Baidoun, Firas

Objectives: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with a very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score—a weighted summary of 17 chronic disease categories where higher scores denote greater baseline comorbidity burden—of 3 or more and patients lost for follow-up, we split the cohort into 3 groups according to the number of treatment modalities they received. Treatment modalities included surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the 3 groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with OS. In addition, propensity score matching (accounting for age, sex, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3460 patients with ATC were included in the analysis, of which 1472 (42.5%) either received one type of therapy or did not receive any therapy (group 1), 1092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.7 and 4.9 mo, respectively, with P <0.001 for all comparisons). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.9 and 5.2 mo, respectively, with P <0.001 for all comparisons). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 vs. 1.9 and 6.1 mo, respectively, with P <0.001 for all), in M1 group (median OS was 5.9 vs. 1.4 and 3.7 mo, respectively, with P <0.001 for all). Modality-specific analyses further demonstrated that surgery, radiation, and systemic therapy each independently prolonged OS in both M0 and M1 cohorts (all P <0.001). These individual benefits explain the additive advantage of trimodal therapy and underscore that offering at least one evidence-based modality is preferable when comprehensive treatment is infeasible. On multivariate analysis, group 1 and group 2 were associated with worse OS compared with trimodal treatment (HR: 2.721; 95% CI: 2.466-3.002 and HR: 1.434; 95% CI: 1.299-1.582, P <0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared with patients who received less intense therapy. This survival benefit was observed in both metastatic and nonmetastatic groups. Although we acknowledge the limitations of this retrospective analysis, our results showed the critical role of an intensive therapy approach in this aggressive malignancy.

Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy and the third leading cause of cancer-related death in the world. Liver transplant is a cornerstone in treating nonmetastatic disease, but a significant portion of patients miss the opportunity of upfront liver transplant given the long waiting time for donor organs. Herein, we compare the survival outcomes between upfront liver transplant, liver transplant with bridge systemic therapy, and systemic therapy only. Methods: The National Cancer Database was queried for patients diagnosed with non-metastatic hepatocellular carcinoma (HCC) between 2004 and 2017. After including only patients with clinical N0 stage who received either systemic therapy alone, liver transplant alone or liver transplant with bridge systemic therapy, we split the cohort into 3 groups: systemic therapy only (including intra-arterial chemotherapy eg, TACE) group, upfront liver transplant group and liver transplant with bridge systemic therapy group. We evaluated overall survival (OS) among the three groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with overall survival (OS). Results: A total of 29,691 patients with nonmetastatic HCC were included for analysis, of which 25,122 (84.6%) were treated with systemic therapy only, 2513 (8.5%) were treated with bridge systemic therapy followed by liver transplant, and 2056 (6.9%) were treated with upfront liver transplant without systemic therapy bridge. We found that patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant had a statistically significantly better OS compared to patients who were treated with systemic therapy only (mean OS was 101.9 mo and 98.2 vs. 39.4 mo, respectively, with P <0.001 for all). Whereas there was no significant difference in OS between patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant (mean OS was 101.9 vs. 98.2 months, P =0.187). On multivariate analysis, factors associated with worse OS were older age (HR: 1.011; 95% CI: 1.010-1.013; P <0.001), Male sex (HR: 1.048; 95% CI: 1.014-1.084; P =0.006), White compared with African American race (HR: 1.055; 95% CI: 1.012-1.099; P =0.011), no insurance status (HR: 1.155; 95% CI: 1.079-1.237; P <0.001), clinical T4 stage compared with T0 stage (HR: 1.366; 95% CI: 1.257-1.483, P <0.001), and systemic therapy alone compared with upfront liver transplant and liver transplant with bridge systemic therapy (HR for upfront liver transplant and transplant with bridge systemic therapy vs. systemic therapy was 0.202; 95% CI: 0.184-0.223, and HR: 0.194, 95% CI: 0.178-0.212, respectively, with P <0.001 for all). Conclusions: Patients with nonmetastatic HCC who were treated with upfront liver transplant or liver transplant with bridge systemic therapy had statistically significant improvement in OS compared with patients who were treated with systemic therapy only. While our study confirms the survival benefit of liver transplant among patients with nonmetastatic HCC, these results raise the importance of proceeding with liver transplant after intra-arterial and/or systemic treatments in patients who are not initially eligible for or missed the opportunity of upfront liver transplant.

