Radiation therapy margin reduction for patients with localized prostate cancer: A prospective study of the dosimetric impact and quality of life.

OBJECTIVES: To investigate the impact of reducing Clinical Target Volume (CTV) to Planning Target Volume (PTV) margins on delivered radiation therapy (RT) dose and patient reported quality-of-life (QOL) for patients with localized prostate cancer. METHODS: Twenty patients were included in a single institution IRB-approved prospective study. Nine were planned with reduced margins (4 mm at prostate/rectum interface, 5 mm elsewhere), and 11 with standard margins (6/10 mm). Cumulative delivered dose was calculated using deformable dose accumulation. Each daily CBCT dataset was deformed to the planning CT (pCT), dose was computed, and accumulated on the resampled pCT using a parameter-optimized, B-spline algorithm (Elastix, ITK/VTK). EPIC-26 patient reported QOL was prospectively collected pre-treatment, post-treatment, and at 2-, 6-, 12-, 18-, 24-, 36-, 48-, and 60-month follow-ups. Post -RT QOL scores were baseline corrected and standardized to a [0-100] scale using EPIC-26 methodology. Correlations between QOL scores and dosimetric parameters were investigated, and the overall QOL differences between the two groups (QOLMargin-reduced -QOLcontrol ) were calculated. RESULTS: The median QOL follow-up length for the 20 patients was 48 months. Difference between delivered dose and planned dose did not reach statistical significance (p > 0.1) for both targets and organs at risk between the two groups. At 4 years post-RT, standardized mean QOLMargin-reduced -QOLcontrol were improved for Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, and Sexual EPIC domains by 3.5, 14.8, 10.2, and 16.1, respectively (higher values better). The control group showed larger PTV/rectum and PTV/bladder intersection volumes (7.2 ± 5.8, 18.2 ± 8.1 cc) than the margin-reduced group (2.6 ± 1.8, 12.5 ± 8.3 cc), though the dose to these intersection volumes did not reach statistical significance (p > 0.1) between the groups. PTV/rectum intersection volume showed a moderate correlation (r = -0.56, p < 0.05) to Bowel EPIC domain. CONCLUSIONS: Results of this prospective study showed that margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the target dose coverage.

Commissioning, clinical implementation, and initial experience with a new brain tumor treatment package on a low-field MR-linac.

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high-resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low-field magnetic resonance imaging (MRI) linear accelerator (MR-linac). Image quality of the high-resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high-resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End-to-end testing was performed simulating a cranial lesion in a phantom. Inter-fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter-fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three-plane (axial, coronal, and sagittal) MR-cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post-processed and evaluated using an in-house program. Contrast resolution of the high-resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high-precision lateral-profile mask clips attach to the overlay. The greatest inter-fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub-millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter-fraction setup variability, attenuation, and end-to-end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems.

Feasibility of radical cardiac-sparing, treatment planning strategies for patients with locally advanced, non-small cell lung cancer.

PURPOSE: A set of treatment planning strategies were designed and retrospectively implemented for locally advanced, non-small cell lung cancer (NSCLC) patients in order to minimize cardiac dose without compromising target coverage goals. METHODS: Retrospective analysis was performed for 20 NSCLC patients prescribed to 60-66 Gy that received a mean heart dose (MHD) ≥10 Gy. Three planning approaches were designed and implemented. The first was a multi-isocentric (MI) volume-modulated arc therapy (VMAT) approach (HEART_MI) with one isocenter located within the tumor and the second chosen up to 10 cm away longitudinally. The second was a noncoplanar (NCP) VMAT approach (HEART_NCP) utilizing up to three large couch angles and a standard arc at couch 0. The final planning strategy took a mixed approach (HEART_HYBRID) utilizing the HEART_NCP strategy for two thirds of the treatment combined with a plan utilizing a pair of opposite-opposed gantry angles for the remaining treatments. Investigational plans were compared to original plans using dose-volume histogram metrics such as organ volume receiving greater than x Gy (Vx) or mean dose (Dmean). RESULTS: Although there was a small but statistically significant decrease in internal target volume coverage for HEART_MI plans and, conversely, a statistically significant increase for HEART_NCP plans, all generated plans met physician-prescribed target constraints. For heart dose, there were statistically significant decreases in all heart metrics and particularly MHD for the HEART_MI (9.8 vs. 15.4 Gy [p < 0.001], respectively), HEART_NCP (9.2 vs. 15.4 Gy [p < 0.001]), respectively), and HEART_HYBRID (7.9 vs. 15.4 Gy [p < 0.001], respectively) strategies. CONCLUSIONS: The strategy providing the best compromise between plan quality and cardiac dose reduction was HEART_NCP, which produced MHD reductions of 37.6% ± 12.9% (6.2 ± 3.4 Gy) relative to original plans. This strategy could potentially reduce adverse cardiac events, leading to improved quality of life for these patients.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

