Error detection during VMAT delivery using EPID-based 3D transit dosimetry

PurposeTo investigate the effectiveness of an EPID-based 3D transit dosimetry system in detecting deliberately introduced errors during VMAT delivery.MethodsAn Alderson phantom was irradiated using four VMAT treatment plans (one prostate, two head-and-neck and one lung case) in which delivery, thickness and setup errors were introduced. EPID measurements were performed to reconstruct 3D dose distributions of “error” plans, which were compared with “no-error” plans using the mean gamma (γ_mean), near-maximum gamma (γ_1%) and the difference in isocenter dose (ΔD_isoc) as metrics.ResultsOut of a total of 42 serious errors, the number of errors detected was 33 (79%), and 27 out of 30 (90%) if setup errors are not included. The system was able to pick up errors of 5 mm movement of a leaf bank, a wrong collimator rotation angle and a wrong photon beam energy. A change in phantom thickness of 1 cm was detected for all cases, while only for the head-and-neck plans a 2 cm horizontal and vertical shift of the phantom were alerted. A single leaf error of 5 mm could be detected for the lung plan only.ConclusionAlthough performed for a limited number of cases and error types, this study shows that EPID-based 3D transit dosimetry is able to detect a number of serious errors in dose delivery, leaf bank position and patient thickness during VMAT delivery. Errors in patient setup and single leaf position can only be detected in specific cases.     

Set-up error validation with EPID images: Measurements vs Egs_cbct simulation

AimIn this study, the egs_cbct code’s ability to replicate an electronic portal imaging device (EPID) is explored.BackgroundWe have investigated head and neck (H&N) setup verification on an Elekta Precise linear accelerator. It is equipped with an electronic portal imaging device (EPID) that can capture a set of projection images over different gantry angles.Methods and materialsCone-beam computed tomography (CBCT) images were reconstructed from projection images of two different setup scenarios. Projections of an Anthropomorphic Rando head phantom were also simulated by using the egs_cbct Monte Carlo code for comparison with the measured projections.Afterwards, CBCT images were reconstructed from this data. Image quality was evaluated against a metric defined as the image acquisition interval (IAI). It determines the number of projection images to be used for CBCT image reconstruction.ResultsFrom this results it was established that phantom shifts could be determined within 2 mm and rotations within one degree accuracy using only 20 projection images (IAI = 10 degrees). Similar results were obtained with the simulated data.ConclusionIn this study it is demonstrated that a head and neck setup can be verified using substantially fewer projection images. Bony landmarks and air cavities could still be observed in the reconstructed Rando head phantom. The egs_cbct code can be used as a tool to investigate setup errors without tedious measurements with an EPID system.     

Initial clinical experience with Epid-based in-vivo dosimetry for VMAT treatments of head-and-neck tumors

We evaluated an EPID-based in-vivo dosimetry algorithm (IVD) for complex VMAT treatments in clinical routine. 19 consecutive patients with head-and-neck tumors and treated with Elekta VMAT technique using Simultaneous Integrated Boost strategy were enrolled. In-vivo tests were evaluated by means of (i) ratio R between daily in-vivo isocenter dose and planned dose and (ii) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ_%) and mean γ-values (γ_mean), using a global 3%–3 mm criteria. Alert criteria of ±5% for R ratio, γ_% < 90% and γ_mean > 0.67 were chosen. A total of 350 transit EPID images were acquired during the treatment fractions. The overall mean R ratio was equal to 1.002 ± 0.019 (1 SD), with 95.9% of tests within ±5%. The 2D portal images of γ-analysis showed an overall γ_mean of 0.42 ± 0.16 with 93.3% of tests within alert criteria, and a mean γ% equal to 92.9 ± 5.1% with 85.9% of tests within alert criteria. Relevant discrepancies were observed in three patients: a set-up error was detected for one patient and two patients showed major anatomical variations (weight loss/tumor shrinkage) in the second half of treatment. The results are supplied in quasi real-time, with IVD tests displayed after only 1 minute from the end of arc delivery. This procedure was able to detect when delivery was inconsistent with the original plans, allowing physics and medical staff to promptly act in case of major deviations between measured and planned dose.     

