A Novel Immobilization Method for the Treatment of Head and Neck Cancer Using 3D Printing.

Proper immobilization is critical for the delivery of high-quality radiation therapy. In cases when traditional immobilization is not feasible, 3-dimensional (3D) printing may provide a better-tolerated custom immobilization that is comparably effective. We present the successful treatment of a patient with inoperable oropharyngeal squamous cell carcinoma who was unable to tolerate traditional immobilization. To avoid covering the face, we created a 3D-printed cradle for the back of his head and neck. This design enabled the patient to tolerate traditional simulation scans with and without intravenous contrast and was subsequently able to undergo volumetric modulated arc therapy treatment. He successfully underwent treatment without evidence of disease more than 2 years after completion. The effect of 3D printing within the context of radiation oncology, as well as in other specialties, will undoubtedly continue to increase the variety of treatment options available to patients.

Redefining trauma deserts: novel technique to accurately map prehospital transport time.

Background: Prehospital transport time has been directly related to mortality for hemorrhaging trauma patients. 'Trauma deserts' were previously defined as being outside of a 5-mile radial distance of an urban trauma center. We postulated that the true 'desert' should be based on transport time rather than transport distance. Methods: Using the Chicagoland area that was used to describe 'trauma deserts,' a sequential process to query a commercial travel optimization product to map transport times over coordinates that covered the entire urban area at a particular time of day. This produces a heat map representing prehospital transport times. Travel times were then limited to 15 minutes to represent a temporally based map of transport capabilities. This was repeated during high and low traffic times and for centers across the city. Results: We demonstrated that the temporally based map for transport to a trauma center in an urban center differs significantly from the radial distance to the trauma center. Primary effects were proximity to highways and the downtown area. Transportation to centers were significantly different when time was considered instead of distance (p<0.001). We were further able to map variations in traffic patterns and thus transport times by time of day. The truly 'closest' trauma center by time changed based on time of day and was not always the closest hospital by distance. Discussion: As the crow flies is not how the ambulance drives. This novel technique of dynamically mapping transport times can be used to create accurate trauma deserts in an urban setting with multiple trauma centers. Further, this technique can be used to quantify the potential benefit or detriment of adding or removing firehouses or trauma centers.

Impact of Routine Surveillance Imaging on Recurrence in Sinonasal Malignancies.

BACKGROUND/AIM: There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examined the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies. PATIENTS AND METHODS: We performed a retrospective review on an IRB-approved dataset of patients with sinonasal malignancies treated at a single institution between 2005 to 2021. Patients were categorized into groups based on the frequency of annual imaging and total number of imaging studies. We compared time-to-recurrence between the groups using log-rank test. A two-sided p-value of <0.05 was considered as the threshold for significance. RESULTS: A total of 93 patients were eligible for this study with a median follow up of 42.3 months and 25.8% (n=24) of patients had documented recurrence. Sensitivity and specificity for recurrence based on computed tomography (CT) scans within one year of treatment completion were 50.0% and 19.5%; positron emission tomography/CT was 90.0% and 19.5%; and magnetic resonance imaging was 60.0% and 61.0%, respectively. Regardless of the type of imaging, symptomatic presentation after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95%CI=1.06-8.22). The frequency of scans was not associated with the risk of recurrence (HR=0.55; 95%CI=0.23-1.29, p=0.17). Similarly, no association was noted between the total number of scans and risk of recurrence (HR=0.64; 95%CI=0.27-1.51, p=0.31). CONCLUSION: The total number of frequency of scans within the first year after treatment had no association with time to recurrence of sinonasal malignancies. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.

A novel use of 3D-printed template in vaginal HDR brachytherapy.

PURPOSE: The High-Dose-Rate (HDR) vaginal cylinder treatment is typically designed using the initial CT, while the subsequent implants are verified using rudimentary methods (i.e., visual inspection, ruler measurements, etc.) and/or X-ray imaging. We are proposing the use of a 3D-printed individualized template that could provide simple and reproducible vaginal cylinder insertion. MATERIAL AND METHODS: Six patients were included in the study with prescriptions of 6 Gy/fraction for 2 to 5 fractions (total 27 treatments). The first 1 to 2 treatments were delivered without the template and the rest with the CT-based 3D-printed templates. Cone beam CTs (CBCTs) were acquired to verify the cylinder placement for all treatments. D2cc of the bladder and rectum are recorded on both planning CT and the following on-treatment CBCTs. RESULTS: By using the templates, the tip position variation on average (±1 SD) reduced from 0.8±0.5 cm to 0.6±0.4 cm, and angular difference decreased from 5.3±3.5° to 4.7±2.4°. The pitch and yaw deviation are reduced from 0.9 ± 5.8° and 0.4±2.9° to 0.0±3.9° and -0.2±3.0°, respectively. The deviation of D2cc to bladder from the plan reduced from 6±4% to 5±3%, and rectum from 5±2% to 4±4%. CONCLUSION: The 3D-printed patient-specific cylinder templates could potentially improve the geometrical reproducibility of cylinder treatments at no cost of additional imaging. The D2cc for the bladder and rectum are determined by the treatment length rather than their respective volumes.

