X Zhu

Cost-comparativeness of proton versus photon therapy

Proton beam radiotherapy (PBT) offers great promise in the treatment of a wide variety of cancers owing to the sharp drop-off in radiation dose at a defined point, known as the Bragg peak, beyond which there is no appreciable dose. However, it is also well-understood that PBT is associated with large economic costs, including both capital investment and operating costs. From a medical as well as societal perspective, therefore, it is important to be aware of the economic implications of new technologies such as PBT, and to evaluate the cost effectiveness based on different clinical and treatment scenarios. This review examines PBT from a health economics perspective, evaluating both the design and results of costeffectiveness (CE) studies that have been performed previously. We further examine several salient variables that can affect CE of PBT, including patient, tumor, treatment, and logistical factors. We discuss the implication of technological advances on PBT delivery, and its impact on overall healthcare delivery costs. Additionally, we evaluate the status of economic analyses for PBT and discuss the role of ongoing and future CE studies in better defining the economic role of PBT as part of modern cancer therapy.

Automatic planning on hippocampal avoidance whole-brain radiotherapy

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D2% and D98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D100% and Dmax of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.

Effect of the normalized prescription isodose line on the magnitude of Monte Carlo vs. pencil beam target dose differences for lung stereotactic body radiotherapy

In lung stereotactic body radiotherapy (SBRT) cases, the pencil beam (PB) dose calculation algorithm is known to overestimate target dose as compared to the more accurate Monte Carlo (MC) algorithm. We investigated whether changing the normalized prescription isodose line affected the magnitude of MC vs. PB target dose differences. Forty-eight patient plans and twenty virtual-tumor phantom plans were studied. For patient plans, four alternative plans prescribed to 60%, 70%, 80%, and 90% isodose lines were each created for 12 patients who previously received lung SBRT treatments. Using 6 MV dynamic conformal arcs, the plans were individually optimized to achieve similar dose coverage and conformity for all plans of the same patient, albeit at the different prescription levels. These plans, having used a PB algorithm, were all recalculated with MC to compare the target dose differences. The relative MC vs. PB target dose variations were investigated by comparing PTV D95, Dmean, and D5 loss at the four prescription levels. The MC-to-PB ratio of the plan heterogeneity index (HI) was also evaluated and compared among different isodose levels. To definitively demonstrate the cause of the isodose line dependence, a simulated phantom study was conducted using simple, spherical virtual tumors planned with uniform block margins. The tumor size and beam energy were also altered in the phantom study to investigate the interplay between these confounding factors and the isodose line effect. The magnitude of the target dose overestimation by PB was greater for higher prescription isodose levels. The MC vs. PB reduction in the target dose coverage indices, D95 and V100 of PTV, were found to monotonically increase with increasing isodose lines from 60% to 90%, resulting in more pronounced target dose coverage deficiency at higher isodose prescription levels. No isodose level-dependent trend was observed for the dose errors in the target mean or high dose indices, Dmean or D5. The phantom study demonstrated that the observed isodose level dependence was caused by different beam margins used for the different isodose levels: a higher prescription line required a larger beam margin, leading to more low-density lung tissues in the field and, therefore, larger dose errors at the target periphery (when calculated with PB). The phantom study also found that the observed isodose level dependence was greater for smaller targets and for higher beam energies. We hereby characterized the effect of normalized prescription isodose line on magnitude of PTV dose coverage as calculated by MC vs. PB. When comparing reported MC dose deficiency values for different patients, the selection of prescription isodose line should be considered in addition to other factors known to affect differences in calculated doses between various algorithms. PACS number(s): 87.55.kh, 87.55.dk, 87.55.de.In lung stereotactic body radiotherapy (SBRT) cases, the pencil beam (PB) dose calculation algorithm is known to overestimate target dose as compared to the more accurate Monte Carlo (MC) algorithm. We investigated whether changing the normalized prescription isodose line affected the magnitude of MC vs. PB target dose differences. Forty‐eight patient plans and twenty virtual‐tumor phantom plans were studied. For patient plans, four alternative plans prescribed to 60%, 70%, 80%, and 90% isodose lines were each created for 12 patients who previously received lung SBRT treatments. Using 6 MV dynamic conformal arcs, the plans were individually optimized to achieve similar dose coverage and conformity for all plans of the same patient, albeit at the different prescription levels. These plans, having used a PB algorithm, were all recalculated with MC to compare the target dose differences. The relative MC vs. PB target dose variations were investigated by comparing PTV D95, Dmean, and D5 loss at the four prescription levels. The MC‐to‐PB ratio of the plan heterogeneity index (HI) was also evaluated and compared among different isodose levels. To definitively demonstrate the cause of the isodose line dependence, a simulated phantom study was conducted using simple, spherical virtual tumors planned with uniform block margins. The tumor size and beam energy were also altered in the phantom study to investigate the interplay between these confounding factors and the isodose line effect. The magnitude of the target dose overestimation by PB was greater for higher prescription isodose levels. The MC vs. PB reduction in the target dose coverage indices, D95 and V100 of PTV, were found to monotonically increase with increasing isodose lines from 60% to 90%, resulting in more pronounced target dose coverage deficiency at higher isodose prescription levels. No isodose level‐dependent trend was observed for the dose errors in the target mean or high dose indices, Dmean or D5. The phantom study demonstrated that the observed isodose level dependence was caused by different beam margins used for the different isodose levels: a higher prescription line required a larger beam margin, leading to more low‐density lung tissues in the field and, therefore, larger dose errors at the target periphery (when calculated with PB). The phantom study also found that the observed isodose level dependence was greater for smaller targets and for higher beam energies. We hereby characterized the effect of normalized prescription isodose line on magnitude of PTV dose coverage as calculated by MC vs. PB. When comparing reported MC dose deficiency values for different patients, the selection of prescription isodose line should be considered in addition to other factors known to affect differences in calculated doses between various algorithms. PACS number(s): 87.55.kh, 87.55.dk, 87.55.de