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.     

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.     

Evaluation of volumetric modulated arc therapy (VMAT) — based total body irradiation (TBI) in pediatric patients

BackgroundThe dosimetric characterization of volumetric modulated arc therapy (VMAT)-based total-body irradiation (TBI) in pediatric patients is evaluated.Materials and methodsTwenty-two patients between the ages of 2 and 12 years were enrolled for VMAT-based TBI from 2018 to 2020. Three isocenters were irradiated over three overlapping arcs. While prescribing 90% of the TBI dose to the planning treatment volume (PTV), two fractions (2 Gy each) were delivered each day; hence 12 Gy was delivered in six fractions. During treatment optimization, the mean lung and kidney doses were set not to exceed 7 Gy and 7.5 Gy, respectively. The maximum lens dose was also set to less than 4 Gy. Patient quality assurance was carried out by comparing treatment planning system doses to the 3-dimensional measured doses by the ArcCHECK^® detector. The electronic portal imaging device (EPID) gamma indices were also obtained.ResultsThe average mean lung dose was 7.75 ± 0.18 Gy, mean kidney dose 7.63 ± 0.26 Gy, maximum lens dose 4.41 ± 0.39 Gy, and the mean PTV dose 12.69 ± 0.16 Gy. The average PTV heterogeneity index was 1.15 ± 0.03. Average differences in mean kidney dose, mean lung dose, and mean target dose were 2.79% ± 0.88, 0.84% ± 0.45 and 0.93% ± 0.47, respectively; when comparing planned and ArcCHECK^® measured doses. Only grade 1–2 radiation toxicities were recorded, based on CTCAE v5.0 scoring criteria.ConclusionsVMAT-TBI was characterized with good PTV coverage, homogeneous dose distribution, planned and measured dose agreement, and low toxicity.     

Analysis of the planned,delivered dose distributions and quality assurance for helical tomotherapy and volumetric modulated arc therapy in locally advanced non-small cell lung cancer

BackgroundWith full access to both helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT), we compared locally advanced non-small cell lung cancer (LA-NSCLC) treatment plans and verified the plans using patient-specific pretreatment quality assurance (PSQA).Materials and methodsFor each of the seventeen patients included in the study, two treatment plans (i.e. HT and VMAT) were created. Optimized plans were evaluated following the ICRU 83 criteria. Planned quality indexes and dosimetric parameters were compared. Lastly, all plans were subjected to PSQA assessment by determining the gamma passing rate (GPR).ResultsAll dosimetry results obtained from the planning target volume passed the ICRU 83 criteria. With regard to similar homogeneity indices, VMAT produced better conformity number values than HT (0.78 vs. 0.64), but differences in the values were insignificant. Furthermore, VMAT was associated with a significantly shorter mean treatment time (1.91 minutes vs. 6.66 minutes). For PSQA assessment, both techniques resulted in adequate GPR values (> 90% at the 3%/3 mm criteria).ConclusionBoth HT and VMAT techniques led to the generation of clinically satisfactory and reliable radiotherapy plans. However, the VMAT plan was associated with a non-significantly better degree of conformity and a significantly shorter treatment time. Thus, VMAT was determined to be a better choice for LA-NSCLC.     

