Mayo Staging System Research Articles

99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Limited Utility of Mayo 2012 Cardiac Staging System for Risk Stratification of Patients with Advanced Cardiac AL Amyloidosis - Analysis of a Uniformly Treated Cohort of 1275 Patients

Introduction: Systemic light chain (AL) amyloidosis is a rare incurable disorder caused by extracellular deposition of misfolded light chain protein fibrils causing organ dysfunction. Cardiac involvement is present in approximately two thirds of cases at diagnosis. Survival depends largely on the severity of cardiac involvement as well as haematological response to treatment. Two validated cardiac staging systems, Mayo 2012 (stage I-IV) (Kumar, Dispenzieri et al. 2012) and European modification of the standard Mayo staging system 2004 (stage I-IIIb) (Wechalekar, Schonland et al. 2013, Palladini, Sachchithanantham et al. 2015), stratify patients according to different thresholds of biomarkers markers of disease involvement (NTproBNP, troponin T and, additionally for Mayo 2012, difference between involved and uninvolved free light chain [dFLC]). Patients included in these original models were not treated with a uniform induction protocol and treated with regimens such as oral melphalan dexamethasone, which are now rarely used. There is a need to re-assess the predictive performance and robustness of these staging systems with current treatment approaches. We report here the comparison of cardiac staging in a large cohort of patients with AL amyloidosis uniformly treated bortezomib-containing regimens in the first-line setting from the ALChemy study. Methods: Patients enrolled in a prospective observational study at the United Kingdom National Amyloidosis Centre from 2010-2019 treated with bortezomib-based regimens were analysed. Outcomes were stratified according to Mayo 2012 and the European modified Mayo classification. Written consent was obtained from all patients in accordance with the Declaration of Helsinki. Results: 1275 patients (755 male, 520 female) were included. Median age at presentation was 67 years (range 29-89), with a median of two involved organs (range 1-5); 812 (64%) had cardiac involvement, 892 (70%) had renal and 154 (12%) liver involvement. All patients were treated with first-line bortezomib-based therapy: bortezomib-cyclophosphamide-dexamethasone in 1190 [93%]; bortezomib-dexamethasone in 48 [4%]; bortezomib-thalidomide-dexamethasone in 21 [2%] and 16 others. None were treated with a daratumumab based combination or autologous stem cell transplant (ASCT) upfront; 95 (7%) had ASCT at a subsequent line of therapy. Patients were classified by Mayo 2012 staging as: stage I, II, III, IV in 199 (16%), 329 (26%), 413 (32%) and 334 (26%) cases, respectively and by European modified staging as: stages I, II, IIIa and IIIb in 219 (17%), 436 (34%), 424 (33%) and 196 (15%), respectively. The median follow-up was 47 months (95% CI 45-50), median overall survival (OS) was 59 months (95% CI 51-67) and 3-year OS was 59% (95% CI 56-61). Whilst both Mayo 2012 and European modification models were predictive of overall survival, the European modification discernibly discriminated those with the poorest and best outcomes. Median OS by European staging for stage I, II, IIIa, IIIb was: not reached (NR), 76, 34 and 8 months respectively, compared with Mayo 2012 stage I, II, III, IV: NR, 74, 36, and 26 months respectively. European stage II, IIIa, IIIb had a hazard ratio (HR) for death of: 2.42 (95% CI 1.69-3.49), 4.65 (95% CI 3.27-6.61) and 9.18 (95% CI 6.36-13.25), respectively. Mayo stage II, III, IV had a HR of: 2.54 (95% CI 1.72-3.76), 4.66 (95% CI 3.21-6.76) and 5.99 (95% CI 4.12-8.71), respectively. Conclusion: Advanced stage cardiac involvement remains a prognostic predictor of adverse outcomes. In a cohort of bortezomib-treated patients, the European modification has a stronger predictive value for poorer outcome. The Mayo 2012 staging, utilising additional dFLC, did not discriminate the most advanced disease as well suggesting that treatment markedly impacts the predictive capability of cardiac staging systems. Daratumumab-based treatments may have an even greater impact in ameliorating the adverse prognostic significance of high presenting dFLC. Until cardiac staging is revalidated for the modern treatment era of AL amyloidosis, our data should be taken into consideration when using cardiac staging systems in the clinic as well as for clinical trial design.

