Faculty Bibliography

PURPOSE/OBJECTIVE:Patients with GI cancers often face significant financial toxicity (FT) and health-related social risks (HRSRs), yet best practices for screening remain unclear. This study aimed to evaluate the prevalence of FT and HRSR and identify associated factors. METHODS:From June 2022 to August 2023, patients were screened using the Comprehensive Score for Financial Toxicity (COST), patient-reported HRSR (eg, housing, food insecurity), and quality of life (QOL). Multivariate regressions were used to assess predictors of FT and HRSR, adjusting for several variables. RESULTS:< .001). CONCLUSION/CONCLUSIONS:High levels of FT and HRSR were observed in patients with GI cancer. Early intervention to address financial and social burdens may improve both disease and survivorship outcomes.

OBJECTIVE:Mismatch repair deficiency (dMMR), high microsatellite instability (MSI-H), and high tumor mutation burden (TMB-H) are predictive and prognostic biomarkers in endometrial cancer. We aimed to characterize the racial/ethnic distribution of molecular markers and the clinical characteristics among endometrial cancer patients with TMB-H and MSI-H/dMMR. METHODS:The Endometrial Cancer Molecularly Targeted Therapy Consortium is a centrally verified clinical and molecular repository. Patients with endometrial cancer who underwent tumor profiling were included. TMB-H was defined as ≥10-12 mutations per megabase. MSI-H was determined by next-generation sequencing or polymerase chain reaction, and dMMR by loss of MLH1, MSH2, MSH6, or PMS2 on immunohistochemistry. Tumor biomarker positivity was defined as TMB-H and/or MSI-H/dMMR. Overall survival was assessed using Kaplan-Meier and Cox proportional hazard models. RESULTS:Among 742 patients, 22 % (n = 164) were biomarker positive: 12 % (n = 87) had both TMB-H and MSI-H/dMMR, 8 % (n = 63) had MSI-H/dMMR alone, and 2 % (n = 14) had 14 TMB-H alone. Only 9 % of non-Hispanic Black patients had biomarker positive tumors compared to 26 % of patients from other racial/ethnic groups. Pathogenic POLE mutations were rare (<1 %, n = 5). Patients with TMB-H had a higher proportion of high-risk histologies (43 %) than those with MSI-H/dMMR (24 %). Biomarker positive tumors were associated with a lower risk of death compared to biomarker negative tumors (aHR 0.63, 95 % CI: 0.46, 0.88). CONCLUSION/CONCLUSIONS:Less than 10 % of non-Hispanic Black patients with endometrial cancer had TMB-H and/or MSI-H/dMMR, and biomarker positivity was associated with improved survival. Prospective studies are necessary to elucidate how these molecular differences impact treatment and outcomes.

BACKGROUND AND AIMS/OBJECTIVE:PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination. METHODS:One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling. The number of treatment escalations, time to first escalation, and need for repeated escalations were compared between the biomarker subgroups. Another 20 patients (13 UC, 7 CD) were longitudinally sampled over 6 weeks after commencing corticosteroids. RESULTS:In corticosteroids-naïve UC and CD patients, all bowel surgeries (n = 6) and multiple therapy escalations (n = 10) occurred in IBDhi patients. IBDhi UC patients required significantly more treatment escalations, had a shorter time to first escalation, and a greater need for multiple escalations than IBDlo patients. No statistically significant differences were observed among CD patients. In corticosteroid-exposed patients, 66.6% of 'misclassifications' were IBDlo patients who required escalations. Among corticosteroid-treated patients with longitudinal sampling, 81.3% of those classified as IBDhi before steroids switched to IBDlo during therapy. CONCLUSIONS:No significant differences in treatment escalations were observed between biomarker-defined subgroups in CD. However, IBDhi UC patients required significantly earlier and more frequent therapy escalations, highlighting the need to further investigate PredictSURE IBD in UC. Notably, the discrimination ability of the biomarker was unreliable in patients receiving corticosteroid therapy.

