Volumetric Modulated Arc Therapy Planning for Primary Prostate Cancer With Selective Intraprostatic Boost Determined by 18F-Choline PET/CT

To investigate the feasibility of volumetric modulated arc therapy (VMAT) for post-mastectomy radiotherapy (PMRT) and to compare dual- arc VMAT treatment plans to helical tomotherapy (HT) plans on the basis of dosimetric quality, radiobiological calculations and delivery efficiency. Dual-arc VMAT and HT treatment plans were created for fifteen patients previously treated at our clinic. Planning target volumes (PTV) included the chest wall (CW) and regional lymph nodes. The following metrics were used to compare treatment plans for each patient: dose homogeneity index (DHI) and conformity index (CI); coverage of the PTV; dose to organs at risk (OAR); tumor control probability (TCP), normal tissue complication probability (NTCP) and secondary cancer complication probability (SCCP); and treatment delivery time. Differences between treatment plans were tested for significance using the paired Student's t-test. Both modalities produced clinically acceptable PMRT plans. VMAT plans showed better CI (p < 0.01), and better OAR sparing at low doses than HT plans. For example, VMAT plans showed a 26% (p < 0.01) and 9% (p < 0.01) decrease in V5Gy in the lungs and heart respectively. On the other hand, HT plans showed better DHI (p < 0.01) and PTV coverage (p < 0.01). HT plans also showed slightly better OAR sparing at higher doses, including 8% (p < 0.01) and 9% (p < 0.01) lower maximum doses to the lungs and heart, respectively. Both modalities achieved nearly 100% tumor control and approximately 1% NTCP in the lungs and heart, with VMAT showing lower SCCP (p < 0.01). VMAT plans also required 66.2% less time to deliver. Both VMAT and HT are suitable treatment options for PMRT. Our study showed that VMAT"'in addition to being significantly faster'"achieved better CI and low dose OAR sparing while HT achieved better DHI. This work was supported in part by a research support from Elekta, Ltd. However, Elekta, Ltd., did not participate in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit.

AimTo evaluate the impact of couch translational shifts on dose–volume histogram (DVH) and radiobiological parameters [tumour control probability (TCP), equivalent uniform dose (EUD) and normal tissue complication probability (NTCP)] of volumetric modulated arc therapy (VMAT) plans and to develop a simple and swift method to predict the same online, on a daily basis.MethodsIn total, ten prostate patients treated with VMAT technology were selected for this study. The plans were generated using Eclipse TPS and delivered using Clinac ix LINAC equipped with a Millennium 120 multileaf collimator. In order to find the effect of systematic translational couch shifts on the DVH and radiobiological parameters, errors were introduced in the clinically accepted base plan with an increment of 1 mm and up to 5 mm from the iso-centre in both positive and negative directions of each of the three axis, x [right–left (R-L)], y [superior–inferior (S-I)] and z [anterior–posterior (A-P)]. The percentages of difference in these parameters (∆D, ∆TCP, ∆EUD and ∆NTCP) were analyzed between the base plan and the error introduced plans. DVHs of the base plan and the error plans were imported into the MATLAB software (R2013a) and an in-house MATLAB code was generated to find the best curve fitted polynomial functions for each point on the DVH, there by generating predicted DVH for planning target volume (PTV), clinical target volume (CTV) and organs at risks (OARs). Functions f(x, vj), f(y, vj) and f(z, vj) were found to represent the variation in the dose when there are couch translation shifts in R-L, S-I and A-P directions, respectively. The validation of this method was done by introducing daily couch shifts and comparing the treatment planning system (TPS) generated DVHs and radiobiological parameters with MATLAB code predicted parameters.ResultsIt was noted that the variations in the dose to the CTV, due to both systematic and random shifts, were very small. For CTV and PTV, the maximum variations in both DVH and radiobiological parameters were observed in the S-I direction than in the A-P or R-L directions. ∆V70 Gy and ∆V60 Gy of the bladder varied more due to S-I shift whereas, ∆V40 Gy, ∆EUD and ∆NTCP varied due to A-P shifts. All the parameters in rectum were most affected by the A-P shifts than the shifts in other two directions. The maximum percentage of deviation between the TPS calculated and MATLAB predicted DVHs of plans were calculated for targets and OARs and were found to be less than 0·5%.ConclusionThe variations in the parameters depend upon the direction and magnitude of the shift. The DVH curves generated by the TPS and predicted by the MATLAB showed good correlation.

