Single isocenter HyperArc treatment of multiple intracranial metastases: Targeting accuracy.

PURPOSE/OBJECTIVES: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS). MATERIALS/METHODS: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts. The phantom was simulated, planned, and delivered. For the purpose of comparing the accuracy of alignment, CBCTs were acquired with the isocenter centered and offset superiorly 8 cm, inferiorly 8 cm, anteriorly 7 cm, posteriorly 7 cm, and right 5 cm. There were six degrees of freedom corrections applied to the plans, as well as intentional rotational and translational errors for dose comparisons. Dose accuracy checks were performed with MOSFET and PTW Pinpoint chamber, and targeting accuracy was assessed with GafChromic films. RESULT: (A) Compared to centered CBCT, off-centered CBCT scan showed some alignment errors, with a maximum difference of 0.6-degree pitch and 0.9 mm translation when the phantom was placed 8 cm inferior off center. (B) For the single isocenter plan, measured doses of the five MOSFET were 95%-100% of the planned dose, whereas the multiple isocenter plans were 96%-100%. With intentional setup errors of 1-degree pitch, doses were 97.1%-100.4% compared to the perfect setup. The same was found for the two pinpoint chamber readings with 1-degree rotation and 1 mm translation. (C) Targeting accuracy for targets at the isocenter is 0.67 mm, within the machine specification of 0.75 mm. Targeting accuracy for isocenters 6-12 cm away from the target is in the range 0.67-1.18 mm. CONCLUSION: (A) Single isocenter HyperArc treatments for multiple brain metastases are feasible and targeting accuracy is clinically acceptable. (B) The vertex in a cranial scan is very important for proper alignment.

Attention-Deficit Hyperactivity Disorder among children of immigrants: immigrant generation and family poverty.

OBJECTIVES: Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common disorders diagnosed among children in the US. However, little knowledge is available about ADHD prevalence among children of immigrants, the fastest-growing population in the US. This study seeks to examine ADHD rates among children of immigrants in different generations compared to children of US-born parents and their association with family poverty. DESIGN: The sample includes 83,362 children aged 0-17 from the National Health Interview Survey (NHIS) 2010-2018 data. Multivariate logistic regression model is used to estimate prevalence of ADHD among children of immigrants compared to children of US-born parents. We then compare ADHD rates among the children sample in different immigrant generations. For all analyses, we examine ADHD occurrence separately for children in families living below the poverty threshold and those at or above the poverty threshold. RESULTS: The odds of having ADHD were significantly lower among children of immigrants compared to children of US-born parents. Both first-generation children and second-generation children of immigrants had significantly lower odds of having ADHD than children of US-born parents. Post hoc tests find that first-generation children had lower odds of having ADHD compared to second-generation children. Likewise, additional analyses showed that children of immigrants, first-generation children in particular, were less likely to have ADHD compared to children of US-born parents, in both lower- and higher-income families. CONCLUSION: Using a nationally representative sample of children, we find that the likelihood of having ADHD increases with higher generations, detecting differences in ADHD prevalence by immigration generation. Importantly, first-generation children had a significantly lower risk of having ADHD conditions compared to second-generation children and children of US-born parents, regardless of family socio-economic status. Public health policy and program development would gain from a clear comprehension of the shielding attributes of ADHD among immigrant families.

The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy.

Inhibitors of the DNA damage signaling kinase ATR increase tumor cell killing by chemotherapies that target DNA replication forks but also kill rapidly proliferating immune cells including activated T cells. Nevertheless, ATR inhibitor (ATRi) and radiotherapy (RT) can be combined to generate CD8+ T cell-dependent antitumor responses in mouse models. To determine the optimal schedule of ATRi and RT, we determined the impact of short-course versus prolonged daily treatment with AZD6738 (ATRi) on responses to RT (days 1-2). Short-course ATRi (days 1-3) plus RT caused expansion of tumor antigen-specific, effector CD8+ T cells in the tumor-draining lymph node (DLN) at 1 week after RT. This was preceded by acute decreases in proliferating tumor-infiltrating and peripheral T cells and a rapid proliferative rebound after ATRi cessation, increased inflammatory signaling (IFN-ß, chemokines, particularly CXCL10) in tumors, and an accumulation of inflammatory cells in the DLN. In contrast, prolonged ATRi (days 1-9) prevented the expansion of tumor antigen-specific, effector CD8+ T cells in the DLN, and entirely abolished the therapeutic benefit of short-course ATRi with RT and anti-PD-L1. Our data argue that ATRi cessation is essential to allow CD8+ T cell responses to both RT and immune checkpoint inhibitors.