PURPOSE: We performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp-Davis-Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms. METHODS: Both FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set. After daily dose distributions were computed, they were mapped to planning CT to obtain deformed doses. Dosimetric and image registration results based CBCT images reconstructed by two algorithms were compared at three levels: (A) voxel doses over entire dose calculation volume, (B) clinical constraint results on targets and sensitive structures, and (C) contours propagated to CBCT images using DIR results based on three algorithms (SmartAdapt, Velocity, and Elastix) were compared with manually delineated contours as ground truth. RESULTS: (A) Average daily dose differences and average normalized DDA differences between FDK_CBCT and iterative_CBCT were ≤1 cGy. Maximum daily point dose differences increased from 0.22 ± 0.06 Gy (before the deformable dose mapping operation) to 1.33 ± 0.38 Gy after the deformable dose mapping. Maximum differences of normalized DDA per fraction were up to 0.80 Gy (0.42 ± 0.19 Gy). (B) Differences in target minimum doses were up to 8.31 Gy (-0.62 ± 4.60 Gy) and differences in critical structure doses were 0.70 ± 1.49 Gy. (C) For mapped prostate contours based on iterative_CBCT (relative to standard FDK_CBCT), dice similarity coefficient increased by 0.10 ± 0.09 (p < 0.0001), mass center distances decreased by 2.5 ± 3.0 mm (p < 0.00005), and Hausdorff distances decreased by 3.3 ± 4.4 mm (p < 0.00015). CONCLUSIONS: The new iterative CBCT reconstruction algorithm leads to different mapped volumes of interest, deformed and cumulative doses than results based on conventional FDK_CBCT.

Charlson Comorbidity score influence on prostate cancer survival and radiation-related toxicity.

INTRODUCTION: In addition to survival endpoints, we explored the impact of Charlson Comorbidity-Index (CCI) on the acute and late toxicities in men with localized prostate cancer who received dose-escalated definitive radiotherapy (RT). MATERIALS AND METHODS: CCI scores at diagnosis and survival outcomes were identified for men with intermediate/high-risk prostate cancer treated with RT (1/2007-12/2012). Study-cohort was accordingly grouped into no, mild and severe comorbidity (CCI-0, 1 or 2+). CCI-groups were compared for demographics, prognostic-factors; and RT-related toxicities based on RTOG/CTCAE criteria. Kaplan-Meier curves and Uni/multivariate (MVA) analyses were used to examine the influence of CCI-group on overall (OS), disease-specific (DSS) and biochemical-relapse free (BRFS) survival. RESULTS: We included 257 patients with median age 73 years (48-85), 53% African-American and 67% had intermediate-risk. Median prostate RT-dose was 76 Gy; and 47% received androgen-deprivation therapy. CCI-0,1,2+ groups encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively and were well-balanced. Ten and 15-years OS were significantly different (76% versus 46% versus 55% for 10-years OS and 53% versus 31% versus 14% for 15-years OS for CCI-0 versus CCI-1[HR:2.25; CI[1.31-3.87]] versus CCI-2+[HR:2.73; CI[1.73-4.31]]; p < 0.001. CCI-0 had better DSS than CCI-2+ (HR:2.23; CI[1.06-4.68]; p = 0.03) and BRFS was similar (p = 0.99). Late G2/3 RT-toxicities were more common in CCI-2+ (47%) than CCI-1 (44%) and CCI-0 (29%), p = 0.032; with non-different acute-toxicities (p = 0.62). On MVA, increased CCI was deterministic for OS (HR:3.65; CI [1.71:7.79]; p < 0.001) and was only marginal for DSS (HR:2.55; CI [0.98-6.6]; p = 0.05) with no impact on BRFS (p > 0.05). CONCLUSIONS: Higher CCI is a significant predictor for late RT-related side-effects and shorter OS in men with localized prostate cancer. Baseline comorbidities should be considered during initial counseling and follow up visits.