The Value of In Vitro Diagnostic Testing in Medical Practice: A Status Report

BackgroundIn vitro diagnostic (IVD) investigations are indispensable for routine patient management. Appropriate testing allows early-stage interventions, reducing late-stage healthcare expenditure (HCE).AimTo investigate HCE on IVDs in two developed markets and to assess the perceived value of IVDs on clinical decision-making. Physician-perceived HCE on IVD was evaluated, as well as desired features of new diagnostic markers.MethodsPast and current HCE on IVD was calculated for the US and Germany. A total of 79 US/German oncologists and cardiologists were interviewed to assess the number of cases where: physicians ask for IVDs; IVDs are used for initial diagnosis, treatment monitoring, or post-treatment; and decision-making is based on an IVD test result. A sample of 201 US and German oncologists and cardiologists was questioned regarding the proportion of HCE they believed to be attributable to IVD testing. After disclosing the actual IVD HCE, the physician’s perception of the appropriateness of the amount was captured. Finally, the association between physician-rated impact of IVD on decision-making and perceived contribution of IVD expenditure on overall HCE was assessed.ResultsIVD costs account for 2.3% and 1.4% of total HCE in the US and Germany. Most physicians (81%) believed that the actual HCE on IVDs was >5%; 19% rated the spending correctly (0–4%, p<0.001). When informed of the actual amount, 64% of physicians rated this as appropriate (p<0.0001); 66% of decision-making was based on IVD. Significantly, more physicians asked for either additional clinical or combined clinical/health economic data than for the product (test/platform) alone (p<0.0001).ConclusionsOur results indicate a poor awareness of actual HCE on IVD, but a high attributable value of diagnostic procedures for patient management. New markers should deliver actionable and medically relevant information, to guide decision-making and foster improved patient outcomes.     

In-vivo EPID dosimetry for IMRT and VMAT based on through-air predicted portal dose algorithm

We have adapted the methodology of Berry et al. (2012) for Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) treatments at a fixed source to imager distance (SID) based on the manufacturer’s through-air portal dose image prediction algorithm. In order to fix the SID a correction factor was introduced to account for the change in air gap between patient and imager. Commissioning data, collected with multiple field sizes, solid water thicknesses and air gaps, were acquired at 150 cm SID on the Varian aS1200 EPID. The method was verified using six IMRT and seven VMAT plans on up to three different phantoms. The method’s sensitivity and accuracy were investigated by introducing errors. A global 3%/3 mm gamma was used to assess the differences between the predicted and measured portal dose images. The effect of a varying air gap on EPID signal was found to be significant – varying by up to 30% with field size, phantom thickness, and air gap. All IMRT plans passed the 3%/3 mm gamma criteria by more than 95% on the three phantoms. 23 of 24 arcs from the VMAT plans passed the 3%/3 mm gamma criteria by more than 95%. This method was found to be sensitive to a range of potential errors. The presented approach provides fast and accurate in-vivo EPID dosimetry for IMRT and VMAT treatments and can potentially replace many pre-treatment verifications.     

EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell lung tumors: Initial clinical experience

PurposeEPID-based in vivo dosimetry (IVD) has been implemented for stereotactic body radiotherapy treatments of non-small cell lung cancer to check both isocenter dose and the treatment reproducibility comparing EPID portal images.Methods15 patients with lung tumors of small dimensions and treated with volumetric modulated arc therapy were enrolled for this initial experience. IVD tests supplied ratios R between in vivo reconstructed and planned isocenter doses. Moreover a γ-like analysis between daily EPID portal images and a reference one, in terms of percentage of points with γ-value smaller than 1, P_γ<1, and mean γ-values, γ_mean, using a local 3%–3 mm criteria, was adopted to check the treatment reproducibility. Tolerance levels of 5% for R ratio, P_γ<1 higher than 90% and γ_mean lower than 0.67 were adopted.ResultsA total of 160 EPID images, two images for each therapy session, were acquired during the treatment of the 15 patients. The overall mean of the R ratios was equal to 1.005 ± 0.014 (1 SD), with 96.9% of tests within ± 5%. The 2 D image γ-like analysis showed an overall γ_mean of 0.39 ± 0.12 with 96.1% of tests within the tolerance level, and an average P_γ<1 value equal to 96.4 ± 3.6% with 95.4% of tests with P_γ<1 > 90%. Paradigmatic discrepancies were observed in three patients: a set-up error and a patient morphological change were identified thanks to CBCT image analysis whereas the third discrepancy was not fully justified.ConclusionsThis procedure can provide improved patient safety as well as a first step to integrate IVD and CBCT dose recalculation.     

