MU variability in CBCT-guided online adaptive radiation therapy.

PURPOSE: CBCT-guided online-adaptive radiotherapy (oART) systems have been made possible by using artificial intelligence and automation to substantially reduce treatment planning time during on-couch adaptive sessions. Evaluating plans generated during an adaptive session presents significant challenges to the clinical team as the planning process gets compressed into a shorter window than offline planning. We identified MU variations up to 30% difference between the adaptive plan and the reference plan in several oART sessions that caused the clinical team to question the accuracy of the oART dose calculation. We investigated the cause of MU variation and the overall accuracy of the dose delivered when MU variations appear unnecessarily large. METHODS: Dosimetric and adaptive plan data from 604 adaptive sessions of 19 patients undergoing CBCT-guided oART were collected. The analysis included total MU per fraction, planning target volume (PTV) and organs at risk (OAR) volumes, changes in PTV-OAR overlap, and DVH curves. Sessions with MU greater than two standard deviations from the mean were reoptimized offline, verified by an independent calculation system, and measured using a detector array. RESULTS: MU variations relative to the reference plan were normally distributed with a mean of -1.0% and a standard deviation of 11.0%. No significant correlation was found between MU variation and anatomic changes. Offline reoptimization did not reliably reproduce either reference or on-couch total MUs, suggesting that stochastic effects within the oART optimizer are likely causing the variations. Independent dose calculation and detector array measurements resulted in acceptable agreement with the planned dose. CONCLUSIONS: MU variations observed between oART plans were not caused by any errors within the oART workflow. Providers should refrain from using MU variability as a way to express their confidence in the treatment planning accuracy. Clinical decisions during on-couch adaptive sessions should rely on validated secondary dose calculations to ensure optimal plan selection.

Case study with dosimetric analysis: Total body irradiation to a patient with a left ventricular assist device.

Key Clinical Message: A patient presented with cardiogenic shock, requiring the implantation of a left ventricular assist device (LVAD), and acute myeloblastic leukemia. This necessitated total body irradiation (TBI) while balancing dose reduction to the LVAD components to avoid potential radiation damage. Here we outline our treatment approach and dose estimates to the LVAD. Abstract: This case report discusses the delivery of TBI to a patient with an LVAD. This treatment required radiation-dose determinations and consequential reductions for the heart, LVAD, and an external controller connected to the LVAD. The patient was treated using a traditional 16MV anterior posterior (AP)/posterior anterior (PA) technique at a source-to-surface-distance of 515 cm for 400 cGy in two fractions. A 3 cm thick Cerrobend block was placed on the beam spoiler to reduce dose to the heart and LVAD to 150 cGy. The external controller was placed in a 1 cm thick acrylic box to reduce neutron dose and positioned as far from the treatment fields as achievable. In vivo measurements were made using optically stimulated luminescence dosimeters (OSLDs) placed inside the box at distances of 2 cm, 8.5 cm, and 14 cm from the field edge, and on the patient along the central axis and centered behind the LVAD block. Further ion chamber measurements were made using a solid water phantom to more accurately estimate the dose delivered to the LVAD. Neutron dose measurements were also conducted. The total estimated dose to the controller ranged from 135.3 cGy to 91.5 cGy. The LVAD block reduced the surface dose to the patient to 271.6 cGy (68.1%). The block transmission factors of the 3 cm Cerrobend block measured in the phantom were 45% at 1 cm depth and decreased asymptotically to around 30% at 3 cm depth. Applying these transmission factors to the in vivo measurements yielded a dose of 120 cGy to the implanted device. The neutron dose the LVAD region is estimated around 0.46 cGy. Physical limitations of the controller made it impossible to completely avoid dose. Shielding is recommended. The block had limited dose reduction to the surface, due to secondary particles, but appropriately reduced the dose at 3 cm and beyond. More research on LVADs dose limits would be beneficial.

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.

A comprehensive evaluation of advanced dose calculation algorithms for brain stereotactic radiosurgery.

