Intensity-modulated vaginal brachytherapy applicator and single- and multi-channel applicators in vaginal cuff brachytherapy.

Purpose: To compare the dosimetric performance of vaginal intensity-modulated brachytherapy (IM-BRT) applicator and single- (SC-BRT) and multi-channel brachytherapy (MC-BRT) applicators for vaginal cuff brachytherapy (VC-BRT). Material and methods: Fifteen patients with uterine-confined endometrium cancer who received adjuvant VC-BRT were included in this study. IM-BRT, SC-BRT, and MC-BRT treatment plans were created for two different clinical target volume (CTV) definitions: 1. Standard CTV, called CTVs; and 2. Virtually defined CTV, called CTVv, with asymmetrical tumor extension > 5 mm in thickness. Plan comparison was performed using dose-volume histogram (DVH) and treatment planning parameters. Results: According to DVH analysis, D98 for CTVv and D2 for both CTVs and CTVv showed statistically significant differences between IM-BRT and SC-BRT plans, but there was no significant difference between IM-BRT and MC-BRT plans in terms of D98 and D2 for both CTVs and CTVv. Additionally, for CTVv plans, IM-BRT was found to be significantly superior to SC-BRT for the rectum (D2cc, V5Gy, and V7Gy), bladder (D2cc and V7Gy), and small bowel (D2cc, V5Gy, and V7Gy). On the other hand, DVH parameters of the sigmoid showed large difference between IM-BRT and SC-BRT plans, but it was not statistically significant. Similarly, the use of IM-BRT applicator demonstrated a noticeable dose reduction in all defined OARs when compared with MC-BRT applicator, but statistically significant for the rectum V7Gy (p = 0.03) only. Conclusions: While the IM-BRT applicator is still in pre-clinical phase, our investigation demonstrated the proof-of-concept in real patient treatment plans with promising dosimetric results compared with SC-BRT and MC-BRT plans in selected patient group.

Inter-observer variation of target volume delineation for CT-guided cervical cancer brachytherapy.

Purpose: Delineation is a critical and challenging step in radiotherapy planning. Differences in delineation among observers are common, despite the presence of contouring guidelines. This study aimed to identify the inter-observer variability in the target volume delineation of computed tomography (CT)-guided brachytherapy for cervical cancer. Material and methods: Four radiation oncologists (ROs) with different expertise levels delineated high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) according to GYN GEC-ESTRO recommendations, in a blinded manner on every CT set of ten locally advanced cervical cancer cases. The most experienced RO's contours were determined as the index and used for comparison. Dice similarity coefficient (DSC) and pairwise Hausdorff distance (HD) metrics were applied to compare the overlap and gross deviations of all contours. Results: Median DSC for HR-CTV and IR-CTV were 0.73 and 0.76, respectively, and a good concordance was achieved for both in majority of contours. While there was no difference in DSC measurements for HR-CTV among the three ROs, RO-3 provided improved DSC values for IR-CTV (p = 0.01). Median HD95 was 5.02 mm and 6.83 mm, and median HDave was 1.69 mm and 2.21 mm for HR-CTV and IR-CTV, respectively. There was no significant difference among ROs in HR-CTV for HD95 or HDave; however, IR-CTV value was significantly improved according to RO-3 (p = 0.01). Case-by-case HD analysis showed no significant inter-observer variations, except for two cases. Conclusions: The inter-observer agreement is generally high for target volumes in CT-guided brachytherapy for cervical cancer. The agreement is lower for IR-CTV than HR-CTV. The individual characteristics of each case and different expertise levels of the ROs may have caused the differences. Despite the good concordance for delineation, dosimetric consequences can still be clinically significant.

Preclinical Dosimetry for Small Animal Radiation Research in Proton Therapy: A Feasibility Study.

