Faculty Bibliography

BACKGROUND/UNASSIGNED:The increasing number of organ transplant recipients has led to a rise in cancer diagnoses in this population. Kidney transplant recipients, in particular, have a two-to-four-fold higher risk of developing cancer due to immunosuppressive therapy. The management of gynecologic cancers in this subset of patients presents unique challenges due to anatomical considerations, immunosuppression, and the nephrotoxicity of oncologic treatments.Case Presentation.A 44-year-old woman with a history of polycystic kidney disease underwent a bilateral nephrectomy followed by a living-related intraperitoneal renal transplant. She presented with pelvic pain and was found to have high-grade ovarian adenocarcinoma, possibly arising from endometriosis. Surgical staging included total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and right pelvic lymph node dissection. The patient underwent six cycles of carboplatin and paclitaxel chemotherapy while maintaining stable renal function with close monitoring of immunosuppressive drug levels. Surveillance imaging detected recurrence in the right pelvic lymph nodes, leading to secondary tumor debulking and whole pelvic radiation therapy. Despite a slight increase in creatinine, kidney function remained stable, and the patient has remained disease-free on subsequent follow-ups. CONCLUSION/UNASSIGNED:The management of ovarian cancer in kidney transplant recipients requires a multidisciplinary approach to balance oncologic control with graft preservation. Close monitoring of renal function, careful surgical planning, and tailored chemotherapy and radiation strategies are critical. More research is needed to establish standardized guidelines for managing gynecologic malignancies in transplant patients.

The psychosocial evaluation plays an essential role in the multidisciplinary assessment of pediatric patients for thoracic organ transplantation or ventricular assist device (VAD) placement. However, there is considerable practice variation with regard to the content and process of the evaluation, with no known recent published guidelines. Furthermore, the pediatric evaluation necessarily differs from the adult evaluation in a number of substantive ways, including caregiver roles and decision-making. A writing committee of 25 multidisciplinary experts in pediatric cardiothoracic transplantation/VAD was established, who conducted a comprehensive literature review which resulted in the development of this consensus-based framework. This framework, which is a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT), the International Pediatric Transplant Association (IPTA), the Pediatric Heart Transplant Society (PHTS), the Advancing Cardiac Therapies Improving Outcomes Network (ACTION), and Transplant Families, represents the first known framework specific to both the content and process of the psychosocial evaluation for pediatric cardiothoracic transplantation/VAD. Attention was paid to relevant ethical, cultural and health equity considerations inherent in the pediatric evaluation process. Rather than provide a proscriptive evaluation process, the goal was to create a flexible framework to encourage consistency across centers, while also acknowledging the complexities inherent in evaluating children and their families for cardiothoracic transplant and VAD.

OBJECTIVE:Recent guidelines suggest that non-invasive prenatal screening (NIPS) should be offered to all patients with singleton and twin pregnancies. Accurate determination of fetal fraction in cell-free DNA (cfDNA) is vital for reliable NIPS outcomes. We propose a methylation-based approach using droplet digital PCR (ddPCR) and methylation-sensitive restriction enzyme (MSRE) digestion for fetal fraction quantification as an affordable and fast solution. METHOD/METHODS:Following biomarker discovery using early pregnancy placental genomic DNA (gDNA) and cfDNA from non-pregnant female individuals, we designed assays targeting MSRE-compatible regions based on contrasting methylation patterns between maternal and fetal cfDNA. We established a proof-of-concept ddPCR workflow on the Bio-Rad Droplet Digital PCR QX600 instrument. RESULTS:Testing the fetal fraction assay multiplex on 137 prospective clinical samples demonstrated high concordance with NGS results for both female and male pregnancies as well as with chromosome Y-based calculations for samples with a male fetus. Reproducibility analysis indicated lower variability compared to previously reported NGS performance. CONCLUSION/CONCLUSIONS:This study showcases the potential of this novel, 6-color, high-multiplex methylation ddPCR panel for accurate measurement of fetal fraction in cfDNA samples. It presents opportunities to integrate such methodology as a standalone measurement to assess the quality of samples undergoing NIPS.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10^-