Positive correlation between latent Epstein-Barr virus infection and severity of illness in inflammatory bowel disease patients.

Emerging studies indicate the critical involvement of microorganisms, such as Epstein-Barr virus (EBV), in the pathogenesis of inflammatory bowel disease (IBD). Immunosuppressive therapies for IBD can reactivate latent EBV, complicating the clinical course of IBD. Moreover, the clinical significance of EBV expression in B lymphocytes derived from IBD patients' intestinal tissues has not been explored in detail. To explore the clinical significance of latent EBV infection in IBD patients. Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection. Based on the staining results, the patients were divided into two groups, according to their latent EBV infection states - negative (n = 33) and positive (n = 10). Illness severity of IBD were assigned according to Crohn's disease activity index (ulcerative colitis) and Mayo staging system (Crohn's disease). The clinic-pathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups. Systolic pressure (P = 0.005), variety of disease (P = 0.005), the severity of illness (P = 0.002), and pre-op corticosteroids (P = 0.025) were significantly different between the EBV-negative and EBV-positive groups. Systolic pressure (P = 0.001), variety of disease (P = 0.000), pre-op corticosteroids (P = 0.011) and EBV infection (P = 0.003) were significantly different between the mild-to-moderate and severe disease groups. IBD patients with latent EBV infection may manifest more severe illnesses. It is suggested that the role of EBV in IBD development should be further investigated, latent EBV infection in patients with serious IBD should be closely monitored, and therapeutic course should be optimized.

Prognostic influence for hilar cholangiocarcinoma and comparisons of prognostic values of Mayo staging and TNM staging systems.

The study was designed to discuss the effect of stratification factors in the Mayo staging on the prognosis of hilar cholangiocarcinoma (HCCA) patients, and to evaluate the predictive value of the Mayo staging on the prognosis. The Kaplan-Meier survival curve and Log-rank test were used to perform univariate analysis on each index and obtain statistically significant influencing factors. The Kaplan-Meier survival curve and Log-rank test were used to analyze the correlation between the two staging systems and the survival period. The receiver operating characteristic (ROC) curves were used for each single staging system trend analysis, and comparison of their curve area to determine prognosis prediction ability for patients with HCCA. According to Kaplan-Meier survival curve changes and Log-rank test results, it was found that both staging systems were correlated with the survival time of the patients (P < .001). Through a pairwise comparison within the stages, it was found that the heterogeneity between the stages within the Mayo staging is very good, which was better than the TNM staging. A single trend analysis of the prognostic assessment capabilities of the two systems found that the area under the ROC curve of Mayo staging system (AUC = 0.587) was the largest and better than the TNM staging system (AUC = 0.501). Mayo staging can be used for preoperative patient prognosis assessment which can provide better stratification ability based on a single-center small sample study, and the predictive value is better than TNM staging.

Abstract 11818: Daratumumab Containing Regimens Improved Survival in Patients With Light-Chain Cardiac Amyloidosis

Background: Immunoglobulin light-chain (AL) amyloidosis is a lethal condition resulting from misfolded immunoglobulin ALs produced by clonal CD38-positive plasma cells. Daratumumab, an anti-human CD38 monoclonal antibody, led to higher frequencies of complete hematologic responses and better clinical outcomes compared to conventional treatment. Therefore, daratumumab-containing regimens has become the standard of care in patients with systemic AL amyloidosis and multiple myeloma. This study sought to evaluate the survival benefit of daratumumab-containing regimens in patients with AL cardiac amyloidosis. Methods and Results: We examined 65 consecutive patients with AL cardiac amyloidosis (mean age: 67.2±10.4 years old, male: 69%) who underwent chemotherapy. We divided the patients into two groups, daratumumab group (n=32: treated with daratumumab containing regimens within the first two lines of chemotherapy) and conventional treatment group (n=33). Compared to conventional treatment group, daratumumab group tended to be older (69.2±9.6 vs. 65.2±11.0; p=0.12), while no significant differences in biomarkers and echocardiographic parameters were observed. A total of 26 patients (40%) were deceased (median follow up period: 395 days). Kaplan-Meier survival curves showed that daratumumab group had significantly lower mortality compared to conventional treatment group (p=0.04; log-rank test; Figure). Cox hazard analysis revealed that daratumumab containing regimens were associated with lower mortality after adjustment for revised Mayo staging system for AL amyloidosis (hazard ratio: 0.32; 95% confidence interval: 0.12 to 0.85; p=0.02). Conclusion: Daratumumab containing regimens might be associated with improved survival in AL cardiac amyloidosis.