Technical Note: Comparison of the internal target volume (ITV) contours and dose calculations on 4DCT, average CBCT, and 4DCBCT imaging for lung stereotactic body radiation therapy (SBRT).

PURPOSE: To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. METHODS: For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. RESULTS: The Dice coefficients were similar for all three comparisons: avgCBCT-to-4DCBCT (0.7 ± 0.1), 4DCT-to-avgCBCT (0.7 ± 0.1), and 4DCT-to-4DCBCT (0.7 ± 0.1); while the mean COM differences were also comparable (2.6 ± 2.2mm, 2.3 ± 1.4mm, and 3.1 ± 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 ± 2.9mm and 8.1 ± 3.2mm) were larger than the comparison without (6.5 ± 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 ± 3.0% and -0.5 ± 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 ± 1.9% and 93.1 ± 8.0% for avgCBCT and 4DCBCT, respectively. CONCLUSION: There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes.

Modeling AeroForm tissue expander for postmastectomy radiation therapy.

The AeroForm chest wall tissue expander (TE) is a silicon shell containing a metallic CO2 reservoir, placed surgically after mastectomy. The patient uses a remote control to release compressed CO2 from the reservoir to inflate the expander. AeroForm poses challenges in a radiation therapy setting: The high density of the metallic reservoir causes imaging artifacts on the planning CT, which encumber structure definition and cause misrepresentation of density information, in turn affecting dose calculation. Additionally, convolution-based dose calculation algorithms may not be well-suited to calculate dose in and around high-density materials. In this study, a model of the AeroForm TE was created in Eclipse treatment planning system (TPS). The TPS model was validated by comparing measured to calculated transmission through the AeroForm. Transmission was measured with various geometries using radiochromic film. Dose was calculated with both Varian's Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB) algorithms. AAA and AXB were compared using dose profile and gamma analyses. While both algorithms modeled direct transmission well, AXB better modeled lateral scatter from the AeroForm TE. Clinical significance was evaluated using clinical data from four patients with AeroForm TEs. The AeroForm TPS model was applied, and RT plans were optimized using AAA, then re-calculated with AXB. Structures of clinical significance were defined and dose volume histogram analysis was performed. Compared to AXB, AAA overestimates dose in the AeroForm device. Changes in clinically significant regions were patient- and plan-specific. This study proposes a clinical procedure for modeling the AeroForm in a commercial TPS, and discusses the limitations of dose calculation in and around the device. An understanding of dose calculation accuracy in the vicinity of the AeroForm is critical for assessing individual plan quality, appropriateness of different planning techniques and dose calculation algorithms, and even the decision to use the AeroForm in a postmastectomy radiation therapy setting.

Kinetic modeling of tumor regression incorporating the concept of cancer stem-like cells for patients with locally advanced lung cancer.

BACKGROUND: Personalized medicine for patients receiving radiation therapy remains an elusive goal due, in part, to the limits in our understanding of the underlying mechanisms governing tumor response to radiation. The purpose of this study was to develop a kinetic model, in the context of locally advanced lung cancer, connecting cancer cell subpopulations with tumor volumes measured during the course of radiation treatment for understanding treatment outcome for individual patients. METHODS: The kinetic model consists of three cell compartments: cancer stem-like cells (CSCs), non-stem tumor cells (TCs) and dead cells (DCs). A set of ordinary differential equations were developed to describe the time evolution of each compartment, and the analytic solution of these equations was iterated to be aligned with the day-to-day tumor volume changes during the course of radiation treatment. A least squares fitting method was used to estimate the parameters of the model that include the proportion of CSCs and their radio-sensitivities. This model was applied to five patients with stage III lung cancer, and tumor volumes were measured from 33 cone-beam computed tomography (CBCT) images for each of these patients. The analytical solution of these differential equations was compared with numerically simulated results. RESULTS: For the five patients with late stage lung cancer, the derived proportions of CSCs are 0.3 on average, the average probability of the symmetry division is 0.057 and the average surviving fractions of CSCs is 0.967, respectively. The derived parameters are comparable to the results from literature and our experiments. The preliminary results suggest that the CSC self-renewal rate is relatively small, compared to the proportion of CSCs for locally advanced lung cancers. CONCLUSIONS: A novel mathematical model has been developed to connect the population of cancer stem-like cells with tumor volumes measured from a sequence of CBCT images. This model may help improve our understanding of tumor response to radiation therapy, and is valuable for development of new treatment regimens for patients with locally advanced lung cancer.

