Optimizing normal tissue objectives (NTO) in eclipse treatment planning system (TPS) for stereotactic treatment of multiple brain metastases using non-coplanar RapidArc and comparison with HyperArc techniques.

PURPOSE: To optimize NTO parameters in non-coplanar RapidArc (RA) stereotactic radiosurgery (SRS) for multiple brain metastases and compare them with HyperArc (HA) plans. MATERIALS AND METHODS: Thirty patients with multiple brain metastases, receiving 21 Gy prescriptions, were retrospectively enrolled, with lesions ranging from two to eight and volumes between 0.27 and 10.56 cm3. Non-coplanar RapidArc plans utilized manual NTO (RA-mNTO) with varying dose fall-off values (0.1 mm-1, 0.5 mm-1, 1.0 mm-1, 2.0 mm-1, 3.0 mm-1) and end doses (50%, 25% & 10%). Additionally, two HyperArc plans were generated: HA-ALDO used Automatic Lower Dose Objectives with SRS NTO, while HA-mNTO used the same beam geometry with manual NTO parameters optimized from RA-mNTO plans. TrueBeam with High-Definition Multi-leaf Collimators (HDMLC), 6 MV Flattening Filter Free (FFF) Beam at a maximum dose rate of 1400 MU/min, and Eclipse version 16.1 TPS were used. Plans were assessed for Paddick Conformity Index (CI), Gradient Index (GI), Homogeneity Index (HI), normal brain doses (V18Gy, V15Gy, and V12Gy), Monitor Units (MUs), and delivery accuracy using aS1200 Digital Megavolt Imager (DMI) with 2%/2 mm gamma criteria. Statistical analysis utilized integrated scoring and the Wilcoxon signed-rank test. RESULTS: RA-mNTO plans with 0.5 mm⁻1 dose fall-off and 10% end-dose showed superior dosimetric outcomes: CI (0.85 ± 0.08), GI (3.63 ± 0.87), and HI (0.36 ± 0.06) compared to HA-ALDO (CI 0.84 ± 0.09, GI: 3.97 ± 0.85, HI: 0.39 ± 0.07) and HA-mNTO (CI 0.83 ± 0.08, GI: 3.60 ± 0.93, HI: 0.40 ± 0.06). MUs were comparable: RA-mNTO (9679 ± 1882), HA-ALDO (9509 ± 1315), and higher for HA-mNTO (10,457 ± 1980). RA-mNTO plans exhibited significantly lower normal brain doses (V18Gy: 1.78 ± 1.23, V15Gy: 3.54 ± 2.37, V12Gy: 6.21 ± 4.09) compared to HA-ALDO (V18Gy: 2.02 ± 1.34, V15Gy: 4.09 ± 2.66, V12Gy: 7.15 ± 4.56) and HA-mNTO (V18Gy: 1.85 ± 1.20, V15Gy: 3.68 ± 2.33, V12Gy: 6.36 ± 3.97). All techniques achieved > 98% gamma pass rate. CONCLUSION: Non-coplanar RA plans with optimized mNTO settings outperformed HyperArc plans in all studied dosimetric parameters for SRS treatment of multiple brain metastases.

Dosimetric evaluation of LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery with more than 20 targets: comparing MME, HyperArc, and RapidArc.

BACKGROUND: To compare the dosimetric quality of three widely used techniques for LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (fSRS) with more than 20 targets: dynamic conformal arc (DCA) in BrainLAB Multiple Metastases Elements (MME) module and volumetric modulated arc therapy (VMAT) using RapidArc (RA) and HyperArc (HA) in Varian Eclipse. METHODS: Ten patients who received single-isocenter fSRS with 20-37 targets were retrospectively replanned using MME, RA, and HA. Various dosimetric parameters, such as conformity index (CI), Paddick CI, gradient index (GI), normal brain dose exposures, maximum organ-at-risk (OAR) doses, and beam-on times were extracted and compared among the three techniques. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: All plans achieved the prescribed dose coverage goal of at least 95% of the planning target volume (PTV). HA plans showed superior conformity compared to RA and MME plans. MME plans showed superior GI compared to RA and HA plans. RA plans resulted in significantly higher low and intermediate dose exposure to normal brain compared to HA and MME plans, especially for lower doses of ≥ 8Gy and ≥ 5Gy. No significant differences were observed in the maximum dose to OARs among the three techniques. The beam-on time of MME plans was about two times longer than RA and HA plans. CONCLUSIONS: HA plans achieved the best conformity, while MME plans achieved the best dose fall-off for LINAC-based single-isocenter multi-target multi-fraction SRS with more than 20 targets. The choice of the optimal technique should consider the trade-offs between dosimetric quality, beam-on time, and planning effort.

Evaluation of Cardiac Substructures Dose Sparing in Single and Dual Isocenter RapidArc™ Radiotherapy Planning for Synchronous Bilateral Breast Cancer.