Urachal carcinoma: A novel staging system utilizing the National Cancer Database.

Urachal carcinoma (UrC) is a rare, aggressive cancer with a poor prognosis that is frequently diagnosed in advanced stages. Due to its rarity, the current staging systems, namely Sheldon, Mayo, and Ontario were established based on relatively small patient cohorts, necessitating further validation. We used a large patient population from the National Cancer Database to model a novel staging system based on the Tumor (T), Node(N), and Metastasis (M) (TNM) staging system and compared it to established staging systems. We identified patients diagnosed with UrC between the years of 2004-2016. To determine median overall survival (OS), a Kaplan-Meier (KM) curve was generated using the Sheldon, Mayo, Ontario, and TNM staging system. A cox proportional-hazards regression model was developed to highlight predictors of overall survival. A total of 626 patients were included in the analysis. The OS for the entire cohort was 58.2months (50.1-67.8) with survival rates at 12, 24, and 60 months of 83%, 70%, and 49%, respectively (p< 0.0001). As compared to the Sheldon, Mayo, and Ontario staging system, our TNM staging system had a more balanced sample and survival distribution per stage and no overlap among stages on KM survival curves. The Mayo, Ontario, and TNM staging systems were more accurate in terms of stage-survival correlation than the Sheldon staging system (p< 0.05 for all stages). The proposed novel TNM staging system for UrC has a more balanced sample distribution and a more accurate stage-survival correlation than the traditional Mayo, Sheldon, and Ontario staging systems. It is clinically applicable and enables better risk stratification, prognosis, and therapeutic decision-making.

Web-Based Prediction Models for Overall Survival and Cancer-Specific Survival of Patients With Primary Urachal Carcinoma: A Study Based on SEER Database.

Objective:We aimed to establish nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary urachal carcinoma (UrC).MethodsInformation on patients diagnosed with UrC from 1975 to 2018 was collected from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data. The independent prognostic factors were determined using univariate and multivariate Cox regression. Backward variable elimination according to the Akaike information criterion (AIC) identified the most accurate and parsimonious model. Nomograms were built based on regression coefficients. The C-index, calibration plot, Brier score, integrated discrimination improvement (IDI), area under the receiver operating curve (AUC), and decision curve analysis (DCA) curve were used to evaluate the efficiency of models.ResultsIn total, 236 patients obtained from SEER were divided randomly into training and validation cohorts in a 70:30 ratio (166 and 70 patients, respectively). In the training cohort, multivariate Cox regression analysis indicated that pTNM/Sheldon/Mayo staging systems (included respectively), age, and tumor grade were independent prognostic factors for OS. A similar result was also found in CSS. While other variables, such as radiotherapy and chemotherapy, did not identify significant correlations. In predicting OS and CSS at 3- and 5- years, the nomograms based on pTNM showed superior discriminative and calibration capabilities in comparison to multiple statistical tools. The C-index values for the training cohort were 0.770 for OS and 0.806 for CSS, and similar outcomes were shown in further internal validation (C-index 0.693 for OS and 0.719 for CSS). We also discovered that the link between age at diagnosis and survival follows a U-shaped curve, indicating that the risk of poor prognosis decreases first and then increases with age.ConclusionThe efficacy of pTNM in predicting the prognosis of patients with UrC was greater than that of the Sheldon and Mayo staging system. Therefore, we recommend pTNM as the preferred system to stage UrC. The novel constructed nomograms based on pTNM, age, and tumor grade showed high accuracy and specificity and could be applied clinically to predict the prognosis of patients with UrC.

