Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study.

ABSTRACT: Patients with hemophilia A require exogenous factor VIII (FVIII) or nonfactor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector-based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain-deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single IV dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in 1 participant within 6 hours of infusion and resolved within 24 hours after infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%), and at week 104 it was 25.4% (range, 0.9%-71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or confirmed inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest dose cohort. This trial was registered at www.clinicaltrials.gov as #NCT03061201.

PET-based primary tumor volumetric parameters and survival of patients with non-small cell lung carcinoma.

OBJECTIVE: The purpose of the study was to assess metabolic tumor volume and total glycolytic activity of the primary tumor as prognostic parameters for outcome in patients with non-small cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Thirty-nine patients who had undergone a baseline staging PET/CT examination at our institution for the diagnosis of NSCLC were retrospectively identified. The maximum standardized uptake value (SUV(max)), metabolic tumor volume, and total glycolytic activity were segmented from PET using the gradient method; 12-month survival and overall survival at the end of follow-up were used as outcome measures. Multivariate logistic regression, receiver operating characteristic curve analysis, and Kaplan-Meier curves for survival analysis were generated and compared using the Mantel-Cox log-rank test. RESULTS: The mean gradient-based metabolic tumor volume and gradient-based total glycolytic activity were significantly greater in the patients who died (93.3 mL and 597.5 g) than in those who survived (19.3 mL and 193.9 g, respectively) (p < 0.003 and p < 0.031). There was no statistically significant difference in the mean SUV(max) between the patients who survived (12.7) at 12 months and those who had died (13.1) (p = 0.85). On multivariate analysis, gradient-based metabolic tumor volume was the only variable associated with 12-month mortality when adjusted for all other factors.(.) The area under the curve (AUC) for gradient-based metabolic tumor volume was 0.77 (p < 0.006). A significant difference in the time to survival was observed between high and low gradient-based metabolic tumor volume (log-rank p < 0.05) cohorts using the median gradient-based metabolic tumor volume (9.7 mL) as the cut point. CONCLUSION: PET-based volumetric imaging parameters are potential prognostic markers of outcome in patients with NSCLC.

The role of PET/CT in the management of cervical cancer.

OBJECTIVE. Cervical cancer is the second most common malignancy in women worldwide and the third most common cause of cancer mortality in the United States. The aim of this article is to describe cervical cancer and outline the value of (18)F-FDG PET/CT in the management of cervical malignancy. CONCLUSION. The value of PET/CT has been found in staging and treatment strategy for cervical cancer. FDG PET/CT facilitates decision-making and radiation treatment planning and provides important information about treatment response, disease recurrence, and long-term survival.

A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.

Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.

Fast Deformable Image Registration for Real-Time Target Tracking During Radiation Therapy Using Cine MRI and Deep Learning.

PURPOSE: We developed a deep learning (DL) model for fast deformable image registration using 2-dimensional sagittal cine magnetic resonance imaging (MRI) acquired during radiation therapy and evaluated its potential for real-time target tracking compared with conventional image registration methods. METHODS AND MATERIALS: Our DL model uses a pair of cine MRI images as input and provides a motion vector field (MVF) as output. The MVF is then applied to align the input images. A retrospective study was conducted to train and evaluate our model using cine MRI data from patients undergoing treatment for abdominal and thoracic tumors. For each treatment fraction, MR-linear accelerator delivery log files, tracking videos, and cine image files were analyzed. Individual MRI frames were temporally sampled to construct a large set of image registration pairs used to evaluate multiple methods. The DL model was optimized using 5-fold cross validation, and model outputs (transformed images and MVFs) using test set images were saved for comparison with 3 conventional registration methods (affine, b-spline, and demons). Evaluation metrics were 3-fold: (1) registration error, (2) MVF stability (both spatial and temporal), and (3) average computation time. RESULTS: We analyzed >21 hours of cine MRI (>629,000 frames) acquired during 86 treatment fractions from 21 patients. In a test set of 10,320 image registration pairs, DL registration outperformed conventional methods in both registration error (affine, b-spline, demons, DL; root mean square error: 0.067, 0.040, 0.036, 0.032; paired t test demons vs DL: t[20] = 4.2, P < .001) and computation time per frame (51, 1150, 4583, 8 ms). Among deformable methods, spatial stability of resulting MVFs was comparable; however, the DL model had significantly improved temporal consistency. CONCLUSIONS: DL-based image registration can leverage large-scale MR cine data sets to outperform conventional registration methods and is a promising solution for real-time deformable motion estimation in radiation therapy.

