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558 citation(s) found for "Núñez, Harold".

Standard-of-Care Bortezomib Dosing in Multiple Myeloma: An International Survey of Physicians
McCaughan, Georgia , Cowan, Andrew J. , Banerjee, Rahul , Kaur, Gurbakhash , Wang, Bo , Anderson, Larry D. , Rajkumar, S. Vincent

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 5073-5073

10.1182/blood-2023-173772 Get It

Background: Bortezomib (Velcade), a mainstay of treatment regimens for newly diagnosed multiple myeloma (MM), is often dosed twice-weekly in trials (i.e., Days 1, 4, 8, 11 in 21-day cycles). However, several analyses have shown that once-weekly bortezomib performs comparably and is associated with less peripheral neuropathy (Sidana PLoS One 2017, Mateos L&L 2020, Cook AJH 2021). Many centers thus use once-weekly bortezomib in MM induction regimens regardless of transplant eligibility, e.g. modified VRd or Dara-VRd in 28-day cycles with once-weekly subcutaneous (SC) bortezomib 1.3 mg/m 2 (McCaughan BJH 2022). Physician attitudes and perceptions regarding how bortezomib should be dosed, an important step toward establishing a global standard of care in MM, have not been investigated. Methods: We conducted a global online survey of hematologists/oncologists who had treated ≥1 patient with MM in the past 12 months. The survey was distributed via social media platforms as well as targeted emails to MM physicians, IMWG members, and outreach through professional societies. The survey comprised 14 questions including usage of once- vs twice-weekly bortezomib, usage of SC vs IV bortezomib, attitudinal questions about potential benefits/disadvantages of each approach, and perceived barriers to using once-weekly bortezomib. Statistics were analyzed descriptively with Wilcoxon rank-sum and signed-rank tests. Results: Of 317 webpage visits, 205 responses were recorded (65% completion rate).Most respondents were from US academic practices (25%, n=52), US community practices (22%, n=46), or Australian academic practices (6%, n=13); however, responses were recorded from 38 countries including 22 low- or middle-income countries (LMICs: 29% of responses, n=60).Over a third of respondents (37%, n=76) practiced in community settings, and most respondents (58%, n=119) reported >20 patients with MM under their personal care . 93 respondents (45%) had previously helped write institutional or societal guidelines, including 21 IMWG members.Respondents reported using once-weekly bortezomib most of the time (median 95% of patients, IQR 80%-100%) and almost always used SC bortezomib (IQR 100%-100%).There were no significant differences in bortezomib frequency or route based on academic vs community practice, experience with MM, US vs non-US, or LMIC vs non-LMIC. Large majorities of respondents (Table 1) felt that once-weekly bortezomib is preferred by patients (94%), associated with comparable durations of response (79%), and associated with less peripheral neuropathy (89%). Conversely, 61% of respondents felt that twice-weekly bortezomib in superior in newly diagnosed MM with acute cast nephropathy.Physician estimates of the incidence of any-grade peripheral neuropathy were significantly lower with once-weekly bortezomib (median 30%, IQR 20-43%) vs twice-weekly bortezomib (median 50%, IQR 40-73%). Similarly, Grade 3+ neuropathy estimates were significantly lower with once-weekly (median 10%, IQR 5-17%) vs twice-weekly bortezomib (median 25%, IQR 15-38%), with p<0.001 in all cases . The most common cited barriers to ordering once-weekly bortezomib (Table 2) were perceived lack of prospective data (31%), difficulty modifying treatment orders (24%), and resistance from pharmacist colleagues who prefer adhering to trial-studied regimens (13%). Discussion: In our survey of over 200 MM-treating physicians from 38 countries (including 22 LMICs), once-weekly subcutaneous bortezomib was overwhelmingly preferred regardless of practice setting or country. The only exception was acute cast nephropathy, where twice-weekly bortezomib may expedite renal recovery and is reasonable to use initially. Neuropathy estimates were similar to published incidences (32% with once-weekly bortezomib vs 47% with twice-weekly bortezomib) from prospective data collected from the ALCYONE, GIMEMA-QW, and VISTA randomized trials (Mateos L&L 2020). Our findings highlight the widening mismatch between what physicians routinely prescribe to patients versus what registrational trials typically require. Given that >90% of physicians personally prefer once-weekly bortezomib and that >90% report that their patients feel similarly, once-weekly bortezomib appears to have become the global standard of care. This consensus should be taken into consideration for clinical trial design in the future.
IPSS-M - Use for Predicting Survival and Progression in Patients with Ccus - a Retrospective Multi-Institutional Study
Nanaa, Ahmad , Al‐Kali, Aref , Nguyen, Phuong L., He, Rong , Patnaik, Mrinal M. , Mangaonkar, Abhishek A. , Anderson, Julia , Chen, Weina , Weinberg, Olga K. , Chung, Stephen S. , Jevremović, Dragan , Greipp, Patricia T. , Alkhateeb, Hassan B. , Madanat, Yazan F.

