Preoperative and intraoperative assessment of myometrial invasion in patients with FIGO stage I non-endometrioid endometrial carcinoma-a large-scale, multi-center, and retrospective study.

INTRODUCTION: Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. METHOD: This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. RESULTS: Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000-2012: Kappa = 0.776; 2013-2014: Kappa = 0.625; 2015-2016: Kappa = 0.545; 2017-2019: Kappa = 0.652). CONCLUSION: In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

Extended HPV Genotyping for Risk Assessment of Cervical Intraepithelial Neoplasia Grade 2/3 or Worse in a Cohort Study.

BACKGROUND: We sought to identify the absolute risk of specific HPV genotype for cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/3+) and to develop a risk-based management strategy in an HPV-positive population. METHODS: HPV genotyping was performed based on a 3-year cervical cancer screening cohort. The study endpoints were histologic CIN2+/3+. The prevalence of specific HPV genotype was calculated by minimum, any type, and hierarchical attribution estimate. The absolute CIN2+/3+ risks of specific HPV genotype were estimated and risk-based management strategy was established according to the American Society for Colposcopy and Cervical Pathology guideline. The efficacy of conventional and risk-based management strategies for non-16/18 HPVs were further evaluated. RESULTS: Eligible data were available for 8,370 women with a median age of 48 years (interquartile range, 42-53 years). At baseline, there were 1,062 women with HPV-positive disease, including 424 with multiple and 639 with single infections. CIN2+/3+ cases represented 113/74, 23/8, 20/7, and 52/31 patients at baseline and first-, second-, and third-year visits, respectively. Women with multiple HPV infections at baseline were more prone to persistent infection than those with single infection (P<.0001). HPV16 and HPV52 were the top 2 ranking among baseline and 3-year cumulative CIN2+/3+ cases. Based on the absolute risk of specific HPV genotype combined with cytology for CIN2+/3+, all non-16/18 HPVs were divided into 4 risk-stratified groups. Compared with conventional strategy, the risk-based strategy had higher specificity (P=.0000) and positive predictive value (P=.0322) to detect CIN3+ and needed fewer colposcopies for each CIN3+ case. CONCLUSIONS: Based on our study findings, we propose a new extended HPV genotyping protocol, which would provide a better strategy for achieving precise risk-based management of HPV-positive populations.

Total value adjustment of Bermudan option valuation under pure jump Lévy fluctuations.

During the COVID-19 pandemic, many institutions have announced that their counterparties are struggling to fulfill contracts. Therefore, it is necessary to consider the counterparty default risk when pricing options. After the 2008 financial crisis, a variety of value adjustments have been emphasized in the financial industry. The total value adjustment (XVA) is the sum of multiple value adjustments, which is also investigated in many stochastic models, such as the Heston [B. Salvador and C. W. Oosterlee, Appl. Math. Comput. 391, 125489 (2020)] and Bates [L. Goudenège et al., Comput. Manag. Sci. 17, 163-178 (2020)] models. In this work, a widely used pure jump Lévy process, the Carr-Geman-Madan-Yor process has been considered for pricing a Bermudan option with various value adjustments. Under a pure jump Lévy process, the value of derivatives satisfies a fractional partial differential equation (FPDE). Therefore, we construct a method that combines Monte Carlo with a finite difference of FPDE to find the numerical approximation of exposure and compare it with the benchmark Monte Carlo simulation and Fourier-cosine series method. We use the discrete energy estimate method, which is different from the existing works, to derive the convergence of the numerical scheme. Based on the numerical results, the XVA is computed by the financial exposure of the derivative value.

Dose kernel decomposition for spot-based radiotherapy treatment planning.