Purpose: To evaluate the feasibility of the three-dimensional (3D) printed small animal phantoms in dosimetric verification of proton therapy for small animal radiation research. Materials and Methods: Two different phantoms were modeled using the computed-tomography dataset of real rat and tumor-bearing mouse, retrospectively. Rat phantoms were designed to accommodate both EBT3 film and ionization chamber. A subcutaneous tumor-bearing mouse phantom was only modified to accommodate film dosimetry. All phantoms were printed using polylactic-acid (PLA) filament. Optimal printing parameters were set to create tissue-equivalent material. Then, proton therapy plans for different anatomical targets, including whole brain and total lung irradiation in the rat phantom and the subcutaneous tumor model in the mouse phantom, were created using the pencil-beam scanning technique. Point dose and film dosimetry measurements were performed using 3D-printed phantoms. In addition, all phantoms were analyzed in terms of printing accuracy and uniformity. Results: Three-dimensionally printed phantoms had excellent uniformity over the external body, and printing accuracy was within 0.5 mm. According to our findings, two-dimensional dosimetry with EBT3 showed acceptable levels of γ passing rate for all measurements except for whole brain irradiation (γ passing rate, 89.8%). In terms of point dose analysis, a good agreement (<0.1%) was found between the measured and calculated point doses for all anatomical targets. Conclusion: Three-dimensionally printed small animal phantoms show great potential for dosimetric verifications of clinical proton therapy for small animal radiation research.

Applicator-guided proton therapy versus multichannel brachytherapy for vaginal vault irradiation.

To dosimetrically compare applicator-guided intensity-modulated proton therapy (IMPT) and multichannel brachytherapy (MC-BRT) for vaginal vault irradiation (VVI) with special focus on dose to organs at risk (OARs) and normal tissues. Ten patients with uterine confined endometrial cancer who received adjuvant vaginal cuff brachytherapy were included in this study. For each patient an additional IMPT treatment plan was created using the same computed tomography dataset and contours segmented for MC-BRT plans. Clinical target volume (CTV) was defined as the proximal 3.5 cm of the vagina including the entire thickness of vaginal wall. Planning target volume for IMPT plans was generated from the CTV with an addition isotropic 3 mm margin. OARs included rectum, bladder, sigmoid, small bowel and femoral heads. The prescribed dose was 21 Gy in 3 fractions. For simplicity, all doses were expressed in Gy and a constant relative biological effectiveness of 1.1 was used for IMPT plans. Plan comparison was performed using dose-volume histogram and treatment planning parameters. A significant improvement of the D98% coverage for CTV was reached by the applicator-guided IMPT plans (p < 0.01). IMPT also provided a dose reduction in all OARs except for femoral heads due to the lateral beam direction, especially significant reduction of V5Gy, D2cc, D0.1 cc, Dmean, V95% values for the rectum and Dmean, D0.1 cc to bladder, sigmoid, small bowel. Additionally, IMPT plans showed a significant reduction of integral dose to normal tissue with respect to MC-BRT (221.5 cGy.L vs. 653.6 cGy.L, p < 0.01). Applicator-guided IMPT has the potential for improving plan quality in VVI while maintaining the high conformity afforded by the state-of-the-art intracavitary brachytherapy.

Dosimetric comparison and secondary malignancy risk estimation for linac-based and robotic stereotactic radiotherapy in uveal melanoma.

It was aimed to investigate the dosimetric differences among linac-based and robotic stereotactic radiotherapy (SRT) techniques for the treatment of uveal melanoma and to evaluate secondary malignancy risks for these different SRT techniques. Ten patients who received robotic SRT with CyberKnife were retrospectively included in this study. A total dose of 54 Gy in three fractions was prescribed to the planning target volume (PTV). For each patient, non-coplanar micro-multileaf collimator based dynamic conformal arc (DCA), intensity-modulated radiotherapy (IMRT) and circular cone based DCA (cDCA) plans were generated. During the analysis dose-volume histogram (DVH) parameters, homogeneity index, new conformity index, the volume received more than or equal to 30% and 50% of the prescribed dose were compared. Additionally, secondary malignancy risk for each technique was estimated using the risk factors recommended by The International Commission on Radiological Protection. Robotic SRT plans provided a high degree of conformity within the PTV and better normal tissue sparing compared to linac-based treatment plans. However, dose distribution was more heterogeneous in robotic SRT plans than that in linac-based techniques. Estimated secondary malignancy risk was also found as 3.4%, 1.4%, 1.4% and 1.6% for robotic SRT and linac-based IMRT, DCA, cDCA plans, respectively. Treatment parameters of uveal melanoma patients planned with robotic SRT had superior conformity and organ-at-risk (OAR) sparing compared with those planned with the linac-based system. However, estimated secondary malignancy risk was almost two-times higher in robotic SRT than that in linac-based techniques.