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4590-4590

10.1182/blood-2023-191048 Get It

Background: Clonal cytopenia of undetermined significance (CCUS) is characterized by the presence of a clone with somatic mutations in genes associated with myeloid neoplasms (MN) or abnormal cytogenetics, along with unexplained and persistent cytopenias in the absence of significant marrow dysplasia. CCUS is considered a premalignant state with a risk of progression to MN. The clinical outcomes of patients (pts) with high risk CCUS (Weeks et al, NEJM Evidence 2023) may be similar that of some patients with myelodysplastic syndromes (MDS). This study aims to predict the outcomes of CCUS patients using the molecular international prognostic scoring system (IPSS-M) developed for MDS. Methods: A retrospective analysis was conducted in patients diagnosed with CCUS between 2015 and 2023, we included patients harboring pathogenic mutations (MUT) identified through next-generation sequencing (NGS) testing at two institutions: Mayo Clinic and the University of Texas Southwestern Medical Center, Dallas, TX, USA were included. Progression was considered present if patients with CCUS progressed into myeloid neoplasm at follow up. Statistical analysis was performed using JMP® 17.1.0 Software. IPSS-M risk scores were calculated via the IPSS-M Risk Calculator (mds-risk-model.com). Results: A total of 103 patients were included in the study. The median age was 72 years, the majority were male patients (73%), and the median bone marrow blast % at the time of NGS was 1%. Forty-five % had an isolated mutation in a single gene, and 55% had co-mutations in ≥1 gene. The median number of mutations was 2 (range 1 - 5), occurring across 43 different genes. The most common mutations were in TET2 (N=28; 27%), ASXL1 (N=21; 20%), SRSF2 (N=21; 20%), U2AF1 (N=18; 17%), DNMT3A (N=16; 16%), and TP53 (N=12; 12%). Additionally, 25% of patients had an abnormal karyotype. Hematologic and genetic characteristics are summarized in (Table 1A). The median IPSS-M score was -0.9 (-3 to +2.34) and the median IPSS- Revised (R) score was 2 (0 - 6). The majority of patients had low (L) IPSS-M risk category (53%), followed by moderate low (ML) (19%) and very low (VL) (17%). Per IPSS-R, the majority had low-risk category (47%), followed by VL (38%) and intermediate (14%). Overall, 26 (25%) pt died after a median follow-up of 34 months and 21% progressed to MN (MDS 14 & CMML 8), and 1 patient with MDS and 1 with CMML progressed to secondary AML (2%). The median overall survival (mOS) was not reached, with a 2-year estimated (YE) OS and leukemia-free survival (LFS) of 80%. Predictive Power: When utilizing the IPSS-M risk category ( L, M, H) * by combining the risk categories into L *(L+VL), M * (ML+MH), and H *(H+VH) to overcome the low sample size limitation, it significantly predicted OS (p < .0001) ( Figure 1A) and median MN-free survival (FS) (p < .0001) ( Figure 1B). The 2YE-OS rates by IPSS-M risk category were as follows: VL - 93%, L - 87%, ML - 75%, high (H) - 25%, very high (VH) - 0% and the 2YE-OS rates by IPSS-M ( L, M, H) are summarized in Table 1B. IPSS-M hazard ratio (HR) for OS was 1.6 for ( M*) compared to 25 for ( H *) risk category (p < .0001). The ( L *) category, being the largest, was used as the reference level. Conclusion: This study provides the first real-world experience of using the IPSS-M and a modified version of the IPSS-M ( L, M, H) * risk category model to predict survival and progression into MN in CCUS (MUT) pt. The IPSS-M risk category was found to be a significant predictor of OS and MN-free survival. We propose that larger cohorts are needed to validate our findings.
Predictors of Cytokine Release Syndrome and Neurotoxicity in Patients with Large B-Cell Lymphoma and Their Impact on Survival
Strouse, Christopher , Oloyede, Temitope, Barba, Pere , Cashen, Amanda F. , Elsawy, Mahmoud , Ganguly, Siddhartha , Geethakumari, Praveen Ramakrishnan , Greenbaum, Uri , Hashmi, Hamza , Kittai, Adam S. , Lulla, Premal , Mead, Elena, Saber, Wael , Pasquini, Marcelo C. , Strouse, Christopher S , Shouval, Roni , Kim, Soyoung , Ahmed, Sairah , Awan, Farrukh T. , Bachanová, Veronika , Badar, Talha , Beitinjaneh, Amer , Dholaria, Bhagirathbhai , Hill, LaQuisa C. , Jain, Michael D. , Jain, Tania , Kebriaei, Partow , Locke, Frederick L. , McGuirk, Joseph P. , Mussetti, Alberto , Nishihori, Taiga , Olson, Amanda L , Pennisi, Martina , Perales, Miguel‐Angel , Riedell, Peter A. , Mirza, Abu‐Sayeef , Magalhaes‐Silverman, Margarida , Shpall, Elizabeth J. , Sorror, Mohamed L. , Wudhikarn, Kitsada , Turtle, Cameron J. , Moskop, Amy

