Gender and the Receipt of the Association of Residents in Radiation Oncology Educator of the Year Award.

Purpose: We hypothesized that there may be a gender disparity in the receipt of the Association of Residents in Radiation Oncology (ARRO) Educator of the Year Award and sought to elucidate factors that contribute to differences in award receipt. Methods and Materials: Using a database provided by the American Society for Radiation Oncology, award recipients were identified from 2010 to 2022. Publicly available websites were accessed to obtain data regarding gender, years since residency graduation, percentage of female faculty, size of residency program, and program director designation. A 1-sample Z-test was used to assess whether the proportion of female ARRO award winners, defined as the proportion of female radiation oncology faculty members in the nominating universities that year, was significantly less than the population average. Secondary analyses used univariable binary logistic regression to identify global associations between gender, year since gradation, or program size. Results: The lowest proportion of female awardees occurred in 2013 (14.3%) and the greatest proportion in 2022 (30.6%). Compared with the proportion of female faculty members in nominating programs for the respective year, there were significantly fewer female awardees in 2010 (18% female awardees vs 32% female faculty members; P = .02) and 2013 (14% female awardees vs 31% female faculty members; P = .01). There was a statistically significant increase in female awardees during the study period (P < .01). On logistic regression analysis, large program size (≥10 residents) (odds ratio [OR], 6.86; 95% CI, 2.71-23.1; P < .001) and medium program size (5-9 residents) (OR, 4.05; 95% CI, 1.60-13.7; P < .001) were associated with a greater proportion of female awardees compared with small program size (1-4 residents). There was no association between awardee gender and years since graduation. Conclusions: A gender disparity was present in the receipt of ARRO Educator Awards. Residency chiefs, program directors, and chairs should work to ensure that a diverse slate of faculty is considered annually for the ARRO Educator Award.

Application of the patient-reported outcomes continual reassessment method to a phase I study of radiotherapy in endometrial cancer.

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe an application of a Bayesian form of the patient-reported outcomes continual reassessment method (PRO-CRMB) in an ongoing Phase I study of adjuvant hypofractionated whole pelvis radiation therapy (WPRT) in endometrial cancer (NCT04458402). The study's primary objective is to determine the MTD per fraction of WPRT, defined by acceptable clinician- and patient-reported DLT rates. We conduct simulation studies of the operating characteristics of the design and compared them to a rule-based approach. We illustrate that the PRO-CRMB makes appropriate dose assignments during the study to give investigators and reviewers an idea of how the method behaves. In simulation studies, the PRO-CRMB demonstrates superior performance to a 5 + 2 stepwise design in terms of recommending target treatment courses and allocating patients to these courses. The design is accompanied by an easy-to-use R shiny web application to simulate operating characteristics at the design stage and sequentially update dose assignments throughout the trial's conduct.

Sebaceous Carcinoma of the Wrist in an Elderly Woman: A Case Report.

Sebaceous carcinoma is a rare, aggressive cutaneous malignancy most commonly arising from the periocular area. Extraocular locations of sebaceous carcinomas, particularly outside of the head and neck region, are rare and not well-described. We report a case of an 89-year-old Caucasian female with sebaceous carcinoma of the right wrist. She initially presented with a 1.2-centimeter friable nodule on the right wrist. Initial shave biopsy and subsequent pathologic evaluation revealed a basaloid neoplasm with sebaceous differentiation, atypia, and frequent mitoses, consistent with sebaceous carcinoma. The presented case reviews common clinical features and the pertinent histopathology of ocular and extraocular sebaceous carcinoma and provides a literature review of diagnosis, prognosis, and treatment.

Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients.

PURPOSE: We hypothesize that hematologic toxicity will be lower in anal cancer patients treated definitively with intensity modulated proton therapy (IMPT) compared with patients treated with intensity modulated radiation therapy (IMRT). METHODS: Patients enrolled on a prospective feasibility trial assessing the use of IMPT for anal cancer were compared with contemporaneous patients treated with IMRT. Blood counts were collected during chemoradiation. Hematologic events were graded according to CTCAE version 5.0. Pelvic bone marrow (PBM) and positron emission tomography-defined active bone marrow (ABM) were defined and contoured for each patient. Toxicity rates, PBM and ABM dose metrics were compared between groups. RESULTS: Forty-one patients treated with definitive chemoradiation for anal cancer between 2015 and 2021 were included in this analysis. Of the evaluable patients, 14 patients were treated with IMPT and 27 were treated with IMRT. All PBM dose metrics were lower in patients receiving IMPT. Patients treated with IMPT versus IMRT also had a significantly lower ABM mean dose (1996 vs. 3073 Gy, P<0.01). However, there was no statistically significant difference in hematologic toxicity between the groups. Seventy percent of patients treated with IMRT had at least 1 grade ≥3 hematologic event compared with 86% in the IMPT group (P=0.48). CONCLUSION: Proton treatment reduced bone marrow doses but was not associated with lower hematologic toxicity when compared with IMRT.