Purpose This study compares the dosimetry and dose sparing of cardiac substructures in single isocenter and dual isocenter RapidArc™ (Varian Medical Systems, Palo Alto, California, United States) radiotherapy planning for synchronous bilateral breast cancer. Methodology Six synchronous bilateral breast cancer (SBBC) patients received adjuvant radiation with the prescribed dose of 40.05 Gy in 15 fractions to the planning target volume (PTV) without local lymph nodal regions. PTVs and organs at risk (OARs), including both lungs, esophagus, spinal cord, heart, and left anterior descending coronary artery (LAD), both atria and ventricles were contoured. Single isocentric RapidArc (SIRA) and dual isocentric RapidArc (DIRA) plans were made for each patient and dosimetric differences between these two techniques were evaluated. Results There was no statistically significant difference in conformity index (CI) values between SIRA and DIRA plans, with 0.9681±0.01 and 0.9721±0.01 (p=0.505), respectively. SIRA planning showed superior homogeneity with homogeneity Index (HI) values of 0.0999±0.01 compared to DIRA planning with HI values of 0.1640±0.12 (p=0.230). The mean LAD dose of SIRA was valued higher than that of DIRA planning. Lower mean doses were obtained for both lungs in SIRA plans compared to DIRA plans. Meanwhile, doses to the right atrium, left atrium, left ventricle, right ventricle, and esophagus showed no statistical significance between these two techniques, except in the spinal cord. Conclusion Both SIRA and DIRA plans have satisfactory outcomes in sparing OARs. Meanwhile, SIRA techniques have less setup time and overall machine time.

Development and Quality Assurance of Multileaf Collimator (MLC) Auto-Feathering Junctions for Multi-Isocenter Supine Volumetric Modulated Arc Therapy (VMAT) Craniospinal Axis Irradiation on Halcyon.

Currently, there is a lack of methods and tools that efficiently evaluate the auto-feathering junctions created by multileaf collimator (MLCs) for supine volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) plans. We have investigated the feasibility of stitching together multi-isocenter fluence maps to then analyze the feathered junctions for patient-specific quality assurance (QA). Furthermore, we investigated the capability of Halcyon for the treatment of CSI patients. Three patients, who previously underwent VMAT CSI treatment on TrueBeam (6-MV flattening filter-free (FFF)) for 36 Gy in 20 fractions were replanned for Halcyon. A multi-isocenter approach with only translational superior-inferior shifts was used for both platforms. Each isocenter consists of two full arcs with anterior avoidance sectors, ±5° collimator rotations between arcs, and 5-8 cm of overlapping MLC auto-feathering junctions. All plans were QA'd via electronic portal imaging device (EPID) portal dosimetry and analyzed with a gamma criteria of 3%/3 mm. A variety of plan quality metrics were analyzed to evaluate dose distributions to the target, doses to organs at risk (OARs), and integral dose to the patient. A MATLAB script was developed to stitch the calculated and measured fluence maps in order to perform patient-specific QA for the composite fluence. The Halcyon plans provided highly conformal and homogenous dose distributions to the entire CSI target, superior to the clinical TrueBeam plans, while sparing critical organs with significantly lower values of V10Gy and V18Gy by up to 2% and 2.5%, respectively. Qualitative depictions of vertical dose profiles from the stitched DICOM of the entire CSI target for both planned and delivered fluence maps demonstrated equivalency, with slightly lower average pass rates with Halcyon (97%) compared to TrueBeam (99.9%). This approach to stitch multiple measured versus calculated EPID fluence maps has shown to be a feasible and accurate method and will be helpful for comprehensive VMAT CSI QA on both platforms. Further implementation of this script will be used in examining dosimetric impacts of daily patient positioning errors at MLC auto-feathering junctions.

Monitor unit verification for Varian TrueBeam VMAT plans using Monte Carlo calculations and phase space data.

To use the open-source Monte Carlo (MC) software calculations for TPS monitor unit verification of VMAT plans, delivered with the Varian TrueBeam linear accelerator, and compare the results with a commercial software product, following the guidelines set in AAPM Task Group 219. The TrueBeam is modeled in EGSnrc using the Varian-provided phase-space files. Thirteen VMAT TrueBeam treatment plans representing various anatomical regions were evaluated, comprising 37 treatment arcs. VMAT plans simulations were performed on a computing cluster, using 107 -109 particle histories per arc. Point dose differences at five reference points per arc were compared between Eclipse, MC, and the commercial software, MUCheck. MC simulation with 5 × 107 histories per arc offered good agreement with Eclipse and a reasonable average calculation time of 9-18 min per full plan. The average absolute difference was 3.0%, with only 22% of all points exceeding the 5% action limit. In contrast, the MUCheck average absolute difference was 8.4%, with 60% of points exceeding the 5% dose difference. Lung plans were particularly problematic for MUCheck, with an average absolute difference of approximately 16%. Our EGSnrc-based MC framework can be used for the MU verification of VMAT plans calculated for the Varian TrueBeam; furthermore, our phase space approach can be adapted to other treatment devices by using appropriate phase space files. The use of 5 × 107 histories consistently satisfied the 5% action limit across all plan types for the majority of points, performing significantly better than a commercial MU verification system, MUCheck. As faster processors and cloud computing facilities become even more widely available, this approach can be readily implemented in clinical settings.