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 355-355

10.1182/blood-2023-181181 Get It

Background: Autologous CAR-T therapy targeting CD19 is an effective treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, morbidity and mortality related to CAR-T toxicity remain significant concerns. This study aims to evaluate the patterns, risk factors, and implications of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19-CAR-T therapy in LBCL. Methods: This retrospective analysis includes 1916 LBCL patients treated with CD19-CAR-T cell therapy (axicabtagene-ciloleucel [axi-cel] 75% and tisagenlecleucel 25%) between 2018 and 2020 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patient demographics, baseline characteristics, treatment-related variables, and clinical outcomes were collected. The incidence, severity and timing of onset of CRS and ICANS (according to median time to onset) were analyzed, factors associated with these outcomes and their impact on overall survival as time dependent covariates were done using Cox Regression multivariate analyses. Results: The median age of the patients was 64 years, with a majority having a Karnofsky performance status (KPS) below 90% (61%) and not receiving bridging therapy (67%). CRS was observed in 75.1% of patients, with 9% experiencing severe CRS (grades ≥ 3). Similarly, 43% of patients experienced ICANS, with 20% having severe ICANS (grade ≥ 3). The median time to toxicity was shorter for CRS (4 days) compared to ICANS (7 days). Nearly all the patients who developed ICANS also experienced CRS (98%; ), and the correlation between these two events and respective severities are shown in the Figure 1a. In the multivariate analyses, factors associated with development of CRS were gender (women, Odds ratio [OR] 1.39, 95% confidence interval [CI] 1.10- 1.76, p=0.006), high LDH at time of infusion (OR 1.56; 95% CI 1.22 - 2.00, p=0.002) and product (axi-cel OR 4.60, 95% CI 3.56 -5.81, p<0.001). Factors associated with the development of ICANS included age (> 65 years, OR 1.83; 1.50-2.24, p<0.001), KPS (<80%, OR 2.48; 1.88-3.27, p<0.001), disease status at infusion (treatment resistant disease, OR 1.98; 1.09-3.58, p=0.024; and untreated relapse OR 2.62, 1.35-5.10, p=0.004) and product (axi-cel, OR 5.85; 4.47-7.64, p<0.0001). Factors associated with severe and early onset CRS and ICANS are listed in the table below. The median follow-up of 14.2 months, the estimated 12-month overall survival, progression-free survival (PFS), and treatment-related mortality were 61.6% (95% CI: 59.4-63.9), 42.2% (39.9-44.5), and 4.3% (3.4-5.3), respectively. Overall CRS, early onset CRS and overall ICANS were not associated with higher mortality, however grade >3 CRS (HR 1.79; 1.41-2.28, p<0.001), grade >3 ICANS (hazard ratio [HR] 1.34; 95% CI 1.13-1.59, p=0.002) and early onset ICANS (<7 days, HR 1.23; 1.05-1.44, p=0.01) were associated with higher mortality. The impact of severe CRS on survival are shown in the landmark analysis at 30 days from infusion in the figure 1B. Conclusion: In the largest analysis of CD19-CAR-T cell therapy toxicities to date, we observed a high burden of CRS and ICANS among LBCL patients. The CAR T cell product type was consistently associated with higher incidence, shorter onset and higher severity of both toxicities. High LDH, older age and low performance score also influence the severity and onset of these outcomes. Additionally, patients who developed higher grades of CRS/ICANS and earlier onset ICANS had a higher mortality, stressing the need to develop novel strategies to mitigate the incidence and optimize management of these patients to improve their outcomes.
Reclassification of Ascertain (ASTX727-02) Myelodysplastic Syndrome (MDS) Patients: Outcomes Including Clinical Response, Overall Survival (OS), and Leukemia Free Survival (LFS) Based on IPSS-R and IPSS-M Scoring Systems
Garcia‐Manero, Guillermo , McCloskey, James, Yee, Karen , Al‐Kali, Aref , Deeg, H. Joachim , Patel, Prapti A. , Keating, Mary‐Margaret, Zhu, Nancy , Gabrail, Nashat , Fazal, Salman, Maly, Joseph, Odenike, Olatoyosi , Busque, Lambert , Buckstein, Rena , Amin, Harsh, Randhawa, Jasleen K., Lee, Shannon, Chan, Winny, Souza, Sônia Buongermino de, Sano, Yuri, Griffiths, Elizabeth A. , Zeidan, Amer M. , Sabloff, Mitchell , Kantarjian, Hagop M. , Dezern, Amy Elizabeth , O'Connell, Casey Lee , Roboz, Gail J. , Leber, Brian F. , Souza, Sonia, Keer, Harold N , Savona, Michael R.