PURPOSE: Accurate dose calculation is important in both target and low dose normal tissue regions for brain stereotactic radiosurgery (SRS). In this study, we aim to evaluate the dosimetric accuracy of the two advanced dose calculation algorithms for brain SRS. METHODS: Retrospective clinical case study and phantom study were performed. For the clinical study, 138 SRS patient plans (443 targets) were generated using BrainLab Elements Voxel Monte Carlo (VMC). To evaluate the dose calculation accuracy, the plans were exported into Eclipse and recalculated with Acuros XB (AXB) algorithm with identical beam parameters. The calculated dose at the target center (Dref), dose to 95% target volume (D95), and the average dose to target (Dmean) were compared. Also, the distance from the skull was analyzed. For the phantom study, a cylindrical phantom and a head phantom were used, and the delivered dose was measured by an ion chamber and EBT3 film, respectively, at various locations. The measurement was compared with the calculated doses from VMC and AXB. RESULTS: In clinical cases, VMC dose calculations tended to be higher than AXB. It was found that the difference in Dref showed > 5% in some cases for smaller volumes < 0.3 cm3 . Dmean and D95 differences were also higher for small targets. No obvious trend was found between the dose difference and the distance from the skull. In phantom studies, VMC dose was also higher than AXB for smaller targets, and VMC showed better agreement with the measurements than AXB for both point dose and high dose spread. CONCLUSION: The two advanced calculation algorithms were extensively compared. For brain SRS, AXB sometimes calculates a noticeable lower target dose for small targets than VMC, and VMC tends to have a slightly closer agreement with measurements than AXB.

Influence of air mapping errors on the dosimetric accuracy of prostate CBCT-guided online adaptive radiation therapy.

PURPOSE: CBCT-guided online adaptive radiotherapy (oART) plans presently utilize daily synthetic CTs (sCT) that are automatically generated using deformable registration algorithms. These algorithms may have poor performance at reproducing variable volumes of gas present during treatment. Therefore, we have analyzed the air mapping error between the daily CBCTs and the corresponding sCT and explored its dosimetric effect on oART plan calculation. METHODS: Abdominopelvic air volume was contoured on both the daily CBCT images and the corresponding synthetic images for 207 online adaptive pelvic treatments. Air mapping errors were tracked over all fractions. For two case studies representing worst case scenarios, dosimetric effects of air mapping errors were corrected in the sCT images using the daily CBCT air contours, then recalculating dose. Dose volume histogram statistics and 3D gamma passing rates were used to compare the original and air-corrected sCT-based dose calculations. RESULTS: All analyzed patients showed observable air pocket contour differences between the sCT and the CBCT images. The largest air volume difference observed in daily CBCT images for a given patient was 276.3 cc, a difference of more than 386% compared to the sCT. For the two case studies, the largest observed change in DVH metrics was a 2.6% reduction in minimum PTV dose, with all other metrics varying by less than 1.5%. 3D gamma passing rates using 1%/1 mm criteria were above 90% when comparing the uncorrected and corrected dose distributions. CONCLUSION: Current CBCT-based oART workflow can lead to inaccuracies in the mapping of abdominopelvic air pockets from daily CBCT to the sCT images used for the optimization and calculation of the adaptive plan. Despite the large observed mapping errors, the dosimetric effects of such differences on the accuracy of the adapted plan dose calculation are unlikely to cause differences greater than 3% for prostate treatments.

New dosimetric guidelines for linear Boltzmann transport equations through comparative evaluation of stereotactic body radiation therapy for lung treatment planning.

PURPOSE: To propose guidelines for lung stereotactic body radiation therapy (SBRT) when using Acuros XB (AXB) equivalent to the existing ones developed for convolution algorithms such as analytic anisotropic algorithm (AAA), considering the difference between the algorithms. METHODS: A retrospective analysis was performed on 30 lung patients previously treated with SBRT. The original AAA plans, which were developed using dynamic conformal arcs, were recalculated and then renormalized for planning target volume (PTV) coverage using AXB. The recalculated and renormalized plans were compared to the original plans based on V100% and V90% PTV coverage, as well as V105%, conformality index, D2cm , Rx/Dmax , R50, and Dmin . These metrics were analyzed nominally and on variations according to RTOG and NRG guidelines. Based on the relative difference between each metric in the AAA and AXB plans, new guidelines were developed. The relative differences in our cohort were compared to previously documented AAA to AXB comparisons found in the literature. RESULTS: AAA plans recalculated in AXB had a significant reduction in most dosimetric metrics. The most notable changes were in V100% (4%) and the conformality index (7.5%). To achieve equal PTV coverage, AXB required an average of 1.8% more monitor units (MU). This fits well with previously published data. Applying the new guidelines to the AXB plans significantly increased the number of minor violations with no change in major violations, making them comparable to those of the original AAA plans. CONCLUSION: The relative difference found between AAA and AXB for SBRT lung plans has been shown to be consistent with previous works. Based on these findings, new guidelines for lung SBRT are recommended when planning with AXB.