ObjectiveThe purpose of this study is to compare the dosimetric and biological evaluation differences between photon and proton radiation therapy.MethodsThirty esophageal squamous cell carcinoma (ESCC) patients were generated for volumetric modulated arc therapy (VMAT) planning and intensity-modulated proton therapy (IMPT) planning to compare with intensity-modulated radiation therapy (IMRT) planning. According to dose–volume histogram (DVH), dose–volume parameters of the plan target volume (PTV) and homogeneity index (HI), conformity index (CI), and gradient index (GI) were used to analyze the differences between the various plans. For the organs at risk (OARS), dosimetric parameters were compared. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was also used to evaluate the biological effectiveness of different plannings.ResultsCI, HI, and GI of IMPT planning were significantly superior in the three types of planning (p < 0.001, p < 0.001, and p < 0.001, respectively). Compared to IMRT and VMAT planning, IMPT planning improved the TCP (p<0.001, p<0.001, respectively). As for OARs, IMPT reduced the bilateral lung and heart accepted irradiation dose and volume. The dosimetric parameters, such as mean lung dose (MLD), mean heart dose (MHD), V5, V10, and V20, were significantly lower than IMRT or VMAT. IMPT afforded a lower maximum dose (Dmax) of the spinal cord than the other two-photon plans. What’s more, the radiation pneumonia of the left lung, which was caused by IMPT, was lower than IMRT and VMAT. IMPT achieved the pericarditis probability of heart is only 1.73% ± 0.24%. For spinal cord myelitis necrosis, there was no significant difference between the three different technologies.ConclusionProton radiotherapy is an effective technology to relieve esophageal cancer, which could improve the TCP and spare the heart, lungs, and spinal cord. Our study provides a prediction of radiotherapy outcomes and further guides the individual treatment.

Dosimetric and Radiobiological Evaluation of Delivered Dose Distribution with Intra-Fractional Motion in Prostate Stereotactic Radiation Therapy Treatments Using VMAT and Helical Tomotherapy

&lt;p&gt;This dissertation investigates the dosimetric influence of mixed photon beams in volumetric modulated arc therapy (VMAT) for prostate cancer and presents new algorithmic frameworks for simultaneous optimization of mixed photon beams in VMAT.&lt;/p&gt; &lt;p&gt;The potential scope of using mixed photon VMAT for prostate cancer was first studied by using a clinical treatment planning software. A significant reduction in doses to bladder (P &lt; 0.05) and rectum (P &lt; 0.05), and similar target dose conformity was achieved by mixed photon (6&amp;15 MV) VMAT compared to single energy (6 or 15 MV) VMAT. Radiobiological effectiveness was evaluated through tumor control probability (TCP) and normal tissue complication probability (NTCP). Across four different parameter sets for grade ≥ 2 rectal bleeding, mixed energy reduced NTCP by 1.3%, 4.1%, 0.1% and 2.6%, respectively, compared to single energy (P &lt; 0.05). For bladder, mixed energy reduced mean equivalent uniform dose by 2 Gy (P &lt; 0.05). In this study, however, each energy plan had to be optimized separately followed by their summation in order to generate a mixed photon VMAT plan. From optimization standpoint, this approach limits the solution search space.&lt;/p&gt; &lt;p&gt;With the aim of furthering current optimization approach, a comprehensive algorithmic framework was presented for simultaneous optimization of mixed photon beams (6 &amp; 18 MV) in VMAT (MP-VMAT). This was solved heuristically in two steps, accounting for dosimetric and mechanical constraints. This novel proof of concept was tested for its practicality and dosimetric outcome on two prostate cancer cases. In both cases, the proposed approach was able to reduce doses to rectum and bladder while maintaining the target dose coverage. Overall results suggested the viability and dosimetric benefits of the proposed concept, compared to single energy approach, in VMAT planning.&lt;/p&gt; &lt;p&gt;Next, the concept of MP-VMAT was expanded for a single-arc treatment, consisting of energy dependent partial arcs. To this end, the first formalism was presented to optimize mixed photon energy (6 &amp; 18 MV) fluences along with corresponding arc locations and lengths over a full 360o gantry rotation. The radiobiological and dosimetric effectiveness of this framework was tested on prostate cases with varying body types. The proposed technique was able to reduce bladder and rectum complication by 14% and 7%, respectively, in large size patients compared to single energy VMAT.&lt;/p&gt; &lt;p&gt;The novel concept of simultaneous optimization of multi-energy introduced in this dissertation can also be employed in learning based approach for beam angle optimization in intensity modulated radiation therapy treatments as well as in optimization of mixed modality treatments.&lt;/p&gt;