PURPOSE: Pre-calculation of accurate dose deposition kernels for treatment planning of spot-based radiotherapies, such as Gamma Knife (GK) and Gamma Pod (GP), can be very time-consuming and may require large data storage with an enormous number of possible spots. We proposed a novel kernel decomposition (KD) model to address accurate and fast (real-time) dose calculation with reduced data storage requirements for spot-based treatment planning. The application of the KD model was demonstrated for clinical GK and GP radiotherapy platforms. METHODS: The dose deposition kernel at each spot (shot position) is modeled as the product of a shift-invariant kernel based on a reference kernel and spatially variant scale factor. The reference kernel, one for each collimator, is defined at the center of the commissioning phantom for GK and at the center of the treatment target for GP and calculated using the Monte Carlo (MC) method. The spatially variant scale factor is defined as the ratio of the mean tissue maximum ratio (TMR) at the candidate shot position to that at the reference kernel position, and the mean TMR map is calculated within the entire volume through parallel beam ray tracing on the density image followed by averaging over all source directions. The proposed KD dose calculations were compared with the MC method and with the GK and GP treatment planning system (TPS) computations for various shot positions and collimator sizes utilizing a phantom and 14 and 12 clinical plans for GK and GP, respectively. RESULTS: For the phantom study, the KD Gamma index (3%/1 mm) passing rates were greater than 99% (median 100%) relative to the MC doses, except for the shots close to the boundary. The passing rates dropped below 90% for 8 mm (16 mm) shots positioned within ∼1 cm (∼2 cm) of the boundary. For the clinical GK plans, the KD Gamma passing rates were greater than 99% (median 100%) compared to the MC and greater than 92% (median 99%) compared to the TPS. For the clinical GP plans, the KD Gamma passing rates were greater than 95% (median 98%) compared to the MC and greater than 91% (median 97%) compared to the TPS. The scale factors were calculated in sub-seconds with GPU implementation and only need to be calculated once before treatment plan optimization. The calculation of the dose kernel was also within sub-seconds without requiring beam-by-beam calculation commonly done in the TPS. CONCLUSION: The proposed model can provide an accurate dose and enables real-time dose and derivative calculations by kernel shifting and scaling without pre-calculating or requiring large data storage for GK and GP dose deposition kernels during treatment planning. This model could be useful for spot-based radiotherapy treatment planning by allowing an efficient global fine search for optimal spots.

POD-DOSI: A dedicated dosimetry system for GammaPod commissioning and quality assurance.

PURPOSE: GammaPod, a stereotactic partial breast irradiator allowing highly conformal radiation dose delivery, has its unique mechanical design and treatment planning system (TPS). However, the uniqueness of the system poses challenges regarding initial GammaPod system commissioning and routine quality assurance (QA). In this study, we report POD-DOSI, a dedicated dosimetry system for accurate and efficient commissioning and QA of GammaPod. MATERIALS AND METHODS: The POD-DOSI system consists of two subsystems, POD-Scanner and POD-Calculator. The POD-Scanner is an automatic ion-chamber positioning system driven by two translational stepper motors for anterior-posterior, longitudinal, and lateral beam scanning. The stepper motors are controlled by a microcomputer through an in-house-developed graphical user interface, which can be remotely accessed by a laptop via wireless connection. The POD-Calculator is a commissioned GPU-based Monte Carlo dose calculation engine, which calculates dose by transporting particles from phase space constructed for GammaPod. In our institution, the POD-DOSI system was used for GammaPod TPS commissioning and dose verification. The POD-Calculator was further developed as a secondary dose calculation tool performing patient-specific plan QA before each treatment. RESULTS: The POD-DOSI system has been fully evaluated and tested, both mechanically and dosimetrically, and applied successfully to drive the commissioning of our GammaPod system. The POD-Scanner achieved 0.1 mm accuracy in ion-chamber positioning tests. The POD-Calculator generated dose profiles matched well with water phantom measurements and TPS calculations to <0.5 mm accuracy. For end-to-end test on 56 different treatment plans, in-water point dose measurements by POD-Scanner were within ±2.20% of the doses calculated by POD-Calculator (range: -2.01% to 2.20%, mean: 0.04%, std_dev: 1.10%). Correspondingly, when switching the calculation medium from water to breast tissue, the point doses calculated by the POD-Calculator were within ±1.60% of the point doses calculated by the GammaPOD TPS (range: -1.59% to 1.51%, mean: -0.02%, std_dev: 0.73%). The average three-dimensional gamma passing rate between the GammaPod TPS doses and the POD-Calculator doses was 97.10% under the 2%/1 mm gamma criteria. The POD-DOSI system substantially shortened the GammaPod dosimetry commissioning time from weeks to days. CONCLUSION: The developed POD-DOSI system resolves the challenges and streamlines the process of GammaPod commissioning and QA. It improves the efficiency and accuracy for both GammaPod commissioning and routine patient-specific QA.

Electron modulated arc therapy (EMAT) using photon MLC for postmastectomy chest wall treatment I: Monte Carlo-based dosimetric characterizations.

PURPOSE: To study the dosimetric properties of electron arc beams delivered by photon-beam multi-leaf collimators (pMLC) in electron modulated arc therapy (EMAT) for postmastectomy chest wall treatments. METHODS: Using the Monte Carlo method, we simulated a 2100EX Varian linear accelerator and verified the beam models in a water tank. Dosimetric characterizations were performed on cylindrical water phantoms of elliptical bases with various field sizes, arc ranges and source-to-surface distances (SSDs) for 6, 9 and 12 MeV beam energy. RESULTS: The arc beam has a higher bremsstrahlung dose than the static beam at the isocenter due to crossfire, but choosing a field size greater than 5 cm effectively reduces the bremsstrahlung dose. The depths of the 90% maximum dose located at 1.7, 2.8 and 4.1 cm for 6, 9 and 12 MeV, respectively, are similar to those of the static beams and independent of the field size and arc range. CONCLUSION: Based on the study, we recommend using the 5 cm field width for electron arc beams considering both bremsstrahlung dose at the isocenter and the arc profile penumbra. To ensure sufficient PTV edge coverage, we recommend a field length extension of at least 4 cm from PTV's edge for all beam energies and an arc extension of around 7°, 5°, and 5° for beam energies 6, 9, and 12 MeV, respectively. These dosimetric characterizations are the basis of pMLC-delivered EMAT treatment planning for postmastectomy chest wall patients.