A novel inverse optimization based three-dimensional conformal radiotherapy technique in craniospinal irradiation.

Our aim was to develop a novel inverse optimization-based three-dimensional conformal radiotherapy (i3DCRT) technique for craniospinal irradiation. The imaging data of 20 patients with medulloblastoma were used retrospectively. The first group included 10 pediatric patients with supine position treated under anesthesia/sedation, and the second group included 10 young adult/adult patients treated with prone position. Three different treatment plans were created for each patient via i3DCRT, forward-planned three-dimensional conformal radiotherapy (f3DCRT) and intensity-modulated radiotherapy (IMRT) techniques. A total dose of 36 Gy was prescribed in 20 fractions for all plans. The comparative evaluation was conducted by using the parameters of conformity-index, homogeneity-index, and doses to the target volumes and organs at risk (OARs). The plans created with i3DCRT technique achieved better conformity and homogeneity compared to f3DCRT. In terms of OARs sparing, we found pronounced dose reductions in esophagus and heart in i3DCRT compared to f3DCRT plans. i3DCRT technique also provided a well-conformed dose distribution not superior, but comparable, to IMRT without increase in the total monitor unit per fraction (MU/fx) with respect to f3DCRT. The average monitor unit per fraction (MU/fx) for i3DCRT, f3DCRT and IMRT plans were found as 379.3, 378.0 and 1051.7 MU for the first group and 577.4, 563.5 and 1368.7 MU for the second group, respectively. Novel i3DCRT technique solves the problems associated with field junctions and beam edge matching encountered in f3DCRT plans. Additionally, i3DCRT technique can create almost similar plans as with IMRT with lower total MU/fx.

Characterization of 3D-printed bolus produced at different printing parameters.

We aimed to analyze the effects of printing parameters on characterization of three-dimensional (3D) printed bolus used in external beam radiotherapy. Two sets of measurements were performed to investigate the dosimetric and physical characterization of 3D-printed bolus at different printing parameters. In the first step, boluses were produced at different infill-percentages, infill-patterns and printing directions. Two-dimensional (2D) dose measurements were performed in Elekta Versa HD linear accelerator using 6 MV photon energy. Measured 2D dose maps for both printed and reference bolus materials were compared using the 2D gamma analysis method. Additionally, patient-specific bolus was produced with defined optimum printing parameters for anthropomorphic head and neck phantom. Then, point dose measurements were performed to evaluate the feasibility of printed bolus in clinical use. In the second step, physical measurements were carried out to evaluate the printing accuracy, the mean hounsfield unit (HU) value and the weight of 3D-printed boluses. According to our measurement, infill-percentage, infill-pattern and printing direction significantly changed the dosimetric and physical properties of the 3D-printed bolus independently. Maximum gamma passing rate at 1.5 and 5 cm depths were found as 93.8% and 98.8%, respectively, for 60% infill-percentage, sunglass fill infill-pattern and horizontal printing direction. The printing accuracy of the products was within 0.4 mm. Dosimetric and physical properties of the printed bolus material changed significantly with the selected printing parameters. Therefore, it is important to note that each combination of these printing parameters that will be used in the production of patient-specific bolus should be investigated separately.

3D printer-based novel intensity-modulated vaginal brachytherapy applicator: feasibility study.

