Citations

7067 Background: High intensity induction with regimens such asDA-EPOCH-R, CODOX-M/IVAC-R and HyperCVAD are often used for young patients with DHL/THL despite no overall survival (OS) benefit compared to R-CHOP. Reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate it. We aimed to investigate outcomes difference between CODOX-M/IVAC-R and DA-EPOCH-R in patients ≤ 60 years with DHL/THL diagnosed via FISH. Methods: Retrospective review of DHL/THL patients from the Mayo Clinic diagnosed between July15th 2010-October19th 2023 treated with CODOX-M/IVAC-R or DA-EPOCH-R at age of up to 60 years. Event free survival (EFS) was defined as time from diagnosis to progression, relapse, next line of treatment or death from any cause. Results: 113 patients were included; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Patient and disease characteristics are in table. 80% (N=39) achieved CR on end of treatment (EOT) PET CT with CODOX-M/IVAC-R compared to only 58% (N=37) with DA-EPOCH-R. CODOX-M/IVAC-R was associated with superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL2 vs BCL6 translocation and receipt of consolidation ASCT (aHR=0.53, 95%CI=0.29-0.95), however, there was no significant influence on OS (aHR=0.97, 95%CI=0.50-1.91). At a median follow-up of 5.3 years and 3.3 years for the CODOX-M-IVAC and DA-R-EPOCH group respectively; EFS was superior in the CODOX-M/IVAC-R group having 1, 2 and 5 years EFS of 68.3%, 64.1 and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group (p=0.035). 33%(16/49) of the CODOX-M/IVAC-R patients had R/R disease (No CR on EOT PET CT or relapsed) with a median OS of 10.3 months compared to 33.7 months in the R/R DA EPOCH-R group (54%, 35/64). Number of patients who were able to receive salvage ASCT, CAR T and Allo-SCT were 5, 17 and 4 respectively in the DA EPOCH-R group compared to 1, 6 and 3 patients respectively in the CODOX-M/IVAC-R group. None died of regimen toxicity in both groups. 19% underwent ASCT consolidation after CR with initial induction (11 patients in each group); no OS was noticed however consolidation with ASCT was associated with increased EFS regardless of the induction regimen with best outcomes being in the CODOX-M/IVAC-R group (P=0.0072). Conclusions: Our study showed that young patients with DHL/THL who received CODOX-M/IVAC-R had superior EFS compared to DA-EPOCH-R with no OS benefit. CODOX-M/IVAC-R can spare patients receiving more subsequent therapies. Patients who have R/R disease following CODOX-M/IVAC-R have poor outcomes. [Table: see text]

7050 Background: The management of Richter transformation (RT) of CLL represents an unmet clinical need. We previously reported modest efficacy of pembrolizumab monotherapy in an initial cohort of patients with RT (Ding, et al, Blood 2017). Here we report updated results of this trial, including an expansion cohort and a combination therapy cohort. Methods: Patients with biopsy proven RT to diffuse large B-cell lymphoma were enrolled and treated with single agent pembrolizumab (200 mg IV Q3W). Patients with progressive disease (PD) or stable disease (SD) after 3 months of pembrolizumab monotherapy were allowed to add a B-cell receptor (BCR) kinase inhibitor. The primary end point was overall response rate (ORR). Results: A total of 26 patients with RT were enrolled (9 in initial cohort and 17 in expansion cohort). The median age was 68.5 years. Ten (38%) patients had del(17p) or TP53 mutation. The median number of prior lines of therapy was 3 (range 1-10). Fifteen (58%) patients had received ibrutinib previously (14 of whom had PD on ibrutinib). With pembrolizumab monotherapy (n=26), the ORR was 23.1%, with 2 (7.7%) complete response (CR), 4 (15.4%) partial response (PR), and 7 (26.9%) SD. Of the 6 patients with confirmed CR or PR, responses occurred after a median of 2 cycles of monotherapy. The median duration of response (DOR) was 3.2 months (95% CI 2.8-NA). The median progression-free survival (PFS) was 2.6 months (95% CI 1.6-3.6). Sixteen patients went on to receive a BCR kinase inhibitor (ibrutinib [n=15], idelalisib [n=1]) in combination with pembrolizumab, after SD or PD on pembrolizumab monotherapy. The ORR to combination therapy was 62.5%, with 4 (25.0%) CR and 6 (37.5%) PR. Of the 10 patients with confirmed CR or PR to combination therapy, responses occurred after a median of 4 cycles of therapy. The median DOR was 4.5 months (95% CI 1.6-NA). The median PFS was 7.6 months (95% CI 2.3-13.3). After a median follow-up of 50.4 (95% CI 34.0-56.0) months, the median overall survival (OS) for all 26 patients with RT was 11.6 months (95% CI 7.5-20.1), and the 2-year OS rate was 27%. Treatment-related adverse events (TRAEs) of any grade occurred in 24 (92%) patients, including anemia (54%), thrombocytopenia (58%), neutropenia (54%), leukopenia (35%), lymphopenia (23%), dyspnea (23%), diarrhea (19%), and nausea (23%). Treatment-related grade 3 or above AEs occurred in 21 (81%) patients, including neutropenia (38%), leukopenia (31%), thrombocytopenia (27%), anemia (15%), febrile neutropenia (12%), and lung infection (12%). Conclusions: This expanded analysis confirmed that pembrolizumab has modest single agent activity in RT. Combination therapy with pembrolizumab and a BCR kinase inhibitor is associated with increased efficacy (ORR >60%), similar to other reports. These results support further investigation of immune checkpoint inhibitor-based combination therapy in RT. Clinical trial information: NCT02332980 .