Proposal of a novel staging system for urachal carcinoma utilizing the national cancer database.

e16530 Background: Urachal carcinoma (UrC) is a rare, aggressive cancer with a poor prognosis that is frequently diagnosed in advanced stages. Due to its rarity, the current staging systems, namely Sheldon and Mayo, were established based on relatively small patient cohorts, necessitating further validation. We used a large patient population from the National Cancer Database (NCDB) to model a novel staging system based on the Tumor (T), Node(N) and Metastasis (M) (TNM) staging system and compared it to established staging systems. Methods: Patients diagnosed with UrC between 2004 and 2016 were identified and included in the analysis using the NCDB. The proposed TNM staging system is defined as such: stage 1: T0, a, IS, or 1 and N0M0; stage 2: T2, T3, T3a and N0M0; stage 3: T3b, T4a and N0M0; stage 4: T4b and N0M0, or any T and/or nodal and/or distant metastasis. The Sheldon and Mayo staging systems were correlated with the TNM staging system. Kaplan-Meier (KM) survival plots were generated and stratified by stage to assess the median overall survival (OS) of corresponding stages of each staging system. A cox proportional-hazards regression model was developed to highlight predictors of overall survival. Results: A total of 626 patients with UrC were identified with a median age of 58, of whom 56% (n = 350) were males. The OS for the entire cohort was 58.2 (50.1-67.8) months (mo) with survival rates of 83%, 70%, and 49% at 12, 24, and 60 mo, respectively (p &lt; 0.0001). With the Sheldon staging system, the median OS was 132.2 (89.2-132.2) for stage 1, undefined for stage 2 due to median OS not reaching 50%, 69.6 (60.8-89.5) for stage 3, and 17.3 (14.2-20.7) mo for stage 4 (p &lt; 0.0001 for all stages). With the Mayo staging system, the median OS was 132.2 (88.6-132.2), 69.5 (58.5-88.4), 19.7 (11.6-32.0), and 16.8 (13.2-20.7) mo for stage 1, 2, 3, and 4, respectively (p &lt; 0.0001). The median OS based on the TNM staging system was 132.2 (88.6-132.2), 64.6 (51.8-83.0), 42.7 (30.1-58.2), and 17.8 (11.0-21.1) mo for stage 1, 2, 3, and 4, respectively (p &lt; 0.0001). Based on the Sheldon system, most patients were staged as stage 3 (n = 349; 56%) and 4 (n = 177; 28%) and KM survival curves overlapped between stages 1 and 2. Per the Mayo system, most patients were staged as stage 1 (n = 209; 33%) and 2 (n = 240; 38%) and KM survival curves overlapped between stages 3 and 4. In comparison, our TNM staging system had a more balanced sample and survival distribution per stage and no overlap among stages on KM survival curves. The Mayo and TNM staging systems were more accurate in terms of stage-survival correlation than the Sheldon staging system (p &lt; 0.05 for all stages). Conclusions: The proposed novel TNM staging system for UrC has a more balanced sample distribution and a more accurate stage-survival correlation than the traditional Mayo or Sheldon staging systems. It is clinically applicable and enables better risk stratification, prognosis, and therapeutic decision-making.

Risk Factors for Early Sudden Cardiac Death in Patients with Systemic Light-Chain Amyloidosis on Treatment