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4619-4619

10.1182/blood-2023-188258 Get It

Background: Oral decitabine/cedazuridine (ASTX727) is a fixed dose combination of decitabine (35 mg) and the cytidine deaminase inhibitor cedazuridine (100 mg) given once daily X 5 days on a 28-day cycle producing pharmacokinetic (PK) exposure equivalent to the standard intravenous (IV) decitabine regimen of 20 mg/m 2 daily X 5 days on a 28-day cycle. This was demonstrated in the pivotal ASCERTAIN study (Garcia-Manero, et al, ASH 2019) as it provided a PK bridge to existing decitabine data and demonstrated median OS was 31.7 mo. (Savona,et al. Intl. MDSF International Congress on MDS, 2021). Subjects were initially classified by the International Prognosis Scoring System (IPSS) for historical reasons, however IPSS-R and IPSS-M are enhancements to IPSS that provide dynamic risk assessment for predicting clinical outcomes in MDS. Here, the objective was to re-classify the MDS subjects enrolled on the ASCERTAIN study by IPSS-R and IPSS-M and measure the impact of informing patient outcomes based on re-calculated risk assessment. Methods: One hundred thirty-three subjects with MDS/CMML (chronic myelomonocytic leukemia) were enrolled in ASCERTAIN and were randomly assigned either IV decitabine for cycle 1 and oral decitabine/cedazuridine for cycle 2 or the opposite treatment sequence. All subjects continuing beyond cycle 2 received oral decitabine/cedazuridine for all subsequent cycles until treatment discontinuation for disease progression, toxicity, patient's decision, or HSCT. Whole blood collected prior to treatment was used for DNA isolation and molecular abnormalities identified using next-generation sequencing (NGS) hematologic malignancy panel of 179 genes including all genes commonly mutated in MDS. In the initial analysis of clinical outcomes, subjects were classified by IPSS with response assessment by IWG 2006 IPSS low and Int-1 risk levels were categorized as lower-risk MDS (LR-MDS), whereas IPSS Int-2 and high-risk categories were categorized as higher-risk MDS (HR-MDS). Subjects with sufficient data based on (e.g., available heme parameters, cytogenetics, NGS etc.) were reclassified by IPSS-R and IPSS-M. Subjects with IPSS-R score of ≤3.5 or IPSS-M of either very low, low, or moderate low were categorized as LR-MDS. Similarly subjects with IPSS-R score of >3.5 or an IPSS-M categorization of either moderate high, high, or very high were categorized as HR-MDS. Reclassified subjects were reassessed for CR (Complete Response), OS, and LFS and Harrell's concordance index (c-index) was used to describe the level of agreement between each scale and outcomes. Results: Based on the available data, the number of MDS subjects in the different risk classifications were the following: IPSS: 117, IPSS-R: 104, and IPSS-M: 105. Thirteen and 12 subjects on the IPSS could not be reclassified in the IPSS-R and IPSS-M, respectively, including 5 Int-1 and 2 low-risk MDS cases. CMML subjects were excluded from these analyses. Re-classification generally resulted in the upgrade of the subjects from LR-MDS to HR-MDS (Fig. 1). Thirty-one (26.5%) subjects from IPSS were reallocated in the IPSS-R to different risk categories; 3 (9.7%) were downgraded and 28 (90.3%) were upgraded. Similarly on reclassification with IPSS-M 34 (32.4%) of the patients reclassified; 5 (14.8%) were downgraded and 29 (85.3%) were upgraded. For IPSS LR-MDS, 23.2% of patients achieved CR, and 22.9% in the IPSS HR-MDS. Similarly, 21.6% patients achieved CR in the IPSS-R LR-MDS, and 23.9% in the IPSS-R HR-MDS; 26.3% patients achieved CR in the IPSS-M LR-MDS, and 20.9% in the IPSS-M HR-MDS. The c-index for the IPSS was .64 (OS) and .67 (LFS), IPSS-R was .70 (OS) and .71 (LFS), and .75 (OS) and .78 (LFS) for the IPSS-M (Table1). Conclusion: Reclassification from IPSS to IPSS-R or IPSS-M upgraded multiple subjects from a LR to a HR category, describing the ASCERTAIN patient population as a majority higher risk population with worse prognosis than previously assumed based on the IPSS. The efficacy as measured by the CR rates did not change when the LR and HR categories were defined by the different risk stratification systems. In contrast, the c-index improves with migration from IPSS to IPSS-R to IPSS-M, indicating an increased discriminatory ability of IPSS-M score in comparison to IPSS and IPSS-R, to predict patient outcomes.
Efficacy of Daratumumab-Based Regimens in Anti-CD38 Treatment-Naïve Relapsed/Refractory Multiple Myeloma with High-Risk Cytogenetics
Mansour, Razan , Mammadzadeh, Aytaj , Hashmi, Hamza , Afrough, Aimaz , Alkharabsheh, Omar , Paul, Barry , Mushtaq, Muhammad Umair , Skikne, Barry, Snyder, Jordan Andrew , Atrash, Shebli , Ahmed, Nausheen , Abdallah, Al-Ola