Fuzzy analytic hierarchy process-based risk priority number for risk assessments of commissioning process of a ring gantry LINAC.

PURPOSE: We propose a fuzzy analytic hierarchy process (AHP)-based risk priority number (RPN) method in failure modes and effects analysis (FMEA) to overcome the shortcomings of traditional RPN-based FMEA. Our research group has previously published the FMEA to mitigate the failure modes (FMs) for the commissioning process of a ring gantry LINAC. However, inter-relationships among FMs were observed in high ranked FMs due to a heavy reliance on imaging system. METHODS: Fuzzy AHP was applied to determine relative weights of risk impacts based on inter-relationships among FMs. Since the time sequence dependency is a major factor for risk factors, a hierarchical structure of AHP was used to reflect the directional impacts such as causal influence and feedback loop. Two fuzzy weighted RPNs, called (RPNW and FRPNW , were calculated depending on the input values of severity (S), occurrence (O), and probability of not being detected (D) from the evaluators. The RPNW used numerical values, whereas the fuzzy values were used for FRPNW . Both RPNs were calculated by multiplying the weighted O, S, and D using the fuzzy AHP method. RESULTS: The differences between the two fuzzy RPN rankings are due to inherent fuzzy uncertainty and deviations in O, S, and D values submitted by the evaluators. Considering all results of traditional and fuzzy-based FMEA, the two most highly ranked FMs were identified: errors in determining the non-isocentric SSD and SSD from MV images because of the unique features of the ring gantry LINAC. CONCLUSION: This study has demonstrated the feasibility of the use of a fuzzy AHP-based RPN to perform comprehensive analysis and prioritization of FMs. The risk analysis using fuzzy AHP can be improved and/or refined based on the department's specific workflow and clinical preferences taking various priority weighting approaches into account.

Alcohol-related problem behaviors among Latin American immigrants in the US.

BACKGROUND: Prior research indicates that Latino immigrants are less likely than US-born individuals to use alcohol and meet criteria for an alcohol use disorder. However, our understanding of alcohol-related problem behaviors among Latino immigrants remains limited. We report the prevalence of alcohol-related problem behaviors among Latino immigrants vis-à-vis the US-born and examine the relationship between alcohol-related problem behavior and key migration-related factors and injury/receipt of emergency medical care. METHODS: The data source used for the present study is the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III, 2012-2013), a nationally representative survey of 36,309 civilian, non-institutionalized adults ages 18 and older in the US. Logistic regression was employed to examine the relationship between immigrant status and key outcomes. RESULTS: Foreign-born Latinos were less likely to report one or more alcohol-related problems compared to US-born Latinos (AOR = 0.41, 95% CI = 0.33-0.50) and the US-born general population (AOR = 0.38, 95% CI = 0.32-0.46). Latino immigrants arriving as children were, compared to those arriving later in life, significantly more likely to report alcohol-related problem behaviors, and experiences of discrimination were linked with greater risk of alcohol-related problem behavior as well. Latino immigrants reporting recurrent injury/emergency medical care utilization were more likely to report alcohol-related problem behavior. CONCLUSIONS: Latino immigrants are significantly less likely than US-born Latinos and the US-born general population to operate a vehicle under the influence of alcohol, take part in risky behaviors or fight while drinking, or to be arrested due to alcohol consumption.

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.

Longitudinal Trajectories of Food Insecurity Among Children of Immigrants.

Although research consistently points to higher rates of food insecurity (FI) among children of immigrants (COI), this is the first study to examine longitudinal trajectories of FI for this group. We used growth curve modeling and data from the 1998 Early Childhood Longitudinal Study-Kindergarten Cohort to compare trajectories of FI for COI and children of U.S.-born parents. After controlling for socioeconomic status and participation in nutrition programs, first- and second-generation COI had significantly higher initial and ongoing rates of FI compared to children of U.S.-born parents. Additional analyses found that all differences between COI and children of U.S.-born parents occurred for families in poverty. We find that COI from poor families have higher rates of FI, with some differences among COI by immigrant generation. Policymakers may need to focus on avenues other than public assistance to reduce FI among COI living in poverty.

Injuries Among School-aged Children of Immigrants.