Introduction: Myeloma therapeutics have tremendously improved in recent times, leading to unprecedented outcomes. Timely initiation of effective treatment is vital to improving survival and quality of life. Patient refusal to receive treatment is infrequent but certainly leads to increased morbidity/mortality. We studied factors associated with treatment refusal. Methods: The National Cancer Database (NCDB) was queried for adult patients diagnosed with MM between 2004-2021. Those who refused treatment for initial management despite physician's recommendation were identified. Patients with multiple primary malignancies or unknown treatment status were excluded. Patients' demographics and socioeconomic factors were collected. Kaplan-Meier and multivariate Cox regression were used to evaluate the likelihood of treatment refusal in the whole cohort and in each racial/ethnic group. Results: Out of 86,350 eligible patients with MM who were recommended to initiate therapy, 2,508 (2.9%) did not receive any treatment due to refusal. Of these, 52.6% were females, 64% were non-Hispanic White (NHW), 21.3% were non-Hispanic African American (NHAA), and 5.2% were Hispanic. On multivariate analysis, patients who were treated at comprehensive and integrated facilities were more likely to refuse treatment as compared to those at academic facilities (OR=1.36; 95% CI: 1.22-1.52, p&lt;0.001 and OR=1.22; 95% CI: 1.07-1.4, p=0.004, respectively). Patients on Medicare (OR=1.42; 95% CI: 1.16-1.73, p&lt;0.001), and presence of higher Charlson Comorbidity Index (CCI) also had a higher likelihood of refusing treatment. Lower refusal rates were seen for male gender (OR=0.83; 95% CI: 0.76-0.91, p&lt;0.001), NHW racial/ethnic group (as against NHAA; OR=0.34; 95% CI: 0.16-0.71, p=0.004), being insured (OR=0.69; 95% CI: 0.52-0.93, p=0.015), having private insurance (compared to Medicaid; OR=0.47; 95% CI: 0.38-0.59, p&lt;0.001) and having a higher income level (OR=0.82; 95% CI: 0.70-0.96, p=0.013). Among NHAA patients, 2.8% refused treatment and were more likely to have Medicare (OR=1.4; 95% CI: 1.03-1.9, p=0.032). Having private insurance (compared to Medicaid; OR=0.61; 95% CI: 0.43-0.88, p=0.008) had a lower likelihood of refusing treatment. Among NHW, 2.9% refused treatment and they were more likely to be treated at community, comprehensive and integrated facilities compared to academic facilities (OR=1.39; 95% CI: 1.12-1.73, p=0.003, OR=1.54; 95% CI: 1.33-1.77, p&lt;0.001 and OR=1.38; 95% CI: 1.16-1.64, p&lt;0.001, respectively), be from rural areas (OR=1.43; 95% CI: 1.05-1.96, p=0.025), and have a higher CCI. On the other hand, male gender (OR=0.79; 95% CI: 0.72-0.89, p&lt;0.001), private insurance (compared to Medicaid; OR=0.42; 95% CI: 0.30-0.59, p&lt;0.001) and higher income level (OR=0.80; 95% CI: 0.66-0.98, p=0.029) had a lower likelihood of refusing treatment. Among Hispanic patients, 2.3% refused treatment and were more likely to have Medicare (OR=1.96; 95% CI: 1.13-3.4, p=0.016), while those with private insurance (compared to Medicaid; OR=0.32; 95% CI: 0.14-0.73, p=0.007) had a lower likelihood of refusing treatment. Conclusions: This large real-world analysis highlights the intricate sociodemographic and economic factors that affect the decision of a MM to not proceed with the recommendation for treatment. (1) NHW are less likely to refuse treatment as compared to NHAA. (2) Insurance status is an important driver of refusal and transcends race/ethnicity. Furthermore, in this study, we highlight characteristics that are specific to different racial/ethnic groups like CCI which affect only certain racial/ethnic groups. This provides an opportunity to develop targeted interventions such that the benefit of therapeutic advancements can be realized by all.