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 1985-1985

10.1182/blood-2023-187487 Get It

Background: Daratumumab-based combination with proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) have revolutionized the treatment outcomes of relapsed/refractory multiple myeloma (RRMM). Several daratumumab-based triplet combinations have been approved for the management of RRMM, but outcomes of daratumumab-based triplets in patients with high-risk cytogenetics RRMM (HC-RRMM) are not well described in the literature. This study aimed to evaluate the clinical outcome of daratumumab-based regimens in patients with HC-RRMM who are daratumumab-naïve. Methods: A retrospective review of 110 patients with HC-RRMM who received daratumumab-containing regimens from 6/2016 through 2/2023 at the University of Kansas Medical Center, in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC) was conducted. Daratumumab was combined with bortezomib/dexamethasone (DVd), carfilzomib/dexamethasone (DKd), and pomalidomide/dexamethasone (DPd) for treatment of RRMM. HC-RRMM was defined as patients with one or more cytogenetic abnormalities (on FISH panel) including -17/del(17p), t(4;14), t(14;16), t(14;20), or amplification of 1q. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. Descriptive statistics were used to summarize patient and disease characteristics, along with efficacy outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier methods. Results: Of the 110 patients with HC-RRMM, the median age was 66 years (range 43-84), 83 (75%) were Caucasian, 60 (54%) had IgG isotype, 41 (37%) had revised international staging system (R-ISS) stage III disease, 35 (32%) had extramedullary disease (EMD), 57 (52%) patients had one high-risk cytogenetic (HC) abnormality, 49 (44%) had 2 HC abnormalities, while four (4%) had 3 HC abnormalities. The median number of previous lines of therapy was 2 (1-4). Eighty-eight patients (80%) were lenalidomide refractory, while 53 patients (48%) had double refractory disease to both a PI and IMiD treatment. A total of 19 (17%), 27 (25%), and 64 (58%) patients received DVd, DKd, and DPd, respectively. The overall response rate (ORR) for the entire patient population was 73%, 45% had VGPR or better, and 35% achieved ≥CR. Median follow-up was 28 months (12.07-53.57), the median OS was 28 months (95% CI 23.2 - 43.9) and PFS was 8.03 months (95% CI 5.8 - 12.2) for all treatment groups. The median PFS for 1 HC vs ³ 2 HC was 14.8 vs 4.57 months (HR 1.72, 95%CI 1.17-2.72 p = 0.006), respectively. Similarly, median OS for 1 HC vs ³ 2 HC was 43.93 vs 22.47 months (HR 1.87, 95%CI 1.15-3.05, p = 0.011), respectively. (Figure 1). On multivariate analysis, R-ISS stage III, -17/del(17p), and the presence of more than one HC abnormality were associated with poor OS. The most common cause for treatment discontinuation was progressive disease, accounting for 73% of patients in the whole cohort. As for each daratumumab-based triplet, discontinuation due progression occurred in 78%, 48%, and 83% in DVd, DKd, and DPd, respectively. Other causes of discontinuation included > grade 3 neuropathy, which occurred in 16% of patients receiving DVd, and cardiac events, which occurred in 11% of patients receiving DKd. Treatment-related mortality occurred in 2% of patients in the whole cohort. At the time of evaluation, 14 patients remain on treatment. Conclusion: Advanced stage R-ISS disease at diagnosis, presence of -17/del(17p), and 2 or more HC abnormalities were associated with poor prognosis reflected by worse PFS and OS in HC-RRMM treated with daratumumab-based therapies. A larger cohort or a prospective study in patients with HC-RRMM is needed to compare long-term outcomes between daratumumab-based therapies (DKd, DVd, and DPd).