Introduction: Despite advances in therapy for patients with light-chain (AL) amyloidosis, mortality remains high in the first 6 months after diagnosis in those on treatment (Blood 2017;129:2111). The early deaths are usually sudden cardiac deaths (SCD); a prior study showed that troponin I level and lack of response to therapy influenced survival (Br J Haematol 2008;143:369). In January 2021 at the approval of daratumumab with cyclophosphamide, bortezomib and dexamethasone for AL (Dara/CyBorD), the FDA label warned that patients with higher cardiac staging may be at risk for fatal cardiac events. We sought to analyze risk factors for SCD in patients on treatment, defining SCD as a sudden unexpected death caused by loss of cardiovascular function (Arrhythm Electrophysiol Rev 2016;5:177).Methods: From a database of 398 patients with AL amyloidosis collected from 2005-2019, we identified patients who suffered out-patient SCD on treatment within 180 days of diagnosis. We recorded baseline age, gender, systolic BP, presence of syncope, LVEF, FLC, cardiac biomarkers, NYHA class, cycles of treatment with bortezomib, and data on SCD. For comparison we identified an age and gender matched group who achieved complete or very good partial responses (CR or VGPR) based on standard criteria and recorded that group's data (J Clin Oncol 2012;30:4541). We compared these datasets by two-tailed Mann-Whitney and where appropriate by contingency table analysis. We computed the medians of the involved FLC, BNP and troponin for all the cases to determine the frequency with which patients in either group had baseline values above or below those medians.Results: Comparative results are shown in Table 1. We identified 13 SCD and 74 age and gender matched CR/VGPR patients. Compared with the CR/VGPR group, both hypotension and exertional syncope were significantly more common in the SCD group, indicating the presence of autonomic dysfunction. NYHA class 3 or 4 status was also more common in the SCD group (40% and 13% vs 26% and 13% in the CR/VGPR group). In addition, more SCD patients were Mayo cardiac stage III (80% vs 46% in the CR/VGPR group) (Blood 2004;104:1881; J Clin Oncol 2004;22:3751). The SCD patients had significantly lower LVEF and higher iFLC and were significantly more likely to have iFLC values above the median. Similarly they had significantly higher BNP and troponin-I levels and were more likely to have values above the medians. The causes of death were unclear in 9 cases but were described by witnesses as due to syncopal events associated with micturition, climbing stairs, or light exertion. In 4 cases seen in emergency rooms, PEA was documented in 3 and septic shock in 1.The SCD patients had a median of 1 cycle of subcutaneous bortezomib-based therapy (CyBorD) (range, 1-5). Three patients received daratumumab subcutaneously with CyBorD. The median starting dose of bortezomib was 1.3mg/m2 (0.7-1.5) usually on a weekly schedule; 2 patients initiated therapy at 1.5mg/m2 weekly, one of whom had had progression of disease (POD) after 2 cycles of oral melphalan and dexamethasone and then had further progression despite completing 3 cycles of CyBorD (POD=1). Eight patients were inevaluable for hematologic response (NR=8), 2 achieved PR after 2 and 4 cycles of CyBorD (PR=2), and of the 3 who got Dara/CyBorD, 1 was inevaluable, 1 achieved VGPR after C1 and 1 CR in C2 (CR/VGPR=2), before having SCD.Conclusion: These findings indicate the contribution that the presence of autonomic dysfunction makes in this population of AL patients with advanced cardiac disease and high levels of iFLC, key variables in the revised Mayo staging system (J Clin Oncol 2012;30:989). The potential pre-morbid significance of exertional syncope has been identified previously (Am J Cardiol 1997;80:1242). In conclusion, this case series suggests that compared with AL amyloid patients who achieve CR or VGPR with treatment, patients who suffer early SCD on treatment have symptoms indicative of autonomic dysfunction and may benefit from in-patient initiation of treatment and from obtaining insurance approval for Dara/CyBorD but starting therapy with weekly subcutaneous daratumumab and dexamethasone, adding cyclophosphamide and bortezomib at a later timepoint based on hematologic response. Moreover, weekly assessment of FLC response is reasonable in these patients in order to guide therapy and adjust supportive care. [Display omitted] DisclosuresComenzo: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Prothena Biosciences: Consultancy, Research Funding; Caelum: Consultancy, Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Janssen: Patents & Royalties: WO2016187546A1, Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis

Clinical and prognostic implications of capillary density in patients with cardiac light chain amyloidosis.

AimsCardiac involvement is crucial factor determining outcomes of light chain (AL) amyloidosis. This study evaluated whether capillary density (CD) quantified from endomyocardial biopsy is associated with structural and functional parameters of amyloid heart. Also, we investigated whether capillary density improves the prognostic value of the current staging system in AL amyloidosis patients with cardiac involvement.Methods and resultsA total of 67 patients with biopsy‐proven AL cardiac amyloidosis were prospectively enrolled in this study. All patients underwent transthoracic echocardiography and EBM at the time of diagnosis. Left ventricle global longitudinal strain was evaluated on two‐dimensional strain echocardiography. The primary endpoint was all‐cause mortality. Amyloid load and capillary density were calculated on endomyocardial biopsy stained immunohistochemically with antibody against amyloid P and CD31, respectively.Among the study population, 37 patients (55.2%) were classified as Stage IV, and the cumulative incidence of death at 1 year was 34% (23 patients). A total of 65 (97%) patients underwent chemotherapy. CD showed a significant correlation with left ventricle global longitudinal strain (r = 0.274, P = 0.025), log N‐terminal pro‐B type natriuretic peptide (r = −0.311, P = 0.005), and amyloid load (r = −0.438, P < 0.001). Patients with a CD ≤ 220/mm2 were at significantly higher risk of death than those with a CD > 220/mm2 (P = 0.026 by log‐rank test). A model based on the 2012 Mayo staging system and CD showed significantly better discrimination and reclassification ability than a model using the 2012 Mayo staging system alone (C‐index 0.582 vs.0.689, P for difference <0.001).ConclusionsCapillary density was significantly related to the severity of amyloid deposits in the myocardium and showed incremental prognostic value in addition to the 2012 Mayo staging system.