Introduction: Scant data exist on prognostic factors, survival and treatment (Tx)-related outcomes in SCNSL. We conducted a multicenter international analysis to identify prognostic factors and outcomes in SCNSL at diagnosis (de novo), or after frontline Tx (1L) either with (concomitant) or without (isolated) systemic (syst) relapse. Methods: This study collected data from patients (pts) treated between 2001-2023 at 35 centers. Overall (OS) and progression-free survival (PFS) were calculated from SCNSL diagnosis to first event (death for OS, relapse/death for PFS) or last follow-up. Uni- (UVA) and multivariable (MVA) Cox analyses were performed to assess prognostic factors; Kaplan-Meier method was used to estimate survival. Results: 1173 (US: 863, UK: 273, Canada: 37) pts with SCNSL were included. Baseline characteristics were median age: 62 years (interquartile range 52.5-69), male sex: 58.7%, elevated LDH: 71.1%, stage III/IV: 88.6%, HIV: 3%, transformed LBCL (tLBCL): 13.8%, non-germinal center B-cell like (non-GCB) subtype: 52.3%, double expressor (DE): 40%, MYC rearrangement (MYC-R): 28.3%, MYC/BCL2 double hit: 16.6%, MYC/BCL2/BCL6 triple hit (TH): 6.1%. Among 522 pts with de novo SCNSL, 84.2% had involvement of a single CNS compartment (44.7% brain parenchyma; 40.4% leptomeningeal [lepto]). 1L regimens included 36.2% R-CHOP with high-dose methotrexate (HD-MTX), 12.5% MARIETTA-type, and 9.8% R-CODOX-M/IVAC; 54.6% received intrathecal chemotherapy. Consolidation Thiotepa-based autologous stem cell transplant (TT-ASCT) occurred in 15.3%. The majority of pts who underwent TT-ASCT had previously achieved CR or PR in syst (92.5%) and CNS (72.5%) compartments. At median follow-up 25.7 months (mos), subsequent relapse was observed in 27.5% TT-ASCT recipients: 36.3% had isolated CNS, 27.4% syst, and 36.3% concomitant. 588 pts presented with SCNS after 1L (66.2% isolated, 33.8% concomitant). Brain parenchyma involvement was observed in 56.8%, lepto in 22.6%. Tx included 31.6% HD-MTX combination (eg, R-MPV, MTR); 18.4% HD-MTX +/- rituximab; 16.2% MARIETTA-type; and 9.4% platinum-based regimen. Consolidation TT-ASCT occurred in 22.4% (n=132), and 13.8% (n=81) received CAR-T cell therapy (excluding subsequent relapses in de novo group). Syst (65.1%) & CNS (69.1%) responses (CR/PR) were higher before TT-ASCT compared to CAR-T cell (49.5% & 54.5%, respectively). After TT-ASCT, 52 pts (39.3%) relapsed, mainly in the CNS (n=30, 57.7%), with only 4 (7.7%) concomitant. After CAR-T, 48 pts (59.3%) relapsed: 15 (31.2%) isolated in CNS and 15 (31.2%) concomitant. 12-month cumulative incidence of relapse (with death as competing risk) was 21.1% after TT-ASCT and 55.8% after CAR-T. In 63 pts (5.4%), the first CNS event occurred &gt;2 lines of Tx. With median follow-up of the entire cohort of 24.6 mos, median PFS and OS were 11 and 21 mos, respectively. mPFS and mOS were significantly better in pts with de novo SCNSL (13.4 & 47.4 mos) compared to SCNSL after 1L (10.4 & 14.2 mos) and &gt;2 lines of Tx (6.5 & 9.7 mos); P&lt;0.0001. Factors associated with significantly shorter OS in UVA across all presentations were age &gt;60, male sex, GCB subtype, MYC-R, tLBCL, DE, TH, elevated LDH, ECOG PS ≥2, SCNSL after 1L (vs. de novo), and failure to achieve syst/CNS response to 1L. Of these, age &gt;60, male sex, MYC-R, ECOG PS ≥2, and failure to achieve response to 1L remained significant in MVA. In de novo cases, age &gt;60, DE, ECOG PS≥2, and failure to achieve syst/CNS response to 1L were associated with poorer OS; for pts with SCNSL after 1L, age &gt;60, GCB subtype, and ECOG PS ≥2 were significant. Pts treated with HD-MTX-based regimens after 1L experienced longer OS than those treated with platinum regimens or high-dose