Faculty Bibliography

BACKGROUND AND OBJECTIVES/UNASSIGNED:Some patients with multiple sclerosis (MS) receiving ocrelizumab (OCR) report worsening symptoms toward the end of the 6-month infusion cycle ('wearing off'). The objective of our study was to comprehensively assess changes in symptom burden across 2 consecutive OCR infusion cycles. METHODS/UNASSIGNED:SYMptom Burden on Ocrelizumab, a Longitudinal Study (SymBOLS; NCT04855617) was an investigator-initiated, 2-center study of patients with MS starting or receiving OCR. Patients' symptoms were assessed with NeuroQoL short forms, SymptoMScreen, and Work Productivity and Activity Impairment Questionnaire at the start-cycle, mid-cycle, and end-cycle time points in each of the 2 infusion cycles. Symptom scores at the 3 time points within each cycle were compared with repeated-measures ANOVA or the Friedman rank-sum test for non-normal variables. The proportions of patients with a meaningful symptomatic change from the start to the end of each infusion cycle were calculated, and patients whose symptoms improved, worsened, and stayed the same from the start to the end of the cycle were compared with respect to demographic and clinical characteristics. RESULTS/UNASSIGNED:One hundred three patients with MS provided longitudinal data for analyses (mean age [SD]: 46.7 [12.2] years, 68% female, 33% non-White, disease duration: 15.5 [5] years, 41% with the Extended Disability Status Scale score >3). On a group level, NeuroQoL and SymptoMScreen scores mostly remained stable or even improved slightly toward the end of each cycle. On an individual level, symptoms remained unchanged across either cycle for most patients, and meaningful symptom worsening from the start to the end of the cycle was no more common than improvement. Meaningful change in symptoms in both cycles was very rare and generally in the direction of improvement toward the end cycle. Despite the lack of evidence for symptom worsening with a longer time from infusion, 54% of patients endorsed feeling of "wearing off" at least sometimes, most commonly as an increase in fatigue. DISCUSSION/UNASSIGNED:Our prospective study failed to uncover evidence for the worsening of symptoms with a longer time from OCR infusion. These findings cast doubt on the existence of wearing off as a physiologic phenomenon in OCR-treated patients with MS. The perception of wearing off is likely the result of natural fluctuations in MS symptoms and attribution bias.

INTRODUCTION/UNASSIGNED:There is a dearth of information about whether lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ+) dancers, who often experience increased psychosocial risk factors, are at increased risk of engaging in harmful behaviors compared to their heterosexual cisgender counterparts. This study explores harmful behaviors dancers engage in according to their self-reported sexual orientation and gender identity (SOGI), utilizing the validated Risky, Impulsive, and Self-Destructive Behavior Questionnaire (RISQ). METHODS/UNASSIGNED:-test were utilized to assess statistical differences among RISQ outcomes in 4 SOGI groups: Cisgender Heterosexual Female (n = 20); Cisgender Heterosexual Male (n = 7); LGBTQ+ Female (n = 19); and LGBTQ+ Male (n = 20). RESULTS/UNASSIGNED: = .006). CONCLUSIONS/UNASSIGNED:This study found significant difference in RISQ scores based on a dancer's SOGI. Harmful behaviors should be taken into consideration when working to improve dancer patient outcomes and quality of life.

OBJECTIVES:Intra-individual variability (IIV), measured across repeated response times (RT) during continuous psychomotor tasks, is an early marker of cognitive change in the context of neurodegeneration. To advance IIV towards broader application in clinical research, we evaluated IIV from a commercial cognitive testing platform and compared it to the calculation approaches used in experimental cognitive studies. METHODS:-transformed standard deviation or "LSD"). We calculated IIV from the raw RTs using coefficient of variation (CoV), regression-based, and ex-Gaussian methods. The IIV from each calculation was then compared by rank across participants. RESULTS:A total of n = 120 participants with MS aged 20-72 (Mean ± SD, 48.99 ± 12.09) completed the baseline cognitive measures. For each task, the interclass correlation coefficient was generated. Each ICC showed that LSD, CoV, ex-Gaussian, and regression methods clustered strongly (Average ICC for DET: 0.95 with 95% CI [0.93, 0.96]; Average ICC for IDN: 0.92 with 95% CI [0.88 to 0.93]; Average ICC for ONB: 0.93 with 95% CI [0.90 to 0.94]). Correlational analyses indicated the strongest correlation between LSD and CoV for all tasks (rs ≥ 0.94). CONCLUSION:The LSD was consistent with research-based methods for IIV calculations. These findings support the use of LSD for the future measurement of IIV for clinical studies.