PURPOSE: To design a novel high-dose-rate intracavitary applicator which may lead to enhanced dose modulation in the brachytherapy of gynecological cancers. MATERIAL AND METHODS: A novel brachytherapy applicator, auxiliary equipment and quality control phantom were modeled in SketchUp Pro 2017 modeling software and printed out from a MakerBot Replicator Z18 three-dimensional printer. As a printing material polylactic acid (PLA) filament was used and compensator materials including aluminum, stainless-steel and Cerrobend alloy were selected according to their radiation attenuation properties. To evaluate the feasibility of the novel applicator, two sets of measurements were performed in a Varian GammaMed iX Plus high-dose rate iridium-192 (192Ir) brachytherapy unit and all of the treatment plans were calculated in Varian BrachyVision treatment planning system v.8.9 with TG43-based formalism. In the first step, catheter and source-dwell positioning accuracy, reproducibility of catheter and source positions, linearity of relative dose with changing dwell times and compensator materials were tested to evaluate the mechanical stability of the designed applicator. In the second step, to validate the dosimetric accuracy of the novel applicator measured point dose and two-dimensional dose distributions in homogeneous medium were compared with calculated data in the treatment planning system using PTW VeriSoft v.5.1 software. RESULTS: In mechanical quality control tests source-dwell positioning accuracy and linearity of the designed applicator were measured as ≤ 0.5 mm and ≤ 1.5%, respectively. Reproducibility of the treatment planning was ≥ 97.7% for gamma evaluation criteria of 1 mm distance to agreement and 1% dose difference of local dose. In dosimetric quality control tests, maximum difference between measured and calculated point dose was found as 3.8% in homogeneous medium. In two-dimensional analysis, the number of passing points was greater than 90% for all measurements using gamma evaluation criteria of 3 mm distance to agreement and 3% dose difference of local dose. CONCLUSIONS: The novel brachytherapy applicator met the necessary requirements in quality control tests.

Dosimetric comparison of two different applicators and rectal retraction methods used in inverse optimization-based intracavitary brachytherapy for cervical cancer.

PURPOSE: The purpose of this study was to evaluate the dosimetric differences between two different applicators and rectal-retraction methods used in image-guided brachytherapy (IGBT) for locally advanced cervical cancer (LACC). MATERIAL AND METHODS: Ten patients with LACC treated with definitive chemoradiotherapy and inverse optimization-based IGBT were included in this study. In each patient, at least one fraction of IGBT was performed using tandem-ovoids (TO) with vaginal gauze packing (VGP) or tandem-ring (TR) with rectal-retractor (RR). High-risk clinical target volume (CTVHR) and intermediate-risk CTV (CTVIR) were defined as CTVs, and bladder, rectum, sigmoid, small bowel, urethra, and vaginal mucosa were defined as organs at risk (OARs). All patients received 50.4 Gy external beam radiotherapy (EBRT) in 28 fractions. After EBRT, 28 Gy high-dose-rate (HDR) IGBT in 4 fractions was delivered to central disease. A plan comparison was performed using dose-volume histogram (DVH) and treatment planning parameters for CTVs and OARs. RESULTS: There were no significant differences in D90 values of CTVHR. In terms of rectum dose, TR with RR was found to be significantly better than TO with VGP (p < 0.0001 for D2cm3 and p < 0.013 for V5Gy). Although, there were no statistically significant differences in D2cm3 value of bladder, sigmoid, small bowel, upper vaginal mucosa, and urethra, mean value of D2cm3 for all defined OARs were found lower in TR than in TO. Bladder V7Gy, upper vaginal mucosa V7Gy, middle and lower vaginal mucosa D2cm3 values were all found to be significantly lower for TR than for TO (p < 0.035). CTVHR and CTVIR volumes contoured in TR were approximately 11% and 9% smaller than TO, respectively. CONCLUSIONS: The results showed that there were no statistically differences in D90 value of CTVHR and CTVIR. However, all DVH parameters for OARs in TR with RR were found to be better than in TO with VGP.

Adjuvant vaginal cuff brachytherapy: dosimetric comparison of conventional versus 3-dimensional planning in endometrial cancer.