cytarabine. In de novo cases, TT-ASCT was significantly associated with longer OS (HR=0.58; P=0.025) in MVA after adjusting for significant factors, 1L type, and response. For SCNSL at relapse, TT-ASCT (HR=0.34; P&lt;.0001) and isolated SCNSL presentation (vs. concomitant HR=0.70, P=0.007) were associated with longer OS, adjusting for significant factors, type of second-line Tx, & site of CNS relapse. Conclusions: This study represents the largest analysis of SCNSL inclusive of all modes of presentation. Concomitant SCNSL at relapse was associated with poor outcomes, while TT-ASCT consolidation was associated with improved OS in de novo & relapsed disease. Despite advances in LBCL SCNSL remains an unmet therapeutic need.

Introduction: Overall outcomes have improved significantly for MM with a 5-year relative survival rate currently of &gt;60%. With effective treatments, patients from all clinical strata and age groups are expected to have meaningful benefit, but despite excellent therapeutic advancements, some patients continue to have early mortality. We conducted this study to investigate factors associated with early mortality. Methods: The National Cancer Database (NCDB) was queried for adult patients with NDMM between 2004 and 2021. We excluded patients with multiple primary malignancies or lost to follow-up (unknown vital status or last contact). Early mortality was defined as death within 6 months from MM diagnosis. Patient demographics and socioeconomic factors available in NCDB were collected. Kaplan-Meier and multivariate Cox regression were used to evaluate the likelihood of early mortality in this large cohort of MM patients using multi-variate analysis. Results: Out of 255,579 eligible patients with MM, 35,302 (13.8%) died within the first 6 months of diagnosis and 108,534 (42.5%) died after the first 6 months of MM diagnosis. The early mortality cohort had significantly higher mean age at MM diagnosis (73.9 vs. 68.5 years, p&lt;0.001) but no significant differences were noted for gender distribution. There was a statistically significant difference for racial/ethnic distribution (p=0.019), but the percentages were very similar among non-Hispanic White (69% vs 68.1%), non-Hispanic African American (18% vs 18.7%) and Hispanic patients (4.7% vs 4.8%). Patients in the early mortality cohort were less likely to be treated at academic institutions (28.4% vs 37.8%, p&lt;0.001) and have significantly different distribution by insurance type (less likely to have private insurance; 17.3% vs. 30%, more likely to have Medicare; 72.1% vs. 58.7%, p&lt;0.001) although overall insurance access was similar between the two groups (95.3% vs 95.2%, p=0.283). Early mortality was associated with higher morbidity scores as per the Charlson-Comorbidity Index (CCI) (p&lt;0.001) and were more likely to have not received any treatment for MM (53.2% in early mortality group vs. 28.4% in late mortality, p&lt;0.001). Early mortality was also associated with a lower literacy rate (high school graduation rate 21.2% vs. 19.7%, p&lt;0.001) and lower household income (&lt;$46,277; 19.1% vs. 17.7%, p&lt;0.001). Conclusion: This large real-world analysis shows that despite therapeutic advances in recent years, there is a significant percentage of patients with NDMM in the U.S. who suffer from early mortality. There are several sociodemographic and economic factors that were found to be associated with early mortality, with some showing clear trends (older age, treatment facility type, insurance type, income, education, CCI), while others like racial differences were significant but somewhat ambiguous. Identifying and addressing these factors at diagnosis will help provide personalized care plans and minimize early mortality.