Still equivalent for dose calculation in the Monte Carlo era? A comparison of free breathing and average intensity projection CT datasets for lung SBRT using three generations of dose calculation algorithms

Purpose Inhomogeneity dose modeling and respiratory motion description are two critical technical challenges for lung stereotactic body radiotherapy, an important treatment modality for small size primary and secondary lung tumors. Recent studies revealed lung density‐dependent target dose differences between Monte Carlo (Type‐C) algorithm and earlier algorithms. Therefore, this study aimed to investigate the equivalence of the two most popular CT datasets for treatment planning, free breathing (FB) and average intensity projection (AIP) CTs, using Type‐C algorithms, and comparing with two older generation algorithms (Type‐A and Type‐B). Methods Twenty patients (twenty‐one lesions) were planned using a Type‐A algorithm on the FB CT. Lung was contoured separately on FB and AIP CTs and compared. Dose comparison was obtained between the two CTs using four commercial dose algorithms including one Type‐A (Pencil Beam Convolution – PBC), one Type‐B (Analytical Anisotropic Algorithm – AAA), and two Type‐C algorithms (Voxel Monte Carlo – VMC and Acuros External Beam – AXB). For each algorithm, the dosimetric parameters of the target (PTV, Dmin, Dmax, Dmean, D95, and D90) and lung (V5, V10, V20, V30, V35, and V40) were compared between the two CTs using the Wilcoxon signed rank test. Correlation between dosimetric differences and density differences for each algorithm were studied using linear regression and Spearman correlation, in which both global and local density differences were evaluated. Results Although the lung density differences on FB and AIP CTs were statistically significant (P = 0.003), the magnitude was small at 1.21 ± 1.45%. Correspondingly, for the two Type‐C algorithms, target and lung dosimetric differences were small in magnitude and statistically insignificant (P > 0.05) for all but one instance, similar to the findings for the older generation algorithms. Nevertheless, a significant correlation was shown between the dosimetric and density differences for Type‐C and Type‐B algorithms, but not for the Type‐A algorithm. Conclusions With the capability to more accurately model inhomogeneity, Monte Carlo (Type‐C) algorithms are sensitive to respiration‐induced local and global tissue density changes and exhibit a strong correlation between dosimetric and density differences. However, FB and AIP CTs may still be considered equivalent for dose calculation in the Monte Carlo era, due to the small magnitude of lung density differences between these two datasets.