Convolution-based modified Clarkson integration (CMCI) for electron cutout factor calculation.

Electron therapy is widely used to treat shallow tumors because of its characteristic sharp dose fall-off beyond a certain range. A customized cutout is typically applied to block radiation to normal tissues. Determining the final monitor unit (MU) for electron treatment requires an output factor for the cutout, which is usually generated by measurement, especially for highly irregular cutouts. However, manual measurement requires a lengthy quality assurance process with possible errors. This work presents an accurate and efficient cutout output factor prediction model, convolution-based modified Clarkson integration (CMCI), to replace patient-specific output factor measurement. Like the Clarkson method, we decompose the field into basic sectors. Unlike the Clarkson integration method, we use annular sectors for output factor estimation. This decomposition method allows calculation via convolution. A 2D distribution of fluence is generated, and the output factor at any given point can be obtained. We applied our method to 10 irregularly shaped cutouts for breast patients for 6E, 9E, and 15E beams and compared the results with measurements and the electron Monte Carlo (eMC) calculation using the Eclipse planning system. While both the CMCI and eMC methods showed good agreement with chamber measurements and film measurements in relative distributions at the nominal source to surface distance (SSD) of 100 cm, eMC generated larger errors than the CMCI method at extended SSDs, with up to -9.28% deviations from the measurement for 6E beam. At extended SSD, the mean absolute errors of our method relative to measurements were 0.92 and 1.14, while the errors of eMC were 1.42 and 1.79 for SSD 105 cm and 110 cm, respectively. These results indicate that our method is more accurate than eMC, especially for low-energy beams, and can be used for MU calculation and as a QA tool for electron therapy.

A slit method to determine the focal spot size and shape of TomoTherapy system.

PURPOSE: To obtain accurate x-ray source profile measurements using a slit-collimator, the slit-collimator should have a narrow width, large height, and be positioned near the source. However, these conditions may not always be met. In this paper, the authors provide a detailed analysis of the slit measurement geometry and the relationship between the slit parameters and the measured x-ray source profile. The slit model allows the use of a shorter and more easily available slit-collimator, while accurate source profile measurements can still be obtained. METHODS: Measurements were performed with a variety of slit widths and/or slit to source distances. The relationship derived between the slit parameters and the measured profile was used to determine the true focal spot profile through a least square fit of the profile data. The model was verified by comparing the predicted profiles at a variety of slit-collimator parameters with the measured results on the TomoTherapy Hi-Art system. RESULTS: Both the treatment beam and the imaging beam were measured. For treatment mode, it was found that a source consisting of one Gaussian with a 0.75 mm full-width-half-maximum (FWHM) and 72% peak amplitude and a second Gaussian with a 2.27 mm FWHM and 18% peak amplitude matched measurement profiles. The overall source profile has a FWHM of 0.93 mm, but with a higher amplitude in the tail region than a single Gaussian. For imaging mode, the source consists of one Gaussian with a 0.68 mm FWHM and 82% peak amplitude and a second Gaussian with a 1.83 mm FWHM and 18% peak amplitude. The overall source profile has a FWHM of 0.77 mm. CONCLUSIONS: Our study of the focal spot measurement using slit-collimators showed that accurate source profile measurements can be achieved through fitting of measurement results at different slit widths and source-to-slit distances (SSD). Quantitative measurements of the TomoTherapy linac focal spot showed that the source distribution could be better described with a model consisting of two Gaussian components rather than a single Gaussian model as assumed in previous studies.

Monte Carlo-based analytical model for small and variable fields delivered by TomoTherapy.

BACKGROUND AND PURPOSE: Extend to very small fields the validity of a Monte Carlo (MC) based model of TomoTherapy called TomoPen for future implementation of the dynamic jaws feature for helical TomoTherapy. MATERIALS AND METHODS: First, the modelling of the electron source was revisited using a new method to measure source obscuration for very small fields (<1cm). The method consisted in MC simulations simulations and measurements of the central dose in a water phantom for a 10 cm x FW field scanned to deliver a 10 x 10 cm(2) fluence. FW, the longitudinal field width, was varied from 0.4 to 5 cm. The second part of the work consisted of adapting TomoPen to account for any configuration of the jaws in a fast and efficient way by using routinely only the phase-space file of the largest field (5 cm) and interpolated analytical information of phase-space files of smaller field widths. RESULTS: For the electron source fine tuning, it was shown that the best results were obtained for a 1.1mm wide spot. Our single phase-space method showed no significant differences compared to MC simulations of various field widths even though only longitudinal intensity and angular analytical functions were applied to the 5 cm phase-space. CONCLUSION: The designed model is able to simulate all jaw openings from the 5 cm field phase-space file by applying a bi-dimensional analytical function accounting for the fluence and the angular distribution in the longitudinal direction.