e19075 Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P<0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.

e19074 Background: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) is an uncommon type of lymphoma predominantly affects elderly patients and is associated with poor outcome. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with PCDLBCL-LT between 2004 and 2020. All patients aged ≥18 years diagnosed with PCDLBL-LT were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 967 patients with PCDLBCL-LT. Out of whom 516 (53%) were females, 841 (87%) were White non-Hispanic, 41 (4%) were White Hispanic and 37 (4%) were African Americans. 276 (29%) received chemotherapy, 203 (21%) received radiation only, 293 (30%) received chemoradiation, 147 (15%) did not receive any treatment and 48 (5%) had unknown treatment status. The median age at diagnosis was 78 years (range 23-90). The median follow-up time was 87 months (95% CI 74-99), the median overall survival (mOS) for the whole cohort was 42 months (95%CI 37-47). Among patients with known treatment status and vital status of last contact (N=841), patient who received chemoradiation had significantly better mOS compared to patients who received chemotherapy only, radiation only and no treatment (64 vs 41, 39 and 9 months, respectively P<0.001). Patient who received chemotherapy only and radiation only as first line therapy had significantly better mOS compared to patients who received no treatment (41 and 39 vs 9 months, respectively P<0.001), but there was no statistically significant difference in the mOS between chemotherapy only and radiation only (41 vs 39 months, P=0.359). On multivariate analysis, older age, male gender, and Charlson-Deyo score 2 and ≥3 were associated with worse OS (HR 1.061 95%CI 1.050-1.072; P<0.001, HR 1.241 95%CI 1.093-1.482; P=0.017, HR 1.396 95%CI 1.004-1.941; P=0.047 and HR 2.454 95%CI 1.619-3.719; P<0.001 respectively), all type of treatments including chemotherapy only, chemoradiation, and radiation only were associated with better OS (HR 0.576 95% CI 0.443-0.749; P<0.001, HR 0.379 95%CI 0.290-0.495; P<0.001 and HR 0.443 95%CI 0.339-0.578; P<0.001, respectively). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in this uncommon type of lymphoma compared to single treatment modality.

Background Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of non-Hodgkin lymphoma. Clinicopathologic features are distinct from diffuse large B cell lymphoma, but it shares some clinical and biologic features with Nodular sclerosis classic Hodgkin lymphoma. Central nervous system (CNS) relapse appears to be rare in patients with PMBCL, with limited literature reporting a rate of approximately 1.5% to 4%. We examined the incidence of CNS relapse, treatment approaches and survival outcomes in patients with PMBCL. Methods Patients with newly diagnosed PMBCL seen at Mayo Clinic between 2002 and 2022 were identified using the prospective Mayo Clinic Lymphoma Database. Clinical features, treatment details and outcomes were abstracted from the medical record. Cumulative incidence of CNS relapse was analyzed with death as a competing risk. The association of CNS-IPI, systemic treatment, and CNS prophylaxis approach with CNS relapse rate was analyzed using competing risk models and descriptively. Event-free survival (EFS) for the cohort was defined as time from PMBCL diagnosis to first recorded CNS and/or systemic relapse or death from any cause. Overall survival (OS) was defined as time from PMBCL diagnosis (or CNS relapse) to death from any cause. Survival analysis was performed using the Kaplan-Meier method. Results A total of 124 PMBCL cases were identified. The median age at diagnosis was 37 years and 61% were female. The distribution of CNS-IPI was low-risk in 67 (61%), intermediate-risk in 41 (37%), and high-risk in 2 (2%). 64 patients (52%) received R-CHOP and 54 patients (44%) received R-DA-EPOCH as frontline therapy. High-dose methotrexate (HD-MTX) for CNS prophylaxis was administered to 6 patients (5%), 5 with R-CHOP and 1 with R-DA-EPOCH. 16 patients received intrathecal (IT) chemotherapy (methotrexate and/or cytarabine) for CNS prophylaxis, 3 with R-CHOP and 13 with R-DA-EPOCH. The median follow-up was 56.0 months. The 5-year EFS rate was 75.1% and the 5-year OS rate was 90.7% for the entire cohort. 