High-intermediate Risk Group Research Articles

Autologous hematopoietic stem cell transplantation treatment for T cell lymphoblastic lymphoma

目的探讨自体造血干细胞移植（auto-HSCT）巩固治疗T淋巴母细胞淋巴瘤（T-LBL）的疗效及相关影响因素。方法对2006年4月至2017年7月在苏州大学附属第一医院血液科和北京大学肿瘤医院淋巴瘤科接受auto-HSCT的41例T-LBL患者进行回顾性分析。结果①41例T-LBL患者中，男30例，女11例，中位年龄24（11～53）岁，12例（29.3％）纵隔累及，20例（48.8％）骨髓累及，Ann Arbor分期Ⅲ期及以上33例（80.5％）；移植前疾病处于第1次完全缓解（CR1）期26例（63.4％），非CR1期15例（36.6％）；移植前国际预后指数（IPI）中低危组（<3分）29例（70.7％），中高危组（≥3分）12例（29.3％）。②移植后中位随访29（3～98）个月，全部41例患者的3年总生存（OS）率、无进展生存（PFS）率分别为（64.3±8.2）％、（66.0±7.8）％，3年累积复发率（CIR）为（30.7±7.4）％，3年非复发死亡率（NRM）为（4.8±4.6）％。③CR1组、非CR1组患者3年OS率分别为（83.4±7.6）％、（38.9±12.9）％（P＝0.010），3年PFS率分别为（83.8±7.4）％、（40.0±12.6）％（P＝0.006），3年CIR分别为（16.2±7.4）％、（53.3±12.9）％（P＝0.015），3年NRM分别为0、（14.3±13.2）％（P＝0.157）。④IPI中低危组、中高危组3年OS率分别为（76.9±8.4）％、（35.7±15.2）％（P＝0.014），3年PFS率分别为（77.4±8.2）％、（40.0±14.6）％（P＝0.011），3年CIR分别为（18.1±7.3）％、（60.0±14.6）％（P＝0.006），3年NRM分别为（5.6±5.4）％、0（P＝0.683）。结论auto-HSCT可显著改善T-LBL患者的预后，移植前疾病状态和IPI评分是影响auto-HSCT疗效的重要因素。

Clinical characteristics and prognostic factors of 40 cases of primary systemic anaplastic large cell lymphoma

目的分析原发系统型间变性大细胞淋巴瘤（ALCL）的临床特征及预后因素。方法回顾性分析2013年1月至2018年12月期间在浙江大学医学院附属第一医院住院治疗的40例ALCL患者的临床资料，总结其临床特征并分析其预后相关因素。结果①40例患者中男29例，女11例，中位年龄41（14～67）岁，Ann Arbor分期Ⅲ～Ⅳ期36例（90.0％），IPI评分中高危、高危23例（57.5％）；25例（62.5％）有B症状，发热最为常见，其次为消瘦、盗汗；38例（95.0％）有结外侵犯；25例（62.5％）LDH升高；25例（62.5％）Ki-67≥80％；ALK阳性22例（55.0％），中位年龄29（14～67）岁，ALK阴性18例（45.0％），中位年龄51.5（19～67）岁，年龄差异有统计学意义（P＝0.003）。②40例患者均接受化疗，采用CHOP（环磷酰胺+多柔比星+长春地辛+泼尼松）方案18例，ECHOP（依托泊苷+CHOP）方案12例，其他方案10例；26例（65.0％）获得完全缓解（CR），ALK阴性（P＝0.029，OR＝13.458）和Ki-67≥80％（P＝0.04，OR＝14.453）是CR的独立影响因素，ECHOP方案的CR率高于CHOP方案［83.3％（10/12）对38.9％（7/18），P＝0.026］。③LDH水平、IPI评分、ALK表达情况以及化疗方案的选择对无进展生存（PFS）和总生存（OS）影响有统计学意义（P<0.05）。结论ALCL发病男性居多，青少年至中老年均有发病，ALK阳性中年轻患者居多，诊断时临床分期晚，多数患者有结外侵犯，半数以上患者有B症状、LDH升高、Ki-67高表达；ALK表达与否、Ki-67表达水平以及化疗方案的选择可影响疗效，LDH水平、IPI评分、ALK表达与否以及化疗方案的选择可影响PFS和OS；ECHOP是较优的化疗方案，可改善预后。

Albumin improves stratification in the low IPI risk patients with diffuse large B-cell lymphoma.

