The robustness of dual isocenter VMAT radiation therapy for bilateral lymph node positive breast cancer

PurposeTo investigate the use of dual isocenters for VMAT planning in patients with lymph node positive synchronous bilateral breast cancer (BBC) compared to a single isocenter option.MethodsTreatment plans of 11 patients with lymph node positive BBC were retrospectively analyzed using two different VMAT planning techniques: dual-isocenter split-arc VMAT plans (Iso2) were compared with mono-isocenter VMAT plans (Iso1). For Iso2 plans, PTV dose was investigated after introducing ±2 and ±5 mm couch shift errors between the two isocenters in the lateral, longitudinal and vertical direction.ResultsFor both techniques the planning aims for PTV coverage and OARs were met. The mean dose for the bilateral lungs and heart was reduced from 11.3 Gy and 3.8 Gy to 10.9 Gy (p < .05) and 3.6 Gy (p < .05), respectively, for Iso2 plans when compared to Iso1 plans. Positive statistically significant correlation (rho = 0.76, p = .006) was found between PTV volume and D2cc_PTV for Iso1 plans. No clinically significant change was seen in the D98_CTV or D2cc_PTV after the 2 and 5 mm errors were introduced between isocenters for Iso2 plans.ConclusionsThe split arc method was shown to be a feasible treatment technique in the case of synchronous BBC for both mono and dual isocenter techniques. The dose parameters were slightly favoring dual-isocenter option instead of mono-isocenter. The dual-isocenter method was shown to be a robust treatment option in the presence of ≤5 mm errors in the shifts between the two isocenters.     

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance

PurposeDynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect.Methods16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5 mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated.ResultsThe change in PTV and organs at risk DVH parameters were 0.4–4.1%. Good correlation (>0.83) between the PTV_mean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3 mm (per beam and composite plan) and 3%G/2 mm (composite plan) for the diode array phantom and 2%G/2 mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6.ConclusionsA DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3 mm per beam gamma setting.     

Evaluation of fully automated a priori MCO treatment planning in VMAT for head-and-neck cancer

PurposeAutomated planning techniques aim to reduce manual planning time and inter-operator variability without compromising the plan quality which is particularly challenging for head-and-neck (HN) cancer radiotherapy. The objective of this study was to evaluate the performance of an a priori-multicriteria plan optimization algorithm on a cohort of HN patients.MethodsA total of 14 nasopharyngeal carcinoma (upper-HN) and 14 “middle-lower indications” (lower-HN) previously treated in our institution were enrolled in this study. Automatically generated plans (autoVMAT) were compared to manual VMAT or Helical Tomotherapy planning (manVMAT-HT) by assessing differences in dose delivered to targets and organs at risk (OARs), calculating plan quality indexes (PQIs) and performing blinded comparisons by clinicians. Quality control of the plans and measurements of the delivery times were also performed.ResultsFor the 14 lower-HN patients, with equivalent planning target volume (PTV) dosimetric criteria and dose homogeneity, significant decrease in the mean doses to the oral cavity, esophagus, trachea and larynx were observed for autoVMAT compared to manVMAT-HT. Regarding the 14 upper-HN cases, the PTV coverage was generally significantly superior for autoVMAT which was also confirmed with higher calculated PQIs on PTVs for 13 out of 14 patients, whereas PQIs calculated on OARs were generally equivalent. Number of MUs and total delivery time were significantly higher for autoVMAT compared to manVMAT. All plans were considered clinically acceptable by clinicians.ConclusionsOverall superiority of autoVMAT compared to manVMAT-HT plans was demonstrated for HN cancer. The obtained plans were operator-independent and required no post-optimization or manual intervention.     