Single Arc VMAT of H&N Cancer

Purpose:To compare tumour dose distribution, conformality, homogeneity, normal tissue avoidance, tumour control probability (TCP) and normal tissue complication probability (NTCP) using 3D conformal radiation therapy (3DCRT), 3- and 4-field intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with locally advanced rectal cancer.Materials and methods:Twenty-four patients staged T1–3N+M0 with locally advanced rectal cancer underwent neoadjuvant chemoradiation therapy. Four different radiotherapy plans were prepared for each patient: 3DCRT, 3- and 4-field IMRT and VMAT are evaluated for target distribution using CI and homogeneity index (HI), normal tissue avoidance using Dmax, V45, V40, V50 and TCP and NTCP using the Lyman–Kutcher–Burman model.Results:VMAT has better HI (HI = 1·32) and 3DCRT exhibited better conformality (CI = 1·05) than the other radiotherapy techniques. With regard to normal tissue avoidance, all radiotherapy plans met the constraints. Dmax in the 3DCRT plans was statistically significant (p = 0·04) for bladder and no significant differences in V40 and V50. In the bowel bag, no significant differences in Dmax for any radiotherapy plan and V40 was lower in 3DCRT than VMAT (p = 0·024). In the case of femoral heads, 3DCRT has a statistically significant lower dose on Dmax than 4-field IMRT (p = 0·00 « 0·05). VMAT has the biggest TCP (80·76%) than the other three radiotherapy plans. With regard to normal tissue complications, probabilities were shown to be very low, of the order of 10-14 and 10-41 for bowel bag and femoral heads respectively.Conclusions:It can be concluded that 3DCRT plan improves conformity and decreases radiation sparing in the organ at risks, but the VMAT plan exhibits better homogeneity and greater TCP.

A biological modelling based comparison of radiotherapy plan robustness using photons vs protons for focal prostate boosting.

The primary aim of radiation therapy planning is to achieve optimal tumor control probability (TCP) while minimizing the risk of normal tissue complications (NTCPs). Traditionally, the dose-volume histogram has been a reliable tool for evaluating volumetric dose distribution in treatment plans. This study aims to assess the radiobiological efficacy of volumetric modulated arc therapy (VMAT), step-and-shoot intensity-modulated radiation therapy (ss-IMRT), and dynamic IMRT (d-IMRT) in the treatment of thoracic tumors. This study involved 13 patients diagnosed with squamous cell carcinoma of the thorax. Thirteen patients with squamous cell carcinoma of the thoracic site were included in this study. For each patient, three treatment plans (VMAT, ss-IMRT, and d-IMRT) were created, and the corresponding radiobiological parameters, such as equivalent uniform dose (EUD), TCP, and NTCP, were computed using Niemierko and LKB model for all 39 treatment plans using BIOSUITE software. The estimated average TCPs for ss-IMRT, d-IMRT, and VMAT are 61.51%, 62.86%, and 63.09%, respectively. Moreover, the average NTCPs observed for the organ at risk, lung, for ss-IMRT, d-IMRT, and VMAT were 3.27%, 1.96%, and 1.29%, respectively. In terms of the spinal cord, the average NTCPs for ss-IMRT, d-IMRT, and VMAT were 0.07%, 0.0%, and 0.0%, respectively. For the heart, the average NTCPs for ss-IMRT, d-IMRT, and VMAT were 0.10%, 0.12%, and 0.13%, respectively. The findings of this study suggest that VMAT might give equivalent TCP with less NTCP when compared to IMRT. The development of treatment planning techniques based on radiobiological factors aided in the prudent selection of physical parameters to attain high TCP and low NTCP.

BackgroundTo compare 3 Dimensional Conformal radiotherapy (3D-CRT) with Intensity Modulated Radiotherapy (IMRT) with Volumetric-Modulated Arc Therapy (VMAT) for bladder cancer.MethodsRadiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB) of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated.ResultsMean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI) index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI) index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293) for 3D-CRT; 824 (range 641–1083) for IMRT; and 403 (range 333–489) for VMAT (P < 0.05). Average treatment delivery time were 2:25min (range 2:01–3:09) for 3D-CRT; 4:39 (range 3:41–6:40) for IMRT; and 1:14 (range 1:13–1:14) for VMAT. In selected patients, the SIB did not result in a higher dose to small bowel or rectum.ConclusionsVMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours.

The radiobiological effect of using Acuros XB vs anisotropic analytical algorithm on hepatocellular carcinoma stereotactic body radiation therapy.