Previous studies showed albumin at diagnosis could be used to predict outcome in patients with diffuse large B-cell lymphoma (DLBCL), but whether albumin could improve the international prognostic index (IPI) risk stratification remains unknown. Herein, we retrospectively analyzed 440 de novo DLBCL patients in this study. The cutoff value of albumin was 39.2g/L. Patients with high serum albumin showed superior OS and PFS (p = 0.002 and p < 0.001, respectively). According to IPI, there were 163 patients (37.0%) in low-risk group, 107 (24.3%) in low-intermediate risk group, 114 (25.9%) in high-intermediate risk group and 56 (12.7%) in high-risk group. Further analysis showed high albumin could identify a subgroup of patients with extremely superior OS and PFS in low IPI risk patients (p = 0.022 and p = 0.034, respectively). Multivariate analysis revealed that high albumin was an independent prognostic factor for OS (relative ratio [RR] 0.122; 95% confidence interval [CI] 0.021-0.715, p = 0.020) and trend for PFS (RR 0.417; 95% CI 0.168-1.035, p = 0.059). In conclusion, our study suggests that albumin at diagnosis is a simple and effective prognostic factor in DLBCL patients, allowing the identification of a superior outcome subgroup in low-risk patients, which may help to guide treatment in clinical trial.

The value of three-dimensional echocardiography in risk stratification in pulmonary arterial hypertension: a cross-sectional study.

To explore the value of right ventricular (RV) parameters detected by three-dimensional echocardiography (3DE) in risk stratification in pulmonary arterial hypertension (PAH) patients. We prospectively recruited 130 pulmonary hypertension patients from National Center for Cardiovascular Diseases, Fuwai Hospital. Each participant was performed a transthoracic echocardiography and 3DE parameters were measured using an off-line software (4D RV Function 2.0, TomTec). Patients were classified into low, intermediate-high risk group based on 2015 ESC Guidelines. A total of 91 PAH patients (34 ± 12years old, 25 males) were enrolled, among which, 42 were classified into low risk group, while 49 were intermediate-high risk group. Compared with low-risk patients, those with intermediate-high risk had significantly larger 3DE-RV volumes, worse ejection fraction (EF) and tricuspid annular plane systolic excursion, and decreased longitudinal strain (LS). Receive operating characteristic curves illustrated all the 3DE parameters were able to predict intermediate-high risk stratification, especially 3D-RVEF (area under curve, 0.82, 95% CI 0.73-0.91, P < 0.001). And 3D-RVEF < 26.39% had a 81.6% sensibility and 73.8% specificity to predict intermediate-high risk stratification. Univariate and multivariate Logistic regression analyses identified 3D-RV end-diastolic (OR 1.02, 95% CI 1.01-1.03, P = 0.002) and end-systolic (OR 1.03, 95% CI 1.01-1.04, P < 0.001) volumes, 3D-RVEF (OR 0.82, 95% CI 0.75-0.90, P < 0.001) and LS of free wall (OR 1.17, 95% CI 1.05-1.31, P = 0.005) as independent predictors of intermediate-high risk stratification. In conclusion, RV volumes, EF and free wall strain detected by 3DE were independent predictors of intermediate-high risk stratification in PAH patients, among which, RVEF showed the best predictive capacity.

A Risk Score Combined Clinical and Molecular Profiles Identifies a High-Risk Subgroup within Intermediate-Risk Acute Myeloid Leukemia

