Novalis TX linac equipped with high definition MLC. The resulting dose distributions were then exported to VeriSoft (PTW) where a 3D gamma was calculated using 3 mm-3% criteria. The Scandidos Delta4 phantom was also used to measure a 2D dose distribution for all 10 patients and a 2D gamma was calculated for each patient using the Delta4 software.Results: The average 3D gamma for all 10 patients using the EPID images was 98.2% ± 2.6%. The average 3D gamma using the dynalog files was 94.6% ± 4.9%. The average 2D gamma from the Delta4 was 98.1% ± 2.5%. The minimum 3D gamma for the EPID and dynalog reconstructed dose distributions was found on the same patient which had a very large PTV, requiring the jaws to open to the maximum field size. Conclusion: Use of the EPID, combined with a TPS is a viable method for QA of IMRT plans. A larger ODM size can be implemented to accommodate larger field sizes. An adaptation of this process to Volumetric Arc Therapy (VMAT) is currently under way.-----------------------------Cite this article as: Defoor D, Mavroidis P, Quino L, Gutierrez A, Papanikolaou N, Stathakis S. On the evaluation of patient specific IMRT QA using EPID, dynalog files and patient anatomy. Int J Cancer Ther Oncol 2014; 2(2):020219. DOI: 10.14319/ijcto.0202.1

Mathematical analysis of approximate biological effective dose (BED) calculation for multi-phase radiotherapy treatment plans

Purpose: There is growing interest about biological effective dose (BED) and its application in treatment plan evaluation due to its stronger correlation with treatment outcome. An approximate biological effective dose (BEDA) equation was introduced in order to simplify BED calculations by treatment planning systems in multi-phase treatments. The purpose of this work is to reveal its mathematical properties relative to the true, multi-phase BED (BEDT) equation.Methods: The BEDT equation was derived and used to reveal the mathematical properties of BEDA. MATLAB (MathWorks, Natick, MA) was used to simulate and analyze common and extreme clinical multi-phase cases. In those cases, percent error and Bland-Altman analysis were used to study the significance of the inaccuracies of BEDA for different combinations of total doses, numbers of fractions, doses per fractions and α/β values. All the calculations were performed on a voxel-basis in order to study how dose distributions would affect the accuracy of BEDA.Results: When the voxel dose-per-fractions (DPF) delivered by both phases are equal, BEDA and BEDT are equal (0% error). In heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the imprecision of BEDA is greater. It was shown that as the α/β ratio increased the accuracy of BEDA would improve. Examining twenty-four cases, it was shown that the range of DPF ratios for 3% Perror varied from 0.32 to 7.50Gy, whereas for Perror of 1% the range varied from 0.50 to 2.96Gy.Conclusion: The DPF between the different phases should be equal in order to render BEDA accurate. OARs typically receive heterogeneous dose distributions hence the probability of equal DPFs is low. Consequently, the BEDA equation should only be used for targets or OARs that receive uniform or very similar dose distributions by the different treatment phases.---------------------------Cite this article as: Kauweloa KI, Gutierrez AN, Bergamo A, Stathakis S, Papaniko-laou N, Mavroidis P. Mathematical analysis of approximate biological effective dose (BED) calculation for multi-phase radiotherapy treatment plans. Int J Cancer Ther Oncol 2014; 2(2):020226. DOI: 10.14319/ijcto.0202.2

Daily fraction dose recalculation based on rigid registration using Cone Beam CT

Purpose: To calculate the daily fraction dose for CBCT recalculations based on rigid registration and compare it to the planned CT doses.Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen) were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. Pinnacle was used to re-contour the regions of interest (ROI) for the specific CBCT by copying the contours from the original CT plan, planned by the prescribing physician, onto each daily CBCT and then manually reshaping contours to match the ROIs. A new plan is then created with the re-contoured CBCT as primary image in order to calculate the daily dose delivered to each ROI. The DVH values are then exported into Excel and overlaid onto the original CT DVH to produce a graph.Results: For the SBRT lung patients, we found that there were small daily volume changes in the lungs, trachea and esophagus. For almost all regions of interest we found that the dose received each day was less than the predicted dose of the planned CT while the PTV dose was relatively the same each day. The results for the prostate patients were similar, showing slight differences in the DVH values for different days in the rectum and bladder but similar PTV.Conclusion: By comparing daily fraction dose between the re-contoured CBCT images and the original planned CT show that PTV coverage for both prostate and SBRT, it has been shown that for PTV coverage, a planned CT is adequate. However, there are differences between the dose for the organs surrounding the PTV. The dose difference is less than the planned in most instances.-----------------------Cite this article as: Bosse C, Tuohy R, Mavroidis P, Shi Z, Crownover R, Gutierrez A, Papanikolaou N, Stathakis S. Daily fraction dose recalculation based on rigid registration using Cone Beam CT. Int J Cancer Ther Oncol 2014; 2(2):020217. DOI: 10.14319/ijcto.0202.1

Evaluation of the generalized gamma as a tool for treatment planning optimization

Purpose: The aim of that work is to study the theoretical behavior and merits of the Generalized Gamma (generalized dose response gradient) as well as to investigate the usefulness of this concept in practical radiobiological treatment planning.Methods: In this study, the treatment planning system RayStation 1.9 (Raysearch Laboratories AB, Stockholm, Sweden) was used. Furthermore, radiobiological models that provide the tumor control probability (TCP), normal tissue complication probability (NTCP), complication-free tumor control probability (P+) and the Generalized Gamma were employed. The Generalized Gammas of TCP and NTCP, respectively were calculated for given heterogeneous dose distributions to different organs in order to verify the TCP and NTCP computations of the treatment planning system. In this process, a treatment plan was created, where the target and the organs at risk were included in the same ROI in order to check the validity of the system regarding the objective function P+ and the Generalized Gamma. Subsequently, six additional treatment plans were created with the target organ and the organs at risk placed in the same or different ROIs. In these plans, the mean dose was increased in order to investigate the behavior of dose change on tissue response and on Generalized Gamma before and after the change in dose. By theoretically calculating these quantities, the agreement of different theoretical expressions compared to the values that the treatment planning system provides could be evaluated. Finally, the relative error between the real and approximate response values using the Poisson and the Probit models, for the case of having a target organ consisting of two compartments in a parallel architecture and with the same number of clonogens could be investigated and quantified. Results: The computations of the RayStation regarding the values of the Generalized Gamma and the objective function (P+) were verified by using an independent software. Furthermore, it was proved that after a small change in dose, the organ that is being affected most is the organ with the highest Generalized Gamma. Apart from that, the validity of the theoretical expressions that describe the change in response and the associated Generalized Gamma was verified but only for the case of small change in dose. Especially for the case of 50% TCP and NTCP, the theoretical values (ΔPapprox.) and those calculated by the RayStation show close agreement, which proves the high importance of the D50 parameter in specifying clinical response levels. Finally, the presented findings show that the behavior of ΔPapprox. looks sensible because, for both of the models that were used (Poisson and Probit), it significantly approaches the real ΔP around the region of 37% and 50% response. The present study managed to evaluate the mathematical expression of Generalized Gamma for the case of non-uniform dose delivery and the accuracy of the RayStation to calculate its values for different organs. Conclusion: A very important finding of this work is the establishment of the usefulness and clinical relevance of Generalized Gamma. That is because it gives the planner the opportunity to precisely determine which organ will be affected most after a small increase in dose and as a result an optimal treatment plan regarding tumor control and normal tissue complications can be found