Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience.

PURPOSE: GammaTile® (GT) is a brachytherapy platform that received Federal Drug Administration (FDA) approval as brain tumor therapy in late 2018. Here, we reviewed our institutional experience with GT as treatment for recurrent glioblastomas and characterized dosimetric parameter and associated clinical outcome. METHODS AND MATERIALS: A total of 20 consecutive patients with 21 (n = 21) diagnosis of recurrent glioblastoma underwent resection followed by intraoperative GT implant between 01/2019 and 12/2020. Data on gross tumor volume (GTV), number of GT units implanted, dose coverage for the high-risk clinical target volume (HR-CTV), measured by D90 or dose received by 90% of the HR-CTV, dose to organs at risk, and six months local control were collected. RESULTS: The median D90 to HR-CTV was 56.0 Gy (31.7-98.7 Gy). The brainstem, optic chiasm, ipsilateral optic nerve, and ipsilateral hippocampus median Dmax were 11.2, 5.4, 6.4, and 10.0 Gy, respectively. None of the patients in this study cohort suffered from radiation necrosis or adverse events attributable to the GT. Correlation was found between pre-op GTV, the volume of the resection cavity, and the number of GT units implanted. Of the resection cavities, 7/21 (33%) of the cavity experienced shrinkage, 3/21 (14%) remained stable, and 11/21 (52%) of the cavities expanded on the 3-months post-resection/GT implant MRIs. D90 to HR-CTV was found to be associated with local recurrence at 6-month post GT implant, suggesting a dose response relationship (p = 0.026). The median local recurrence-free survival was 366.5 days (64-1,098 days), and a trend towards improved local recurrence-free survival was seen in patients with D90 to HR-CTV ≥ 56 Gy (p = 0.048). CONCLUSIONS: Our pilot, institutional experience provides clinical outcome, dosimetric considerations, and offer technical guidance in the clinical implementation of GT brachytherapy.

A Patient-Specific correspondence model to track tumor location in thorax during radiation therapy.

PURPOSE: We present a patient-specific model to estimate tumor location in the thorax during radiation therapy using chest surface displacement as the surrogate signal. METHODS: Two types of data are used for model construction: Four-dimensional computed tomography (4D-CT) images of the patient and the displacement of two points on the patient's skin on the thoracic area. Principal component analysis is used to fit the correspondence model. This model incorporates the recorded surrogate signals during radiation delivery as input and delivers the 3D trajectory of the tumor as output. We evaluated the accuracy of the proposed model on a respiratory phantom and five lung cancer patients. RESULTS: For the respiratory phantom, the location of the center of the sphere during treatment was calculated in three directions: Left-Right (LR), Anterior-Posterior (AP) and, Superior-Inferior (SI). The error of localization was less than 1 mm in the LR and AP directions and less than 2 mm in the SI direction. The location of the tumor center for two of the patients, and the location of the apex of the diaphragm for the other three, was calculated in three directions. For all patients, the localization error in the LR and AP directions was less than 1.1 mm for two fractions and the maximum localization error in the SI direction was 6.4 mm. CONCLUSIONS: This work presents a feasibility study of utilizing surface displacement data to locate the tumor in the thorax during radiation treatment. Future work will validate the model on a larger patient population.

A linear optimization model for high dose rate brachytherapy using a novel distance metric.

Purpose.We propose a linear network-based optimization model (LNBM) for high dose rate brachytherapy (HDR-BT) that uses a novel distance metric to measure the discrepancy between the dose delivered and the prescription. Unlike models in the literature, LNBM takes advantage of the adjacency structure of the patients' voxels by formalizing them into a network.Methods.We apply LNBM to a set of 7 cervical cancer cases treated with HDR-BT. State-of-the-art commercial optimization software solves LNBM to global optimality. The results of LNBM are compared with those of inverse planning by simulated annealing (IPSA) based on tumor coverage, dosimetric indices for the critical organs at risk (OARs), isodose contour plots, and two metrics of homogeneity new to this work (hot-spots volumes and diameters).Results.LNBM produces plans with improved tumor coverage and with improved isodose contour plots and dosimetric indices for OARs that receive highest dose (bladder and rectum in this study) when compared with IPSA. Using new metrics of homogeneity, we also demonstrate that LNBM produces more homogeneous plans on these cases. An analysis of the solutions of LNBM shows that they use a significant part of the voxel network structure, providing evidence that the plans produced are different from those created using traditional penalty approaches and are more directly guided by the geometry of the patients' anatomy.Conclusions.The proposed linear network-based optimization model efficiently generates more homogeneous high quality treatment plans for HDR-BT.