Construction and Validation of Novel Prediction Tools Based on Large Population-Based Database to Predict the Prognosis of Urachal Cancer After Surgery.

BackgroundUrachal cancer is a rare neoplasm in the urological system. To our knowledge, no published study has explored to establish a model for predicting the prognosis of urachal cancer. The present study aims to develop and validate nomograms for predicting the prognosis of urachal cancer based on clinicopathological parameters.MethodsBased on the data from the Surveillance, Epidemiology, and End Results database, 445 patients diagnosed with urachal cancer between 1975 and 2018 were identified as training and internal validation cohort; 84 patients diagnosed as urachal cancer from 2001 to 2020 in two medical centers were collected as external validation cohort. Nomograms were developed using a multivariate Cox proportional hazards regression analysis in the training cohort, and their performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness by statistical analysis.ResultsThree nomograms based on tumor–node–metastasis (TNM), Sheldon and Mayo staging system were developed for predicting cancer-specific survival (CSS) of urachal cancer; these nomograms all showed similar calibration and discrimination ability. Further internal (c-index 0.78) and external (c-index 0.81) validation suggested that Sheldon model had superior discrimination and calibration ability in predicting CSS than the other two models. Moreover, we found that the Sheldon model was able to successfully classify patients into different risk of mortality both in internal and external validation cohorts. Decision curve analysis proved that the nomogram was clinically useful and applicable.ConclusionsThe nomogram model with Sheldon staging system was recommended for predicting the prognosis of urachal cancer. The proposed nomograms have promising clinical applicability to help clinicians on individualized patient counseling, decision-making, and clinical trial designing.

The Prognosis and Oncological Predictor of Urachal Carcinoma of the Bladder: A Large Scale Multicenter Cohort Study Analyzed 203 Patients With Long Term Follow-Up.

AimThis study evaluated the prognosis and survival predictors for bladder urachal carcinoma (UC), based on large scale multicenter cohort with long term follow-up database.MethodsA total 203 patients with bladder UC treated at 19 hospitals were enrolled. Clinical parameters on carcinoma presentation, diagnosis, and therapeutic methods were reviewed for the primary cancer and for all subsequent recurrences. The stage of UC was stratified by Mayo and Sheldon pathological staging system. Oncological outcomes and the possible clinicopathological parameters associated with survival outcomes were investigated.ResultsThe mean age of the patients was 54.2 years. Among the total of 203 patients, stages I, II, III, and IV (Mayo stage) were 48 (23.8%), 108 (53.5%), 23 (11.4%), and 23 (11.4%), respectively. Gross hematuria and bladder irritation symptoms were the two most common initial symptoms. The mean follow-up period was 65 months, and 5-year overall survival rates (OS), cancer-specific survival rates (CSS), and recurrence-free survival rates (RFS) were 88.3, 83.1, and 63.9%, respectively. For the patients with Mayo stage ≥III, OS, CSS, and RFS were significantly decreased to 38.0, 35.2, and 28.4%, respectively. The higher pathological stage (Mayo stage ≥III, Sheldon stage ≥IIIc), positive surgical margin (PSM), and positive lymphovascular invasion (PLM) were independent predictors of shorter OS, CSS, and RFS.ConclusionThe pathological stage, PSM, and PLM were significantly associated with the survival of UC patients, emphasizing an importance of the complete surgical resection of tumor lesion.