Evaluation and verification of the QFix EncompassTM couch insert for intracranial stereotactic radiosurgery.

The QFix EncompassTM stereotactic radiosurgery (SRS) immobilization system consists of a thermoplastic mask that attaches to the couch insert to immobilize patients treated with intracranial SRS. This study evaluates the dosimetric impact and verifies a vendor provided treatment planning system (TPS) model in the Eclipse TPS. A thermoplastic mask was constructed for a Lucy 3D phantom, and was scanned with and without the EncompassTM system. Attenuation measurements were performed in the Lucy phantom with and without the insert using a pinpoint ion chamber for energies of 6xFFF, 10xFFF and 6X, with three field sizes (2 × 2, 4 × 4, and 6 × 6 cm2 ). The measurements were compared to two sets of calculations. The first set utilized the vendor provided Encompass TPS model (EncompassTPS ), which consists of two structures: the Encompass and Encompass base structure. Three HU values for the Encompass (200, 300, 400) and Encompass Base (-600, -500, -400) structures were evaluated. The second set of calculations consists of the Encompass insert included in the external body contour (EncompassEXT ) for dose calculation. The average measured percent attenuation in the posterior region of the insert ranged from 3.4%-3.8% for the 6xFFF beam, 2.9%-3.4% for the 10xFFF, and 3.3%-3.6% for the 6X beam. The maximum attenuation occurred at the region where the mask attaches to the insert, where attenuation up to 17% was measured for a 6xFFF beam. The difference between measured and calculated attenuation with either the EncompassEXT or EncompassTPS approach was within 0.5%. HU values in the EncompassTPS model that provided the best agreement with measurement was 400 for the Encompass structure and -400 for the Encompass base structure. Significant attenuation was observed at the area where the mask attaches to the insert. Larger differences can be observed when using few static beams compared to rotational treatment techniques.

On the improvement of CBCT image quality for soft tissue-based SRS localization.

PURPOSE: We explore the optimal cone-beam CT (CBCT) acquisition parameters to improve CBCT image quality to enhance intracranial stereotactic radiosurgery (SRS) localization and also assess the imaging dose levels associated with each imaging protocol. METHODS: Twenty-six CBCT acquisition protocols were generated on an Edge® linear accelerator (Varian Medical Systems, Palo Alto, CA) with different x-ray tube current and potential settings, gantry rotation trajectories, and gantry rotation speeds. To assess image quality, images of the Catphan 504 phantom were analyzed to evaluate the following image quality metrics: uniformity, HU constancy, spatial resolution, low contrast detection, noise level, and contrast-to-noise ratio (CNR). To evaluate the imaging dose for each protocol, the cone-beam dose index (CBDI) was measured. To validate the phantom results, further analysis was performed with an anthropomorphic head phantom as well as image data acquired for a clinical SRS patient. RESULTS: The Catphan data indicates that adjusting acquisition parameters had direct effects on the image noise level, low contrast detection, and CNR, but had minimal effects on uniformity, HU constancy, and spatial resolution. The noise level was reduced from 34.5 ± 0.3 to 18.5 ± 0.2 HU with a four-fold reduction in gantry speed, and to 18.7 ± 0.2 HU with a four-fold increase in tube current. Overall, the noise level was found to be proportional to inverse square root of imaging dose, and imaging dose was proportional to the product of total tube current-time product and the cube of the x-ray potential. Analysis of the anthropomorphic head phantom data and clinical SRS imaging data also indicates that noise is reduced with imaging dose increase. CONCLUSIONS: Our results indicate that optimization of the imaging protocol, and thereby an increase in the imaging dose, is warranted for improved soft-tissue visualization for intracranial SRS.