In Vivo Imaging of the Microglial Landscape After Whole Brain Radiation Therapy.

PURPOSE: Whole brain radiation therapy (WBRT) is an important treatment for patients with multiple brain metastases, but can also cause cognitive deterioration. Microglia, the resident immune cells of the brain, promote a proinflammatory environment and likely contribute to cognitive decline after WBRT. To investigate the temporal dynamics of the microglial reaction in individual mice to WBRT, we developed a novel in vivo experimental model using cranial window implants and longitudinal imaging. METHODS AND MATERIALS: Chronic cranial windows were surgically implanted over the somatosensory cortex of transgenic Cx3cr1-enhanced green fluorescent protein (EGFP)/+ C57BL/6 mice, where microglia were fluorescently tagged with EGFP. Cx3cr1-EGFP/+ mice were also crossed with Thy1-YFP mice to fluorescently dual label microglia and subsets of neurons throughout the brain. Three weeks after window implantation and recovery, computed tomography image guided WBRT was delivered (single dose 10 Gy using two 5 Gy parallel-opposed lateral beams). Radiation dosing was confirmed using radiochromic film. Then, in vivo 2-photon microscopy was used to longitudinally image the microglial landscape and microglial motility at 7 days and 16 days after irradiation in the same mice. RESULTS: Film dosimetry confirmed the average delivered dose per beam at midpoint was accurate within 2%, with no attenuation from the window frame. By 7 days after WBRT, significant changes in the microglial landscape were seen, characterized by apparent loss of microglial cells (20%) and significant rearrangements of microglial location with time after irradiation (36% of cells not found in original location). CONCLUSIONS: Using longitudinal in vivo 2-photon imaging, this study demonstrated the feasibility of imaging microglia-neuron interactions and defining how microglia react to WBRT in the same mouse. Having demonstrated utility of the model, this experimental paradigm can be used to investigate the dynamic changes of many different brain cell types and their interactions after WBRT and uncover the underlying cellular mechanisms of WBRT-induced cognitive decline.

Advantages of real-time transabdominal ultrasound guidance in combined interstitial/intracavitary cervical brachytherapy: a case-based review.

Sub-optimal placement of both intracavitary devices and interstitial needles is a relatively common occurrence in cervical brachytherapy, which may reduce the accuracy of dose distribution and contribute to adverse toxicities. To mitigate complications, improve target dose coverage, and verify proper device placement, implants may be placed under real-time image guidance. Traditionally, transrectal ultrasound has been used for needle guidance. However, we have utilized transabdominal ultrasound (TA-US) in our brachytherapy center. The purpose of this pictorial essay was to provide a pictorial description of TA-US technique, present a retrospective review of our preliminary outcomes adopting TA-US into routine practice, and to discuss the advantages of real-time ultrasound image guidance for placement of intrauterine tandem and interstitial needles.

Heterogeneous Versus Homogeneous Radiation Dose Calculations of Twice-Daily Fractionation in Small Cell Lung Carcinoma.