OBJECTIVE:To estimate the association between third-trimester maternal low blood pressure (BP) and delivery of a neonate with small-for-gestational-age (SGA) birth weight in patients treated for mild chronic hypertension. METHODS:This is a secondary analysis of the CHAP (Chronic Hypertension and Pregnancy) study, which randomized pregnant participants with mild chronic hypertension to treatment to achieve goal BP below 140/90 mm Hg compared with usual care. We calculated mean systolic and diastolic BPs between 28 and 34 weeks of gestation and excluded those with systolic BP of 140 mm Hg or higher or diastolic BP of 90 mm Hg or higher. We defined low BP as mean systolic BP below 110 and mean diastolic BP below 70 mm Hg or mean arterial pressure below 80 mm Hg and compared those individuals with participants with mean systolic BP of 110-139 mm Hg or mean diastolic BP of 71-89 mm Hg or both or mean arterial pressure of 80 mm Hg or higher. Our primary outcome was delivery of a neonate with SGA birth weight (birth weight below the 5th percentile). Logistic regression estimated the association between low BP and SGA birth weight, and adjusted odds ratios (aORs) and 95% CIs were reported. RESULTS:Of 2,408 CHAP participants, 1,205 (50.0%) met analysis criteria. Of those 1,205, 31 (2.6%) had low BP and 1,174 (97.4%) had mean BP 110/70-139/89 mm Hg; 33 (2.7%) had mean arterial pressure below 80 mm Hg, and 1,172 (97.3%) had mean arterial pressure of 80 mm Hg or higher. Having a neonate with SGA birth weight below the 5th percentile occurred in 62 participants (5.1%): 1 of the 31 (3.2%) with BP below 110/70 mm Hg and 1 of the 33 (3.0%) with mean arterial pressure below 80 mm Hg. There was no significant association between delivery of a neonate with SGA birth weight less than the 5th percentile and low BP by either mean systolic BP and mean diastolic BP (aOR 0.46, 95% CI, 0.06-3.58) or mean arterial pressure (aOR 0.53, 95% CI, 0.07-4.01). We found a nonlinear relationship between mean arterial pressure and delivery of a neonate with SGA birth weight less than the 5th percentile, and, as mean arterial pressure decreased, there was lower probability of having a neonate with SGA birth weight (P=.02). CONCLUSION/CONCLUSIONS:Pharmacologic treatment of mild chronic hypertension infrequently results in low BP and does not appear to be associated with delivery of a neonate with SGA birth weight less than the 5th percentile for birth weight.

BACKGROUND:Osteogenesis imperfecta (OI) is a rare hereditary disorder of connective tissue. A Danish national registry study surprisingly identified digestive causes as one of the leading causes of OI mortality. However, there is a dearth of prospective data describing gastrointestinal symptoms in OI. Our aim was to assess common gastrointestinal symptoms in an OI patient population and compare it to the general U.S. METHODS:OI patients enrolled in a natural history protocol (NCT03575221) were prospectively evaluated for gastrointestinal symptoms and provided with PROMIS questionnaires for six gastrointestinal symptoms. The HMSS application was used to obtain T scores, score of 50 (and standard deviation of 10) representing the average of the general U.S. RESULTS:(IQR 21-34), and 54 % female. OI type IV 61 %, OI type III 20 %, and remaining patients had OI type VI, VII, XIV. The mean T score for the six gastrointestinal symptoms ranged from 46 to 49, within 1 SD from the general U.S. POPULATION/METHODS:Subgroup analyses showed no differences based on age, mobility, BMI, type of OI and genetic mutations (COL1A1 vs COL1A2), except increased abdominal pain with age. Patients with severe scoliosis (>50°) reported increased nausea and vomiting, and diarrhea compared to patients with mild to moderate scoliosis. DISCUSSION/CONCLUSIONS:We report the largest cohort of OI patients evaluated prospectively and directly for gastrointestinal complaints. Study patients, which excluded type I OI, did not report gastrointestinal symptoms higher than the general population except for abdominal pain in older patients. OI patients should be carefully evaluated in the same way as any other patient presenting with gastrointestinal complaints.

BACKGROUND:Older adults sustain disproportionately morbid injuries from low energy mechanisms, yet guidance around computed tomography imaging is lacking for this demographic. We hypothesize that current imaging practices may lead to potentially missed injuries, increasing morbidity and mortality. METHODS:A secondary analysis of a prospective multicenter study (11/2020-12/2021) of older blunt trauma patients was performed. Suboptimal imaging was defined as a mismatch between final injury diagnosis and initial computed tomography imaging. We compared optimally vs not optimally imaged patients to determine factors associated with suboptimal imaging and examined mortality, hospital length of stay, and critical care use with a multivariable logistic regression. RESULTS:Among 5,496 patients from 18 trauma centers (median age 79), 5,023 (91.4%) were optimally imaged, and 473 (8.6%) were suboptimally imaged initially. Falls (75.1%) were the predominant injury mechanism. Computed tomography imaging was performed in 95% of cases. Most potentially missed injuries were in the thoracic and lumbar spine. Suboptimally imaged patients had higher mortality and longer median hospital stays. Patients imaged prior to transfer (odds ratio 1.39, 95% confidence interval 1.04-1.87, P = .027) or not triggering full or limited trauma activations (odds ratio 1.64, 95% confidence interval 1.09-2.45, P = .017) were more likely to have missed injuries. CONCLUSIONS:More than 1 in 12 older blunt trauma patients received suboptimal computed tomography imaging initially. Our findings suggest that clinicians should maintain heightened awareness when evaluating older trauma patients as consults, those transferred from other facilities, or those facing language barriers, as these factors were associated with suboptimal imaging practices.

BACKGROUND:Extrinsic compression of the pulmonary artery (PA) has been described with mediastinal and other thoracic masses. This compression can lead to acquired pulmonic stenosis and pulmonary hypertension. CASE SUMMARY/METHODS:A 27-year-old woman was diagnosed with Hodgkin lymphoma with a mediastinal mass compressing her PA leading to severe pulmonary hypertension, without hemodynamic compromise. She was treated with chemotherapy and had rapid resolution of the pulmonary artery compression on subsequent transthoracic echocardiogram 1 month after starting treatment. DISCUSSION/CONCLUSIONS:The current literature on the rare entity of extrinsic PA compression includes cases of surgical or percutaneous intervention to relieve compression and cases with resolution of compression based on changes in physical examination or transthoracic echocardiogram several months after initial diagnosis. This case is novel in reporting echocardiographic evidence of complete resolution of PA compression within 1 month of treatment without invasive intervention. TAKE-HOME MESSAGES/CONCLUSIONS:Pulmonary hypertension secondary to extrinsic PA compression from a mediastinal tumor is rare, but this case demonstrates that it may completely and rapidly resolve after initiation of chemotherapy. Short-interval follow-up echocardiography is helpful to reassess the degree of pulmonary hypertension after treatment.

INTRODUCTION/BACKGROUND:High-volume (≥ 50 %) biopsy core involvement (HVCI) is an independent risk factor for unfavorable intermediate-risk prostate cancer by NCCN guidelines. The studies demonstrating increased recurrence in high-volume disease were conducted in an era of conventional fractionation, often without dose-escalation. In the SBRT era, we explore the value of this pathologic criteria in intermediate-risk disease. METHODS:A large institutional database was reviewed to identify patients diagnosed with localized intermediate-risk (Gleason Grade [GG] 2 and 3) disease, who were treated with definitive five-fraction SBRT without ADT. HVCI was analyzed (1) traditionally with all positive cores given equal weight as well as weighted with a positive core of GG1 to GG3 given (2) linearly and (3) exponentially increased weight. Oncologic outcomes were analyzed using Cox and linear regression analysis. RESULTS:From 2009 to 2018, 888 patients with intermediate-risk prostate cancer were treated with five-fraction SBRT monotherapy to a median dose of 3500 cGy. The majority (68 %) had GG2 disease. HVCI was present in the 22 % and was inversely related to prostate volume and directly related to T-stage. Biochemical disease-free survival (BDFS) was not significantly associated with HVCI in the cohort (p = 0.47) nor in the GG2 (p = 0.85) and GG3 (p = 0.26) sub-cohorts. Similarly, when linear or exponential weight was given to a core with higher-grade disease, there was no association with BDFS. Finally, PSA nadir was not associated with HVCI; however, time to PSA nadir (TTN) was negatively associated with HVCI in the GG3 sub-cohort (p = 0.04). CONCLUSION/CONCLUSIONS:With a median follow-up of 4.1 years, HVCI was not associated with BDFS following SBRT monotherapy, particularly in patients with otherwise favorable intermediate-risk disease (GG2). TTN analysis suggests that HVCI may remain prognostic in GG3 disease (by definition unfavorable intermediate-risk). Further work should prospectively confirm whether HVCI is unnecessary in risk-stratifying GG2 disease in the SBRT era.

OBJECTIVE:To obtain perspectives about existing compensation structures in gynecologic oncology, including common challenges and successful strategies within diverse systems. METHODS:Electronic mail was used to recruit OB/GYN department chairs and directors of cancer centers who were gynecologic oncologists and responsible for administering compensation structures at their institution. Using a semi-structured guide, three interviewers conducted 30-min qualitative interviews, which were recorded and transcribed. Two coders used the constant comparative method to summarize key themes. RESULTS:Response rate was 65 %, resulting in 17 interviewees. Participants were a third women and in their current position for a median of 7 years. The most prominent theme was the tension of balancing reimbursement for revenue-generating clinical activities with non-clinical work in research and education. Chair discretionary funds were useful to offset unfunded responsibilities. Broad clinical productivity measures were used: from more traditional work Relative Value Units (wRVUs) to measures that captured downstream impact, such as number of new patients or surgeries. Even in institutions with centralized funds flow systems, disparities were frequently noted for the monetary value assigned per wRVU. Academic scorecards were described as a method to ascribe value for academic work, often for bonus incentives. Another common stressor unique to gynecologic oncology was low reimbursement for chemotherapy-related services compared to surgery. Provision of regular productivity reports was common, but full transparency was controversial. CONCLUSIONS:Our inquiry demonstrates that our academic leaders are unable to use compensation to fully support areas they deem important.