An adaptive model for rapid and direct estimation of extravascular extracellular space in dynamic contrast enhanced MRI studies.

Extravascular extracellular space (ve ) is a key parameter to characterize the tissue of cerebral tumors. This study introduces an artificial neural network (ANN) as a fast, direct, and accurate estimator of ve from a time trace of the longitudinal relaxation rate, ΔR1 (R1  = 1/T1 ), in DCE-MRI studies. Using the extended Tofts equation, a set of ΔR1 profiles was simulated in the presence of eight different signal to noise ratios. A set of gain- and noise-insensitive features was generated from the simulated ΔR1 profiles and used as the ANN training set. A K-fold cross-validation method was employed for training, testing, and optimization of the ANN. The performance of the optimal ANN (12:6:1, 12 features as input vector, six neurons in hidden layer, and one output) in estimating ve at a resolution of 10% (error of ±5%) was 82%. The ANN was applied on DCE-MRI data of 26 glioblastoma patients to estimate ve in tumor regions. Its results were compared with the maximum likelihood estimation (MLE) of ve . The two techniques showed a strong agreement (r = 0.82, p < 0.0001). Results implied that the perfected ANN was less sensitive to noise and outperformed the MLE method in estimation of ve .

DCE-MRI prediction of survival time for patients with glioblastoma multiforme: using an adaptive neuro-fuzzy-based model and nested model selection technique.

This pilot study investigates the construction of an Adaptive Neuro-Fuzzy Inference System (ANFIS) for the prediction of the survival time of patients with glioblastoma multiforme (GBM). ANFIS is trained by the pharmacokinetic (PK) parameters estimated by the model selection (MS) technique in dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data analysis, and patient age. DCE-MRI investigations of 33 treatment-naïve patients with GBM were studied. Using the modified Tofts model and MS technique, the following physiologically nested models were constructed: Model 1, no vascular leakage (normal tissue); Model 2, leakage without efflux; Model 3, leakage with bidirectional exchange (influx and efflux). For each patient, the PK parameters of the three models were estimated as follows: blood plasma volume (vp ) for Model 1; vp and volume transfer constant (Ktrans ) for Model 2; vp , Ktrans and rate constant (kep ) for Model 3. Using Cox regression analysis, the best combination of the estimated PK parameters, together with patient age, was identified for the design and training of ANFIS. A K-fold cross-validation (K = 33) technique was employed for training, testing and optimization of ANFIS. Given the survival time distribution, three classes of survival were determined and a confusion matrix for the correct classification fraction (CCF) of the trained ANFIS was estimated as an accuracy index of ANFIS's performance. Patient age, kep and ve (Ktrans /kep ) of Model 3, and Ktrans of Model 2, were found to be the most effective parameters for training ANFIS. The CCF of the trained ANFIS was 84.8%. High diagonal elements of the confusion matrix (81.8%, 90.1% and 81.8% for Class 1, Class 2 and Class 3, respectively), with low off-diagonal elements, strongly confirmed the robustness and high performance of the trained ANFIS for predicting the three survival classes. This study confirms that DCE-MRI PK analysis, combined with the MS technique and ANFIS, allows the construction of a DCE-MRI-based fuzzy integrated predictor for the prediction of the survival of patients with GBM.

Tuning of AcurosXB source size setting for small intracranial targets.