Purpose The standard radiotherapy regimen for small cell lung cancer (SCLC) was determined using dose calculations without corrections for tissue heterogeneity, while modern treatments are planned using algorithms accounting for tissue heterogeneity. We assessed differences in dose delivered using heterogeneous and homogeneous dose calculations in a cohort of patients treated for limited-stage small cell lung cancer (LS-SCLC). Methods This is a retrospective analysis of 35 patients (three-dimensional conformal radiation therapy (3D-CRT), n = 22; intensity-modulated radiation therapy (IMRT), n = 13) with LS-SCLC treated with chemoradiotherapy from 2011 to 2017. Treatment plans were developed in the Eclipse Treatment Planning System (TPS) version 13.6 using the Analytical Anisotropic Algorithm (AAA). Two plans were generated for each patient with one using the unit relative electron density and the other maintaining the same monitor units (MUs) with tissue density corrections. The prescription was 45 Gy in 30 fractions of 1.5 Gy delivered twice daily. Individuals who underwent replanning within the same treatment course were evaluated using a separate corrected and uncorrected plan sum. Variations greater than 5% in dose to the tumor or organs at risk were considered clinically relevant. A two-sided paired t-test was used to evaluate the statistical significance of the dosimetric differences. Results The percent dose difference between plans without tissue heterogeneity corrections to those with corrections resulted in an overall median difference of -3% (range: -15.1% to 9.6%; p < 0.01) for the dose covering 95% of the planning target volume (PTV D95) and was -5.6% (range: -17.3% to 5.4%; p < 0.01) for lung volume receiving ≥20 Gy (lung V20). For 3D-CRT, the median difference for the PTV D95 was -0.1% (range: -4.7% to 9.6%; p = 0.62) and the lung V20 was -4.2% (range: -9.4 to 5.4; p < 0.01). For IMRT, the median difference for the PTV D95 was -10.0% (range: -15.1% to -5.3%; p < 0.01) and the lung V20 was -8.9% (range: -17.3 to -3.5; p < 0.01). Conclusion Traditional planning without tissue heterogeneity corrections results in an overall decrease in the dose delivered to the target compared with those that incorporate tissue heterogeneity corrections. These differences are modest for 3D treatment plans but may result in clinically relevant differences for the IMRT cohort (>5% deviation).

Dosimetric comparison of the INTRABEAM and Axxent for intraoperative breast radiotherapy.

PURPOSE: Breast intraoperative radiotherapy with electronic brachytherapy (eBT) sources, such as the Zeiss INTRABEAM and the Xoft Axxent, are used to treat the lumpectomy cavity using a stationary or a stepped 50 kVp X-ray source, respectively. For three comparable applicator sizes with volume differences <11%, we compare the dosimetry using clinical planning data. METHODS AND MATERIALS: A dosimetric comparison between the INTRABEAM and Axxent to the proximal 1.0 cm of tissue surrounding the applicator is performed using dose-volume parameters (DVPs): V90, V80, V50, Dmin, and Homogeneity Index (HI); HI was calculated as Dmax/Dmin. The dose-volume histograms of the INTRABEAM and Axxent were computed with measured percent depth dose data and with TG-43 parameters, respectively. The skin dose of 0.7-1.0 cm from the applicator surface was also computed. RESULTS: The mean DVPs were 5.5 ± 0.8% V90, 12.1 ± 1.5% V80, 47.5 ± 5.8% V50, 6.4 ± 0.6 Gy Dmin, and 3.2 ± 0.3 HI for the INTRABEAM applicators compared with 7.4 ± 0.3% V90, 14.7 ± 0.8% V80, 55.2 ± 4.7% V50, 4.0 ± 0.6 Gy Dmin, and 6.4 ± 1.1 HI for the Axxent applicators. INTRABEAM skin doses ranged from 7.7 to 9.0 Gy at 0.7 cm to 5.5-6.8 Gy at 1.0 cm, whereas Axxent skin doses ranged from 10.7 to 13.0 Gy at 0.7 cm to 7.8 to 9.3 Gy at 1.0 cm. CONCLUSIONS: We demonstrated ±5% comparable dosimetric coverage for tissue ≤0.5 cm from the cavity and higher skin dose for Axxent plans. The DVPs increased with applicator size and with stepped treatment delivery.

Outcomes Following Stereotactic Body Radiotherapy with Intensity-Modulated Therapy versus Three-Dimensional Conformal Radiotherapy in Early Stage Non-Small Cell Lung Cancer.