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

PURPOSE H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori–positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection ( H. pylori–negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma. MATERIALS AND METHODS We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy. RESULTS Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients—14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients ( P = .033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months. CONCLUSION For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline.

BACKGROUND: There has been concern among colon and rectal surgery residency programs in the United States that IPAA procedures have been decreasing, but evidence is limited. OBJECTIVE: The study aimed to evaluate the number of IPAAs performed by colon and rectal surgery residents in the United States and analyze the distribution of these cases on a national level. DESIGN: Retrospective. SETTINGS: The Accreditation Council for Graduate Medical Education Case Log National Data Reports were used to evaluate the number of IPAAs performed by residents from 2005 to 2021. The Nationwide Inpatient Sample database was used to identify all patients undergoing these procedures from 2005 to 2019. PATIENTS: All IPAA procedures regardless of indication. MAIN OUTCOME MEASURES: The primary outcome was the number of IPAAs performed by residents yearly. The secondary outcome was the national distribution of these procedures. RESULTS: Among colon and rectal surgery residents, case log data revealed an increase in mean and total number of IPAAs from 2005 to 2013, followed by a decline in both metrics after 2013. Despite the decrease, the mean number of cases per resident remained fewer than 6 between 2011 and 2021. A weighted national estimate of 48,532 IPAA patients were identified in the Nationwide Inpatient Sample database. A significant decrease was noted in the number of IPAAs after 2015 that persisted through 2019. There was a significant decrease in rural and urban nonteaching hospitals (from 2.1% to 1.6% and 25.6% to 4.3%, respectively; p < 0.001) and an increase in urbanteaching hospitals (from 72.4% to 94.1%; p < 0.001). LIMITATIONS: Nonrandomized retrospective study design. CONCLUSIONS: Despite the recent increase in the percentage of IPAAs performed at urban academic centers, there has been a decrease in cases performed by colon and rectal surgery residents. This can have significant implications for residents who graduate without adequate experience in performing this complex procedure independently, as well as training programs that may face challenges with maintaining accreditation. See Video Abstract. TENDENCIAS Y DISTRIBUCIÓN DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL EN LOS ESTADOS UNIDOS: ¿SE ESTÁ VOLVIENDO MÁS DIFÍCIL DE ENCONTRAR EN LA CAPACITACIÓN DE RESIDENCIA EN CIRUGÍA DE COLON Y RECTO? ANTECEDENTES: Ha habido preocupación entre los programas de capacitación de residencia en cirugía de colon y recto en los Estados Unidos porque los procedimientos de anastomosis anal con bolsa ileal han estado disminuyendo; sin embargo, la evidencia es limitada. OBJETIVO: Evaluar el número de anastomosis anales con bolsa ileal realizadas por residentes de cirugía de colon y recto en los Estados Unidos y examinar la distribución de estos casos a nivel nacional. DISEÑO: Retrospectivo. AJUSTES: Se utilizaron los informes de datos nacionales del registro de casos de educación médica de posgrado del Consejo de Acreditación para examinar el número de anastomosis anales con bolsa ileal realizadas por residentes de 2005 a 2021. Se utilizó la base de datos de muestra nacional de pacientes hospitalizados para identificar a todos los pacientes sometidos a estos procedimientos de 2005 a 2019. PACIENTES: Todos los procedimientos de anastomosis anal con bolsa ileal independientemente de la indicación. MEDIDA DE RESULTADO PRINCIPAL: El resultado primario es el número de anastomosis anales con bolsa ileal realizadas por los residentes anualmente. El resultado secundario es la distribución nacional de estos procedimientos. RESULTADOS: Entre los residentes de cirugía de colon y recto, los datos de los registros de casos revelaron un aumento en el número medio y total de anastomosis anal con bolsa ileal de 2005 a 2013, seguido de una disminución en ambas métricas después de 2013. A pesar de la disminución, el número medio de casos por El residente permaneció >6 entre 2011 y 2021. Se identificó una estimación nacional ponderada de 48 532 pacientes con anastomosis anal con bolsa ileal en la base de datos de la Muestra Nacional de Pacientes Hospitalizados. Se observó una disminución significativa en el número de anastomosis anales con bolsa ileal después de 2015 que persistió hasta 2019. Hubo una disminución significativa en los hospitales no docentes rurales y urbanos (del 2,1% al 1,6% y del 25,6% al 4,3% respectivamente, p < 0,001) y un aumento en los hospitales universitarios urbanos (del 72,4% al 94,1%, p < 0,001). LIMITACIONES: Estudio retrospectivo no aleatorizado. CONCLUSIÓN: A pesar del reciente aumento en el porcentaje de anastomosis anal con bolsa ileal realizadas en centros académicos urbanos, ha habido una disminución en los casos realizados por residentes de cirugía de colon y recto. Esto puede tener implicaciones significativas para los residentes que se gradúan sin la experiencia adecuada en la realización de este complejo procedimiento de forma independiente, así como para los programas de capacitación que pueden enfrentar desafíos para mantener la acreditación. (Traduccion—AI-generated)