In response to a dearth of research on injuries among children of immigrants, this study examined child injury rates by immigrant generation. We used generalized estimating equations and nationally representative data to estimate injury risk for school-aged children of immigrants of different generations compared to children of native, US-born parents. After controlling for multiple other factors including socioeconomic status, citizenship, and children's general health, both 1st and 2nd generation school-aged children had significantly lower odds of having injuries compared to children of natives. Additional analyses also found lower odds of injuries among 1st and 2nd generation children relative to children of natives that persisted in both lower- and higher-income families. The findings suggest that 1st and 2nd generation immigrant families possess factors that protect children from injury independent of socioeconomic status. Policy and program development would benefit from a clearer understanding of these protective factors.

A novel geometry-dosimetry label fusion method in multi-atlas segmentation for radiotherapy: a proof-of-concept study.

Multi-atlas segmentation (MAS) has been widely used to automate the delineation of organs at risk (OARs) for radiotherapy. Label fusion is a crucial step in MAS to cope with the segmentation variabilities among multiple atlases. However, most existing label fusion methods do not consider the potential dosimetric impact of the segmentation result. In this proof-of-concept study, we propose a novel geometry-dosimetry label fusion method for MAS-based OAR auto-contouring, which evaluates the segmentation performance in terms of both geometric accuracy and the dosimetric impact of the segmentation accuracy on the resulting treatment plan. Differently from the original selective and iterative method for performance level estimation (SIMPLE), we evaluated and rejected the atlases based on both Dice similarity coefficient and the predicted error of the dosimetric endpoints. The dosimetric error was predicted using our previously developed geometry-dosimetry model. We tested our method in MAS-based rectum auto-contouring on 20 prostate cancer patients. The accuracy in the rectum sub-volume close to the planning tumor volume (PTV), which was found to be a dosimetric sensitive region of the rectum, was greatly improved. The mean absolute distance between the obtained contour and the physician-drawn contour in the rectum sub-volume 2 mm away from PTV was reduced from 3.96 mm to 3.36 mm on average for the 20 patients, with the maximum decrease found to be from 9.22 mm to 3.75 mm. We also compared the dosimetric endpoints predicted for the obtained contours with those predicted for the physician-drawn contours. Our method led to smaller dosimetric endpoint errors than the SIMPLE method in 15 patients, comparable errors in 2 patients, and slightly larger errors in 3 patients. These results indicated the efficacy of our method in terms of considering both geometric accuracy and dosimetric impact during label fusion. Our algorithm can be applied to different tumor sites and radiation treatments, given a specifically trained geometry-dosimetry model.

A method for online verification of adapted fields using an independent dose monitor.

PURPOSE: Clinical implementation of online adaptive radiotherapy requires generation of modified fields and a method of dosimetric verification in a short time. We present a method of treatment field modification to account for patient setup error, and an online method of verification using an independent monitoring system. METHODS: The fields are modified by translating each multileaf collimator (MLC) defined aperture in the direction of the patient setup error, and magnifying to account for distance variation to the marked isocentre. A modified version of a previously reported online beam monitoring system, the integral quality monitoring (IQM) system, was investigated for validation of adapted fields. The system consists of a large area ion-chamber with a spatial gradient in electrode separation to provide a spatially sensitive signal for each beam segment, mounted below the MLC, and a calculation algorithm to predict the signal. IMRT plans of ten prostate patients have been modified in response to six randomly chosen setup errors in three orthogonal directions. RESULTS: A total of approximately 49 beams for the modified fields were verified by the IQM system, of which 97% of measured IQM signal agree with the predicted value to within 2%. CONCLUSIONS: The modified IQM system was found to be suitable for online verification of adapted treatment fields.

Correlation between the molecular subtype of breast cancer and the in vitro adenosine triphosphate-based chemosensitivity assay.

PURPOSE: The empirical use of a chemotherapy regimen shows different results in individual breast cancer patient treatment. Recent studies showed the effectiveness of the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). However, little is known about the correlation between chemosensitivity and breast cancer molecular subtypes. Therefore, we investigated whether the result of ATP-CRA is associated with a molecular subtype of breast cancer. METHODS: Two hundred eighty-seven patients diagnosed with breast cancer and receiving ATP-CRA at Mokdong Hospital, Ewha Womans University between September 2007 and December 2010 were enrolled in this study. Hormone receptor status, HER2/neu expression, and results of chemosensitivity tests of the patients was analyzed. RESULTS: In all of four subtypes, the combination of two agents showed significant higher mean cell death rate than a single agent. Within the breast cancer cell lines in this study, the range of chemosensitivity response was very wide and varied for each patient. For this reason, the molecular subtype of breast cancer is inconclusive in choosing an effective chemotherapeutic agent and in vitro chemosensitivity test, prior to therapy, could be a useful method for planning chemotherapy for each patient. CONCLUSION: Chemosensitivity response to anticancer agents was found to vary depending on the individual breast cancer patients. The molecular subtype of breast cancer is inconclusive to choose the effective chemotherapeutic agent and the in vitro chemosensitivity test, prior to therapy, could be more useful for planning chemotherapy for each patient.