Does Fracture Pattern Really Predict Displacement of LC1 Sacral Fractures?
Livesey, Michael G. , Salmons, Harold I. , Butler, B. , Edmond, Tyler , Slobogean, Gerard P. , O’Toole, Robert V. , Butler, Bennet A , Edmond, Tyler J

Journal of Bone and Joint Surgery | November 15, 2023 | Volume: 106 | Issue: 2 | Pages: 138-144

10.2106/jbjs.23.00614 | PMID 37967162 Get It

Background: Operative management of minimally displaced lateral compression type-1 (LC1) pelvic ring injuries remains controversial. We aimed to assess the proportion of LC1 pelvic fractures that displaced following nonoperative management as a function of specific ring fracture patterns, and we quantified the magnitude of this displacement. Methods: A retrospective review of the billing registry of a level-I trauma center was performed. Two hundred and seventy-three patients with a high-energy LC1 pelvic ring fracture and <5 mm of sacral displacement were included. The fracture pattern was characterized with use of computed tomography (CT) scans and radiographs. Absolute and interval pelvic ring displacement were quantified with use of previously described methodology. Results: Thirty-five pelvic ring injuries (13%) were displaced. The rate of displacement was 31% (15 of 49) for LC1 injuries involving a complete sacral fracture and bilateral ramus fractures, 12% (7 of 58) for injuries involving a complete sacral fracture and a unilateral ramus fracture, and 10% (5 of 52) for injuries involving an incomplete sacral fracture and bilateral ramus fractures. In displaced injuries, the average interval displacement was 4.2 mm (95% confidence interval [CI], 1.8 to 6.8) and the final displacement was 9.9 mm ± 4.2 mm. Conclusions: Our study suggests that fracture characteristics can be used to predict the likelihood of displacement of LC1 fractures that are treated without surgery. To our knowledge, the present study is the first to describe the magnitude of displacement that may occur in association with LC1 pelvic ring injuries that are treated nonoperatively; however, further studies are needed to determine the clinical impact of this displacement. Level of Evidence: Diagnostic Level IV . See Instructions for Authors for a complete description of levels of evidence.
BIOM-03. LACK OF CORRELATION OF MR-DETERMINED WHITE MATTER INJURY(WMI)WITH NEUROCOGNITIVE FUNCTION (NCF)6 MONTHS FOLLOWING WBRT+/-HIPPOCAMPAL AVOIDANCE(HA)+MEMANTINE:SECONDARY ANALYSIS OF NRG ONCOLOGY NRGCC001
Bovi, Joseph , Pugh, Stephanie L. , Brown, Paul D. , Gondi, Vinai , Sabsevitz, David S. , Sprenger, Markus , Devisetty, Kiran , Shah, Sunjay, Usuki, Kenneth Y., Yoon, Harold, Donnelly, Eric D. , Baschnagel, Andrew, Kachnic, Lisa A. , Robinson, Clifford G. , Wefel, Jeffrey S. , Kundapur, Vijayananda , Roberge, David , Stea, Baldassarre , Laack, Nadia N. , Baschnagel, Andrew, Paulus, Rebecca