Comparison of dosimetric variation between prostate IMRT and VMAT due to patient's weight loss: Patient and phantom study

Aim

This study compared the dosimetric impact between prostate IMRT and VMAT due to patient''s weight loss.

Background

Dosimetric variation due to change of patient''s body contour is difficult to predict in prostate IMRT and VMAT, since a large number of small and irregular segmental fields is used in the delivery.

Materials and methods

Five patients with prostate volumes ranging from 32.0 to 86.5 cm³ and a heterogeneous pelvis phantom were used for prostate IMRT and VMAT plans using the same set of dose–volume constraints. Doses in IMRT and VMAT plans were recalculated with the patient''s and phantom''s body contour reduced by 0.5–2 cm to mimic size reduction. Dose coverage/criteria of the PTV and CTV and critical organs (rectum, bladder and femoral heads) were compared between IMRT and VMAT.

Results

In IMRT plans, increases of the D99% for the PTV and CTV were equal to 4.0 ± 0.1% per cm of reduced depth, which were higher than those in VMAT plans (2.7 ± 0.24% per cm). Moreover, increases of the D30% of the rectum and bladder per reduced depth in IMRT plans (4.0 ± 0.2% per cm and 3.5 ± 0.5% per cm) were higher than those of VMAT (2.2 ± 0.2% per cm and 2.0 ± 0.6% per cm). This was also true for the increase of the D5% for the right femoral head in a patient or phantom with size reduction due to weight loss.

Conclusions

VMAT would be preferred to IMRT in prostate radiotherapy, when a patient has potential to suffer from weight loss during the treatment.     

EPID-based daily verification of reproducibility of patients’ irradiation with IMRT plans

Aim

The aim of the work was to catch potential errors with daily EPID measurements of repeatability of the dose distribution during irradiation of IMRT patients.

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot‘em all!

BackgroundAbout 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients.Materials and methodsPatients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel.ResultsBetween 2015–2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52–84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1–6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3–65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27–56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded.ConclusionsSimultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.     

Individually selected teletherapy technique for accelerated partial breast irradiation

BackgroundThe aim of the study was to individualize accelerated partial breast irradiation based on optimal dose distribution, protect risk organ and predict most advantageous technique.Materials and methods138 breast cancer patients receiving postoperative APBI were enrolled. APBI plans were generated using 3D-conformal (3D-CRT), sliding window intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). In the case of superficial tumours, additional plans were developed by adding electron beam. To planning target volume (PTV) 37.5 Gy/10 fractions, 1 fraction/day was prescribed. A novel plan quality index (PQI) served as the basis for comparisons.ResultsIMRT was the most advantageous technique regarding homogeneity. VMAT provided best conformity, 3D-CR T — the lowest lung and heart exposure. PQI was the best in 45 (32.61%) VMAT, 13 (9.42%) IMRT, 9 (6.52%) 3D-CRT plans. In 71 cases (51.45%) no difference was detected. In patients with large PTV, 3D-CRT was the most favourable. Additional electron beam improved PQI of 3D-CRT plans but had no meaningful effect on IMRT or VMAT. IMRT was superior to VMAT if the tumour was superficial (p < 0.001), situated in the medial (p = 0.032) or upper quadrant (p = 0.046).ConclusionsIn half of all cases, individually selected teletherapy techniques provide superior results over others; relevance of a certain technique may be predicted by volume and PTV localization.     