The release of a homogeneous high dose to the tumour region has been one of the cornerstones of radiotherapy (RT) treatment since its early days. According to the organ type and to the cancer histology, different doses are required in order to inactivate malignant cells, thus stopping proliferation. However, radiation-induced cell killing is a stochastic process. Tumour control probability (TCP) models have been developed in order to assign a success rate to a given RT treatment. At the same time, there is the need to keep the risks of normal tissue toxicity at an acceptable level. Normal tissue complication probability (NTCP) models provide a means of doing this. Traditionally, TCP and NTCP models combine clinical outcomes with dosimetric information in terms of dose-volume histograms (DVH). Model parameters are derived by mathematical fits to clinical observations and are subsequently used to estimate the risk of tumour relapse or toxicity. In both types of models, all of the patient dosimetric information is condensed into the DVHs, which represents a potential limitation on their descriptive and predictive power. This choice, related to historical and practical reasons, does not allow the full complexity of the 3D dose distribution in the patient to be taken into account. Neglecting these aspects might be relevant in a modern RT setting, which often includes the presence of high dose gradient regions. This has motivated research on ‘advanced’ TCP and NTCP models, able to tackle the problem by looking at a different scale, e.g. in tumour sub-regions or at the single voxel level. This is relevant not only from the purely dosimetric point of view. Increasing evidence is reported on the heterogeneity of cancer tissues, suggesting that non-uniform dose distributions could result in improved survival, for instance if targeted to take into account sub volumes with high clonogen density or hypoxic radioresistant regions. Similarly, radiation-induced side effects are part of a complex biological response, which depends not only on cell killing, but also on the inflammatory response and in some cases on the interplay among different organs. Obviously, conventional NTCP models cannot describe this scenario, and the development of more advanced mathematical tools is needed. This review will be focused on the discussion of recent studies showing possible directions for moving the field of TCP and NTCP modelling forward. Without diminishing the role and usefulness of available models, the aim is to shed light on the benefits that might be achieved by ‘enhanced’ modelling. This could represent an important step in the gradual transition of radiation therapy towards a form of precision medicine.

A treatment planning system (TPS) produces volumetric modulated arc therapy (VMAT) plans by applying an optimization process to an objective function, followed by an accurate calculation of the final, deliverable dose. However, during the optimization step, a rapid dose calculation algorithm is required, which reduces its accuracy and its representation of the objective function space. Monte Carlo (MC) routines, considered the gold standard in accuracy, are currently too slow for practical comprehensive VMAT optimization. Therefore, we propose a novel approach called enhanced optimization (EO), which employs the TPS VMAT plan as a starting point, and applies small perturbations to nudge the solution closer to a true objective minimum. The perturbations consist of beamlet dose matrices, calculated using MC routines on a distributed-computing framework. DICOM files for clinical VMAT plans files are exported from the TPS and used to generate input files for the EGSnrc MC toolkit. Beamlet doses are calculated using the MC routines, each corresponding to a single multileaf collimator leaf from a single control point traveling 0.5cm in or out of the field. A typical VMAT plan requires 5000 to 10000 beamlets, which may be calculated overnight. This results in a ternary-valued objective function, which may use the same clinical objectives as the original VMAT plan. A simple greedy search algorithm is applied to minimize this function and determine the optimal set of ternary variables. The resulting modified control point parameters are imported into the TPS to calculate the final, deliverable dose, and to compare the EO plan with the original. EO was evaluated retrospectively on seven VMAT plans (two adult brain, one pediatric brain, two head and neck, and two prostate). Additionally, the use of stricter objectives was investigated for two of the cases: the left cochlea planning organ at risk (OAR) volume objective for the pediatric brain case, and the rectum objective for a prostate case. EO produced improved objective scores (by 6% to 60%) and dose-volume histograms (DVH) for the brain plans and the head and neck plans. For each of these plans, the target dose minimum and homogeneity were preserved, while one or more of the OAR DVH's was reduced. Although EO also reduced the objective scores for the prostate plans (by 46% and 79%), their absolute score and DVH improvements were not substantial. The stricter objective on the pediatric brain case resulted in lower dose to the OAR without compromising the target dose. However, the rectum dose in the prostate case could not be improved without reducing dose homogeneity to the planning target volume, suggesting that VMAT prostate cases may already be highly optimized by the TPS. We have developed a novel approach to improving the dose distribution of VMAT plans, which relies on MC calculations to provide small modifications to the control points. This method may be particularly useful for complex treatments in which a certain OAR is of concern and it is difficult for the treatment planner to obtain an acceptable solution with the TPS. Further development will reduce the beamlet computation time and result in more sophisticated EO treatment planning methods.