20 patients had systemic relapse only and 3 had CNS relapse. The cumulative incidence of CNS relapse was 1.84% (95% CI 0.46%-7.17%) at 2 years and 2.92% (95% CI 0.50%-8.84%) at 5 years (Figure 1). No statistically significant association of CNS-IPI, systemic therapy or CNS prophylaxis regimen with CNS relapse rate was found in competing risk models; however, this analysis was limited by a small event number (n=3). Among the 3 patients with CNS relapse, 1 had high-risk CNS-IPI and 2 had intermediate risk. All 3 patients were treated initially with R-CHOP. Two patients did not receive any CNS prophylaxis and 1 patient received IT CNS prophylaxis. All three patients who had CNS relapse were female. Patient #1 was diagnosed at age 48 and had simultaneous CNS and systemic relapse 6 months later. The patient was treated with HD-MTX, temozolomide and rituximab for CNS relapse, and subsequently received multiple therapies for systemic disease including R-DHAP, R-ICE, and died 17 months after CNS relapse. Patient #2 was diagnosed at age 22 and had CNS relapse after 8.7 months, followed by systemic relapse 2 months later. The patient received HD-MTX, temozolomide and rituximab for CNS relapse, followed by systemic and whole-brain radiation therapy (RT) for both systemic and CNS relapse. Subsequently the patient received salvage chemotherapy, autologous and allogeneic stem cell transplant for systemic relapse. The patient died 26.8 months after CNS relapse. Patient #3 was diagnosed at age 24 and had systemic relapse after 20.7 months, followed by CNS relapse 5.4 months later. The patient received methotrexate and whole-brain RT following CNS relapse and died 1.2 months after CNS relapse. Besides these 3 patients, we identified 6 PMBCL patients with CNS relapse who were diagnosed at other medical centers and subsequently referred to our institution for management of refractory disease. The survival after CNS relapse was poor, with a median OS of 10.4 months (95% CI 5.6-15.2). Conclusion Our study showed that the CNS relapse rate (1.84% at 2 years and 2.92% at 5 years) was overall low in patients with PMBCL, consistent with previous reports. CNS relapse was associated with poor survival despite aggressive treatment approaches. Novel approaches utilizing biological risk factors for CNS relapse, such as circulating tumor DNA, are needed to identify patients with CNS relapse.

Introduction Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive type of non-Hodgkin B-cell lymphoma, accounting for about 3% of all non-Hodgkin lymphomas. The role of radiation therapy following immunochemotherapy is controversial and lately there has been more studies suggesting there is less benefit of adding radiation therapy. Large-scale studies describing and evaluating the effect of radiation therapy on survival outcome are lacking. Materials and Methods The National Cancer Database (NCDB) was queried for patients diagnosed with PMLBCL between 2004 and 2019. All patients aged ³18 years diagnosed with PMLBCL were included. We excluded patients with unknown chemotherapy and radiation therapy status, or received radiation prior to chemotherapy, or received radiation 6 months after chemotherapy or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results The total cohort consisted of 1,899 patients with PMLBCL. Out of whom 1,177 (62%) were females, 1,560 (76%) were White non-Hispanic, 113 (6%) were White Hispanic and 205 (11%) were African Americans. Among patients with known disease stage, 1,164 (61%) had early-stage disease (stage I and II) and 351 (19%) had advanced stage disease (stage III and IV). 1,443 (76%) received chemotherapy only and 456 (24%) received chemotherapy followed by radiation therapy. The median age at diagnosis was 35 years (range 18-90), 1,215 (64%) were diagnosed at younger age (40 years or less). The median follow-up time was 60 months (95% CI 57-62), the median overall survival (OS) for the whole cohort was not reached, and the 5-year OS was 91%. The 5-year OS for early and advanced stage were 93% and 83%, respectively. In patients with early-stage disease, there was no statistically significant difference in the median OS between patients who received chemotherapy only (N=824) compared to patients who received chemotherapy followed by radiation therapy (N=340) (not reached in both groups, P=0.130) with 5-year OS of 92% and 93%, respectively. In patients