An analysis of factors associated with increased perineal descent in women.

PURPOSE: Treatment of descending perineal syndrome is focused on personal etiology and on improving symptoms. However, the etiology of increased perineal descent (PD) is unclear. Therefore, the aim of the present study was to evaluate factors associated with increased resting and dynamic PD in women. METHODS: From January 2004 to August 2010, defecographic findings in 201 female patients were reviewed retrospectively. Patient's age, surgical history, manometric results and defecographic findings were compared with resting and dynamic PD. RESULTS: Age (P < 0.01), number of vaginal deliveries (P < 0.01) and resting anorectal angle (P < 0.01) were correlated with increased resting PD. Also, findings of rectoceles (P < 0.05) and intussusceptions (P < 0.05) were significantly correlated with increased resting PD. On the other hand, increased dynamic PD was correlated with age (P < 0.05), resting anal pressure (P < 0.01) and sigmoidoceles (P < 0.05). No significant correlation existed between non-relaxing puborectalis, history of pelvic surgery and increased PD. Also, no significant differences in PD according to the symptoms were observed. CONCLUSION: Increased number of vaginal deliveries and increased resting rectoanal angle are associated with increased resting PD whereas increased resting anal pressure is correlated with increased dynamic PD. Older age correlates with both resting and dynamic PD. Defecographic findings, such as rectoceles and intussusceptions, are associated with resting PD, and sigmoidoceles correlated with dynamic PD. These results can serve as foundational research for understanding the pathophysiology and causes of increasing PD in women better and for finding a fundamental method of treatment.

Effectiveness of breast-specific gamma imaging (BSGI) for breast cancer in Korea: a comparative study.

Despite the fact that mammography has been the golden standard in breast cancer detection for several decades, its sensitivity decreases for women with dense breast tissue, which happens to be common in Korea. As an alternative, breast ultrasonography can be effective diagnostic modalities that complement the defect of mammography. Recently, breast-specific gamma imaging (BSGI) has been introduced as a new diagnostic modality for breast cancer. This study was designed to analyze the effectiveness of BSGI in particular. In a retrospective study, 471 patients underwent BSGI, breast ultrasonography, and mammography simultaneously during the period between February 2009 and March 2010. The indications of BSGI were as follows: (a) patient who was diagnosed with malignancy prior to surgery, (b) patient who is under follow up after cancer surgery, (c) patient with lesions which cannot be evaluated by breast ultrasonography or mammography, (d) patient with multiple benign lesions, and (e) patient with suspicious lesion who refuses biopsy. Among these patients, 121 patients underwent biopsy, whereas others were followed up with imaging studies. We compared the BSGI results with those of mammography, breast ultrasonography, and pathology. The mean age of the patients was 49.63 ± 10.43 years. There were 107 patients with 110 malignant lesions and 364 patients with benign lesions. Total 474 lesions were evaluated. The sensitivities of BSGI, mammography, and breast ultrasonography were 94.45%, 93.64%, and 98.18%, respectively, whereas the specificities of BSGI, mammography, and breast ultrasonography were 90.93%, 90.66%, and 87.09%, respectively. The sensitivity and specificity of BSGI for axillary lymph node (LN) status were 44.7 4% and 87.88%, respectively. BSGI is a good complementary imaging modality with high sensitivity and high specificity for breast cancer detection. However, it has low efficacy for the evaluation for axillary LN status.

Outcomes of breast conserving surgery with immediate vicryl-mesh insertion: is it safe and effective?