Introduction Acute myeloid leukemia (AML) is categorized into favorable-, intermediate- and adverse-risk groups according to European LeukemiaNet (ELN) risk stratification. The intermediate-risk AML comprises a substantial proportion of AML, and even within the intermediate-risk AML, the biology and prognosis are highly different, which suggests that more prognostic factors are needed to be identified. Method A total of 265 newly diagnosed AML patients treated between January 2010 and January 2019 who had cryopreserved DNA for mutational analyses diagnosed and treated in Changhai Hospital were included. 121 patients were aged ≤ 65y, and classified as intermediate-risk (IR)-AML. A Custom Amplicon panel targeting exons of 210 genes was used for deep sequencing at diagnosis. We used a LASSO Cox regression model to achieve shrinkage and variable selection from prognostic factors (P&lt;0.1 in log-rank tests) to build risk score for predicting overall survival. A nomogram was constructed to display the risk of death in individuals. The discrimination of the risk score was measured by the concordance index (C-index) and areas under time-dependent receiver-operating characteristics (ROC) curves (AUCs), and the calibration of the risk score was explored graphically by calibration plots. Patients with IR-AML and aged ≤ 65y in The Cancer Genome Atlas (TCGA) data (n= 41) was used as a validation cohort. Results The median age was 44 (11-75) years, and 54% had normal karyotype. NRAS and CEBPA were the most recurrently mutated genes (both 26%), followed by KIT (24%), DNMT3A (23%), ARID1B (20%), FLT3-ITD (19%), PCLO (17%), and TET2 (17%). In univariate analyses, age ≥ 55 years, WBC ≥ 10×109/L , PLT &gt; 40×109/L, high LDH counts at diagnosis, DNMT3A and Signaling Pathway genes mutations and the number of mutated genes ≥ 8 were significantly associated with poor OS (P &lt; 0.05), and age ≥ 55 years, WBC≥ 10×109/L, DNMT3A and FLT3-ITD mutations were associated with worse relapse free survival(RFS, P &lt; 0.05). Three variables were incorporated in our scoring model by LASSO, including Signaling Pathway genes mutations (including NRAS, KIT, FLT3, KRAS etc), DNMT3A mutation and WBC≥ 10×109/L. A risk scoring model was developed incorporating the weighted coefficients of these variables:0.6749 × Signaling Pathway + 1.1147 × DNMT3A + 0.7829 × WBC. The risk score grouped IR-AML patients into two subgroups: intermediate-low risk (ILR, score &lt; 1, n= 48) and intermediate-high risk (IHR, score ≥ 1, n= 62) groups (Table1). Concordance index[OS: 0.703, 95% CI (0.643, 0.763); RFS: 0.681, 95%CI (0.620, 0.741)] demonstrated well discrimination power and calibration plots showed that the nomograms did well compared with an ideal model. The 3-year OS for ILR and IHR groups were 72.3% and 29.4% (P &lt; 0.0001), and 3-year RFS were 63.9% and 19.4% (P &lt; 0.0001), respectively (Figure 1A-B). The similar results were also observed in TCGA cohort (3-year OS 57.7% vs. 26.2%, P= 0.019; Figure 1C). The survival was equivalent for patients with ILR when treated with chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT, 3-year OS: 74.7% vs. 70.8%, P= 0.936, RFS: 76.4% vs. 55.0%, P= 0.225; Figure 2A-B). However, alloHSCT benefited patients with IHR. Patients who received alloHSCT had survival advantages over those who treated with chemotherapy only (3-year OS: 51.6% vs. 20.7%, P= 0.022; 3-year RFS: 38.1% vs. 7.8%, P= 0.008; Figure 2C-D). The prognosis of patients with IHR was as poor as those with adverse-risk AML (n=65 , 3-year OS: 29.5% vs. 33.3%, P= 0.794; 3-year RFS: 19.4% vs. 39.1, P= 0.294). Conclusions In this study, we developed and validated a novel scoring model that incorporated molecular and clinical profiles. According to our score model, IR-AML patients could be further stratified into two subgroups with distinct clinical outcomes. And the prognosis of patients with IHR was similar with patients with adverse-risk. Moreover, alloHSCT would override the poor outcome of patients with IHR. In summary, our scoring model might help identify patients with IR-AML who are most likely to benefit from alloHSCT. The results are needed to be validated in other independent cohorts and prospective studies before implementation into clinics. Disclosures No relevant conflicts of interest to declare.

P4363The predictive capacity of two- and three-dimensional echocardiography detected right ventricular strain in disease severity of pre-capillary pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) patients have poor prognosis due to progressive right ventricular (RV) dysfunction. As a low-cost and non-invasive tool, echocardiography is by far the most widely used technique to investigate the RV structure and function in PH patients. Recent studies showed that RV longitudinal strain (RVLS) measured by two- or three-dimensional echocardiography (2DE, 3DE) was correlated with RV function parameters and have the potential to predict the prognosis of PH patients. However, few studies have compared the value of 2DE- and 3DE- RVLS to predict disease severity of pre-capillary PH patients. Therefore, our study aims to compare the capacity of RVLS assessed by 3DE and 2DE in predicting disease severity of pre-capillary PH patients. Methods We consecutively enrolled 57 patients (18 males and 39 females, 35±13 years) with pre-capillary PH diagnosed by right heart catheterization in our center. Standard transthoracic echocardiography was performed in all participants. 2DE- RVLS were obtained from speckle-tracking analyses using GE EchoPAC version 201; while 3DE- RVLS were analyzed by TomTec 4D RV-Function 2.0. On the basis of the risk assessment strategy of 2015 ESC Guidelines for the diagnosis and treatment of pulmonary hypertension, all the participants were classified into low risk or intermediate-high risk groups. Linear regression analyses were performed to evaluate the correlations between RVLS and peak oxygen consumption (PVO2). In addition, receive operating characteristic curves (ROC) were used to compare the predictive values of 2DE- and 3DE-RVLS and identify the optimal cut points for the detection of low risk based on the risk assessment strategy of 2015 ESC Guidelines. Results Linear regression analyses showed a significant correlation between PVO2 and 2DE- RVLS (r=−0.484, P&lt;0.001), while a relatively weaker correlation was observed between PVO2 and 3DE- RVLS (r=−0.299, P=0.024). ROC curve showed 2DE-RVEF had a better capacity to classify pre-capillary PH patients into low or intermediate-high risk groups (2DE- vs 3DE-: AUC=0.78, P=0.003 vs AUC=0.69, P=0.044). Optimal cut-offs found 2DE-RVEF &lt;−13.85% had a 73.3% sensibility and 75.0% specificity to predict low risk. Conclusions Both two- and three-dimensional echocardiography detected RVLS had the potential to evaluate disease severity of pre-capillary PH patients, but the former may have a better predictive capacity.