Medical physics practice guideline 4.b: Development, implementation, use and maintenance of safety checklists.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the US. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the US. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. While must is the term to be used in the guidelines, if an entity that adopts the guideline has shall as the preferred term, the AAPM considers that must and shall have the same meaning. Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Pleomorphic Adenoma of the Palate: A Rare Case in an Adolescent With Cleft lip and Palate.

Benign salivary gland tumors are rarely found in children and adolescents compared with adults. Pleomorphic adenomas (PAs), the most common benign salivary gland tumor, account for only 1% of all head and neck lesions and fewer than 5% of all salivary gland tumors in individuals under the age of 16 years. The data on palatal PA in the first 2 decades of life is confined to published case reports and case series. To date, there has never been a report of palatal PA in a patient with cleft lip and palate. Here we describe an adolescent female with bilateral cleft lip and palate with PA of the hard and soft palate who underwent wide local excision and reconstruction with a buccal fat pad and buccal myo-mucosal flap.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist.

In 2020, Beck et al1 described a novel adult autoinflammatory syndrome entitled VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic), a newly-discovered disorder that connected previously unrelated inflammatory syndromes and a prototype for a new class of hematoinflammatory diseases.2 Eighty-nine percent of published cases have documented skin involvement, but despite the high incidence and diagnostic accessibility of skin manifestations, there has been little focus on the dermatological features of VEXAS syndrome thus far. A PubMed search of all published case reports of VEXAS syndrome to date was performed, with inclusion of all cases confirmed by genetic sequencing, and this review summarizes the reported dermatological signs. There have already been 141 confirmed published cases since original publication, 126 of which had documented cutaneous signs.1-34 A wide range of skin presentations are reported, including Sweet-like urticated and tender erythematous nodules, cartilaginous involvement with chondritis, cutaneous vasculitis, and periorbital angiodema.1-34 Many patients had been diagnosed with Sweet syndrome, relapsing polychondritis, polyarteritis nodosa, or erythema nodosum.1-34 Hallmarks of skin histopathology are a neutrophilic dermatosis with coexisting or exclusive leukocytoclastic vasculitis.1 The new classification therefore helps link previously disparate inflammatory skin conditions into a unifying pathophysiological pathway.

Perceptions of Attractiveness in Dorsal Aesthetic Lines of the Nose: A Crowd Sourcing Analysis.

Background: Some surgeons have recently advocated for a fusiform pattern with a flare around the keystone area over the more traditional straight/curvilinear shape for the ideal shape of the nasal dorsal aesthetic lines (DALs). Objective: To compare the lay persons judgment of what constitutes an ideal nasal dorsum outline. Methods: An observational crowdsourcing survey-based study was designed and conducted by the authors to determine how the public viewed these two nasal dorsum aesthetic configurations. In total, 1034 surveys comparing various altered images with these variants were analyzed. Results: Our crowd-based cohort preferences for DALs favored as more attractive, the traditional concept of paired straight or curvilinear lines sweeping gently from the glabella to the nasal tip. The fusiform nose was seen as more natural. Conclusion: Our study suggests that individuals may view a straight/curvilinear nasal dorsum as a more attractive result, whereas a fusiform nasal dorsum may be viewed as a more natural result.

Pediatric Odontogenic and Maxillofacial Bone Pathology: A Global Analysis.

BACKGROUND: Although pathology in the maxillary and mandibular bones is rare in young patients, the differential diagnosis is broad. The World Health Organization (WHO) updated its classification of maxillofacial bone pathology in 2017. Using these updated guidelines, a systematic review of common maxillofacial bone lesions in the pediatric population was performed. METHODS: A PubMed search was conducted capturing English language articles from inception to July 2020. Thirty-one articles were identified that described the frequency of maxillofacial bone pathology. Data were extracted and organized using the WHO 2017 classification of odontogenic and maxillofacial bone tumors. Prevalence data were analyzed among diagnostic categories and geographical regions. The SAS version 9.4 was used to complete statistical analyses. RESULTS: The articles included patients from birth to a maximum age of 14 to 19 years. The most common odontogenic cysts included radicular cyst (42.7%) and dentigerous cyst (39.0%) followed by odontogenic keratocyst (15.0%). Among odontogenic bone tumors, odontoma (49.3%) was most common followed by ameloblastoma (29.1%). The most common nonodontogenic bone tumor was fibrous dysplasia (42.4%), and the most common malignant bone tumor was osteosarcoma (75.0%). Significant variations were found by geographic region, with dentigerous cyst more common than radicular cyst, and ameloblastoma more common than odontoma in African and Asian countries (P < 0.0001). CONCLUSIONS: This systematic review uses the WHO 2017 guidelines to classify common odontogenic and nonodontogenic maxillofacial bone lesions around the world. Pathogenesis, presentation, and available treatment options for the most common maxillofacial bone lesions are reviewed.