Although breast-conserving surgery (BCS) has become a standard for breast-cancer surgery with improved cosmetic outcomes, there have been many attempts to achieve superior results. Vicryl-mesh insertion, one such method, is a simple technique involving a relatively short period of time. However, doubts regarding its safety and efficacy remain. Therefore, we attempted to analyze the aesthetic outcomes, patient satisfaction, and safety with respect to Vicryl mesh. From May 2007 to March 2009, 38 patients underwent BCS with immediate Vicryl-mesh insertion at Ewha Womans University Mokdong Hospital, Seoul, Korea. In the same period, 31 patients who underwent BCS for breast cancer were randomly selected as a control group. Five patients who underwent BCS with Vicryl-mesh insertion were excluded because they were lost to follow-up shortly after surgery. Retrospective analysis of patient records and oral interviews were performed. We analyzed patients' overall satisfaction, postoperative satisfaction with breast shape, pain, and postoperative complications in the two groups. The mean age, body mass index, follow-up period, specimen size, and ratio of benign to malignant tumors did not differ significantly between the two groups. With regard to tumor location, more tumors were in the upper and lower inner portions of the breast among patients who underwent BCS with Vicryl mesh. There were no significant differences in overall satisfaction or satisfaction with breast shape (p > 0.05), but differences in pain scores were significant (p = 0.016). In terms of the complication rate, four cases with complications (11.8%) were observed in the Vicryl-mesh group and no complications in the BCS-only group. Vicryl-mesh insertion showed a higher complication rate and no cosmetic gain. Therefore, we believe that Vicryl-mesh insertion should be performed carefully. In addition, studies involving many more cases and longer follow-up periods are needed.

A static multi-slit collimator system for scatter reduction in cone-beam CT.

A multiple-slit collimator (MSC) design was introduced for scatter reduction in cone-beam computed tomography (CBCT). Unlike most other collimators, the open and closed septa of the proposed MSC are placed in an equi-angular interval on a circular track of the central sagittal plane. Therefore, one gantry rotation provides only the half of necessary dataset and two gantry rotations are needed to obtain full information. During the first gantry rotation, the MSC position relative to the source is fixed. For the second rotation, the MSC is rotated by the equi-angle interval. We assume signals under the closed septa are totally attributed to scatter radiation. Then, scatter contributions under open septa are determined by interpolating them.Monte Carlo (MC) simulations for two virtual phantoms (one with a simple geometry and the other with two heterogeneities simulating the bone and the lung) were performed to evaluate the effectiveness of the system. Using the method developed, we could obtain images with significant scatter reduction. Contrast ratio (CR) improvement factors were 1.165 in a 2D projection view, and 1.210 and 1.223 at the central and peripheral slice of the reconstructed CBCT image of the simple geometry phantom.This preliminary study demonstrated that the proposed MSC, together with the imaging process technique, had a great potential to reduce scatter contribution in CBCT. Further studies will be performed to investigate the effect of various factors, such as reducing the detector size, increasing the number of history of MC simulation, and including many structures with different densities.

Development of a deformable lung phantom for the evaluation of deformable registration.

The deformable lung phantom was developed to account for the patient breathing motion, and to evaluate for a deformable image registration algorithm. The phantom consisted of an acryl cylinder filled with water and a latex balloon located in the inner space of the cylinder. A silicon membrane was attached to the inferior end of the phantom. This silicon membrane was designed to simulate a real lung diaphragm and to reduce motor workload. This specific design was able to reduce the metal use which may prevent infrared sensing of the real position management (RPM) gating system on 4D CT image acquisition. Verification of intensity based 3D demon deformable registration was based on peak exhale and peak inhale breathing phases. The registration differences ranged from 0.85 mm to 1.47 mm, and accuracy was determined according to inner target deformation. This phantom was able to simulate the features and deformation of real human lung and has the potential for wide application in 4D radiation treatment planning.

A dual-energy technique for enhanced localization accuracy in intracavitary brachytherapy.

The orthogonal imaging method is commonly used for source localization in brachytherapy. In some cases, however, difficulty is encountered in determining the dummy sources because of the presence of either contrast materials or bony structures. We here offer a novel method for source localization utilizing a dual-energy, radiographic technique. In this approach, two sets of orthogonal radiographic images (anterior-posterior and lateral views) are obtained using two different x-ray energies. Image processing (i.e., subtraction between two image sets) is carried out to enhance the source image. In a study performed using a laboratory developed pelvic phantom, it was demonstrated that the dual-energy method could significantly enhance the image quality of the dummy sources, and improve the achievable precision and relative accuracy in localization of source positions. When directly combined with digital imaging modalities, the dual-energy method can be a useful technique to improve the accuracy in brachytherapy source localization from planar radiographs.