Feasibility and potential advantages using VMAT in SRS metastasis treatments

BackgroundUtilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has become the technique of choice as opposed to whole brain radiation therapy (WBRT). The aim of this work is to evaluate the feasibility and potential benefits in terms of normal tissue (NT) and dose escalation of volumetric modulated arc therapy (VMAT) in SRS metastasis treatment. A VMAT optimization procedure has therefore been developed for internal dose scaling which minimizes planner dependence.Materials and methodsFive patient-plans incorporating treatment with frame-based SRS with dynamic conformal arc technique (DA) were re-planned for VMAT. The lesions selected were between 4–6 cm³. The same geometry used in the DA plans was maintained for the VMAT cases. A VMAT planning procedure was performed attempting to scale the dose in inner auxiliary volumes, and to explore the potential for dose scaling with this technique. Comparison of dose-volume histogram (DVH) parameters were obtained.ResultsVMAT allows a superior NT sparing plus conformity and dose scaling using the auxiliary volumes. The VMAT results were significantly superior in NT sparing, improving both the V₁₀ and V₁₂ values in all cases, with a 2–3 cm³ saving. In addition, VMAT improves the dose coverage D₉₅ by about 0.5 Gy. The objective of dose escalation was achieved with VMAT with an increment of the Dmean and the Dmedian of about 2 Gy.ConclusionsThis work shows a benefit of VMAT in SRS treatment with significant NT sparing. A VMAT optimization procedure, based on auxiliary inner volumes, has been developed, enabling internal dose escalation.     

Dosimetric impact of uncorrected systematic yaw rotation in VMAT for peripheral lung SABR

AimThis study aimed to evaluate the dosimetric impact of uncorrected yaw rotational error on both target coverage and OAR dose metrics in this patient population.BackgroundRotational set up errors can be difficult to correct in lung VMAT SABR treatments, and may lead to a change in planned dose distributions.Materials and methodsWe retrospectively applied systematic yaw rotational errors in 1° degree increments up to −5° and +5° degrees in 16 VMAT SABR plans. The impact on PTV and OARs (oesophagus, spinal canal, heart, airway, chest wall, brachial plexus, lung) was evaluated using a variety of dose metrics. Changes were assessed in relation to percentage deviation from approved planned dose at 0 degrees.ResultsTarget coverage was largely unaffected with the largest mean and maximum percentage difference being 1.4% and 6% respectively to PTV D98% at +5 degrees yaw.Impact on OARs was varied. Minimal impact was observed in oesophagus, spinal canal, chest wall or lung dose metrics. Larger variations were observed in the heart, airway and brachial plexus. The largest mean and maximum percentage differences being 20.77% and 311% respectively at −5 degrees yaw to airway D0.1cc, however, the clinical impact was negligible as these variations were observed in metrics with minimal initial doses.ConclusionsNo clinically unacceptable changes to dose metrics were observed in this patient cohort but large percentage deviations from approved dose metrics in OARs were noted. OARs with associated PRV structures appear more robust to uncorrected rotational error.     

Assessment of the Monitor Unit Objective tool for VMAT in the Eclipse treatment planning system

Aim

This work aims to achieve the highest possible monitor units (MU) reduction using the MU Objective tool included in the Eclipse treatment planning system, while preserving the plan quality.

Dosimetric effect of limited aperture multileaf collimator on VMAT plan quality: A study of prostate and head-and-neck cancers

Aim

The aim of study was to evaluate the dosimetric effect of collimator-rotation on VMAT plan quality, when using limited aperture multileaf collimator of Elekta Beam Modulator? providing a maximum aperture of 21 cm × 16 cm.

Evaluation of MLC performance in VMAT and dynamic IMRT by log file analysis

PurposeThis multi-institution study assessed the positioning accuracy of multileaf collimators (MLC) by analyzing log files. It determined the main machine parameters that affect MLC positioning errors for pre-TrueBeam (Clinac) and TrueBeam linacs.MethodsAround 30,000 dIMRT and VMAT log files belonging to 6 linacs from 4 different centers were analyzed. An in-house software was used to calculate 95th percentile and RMS error values and their correlation with certain parameters such as maximum leaf speed, mean leaf speed and gantry angle. The effect of MLC communication delay on error statistics was assessed in Clinac linacs. To that end MLC positioning error statistics were calculated with and without the delay effect.ResultsFor dIMRT treatments in Clinac linacs the mean leaf RMS error was 0.306 mm with and 0.030 mm without the delay effect. Leaf RMS error was closely linked to maximum and mean leaf speeds, but without the delay effect that link was weaker. No trend was observed between bank RMS error and gantry angle. Without the delay effect larger bank RMS errors were obtained for gantry angles with leaf movements against gravity. For VMAT treatments in TrueBeam linacs the mean leaf RMS error was 0.038 mm. A link was also observed between leaf RMS error and maximum and mean leaf speeds.ConclusionTrueBeam MLC positioning errors are substantially lower than those of Clinac linacs. In Clinac machines the analysis of dynalogs without the delay effect allows us to study the influence of factors that are masked by the delay effect.     