OBJECTIVE/UNASSIGNED:Early detection and removal of suspicious polyps during routine colonoscopies play an important role in reducing the risk of colorectal cancer. Patient management and follow-up are determined by the type of polyps removed and the degree of dysplasia present on histological evaluation. Whereas discerning between a benign polyp and a dysplastic one is a trivial task, distinguishing between tubular adenomas with low-grade dysplasia (LGD) and high-grade dysplasia (HGD) is a challenging task. In this study, we trained a deep learning model to distinguish between colorectal adenomas with LGD and HGD. DESIGN/UNASSIGNED:We retrieved 259 slides of adenomatous polyps taken between January 2011 and October 2024. Slides with HGD were reviewed by a subspecialty-trained GI pathologist. After excluding discordant and duplicate cases, 200 slides remained: 71 (35.5%) with HGD and 129 (64.5%) with LGD. The slides were divided into training (160 slides, 80%) and test (40 slides, 20%) sets. After patch generation and stain normalization, a ResNet34 model (pre-trained on ImageNet) was trained using 5-fold cross-validation. Slide classification was determined by aggregating patch-level predictions. RESULTS/UNASSIGNED:The model's slide-level prediction accuracy was 95.0%, correctly classifying all but 2 out of 40 slides. The model achieved an area under the receiver operating characteristic curve score of 0.981 and an F1 score of 0.923. CONCLUSIONS/UNASSIGNED:This study demonstrates that deep learning models can accurately distinguish between colonic adenomas with LGD and HGD. Training on a larger dataset could increase the accuracy and generalizability of the model and should be a focus of further studies.

BACKGROUND:Multiple surgical virtual reality (VR) simulators are currently available; however, there is lack of comparison between performance after practice on these simulators compared to bench top models. Utilizing the Intuitive Data recorder (IDR) and Objective performance indicators (OPI), we aim to objectively assess robotic surgical skills using a dry lab model. We hypothesize that practicing surgical skills will improve OPIs and that those who practice on the dry lab model will have a greater improvement in their OPIs compared to those who practice with Fundamentals of Robotic Surgery (FRS) SimNow VR. METHODS:The IDR was used to record kinematics as each participant went through five basic surgery tasks on a dry lab benchtop model to record baseline performance. Participants were then randomized to practice on the dry lab model or the corresponding SimNow Virtual reality (VR) tasks. The participants repeated the tasks again on the benchtop model. Statistical analysis was performed using paired samples t tests, independent samples t tests, and ANOVA tests. RESULTS:Twenty-seven surgeons participated in our study ranging from interns to attendings. Randomization to VR vs benchtop practice resulted in 11 and 13 participants in each group. For the rollercoaster, backhand suturing, railroad, and knot tying tasks, a significant improvement in kinematic profiles was observed. Bimanual dexterity, angular motion, and smoothness metrics improved most consistently across the tasks after practice. Kinematic profiles between those practicing on VR versus benchtop had no significant differences. CONCLUSIONS:This study shows that OPIs can be used to benchmark surgical trainees. VR appears to be non-inferior to dry lab model for practice for trainees. We identified patterns in OPI improvement that can be tailored to specific skills depending on the trainees needs. Our study is the first step in developing a standardized training and assessment tool to assess competency in robotic surgery training.