Assessment of parotid gland dose changes during head and neck cancer radiotherapy using daily megavoltage computed tomography and deformable image registration.

PURPOSE: To analyze changes in parotid gland dose resulting from anatomic changes throughout a course of radiotherapy in a cohort of head-and-neck cancer patients. METHODS AND MATERIALS: The study population consisted of 10 head-and-neck cancer patients treated definitively with intensity-modulated radiotherapy on a helical tomotherapy unit. A total of 330 daily megavoltage computed tomography images were retrospectively processed through a deformable image registration algorithm to be registered to the planning kilovoltage computed tomography images. The process resulted in deformed parotid contours and voxel mappings for both daily and accumulated dose-volume histogram calculations. The daily and cumulative dose deviations from the original treatment plan were analyzed. Correlations between dosimetric variations and anatomic changes were investigated. RESULTS: The daily parotid mean dose of the 10 patients differed from the plan dose by an average of 15%. At the end of the treatment, 3 of the 10 patients were estimated to have received a greater than 10% higher mean parotid dose than in the original plan (range, 13-42%), whereas the remaining 7 patients received doses that differed by less than 10% (range, -6-8%). The dose difference was correlated with a migration of the parotids toward the high-dose region. CONCLUSIONS: The use of deformable image registration techniques and daily megavoltage computed tomography imaging makes it possible to calculate daily and accumulated dose-volume histograms. Significant dose variations were observed as result of interfractional anatomic changes. These techniques enable the implementation of dose-adaptive radiotherapy.

Objective assessment of deformable image registration in radiotherapy: a multi-institution study.

The looming potential of deformable alignment tools to play an integral role in adaptive radiotherapy suggests a need for objective assessment of these complex algorithms. Previous studies in this area are based on the ability of alignment to reproduce analytically generated deformations applied to sample image data, or use of contours or bifurcations as ground truth for evaluation of alignment accuracy. In this study, a deformable phantom was embedded with 48 small plastic markers, placed in regions varying from high contrast to roughly uniform regional intensity, and small to large regional discontinuities in movement. CT volumes of this phantom were acquired at different deformation states. After manual localization of marker coordinates, images were edited to remove the markers. The resulting image volumes were sent to five collaborating institutions, each of which has developed previously published deformable alignment tools routinely in use. Alignments were done, and applied to the list of reference coordinates at the inhale state. The transformed coordinates were compared to the actual marker locations at exhale. A total of eight alignment techniques were tested from the six institutions. All algorithms performed generally well, as compared to previous publications. Average errors in predicted location ranged from 1.5 to 3.9 mm, depending on technique. No algorithm was uniformly accurate across all regions of the phantom, with maximum errors ranging from 5.1 to 15.4 mm. Larger errors were seen in regions near significant shape changes, as well as areas with uniform contrast but large local motion discontinuity. Although reasonable accuracy was achieved overall, the variation of error in different regions suggests caution in globally accepting the results from deformable alignment.

Motion-encoded dose calculation through fluence/sinogram modification.

Conventional radiotherapy treatment planning systems rely on a static computed tomography (CT) image for planning and evaluation. Intra/inter-fraction patient motions may result in significant differences between the planned and the delivered dose. In this paper, we develop a method to incorporate the knowledge of intra/inter-fraction patient motion directly into the dose calculation. By decomposing the motion into a parallel (to beam direction) component and perpendicular (to beam direction) component, we show that the motion effects can be accounted for by simply modifying the fluence distribution (sinogram). After such modification, dose calculation is the same as those based on a static planning image. This method is superior to the "dose-convolution" method because it is not based on "shift invariant" assumption. Therefore, it deals with material heterogeneity and surface curvature very well. We test our method using extensive simulations, which include four phantoms, four motion patterns, and three plan beams. We compare our method with the "dose-convolution" and the "stochastic simulation" methods (gold standard). As for the homogeneous flat surface phantom, our method has similar accuracy as the "dose-convolution" method. As for all other phantoms, our method outperforms the "dose-convolution." The maximum motion encoded dose calculation error using our method is within 4% of the gold standard. It is shown that a treatment planning system that is based on "motion-encoded dose calculation" can incorporate random and systematic motion errors in a very simple fashion. Under this approximation, in principle, a planning target volume definition is not required, since it already accounts for the intra/inter-fraction motion variations and it automatically optimizes the cumulative dose rather than the single fraction dose.