Virtual patient 3D dose reconstruction using in air EPID measurements and a back-projection algorithm for IMRT and VMAT treatments

PurposeAt our institute, a transit back-projection algorithm is used clinically to reconstruct in vivo patient and in phantom 3D dose distributions using EPID measurements behind a patient or a polystyrene slab phantom, respectively. In this study, an extension to this algorithm is presented whereby in air EPID measurements are used in combination with CT data to reconstruct ‘virtual’ 3D dose distributions. By combining virtual and in vivo patient verification data for the same treatment, patient-related errors can be separated from machine, planning and model errors.Methods and materialsThe virtual back-projection algorithm is described and verified against the transit algorithm with measurements made behind a slab phantom, against dose measurements made with an ionization chamber and with the OCTAVIUS 4D system, as well as against TPS patient data. Virtual and in vivo patient dose verification results are also compared.ResultsVirtual dose reconstructions agree within 1% with ionization chamber measurements. The average γ-pass rate values (3% global dose/3 mm) in the 3D dose comparison with the OCTAVIUS 4D system and the TPS patient data are 98.5 ± 1.9%(1SD) and 97.1 ± 2.9%(1SD), respectively. For virtual patient dose reconstructions, the differences with the TPS in median dose to the PTV remain within 4%.ConclusionsVirtual patient dose reconstruction makes pre-treatment verification based on deviations of DVH parameters feasible and eliminates the need for phantom positioning and re-planning. Virtual patient dose reconstructions have additional value in the inspection of in vivo deviations, particularly in situations where CBCT data is not available (or not conclusive).     

Multi-institutional comparison of simulated treatment delivery errors in ssIMRT,manually planned VMAT and autoplan-VMAT plans for nasopharyngeal radiotherapy

PurposeTo quantify the impact of simulated errors for nasopharynx radiotherapy across multiple institutions and planning techniques (auto-plan generated Volumetric Modulated Arc Therapy (ap-VMAT), manually planned VMAT (mp-VMAT) and manually planned step and shoot Intensity Modulated Radiation Therapy (mp-ssIMRT)).MethodsTen patients were retrospectively planned with VMAT according to three institution’s protocols. Within one institution two further treatment plans were generated using differing treatment planning techniques. This resulted in mp-ssIMRT, mp-VMAT, and ap-VMAT plans. Introduced treatment errors included Multi Leaf Collimator (MLC) shifts, MLC field size (MLCfs), gantry and collimator errors. A change of more than 5% in most selected dose metrics was considered to have potential clinical impact. The original patient plan total Monitor Units (MUs) were correlated to the total number of dose metrics exceeded.ResultsThe impact of different errors was consistent, with ap-VMAT plans (two institutions) showing larger dose deviations than mp-VMAT created plans (one institution). Across all institutions’ VMAT plans the significant errors included; ±5° for the collimator angle, ±5 mm for the MLC shift and +1, ±2 and ±5 mm for the MLC field size. The total number of dose metrics exceeding tolerance was positively correlated to the VMAT total plan MUs (r = 0.51, p < 0.001), across all institutions and techniques.ConclusionsDifferences in VMAT robustness to simulated errors across institutions occurred due to planning method differences. Whilst ap-VMAT was most sensitive to MLC errors, it also produced the best quality treatment plans. Mp-ssIMRT was most robust to errors. Higher VMAT treatment plan complexity led to less robust plans.     

A dosemetric and radiobiological impact of VMAT and 3DCRT on lumbosacral plexuses,an underestimated organ at risk in cervical cancer patients

BackgroundThe purpose of this study was to evaluate dosimetric and radiobiological difference between volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiotherapy (3DCRT) in organ at risk (OAR) lumbosacral plexus (LSP) in cervical cancer patients.Materials and methods30 patients of cervical cancer who were treated using 3DCRT or VMAT along with chemotherapy followed by brachytherapy were enrolled. LSP was delineated retrospectively. Dosimetric and radiobiological difference was evaluated. Patients were followed for radiation induced lumbosacral plexopathy (RILSP).ResultsMedian follow-up was 12 months (3–16 months). 53.3% of patients were treated by 3DCRT and 46.7% by VMAT. The mean (±SD) LSP volume: 119.03 ± 15 cm³. The mean volume percentages (%) of the LSP: V5, V10, V20, V30, V40, V50, V55, and V60 were 100%, 99.8%, 99.2%, 94.3%, 84.03%, 59.7%, 0%, 0%, respectively. All patients received doses to the LSP in excess of 50 Gy, one patient received 55 Gy. A statistically significant difference was observed in the median value of V20, V30, V40, V50, D50, P2, P4, P7, P8, P9, and P10 across two different techniques of radiotherapy — VMAT and 3DCRT. None of the patients presented with RILSP. NTCP value was less in VMAT plans compared to 3DCRT, which is also statistically significant.ConclusionRILSP is a rare and often refractory complication of pelvic radiotherapy. Advance radiotherapy technique with proper OAR delineation and constraint can prevent the occurrence of RILSP. VMAT has potential benefits for the probability of dose reduction in LSP. Further studies are required focusing on dose distribution in LSP–OAR and radiotherapy modality.     