This study details a method to evaluate the source size selection for small field intracranial stereotactic radiosurgery (SRS) deliveries in Eclipse treatment planning system (TPS) for AcurosXB dose calculation algorithm. Our method uses end-to-end dosimetric data to evaluate a total of five source size selections (0.50 mm, 0.75 mm, 1.00 mm, 1.25 mm, and 1.50 mm). The dosimetric leaf gap (DLG) was varied in this analysis (three DLG values were tested for each scenario). We also tested two MLC leaf designs (standard and high-definition MLC) and two delivery types for intracranial SRS (volumetric modulated arc therapy [VMAT] and dynamic conformal arc [DCA]). Thus, a total of 10 VMAT plans and 10 DCA plans were tested for each machine type (TrueBeam [standard MLC] and Edge [high-definition MLC]). Each plan was mapped to a solid water phantom and dose was calculated with each iteration of source size and DLG value (15 total dose calculations for each plan). To measure the dose, Gafchromic film was placed in the coronal plane of the solid water phantom at isocenter. The phantom was localized via on-board CBCT and the plans were delivered at planned gantry, collimator, and couch angles. The planned and measured film dose was compared using Gamma (3.0%, 0.3 mm) criteria. The vendor-recommended 1.00 mm source size was suitable for TrueBeam planning (both VMAT and DCA planning) and Edge DCA planning. However, for Edge VMAT planning, the 0.50 mm source size yielded the highest passing rates. The difference in dose calculation among the source size variations manifested primarily in two regions of the dose calculation: (1) the shoulder of the high-dose region, and (2) for small targets (volume ≤ 0.30 cc), in the central portion of the high-dose region. Selection of a larger than optimal source size can result in increased blurring of the shoulder for all target volume sizes tested, and can result in central axis dose discrepancies in excess of 10% for target volumes sizes ≤ 0.30 cc. Our results indicate a need for evaluation of the source size when AcurosXB is used to model intracranial SRS delivery, and our methods represent a feasible process for many clinics to perform tuning of the AcurosXB source size parameter.

Deriving detector-specific correction factors for rectangular small fields using a scintillator detector.

The goal of this study was to investigate small field output factors (OFs) for flat-tening filter-free (FFF) beams on a dedicated stereotactic linear accelerator-based system. From this data, the collimator exchange effect was quantified, and detector-specific correction factors were generated. Output factors for 16 jaw-collimated small fields (from 0.5 to 2 cm) were measured using five different detectors including an ion chamber (CC01), a stereotactic field diode (SFD), a diode detector (Edge), Gafchromic film (EBT3), and a plastic scintillator detector (PSD, W1). Chamber, diodes, and PSD measurements were performed in a Wellhofer water tank, while films were irradiated in solid water at 100 cm source-to-surface distance and 10 cm depth. The collimator exchange effect was quantified for rectangular fields. Monte Carlo (MC) simulations of the measured configurations were also performed using the EGSnrc/DOSXYZnrc code. Output factors measured by the PSD and verified against film and MC calculations were chosen as the benchmark measurements. Compared with plastic scintillator detector (PSD), the small volume ion chamber (CC01) underestimated output factors by an average of -1.0% ± 4.9% (max. = -11.7% for 0.5 × 0.5 cm2 square field). The stereotactic diode (SFD) overestimated output factors by 2.5% ± 0.4% (max. = 3.3% for 0.5 × 1 cm2 rectangular field). The other diode detector (Edge) also overestimated the OFs by an average of 4.2% ± 0.9% (max. = 6.0% for 1 × 1 cm2 square field). Gafchromic film (EBT3) measure-ments and MC calculations agreed with the scintillator detector measurements within 0.6% ± 1.8% and 1.2% ± 1.5%, respectively. Across all the X and Y jaw combinations, the average collimator exchange effect was computed: 1.4% ± 1.1% (CC01), 5.8% ± 5.4% (SFD), 5.1% ± 4.8% (Edge diode), 3.5% ± 5.0% (Monte Carlo), 3.8% ± 4.7% (film), and 5.5% ± 5.1% (PSD). Small field detectors should be used with caution with a clear understanding of their behaviors, especially for FFF beams and small, elongated fields. The scintillator detector exhibited good agreement against Gafchromic film measurements and MC simulations over the range of field sizes studied. The collimator exchange effect was found to be impor-tant at these small field sizes. Detector-specific correction factors were computed using the scintillator measurements as the benchmark.

Development and evaluation of a clinical model for lung cancer patients using stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning.