Rapid Interval Recurrence of Glioblastoma Following Gross Total Resection: A Possible Indication for GammaTileⓇ Brachytherapy.

Glioblastoma recurrence between initial resection and standard-of-care adjuvant chemoradiotherapy (CRT) is a negative prognostic factor in an already highly aggressive disease. Re-resection with GammaTileⓇ(GT Medical Technologies Inc., Tempe, AZ) placement affords expedited adjuvant radiation to mitigate the likelihood of such growth. Here, we report a glioblastoma patient who underwent re-resection and GammaTileⓇ (GT) placement within two months of the initial gross total resection due to regrowth that reached the size of the original presenting tumor. The patient subsequently received concurrent temozolomide and 60 Gy external beam to regions outside of the brachytherapy range, fulfilling the generally accepted Stupp regimen. The patient tolerated the treatment without complication. The dosimetrics and implications of the case presentation are reviewed.

First clinical implementation of GammaTile permanent brain implants after FDA clearance.

PURPOSE: GammaTile cesium-131 (131Cs) permanent brain implant has received Food and Drug Administration (FDA) clearance as a promising treatment for certain brain tumors. Our center was the first institution in the United States after FDA clearance to offer the clinical use of GammaTile brachytherapy outside of a clinical trial. The purpose of this work is to aid the medical physicist and radiation oncologist in implementing this collagen carrier tile brachytherapy (CTBT) program in their practice. METHODS: A total of 23 patients have been treated with GammaTile to date at our center. Treatment planning system (TPS) commissioning was performed by configuring the parameters for the 131Cs (IsoRay Model CS-1, Rev2) source, and doses were validated with the consensus data from the American Association of Physicists in Medicine TG-43U1S2. Implant procedures, dosimetry, postimplant planning, and target delineations were established based on our clinical experience. Radiation safety aspects were evaluated based on exposure rate measurements of implanted patients, as well as body and ring badge measurements. RESULTS: An estimated timeframe of the GammaTile clinical responsibilities for the medical physicist, radiation oncologist, and neurosurgeon is presented. TPS doses were validated with published dose to water for 131Cs. Clinical aspects, including estimation of the number of tiles, treatment planning, dosimetry, and radiation safety considerations, are presented. CONCLUSION: The implementation of the GammaTile program requires collaboration from multiple specialties, including medical physics, radiation oncology, and neurosurgery. This manuscript provides a roadmap for the implementation of this therapy.

Cartilage Grafting Outcomes in Intermediate and Definitive Cleft Rhinoplasty.

OBJECTIVE: To compare cartilage grafting outcomes in intermediate versus definitive cleft rhinoplasty. DESIGN: A retrospective chart review was conducted. The χ2 and Fisher exact tests were used for statistical analyses. Results were considered statistically significant at P < .05. PARTICIPANTS: All subjects who underwent revision cleft rhinoplasties between July 2011 and June 2019 were included. Subjects with syndromic conditions were excluded. RESULTS: A total of 46 subjects with a cleft nose deformity underwent 65 rhinoplasty procedures. The ages averaged 17 years (range 5-50) with 34 (73.9%) males and 12 (26.1%) females. In the intermediate group, 6 (28.6%) subjects required cartilage grafting as part of 6 cleft rhinoplasties, whereas 15 (71.4%) subjects underwent a total of 26 cleft rhinoplasties that did not require grafting. In the definitive group, 18 (76%) subjects required cartilage grafting over 21 cleft rhinoplasties, whereas 7 (24%) subjects underwent a total of 9 cleft rhinoplasties where cartilage grafting was not required. The difference between the number of subjects requiring cartilage grafting in the intermediate versus the definitive group was statistically significant (P = .007). Ear concha and nose were the most frequently used cartilage donor sites, with no observed complications. CONCLUSIONS: Cartilage grafting was significantly more common in the definitive rhinoplasty group. Intermediate cleft rhinoplasty during the 5- to 13-year age period was effective, with a low-risk profile. In our experience, ear concha and nose were the preferred cartilage donor sites, with effective results and an excellent safety profile.