A plan comparison study between rapid arc and conventional intensity-modulated radiation treatment plans in nasopharyngeal carcinoma patients.

Introduction: Head and neck cancers are one of the common malignancies in Indian population. It's entity, nasopharyngeal carcinoma is among the aggressive malignancies with its location and spread near very critical structures. Thus requires a highly conformal radiotherapy delivery techniques. Purpose: The aim of the study is to dosimetrically evaluate and to compare Intensity modulated radiation therapy (IMRT) plans and RAPID ARC plans for irradiation of nasopharyngeal carcinoma. Material and Method: A retrospective study is done on 10 nasopharyngeal carcinoma patients, who were treated with Radiotherapy at ATRCTRI Bikaner. Radiotherapy was delivered by IMRT technique (Total of 70 Gy in 33 fractions). Same patients are now planned on Rapid arc technique. Dosimetric comparison is done in terms of PTV coverage, OAR dose, conformity index, homogeneity index. Result: PTV coverage is similar with both the plans. Homogeneity index is higher for IMRT plans 0.119+/- 0.020 compared to 0.104 +/- 0.018 for Rapid arc plans (statistically significant).The Rapid arc plans achieved slightly better conformity 1.018+/-0.09, whereas 1.105+/-0.12 for IMRT plans. Rapid arc achieved better results for OAR, statistically significant for Brainstem (54.4 +/-10.4 Gy for IMRT and 49.7+/-4.2 Gy for Rapid Arc, Lens (Left lens and Right lens received 10.55+/-5.8 Gy and 9.44+/-9.08 by IMRT and 6.12+/-6.1 Gy and 5.45+/-6.05 Gy for Rapid Arc), optic nerves (Right and Left optic nerve received 34.36 and 35.01 Gy for IMRT plans and 30.06 and 30.05 Gy for Rapid Arc plans. However the gains are statistically insignificant for spinal cord and vestibulocochlear nerve. No major difference found for Right and left parotid between both the arms. Conclusions: Rapid Arc is better technique compared to IMRT for Nasopharyngeal carcinoma treatment, that provides better dose conformity, more homogeneous coverage and OAR sparing. However study is retrospective and has lesser patients, thus requires prospective study with more number of patients along with comparison of clinical outcome.

Volumetric Modulated Arc Therapy Planning for Craniospinal Irradiation With a New O-ring Linac.

This study aims to determine the feasibility of using a new O-ring linear accelerator (Halcyon, Varian Medical Systems, CA, USA) to perform treatment planning using volumetric modulated arc therapy (VMAT) for craniospinal irradiation (CSI). A 20-year-old male patient with leukemia was selected. The planning target volume (PTV) was contoured to include the entire contents of the brain and spinal canal. The PTV margin was 10 mm applied to the clinical target volume (CTV). VMAT (RapidArc, Varian Medical Systems, CA, USA) planning was performed using four isocenter with five arcs, two full rotation arcs to cover the brain and upper part of the spinal cord, and one full rotation arc for the lower part of the spinal cord. The plan was created using the auto-feathering photon optimizer calculation of the planning system. The conformity index (CI) and heterogeneity index (HI) as well as dose-volume histograms of organs at risk (OAR) were evaluated. The patient position of ±3.0 mm in the craniocaudal direction was moved in to simulate the effect of treatment inaccuracy. The total treatment time was also measured. The CI and HI were 1.09 and 8.44, respectively. The mean dose (PTV) was 105.5%, and the mean dose (OARs) was lower than the planning dose constraints. Simulations with a patient position shift of ±3.0 mm resulted in an error of less than ±10.0% of the planned dose to the spinal cord. The total treatment time was within 15 minutes. VMAT planning for CSI with Halcyon achieved high conformality, uniform dose distribution, low dose to the surrounding normal tissues, and reduced treatment time.

A Dosimetric Analysis of Modified Volumetric Modulated Arc Therapy for Bone Marrow Sparing Radiotherapy in Cervical Cancer-An alternative Approach to Conventional VMAT.