PURPOSE: To evaluate dosimetric differences between point-based 2-dimensional (2D) vaginal brachytherapy (VBT) treatment planning technique and volume-based 3-dimensional (3D) VBT method for endometrial cancer (EC). MATERIAL AND METHODS: Ten patients with uterine-confined EC treated with VBT were included in this study. All patients received 27.5 Gy in 5 fractions. Three different treatment plans were performed for each patient: plan A for dose prescribed to the entire vaginal wall thickness delineated via computed tomography guidance, plan B for dose prescribed to the vaginal mucosa/cylinder surface, and plan C for dose prescribed to 5 mm beyond the vaginal mucosa/cylinder surface. Dose-volume histograms (DVH) of treatment volumes and organs at risk (OARs) were evaluated and compared. RESULTS: DVH analysis of target volume doses (D100, D95, and D90) showed a significant difference between plan A and plan B (p = 0.005), and plan B was found lower. D100 for plan C was significantly higher than plan A (p = 0.009), but for D95 and D90, no statistically significant difference was found (p = 0.028 and p = 0.028, respectively). In terms of OARs doses, including vagina, rectum, bladder, and sigmoid, D2cm3 doses were significantly higher in plan A than plan B (p = 0.009, p = 0.009, p = 0.005, and p = 0.005, respectively). All these doses were also significantly lower than in plan C (p = 0.005, p = 0.012, and p = 0.013, respectively), except for sigmoid (p = 0.155). CONCLUSIONS: In this dosimetric analysis, we have shown that the volume-based 3D VBT technique provides the ability to balance the target dose against the sparing of OARs. Therefore, in the new modern 3D treatment era, instead of normalization of the dose to standard reference points, customized 3D volume-based VBT planning should be recommended.

Feasibility of novel in vivo EPID dosimetry system for linear accelerator quality control tests.

The main aim was to validate the capability of a novel EPID-based in vivo dosimetry system for machine-specific quality control (QC) tests. In current study, two sets of measurements were performed in Elekta Versa HD linear accelerator using novel iViewDose™ in vivo dosimetry software. In the first part, measurements were carried out to evaluate the feasibility of novel in vivo system for daily dosimetric QC tests including output constancy, percentage depth dose (PDD) and beam profile measurements. In addition to daily QC tests, measured output factor as a function of field size, leaf transmission and tongue and groove effect were compared with calculated TPS data. In the second part of the measurements, detection capability of iViewDose software for basic mechanical QC tests were investigated for different setup conditions. In dosimetric QC tests, measured output factor with changing field size, PDD, beam profile and leaf transmission factors were found to be compatible with calculated TPS data. Additionally, the EPID-based system was capable to detect given dose calibration errors of 1% with ± 0.02% deviation. In mechanical QC tests, it was found that iViewDose software was sensitive for catching errors in collimator rotation (≥ 1°), changes in phantom thickness (≥ 1 cm) and major differences in irradiated field size down to 1 mm. In conclusion, iViewDose was proved to be as useful EPID-based software for daily monitoring of linear accelerator beam parameters and it provides extra safety net to prevent machine based radiation incidents.

Feasibility study of an electronic portal imaging based in vivo dose verification system for prostate stereotactic body radiotherapy.

PURPOSE: We evaluated the feasibility of electronic portal imaging based 3D in-vivo dosimetry for stereotactic body radiation therapy (SBRT) technique in prostate cancer. METHODS AND MATERIALS: To investigate error detectability limitations of iViewDose™ v.1.0.1 (Elekta, Stockholm, Sweden) for prostate SBRT cases, ten prostate cancer patients were selected and in-vivo electronic portal imaging devices dosimetry was performed. Also possible error scenarios including dose calibration, setup, collimator, multi leaf collimator and patient anatomy related inaccuracies were created to investigate detectability of EPID. For this purpose, a SBRT treatment was planned on BrainLab pelvis phantom (BrainLab Medical Systems, Westchester, IL) and irradiated after proving setup with cone beam computer tomography. After that incorrect plans were irradiated and obtained results were compared with original in vivo measurements. RESULTS: Mean gamma analysis (γ% ≤ 1) passing rate of ten patients was found as 96.2%. Additionally, mean dose reference point difference between measurement and calculated in treatment planning system for clinical target volume, rectum, bladder, left and right femur heads were found as 1.4%, 8%, 20.8%, 2.3% and 4.5%, respectively. Phantom measurements showed that positional errors can be escape from detection. However, the incorrect treated plans including linac calibration, MLC positions and patient anatomy based errors could not have passed the in vivo dosimetry analysis. CONCLUSIONS: EPID-based 3D in vivo dosimetry software (iViewDose) provides an efficient safety check on the accuracy of dose delivery during prostate SBRT treatments. However, phantom results showed some limitation of the system.