Background Expedited Partner Therapy (EPT) is the practice of treating sexual partner(s) of patients diagnosed with STIs without examining the partner(s) and is effective in reducing reinfection. It has been permissible in Virginia since 2020. This study aimed to assess knowledge and practices surrounding prescription of EPT at an academic medical center in Virginia before and after an online learning module. Methods Data were obtained via online anonymous RedCap surveys. The first was distributed via e-mail to providers who regularly diagnose and treat STIs at an academic medical center in Virginia. The survey assessed provider knowledge and practices regarding EPT and preference of future education. On the basis of the results, an online learning module with information on EPT was created and distributed to the same population of providers. The module contained pre- and post-module surveys evaluating participant knowledge of the legal status, methods of prescription, and attitudes surrounding EPT. Results The initial survey showed that 10% of participants were aware of the new legal status of EPT. In terms of EPT prescription, 4% always prescribed EPT, 14% prescribed it sometimes, and 61% never prescribed it. In the pre-module survey, 31% of respondents correctly identified one option for prescription of EPT. Knowledge surrounding the legal status and prescription methods was significantly improved in the post-module responses, with 100% of participants able to identify one correct prescription option. Conclusion These results show knowledge gaps surrounding the Virginia EPT provision and policy change. These gaps improved with the implementation of an online learning module. Further evaluation is needed to assess the continued implementation of EPT.

BACKGROUND:Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), approved by the US Food and Drug Administration for the treatment of platinum-resistant ovarian cancer in the USA. Here, we report patient-reported outcomes for participants treated with MIRV compared with investigator's choice of chemotherapy from the phase 3 MIRASOL trial, which met its primary endpoint of progression-free survival and key secondary endpoints of objective response rate and overall survival. METHODS:The MIRASOL trial was a confirmatory, phase 3, randomised, controlled, open-label trial, building on the phase 2 SORAYA trial which had previously demonstrated the safety and efficacy of MIRV in platinum-resistant ovarian cancer. Patients 18 years or older with a confirmed platinum-resistant, recurrent high-grade serous epithelial ovarian cancer diagnosis were recruited from 253 sites including hospitals, academic centres, and community centres in 21 countries. Patients must have received one to three previous systemic anticancer therapies, and have high FRα tumour expression (≥75% tumour cells with an immunohistochemistry score of ≥2+ membrane staining using the PS2+ scoring method), one or more lesions with measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to MIRV or investigator's choice of chemotherapy, stratified by number of previous therapy lines and the type of investigator's choice of chemotherapy. Therapies were administered in an open-label manner; MIRV was administered intravenously at 6 mg/kg of adjusted ideal bodyweight every 3 weeks. The primary endpoint was progression-free survival. Key secondary endpoints were objective response rate, overall survival, and a 15·0-point or greater improvement at week 8 or 9 in abdominal and gastrointestinal symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (EORTC QLQ-OV28) in the intention-to-treat population. The MIRASOL trial was registered at ClinicalTrials.gov (NCT04209855), the Gynecologic Oncology Group (GOG 3045), and the European Network of Gynaecological Oncological Trial Groups (ENGOT-ov55), and is complete. FINDINGS/RESULTS:Between Feb 3, 2020, and Aug 3, 2022, 453 patients were enrolled and randomly assigned to treatment (227 to the MIRV group and 226 to the investigator's choice of chemotherapy group). All patients were female; 301 (66%) participants were White, 53 (12%) were Asian, 13 (3%) were Black, and 86 (19%) were of another race or not reported; 27 (6%) were Hispanic or Latino. The median follow-up for the study, determined by the reverse Kaplan-Meier method, was 13·1 months (95% CI 12·1-14). QLQ-OV28 completion rates were 86% (365 of 425) at baseline and 81% (282 of 349) at week 8 or 9. 34 (21·0%; 95% CI 15·0-28·1) of 162 patients treated with MIRV reported improvement in QLQ-OV28 abdominal and gastrointestinal scores, compared with 23 (15·3%; 10·0-22·1) of 150 patients treated with the investigator's choice of chemotherapy. These differences were not statistically significant (odds ratio 1·5 [95% CI 0·8-2·6]; p=0·26). INTERPRETATION/CONCLUSIONS:MIRV did not seem to impair or improve patient quality of life compared with investigator's choice of chemotherapy. The similar quality-of-life outcomes in the two treatment groups, combined with the previously reported higher efficacy of MIRV compared with single-agent chemotherapy, support MIRV as new treatment option for FRα-positive platinum-resistant ovarian cancer. FUNDING/BACKGROUND:AbbVie.