BACKGROUND: External beam radiotherapy remains the primary treatment modality in cervical cancer. Nowadays Intensity Modulated Radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are increasingly being used to reduce normal tissue toxicity. The drawback of conventional  VMAT is that a considerable volume of pelvic bone marrow receives a low dose. AIM: We analyzed whether there was a way to reduce the volume of the low dose regions of bone marrow, and assessed the potential benefit of conventional-4Arc (C-4Arc VMAT), and Modified-4Arc (M-4Arc VMAT) over the conventional 2 ARC VMAT. MATERIALS AND METHODS: Twelve clinically proven locally advanced cervical cancer patients treated with concurrent chemo-radiotherapy by Conventional VMAT (RapidArc) in dual rotation mode (C-2Arc VMAT) were selected for this study.C-4Arc VMAT and M-4Arc VMAT dose plans were generated for these twelve patients and these three different types of plans were evaluated for the quality and compared dosimetrically. RESULTS: M-4Arc VMAT designs exhibited a greater bone marrow sparing when compared with conventional VMATs with respect to volume receiving 5Gy to 35Gy without compromising PTV dose coverage. M-4Arc VMAT plans, the bone marrow volume receiving 30 Gy (V30Gy),40Gy (V40Gy), and mean doses were lower than the C- 4 Arc plan and a similar result was observed for V50(Gy) also when comparing with the standard 2 Arc plan. In modified VMAT plans, the rectum and bladder dose volumes were lower than standard VMAT. Similarly, the bowel bag V35(Gy), V40(Gy), V50(Gy), mean doses. The right and left femoral head doses were reduced significantly when compared to conventional VMAT plans. CONCLUSION: The M-4Arc VMAT plans are better than the C-2Arc and C-4Arc VMAT plans for reducing the dose to bone marrow by limiting the MLC field width travel.

Assessment of Statistical Process Control Based DVH Action Levels for Systematic Multi-Leaf Collimator Errors in Cervical Cancer RapidArc Plans.

Background: In the patient-specific quality assurance (QA), DVH is a critical clinically relevant parameter that is finally used to determine the safety and effectiveness of radiotherapy. However, a consensus on DVH-based action levels has not been reached yet. The aim of this study is to explore reasonable DVH-based action levels and optimal DVH metrics in detecting systematic MLC errors for cervical cancer RapidArc plans. Methods: In this study, a total of 148 cervical cancer RapidArc plans were selected and measured with COMPASS 3D dosimetry system. Firstly, the patient-specific QA results of 110 RapidArc plans were retrospectively reviewed. Then, DVH-based action limits (AL) and tolerance limits (TL) were obtained by statistical process control. Secondly, systematic MLC errors were introduced in 20 RapidArc plans, generating 380 modified plans. Then, the dose difference (%DE) in DVH metrics between modified plans and original plans was extracted from measurement results. After that, the linear regression model was used to investigate the detection limits of DVH-based action levels between %DE and systematic MLC errors. Finally, a total of 180 test plans (including 162 error-introduced plans and 18 original plans) were prepared for validation. The error detection rate of DVH-based action levels was compared in different DVH metrics of 180 test plans. Results: A linear correlation was found between systematic MLC errors and %DE in all DVH metrics. Based on linear regression model, the systematic MLC errors between -0.94 mm and 0.88 mm could be caught by the TL of PTV95 ([-1.54%, 1.51%]), and the systematic MLC errors between -1.00 mm and 0.80 mm could also be caught by the TL of PTVmean ([-2.06%, 0.38%]). In the validation, for original plans, PTV95 showed the minimum error detection rate of 5.56%. For error-introduced plans with systematic MLC errors more than 1mm, PTVmean showed the maximum error detection rate of 88.89%, and then was followed by PTV95 (86.67%). All the TL of DVH metrics showed a poor error detection rate in identifying error-induced plans with systematic MLC errors less than 1mm. Conclusion: In 3D quality assurance of cervical cancer RapidArc plans, process-based tolerance limits showed greater advantages in distinguishing plans introduced with systematic MLC errors more than 1mm, and reasonable DVH-based action levels can be acquired through statistical process control. During DVH-based verification, main focus should be on the DVH metrics of target volume. OARs in low-dose regions were found to have a relatively higher dose sensitivity to smaller systematic MLC errors, but may be accompanied with higher false error detection rate.

3D-CRT versus RapidArc in Deep Tempero-Parietal High Grade Gliomas: Do We Really Need Higher Technology?

PURPOSE: The aim of this study was to dosimetrically compare single arc RapidArc with conventional 3D-CRT plans for tempero-parietal high grade gliomas with respect to PTV coverage and doses perceived by surrounding critical organs at risk. METHODS: Thirty patients with the pathological diagnosis of high grade gliomas (WHO grade III-IV) were selected to be enrolled in our study. Patients were referred to our center (center of Clinical Oncology and Radiotherapy, Cairo University) during the period March 2020 till June 2021 for post-operative irradiation using 3D-CRT technique. For all patients, the dose prescribed to the planning target volume (PTV) was 60 Gy in 30 fractions. A RA plan was performed for each patient and dosimetrically was compared to the 3D-CRT plan. RESULTS: The PTV coverage in terms of V95% was significantly superior in the RA plans with values of 98.4 ± 1.7 compared to 94.4 ± 2.6 for the 3D-CRT plans (p-value of 0.004). The doses risk structures ( eyes, optic nerves and cochleae)  was lower with the RA plans as contrasted to the 3D-CRT plan with an exception for the  intraocular lens which received higher doses in the RA plan with a statistically significant p-value of 0.001 and 0.002 for the  Ipsilateral and contralateral lens, respectively. The average number of MUs ± SD was 358.6± 44.4 for the RA plans versus 247.6 ± 16.1 for 3D-CRT plans (p-value 0.001). The Dmean of healthy brain tissue was nearly equal for both plans (p-value of 0.071). CONCLUSION: The plans achieved by RA showed superior dose conformity, PTV coverage, more homogeneous dose distribution when contrasted to 3D-CRT plans. With the exception of both intraocular lenses, the RA plans showed better OAR sparing and utilized a higher number of MUs compared to the 3D-CRT.