Primary urachal carcinoma: A systematic review.

e16502 Background: Primary urachal carcinoma (PUC) is a rare cancer of unknown definite cause, and various treatment approaches given its very low incidence and the scarcity of prospective studies. This review aimed to assess the clinicopathologic findings, treatment, and outcomes of PUC cases reported in the literature. Methods: We performed PubMed, Medline, ScienceDirect, and Scopus literature search for "urachus cancer" in adults (19+ years) from data inception through 2020, pooled with six cases from our institution. Results: We included 152 patients with a male: female ratio of 1.61:1 and mean age at diagnosis (±SD, range) of 50.0 (±13.5, 20–86) years. Most common presenting symptoms were hematuria, irritative voiding, abdominal pain, mucinuria, and a palpable mass in 49.5%, 17.3%, 10.2%, 8.7%, and 6.6% of patients, respectively, with a median duration of symptoms of 3 (range 0.25-240) months. Most common locations were the urinary bladder dome (83.6%), supero-anterior (7.03%), and the anterior wall (3.9%), with a median size of 4.9 (range 0.5–96) cm. Subgroups, according to tumor size, were divided into &lt; 4 cm (n = 54, 35.5%) vs ≥4 cm (n = 98, 64.5%) with a significant survival differences according to a log-rank test (p-value &lt; 0.0001). Histologically, the most common diagnoses were urachal adenocarcinoma (43.4%), followed by mucinous adenocarcinoma (24.1%), adenocarcinoma of enteric type (8.9%), and adenocarcinoma with signet ring cell (6.9%). 17.5% and 72.2% of patients were diagnosed at an early stage (stage I and II) while 82.5% and 27.8% were diagnosed at an advanced stage ( III and IV) using Sheldon staging system and Mayo staging system, respectively. Only 9.9% of patients lived for more than five years after their diagnosis. Early Sheldon stage is associated with a high survival probability based on a log-rank test (p-value: 0.003). Overall, most common treatment modalities included surgery alone (71.0%), followed by surgery with chemotherapy (18.6%), and surgery with chemoradiation (4.1%). Patients underwent partial cystectomy (65.4%), en bloc radical resection/exenteration (25.7%), local resection (8.8%), pelvic lymphadenectomy (38.2%), and umbilectomy (16.9%). Almost 79% of patients were alive with an average duration of follow-up of 12 (range 0.9-240) months, and 20.9% were deceased with an average time to death of 23.9 (range 5-139) months. Conclusions: Early Sheldon stage and smaller tumor size were notable predictors of higher survival probability in PUC patients. Hence, early and correct diagnosis is crucial in improving outcomes. This review serves as real-world evidence to promote our understanding of this rare entity and shed light on future clinical trial design.

Outcomes By Cardiac Stage in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Outcomes By Cardiac Stage in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Prognostic Impact of Beta 2 Microglobulin in Patients with Immunoglobulin Light-Chain Amyloidosis Undergoing Autologous Hematopoietic Stem Cell Transplantation

Prognostic Impact of Beta 2 Microglobulin in Patients with Immunoglobulin Light-Chain Amyloidosis Undergoing Autologous Hematopoietic Stem Cell Transplantation

Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with t(11;14) Undergoing Autologous Hematopoietic Stem Cell Transplantation

Background- In patients with light chain amyloidosis (AL), t(11;14) detected by fluorescence in situ hybridization (FISH) is the most common cytogenetic aberration. Several studies have shown that t(11;14) is associated with inferior outcomes in newly diagnosed AL patients [1, 2]. In contrast, at least one study in patients with t(11;14) who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (auto-HCT) showed improved complete response (CR) rate and prolonged hematologic event-free survival[3]. In this single-center, retrospective analysis, we evaluated the outcome of patients with AL and t(11;14) who underwent auto-HCT at our institution. Method- We identified 122 consecutive patients with AL with cardiac or renal involvement who received an auto-HCT between 2011 and 2019. Baseline FISH data were available for 92 patients, 15 (16 %) of whom had t(11;14). Seventy-seven (84%) patients without t(11;14) were included as control . Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL [4]. Revised Mayo staging system was utilized for Cardiac staging [5]. Result- The median age at auto-HCT was 60 years (range, 27 to 77). There were no significant differences in baseline characteristics between the two groups (Table 1). The median follow-up from auto-HCT was 28 months (range, 1 to 100). Overall, 40%, and 42% of patients with or without t(11;14), respectively (p=0.573), received post-auto-HCT maintenance therapy. One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 0 and 2.6% (n=2) in patients with or without t(11;14) (p=0.366). Hematologic CR after auto-HCT was seen in 7 (47%) and 33 (42%) patients with or without t(11;14), respectively (p=0.78). Organ response (OR) after auto-HCT was seen in 10 (71%) and 50 (67%) patients with or without t(11;14), respectively (p=0.586). The 2-year hematologic disease-free survival (Heme DFS) was 93% and 87% with or without t(11;14), respectively (p=0.422). The 2-year progression-free survival (PFS) was 92%, and 87% in patients with or without t(11;14) (p=0.6) (Figure 1A).The 2-year overall survival was 100%, ad 87% in patients with or without t(11;14) (p=0.2) (Figure 1B). Cardiac involvement with AL was associated with a shorter OS (p=0.012). Conclusion- In this single-center retrospective analysis, we showed that auto-HCT is safe and feasible in selected patients with AL and t(11;14), and these patients have comparable outcomes to patients without t(11;14). Disclosures Bashir: Celgene: Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Amgen: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support; Jazz: Consultancy. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Adaptive Biotechnologies: Honoraria; Sanofi: Research Funding; Novartis: Research Funding; JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Oncopeptides: Consultancy; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Thomas:Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding; BMS: Research Funding. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents &amp; Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Actinium: Consultancy; Omeros: Consultancy; Takeda: Patents &amp; Royalties; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy. Qazilbash:Janssen: Research Funding; Bioline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy.