Neuro-Oncology | November 11, 2023 | Volume: 25 | Issue: Supplement_5 | Pages: v4-v4

10.1093/neuonc/noad179.0014 Get It

Abstract PURPOSE Previous analysis of NRG-CC001 suggested pre-treatment WMI volume was a significant imaging-biomarker predictor of post-treatment neurocognitive decline at 4-and 12-months following HA-WBRT+Memantine. This suggested patients with greater pre-treatment WMI were more susceptible to neurocognitive decline, specifically when undergoing HA-WBRT, but not standard-WBRT. The current analysis examined the relationship between changes in MR-determined WMI and NCF 6-months following WBRT+memantine+/-HA. METHODS NCF-testing was performed at baseline, 2, 4, 6, and 12 months post-WBRT, and included Hopkins Verbal Learning Test–Revised (HVLT-R), Trail Making Test (TMT) Parts A and B, and Controlled Oral Word Association (COWA). Pre-treatment WMI was measured by FLAIR-volume corrected for whole brain volume and corrected for the FLAIR volume associated with metastases (met vol) (FLAIR-volume/(whole brain volume–met-vol). Pearson correlation coefficients were used to assess the correlation between pre-treatment WMI and change from baseline to 6-months for each standardized NCF score. RESULTS Of the 518 randomized patients, 443 (217 patients WBRT+Memantine and 226 HA-WBRT+Memantine) had WMI data available at baseline, and of those, 162 patients (89 patients WBRT+Memantine and 73 HA-WBRT+Memantine) had both baseline and 6-month imaging available. For these patients, there was only a trend toward significance for change in corrected FLAIR-volume from baseline to 6-months (p = 0.174) but no significant change in met-vol (p = 0.438) or whole brain volume (p = 0.977). The change in standardized TMT Part A and B and the change in composite 6-month change scores were moderately correlated with change in corrected FLAIR volume adjusted for met-vol but only in the WBRT+Memantine arm (rho=-0.35, -0.34, -0.39 and p-value = 0.003, 0.006, 0.001). CONCLUSIONS Despite an increase in post-WBRT MR-WMI at 6-months, analysis did not show strong correlation between NCF and MR-WMI as determined by FLAIR-volume change between baseline and 6-months. Similar analyses are underway for the NRG-CC003 imaging data.
RADT-01. BASELINE HIPPOCAMPAL VOLUME AS A PREDICTOR OF NEUROCOGNITIVE CHANGES AFTER WBRT OR HA-WBRT: SECONDARY ANALYSIS OF NRG ONCOLOGY CC001
Abraham, Christopher , Pugh, Stephanie L. , Brown, Paul D. , Gondi, Vinai , Bovi, Joseph , Devisetty, Kiran , Shah, Sunjay, Usuki, Kenneth Y., Baschnagel, Andrew, Yoon, Harold, Laack, Nadia, Jindal, Saurahb, Borges, Monica, Kachnic, Lisa A. , Robinson, Clifford G. , Wefel, Jeffrey S. , Roberge, David , Kundapur, Vijayananda , Baschnagel, Andrew, Stea, Baldassarre , Li, Jing , Borges, Monica

Neuro-Oncology | November 11, 2023 | Volume: 25 | Issue: Supplement_5 | Pages: v48-v48