Normal tissue exposure and second malignancy risk in vertebral-body-sparing craniospinal irradiation.

The purpose of this study was to compare dose to anterior organs at risk (OARs) and quantify the risk of developing secondary malignancy (SMN) in pediatric patients treated with vertebral-body-sparing (VBS) vs vertebral body (VB) pencil beam scanning proton craniospinal irradiation (CSI). Comparative plans of VBS and VB CSI were created for 10 previously treated patients. Dose-volume histograms were used to evaluate dose to OARs. Absolute excess risk of SMN was calculated according to the organ-specific, radiation-induced cancer incidence based on the organ equivalent dose. OAR dosimetric parameters and absolute excess risk of SMN were compared for VBS and VB plans using the Kruskal-Wallis H test (α = 0.05). VBS CSI leads to significantly lower radiation dose to the heart, esophagus, kidney, liver and bowel. Excluding the vertebral body also significantly decreases the absolute excess risk of SMN for liver, esophagus and bowel. For these reasons, implementation of VBS pencil beam scanning proton CSI should be considered.

Relationship of dose to vascular target volumes and local failure in pancreatic cancer patients undergoing neoadjuvant chemoradiation.

Objective: The objectives of this study were to evaluate whether dose to the vasculature is associated with local control after surgery in patients with borderline resectable (BLR) and resectable pancreatic cancer (PCA) receiving neoadjuvant radiation therapy (RT) and to identify a dose threshold for clinical use. Methods: Patients with BLR and resectable PCA treated with neoadjuvant RT were retrospectively reviewed. During this period, the institutional paradigm shifted from standard fractionation to hypofractionation/stereotactic body radiation therapy (SBRT). A vasculature clinical target volume (Vasc CTV) was contoured for each patient and defined as a 5-mm margin around the superior mesenteric artery (SMA) from its origin to the pancreatic head, the celiac artery from its origin to the level of the trifurcation and any involved vein. The Vasc CTV D95 was normalized to a 2-Gy equivalent dose to determine the optimal dose associated with optimal local failure-free survival (LFFS). Results: Forty-seven patients were included in the analysis. A Vasc CTV D95 of 32.7 Gy was the optimal cutoff for LFFS. Patients with Vasc CTV D95 Equivalent dose in 2 Gy per fraction (EQD2) >32.7 Gy had significantly longer LFFS compared to patients with Vasc CTV D95 EQD2 ≤32.7 Gy at 12 months (91% vs. 51%, respectively) and 24 months (86% vs. 12%, respectively). The median disease-free survival (DFS) for patients with EQD2 >32.7 Gy was 30.4 months compared to 14.0 months in patients with EQD2 ≤32.7 Gy (p = 0.01). There was no significant difference in overall survival (OS) between the two groups. Conclusions: During neoadjuvant treatment, dose to the Vasc CTV is associated with durability of local control (LC) after resection and should be intentionally included in the treatment volume with an EQD2 goal of 31-33 Gy.

The Radiation Oncology Education Collaborative Study Group 2020 Spring Symposium: Is Virtual the New Reality?

PURPOSE: Because of the COVID-19 pandemic, the Radiation Oncology Education Collaborative Study Group (ROECSG) hosted its annual international symposium using a virtual format in May 2020. This report details the experience of hosting a virtual meeting and presents attendee feedback on the platform. METHODS AND MATERIALS: The ROECSG symposium was hosted virtually on May 15, 2020. A postsymposium survey was distributed electronically to assess attendee demographics, participation, and experience. Attendee preference and experience were queried using 3-point and 5-point Likert-type scales, respectively. Symplur LLC was used to generate analytics for the conference hashtag (#ROECSG). RESULTS: The survey was distributed to all 286 registrants, with a response rate of 67% (191 responses). Seventeen nonattendee responses were omitted from this analysis, for a total of 174 included respondents. Eighty-two attendees (47%) were present for the entire symposium. A preference for a virtual symposium was expressed by 78 respondents (45%), whereas 44 (25%) had no preference and 52 (30%) preferred an in-person meeting. A total of 150 respondents (86%) rated the symposium as "extremely" well organized. Respondents who had not attended a prior in-person ROECSG symposium were more likely to prefer the virtual format (P = .03). Seventy-eight respondents (45%) reported a preference for the virtual platform for reviewing scholarly work, and 103 (59%) reported a preference for an in-person platform for networking. On the day of the symposium, #ROECSG had 408 tweets and 432,504 impressions. CONCLUSIONS: The 2020 ROECSG symposium was well received and can serve as a framework for future virtual meetings. Although the virtual setting may facilitate sharing research, networking aspects are more limited. Effort is needed to develop hybrid virtual and in-person meetings that meet the needs of participants in both settings. Social media is a significant avenue for dissemination and discussion of information and may be valuable in the virtual setting.