Evaluation of Photoneutron Dose Measured by Bubble Detectors in Conventional Linacs and Cyberknife Unit: Effective Dose and Secondary Malignancy Risk Estimation.

This study aims to reduce the uncertainty about the photoneutron dose produced over a course of radiotherapy with high-energy photon beams and evaluate photoneutron contamination-based secondary malignancy risk for different treatment modalities. Dosimetric measurements were taken in Philips SL25/75, Elekta Synergy Platform (Elekta AB, Stockholm, Sweden), Varian Clinac DHX High Performance systems (Varian Medical Systems, Palo Alto, CA), and Cyberknife Robotic Radiosurgery Unit (Accuray Inc., Sunnyvale, CA) using bubble detector for neutron dosimetry. The measurement data were used to determine in-field and out-of-field neutron equivalent dose in 6-MV 3D conformal radiotherapy, sliding window-intensity-modulated radiotherapy, and stereotactic body radiotherapy and to calculate the effective dose in 18-MV 3D conformal radiotherapy and sliding window-intensity-modulated radiotherapy techniques for patients with prostate cancer undergoing a standard treatment. For the 18-MV treatment techniques, the secondary malignancy risk due to the neutron contamination was estimated using the risk factors published by The International Commission on Radiological Protection. The neutron contamination-based secondary malignancy risk for the 18-MV 3D conformal radiotherapy and sliding window-intensity-modulated radiotherapy modalities was found to be 0.44% and 1.45% for Elekta Synergy Platform and 0.92% and 3.0% for the Varian Clinac DHX High Performance, respectively. For 6-MV 3D conformal radiotherapy, sliding window-intensity-modulated radiotherapy, and stereotactic body radiotherapy treatment techniques, neutron equivalent doses inside the treatment field were found to be lower than 40 mSv. Our measurements reveal that equivalent dose and effective dose due to the neutron contamination are at a considerable level for 18-MV sliding window-intensity-modulated radiotherapy treatments, while 6-MV photon beams used in different modalities still induce only negligible photoneutrons. The secondary malignancy risk based on photoneutron should be therefore taken into consideration in case of selecting 18-MV photons in a sliding window-intensity-modulated radiotherapy treatment instead of 6 MV.

Investigating in-field and out-of-field neutron contamination in high-energy medical linear accelerators based on the treatment factors of field size, depth, beam modifiers, and beam type.

PURPOSE: We analysed the effects of field size, depth, beam modifier and beam type on the amount of in-field and out-of-field neutron contamination for medical linear accelerators (linacs). METHODS: Measurements were carried out for three high-energy medical linacs of Elekta Synergy Platform, Varian Clinac DHX High Performance and Philips SL25 using bubble detectors. The photo-neutron measurements were taken in the first two linacs with 18 MV nominal energy, whereas the electro-neutrons were measured in the three linacs with 9 MeV, 10 MeV, 15 MeV and 18 MeV. RESULTS: The central neutron doses increased with larger field sizes as a dramatic drop off was observed in peripheral areas. Comparing with the jaws-shaped open-field of 10 × 10 cm, the motorised and physical wedges contributed to neutron contamination at central axis by 60% and 18%, respectively. The similar dose increment was observed in MLC-shaped fields. The contributions of MLCs were in the range of 55-59% and 19-22% in Elekta and Varian linacs comparing with 10 × 10 and 20 × 20 cm open fields shaped by the jaws, respectively. The neutron doses at shallow depths were found to be higher than the doses found at deeper regions. The electro-neutron dose at the 18 MeV energy was higher than the doses at the electron energies of 15 MeV and 9 MeV by a factor of 3 and 50, respectively. CONCLUSION: The photo- and electro-neutron dose should be taken into consideration in the radiation treatment with high photon and electron energies.