Hypofractionated radiation in secretory breast cancer: A case report.

Secretory carcinoma is a rare and indolent breast cancer with a lack of established treatment paradigms. We describe a case of a woman who underwent breast conservative therapy in the modern era. A 48 year old woman with a screen-detected left breast cancer was found to have early-stage secretory carcinoma after definitive breast conservation surgery. Further management with adjuvant radiation was recommended. After definitive breast conservative surgery, final pathology was notable for secretory breast carcinoma due to the immunohistologic characteristics of the tumor, ETV6-NTRK3 gene fusion, and histologic findings. After multi-disciplinary discussion, it was recommended that the patient proceed with adjuvant radiation. She was treated using a modestly hypofractionated regimen of 4256 cGy in 16 fractions. She tolerated the treatment well, developing only grade 1 radiation dermatitis. At 1 year follow-up she was clinically and radiographically free of disease. With a shift in management toward breast conservative therapy, defining the role of adjuvant radiation for secretory carcinomas in the modern era is of increasing importance. Modestly hypofractionated radiation is well-tolerated. Oncologic outcomes will be assessed with continued long-term follow-up.

Suppression of local type I interferon by gut microbiota-derived butyrate impairs antitumor effects of ionizing radiation.

The antitumor effects of ionizing radiation (IR) are mediated in part through activation of innate and adaptive immunity. Here we report that gut microbiota influences tumor control following IR. Vancomycin decreased the abundance of butyrate-producing gut bacteria and enhanced antitumor responses to IR. Oral administration of Lachnospiraceae, a family of vancomycin-sensitive bacteria, was associated with increased systemic and intratumoral butyric acid levels and impaired the efficacy of IR in germ-free (GF) mice. Local butyrate inhibited STING-activated type I IFN expression in dendritic cells (DCs) through blockade of TBK1 and IRF3 phosphorylation, which abrogated IR-induced tumor-specific cytotoxic T cell immune responses without directly protecting tumor cells from radiation. Our findings demonstrate that the selective targeting of butyrate-producing microbiota may provide a novel therapeutic option to enhance tumor radiation sensitivity.

Three-dimensional printing in radiation oncology: A systematic review of the literature.

PURPOSE/OBJECTIVES: Three-dimensional (3D) printing is recognized as an effective clinical and educational tool in procedurally intensive specialties. However, it has a nascent role in radiation oncology. The goal of this investigation is to clarify the extent to which 3D printing applications are currently being used in radiation oncology through a systematic review of the literature. MATERIALS/METHODS: A search protocol was defined according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Included articles were evaluated using parameters of interest including: year and country of publication, experimental design, sample size for clinical studies, radiation oncology topic, reported outcomes, and implementation barriers or safety concerns. RESULTS: One hundred and three publications from 2012 to 2019 met inclusion criteria. The most commonly described 3D printing applications included quality assurance phantoms (26%), brachytherapy applicators (20%), bolus (17%), preclinical animal irradiation (10%), compensators (7%), and immobilization devices (5%). Most studies were preclinical feasibility studies (63%), with few clinical investigations such as case reports or series (13%) or cohort studies (11%). The most common applications evaluated within clinical settings included brachytherapy applicators (44%) and bolus (28%). Sample sizes for clinical investigations were small (median 10, range 1-42). A minority of articles described basic or translational research (11%) and workflow or cost evaluation studies (3%). The number of articles increased over time (P < 0.0001). While outcomes were heterogeneous, most studies reported successful implementation of accurate and cost-effective 3D printing methods. CONCLUSIONS: Three-dimensional printing is rapidly growing in radiation oncology and has been implemented effectively in a diverse array of applications. Although the number of 3D printing publications has steadily risen, the majority of current reports are preclinical in nature and the few clinical studies that do exist report on small sample sizes. Further dissemination of ongoing investigations describing the clinical application of developed 3D printing technologies in larger cohorts is warranted.

Adjuvant vaginal brachytherapy and chemotherapy versus pelvic radiotherapy in early-stage endometrial cancer: Outcomes by risk factors.