First Glimpse on Real-World Efficacy Outcomes for 2000 Patients with Systemic Light Chain Amyloidosis in Europe: A Retrospective Observational Multicenter Study By the European Myeloma Network

First Glimpse on Real-World Efficacy Outcomes for 2000 Patients with Systemic Light Chain Amyloidosis in Europe: A Retrospective Observational Multicenter Study By the European Myeloma Network

Outcomes in Patients with AL (Light-Chain) Cardiac Amyloidosis

Outcomes in Patients with AL (Light-Chain) Cardiac Amyloidosis

Front-line daratumumab in newly diagnosed AL amyloidosis patients.

e20569 Background: Light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by organ dysfunction, morbidity, and early mortality. Treatment focuses on suppressing monoclonal light chain production as measured by hematologic response criteria (Comenzo et al., 2012). Daratumumab (DARA), a monoclonal CD38 antibody, has demonstrated efficacy in heavily pretreated AL patients (Kaufman et al., 2017). We report the outcomes of newly diagnosed AL patients treated with a DARA-based regimen. Methods: A single-center retrospective chart review with an IRB-approved protocol was performed on newly diagnosed AL patients treated with first line DARA-based regimens between 1/2018 – 12/2019. Results: Fourteen patients were evaluated. The median age was 69 years (45 – 87), 50% were male, and 50% produced monoclonal lambda light chains. All patients had cardiac and renal involvement. Per the 2004 Mayo staging system, 1/14 (7%) patients had stage I cardiac disease, 2/14 (14%) had stage II, and 11/14 (79%) had stage III, of which two were stage IIIb. Regarding renal staging (Palladini et al., 2014), 10/14 (71%) patients were stage I, 3/14 (21%) stage II, and 1/4 (7%) stage III. Most patients (11/14) received DARA in combination with bortezomib and dexamethasone, while one patient received DARA and dexamethasone (DEX). Two patients received DARA in combination with bortezomib, cyclophosphamide, and DEX. Patients received a median of 5 cycles of DARA (1 – 14). After a median follow-up of 4.4 months (1 – 19), all patients were still receiving DARA. DARA was well tolerated, with 4 patients (29%) experiencing grade 1 infusion reactions and no additional toxicities observed. Responses were rapid, with a median time of 11 days (7 – 61) to first response and 46 days (9 8– 168) to best response. First response was classified as partial response (PR) in 8/14 patients (57%), very good PR (VGPR) in 3/14 (21%), and complete response (CR) in 1/14 (7%). Best response included a PR in 3/14 (21%), VGPR in 7/14 (50%), and CR in 2/14 (14%). In most patients, responses deepened over time. Cardiac response was seen in 5/7 (71%) evaluable patients with median time to response of 39 days (21 – 263). Renal response was seen in 2/4 (50%) evaluable patients with median time to response of 152 days (94 – 194). Conclusions: First line use of DARA in AL amyloidosis produced rapid and deep hematologic and organ response, resulting in a 93% objective hematologic response rate. DARA was well-tolerated and efficacious even among patients with extensive organ involvement and cardiac dysfunction. Prospective studies of first line DARA are warranted.