10.1093/neuonc/noad179.0190 Get It

Abstract PURPOSE Hippocampal volume (HV) is a predictor of neurocognitive function (NCF) in neurodegenerative disease. The role of patient-specific anatomic variables has not been well investigated in patients with brain metastases. This work aimed to evaluate HV at baseline and 6 months as a predictor of NCF and differential benefit from HA-WBRT for patients enrolled on CC001. MATERIALS HV was calculated at baseline and 6 months. HV at baseline and 6 months were correlated with baseline and 2, 4, and 6-month NCF scores (HVLT-R Total and Delayed Recall, Delayed Recognition, TMT Parts A and B, and COWA) using Pearson correlation. Correlation was defined as weak if ρ ≤0.35. A cox proportional hazards model was used to determine the impact of baseline HV on time to NCF failure. RESULTS Of 518 patients randomized on CC001, 277 had baseline imaging, and 135 had 6-month imaging. However, only 87 patients were analyzable at both baseline and 6-month periods. At baseline, HV was not significantly associated with NCF score for any measure (p-value range: 0.06-0.72). Additionally, there was no association between baseline HV and time to NCF failure (p = 0.16). Additionally, the impact of treatment arm allocation on HV was examined but found to be non-significant (p = 0.06). Lastly, baseline HV and NCF scores were noted to have weak correlation at 2, 4, 6, and 12 month timepoints (ρ: range, -0.17-0.15; P-value range, 0.04-0.98). At 6 months, the correlation between HV, baseline NCF change, and 6 month standardized NCF change were also noted to be weak (ρ: range, 0.05-0.16; P-value range, 0.06-0.76). CONCLUSIONS Radiotherapy is known to have deleterious effects on neurocognition. In neurodegenerative disease, HV and rate of HV change are known predictors for NCF. However, baseline HV is not an independent predictor of neurocognitive changes after WBRT or HA-WBRT for patients with brain metastases.
Clinician Perspectives Regarding the Impact of Information Technology on Multidisciplinary Tumor Boards: A National Comprehensive Cancer Network Survey
Arafat, Waddah , Wagner, Andrew J. , Osterman, Travis , Martin, Daniel , Sugalski, Jessica , Heinrichs, Tricia , Racz, Jennifer M. , Tevaarwerk, Amyé , Wagner, Andrew J , Osterman, Travis , Martin, Daniel B , Sugalski, Jessica , Heinrichs, Tricia , Racz, Jennifer , Tevaarwerk, Amye J , Fu, Paul C.

JCO Clinical Cancer Informatics | November 9, 2023 | Volume: No volume available | Issue: 7 | Pages: No page available

10.1200/cci.23.00056 | PMID 37944060 Get It

PURPOSE Multidisciplinary tumor boards (MTBs) support high-quality cancer care. Little is known about the impact of information technology (IT) tools on the operational and technical aspects of MTBs. The National Comprehensive Cancer Network EHR Oncology Advisory Group formed a workgroup to investigate the impact of IT tools such as EHRs and virtual conferencing on MTBs. METHODS The workgroup created a cross-sectional survey for oncology clinicians (eg, pathology, medical, surgical, radiation, etc) participating in MTBs at 31 National Comprehensive Cancer Network member institutions. A standard invitation e-mail was shared with each EHR Advisory Group Member with a hyperlink to the survey, and each member distributed the survey to MTB participants at their institution or identified the appropriate person at their institution to do so. The survey was open from February 26, 2022, to April 26, 2022. Descriptive statistics were applied in the analysis of responses, and a qualitative thematic analysis of open-ended responses was completed. RESULTS Individuals from 27 institutions participated. Almost all respondents (99%, n = 764 of 767) indicated that their MTBs had participants attending virtually. Most indicated increased attendance (69%, n = 514 of 741) after virtualization with the same or improved quality of discussion (75%, n = 557 of 741) compared with in-person MTBs. Several gaps between the current and ideal state emerged regarding EHR integration: 57% (n = 433 of 758) of respondents noted the importance of adding patients for MTB presentation via the EHR, but only 40% (n = 302 of 747) reported being able to do so most of the time. Similarly, 87% (n = 661 of 760) indicated the importance of documenting recommendations in the EHR, but only 53% (n = 394 of 746) reported this occurring routinely. CONCLUSION Major gaps include the lack of EHR integration for MTBs. Clinical workflows and EHR functionalities could be improved to further optimize EHRs for MTB management and documentation.
AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis
Karvellas, Constantine , Bajaj, Jasmohan S. , Kamath, Patrick S. , Napolitano, Lena M. , O’Leary, Jacqueline G. , Subramanian, Ram, Wong, Florence , Asrani, Sumeet K. , Karvellas, Constantine , Napolitano, Lena , Wong, Florence , Asrani, Sumeet K , O’Leary, Jacqueline G. , Solà, Elsa

Hepatology | November 8, 2023 | Volume: 79 | Issue: 6 | Pages: 1463-1502

10.1097/hep.0000000000000671 | PMID 37939273 Get It