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub-KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model's ability to handle suboptimal beam placements. Dose differences to organs-at-risk (OAR) were evaluated between the plans gener-ated by each KBM. Knowledge-based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by 1.0 ± 1.6 Gy compared to clinical plans, p = 0.007. Sub-KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub-KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by 0.4Gy ± 0.8Gy, p = 0.025. For all lesions, compared to the full KBM, the posterior sub-KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by 0.2 ± 0.4Gy, p = 0.01. Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (1.2 ± 2.2Gy, p = 0.01) and GI (0.2 ± 0.4, p = 0.01) for the nine-field plans relative to KBPs planned with custom beam angles. A knowledge-based model for lung SBRT consisting of multiple treatment modalities and lesion loca-tions produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations.

Impact of incorporating visual biofeedback in 4D MRI.

Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved con-trast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB-approved protocol. Prospective respiratory-triggered, T2-weighted, coronal 4D MRIs were acquired on an open 1.0T MR-SIM. VBF was integrated using an MR-compatible interactive breath-hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2- and 8-phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end-inhale coefficient of variation, EI-COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration-induced liver motion was calculated via centroid difference analysis of end-exhale (EE) and EI liver contours. Incorporating VBF reduced 2-phase acquisition time (4.7 ± 1.0 and 5.4 ± 1.5 min with and without VBF, respectively) while reducing EI-COV by 43.8% ± 16.6%. For 8-phase acquisitions, VBF reduced acquisition time by 1.9 ± 1.6 min and EI-COVs by 38.8% ± 25.7% despite breathing rate remaining similar (11.1 ± 3.8 breaths/min with vs. 10.5 ± 2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4% ± 5.8% vs. 28.1% ± 6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid-exhale and EI. Increased liver excursion was observed with VBF, where superior-inferior, anterior-posterior, and left-right EE-EI displacements were 14.1± 5.8, 4.9 ± 2.1, and 1.5 ± 1.0 mm, respectively, with VBF compared to 11.9 ± 4.5, 3.7 ± 2.1, and 1.2 ± 1.4 mm without. Incorporating VBF into 4D MRI substantially reduced acquisition time, breathing irregularity, and image artifacts. However, differences in excursion were observed, thus implementation will be required throughout the RT workflow.

Characterization and evaluation of 2.5 MV electronic portal imaging for accurate localization of intra- and extracranial stereotactic radiosurgery.

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging. Scatter effect in large patient body was simulated by adding solid water slabs along the beam path. The 2.5 MV imaging mode was also evaluated using clinically acquired images from 24 patients for the sites of brain, head and neck, lung, and abdomen. With respect to 6 MV, the 2.5 MV achieved higher contrast and preserved sharpness on bony structures with only half of the imaging dose. The quality of 2.5 MV imaging was comparable to that of kV imaging when the lateral separation of patient was greater than 38 cm, while the kV image quality degraded rapidly as patient separation increased. Based on the results of patient images, 2.5 MV imaging was better for cranial and extracranial SRS than the 6 MV imaging.

Generation and verification of QFix kVue Calypso-compatible couch top model for a dedicated stereotactic linear accelerator with FFF beams.

This study details the generation, verification, and implementation of a treatment planning system (TPS) couch top model for patient support system used in conjunction with a dedicated stereotactic linear accelerator. Couch top model was created within the TPS using CT simulation images of the kVue Calpyso-compatible couchtop (with rails). Verification measurements were compared to TPS dose prediction for different energies (6 MV FFF and 10 MV FFF) and rail configurations (rails in and rails out) using: 1) central axis point-dose measurements with pinpoint chamber in water-equivalent phantom at 42 gantry angles for various field sizes (2 × 2 cm², 4 × 4 cm², 10 × 10 cm²); and 2) Gafchromic EBT3 film parallel to beam in acrylic slab to assess changes in surface and percent depth doses in PA geometry. To assess sensitivity of delivered dose to variations in patient lateral position, measurements at central axis using the pinpoint chamber geometry were taken at lateral couch displacements of 2, 5, and 10 mm for 6 MV FFF. The maximum percent difference for point-dose measurements was 3.24% (6 MV FFF) and 2.30% (10 MV FFF). The average percent difference for point-dose measurements was less than 1.10% for all beam energies and rail geometries. The maximum percent difference between calculated and measured dose can be as large as 13.0% if no couch model is used for dose calculation. The presence of the couch structures also impacts surface dose and PDD, which was evaluated with Gafchromic film measurements. The upstream shift in the depth of dose maximum (dmax) was found to be 10.5 mm for 6 MV FFF and 5.5 mm for 10 MV FFF for 'Rails In' configuration. Transmission of the treatment beam through the couch results in an increase in surface dose (absolute percentage) of approximately 50% for both photon energies (6 MV FFF and 10MV FFF). The largest sensitivity to lateral shifts occurred at the lateral boundary of the rail structures. The mean magnitude (standard deviation) of the deviation between shifted and centered measurements over all field sizes tested was 0.61% (0.61%) for 2 mm shifts, 0.46% (0.67%) for 5 mm shifts, and 0.86% (1.46%) for 10 mm shifts.