An assessment of a 3D EPID-based dosimetry system using conventional two- and three-dimensional detectors for VMAT

PurposeTo provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT.MethodsA 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment ‘fluence’ EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions.ResultsFluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition.Conclusions3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry.     

VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease

We used positron emission tomography (PET) to measure the earliest change in dopaminergic synapses and glial cell markers in a chronic, low-dose MPTP non-human primate model of Parkinson's disease (PD). In vivo levels of dopamine transporters (DAT), vesicular monoamine transporter-type 2 (VMAT2), amphetamine-induced dopamine release (AMPH-DAR), D2-dopamine receptors (D2R) and translocator protein 18 kDa (TSPO) were measured longitudinally in the striatum of MPTP-treated animals. We report an early (2 months) decrease (46%) of striatal VMAT2 in asymptomatic MPTP animals that preceded changes in DAT, D2R, and AMPH-DAR and was associated with increased TSPO levels indicative of a glial response. Subsequent PET studies showed progressive loss of all pre-synaptic dopamine markers in the striatum with expression of parkinsonism. However, glial cell activation did not track disease progression. These findings indicate that decreased VMAT2 is a key pathogenic event that precedes nigrostriatal dopamine neuron degeneration. The loss of VMAT2 may result from an association with α-synuclein aggregation induced by oxidative stress. Disruption of dopamine sequestration by reducing VMAT2 is an early pathogenic event in the dopamine neuron degeneration that occurs in the MPTP non-human primate model of PD. Genetic or environmental factors that decrease VMAT2 function may be important determinants of PD.     

Estimation of radiation-induced second cancer risk associated with the institutional field matching craniospinal irradiation technique: A comparative treatment planning study

AimTo estimate and compare the lifetime attributable risk (LAR) of radiation-induced second cancer (SC) in pediatric medulloblastoma patients planned with institutional 3D conformal field matching method, gap junction method and Intensity Modulated Radiotherapy (IMRT).BackgroundThe epidemiological studies on childhood cancer survivors reported that long-term cancer survivors who received radiotherapy are at a significantly increased risk for the development of SC. Hence, the increased concern to predict the SC risk for long-term survivors.Materials and methodsIn addition to institutional field matching planning method, IMRT and gap junction methods were created for ten pediatric medulloblastoma patients. The risk estimates were made based on the site-specific cancer risk coefficient provided by the BEIR VII committee according to the organ equivalent dose for various critical organs. Also, plans were compared for target volume dose distribution and dose received by critical organs.ResultsWhen compared to the gap junction method, the IMRT and institutional field matching method were superior in normal tissue sparing and dose conformity. However, highly significant volume of low dose associated with IMRT was the main concern for the SC risk. The accumulated LAR for all the critical organs with 3D conformal gap junction and IMRT method was 23–25% while for the 3D conformal field matching method it was 21%.ConclusionThe LAR associated with the institutional field matching technique was substantially lower. As this method is highly robust and easy to set up, it can be a better choice of a craniospinal irradiation technique where 3DCRT is the only choice of treatment.     