ACR Appropriateness Criteria® Right Upper Quadrant Pain: 2022 Update.

Acute right upper quadrant pain is one of the most common presenting symptoms in hospital emergency departments, as well as outpatient settings. Although gallstone-related acute cholecystitis is a leading consideration in diagnosis, a myriad of extrabiliary sources including hepatic, pancreatic, gastroduodenal, and musculoskeletal should also be considered. This document focuses on the diagnostic accuracy of imaging studies performed specifically to evaluate acute right upper quadrant pain, with biliary etiologies including acute cholecystitis and its complications being the most common. An additional consideration of extrabiliary sources such as acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms remain a diagnostic consideration in the right clinical setting. The use of radiographs, ultrasound, nuclear medicine, CT, and MRI for these indications are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Abnormal Liver Function Tests.

Liver function tests are commonly obtained in symptomatic and asymptomatic patients. Various overlapping lab patterns can be seen due to derangement of hepatocytes and bile ducts function. Imaging tests are pursued to identify underlying etiology and guide management based on the lab results. Liver function tests may reveal mild, moderate, or severe hepatocellular predominance and can be seen in alcoholic and nonalcoholic liver disease, acute hepatitis, and acute liver injury due to other causes. Cholestatic pattern with elevated alkaline phosphatase with or without elevated γ-glutamyl transpeptidase can be seen with various causes of obstructive biliopathy. Acute or subacute cholestasis with conjugated or unconjugated hyperbilirubinemia can be seen due to prehepatic, intrahepatic, or posthepatic causes. We discuss the initial and complementary imaging modalities to be used in clinical scenarios presenting with abnormal liver function tests. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

ACR Appropriateness Criteria® Epigastric Pain.

Epigastric pain can have multiple etiologies including myocardial infarction, pancreatitis, acute aortic syndromes, gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, and hiatal hernia. This document focuses on the scenarios in which epigastric pain is accompanied by symptoms such as heartburn, regurgitation, dysphagia, nausea, vomiting, and hematemesis, which raise suspicion for gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, or hiatal hernia. Although endoscopy may be the test of choice for diagnosing these entities, patients may present with nonspecific or overlapping symptoms, necessitating the use of imaging prior to or instead of endoscopy. The utility of fluoroscopic imaging, CT, MRI, and FDG-PET for these indications are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Impact of neuroimaging in the pretreatment evaluation of early stage non-small cell lung cancer.

BACKGROUND: There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. RESULTS: We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. CONCLUSIONS: In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed.

An in-silico quality assurance study of contouring target volumes in thoracic tumors within a cooperative group setting.

INTRODUCTION: Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee's multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a "dry run" for trial implementation. METHODS: CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).Six board-certified thoracic radiation oncologists were designated as the 'Experts' for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants' contours were then compared with Experts' STAPLE contours. RESULTS: When compared to the Experts' STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. CONCLUSIONS: High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

Radiation treatment breaks and ulcerative mucositis in head and neck cancer.

Unplanned radiation treatment breaks and prolongation of the radiation treatment time are associated with lower survival and locoregional control rates when radiotherapy or concurrent chemoradiotherapy is used in the curative treatment of head and neck cancer. Treatment of head and neck cancer is intense, involving high-dose, continuous radiotherapy, and often adding chemotherapy to radiotherapy. As the intensity of treatment regimens has escalated in recent years, clinical outcomes generally have improved. However, more intensive therapy also increases the incidence of treatment-related toxicities, particularly those impacting the mucosal lining of the oral cavity, pharynx, and cervical esophagus, and results in varying degrees of ulcerative mucositis. Ulcerative mucositis is a root cause of unscheduled radiation treatment breaks, which prolongs the total radiation treatment time. Alterations in radiotherapy and chemotherapy, including the use of continuous (i.e., 7 days/week) radiotherapy to ensure constant negative proliferative pressure, may improve efficacy outcomes. However, these approaches also increase the incidence of ulcerative mucositis, thereby increasing the incidence of unplanned radiation treatment breaks. Conversely, the reduction of ulcerative mucositis to minimize unplanned breaks in radiotherapy may enhance not only tolerability, but also efficacy outcomes. Several strategies to prevent ulcerative mucositis in radiotherapy for head and neck cancer have been evaluated, but none have demonstrated strong efficacy. Continued investigation is needed to identify superior radiation treatment regimens, technology, and supportive care that reduce unplanned radiation treatment breaks with the goal of improving clinical outcomes in head and neck cancer.