Background: Given the physical and economic burden of complications in spine surgery, reducing the prevalence of perioperative adverse events is a primary concern of both patients and health care professionals. This study aims to identify specific perioperative factors predictive of developing varying grades of postoperative complications in adult spinal deformity (ASD) patients, as assessed by the Clavien-Dindo complication classification (Cc) system. Methods: Surgical ASD patients ≥18 years were identified in the American College of Surgeons"™ National Surgical Quality Improvement Program from 2005 to 2015. Postoperative complications were stratified by Cc grade severity: minor (I, II, and III) and severe (IV and V). Stepwise regression models generated dataset-specific predictive models for Cc groups. Model internal validation was achieved by bootstrapping and calculating the area under the curve (AUC) of the model. Significance was set at P < 0.05. Results: Included were 3936 patients (59 ± 16 years, 63% women, 29 ± 7 kg/m²) undergoing surgery for ASD (4.4 ± 4.7 levels, 71% posterior approach, 11% anterior, and 18% combined). Overall, 1% of cases were revisions, 39% of procedures involved decompression, 27% osteotomy, and 15% iliac fixation. Additionally, 66% of patients experienced at least 1 complication, 0% of which were Cc grade I, 51% II, 5% III, 43% IV, and 1% V. The final model predicting severe Cc (IV"“V) complications yielded an AUC of 75.6% and included male sex, diabetes, increased operative time, central nervous system tumor, osteotomy, cigarette pack-years, anterior decompression, and anterior lumbar interbody fusion. Final models predicting specific Cc grades were created. Conclusions: Specific predictors of adverse events following ASD-corrective surgery varied for complications of different severities. Multivariate modeling showed smoking rate, osteotomy, diabetes, anterior lumbar interbody fusion, and higher operative time, among other factors, as predictive of severe complications, as classified by the Clavien-Dindo Cc system. These factors can help in the identification of high-risk patients and, consequently, improve preoperative patient counseling. Clinical Relevance: The findings of this study provide a foundation for identifying ASD patients at high risk of postoperative complications .

PURPOSE/OBJECTIVE:Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS/METHODS:Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS:Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION/CONCLUSIONS:In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

OBJECTIVE:The real-world management of patients with non-BRCA, homologous recombination repair pathway variants with increased or uncertain risks of ovarian cancer is unknown. The objective was to determine the adoption of risk-reducing salpingo-oophorectomy (RRSO) for carriers of variants with increased or uncertain risks of ovarian cancer beyond BRCA. METHODS:This was a retrospective cohort study of patients at three hospitals with non-BRCA, homologous recombination repair pathway variants with increased risk (BRIP1, RAD51C, RAD51D) and uncertain risk (ATM, BARD1, NBN, PALB2) of ovarian cancer. Outcomes of interest were adoption of RRSO and factors associated with adoption of RRSO. Wilcoxon rank-sum, chi-square, and logistic regression were performed with p < 0.05. RESULTS:Of 318 patients, 76 (24%) had pathogenic variants with increased risks of ovarian cancer (BRIP1, 45; RAD51C, 20; RAD51D, 11), and 242 (76%) had variants with uncertain risks of ovarian cancer (ATM, 145; PALB2, 69; NBN, 23; BARD1, 5). Of 64 patients eligible for RRSO by National Comprehensive Cancer Network (NCCN) criteria or family history, 31 (48%) underwent RRSO. Among eligible patients who did not undergo RRSO, 24 (73%) were not referred for gynecologic oncology consultation. Older age at testing (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.03-1.13) and referral to gynecologic oncology (aOR 33.48, CI 8.10-138.39) were associated with increased adoption of RRSO when adjusting for personal and family history of breast and ovarian cancer. CONCLUSION/CONCLUSIONS:Half of RRSO-eligible patients by NCCN criteria beyond BRCA did not undergo RRSO. Opportunities exist for improving education to increase referrals to facilitate RRSO for these patients.