This work presents a method for fast volumetric modulated arc therapy (VMAT) adaptation in response to interfraction anatomical variations. Additionally, plan parameters extracted from the adapted plans are used to verify the quality of these plans. The methods were tested as a prostate class solution and compared to replanning and to their current clinical practice. The proposed VMAT adaptation is an extension of their previous intensity modulated radiotherapy (IMRT) adaptation. It follows a direct (forward) planning approach: the multileaf collimator (MLC) apertures are corrected in the beam's eye view (BEV) and the monitor units (MUs) are corrected using point dose calculations. All MLC and MU corrections are driven by the positions of four fiducial points only, without need for a full contour set. Quality assurance (QA) of the adapted plans is performed using plan parameters that can be calculated online and that have a relation to the delivered dose or the plan quality. Five potential parameters are studied for this purpose: the number of MU, the equivalent field size (EqFS), the modulation complexity score (MCS), and the components of the the aperture area variability (AAV) and the leaf sequence variability (LSV). The full adaptation and its separate steps were evaluated in simulation experiments involving a prostate phantom subjected to various interfraction transformations. The efficacy of the current VMAT adaptation was scored by target mean dose (CTVmean), conformity (CI95%), tumor control probability (TCP), and normal tissue complication probability (NTCP). The impact of the adaptation on the plan parameters (QA) was assessed by comparison with prediction intervals (PI) derived from a statistical model of the typical variation of these parameters in a population of VMAT prostate plans (n = 63). These prediction intervals are the adaptation equivalent of the tolerance tables for couch shifts in the current clinical practice. The proposed adaptation of a two-arc VMAT plan resulted in the intended CTVmean (Δ ≤ 3%) and TCP (ΔTCP ≤ 0.001). Moreover, the method assures the intended CI95% (Δ ≤ 11%) resulting in lowered rectal NTCP for all cases. Compared to replanning, their adaptation is faster (13 s vs 10 min) and more intuitive. Compared to the current clinical practice, it has a better protection of the healthy tissue. Compared to IMRT, VMAT is more robust to anatomical variations, but it is also less sensitive to the different correction steps. The observed variations of the plan parameters in their database included a linear dependence on the date of treatment planning and on the target radius. The MCS is not retained as QA metric due to a contrasting behavior of its components (LSV and AAV). If three out of four plan parameters (MU, EqFS, AAV, and LSV) need to lie inside a 50% prediction interval (3/4-50%PI), all adapted plans will be accepted. In contrast, all replanned plans do not meet this loose criterion, mainly because they have no connection to the initially optimized and verified plan. A direct (forward) VMAT adaptation performs equally well as (inverse) replanning but is faster and can be extended to real-time adaptation. The prediction intervals for the machine parameters are equivalent to the tolerance tables for couch shifts in the current clinical practice. A 3/4-50%PI QA criterion accepts all the adapted plans but rejects all the replanned plans.

Simple SummaryThe radiotherapy plans are usually judged using physical quantities, including dose and dose-volume values. Biological indices may also be applied for plan evaluation. A new software was developed for the quick and automatic calculation of tumor control probability (TCP) and normal tissue control probability (NTCP) from any radiation therapy plan and any fractionation scheme. Limited information has been published about the radiobiological metrics associated with gastric cancer irradiation. The new software was applied to radiobiologically compare photon plans for gastric malignancies generated with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). The IMRT and VMAT plans provided higher TCPs than 3D-CRT. They also reduced the NTCPs and the risk of late adverse effects in most of the surrounding healthy organs compared to 3D-CRT. The presented results are useful for the plan optimization and choice of the appropriate radiotherapy technique for gastric cancer.(1) Aim: This study was conducted to radiobiologically compare radiotherapy plans for gastric cancer with a newly developed software tool. (2) Methods: Treatment planning was performed on two computational phantoms simulating adult male and female patients. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for gastric cancer were generated with three-photon beam energies. The equivalent uniform dose (EUD), tumor control probability (TCP) of the target and normal tissue control probability (NTCP) of eight different critical organs were calculated. A new software was employed for these calculations using the EUD-based model and dose-volume-histogram data. (3) Results: The IMRT and VMAT plan led to TCPs of 51.3–51.5%, whereas 3D-CRT gave values up to 50.2%. The intensity-modulated techniques resulted in NTCPs of (5.3 × 10−6–3.3 × 10−1)%. The corresponding NTCPs from 3D-CRT were (3.4 × 10−7–7.4 × 10−1)%. The above biological indices were automatically calculated in less than 40 s with the software. (4) Conclusions: The direct and quick radiobiological evaluation of radiotherapy plans is feasible using the new software tool. The IMRT and VMAT reduced the probability of the appearance of late effects in most of the surrounding critical organs and slightly increased the TCP compared to 3D-CRT.