OBJECTIVE: To report on patterns of care as well as evaluate the two treatment regimens using a large retrospective hospital-based registry to identify possible subgroups of patients who may experience benefit with VBT + CT vs. EBRT. METHODS: Patients from the National Cancer Database (NCDB) were identified who met the inclusion criteria for GOG 249 and were treated with either VBT + CT or WPRT. Demographic, clinicopathologic, and treatment factors were collected. Association of treatment type and other variables with overall survival was analyzed using Cox proportional hazards model. Subset analyses were performed based on a variety of risk factors, including high risk pathologies, surgical nodal sampling, and grade. RESULTS: A total of 4,602 patients were included in the analysis, with 41% receiving VBT + CT and 59% receiving WPRT. For the entire cohort, VBT + CT was associated with improved survival, with 3-year overall survival 89.6% vs. 87.8% (hazard ratio 1.24, 95%CI 1.01-1.52, p = 0.04). On subset analysis, patients with serous histology experienced benefit with VBT + CT, while high-grade endometrial patients without lymph node dissection experienced improved survival associated with EBRT. After exclusion of serous histology, there was no survival difference associated with treatment type. CONCLUSIONS: VBT + CT was associated with superior survival outcomes in patients with early-stage serous carcinoma. For non-serous histology, treatment modality was not associated with a difference in survival, although patients with high-grade disease and no nodal dissection experienced benefit from EBRT.

Current recommendations and recent progress in endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

Socioeconomic factors and parity of access to robotic surgery in a county health system.

Equal access to novel surgical technologies remains a policy concern as hospitals adopt robotic surgery with increasing prevalence. This study sought to determine whether socioeconomic factors influence access to robotic surgery. All laparoscopic and robotic fundoplications and paraesophageal hernia repairs performed by a surgical group over 6 years at a county and two neighboring private hospitals were identified. Robotic use by hospital setting, age, gender, reported ethnicity, estimated income, insurance payer, and diagnosis were examined. Of 418 patients identified, 180 (43%) presented to the county hospital, where subjects were younger (51.1 versus 56.2 years, p < 0.001) with lower estimated income ($50,289 versus $62,959, p < 0.001). In the county setting, there was no difference in reported ethnicity (p = 0.169), estimated income (p = 0.081), or insurance payer (p = 0.535) between groups treated laparoscopically versus robotically. There was no difference in the treatment groups by estimated income in the private hospital setting (p = 0.308). Overall higher estimated income and insurance payer were associated with a higher chance of undergoing robotic procedures (p < 0.001). Presence of a paraesophageal hernia was associated with increased chance of undergoing robotic therapy in all comparisons (p < 0.001). No disparity in access to robotic surgery offered in the county hospital was observed based on age, gender, reported ethnicity, estimated income, or insurance payer. Patients with higher income and private insurers were more likely to present to the private hospital setting where robotics is utilized more often. The presence of a paraesophageal hernia was a significant factor in determining robotic therapy in both settings.

Traumatic colon injury in damage control laparotomy-A multicenter trial: Is it safe to do a delayed anastomosis?

BACKGROUND: Delayed colonic anastomosis after damage control laparotomy (DCL) is an alternative to colostomies during a single laparotomy (SL) in high-risk patients. However, literature suggests increased colonic leak rates up to 27% with DCL, and various reported risk factors. We evaluated our regional experience to determine if delayed colonic anastomosis was associated with worse outcomes. METHODS: A multicenter retrospective cohort study was performed across three Level I trauma centers encompassing traumatic colon injuries from January 2006 through June 2014. Patients with rectal injuries or mortality within 24 hours were excluded. Patient and injury characteristics, complications, and interventions were compared between SL and DCL groups. Regional readmission data were utilized to capture complications within 6 months of index trauma. RESULTS: Of 267 patients, 69% had penetrating injuries, 21% underwent DCL, and the mortality rate was 4.9%. Overall, 176 received primary repair (26 in DCL), 90 had resection and anastomosis (28 in DCL), and 26 had a stoma created (10 end colostomies and 2 loop ileostomies in DCL). Thirty-five of 56 DCL patients had definitive colonic repair subsequent to their index operation. DCL patients were more likely to be hypotensive; require more resuscitation; and suffer acute kidney injury, pneumonia, adult respiratory distress syndrome, and death. Five enteric leaks (1.9%) and three enterocutaneous fistulas (ECF, 1.1%) were identified, proportionately distributed between DCL and SL (p = 1.00, p = 0.51). No difference was seen in intraperitoneal abscesses (p = 0.13) or surgical site infections (SSI, p = 0.70) between cohorts. Among SL patients, pancreas injuries portended an increased risk of intraperitoneal abscesses (p = 0.0002), as did liver injuries in DCL patients (p = 0.06). CONCLUSIONS: DCL was not associated with increased enteric leaks, ECF, SSI, or intraperitoneal abscesses despite nearly two-thirds having delayed repair. Despite this being a multicenter study, it is underpowered, and a prospective trial would better demonstrate risks of DCL in colon trauma. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Influence of geometric and material properties on artifacts generated by interventional MRI devices: Relevance to PRF-shift thermometry.