Commissioning and initial experience with a commercial software for in vivo volumetric dosimetry

Introduction and purposeDosimetry Check (DC) (Math Resolutions) is a commercial EPID-based dosimetry software, which allows performing pre-treatment and transit dosimetry. DC provides an independent verification of the treatment, being potentially of great interest due to the high benefits of the in vivo volumetric dosimetry, which guarantee the treatment delivery and anatomy constancy. The aim of this work is to study the differences in dose between DC and the Treatment Planning System (TPS) to establish an accuracy level of the system.Material and methodsDC v.3.8 was used along with Varian Clinac iX accelerator equipped with EPID aS1000 and Eclipse v.10.0 with AAA and Acuros XB calculation algorithms. The DC evaluated version is based on a pencil beam calculation algorithm. Various plans were generated over several homogeneous and heterogeneous phantoms. Isocentre point doses and gamma analysis were evaluated.ResultsTotal dose differences at the isocentre between DC and TPS for the studied plans are less than 2%, but single field contributions achieve greater values. In the presence of heterogeneities, the discrepancies can reach up to 15%. In transit mode, DC does not consider properly the couch attenuation, especially when there is an air gap between phantom and couch.ConclusionsThe possibility of this in vivo evaluation and the potentiality of this new system have a very positive impact on improving patient QA. But improvements are required in both calculation algorithm and integration with the record and verify system.     

Machine log file-based dose verification using novel iterative CBCT reconstruction algorithm in commercial software during volumetric modulated arc therapy for prostate cancer patients

PurposeTo evaluate the utility of the use of iterative cone-beam computed tomography (CBCT) for machine log file-based dose verification during volumetric modulated arc therapy (VMAT) for prostate cancer patients.MethodsAll CBCT acquisition data were used to reconstruct images with the Feldkamp-Davis-Kress algorithm (FDK-CBCT) and the novel iterative algorithm (iCBCT). The Hounsfield unit (HU)-electron density curves for CBCT images were created using the Advanced Electron Density Phantom. The I’mRT and anthropomorphic phantoms were irradiated with VMAT after CBCT registration. Subsequently, fourteen prostate cancer patients received VMAT after CBCT registration. Machine log files and both CBCT images were exported to the PerFRACTION software, and a 3D patient dose was reconstructed. Mean dose for planning target volume (PTV), the bladder, and rectum and the 3D gamma analysis were evaluated.ResultsFor the phantom studies, the variation of HU values was observed at the central position surrounding the bones in FDK-CBCT. There were almost no changes in the difference of doses at the isocenter between measurement and reconstructed dose for planning CT (pCT), FDK-CBCT, and iCBCT. Mean dose differences of PTV, rectum, and bladder between iCBCT and pCT were approximately 2% lower than those between FDK-CBCT and pCT. For the clinical study, average gamma analysis for 2%/2 mm was 98.22% ± 1.07 and 98.81% ± 1.25% in FDK-CBCT and iCBCT, respectively.ConclusionsA similar machine log file-based dose verification accuracy is obtained for FDK-CBCT and iCBCT during VMAT for prostate cancer patients.     

Comparison of two different EPID-based solutions performing pretreatment quality assurance: 2D portal dosimetry versus 3D forward projection method

PurposeThe aim of this paper is to characterize two different EPID-based solutions for pre-treatment VMAT quality assurance, the 2D portal dosimetry and the 3D projection technique. Their ability to catch the main critical delivery errors was studied.MethodsMeasurements were performed with a linac accelerator equipped with EPID aSi1000, Portal Dose Image Prediction (PDIP), and PerFRACTION softwares. Their performances were studied simulating perturbations of a reference plan through systematic variations in dose values and micromultileaf collimator position. The performance of PDIP, based on 2D forward method, was evaluated calculating gamma passing rate (%GP) between no-error and error-simulated measurements. The impact of errors with PerFRACTION, based on 3D projection technique, was analyzed by calculating the difference between reference and perturbed DVH (%ΔD). Subsequently pre-treatment verification with PerFRACTION was done for 27 patients of different pathologies.ResultsThe sensitivity of PerFRACTION was slightly higher than sensitivity of PDIP, reaching a maximum of 0.9. Specificity was 1 for PerFRACTION and 0.6 for PDIP. The analysis of patients’ DVHs indicated that the mean %ΔD was (1.2 ± 1.9)% for D2%, (0.6 ± 1.7)% for D95% and (−0.0 ± 1.2)% for Dmean of PTV. Regarding OARs, we observed important discrepancies on DVH but that the higher dose variations were in low dose area (<10 Gy).ConclusionsThis study supports the introduction of the new 3D forward projection method for pretreatment QA raising the claim that the visualization of the delivered dose distribution on patient anatomy has major advantages over traditional portal dosimetry QA systems.     