OBJECTIVE:The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. METHODS:This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. RESULTS:Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23). CONCLUSION/CONCLUSIONS:Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

STUDY DESIGN/METHODS:Retrospective review of a multicenter comprehensive cervical deformity (CD) database. OBJECTIVE:To develop a novel risk index specific to each patient to aid in patient counseling and surgical planning to minimize postop DJK occurrence. BACKGROUND:Distal junctional kyphosis(DJK) is a radiographic finding identified after patients undergo instrumented spinal fusions which can result in sagittal spinal deformity, pain and disability, and potentially neurological compromise. DJK is considered multifactorial in nature and there is a lack of consensus on the true etiology of DJK. METHODS:CD pts with baseline(BL) and at least 1-year postoperative(1Y) radiographic follow-up were included. A patient-specific DJK score was created through use of unstandardized Beta weights of a multivariate regression model predicting DJK(end of fusion construct to the 2nd distal vertebra change in this angle by<-10° from BL to postop). RESULTS:110 CD pts included(61yrs, 66.4%F, 28.8kg/m2). 31.8% of these pts developed DJK (16.1% 3M, 11.4% 6M, 62.9% 1Y). At BL, DJK pts were more frail and underwent combined approach more (both P<0.05). Multivariate model regression analysis identified individualized scores through creation of a DJK equation: -0.55+0.009(BL Inclination) -0.078(Pre Inflection)+5.9×10-5(BL LIV angle) + 0.43(combine approach) - 0.002(BL TS-CL)- 0.002(BL PT)- 0.031(BL C2-C7)+ 0.02(∆T4-T12)+ 0.63(Osteoporosis)- 0.03(anterior approach) - 0.036( Frail) - 0.032(3 column osteotomy). This equation has a 77.8% accuracy of predicting DJK. A score ≥81 predicted DJK with an accuracy of 89.3%. The BL reference equation correlated with 2Y outcomes of NSR-Back percentage(P=0.003), reoperation(P=0.04), and MCID for EQ. 5D(P=0.04). CONCLUSIONS:This study proposes a novel risk index of DJK development that focuses on potentially modifiable surgical factors as well as established patient-related and radiographic determinants. The reference model created demonstrated strong correlations with relevant two year outcome measures, including axial pain-related symptoms, occurrence of related reoperations, and the achievement of minimal clinically importance differences for EQ. 5D.

PURPOSE/OBJECTIVE:The optimal local therapy of patients with nodal disease in supraclavicular (SCV), internal mammary nodes (IMN) and level III axilla is not well studied. We aimed to evaluate the outcomes of patients with breast cancer and advanced nodal disease that received a nodal boost. METHODS AND MATERIALS/METHODS:This retrospective study included 79 patients with advanced nodal disease who underwent adjuvant radiation with a nodal boost to the SCV, IMNs, and/or axilla. All patients had radiographic changes after systemic therapy concerning for gross nodal disease. Overall survival, disease-free survival (DFS), and local recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS:All patients received an initial 50 Gy to the breast/chest wall and regional nodes, of whom 46.8% received an IMN boost, 38.0% axillary (ax)/SCV boost, and 15.2% both IMN and ax/SCV boost (IMN + ax/SCV). Most patients had hormone receptor positive (74.7%) and human epidermal growth factor receptor 2 negative disease (83.5%). In addition, 12.7% of patients had clinical (c) N2 disease, 21.5% cN3A disease, 51.9% cN3B disease, and 5.1% cN3C disease. Most patients received chemotherapy (97.5%). The median nodal boost dose was 10 Gy (range, 10-20 Gy), with 21.6% of IMN, 16.7% of ax/SCV, and 16.7% of IMN + ax/SCV receiving 14 to 20 Gy. With a median follow up of 30 months, the 3-year local recurrence-free survival, DFS, and overall survival rates were 94.5%, 86.3%, and 93.8%, respectively. Crude rates of failure were 13.9% (10.1% distant failure [DF] alone; 3.8% DF + locoregional failure [LRF]). Rates of failure by boost group were 13.3% for ax/SCV (10.0% DF alone; 3.3% DF + LRF), 5.4% for IMN (2.7% DF alone, 2.7% DF + LRF), and 41.7% for IMN + ax/SCV (33.3% DF, 8.3% DF + LRF). There were no LRFs without DFs. The median time to failure was 22.8 months (interquartile range, 18-34 months). Clinical tumor size and IMN + ax/SCV versus IMN or ax/SCV alone was associated with worse DFS (hazard ratio [HR]: 9.78; 95% confidence interval [CI], 2.07-46.2; P = .004 and HR: 9.49; 95% CI, 2.67-33.7; P = .001, respectively). On multivariate analysis, IMN + ax/SCV versus IMN or ax/SCV alone retained significance (HR: 4.80; 95% CI, 1.27-18.13; P = .02). CONCLUSIONS:In this population of patients with locally advanced breast cancer, the majority of failures were distant with no isolated LRFs. Failures were the highest in the IMN + ax/SCV group (∼40%). Further treatment escalation is necessary for these patients.