Dosimetric Influence of Acuros XB Dose-to-Medium and Dose-to-Water Reporting Modes on Carcinoma Cervix Using Intensity-Modulated Radiation Therapy and Volumetric RapidArc Technique.

Aim: We aimed to evaluate the dosimetric influence of Acuros XB (AXB) dose-to-medium (Dm) and dose-to-water (Dw) reporting mode on carcinoma cervix using intensity-modulated radiation therapy (IMRT) and RapidArc (RA) technique. Materials and Methods: A cohort of thirty patients cared for carcinoma cervix was retrospectively selected for the study. Plans were computed using analytical anisotropic algorithm (AAA), AXB-Dm, and AXB-Dw algorithms for dosimetric comparison. A paired t-test and Pitman-Morgan dispersion test were executed to appraise the difference in mean values and the inter-patient variability of the differences. Results: The dose-volume parameters were higher for AXB-Dw in contrast to AAA for IMRT and RA plans, excluding D98%, minimum dose to planning target volume (PTV) and rectum mean dose (RA). There was no systematic trend observed in dose-volume parameters for PTV and organs at risk (OARs) between AXB-Dm and AXB-Dw for IMRT and RA plans. The dose-volume parameters for target were higher for AXB-Dm in comparison to AAA in IMRT and RA plans, except D98% and minimum dose to PTV. Analysis envisaged less inter-patient variability while switching from AAA to AXB-Dm in comparison to those switching from AAA to AXB-Dw. Conclusions: The present study reveals the important difference between AAA, AXB-Dm, and AXB-Dw computations for cervix carcinoma using IMRT and RA techniques. The inter-patient variability and systematic difference in dose-volume parameters computed using AAA, AXB-Dm, and AXB-Dw algorithms present the possible impact on the dose prescription to PTV and their relative constraints to OARs for IMRT and RA techniques. This may help in the decision-making in clinic while switching from AAA to AXB (Dm or Dw) algorithm for cervix carcinoma using IMRT and RA techniques.

Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients.

PURPOSE: To investigate the role of infra diaphragmatic intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for female Hodgkin Lymphoma (HL) patients and to estimate the risk of secondary cancer and ovarian failure. METHODS: A comparative treatment planning study was performed on 14 patients, and the results were compared according to conventional dose-volume metrics. In addition, estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the bowel, the bladder and the rectum. For the ovaries, the risk of ovarian failure was estimated. RESULTS: The dosimetric findings demonstrate the equivalence between VMAT and IMPT in terms of target coverage. A statistically significant reduction of the mean and near-to-maximum doses was proven for the organs at risk. The EAR ratio estimated for IMPT to VMAT was 0.51 ± 0.32, 0.32 ± 0.35 and 0.05 ± 0.11 for the bowel, bladder and rectum, respectively. Concerning the risk of ovarian failure for the chronologic age ranging from 18 to 46 years, the expected net loss in fertility years ranged from 4.8 to 3.0 years for protons and 12.0 to 5.7 years for photons. CONCLUSION: This in-silico study confirmed the beneficial role of IMPT from a dosimetric point of view. Mathematical models suggested that the use of protons might be further advantageous due to the expected reduction of the risk of secondary cancer induction and its milder impact on the reduction of fertility.

Dosimetric comparison and validation of Eclipse Anisotropic Analytical Algorithm (AAA) and AcurosXB (AXB) algorithms in RapidArc-based radiosurgery plans of patients with solitary brain metastasis.