Estimation of internal organ motion-induced variance in radiation dose in non-gated radiotherapy

In the delivery of non-gated radiotherapy (RT), owing to intra-fraction organ motion, a certain degree of RT dose uncertainty is present. Herein, we propose a novel mathematical algorithm to estimate the mean and variance of RT dose that is delivered without gating. These parameters are specific to individual internal organ motion, dependent on individual treatment plans, and relevant to the RT delivery process. This algorithm uses images from a patients 4D simulation study to model the actual patient internal organ motion during RT delivery. All necessary dose rate calculations are performed in fixed patient internal organ motion states. The analytical and deterministic formulae of mean and variance in dose from non-gated RT were derived directly via statistical averaging of the calculated dose rate over possible random internal organ motion initial phases, and did not require constructing relevant histograms. All results are expressed in dose rate Fourier transform coefficients for computational efficiency. Exact solutions are provided to simplified, yet still clinically relevant, cases. Results from a volumetric-modulated arc therapy (VMAT) patient case are also presented. The results obtained from our mathematical algorithm can aid clinical decisions by providing information regarding both mean and variance of radiation dose to non-gated patients prior to RT delivery.

Technical Note: Fabricating Cerrobend grids with 3D printing for spatially modulated radiation therapy: A feasibility study.

PURPOSE Grid therapy has promising applications in the radiation treatment of large tumors. However, research and applications of grid therapy are limited by the accessibility of the specialized blocks that produce the grid of pencil-like radiation beams. In this study, a Cerrobend grid block was fabricated using the 3D printing technique. METHODS A grid block mold was designed with flared tubes which follow the divergence of the beam. The mold was 3D printed using a resin with the working temperature below 230 °C. The melted Cerrobend liquid at 120 °C was cast into the resin mold to yield a block with a thickness of 7.4 cm. At the isocenter plane, the grid had a hexagonal pattern, with each pencil beam diameter of 1.4 cm; the distance between the beam centers was 2.1 cm. RESULTS The dosimetric properties of the grid block were studied using small field dosimeters: a pinpoint ionization chamber and a stereotactic diode. For a 6 MV photon beam, its valley-to-peak ratio was 20% at dmax and 30% at 10 cm depth; the output factor was 84.9% at dmax and 65.1% at 10 cm depth. CONCLUSIONS This study demonstrates that it is feasible to implement 3D printing technique in applying grid therapy in clinic.

Target migration from re-inflation of adjacent atelectasis during lung stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) is a widely accepted option for the treatment of medically inoperable early-stage non-small cell lung cancer (NSCLC). Herein, we highlight the importance of interfraction image guidance during SBRT. We describe a case of early-stage NSCLC associated with segmental atelectasis that translocated 15 mm anteroinferiorly due to re-expansion of the adjacent segmental atelectasis following the first fraction. The case exemplifies the importance of cross-sectional image-guided radiotherapy that shows the intended target, as opposed to aligning based on rigid anatomy alone, especially in cases associated with potentially “volatile” anatomic areas.