3D printed copper-plastic composite material for use as a radiotherapy bolus.

The purpose of this work is to evaluate a commercially available copper-plastic composite material for use as a custom fit 3D printed bolus. Superficial dose under copper-plastic composite bolus was assessed for 0.4 mm, 0.6 mm, and 0.8 mm thicknesses. Superficial dose measurements were performed with an Attix parallel plate ionization chamber and radiochromic film. Additionally, a custom-fit bolus was designed for the temporal-frontal cranial region of an anthropomorphic phantom. A treatment plan with a tangential field arrangement was designed, and radiochromic film was used to measure the dose enhancement to the surface of the phantom from the bolus and compared to the calculated dose. It was shown that 3D printed copper-plastic composite bolus can provide the equivalent dose enhancement of thicker conventional bolus. Due to the limited thickness of the copper-plastic composite the bolus can remain flexible, which can aid in the placement of the bolus and improve patient comfort.

Dissemination of Evidence-Based School Asthma Management Programs: Piloting Asthma 411 in an Urban Texas School District.

BACKGROUND: The dissemination and implementation (D&I) of evidence-based initiative (EBIs) is critical to improved public health. The Asthma 411 EBI was piloted in Texas from 2013 to 2015. The pilot's evaluation assessed its effectiveness and identified approaches to support D&I of school-health EBIs. METHODS: The pilot study was conducted in two schools; service categories included: a consulting physician, enhanced school asthma services, and support for links to community health resources. Data was collected on Emergency Medical Service (EMS) calls, aggregated nursing services, demographic characteristics, availability of medication provided through existing policies, and informal interviews. RESULTS: During the pilot, school-day asthma-related Emergency Medical Service (EMS) calls were eliminated. Documented asthma self-management education, authorization for rescue medication, and efforts to communicate with parents and health providers increased. Between year-1 and year-2, the gap between unadjusted, weighted mean absences among students with and without asthma was reduced by 1.1 days. However, this difference was not seen in a fully adjusted negative, binomial regression model. CONCLUSIONS: Evaluation of the Asthma 411 pilot suggests many EBI benefits were retained and identifies factors that may facilitate D&I of school health EBIs. Future research will clarify impacts on absenteeism and determine if observed benefits are sustained.

Happiness in Plastic Surgery: A Cross-Sectional Analysis of 595 Practicing Plastic Surgeons, Fellows, Residents, and Medical Students.

BACKGROUND: Despite a heightened appreciation for wellness in medicine, there exists little information specific to plastic surgery. The purpose of this research was to assess happiness within the field of plastic surgery. METHODS: A cross-sectional study was conducted in July of 2017 by distributing an American Society of Plastic Surgeons sponsored survey to a random cohort of current practicing American Society of Plastic Surgeons members, residents and fellows. In addition, the same survey was sent to medical students applying to integrated plastic surgery residency. Total happiness scores (Subjective Happiness Scale) were averaged and compared between and within surveyed groups. RESULTS: A total of 595 individuals completed surveys, including 287 practicing surgeons, 116 residents, 12 fellows, and 180 medical students. Differences in happiness scores between the groups were statistically significant (P < 0.01). For practicing physicians, happiness scores were significantly greater for those more than 20 years out from training (P < 0.01). Furthermore, a significantly positive correlation was found between practice expectations coming out of residency and happiness scores (Pearson correlation coefficient, 0.2; P < 0.01). CONCLUSIONS: Despite the prevalence of burnout and mental health disorders associated with a career in medicine, plastic surgeons and trainees report high levels of happiness. Practicing plastic surgeons report increased happiness further out from training and when meeting practice expectations coming out of training. Otherwise, there were no significant differences in happiness between groups. Regarding sex, it is encouraging to report no significant sex discrepancies with happiness in a field where women still face significant adversity.

Correction: Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1002781.].

Using machine learning to examine the relationship between asthma and absenteeism.

In this study, we found that machine learning was able to effectively estimate student learning outcomes geo-spatially across all the campuses in a large, urban, independent school district. The machine learning showed that key factors in estimating the student learning outcomes included the number of days students were absent from school. In turn, one of the most important factors in estimating the number of days a student was absent was whether or not the student had asthma. This highlights the importance of environmental public health for student learning outcomes.

Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study.