Stereotactic radiosurgery (SRS) is increasingly being used to manage solitary or multiple brain metastasis. This study aims to compare and validate Anisotropic Analytical Algorithm (AAA) and AcurosXB (AXB) algorithms of Eclipse Treatment Planning System (TPS) in RapidArc-based SRS plans of patients with solitary brain metastasis. Twenty patients with solitary brain metastasis who have been already treated with RapidArc SRS plans calculated using AAA plans were selected for this study. These plans were recalculated using AXB algorithm keeping the same arc orientations, multi-leaf collimator apertures, and monitor units. The two algorithms were compared for target coverage parameters, isodose volumes, plan quality metrics, dose to organs at risk and integral dose. The dose calculated by the TPS using AAA and AXB algorithms was validated against measured dose for all patient plans using an in-house developed cylindrical phantom. An Exradin A14SL ionization chamber was positioned at the center of this phantom to measure the in-field dose. NanoDot Optically Stimulated Luminescent Dosimeters (OSLDs) (Landauer Inc.) were placed at distances 3.0 cm, 4.0 cm, 5.0 cm, and 6.0 cm respectively from the center of the phantom to measure the non-target dose. In addition, the planar dose distribution was measured using amorphous silicon aS1000 Electronic Portal Imaging Device. The measured 2D dose distribution was compared against AAA and AXB estimated 2D distribution using gamma analysis. All results were tested for significance using the paired t-test at 5% level of significance. Significant differences between the AAA and AXB plans were found only for a few parameters analyzed in this study. In the experimental verification using cylindrical phantom, the difference between the AAA calculated dose and the measured dose was found to be highly significant (p < 0.001). However, the difference between the AXB calculated dose and the measured dose was not significant (p = 0.197). The difference between AAA/AXB calculated and measured at non-target locations was statistically insignificant at all four non-target locations and the dose calculated by both AAA and AXB algorithms shows a strong positive correlation with the measured dose. The results of the gamma analysis show that the AXB calculated planar dose is in better agreement with measurements compared to the AAA. Even though the results of the dosimetric comparison show that the differences are mostly not significant, the measurements show that there are differences between the two algorithms within the target volume. The AXB algorithm may be therefore more accurate in the dose calculation of VMAT plans for the treatment of small intracranial targets. For non-target locations either algorithm can be used for the estimation of dose accounting for their limitations in non-target dose estimations.

Dosimetric validation of Acuros® XB algorithm for RapidArc™ treatment technique: A post software upgrade analysis.

AIM: To validate the Acuros® XB (AXB) algorithm in Eclipse treatment planning system (TPS) for RapidArc™ (RA) technique following the software upgrades. MATERIALS AND METHODS: A Clinac-iX (2300CD) linear accelerator and Eclipse TPS (Varian Medical System, Inc., Palo Alto, USA) was used for commissioning of AXB algorithm using a 6 megavolts photon beam. Percentage depth dose (PDD) and profiles for field size 2 cm × 2 cm, 4 cm × 4 cm, 6 cm × 6 cm, 10 cm × 10 cm, 20 cm × 20 cm, 30 cm × 30 cm to 40 cm × 40 cm were taken. AXB calculated PDDs and profiles were evaluated against the measured and analytical anisotropic algorithm (AAA)-calculated PDDs and profiles. Test sites recommended by American Association of Physicists in Medicine task group (AAPM TG)-119 recommendation were used for RA planning and delivery verification using AXB algorithm.Dosimetric analysis of AXB calculated data showed that difference between calculated and measured data for PDD curves were maximum <1% beyond the depth of dose maximum and computed profiles in central region matches with maximum <1% for all considered field sizes. Ion-chamber measurements showed that the average confidence limit (CLs) was 0.034 and 0.020 in high-gradient and 0.047 and 0.042 in low-gradient regions, respectively, for AAA and AXB calculated RA plans. Portal measurements show the average CLs were 2.48 and 2.58 for AAA and AXB-calculated RA plans, with gamma passing criteria of 3%/3 mm. CONCLUSIONS: AXB shows excellent agreement with measurements and AAA calculated data. The CLs were consistent with the baseline values published by TG-119. AXB algorithm has the potential to perform photon dose calculation with comparable fast calculation speed without negotiating the accuracy. AAPM TG-119 was successfully implemented to access the proper configuration of AXB algorithm following the TPS upgrade.

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy.

BACKGROUND: This study aimed to investigate radiation-induced lymphopenia and its potential risk factors in patients with breast cancer receiving adjuvant radiotherapy. METHODS: Breast cancer patients received adjuvant radiotherapy (RT) at our hospital with peripheral lymphocyte counts (PLC) at pre-and immediately after RT (post-RT) were eligible. The primary endpoints were any grade of lymphopenia post-RT and nadir-PLC/pre-PLC <0.8. Patient characteristics, tumor factors, and treatment factors were collected for risk assessment. Data are presented as mean and 95% confidence interval (CI) unless otherwise specified. Matched analysis was used to compare the statistical significance between different RT techniques. RESULTS: A total of 735 consecutive patients met the study criteria. The mean PLC was 1.58×109/L before and 0.99×109/L post-RT (P<0.001). At the end of RT, 60.5% of patients had lymphopenia. Univariate and multivariable logistic analyses showed that RT technique involving RapidArc, mean lung dose, and chemotherapy were significant risk factors (P<0.05) for lymphopenia. RT technique was the only significant risk factor (P<0.05) for nadir-PLC/pre-PLC <0.8. Patients treated with RapidArc had a significantly greater reduction of PLC along with greater V5 of the lungs, even after matching mean lung dose and radiated volume. CONCLUSIONS: Lymphopenia is common in patients with breast cancer after adjuvant RT. RT technique is the only significant factor for lymphopenia and nadir-PLC/pre-PLC <0.8, suggesting the significance of RT technique choice to minimize lymphopenia and improve treatment outcomes.