Dosimetric comparison of analytic anisotropic algorithm and Acuros XB algorithm in VMAT plans for high-grade glioma

PurposeTo investigate the dosimetric impact between the anisotropic analytical algorithm (AAA) and the Acuros XB (AXB) algorithm in volumetric-modulated arc therapy (VMAT) plans for high-grade glioma (HGG).MethodsWe used a heterogeneous phantom to quantify the agreement between the measured and calculated doses from the AAA and from the AXB. We then analyzed 14 patients with HGG treated by VMAT, using the AAA. We newly created AXB plans for each corresponding AAA plan under the following conditions: (1) re-calculation for the same number of monitor units with an identical beam and leaf setup, and (2) re-optimization under the same conditions of dose constraints. The dose coverage for the planning target volume (PTV) was evaluated by dividing the coverage into the skull, air, and soft-tissue regions.ResultsCompared to the results obtained with the AAA, the AXB results were in good agreement with the measured profiles. The dose differences in the PTV between the AAA and re-calculated AXB plans were large in the skull region contained in the target. The dose difference in the PTV in both types of plan was significantly correlated with the volume of the skull contained in the target (r = 0.71, p = 0.0042). A re-optimized AXB plan's dose difference was lower vs. the re-calculated AXB plan's.ConclusionsWe observed dose differences between the AAA and AXB plans, in particular in the cases in which the skull region of the target was large. Considering the phantom measurement results, the AXB algorithm should be used in VMAT plans for HGG.     

A comparative analysis of Acuros XB and the analytical anisotropic algorithm for volumetric modulation arc therapy

BackgroundThis study aimed to verify the dosimetric impact of Acuros XB (AXB) (AXB, Varian Medical Systems Palo Alto CA, USA), a two model-based algorithm, in comparison with Anisotropic Analytical Algorithm (AAA ) calculations for prostate, head and neck and lung cancer treatment by volumetric modulated arc therapy (VMAT ), without primary modification to AA. At present, the well-known and validated AA algorithm is clinically used in our department for VMAT treatments of different pathologies. AXB could replace it without extra measurements. The treatment result and accuracy of the dose delivered depend on the dose calculation algorithm.Materials and methodNinety-five complex VMAT plans for different pathologies were generated using the Eclipse version 15.0.4 treatment planning system (TPS). The dose distributions were calculated using AA and AXB (dose-to-water, AXB_w and dose-to-medium, AXB_m), with the same plan parameters for all VMAT plans. The dosimetric parameters were calculated for each planning target volume (PTV) and involved organs at risk (OA R). The patient specific quality assurance of all VMAT plans has been verified by Octavius^®-4D phantom for different algorithms.ResultsThe relative differences among AA, AXB_w and AXB_m, with respect to prostate, head and neck were less than 1% for PTV D_95%. However, PTV D_95% calculated by AA tended to be overestimated, with a relative dose difference of 3.23% in the case of lung treatment. The absolute mean values of the relative differences were 1.1 ± 1.2% and 2.0 ± 1.2%, when comparing between AXB_w and AA, AXB_m and AA, respectively. The gamma pass rate was observed to exceed 97.4% and 99.4% for the measured and calculated doses in most cases of the volumetric 3D analysis for AA and AXB_m, respectively.ConclusionThis study suggests that the dose calculated to medium using AXB_m algorithm is better than AAA and it could be used clinically. Switching the dose calculation algorithm from AA to AXB does not require extra measurements.     

Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells

IntroductionNutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells.MethodsThirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting.ResultsCells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II.ConclusionsSIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease.