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Abstract Introduction: Up to 40% of newly diagnosed diffuse large B cell lymphoma (DLBCL) will relapse after frontline rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (RCHOP), with subsequent poor prognosis. Identification of patients (pts) at high risk of relapse early in the treatment can allow for development of risk adapted therapies to improve outcomes. Positron Emission Tomography scan after 2 cycles of therapy (PET2) has been evaluated as a predictor of relapse but study treatments were heterogenous and results were conflicting. A substudy of CALGB 50303 trial did not find association of PET2 response by Deauville Score (DS) with survival in RCHOP and DA-EPOCH-R treated pts. In the UK National Cancer Research Institute Prospective Study, DS of 5 on PET2 predicted worse progression free survival but not overall survival (OS) in RCHOP-21 and RCHOP-14 treated pts. Here we report impact of PET2 response on outcomes in two large independent, prospective cohorts of newly diagnosed DLBCL treated homogenously with two RCHOP-based regimens of similar efficacy. Methods: Discovery was done in adult pts with DLBCL enrolled into a single arm phase 2 trial of lenalidomide plus standard RCHOP (R2CHOP) (MC078E, NCT00670358). The validation cohort comprised of adult pts with newly diagnosed DLBCL treated with standard RCHOP prospectively enrolled into the Mayo component of the University of Iowa/Mayo Clinic Molecular Epidemiology Resource (MER). Both MC078E and MER cohorts included patients who received at least 3-6 cycles of therapy and had a PET2. Pts who progressed on PET2 were excluded. End of treatment (EOT) PET was done 3-12 weeks after last cycle of therapy. The revised response criteria for malignant lymphoma (Cheson, et al 2007) was used to assess PET in MC078E. In MER, revised response criteria for malignant lymphoma (Cheson et al 2007) or Lugano classification was used, depending on era of diagnosis. Positive PET was defined as FDG uptake above background (Cheson 2007) or DS 4 or 5 (Lugano 2014). Study endpoints were event-free survival (EFS) and OS by PET2 status. Results: Out of 118 pts treated on MC078E, 102 had PET2 (MC078E). The median age at diagnosis was 64 years (range 19-87), 61 (60%) were male, 89 (87%) had advanced stage disease, 46 (45%) had international prognostic index (IPI) of 3-5. 58 (57%) were PET2 Negative (PET2-ve) and 44 (43%) were PET2 Positive (PET2+ve). At EOT PET, 83 (81%) had -ve PET and 15 (15%) had +ve PET. Out of 44 PET2+ve pts, 15 remained +ve at EOT PET. Out of 58 PET2-ve pts, 56 had EOT PET available and all were -ve. Out of 866 DLBCL pts enrolled into MER between August 2005 and June 2015, 621 were treated with RCHOP for 3-6 cycles and 272 had available PET2 (MER). The median age was 65 years (range 55-73), 152 (56%) were male, 174 (64%) had advanced stage, 103 (38%) had IPI 3-5. 186 (68%) were PET2-ve and 86 (32%) were PET2+ve. Out of 235 with EOT PET available, 182 (77%) had -ve EOT PET and 25 (11%) had +ve EOT PET. PET2+ve pts had higher odds of +ve EOT PET (OR: 17.4 (CI 95 8.3-40.0), p<0.001) and progression on EOT PET (OR: 4.3 (CI 95 1.9-10.2), p<0.001) in MER cohort. This analysis was not possible on MC078E as all PET2-ve had -ve EOT PET. In MC078E, 2-year EFS and OS were 69.5% (CI 95 61.1-79.1) and 88.1% (CI 95 82-94.7). In MER, 2-year EFS and OS were 71.6% (CI 95 67.7-76.8) and 82.3% (CI 95 79.3-85.3). Compared to PET2-ve, PET2+ve pts had significantly inferior EFS in both MC078E (HR 4.0, CI 95 2.1-7.88, p<0.0001, figure 1a) and MER (HR 2.9, CI 95 1.9-4.1, p<0.0001, figure 1c). Compared to PET2-ve , PET2+ve pts had a trend towards lower OS in MC078E (HR 2.0, CI 95 0.9-4.9, p=0.1, figure 1b) and a significantly lower OS in MER (HR 2.3, CI 95: 1.5-3.4, p<0.0001, figure 1d). In subgroup analysis of MC078E, PET2+ve pts had lower EFS and a trend towards lower OS in all subgroups except IPI 0-2 (Table 1). In MER, PET2+ve pts had lower EFS and OS in all the subgroups except stage I-II and IPI 0-2 (Table 1). Conclusions: Positive PET2 was associated with increased risk of disease progression and death in newly diagnosed DLBCL. Results of our study provide robust evidence of importance of PET2 as an early predictor DLBCL pts at high risk of progression in two independent prospective cohorts. PET2-guided risk-adapted strategies using chimeric antigen receptor T-cell therapy and bispecific antibodies may potentially improve outcomes, should be explored in clinical trials and results of our study serve as a benchmark for such studies. Figure 1 Figure 1. Disclosures Maurer: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Nanostring: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang: Genentech: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; MorphoSys: Research Funding; InnoCare: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Cerhan: Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; Regeneron Genetics Center: Other: Research Collaboration; NanoString: Research Funding; Genentech: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Habermann: Seagen: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding; Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Vaccinations have been hypothesized to play a role in lymphoma etiology, but there are few studies, mixed results, and limited data on lymphoma subtypes. Herein, we investigate the association of vaccinations with risk of major lymphoma subtypes. Methods: We studied 2,461 lymphoma cases and 2,253 controls enrolled from 2002 to 2014. Participants self-reported history of vaccinations against hepatitis A, hepatitis B, yellow fever, and influenza. Polytomous logistic regression was used to estimate OR and 95% confidence intervals (CI), adjusting for potential confounders. Results: After multivariable adjustment, vaccination against influenza was inversely associated with lymphoma (OR = 0.82; 95% CI, 0.66–1.02), which was stronger for last vaccination 1+ years before enrollment (OR = 0.71; 95% CI, 0.56–0.91) and for >5 influenza vaccinations (OR = 0.56; 95% CI, 0.46–0.68). Ever vaccination against hepatitis A (OR = 0.81; 95% CI, 0.66–1.00) but not hepatitis B (OR = 0.97; 95% CI, 0.81–1.18) was associated with lymphoma risk, although more recent vaccinations were inversely associated with lymphoma risk for both hepatitis A (<6 years before enrollment, OR = 0.56; 95% CI, 0.40–0.77) and hepatitis B (<9 years before enrollment, OR = 0.72; 95% CI, 0.55–0.93). Ever vaccination against yellow fever was inversely associated with risk (OR = 0.73; 95% CI, 0.55–0.96), and this did not vary by time since last vaccination. Although there was no overall statistical evidence for heterogeneity of vaccination history by lymphoma subtype, the only statistically significant inverse associations were observed for influenza and yellow fever vaccinations with diffuse large B-cell and follicular lymphoma. Conclusions: Selected vaccinations were inversely associated with lymphoma risk, with time since last vaccination relevant for some of these vaccines. Impact: Vaccinations against hepatitis A, hepatitis B, yellow fever, and influenza are unlikely to increase lymphoma risk.

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

While the safety of video follow-up in bariatric surgery is established, patients’ perception of telemedicine visits remained unknown. A randomized clinical trial evaluating patients’ perception of video postoperative follow-up (F/U) visits was conducted in the pre COVID-19 era. 24 patients were randomized in the preoperative clinic to receive either in-person or video F/U, and then surveyed about their experience and preference. The majority reported that if they had to do it over, they would prefer a video visit. Among those who received video visits, 11/12 reported that the lack of physical contact was acceptable. 82% of the video group expressed that their visit was better or as good as an in-person visit, while 9% were not sure, and 9% reported that video was worse. This finding suggests that postoperative video follow-up visits are acceptable among bariatric surgery patients and should be offered as an alternative to traditional visits.

Abstract The prognosis of several lymphoid malignancies has improved through development of novel therapies, combination with traditional chemotherapies, and delineation of appropriate therapeutic sequencing. Toxicities that are arising because of prolonged or multiple sequential therapeutic interventions are becoming increasingly impactful. Among the broad spectrum of complications that patients with lymphoid malignancies may experience, cardiovascular toxicities are significant in terms of morbidity and mortality. The entire cardiovascular system can be affected, but cardiomyopathy, heart failure, and arrhythmias remain of greatest concerns with the use of anthracyclines, hematopoietic stem cell transplantation, and radiation therapy in patients with lymphoid malignancies. These aspects will be covered in this article within the framework of case-based discussions. Key to the management of cardiovascular complications in patients with lymphoid malignancies is awareness and preparedness across the cancer continuum. Baseline risk stratification helps to direct surveillance and early intervention efforts before, during, and after cancer therapy, which are paramount for the best possible outcomes. Along these lines, the overall goal is to enable the best possible therapies for lymphoid malignancies without the complications of clinically significant cardiovascular events.

Abstract Background Consolidation of healthcare in the US has resulted in integrated organizations encompassing large geographic areas, with varying services and complex patient flows. Profound changes in patient volumes and behavior have occurred during the SARS Cov2 pandemic, but understanding these changes across organizations is challenging. Network analysis provides a novel approach to address this. Methods We retrospectively evaluated hospital-based encounters with an index emergency department visit in a healthcare system comprising 18 hospitals, using patient transfer as a marker of unmet clinical need. We developed quantitative models of transfers using network analysis incorporating the level of care provided (ward, progressive care, intensive care) during pre-pandemic (May 25, 2018 to March 16, 2020) and mid-pandemic (March 17, 2020 to March 8, 2021) time periods. Results 829,455 encounters were evaluated. The system functioned as a non-small-world, non-scale-free, dissociative network. Our models reflected transfer destination diversification and variations in volume between the two time points – results of intentional efforts during the pandemic. Known hub-spoke architecture correlated with quantitative analysis. Conclusion Applying network analysis in an integrated US healthcare organization demonstrates changing patterns of care and the emergence of bottlenecks in response to the SARS Cov2 pandemic, consistent with clinical experience, providing a degree of face validity. The modeling of multiple influences can identify susceptibility to stress and opportunities to strengthen the system where patient movement is common and voluminous. The technique provides a mechanism to analyze the effects of intentional and contextual changes on system behavior.

AbstractBecause there have been a dvances in frontline treatment for mantle cell lymphoma (MCL) over the last 2 decades, we sought to characterize the changes in frontline treatment patterns and their association with outcomes. Patients with newly diagnosed MCL from September 2002 through June 2015 were enrolled in a prospective cohort study, and clinical characteristics, treatment, and clinical outcomes were compared between patients diagnosed from 2002 to 2009 (Era 1) compared with 2010 to 2015 (Era 2). Patient age, sex, and simplified MCL International Prognostic Index (sMIPI) score were similar between the 2 groups. In patients age 65 years or younger, there was less use of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-Hyper-CVAD) (16.1% vs 8.8%) but more use of rituximab plus maximum-strength cyclophosphamide, doxorubicin, vincristine, and prednisone (R-maxi-CHOP) alternating with rituximab plus high-dose cytarabine (R-HiDAC), also known as the Nordic regimen, and R-CHOP alternating with rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) (1.1% vs 26.4%) and less use of R-CHOP or R-CHOP-like regimens (64.5% vs 35.2%) but more use of R-bendamustine (0% vs 12.1%) in Era 2 (P < .001). These changes were associated with improved event-free survival (EFS; 5-year EFS, 34.3% vs 50.0%; P = .010) and overall survival (OS; 5-year OS, 68.8% vs 81.6%; P = .017) in Era 2. In patients older than age 65 years, there was less use of R-CHOP or R-CHOP-like therapy (39.0% vs 14.3%) and nonstandard systemic therapy (36.6% vs 13.0%) but more use of R-bendamustine (0% vs 49.4%). These changes were associated with a trend for improved EFS (5-year EFS, 25.4% vs 37.5%; P = .051) in Era 2. The shift from R-CHOP or R-CHOP-like regimens to R-bendamustine was associated with improved EFS (5-year EFS, 25.0% vs 44.6%; P = .008) in Era 2. Results from this prospective cohort study provide critical real-world evidence for improved outcomes with evolving frontline patterns of care in patients with MCL.