Dosimetric impact of Acuros XB on cervix radiotherapy using RapidArc technique: a dosimetric study.

BACKGROUND: Acuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations. MATERIALS AND METHODS: A cohort of 30 patients previously cared for cervix carcinoma (stages II-IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern. RESULTS: There was no significant (p > 0.05) difference in D95% and D98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D50% (0.26%), D2% (0.80%) and V110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D2% of the left femur and right femur, respectively, between AA and AXB dose estimations. CONCLUSION: For similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V50Gy of the rectum and overestimates the mean dose and D2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.

A novel external beam radiotherapy method for cervical cancer patients using virtual straight or bending boost areas; an in-silico feasibility study.

AIM: To investigate the potential role of a novel spatially fractionated radiation therapy (SFRT) method where heterogeneous dose patterns are created in target areas with virtual rods, straight or curving, of variable position, diameter, separation and alignment personalised to a patient's anatomy. The images chosen for this study were CT scans acquired for the external beam part of radiotherapy. METHODS: Ten patients with locally advanced cervical cancer were retrospectively investigated with SFRT. The dose prescription was 30 Gy in 5 fractions to 90% target volume coverage. Peak-and-valley (SFRT_1) and peak-only (SFRT_2) strategies were applied to generate the heterogeneous dose distributions. The planning objectives for the target (CTV) were D90% ≥ 30 Gy, V45Gy ≥ 50-55% and V60Gy ≥ 30%. The planning objectives for the organs at risk (OAR) were: D2cm3 ≤ 23.75 Gy, 17.0 Gy, 19.5 Gy, 17.0 Gy for the bladder, rectum, sigmoid and bowel, respectively. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. RESULTS: The D2cm3 was 22.4 ± 2.0 (22.6 ± 2.1) and 13.9 ± 2.9 (13.2 ± 3.0) for the bladder and the rectum for SFRT_1 (SFRT_2). The results for the sigmoid and the bowel were 2.6 ± 3.1 (2.8 ± 3.0) and 9.1 ± 5.9 (9.7 ± 7.3), respectively. The hotspots in the target volume were V45Gy = 43.1 ± 7.5% (56.6 ± 5.6%) and V60Gy = 15.4 ± 5.6% (26.8 ± 6.6%) for SFRT_1 (SFRT_2). To account for potential uncertainties in the positioning, the dose prescription could be escalated to D90% = 33-35 Gy to the CTV without compromising any constraints to the OARs CONCLUSION: In this dosimetric study, the proposed novel planning technique for boosting the cervix uteri was associated with high-quality plans, respecting constraints for the organs at risk and approaching the level of dose heterogeneity achieved with routine brachytherapy. Based on a sample of 10 patients, the results are promising and might lead to a phase I clinical trial.

Knowledge-Based Volumetric Modulated Arc Therapy Treatment Planning for Breast Cancer.

Purpose: To create and to validate knowledge-based volumetric modulated arc therapy (VMAT) models for breast cancer treatments without lymph node irradiation. Materials and Methods: One hundred VMAT-based breast plans (manual plans [MP]) were selected to create two knowledge-based VMAT models (breast left and breast right) using RapidPlan™. The plans were generated on Eclipse v15.5 (Varian Medical Systems, Palo Alto, CA) with 6 MV of a Novalis Tx equipped with a high-resolution multileaf collimator. The models were verified based on goodness-of-fit statistics using the coefficients of determination (R 2) and Chi-square (χ2), and the goodness-of-estimation statistics through the mean square error (MSE). Geometrical and dosimetrical constraints were identified and removed from the RP models using statistical evaluation metrics and plots. For validation, 20 plans that integrate the models and 20 plans that do not were reoptimized with RP (closed and opened validation). Dosimetrical parameters of interest were used to compare MP versus RP plans for the Heart, Homolateral_Lung, Contralateral_Lung, and Contralateral_Breast. Optimization planning time and user independency were also analyzed. Results: The most unfavorable results of R2 in both models for the organs at risk were as follows: for Contralateral_Lung 0.51 in RP right breast (RP_RB) and for Heart 0.60 in RP left breast (RP_LB). The most unfavorable results of χ2 test were: for Contralateral_Breast 1.02 in RP_RB and for Heart 1.03 in RP_LB. These goodness-of-fit results show that no overfitting occurred in either of the models. There were no unfavorable results of mean square error (MSE, all < 0.05) in any of the two models. These goodness-of-estimation results show that the models have good estimation power. For closed validation, significant differences were found in RP_RB for Homolateral_Lung (all P ≤ 0.001), and in the RP_LB differences were found for the heart (all P ≤ 0.04) and for Homolateral_Lung (all P ≤ 0.022). For open validation, no statistically significant differences were obtained in either of the models. RP models had little impact on reducing optimization planning times for expert planners; nevertheless, the result showed a 30% reduction time for beginner planners. The use of RP models generates high-quality plans, without differences from the planner experience. Conclusion: Two RP models for breast cancer treatment using VMAT were successfully implemented. The use of RP models for breast cancer reduces the optimization planning time and improves the efficiency of the treatment planning process while ensuring high-quality plans.