Validation of the Calypso Surface Beacon Transponder

Calypso L-shaped Surface Beacon transponder has recently become available for clinical applications. We herein conduct studies to validate the Surface Beacon transponder in terms of stability, reproducibility, orientation sensitivity, cycle rate dependence, and respiratory waveform tracking accuracy. The Surface Beacon was placed on a Quasar respiratory phantom and positioned at the isocenter with its two arms aligned with the lasers. Breathing waveforms were simulated, and the motion of the transponder was tracked. Stability and drift analysis: sinusoidal waveforms (200 cycles) were produced, and the amplitudes of phases 0% (inhale) and 50% (exhale) were recorded at each breathing cycle. The mean and standard deviation (SD) of the amplitudes were calculated. Linear least-squares fitting was performed to access the possible amplitude drift over the breathing cycles. Reproducibility: similar setting to stability and drift analysis, and the phantom generated 100 cycles of the sinusoidal waveform per run. The Calypso systems was re-setup for each run. Recorded amplitude and SD of 0% and 50% phase were compared between runs to assess contribution of Calypso electromagnetic array setup variation. Beacon orientation sensitivity: the Calypso tracks sinusoidal phantom motion with a defined angular offset of the beacon to assess its effect on SD and peak-to-peak amplitude. Rate dependence: sinusoidal motion was generated at cycle rates of 1 Hz, .33 Hz, and .2 Hz. Peak-to-peak displacement and SDs were assessed. Respiratory waveform tracking accuracy: the phantom reproduced recorded breathing cycles (by volunteers and patients) were tracked by the Calypso system. Deviation in tracking position from produced waveform was used to calculate SD throughout entire breathing cycle. Stability and drift analysis: Mean amplitude ± SD of phase 0% or 50% were 20.01±0.04 mm and -19.65±0.08 mm, respectively. No clinically significant drift was detected with drift measured as 5.1×10-5 mm/s at phase 0% and -6.0×10-5 mm/s at phase 50%. Reproducibility: The SD of the setup was 0.06 mm and 0.02 mm for phases 0% and 50%, respectively. The combined SDs, including both setup and intrarun error of all runs at phases 0% and 50%, were 0.07 mm and 0.11 mm, respectively. Beacon orientation: SD ranged from 0.032 mm to 0.039 mm at phase 0% and from 0.084 mm to 0.096 mm at phase 50%. The SD was found not to vary linearly with Beacon angle in the range of 0° and 15°. A positive systematic error was observed with amplitude 0.07 mm/degree at phase 0% and 0.05 mm/degree at phase 50%. Rate dependence: SD and displacement amplitudes did not vary significantly between 0.2 Hz and 0.33 Hz. At 1 Hz, both 0% and 50% amplitude measurements shifted up appreciably, by 0.72 mm and 0.78 mm, respectively. As compared with the 0.33 Hz data, SD at phase 0% was 1.6 times higher and 5.4 times higher at phase 50%. Respiratory waveform tracking accuracy: SD of 0.233 mm with approximately normal distribution in over 134 min of tracking (201468 data points). The Surface Beacon transponder appears to be stable, accurate, and reproducible. Submillimeter resolution is achieved throughout breathing and sinusoidal waveforms. PACS number(s): 87.50.ct, 87.50.st, 87.50.ux, 87.50.wp, 87.50.yt.Calypso L‐shaped Surface Beacon transponder has recently become available for clinical applications. We herein conduct studies to validate the Surface Beacon transponder in terms of stability, reproducibility, orientation sensitivity, cycle rate dependence, and respiratory waveform tracking accuracy. The Surface Beacon was placed on a Quasar respiratory phantom and positioned at the isocenter with its two arms aligned with the lasers. Breathing waveforms were simulated, and the motion of the transponder was tracked. Stability and drift analysis: sinusoidal waveforms (200 cycles) were produced, and the amplitudes of phases 0% (inhale) and 50% (exhale) were recorded at each breathing cycle. The mean and standard deviation (SD) of the amplitudes were calculated. Linear least‐squares fitting was performed to access the possible amplitude drift over the breathing cycles. Reproducibility: similar setting to stability and drift analysis, and the phantom generated 100 cycles of the sinusoidal waveform per run. The Calypso systems was re‐setup for each run. Recorded amplitude and SD of 0% and 50% phase were compared between runs to assess contribution of Calypso electromagnetic array setup variation. Beacon orientation sensitivity: the Calypso tracks sinusoidal phantom motion with a defined angular offset of the beacon to assess its effect on SD and peak‐to‐peak amplitude. Rate dependence: sinusoidal motion was generated at cycle rates of 1 Hz, .33 Hz, and .2 Hz. Peak‐to‐peak displacement and SDs were assessed. Respiratory waveform tracking accuracy: the phantom reproduced recorded breathing cycles (by volunteers and patients) were tracked by the Calypso system. Deviation in tracking position from produced waveform was used to calculate SD throughout entire breathing cycle. Stability and drift analysis: Mean amplitude ± SD of phase 0% or 50% were 20.01±0.04 mm and ‐19.65±0.08 mm, respectively. No clinically significant drift was detected with drift measured as 5.1×10‐5 mm/s at phase 0% and ‐6.0×10‐5 mm/s at phase 50%. Reproducibility: The SD of the setup was 0.06 mm and 0.02 mm for phases 0% and 50%, respectively. The combined SDs, including both setup and intrarun error of all runs at phases 0% and 50%, were 0.07 mm and 0.11 mm, respectively. Beacon orientation: SD ranged from 0.032 mm to 0.039 mm at phase 0% and from 0.084 mm to 0.096 mm at phase 50%. The SD was found not to vary linearly with Beacon angle in the range of 0° and 15°. A positive systematic error was observed with amplitude 0.07 mm/degree at phase 0% and 0.05 mm/degree at phase 50%. Rate dependence: SD and displacement amplitudes did not vary significantly between 0.2 Hz and 0.33 Hz. At 1 Hz, both 0% and 50% amplitude measurements shifted up appreciably, by 0.72 mm and 0.78 mm, respectively. As compared with the 0.33 Hz data, SD at phase 0% was 1.6 times higher and 5.4 times higher at phase 50%. Respiratory waveform tracking accuracy: SD of 0.233 mm with approximately normal distribution in over 134 min of tracking (201468 data points). The Surface Beacon transponder appears to be stable, accurate, and reproducible. Submillimeter resolution is achieved throughout breathing and sinusoidal waveforms. PACS number(s): 87.50.ct, 87.50.st, 87.50.ux, 87.50.wp, 87.50.yt