Initial clinical experience with a radiation oncology dedicated open 1.0T MR-simulation.

The purpose of this study was to describe our experience with 1.0T MR-SIM including characterization, quality assurance (QA) program, and features necessary for treatment planning. Staffing, safety, and patient screening procedures were developed. Utilization of an external laser positioning system (ELPS) and MR-compatible couchtop were illustrated. Spatial and volumetric analyses were conducted between CT-SIM and MR-SIM using a stereotactic QA phantom with known landmarks and volumes. Magnetic field inhomogeneity was determined using phase difference analysis. System-related, in-plane distortion was evaluated and temporal changes were assessed. 3D distortion was characterized for regions of interest (ROIs) 5-20 cm away from isocenter. American College of Radiology (ACR) recommended tests and impact of ELPS on image quality were analyzed. Combined ultrashort echotime Dixon (UTE/Dixon) sequence was evaluated. Amplitude-triggered 4D MRI was implemented using a motion phantom (2-10 phases, ~ 2 cm excursion, 3-5 s periods) and a liver cancer patient. Duty cycle, acquisition time, and excursion were evaluated between maximum intensity projection (MIP) datasets. Less than 2% difference from expected was obtained between CT-SIM and MR-SIM volumes, with a mean distance of < 0.2 mm between landmarks. Magnetic field inhomogeneity was < 2 ppm. 2D distortion was < 2 mm over 28.6-33.6 mm of isocenter. Within 5 cm radius of isocenter, mean 3D geometric distortion was 0.59 ± 0.32 mm (maximum = 1.65 mm) and increased 10-15 cm from isocenter (mean = 1.57 ± 1.06 mm, maximum = 6.26 mm). ELPS interference was within the operating frequency of the scanner and was characterized by line patterns and a reduction in signal-to-noise ratio (4.6-12.6% for TE = 50-150 ms). Image quality checks were within ACR recommendations. UTE/Dixon sequences yielded detectability between bone and air. For 4D MRI, faster breathing periods had higher duty cycles than slow (50.4% (3 s) and 39.4% (5 s), p < 0.001) and ~fourfold acquisition time increase was measured for ten-phase versus two-phase. Superior-inferior object extent was underestimated 8% (6 mm) for two-phase as compared to ten-phase MIPs, although < 2% difference was obtained for ≥ 4 phases. 4D MRI for a patient demonstrated acceptable image quality in ~ 7 min. MR-SIM was integrated into our workflow and QA procedures were developed. Clinical applicability was demonstrated for 4D MRI and UTE imaging to support MR-SIM for single modality treatment planning.

ACR Appropriateness Criteria® nonsurgical treatment for locally advanced non-small-cell lung cancer: good performance status/definitive intent.

Concurrent chemotherapy/radiotherapy has been considered the standard treatment for patients with a good performance status and inoperable stage III non-small-cell lung cancer (NSCLC). Three-dimensional chemoradiation therapy and intensity-modulated radiation therapy have been reported to reduce toxicity and allow a dose escalation to 70 Gy and beyond. However, the Radiation Therapy Oncology Group 0617 trial recently showed that dose escalation from 60 Gy to 74 Gy with concurrent chemotherapy in stage III NSCLC was associated with higher toxicity and worse survival. A "one size fits all" treatment approach may need to be changed and adapted to each patient's particular disease and unique biologic/anatomic features, as well as the most appropriate radiotherapy modalities for that patient. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application, by the panel, of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures. In instances in which evidence is lacking or not definitive, expert opinion may be used as the basis for recommending imaging or treatment.