with advanced stage disease, there was no statistically significant difference in the median OS between patients who received chemotherapy only (N=294) and patients who received chemotherapy followed by radiation therapy (N=57) (median OS not reached in both groups, P=0.067) with 5-year OS of 82% and 88%, respectively. On multivariate analysis, older age and Charlson-Deyo score ≥3 were associated with worse OS (HR 1.062 95% CI 1.047-1.078; P&lt;0.001 and HR 6.032 95% CI 1.853-19.634; P=0.003, respectively), early stage was associated with better OS (HR 0.508 95% CI 0.364-0.708; P&lt;0.001), whereas adding radiation to chemotherapy did not affect the OS (HR 0.713 95% CI 0.491-1.035; P=0.075). Over the years, there was a significant down trend in using radiation therapy (Figure 1). Using univariate and multivariate logistic regression analysis, we found early-stage disease was associated with increased use of radiation therapy after chemotherapy. Whereas patients who were treated at academic/research programs were less likely to receive radiation therapy (Table 1). Conclusion This large real-world analysis shows a practice change in PMLBCL treatment with a trend in omitting radiation therapy. In our analysis, we found that adding radiation therapy to systemic therapy did not affect the survival outcome in both early and advanced stage disease.

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell non-Hodgkin lymphoma that originates in lymphoid tissue of epithelial lined structures. The commonest site for this lymphoma is the stomach (gastric MALT lymphoma). MALT lymphoma in other mucosal sites, including other gastrointestinal sites, lungs, salivary glands, and lacrimal glands, has been well-described. However, MALT lymphoma in urothelial organs (kidneys, ureters, and urinary bladder) has not been well-characterized. This study aimed to investigate the clinicopathological features and therapeutic outcomes in urologic MALT lymphoma (U-MALT). Methods: We identified patients with U-MALT who were treated at the Mayo Clinic Cancer Center between March 2013 and May 2022 through electronic medical chart review. Clinical, pathologic, radiologic, therapeutic, and survival data were extracted. Kaplan-Meier analysis was used to determine the survival outcomes. Results: The characteristic features of six patients (N=6) with U-MALT are summarized in Table-1. 4/6 (67%) are Caucasian, and 3/6 (50%) are males. The median age at diagnosis was 73.5 years. Urologic sites are the urinary bladder (3/6), kidneys (3/6), and ureter (1/6, this patient had both kidney and ureter involvement). 4/6 patients had primary U-MALT. Concurrent non-urologic involvement was identified in 3/6 patients and included bone marrow, lungs, stomach, and axillary lymph nodes. Bone marrow involvement was observed in 2/6 patients.Next-generation sequencing was performed on one patient's peripheral blood, revealing an ATM mutation. Regarding the initial clinical presentation, kidney-involved U-MALT patients presented with renal failure, and those with urinary bladder/ureteric involvement, U-MALT was diagnosed incidentally upon cystoscopic evaluation and biopsy. Various management strategies were used, including observation, surgical resection, and rituximab treatment. Notably, all patients achieved complete remission (CR) except one with partial response to rituximab, who subsequently achieved CR with the Bendamustine/Rituximab regimen. Median follow-up is 6 years (range, 1-10). All six patients are alive without relapse at the time of analysis, with the flat overall survival curve at 100%, indicating excellent long-term survival. Conclusions: Our study indicates that urologic MALT lymphomas are extremely rare and predominantly affect elderly people. The most common urologic sites are the kidneys and urinary bladder. Urologic manifestations are dependent on the urologic site involved. They can be primary to the urologic structures or part of the disseminated systemic marginal zone lymphoma. They can be treated like other low-grade lymphomas with observation, surgical resection, and systemic therapy. They appear to be quite responsive to CD-20 targeted therapy with Rituximab. Prognosis appears to be excellent with long overall survival. Further research with multi-institutional studies is needed to study this rare lymphoma entity and identify optimal therapy.