The Impact of a Multidisciplinary Third-Year Oncology Elective Rotation on Decisions to Pursue Oncologic Careers and Oncology Exposure.

PURPOSE: The majority of oncologic care is provided in the outpatient setting, yet at many medical schools, the dominant means of exposure to oncology occurs during inpatient rotations. Given the multidisciplinary nature of the specialty, radiation oncology departments are well positioned to lead outpatient oncology rotations within medical schools. Since 1992, the University of Cincinnati's Department of Radiation Oncology has administered a 2-week, third-year clinical oncology elective. This report characterizes the rotation and evaluates the impact of the rotation on students' oncology exposure and career choices over the past 10 years. METHODS AND MATERIALS: A list of medical students who participated in the MS3 clinical oncology elective rotation from 2008 to 2018 was reviewed. A search engine was used to locate the physicians and identify their specialty choices. A survey of 7 questions was distributed to the oncologists to evaluate how the rotation influenced their oncology exposure and career choice. RESULTS: Two hundred sixty-eight medical students participated in the MS3 Clinical Oncology Specialty Clerkship from 2008 to 2018. Thirty-nine students (15%) ultimately pursued a career in oncology. Seventy-four percent of the oncologists are radiation oncologists. Eighty-eight percent of the physicians surveyed had a positive to very positive experience with the rotation. The rotation was the first clinical exposure to the field of oncology for 48% of the respondents and the first exposure to the field of radiation oncology for 69% of the physicians. Seventy-two percent of the oncologists attributed the MS3 rotation as providing a moderate or great deal of early exposure to the field of oncology. CONCLUSIONS: Radiation oncology departments are well positioned to lead multidisciplinary, ambulatory oncology electives within US medical schools. A majority of participating oncologists viewed the rotation positively and attributed the rotation with their entrance into oncology.

Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

BACKGROUND: Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. METHODS: DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. RESULTS: Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. CONCLUSION: Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response to preoperative neoadjuvant therapy.

N-glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on host stress response, production yield and vaccine potential.

Plant-based transient overexpression systems enable rapid and scalable production of subunit vaccines. Previously, we have shown that cholera toxin B subunit (CTB), an oral cholera vaccine antigen, is N-glycosylated upon expression in transgenic Nicotiana benthamiana. Here, we found that overexpression of aglycosylated CTB by agroinfiltration of a tobamoviral vector causes massive tissue necrosis and poor accumulation unless retained in the endoplasmic reticulum (ER). However, the re-introduction of N-glycosylation to its original or an alternative site significantly relieved the necrosis and provided a high CTB yield without ER retention. Quantitative gene expression analysis of PDI, BiP, bZIP60, SKP1, 26Sα proteasome and PR1a, and the detection of ubiquitinated CTB polypeptides revealed that N-glycosylation significantly relieved ER stress and hypersensitive response, and facilitated the folding/assembly of CTB. The glycosylated CTB (gCTB) was characterized for potential vaccine use. Glycan profiling revealed that gCTB contained approximately 38% plant-specific glycans. gCTB retained nanomolar affinity to GM1-ganglioside with only marginal reduction of physicochemical stability and induced an anti-cholera holotoxin antibody response comparable to native CTB in a mouse oral immunization study. These findings demonstrated gCTB's potential as an oral immunogen and point to a potential role of N-glycosylation in increasing recombinant protein yields in plants.

Characterization of microsatellite markers for pinedrops, Pterospora andromedea (Ericaceae), from Illumina MiSeq sequencing.

PREMISE OF THE STUDY: Pterospora andromedea (Ericaceae) is a mycoheterotrophic plant endemic to North America with a disjunct distribution. Eastern populations are in decline compared to western populations. Microsatellite loci will allow comparison of genetic diversity in endangered to nonthreatened populations. • METHODS AND RESULTS: Illumina MiSeq sequencing resulted in development of 12 polymorphic microsatellite loci from 63 perfect microsatellite loci tested. One polymorphic locus was obtained from a traditional enrichment method. These 13 loci were screened across two western and two eastern populations. For western and eastern populations, respectively, number of alleles ranged from one to 10 and one to four, and observed heterozygosity ranged from 0.000 to 0.389 and 0.000 to 0.143. • CONCLUSIONS: These are the first microsatellite loci developed for Pterospora. They will be useful in conservation efforts of the eastern populations and for examination of population genetic parameters at different geographic scales and comparison with mycorrhizal fungal hosts.