6X Acuros algorithm validation in the presence of inhomogeneities for VMAT treatment planning

AimTo validate the Acuros®XB (AXB) dose calculation algorithm for a 6 MV beam from the Varian TrueBeam treatment units.BackgroundCurrently Anisotropic Analytic Algorithm (AAA) is clinically used on authors’ department but AXB could replace it for VMAT treatments in regions where inhomogeneities and free air are present.Materials and methodsTwo steps are followed in the validation process of a new dose calculation algorithm. The first is to check the accuracy of algorithm for a homogenous phantom and regular fields. Multiple fields of increasing complexity have been acquired using a MapCheck diode array. The accuracy of the algorithm was evaluated using the gamma analysis method. The second is to validate the algorithm in the presence of heterogeneous media. Planar absolute dose was measured with GafChromic®EBT2 film and was compared with the dose calculated by AXB. Gamma analysis was performed between MapCheck measurements and AXB dose calculations, at a range of clinical source-surface distance.ResultsFor SSDs ranging from 80 to 100 cm, the results show a minimum pass rate of 95% between AXB and MapCheck acquisition. For open 6 MV photon beam interacting with a phantom with an air gap, the agreement after the air gap between AXB and GafChromic®EBT2 is less than 1% in the 3 × 3cm² field and less than 2% in the 10 × 10 cm² field.ConclusionsAXB has advanced modelling of lateral electron transport that enables a more accurate dose calculation in heterogeneous regions and, compared with AAA, improves accuracy between different density interfaces. This will be of particular benefit for head/neck treatments.     

Time and frequency to observe fiducial markers in MLC-modulated fields during prostate IMRT/VMAT beam delivery

ObjectiveThis work investigates the time and frequency to observe fiducial markers in MLC-modulated fields during intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) beam delivery for real-time prostate localization.MethodsThirty seven prostate patients treated with IMRT or VMAT were included in this retrospective study. DRR images were generated for all MLC segments/control points using the TPS. The MLC leaf pattern of each control point was overlaid on the DRR, and the number of fiducials within the MLC opening was analyzed. EPID images of fiducials in a pelvic phantom were obtained to demonstrate the fiducial visibility during modulated beam delivery.ResultsGold fiducials were visible on EPID images. The probability of seeing a number of fiducials within the MLC opening was analyzed. At least one fiducial was visible during 42 ± 2% and 52 ± 2% beam-on time for IMRT of the prostate with and without lymph nodes, and during 81 ± 4% and 80 ± 5% beam-on time for VMAT of the prostate with and without lymph nodes, respectively. The mean time interval to observe at least one fiducial was 8.4 ± 0.7 and 5.9 ± 0.5 s for IMRT of the prostate with and without the lymph nodes, respectively, and 1.6 ± 0.1 s for VMAT prostate patients. The estimated potential dosimetric uncertainty was 7% and 2% for IMRT and VMAT, respectively.ConclusionsOur results demonstrated that the time and frequency to observe fiducial markers in MLC-modulated fields during IMRT/VMAT beam delivery were adequate for real-time prostate localization. The beam’s eye view fiducial positions could be used for intrafractional target monitoring and motion correction in prostate radiotherapy.     

Effects of VMAT2 inhibitors lobeline and GZ‐793A on methamphetamine‐induced changes in dopamine release,metabolism and synthesis in vivo

Vesicular monoamine transporter‐2 (VMAT2) inhibitors reduce methamphetamine (METH) reward in rats. The current study determined the effects of VMAT2 inhibitors lobeline (LOB; 1 or 3 mg/kg) and N‐(1,2R‐dihydroxylpropyl)‐2,6‐cis‐di(4‐methoxyphenethyl)piperidine hydrochloride (GZ‐793A; 15 or 30 mg/kg) on METH‐induced (0.5 mg/kg, SC) changes in extracellular dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the reward‐relevant nucleus accumbens (NAc) shell using in vivo microdialysis. The effect of GZ‐793A (15 mg/kg) on DA synthesis in tissue also was investigated in NAc, striatum, medial prefrontal cortex and orbitofrontal cortex. In NAc shell, METH produced a time‐dependent increase in extracellular DA and decrease in DOPAC. Neither LOB nor GZ‐793A alone altered extracellular DA; however, both drugs increased extracellular DOPAC. In combination with METH, LOB did not alter the effects of METH on DA; however, GZ‐793A, which has greater selectivity than LOB for inhibiting VMAT2, reduced the duration of the METH‐induced increase in extracellular DA. Both LOB and GZ‐793A enhanced the duration of the METH‐induced decrease in extracellular DOPAC. METH also increased tissue DA synthesis in NAc and striatum, whereas GZ‐793A decreased synthesis; no effect of METH or GZ‐793A on DA synthesis was found in medial prefrontal cortex or orbitofrontal cortex. These results suggest that selective inhibition of VMAT2 produces a time‐dependent decrease in DA release in NAc shell as a result of alterations in tyrosine hydroxylase activity, which may play a role in the ability of GZ‐793A to decrease METH reward.