INTRODUCTION: The treatment techniques used for stereotactic body radiation therapy (SBRT) for early-stage lung cancer continue to evolve. In this study, clinical outcomes following SBRT were evaluated according to the use of either 3D conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: Patients with stage I NSCLC who received SBRT from 2007 to 2015 were retrospectively reviewed. Disease control and survival were assessed using Kaplan-Meier estimates. Dosimetric analyses for target dose heterogeneity and coverage were performed. RESULTS: A total of 297 patients with 351 lesions were included. 3DCRT was used in 52% and IMRT in 48%. IMRT was utilized at a higher rate in more recent years. The most common regimens were 48 Gy in 4 fractions and 54-60 Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local failure did not differ in patients treated with 3DCRT and IMRT (4.9% vs 6.5%, p=0.573). Mean dose to gross tumor volume (GTV) as a percent of prescription dose was higher with 3DCRT compared with IMRT (107.7% vs 103.6%, p < 0.0001). Tumor stage, histology, and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment was well tolerated with 6 documented grade 3+ events. CONCLUSION: In this single-institution cohort of SBRT for early-stage NSCLC, there was no discernible difference in clinical outcomes between those treated with 3DCRT and IMRT.

Clinical outcomes following advanced respiratory motion management (respiratory gating or dynamic tumor tracking) with stereotactic body radiation therapy for stage I non-small-cell lung cancer.

PURPOSE: To report the outcomes of stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) according to respiratory motion management method. METHODS: Patients with stage I NSCLC who received SBRT from 2007 to 2015 were reviewed. Computed tomography (CT) simulation with four-dimensional CT was performed for respiratory motion assessment. Tumor motion >1 cm in the craniocaudal direction was selectively treated with advanced respiratory management: either respiratory gating to a pre-specified portion of the respiratory cycle or dynamic tracking of an implanted fiducial marker. Comparisons were made with internal target volume approach, which treated all phases of respiratory motion. RESULTS: Of 297 patients treated with SBRT at our institution, 51 underwent advanced respiratory management (48 with respiratory gating and three with tumor tracking) and 246 underwent all-phase treatment. Groups were similarly balanced with regard to mean age (P=0.242), tumor size (P=0.315), and histology (P=0.715). Tumor location in the lower lung lobes, as compared to middle or upper lobes, was more common in those treated with advanced respiratory management (78.4%) compared to all-phase treatment (25.6%, P<.0001). There were 17 local recurrences in the treated lesions. Kaplan-Meier analyses showed that there were no differences with regard to mean time to local failure (91.5 vs 98.8 months, P=0.56), mean time to any failure (73.2 vs 78.7 months, P=0.73), or median overall survival (43.3 vs 45.5 months, P=0.56) between patients who underwent advanced respiratory motion management and all-phase treatment. CONCLUSION: SBRT with advanced respiratory management (the majority with respiratory gating) showed similar efficacy to all-phase treatment approach for stage I NSCLC.

Correction factor measurements for multiple detectors used in small field dosimetry on the Varian Edge radiosurgery system.

PURPOSE: Accurate dosimetry of small fields remains a challenge to the clinical physicist. Choosing the appropriate detector and determination of kQclin,Qmsr (fclin,fmsr) factors continue to be an area of active research. The purpose of this study is to evaluate the output factors for a dedicated stereotactic accelerator using multiple dosimeters designed for use in small fields and evaluate published kQclin,Qmsr (fclin,fmsr) factors relative to measured values using a commercial scintillating fiber. METHODS: Four microionization chambers, a commercial plastic scintillation detector, and a semiconducting diode were used to measure output factors for a linear accelerator. Field sizes ranging from 6 × 6 to 0.6 × 0.6 cm(2) were measured in a water phantom at 10 cm depth for 100 cm SSD. All microionization chambers were mounted in both vertical and horizontal configurations. Fields were normalized to the output at 5 × 5 cm(2). Output correction factors, kQclin,Qmsr (fclin,fmsr), were calculated as the ratio of a detector response relative to the scintillating fiber response for a given clinical field size, fclin. RESULTS: Ionization chambers consistently under-responded for small fields relative to the scintillating fiber. Variations in response between horizontal and vertical mounting were most notable for the microchambers, with the vertical mounting which reduced the magnitude of the necessary correction factor, kQclin,Qmsr (fclin,fmsr), for the microionization chambers ranging from 1.1 to 1.2 for the smallest field size at all energies. The semiconducting diode over-responded by 7% for the smallest field size across all energies, resulting in a kQclin,Qmsr (fclin,fmsr) of ∼ 0.93. CONCLUSIONS: The commercial scintillating fiber, which produces accurate and consistent ratios of dose to water for nonstandard fields, can be used to measure correction factors for various detectors used in a clinical setting. This can allow for comparison of measured correction factors to previously published values.