Accuracy evaluation of a six‐degree‐of‐freedom couch using cone beam CT and IsoCal phantom with an in‐house algorithm

Purpose: The accuracy of a six degree of freedom (6DoF) couch was evaluated using a novel method. Methods: Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were acquired with different, known combinations of couch pitch and roll angles. Pitch and roll angles between the maximum allowable values of 357 and 3 degrees were tested in one degree increments. A total of 49 combinations were tested at 0 degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry within the IsoCal phantom, were determined in the 49 image sets with in‐house software. The BB positions at different rotation angles were determined using a rotation matrix from the original BB positions at zero pitch and roll angles. A linear least squares fit method estimated the rotation angles and differences between detected and nominal rotation angles were calculated. This study was conducted for the case with and without extra weight on the couch. Couch walk shifts for the system were investigated using eight combinations of rotation, roll and pitch. Results: A total of 49 CBCT images with voxel sizes 0.5 × 0.5 × 1.0 mm3 were taken for the case without extra weight on the couch. The 16 BBs were determined to evaluate the isocenter translation and rotation differences between the calculated and nominal couch values. Among all 49 calculations, the maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for roll and 0.09 degrees for yaw. The corresponding mean and standard deviation values were 0.028 ± 0.032, −0.043 ± 0.058, and −0.009 ± 0.033 degrees. The maximum translation differences were 0.3 mm in the left–right direction, 0.5 mm in the anterior–posterior direction and 0.4 mm in the superior–inferior direction. The mean values and corresponding standard deviations were 0.07 ± 0.12, −0.05 ± 0.25, and −0.12±0.14 mm for the planes described above. With an 80 kg phantom on the couch, the maximum translation shift was 0.69 mm. The couch walk translation shifts were less than 0.1 mm and rotation shifts were less than 0.1 degree. Conclusions: Errors of a new 6DoF couch were tested using CBCT images of a 3D phantom. The rotation errors were less than 0.3 degree and the translation errors were less than or equal to 0.8 mm in each direction. This level of accuracy is warranted for clinical radiotherapy utilization including stereotactic radiosurgery.

A feasibility study of applying thermal imaging to assist quality assurance of high-dose rate brachytherapy

Aim: High-dose rate (HDR) brachytherapy poses a special challenge to radiation safety and quality assurance (QA) due to its high radioactivity, and it is thus critical to verify the HDR source location and its radioactive strength. This study explores a new application for thermal imaging, to visualize/locate the HDR source and measure radioactivity using temperature information. A potential application would relate to HDR QA and safety improvement. Methods: Heating effects by an HDR source were studied using finite element analysis (FEA). Thermal cameras were used to visualize an HDR source inside a plastic catheter made of polyvinylidene difluoride (PVDF). Using different source dwell times, relationships between the HDR source strength and heating effects were studied, thus establishing potential daily QA criteria using thermal imaging. Results: For an Ir-192 source with a source radioactivity of 10 Ci, the decay-induced heating power inside the source was about 13.3 mW. After the HDR source was extended into the PVDF applicator and reached thermal equilibrium, thermal imaging visualized the temperature gradient of 10 K/cm along the PVDF catheter surface, which agreed with FEA modeling. For the Ir-192 source strengths ranging from 16.9 to 41.1 kU, thermal imaging could verify source activity with a relative error of 6.3% with a dwell time of 10 s, and a relative error of 2.5% with 100 s. Conclusion: Thermal imaging could be a feasible tool to visualize HDR source dwell positions and verify source integrity. Potentially, patient safety and treatment quality may be improved by integrating thermal measurements into HDR QA procedures.