The role of a knowledge based dose-volume histogram predictive model in the optimisation of intensity-modulated proton plans for hepatocellular carcinoma patients : Training and validation of a novel commercial system.

PURPOSE: To investigate the performance of a knowledge-based RapidPlan, for optimisation of intensity-modulated proton therapy (IMPT) plans applied to hepatocellular cancer (HCC) patients. METHODS: A cohort of 65 patients was retrospectively selected: 50 were used to "train" the model, while the remaining 15 provided independent validation. The performance of the RapidPlan model was benchmarked against manual optimisation and was also compared to volumetric modulated arc therapy (RapidArc) photon plans. A subanalysis appraised the performance of the RapidPlan model applied to patients with lesions ≤300 cm3 or larger. Quantitative assessment was based on several metrics derived from the constraints of the NRG-GI003 clinical trial. RESULTS: There was an equivalence between manual plans and RapidPlan-optimised IMPT plans, which outperformed the RapidArc plans. The planning dose-volume objectives were met on average for all structures except for D0.5 cm3 ≤30 Gy in the bowels. Limiting the results to the class-solution proton plans (all values in Gy), the data for manual plans vs RapidPlan-based IMPT plans, respectively, showed the following: D99% to the target of 47.5 ± 1.4 vs 47.2 ± 1.2; for organs at risk, the mean dose to the healthy liver was 6.7 ± 3.6 vs 6.7 ± 3.7; the mean dose to the kidneys was 0.2 ± 0.5 vs 0.1 ± 0.2; D0.5 cm3 for the bowels was 33.4 ± 16.4 vs 30.2 ± 16.0; for the stomach was 17.9 ± 19.9 vs 14.9 ± 18.8; for the oesophagus was 17.9 ± 15.1 vs 14.9 ± 13.9; for the spinal cord was 0.5 ± 1.6 vs 0.2 ± 0.7. The model performed similarly for cases with small or large lesions. CONCLUSION: A knowledge-based RapidPlan model was trained and validated for IMPT. The results demonstrate that RapidPlan can be trained adequately for IMPT in HCC. The quality of the RapidPlan-based plans is at least equivalent compared to what is achievable with manual planning. RapidPlan also confirmed the potential to optimise the quality of the proton therapy results, thus reducing the impact of operator planning skills on patient results.

The Potential Role of Intensity-Modulated Proton Therapy in Hepatic Carcinoma in Mitigating the Risk of Dose De-Escalation.

PURPOSE: To investigate the role of intensity-modulated proton therapy (IMPT) for hepatocellular carcinoma (HCC) patients to be treated with stereotactic body radiation therapy (SBRT) in a risk-adapted dose prescription regimen. METHODS: A cohort of 30 patients was retrospectively selected as "at-risk" of dose de-escalation due to the proximity of the target volumes to dose-limiting healthy structures. IMPT plans were compared to volumetric modulated arc therapy (VMAT) RapidArc (RA) plans. The maximum dose prescription foreseen was 75 Gy in 3 fractions. The dosimetric analysis was performed on several quantitative metrics on the target volumes and organs at risk to identify the relative improvement of IMPT over VMAT and to determine if IMPT could mitigate the need of dose reduction and quantify the consequent potential patient accrual rate for protons. RESULTS: IMPT and VMAT plans resulted in equivalent target dose distributions: both could ensure the required coverage for CTV and PTV. Systematic and significant improvements were observed with IMPT for all organs at risk and metrics. An average gain of 9.0 ± 11.6, 8.5 ± 7.7, 5.9 ± 7.1, 4.2 ± 6.4, 8.9 ± 7.1, 6.7 ± 7.5 Gy was found in the near-to-maximum doses for the ribs, chest wall, heart, duodenum, stomach and bowel bag respectively. Twenty patients violated one or more binding constraints with RA, while only 2 with IMPT. For all these patients, some dose de-intensification would have been required to respect the constraints. For photons, the maximum allowed dose ranged from 15.0 to 20.63 Gy per fraction while for the 2 proton cases it would have been 18.75 or 20.63 Gy. CONCLUSION: The results of this in-silico planning study suggests that IMPT might result in advantages compared to photon-based VMAT for HCC patients to be treated with ablative SBRT. In particular, the dosimetric characteristics of protons may avoid the need for dose de-escalation in a risk-adapted prescription regimen for those patients with lesions located in proximity of dose-limiting healthy structures. Depending on the selection thresholds, the number of patients eligible for treatment at the full dose can be significantly increased with protons.