BACKGROUND: A nonsputum blood test capable of predicting progression of healthy individuals to active tuberculosis (TB) before clinical symptoms manifest would allow targeted treatment to curb transmission. We aimed to develop a proteomic biomarker of risk of TB progression for ultimate translation into a point-of-care diagnostic. METHODS AND FINDINGS: Proteomic TB risk signatures were discovered in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents aged 12-18 years (68% female) who participated in the Adolescent Cohort Study (ACS) between July 6, 2005 and April 23, 2007, through either active (every 6 months) or passive follow-up over 2 years. Forty-six individuals developed microbiologically confirmed TB disease within 2 years of follow-up and were selected as progressors; 106 nonprogressors, who remained healthy, were matched to progressors. Over 3,000 human proteins were quantified in plasma with a highly multiplexed proteomic assay (SOMAscan). Three hundred sixty-one proteins of differential abundance between progressors and nonprogressors were identified. A 5-protein signature, TB Risk Model 5 (TRM5), was discovered in the ACS training set and verified by blind prediction in the ACS test set. Poor performance on samples 13-24 months before TB diagnosis motivated discovery of a second 3-protein signature, 3-protein pair-ratio (3PR) developed using an orthogonal strategy on the full ACS subcohort. Prognostic performance of both signatures was validated in an independent cohort of 1,948 HIV-negative household TB contacts from The Gambia (aged 15-60 years, 66% female), longitudinally followed up for 2 years between March 5, 2007 and October 21, 2010, sampled at baseline, month 6, and month 18. Amongst these contacts, 34 individuals progressed to microbiologically confirmed TB disease and were included as progressors, and 115 nonprogressors were included as controls. Prognostic performance of the TRM5 signature in the ACS training set was excellent within 6 months of TB diagnosis (area under the receiver operating characteristic curve [AUC] 0.96 [95% confidence interval, 0.93-0.99]) and 6-12 months (AUC 0.76 [0.65-0.87]) before TB diagnosis. TRM5 validated with an AUC of 0.66 (0.56-0.75) within 1 year of TB diagnosis in the Gambian validation cohort. The 3PR signature yielded an AUC of 0.89 (0.84-0.95) within 6 months of TB diagnosis and 0.72 (0.64-0.81) 7-12 months before TB diagnosis in the entire South African discovery cohort and validated with an AUC of 0.65 (0.55-0.75) within 1 year of TB diagnosis in the Gambian validation cohort. Signature validation may have been limited by a systematic shift in signal magnitudes generated by differences between the validation assay when compared to the discovery assay. Further validation, especially in cohorts from non-African countries, is necessary to determine how generalizable signature performance is. CONCLUSIONS: Both proteomic TB risk signatures predicted progression to incident TB within a year of diagnosis. To our knowledge, these are the first validated prognostic proteomic signatures. Neither meet the minimum criteria as defined in the WHO Target Product Profile for a progression test. More work is required to develop such a test for practical identification of individuals for investigation of incipient, subclinical, or active TB disease for appropriate treatment and care.

Dose calibration of Gafchromic EBT3 film for Ir-192 brachytherapy source using 3D-printed PLA and ABS plastics.

3D printing technology has allowed the creation of custom applicators for high dose rate (HDR) brachytherapy, especially for complex anatomy. With conformal therapy comes the need for advanced dosimetric verification. It is important to demonstrate how dose to 3D printed materials can be related to dose to water. This study aimed to determine dose differences and uncertainties using 3D printed PLA and ABS plastics for Radiochromic film calibration in HDR brachytherapy.Gafchromic EBT3 film pieces were irradiated in water with an Ir-192 source at calculated dose levels ranging from 0 to 800 cGy, to create the control calibration curve. Similarly, film was placed below 3D printed PLA and ABS blocks and irradiated at the same dose levels calculated for water, ranging from 0 to 800 cGy. After a 72-h development time, film pieces were scanned on a flatbed scanner and the median pixel value was recorded in the region of highest dose. This value was converted to net optical density (NOD). A rational function was used to fit a calibration curve in water that relates NOD to dose for red, green, and blue color channels. Based on this fitted curve, ABS and PLA NOD values were used to estimate dose in 3D printed plastics.From the fitted calibration curve, mean residual error between measured and planned dose to water was less than 1% for each color channel at high dose levels. At high dose levels, ABS and PLA mean residual errors were about 6.9 and 7.8% in the red channel, while 5.2 and 5.7% in the green channel. Combined uncertainties measured to be about 6.9% at high dose levels. This study demonstrated dose differences and uncertainties using 3D printed applicators for HDR Ir-192 brachytherapy.