Perceptions and practices regarding women's vaginal health following radiation therapy: A survey of radiation oncologists practicing in the United States.

PURPOSE: Vaginal stenosis (VS) is a recognized complication of pelvic and vaginal radiation therapy (RT). METHODS AND MATERIALS: A 26-item survey assessing the signs/symptoms, risk factors, diagnosis, prevention, treatment, and impact of VS on women's sexual health was distributed to radiation oncologists. Descriptive statistics were calculated. Chi-square tests examined differences in categorical responses. RESULTS: A total of 233 (10.5%) participants completed the entire survey. Twelve percent, 21%, and 68% report treating gynecologic (GYN) tumors only, non-GYN pelvic tumors only, or both, respectively. Regarding risk factors, 78% believed that VS can be caused by pelvic RT alone, 91% by vaginal brachytherapy alone, and 98% by combined pelvic RT and vaginal brachytherapy. Approximately one-half of respondents felt that being postmenopausal and having a hysterectomy before radiation therapy were risk factors for VS, whereas the other half felt that these were not risk factors. All respondents agreed that VS is a clinical diagnosis. Respondents indicated that VS symptoms include dyspareunia, vaginal pain, dryness, and/or bleeding (100%, 90%, 85%, and 72%, respectively); 65% indicated all 4. The most commonly recommended treatment for VS is vaginal dilator use. Radiation oncologists who treat GYN-only versus non-GYN cancers were more likely to perform a vaginal examination, to distribute written instructions regarding vaginal dilator use (P = .002), to have vaginal bleeding reported after RT (P = .001), and to refer patients to a sexual counselor (P = .007). Most providers (73%) expressed willingness to participate in prospective research on the diagnosis and treatment of VS. CONCLUSIONS: This is the first large-scale survey of radiation oncologists' perceptions and practices regarding VS. There is agreement among providers regarding the signs/symptoms of VS and strategies for its prevention/treatment using vaginal dilators. Further prospective and observational research is needed. This survey shows a willingness on the part of providers to take part in prospective research regarding the diagnosis, impact, and treatment of VS on women's sexual health.

Single ventricle palliation: greater risk of complications with the Fontan procedure than with the bidirectional Glenn procedure alone.

BACKGROUND: This study was performed to evaluate and compare the early, intermediate, and long-term outcomes of the bidirectional Glenn procedure and Fontan procedure in patients who live at moderately high altitude. METHODS: The outcome of each method of palliation for patients with a functionally single ventricle was retrospectively evaluated from a review of medical records. RESULTS: The bidirectional Glenn procedure was performed in 177 patients from October 1984 to June 2004. The Fontan procedure was performed in 149 patients from June 1978 to June 2004. Cardiovascular death or heart transplantation occurred in 8% of patients after the bidirectional Glenn procedure and 17% of patients after the Fontan procedure. Complications of systemic thromboembolic events, bleeding associated with anticoagulation therapy, protein losing enteropathy, and arrhythmias requiring implantation of a pacemaker, cardioversion, or radiofrequency ablation occurred in 7% of patients after the bidirectional Glenn procedure and 47% of patients after the Fontan procedure. Cardiovascular deaths and heart transplantation occurred less frequently when the Fontan procedure was performed in patients with a previous bidirectional Glenn procedure. However, the actuarial transplant-free survival and freedom from complications was not superior for a subgroup of patients who had a Fontan procedure after a bidirectional Glenn procedure in comparison to a subgroup of patients who had a bidirectional Glenn procedure alone. CONCLUSIONS: The bidirectional Glenn procedure can be used for long-term palliation of patients with a functionally single ventricle. Additional palliation with a Fontan procedure may increase the risk of stroke, protein losing enteropathy and arrhythmias without improving survival.

Extracorporeal membrane oxygenation for cardiac disease: no longer a mistaken diagnosis.