Objectives: To characterize 30-day morbidity of upper ureteral reconstruction (UUR) and lower ureteral reconstruction (LUR) surgery by comparing open and minimally invasive surgery (MIS) approaches using a national surgical outcomes registry. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed for patients who underwent UUR and LUR between 2007 and 2017. Primary endpoints included 30-day complications, transfusion, readmission, return to operating room (ROR), and prolonged postoperative length of stay (LOS). Multivariable logistic regression was performed to observe the association of MIS approach on 30-day outcomes. Results: Three thousand forty-two patients were identified with 2116 undergoing UUR and 926 undergoing LUR. Of 2116 patients undergoing UUR, 1733 (82%) were performed through an MIS approach. On multivariable analysis, open approach for UUR was associated with increased odds of any 30-day complication (odds ratio (OR) 1.6 [1.1–2.4]; p = 0.014), major complication (OR 1.8 [1.04–3.0]; p = 0.034), transfusion (OR 3.7 [1.2–11.5]; p = 0.025), ROR (OR 2.0 [1.0–3.9]; p = 0.047), and prolonged LOS (OR 5.4 [3.9–7.6]; p < 0.001). Of the 926 patients undergoing LUR, 458 (49%) were performed through an MIS approach. On multivariable analysis, open approach for LUR was associated with increased odds of any 30-day complication (OR 1.5 [1.1–2.1]; p = 0.028), minor complication (OR 1.7 [1.1–2.6]; p = 0.02), transfusion (OR 8.1 [2.7–23.7]; p < 0.001), and prolonged LOS (OR 4.2 [2.4–7.3]; p < 0.001). Conclusion: Utilization of a national surgical database revealed an open approach was associated with increased 30-day morbidity across multiple postoperative outcome measures. These findings suggest an MIS approach should be considered, when feasible, for upper and lower ureteral reconstruction.

Background: Data regarding opioid prescribing patterns following pediatric orthopaedic procedures is limited. The aim of this work was to evaluate the effects of tiered guidelines for discharge opioid prescriptions following common pediatric orthopaedic procedures. Methods: Quality improvement project conducted at a single academic institution. Guidelines for discharge opioid prescriptions were implemented January 2018 and established 4 tiers of increasing invasiveness for 28 common pediatric orthopaedic procedures. Patients who underwent these procedures in 2017 comprised the preguideline cohort (N=258), while patients treated in 2019 comprised the postguideline cohort (N=212). Opioid prescriptions were reported as oral morphine equivalents (OMEs). Univariate tests were performed to assess statistically significant differences before and after implementation of the guidelines. Results: There was a significant decrease in OME prescribed between preguideline and postguideline cohorts (median OME 97.5 vs. 37.5). When analyzed according to procedure tiers, tiers 1, 2, and 4 showed significant decreases in OME prescribed between 2017 and 2019. The rate of no opioids prescribed at discharge increased from 13% to 23% between preguideline and postguideline cohorts. The 30-day refill rate did not significantly change. After implementation of guidelines, 91% of all prescriptions were within the guideline parameters, and there was a significant reduction in prescription variability. In tier 4 procedures, median OME prescribed decreased from 375 preguideline to 188 postguideline, but was associated with greater opioid refills within 30 days of discharge (10.2% preguideline vs. 28.8% postguideline). Conclusions: Tiered guidelines for discharge opioid prescriptions following pediatric orthopaedic procedures can significantly decrease the quantity of opioids prescribed. Furthermore, we noted excellent adherence and no overall increase in the rates of narcotic refills. Such guidelines may improve pediatric orthopaedists’ ability to responsibly treat postoperative pain while limiting the distribution of unneeded opioids. Level of Evidence: Level IV—quality improvement project.