PURPOSE: Magnetic resonance imaging (MRI) is capable of providing valuable real-time feedback during medical procedures, partly due to the excellent soft-tissue contrast available. Several technical hurdles still exist to seamless integration of medical devices with MRI due to incompatibility of most conventional devices with this imaging modality. In this study, the effect of local perturbations in the magnetic field caused by the magnetization of medical devices was examined using finite element analysis modeling. As an example, the influence of the geometric and material characteristics of a transurethral high-intensity ultrasound applicator on temperature measurements using proton resonance frequency (PRF)-shift thermometry was investigated. METHODS: The effect of local perturbations in the magnetic field, caused by the magnetization of medical device components, was examined using finite element analysis modeling. The thermometry artifact generated by a transurethral ultrasound applicator was simulated, and these results were validated against analytic models and scans of an applicator in a phantom. Several parameters were then varied to identify which most strongly impacted the level of simulated thermometry artifact, which varies as the applicator moves over the course of an ablative high-intensity ultrasound treatment. RESULTS: Key design parameters identified as having a strong influence on the magnitude of thermometry artifact included the susceptibility of materials and their volume. The location of components was also important, particularly when positioned to maximize symmetry of the device. Finally, the location of component edges and the inclination of the device relative to the magnetic field were also found to be important factors. CONCLUSIONS: Previous design strategies to minimize thermometry artifact were validated, and novel design strategies were identified that substantially reduce PRF-shift thermometry artifacts for a variety of device orientations. These new strategies are being incorporated into the next generation of applicators. The general strategy described in this study can be applied to the design of other interventional devices intended for use with MRI.

An MRI-compatible platform for one-dimensional motion management studies in MRI.

PURPOSE: Abdominal MRI remains challenging because of respiratory motion. Motion compensation strategies are difficult to compare clinically because of the variability across human subjects. The goal of this study was to evaluate a programmable system for one-dimensional motion management MRI research. METHODS: A system comprised of a programmable motorized linear stage and computer was assembled and tested in the MRI environment. Tests of the mutual interference between the platform and a whole-body MRI were performed. Organ trajectories generated from a high-temporal resolution scan of a healthy volunteer were used in phantom tests to evaluate the effects of motion on image quality and quantitative MRI measurements. RESULTS: No interference between the motion platform and the MRI was observed, and reliable motion could be produced across a wide range of imaging conditions. Motion-related artifacts commensurate with motion amplitude, frequency, and waveform were observed. T2 measurement of a kidney lesion in an abdominal phantom showed that its value decreased by 67% with physiologic motion, but could be partially recovered with navigator-based motion-compensation. CONCLUSION: The motion platform can produce reliable linear motion within a whole-body MRI. The system can serve as a foundation for a research platform to investigate and develop motion management approaches for MRI. Magn Reson Med 76:702-712, 2016. © 2015 Wiley Periodicals, Inc.

Response network analysis of differential gene expression in human epithelial lung cells during avian influenza infections.

BACKGROUND: The recent emergence of the H5N1 influenza virus from avian reservoirs has raised concern about future influenza strains of high virulence emerging that could easily infect humans. We analyzed differential gene expression of lung epithelial cells to compare the response to H5N1 infection with a more benign infection with Respiratory Syncytial Virus (RSV). These gene expression data are then used as seeds to find important nodes by using a novel combination of the Gene Ontology database and the Human Network of gene interactions. Additional analysis of the data is conducted by training support vector machines (SVM) with the data and examining the orientations of the optimal hyperplanes generated. RESULTS: Analysis of gene clustering in the Gene Ontology shows no significant clustering of genes unique to H5N1 response at 8 hours post infection. At 24 hours post infection, however, a number of significant gene clusters are found for nodes representing "immune response" and "response to virus" terms. There were no significant clusters of genes in the Gene Ontology for the control (Mock) or RSV experiments that were unique relative to the H5N1 response. The genes found to be most important in distinguishing H5N1 infected cells from the controls using SVM showed a large degree of overlap with the list of significantly regulated genes. However, though none of these genes were members of the GO clusters found to be significant. CONCLUSIONS: Characteristics of H5N1 infection compared to RSV infection show several immune response factors that are specific for each of these infections. These include faster timescales within the cell as well as a more focused activation of immunity factors. Many of the genes that are found to be significantly expressed in H5N1 response relative to the control experiments are not found to cluster significantly in the Gene Ontology. These genes are, however, often closely linked to the clustered genes through the Human Network. This may suggest the need for more diverse annotations of these genes and verification of their action in immune response.