Abstract Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have “primary refractory disease.” However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological Resource cohort (MER; N = 949) or the Lymphoma Epidemiology of Outcomes cohort (LEO; N = 2755) from September 2002 to May 2021. Primary refractory LBCL was defined as no response (stable disease [SD]) or progressive disease (PD) during, or by the end of, frontline (1L) IC (primary PD; PPD); partial response at end of treatment (EOT PR); or relapse within 3 to 12 months after achieving CR at EOT to 1L IC (early relapse). In the MER cohort, patients with PPD had inferior overall survival (OS; 2-year OS rate: 15% MER, 31% LEO) when compared with other subgroups considered in defining primary refractory disease, EOT PR (2-year OS rate: 38% MER, 50% LEO) and early relapse (2-year OS rate: 44% MER, 58% LEO). Among patients receiving 1L IC with curative intent, we identified that patients with PPD are the key subgroup with poor outcomes. We propose a definition of primary refractory LBCL as SD or PD during, or by the end of, 1L treatment.

SummaryMultiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma.

Background: Despite numerous potential benefits of outpatient surgery, there is currently a lack of national benchmarking data available for hospitals and surgeons to compare their own outcomes as they transition toward outpatient surgery. Materials and methods: Patients who underwent 14 common general surgery operations from 2016 to 2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Operations were selected based on frequency and the ability to be performed both inpatient and outpatient. Postoperative complications and readmissions were compared between patients who underwent inpatient vs outpatient surgery. After adjusting for patient comorbidities, multivariable models assessed the effect of patient characteristics on the odds of experiencing postoperative complications. A separate multi-institutional study of 21 affiliated hospitals assessed practice variation. Results: In 13 of the 14 studied procedures, complications were lower for patients who were selected for outpatient surgery (all P<0.01); minimally invasive (MIS) adrenalectomy showed no difference (P=0.61). Multivariable analysis confirmed these findings; the odds of experiencing any adverse events were lower following outpatient surgery in all operations but MIS adrenalectomy (OR 0.97; 95% CI: 0.47–2.02). Analysis of institutional practices demonstrated variation in the rate of outpatient surgery in certain breast, endocrine, and hernia repair operations. Conclusions: Institutional practice patterns may explain the national variation in the rate of outpatient surgery. While the present data does not support the adoption of outpatient surgery to less optimal candidates, addressing unexplained practice variations could result in improved utilization of outpatient surgery.

Importance Racial and ethnic disparities exist in urogynecologic surgery; however, literature identifying specific disparities after sling operations for stress incontinence are limited. Objective The objective of this study was to evaluate racial and ethnic disparities in surgical complications within 30 days of midurethral sling operations. Study Design This retrospective cohort study identified women who underwent an isolated midurethral sling operation between 2014 and 2021 using the American College of Surgeons National Surgical Quality Improvement Program database. Women were stratified by racial and ethnic category to assess the primary outcome, 30-day surgical complications, and the secondary outcome, comparison of urinary tract infections (UTIs). Results There were 20,066 patients included. Mean age and body mass index were 53.9 years and 30.8, respectively. More Black or African American women had diabetes and hypertension, and more American Indian or Alaska Native women used tobacco. The only difference in 30-day complications was stroke/cerebrovascular accident, which occurred in only 1 Asian, Native Hawaiian or other Pacific Islander patient (0.1%, P < 0.0001). The most frequent complication was UTI (3.3%). Black or African American women were significantly less likely to have a diagnosis of UTI than non-Hispanic White (P = 0.04), Hispanic White (P = 0.03), and American Indian or Alaska Native women (P = 0.04). Conclusions Surgical complications within 30 days of sling operations are rare. No clinically significant racial and ethnic differences in serious complications were observed. Urinary tract infection diagnoses were lower among Black or African American women than in non-Hispanic White, Hispanic White, and American Indian or Alaska Native women despite a greater comorbidity burden. No known biologic reason exists to explain lower UTI rates in this population; therefore, this finding may represent a disparity in diagnosis and treatment.