Extracorporeal membrane oxygenation (ECMO) has become a valuable adjunct in caring for infants and children with heart disease. Since the initial reports of ECMO support for cardiac failure in children, the number of centers providing cardiac support and the number of cases of cardiac ECMO have steadily increased. The International Registry for Extracorporeal Life Support Organization has reported survival statistics for cardiac cases in neonates, children, and adults ranging from 33% to 43%. These numbers are similar to the survival from recent reports by Morris (39%) and Chaturvedi (49%). Survival is influenced by ability to be weaned from bypass in the operating room and by residual structural disease and multi-organ system failure but not by cardiac arrest and single ventricle physiology. To improve results in the future, we need to focus on better predicting the need for support and avoiding multi-organ system failure before initiating ECMO. Rapid deployment of ECMO may further improve results for patients who deteriorate suddenly in the intensive care unit.

Optimizing efficiency and safety in a radiation oncology department through the use of ARIA 11 Visual Care Path.

PURPOSE: Visual Care Path (VCP) is a workflow tool within the ARIA 11 Record and Verify System. The purpose of this study was to quantify the impact of VCP implementation on the metrics of efficiency, safety, and staff satisfaction. METHODS AND MATERIALS: Our multidisciplinary quality improvement team reviewed the entire process of patient care and constructed VCP modules to chart serial and parallel events from consultation to treatment completion. A failure mode and effects analysis was performed to identify high-risk tasks within existing patient care workflow. Data on timeliness of task completion were collected for 612 patients (6560 tasks) in 3 time phases: pre-VCP, transition, and post-VCP. Errors detected during a physics plan check were also monitored. A survey about the VCP was distributed to all staff to evaluate the impact of the VCP on the department. Descriptive statistics were calculated for the metrics of efficiency, safety, and staff satisfaction. RESULTS: Notable improvements in efficiency and safety were observed. Radiation oncologists' compliance with timely completion of the Simulation Preparation VCP tasks increased from 45.9% ± 14.3% during the pre-VCP phase to 85.8% ± 10.9% during the post-VCP phase. Compliance with Treatment Planning VCP tasks also increased from 52.6% ± 9.9% during the pre-VCP phase to 76.0% ± 9.7% during the post-VCP phase. The monthly defect rate (ratio of plans with errors to the total number of plans checked by a physicist) decreased from 19.1% ± 1.3% during the pre-VCP phase to 5.2% ± 4.1% during the post-VCP phase. Ninety-four percent of staff members responded to the VCP survey; more than 80% of respondents found the VCP to have a favorable impact. CONCLUSIONS: Implementation of the VCP in our department improved workflow efficiency, reduced the number of errors, and was very well received within the department.

Medical student mentorship in radiation oncology at a single academic institution: A 10-year analysis.

PURPOSE: Mentorship has been identified by medical students, residents, and faculty as an important component of specialty selection and research productivity in radiation oncology. This study quantitatively analyzes the impact of a mentorship program in radiation oncology targeted to medical students at our institution. METHODS AND MATERIALS: We performed a retrospective review of 76 current or former medical students who were mentored by faculty radiation oncologists at our institution between 2004 and 2013. Data were collected from the medical school's Office of Student Affairs and from internal departmental records. Mentees were organized by mentorship tracks, which included a clinical track and a research track. For each track, data were compiled and analyzed for student specialty selection, and Fisher exact tests were used to determine the relative significance of exposure to clinical, research, or both tracks on student likelihood of pursuing residency in radiation oncology relative to other specialties. We further tracked the research productivity of mentees in the program, as determined by the number publications that were coauthored by mentees and mentors each year. RESULTS: The absolute number of mentees has grown each year, with a total of 76 mentees, including 58 alumni, at the end of 2013. Mentees in the program have produced a total of 53 manuscripts, given 75 presentations at national conferences, and received numerous national and internal medical school research awards. Of the 58 alumni, 17 (29.3%) applied to and matched into radiation oncology residencies. Alumni of both the research and the clinical track were 5.76 (P < .01) times more likely to enter a radiation oncology residency program than the average single-track alumnus. CONCLUSIONS: Mentorship in medical school is an important factor in the development of future radiation oncologists. These results demonstrate the positive impact mentorship has on specialty selection and research productivity.

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts.

BACKGROUND: Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material. METHODS: We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 +/- 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 +/- 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique. RESULTS: We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P >.05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 +/- 15 mm Hg at 8 +/- 2.6 months postoperatively as compared to a gradient of 24 +/- 18 mm Hg measured 12 +/- 6 months postoperatively in standard allografts (P =.11). CONCLUSIONS: Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.