Clinical Practice Pattern Of Adjuvant Vaginal Brachytherapy In Early-stage Endometrial Carcinoma According To ESMO-ESGO-ESTRO Risk Classification: Long-term updated Data From A Multi-institutional Analysis In China

To evaluate the clinical practice pattern of adjuvant vaginal brachytherapy (VBT) in early-stage endometrial carcinoma (EC) according to ESMO-ESGO-ESTRO risk classification in China from long-term updated data of a multi-institutional analysis. We retrospectively evaluated clinical data of patients with early-stage EC at 13 institutions in China between 2000 and 2015. Eligibility requirements included the primary hysterectomy/bilateral salpingo-oophorectomy and adjuvant radiotherapy, stage I and II disease (FIGO 2009 staging), and complete clinicopathologic and follow-up information. All patients were divided into low-risk (LR), intermediate-risk (IR), high-intermediate risk (HIR) and high-risk (HR) groups according to ESMO-ESGO-ESTRO risk classification. We evaluated clinical practice pattern and tendency of VBT in different risk groups during various periods. Proportions were compared by using the Chi square test for values of 5 or higher and with Fisher’s exact test for values of less than 5. All data were examined using statistical analysis software. A total of 1268 early-stage patients were reviewed and 1108 cases with intact data were included in the analysis. The median follow-up time was 53 months (range 6–207 months). The median age was 56 years (range 23–86 years). Stage Ia/b disease represented 86.0% of the cohort, HR patients 22.9%, HIR patients 20.0%, IR patients 29.2%. Patients received VBT alone (43.2%, n = 479), EBRT alone (14.3%, n = 158), EBRT+VBT (42.5%, n = 471), and chemotherapy (22.9%, n = 235). In HR and HIR groups, the proportion of VBT alone increased 33.3% (0 vs. 33.3%) and the proportion of VBT boost after EBRT decreased 10.5% (61.3% vs. 50.8%) from 2000 to 2015. In IR and LR groups, VBT alone increased 61.7% (4.7% vs. 66.4%) and VBT boost decreased 29.4% (51.6% vs. 22.2%) in the corresponding period. All institutions commonly use High-dose-rate(HDR) VBT. The commonly used applicators include the multichannel vaginal cylinder (77.7%), single channel vaginal cylinder (16.7%) and ovoids (5.6%). A fixed 3-4cm length of the proximal vagina was reported by 62.9%, a proximal 1/3-1/2 length of the vagina by 36.2%, and Entire vagina by 0.8%. Specify dose: 77.7% specify to 0.5-cm depth from the vaginal surface, and 22.3% specify elsewhere. There were 11 and 13 different dose-fractionation schedules for VBT alone and VBT boost, respectively. The most common fractionation for VBT alone and VBT boost is 5 Gy for six fractions and 5 Gy for two fractions, both to 0.5-cm depth. Our study provides an assessment of clinical practice pattern for adjuvant VBT management of early-stage EC in China. Historical data demonstrate that the clinical practice of adjuvant VBT alone increased significantly in different risk classification groups over the past 15 years, especially in IR to HR groups.

Role of Pelvic Lymphadenectomy in Intermediate-Risk Endometrial Cancer and Predictors of Nodal Positivity in Indian Patients.

One of the most intense controversies in endometrial cancer revolves around the need for lymphadenectomy at the time staging. The study carried out to analyze the role of staging with pelvic lymphadenectomy in intermediate-risk stage I endometrial cancer-stage IA grade III and stage IB grades I and II. Review analysis of all the patients with stage I carcinoma endometrium intermediate risk treated at our institution between January 2006 and December 2014. All demographic data, tumor factors, adjuvant treatment, follow-up, and recurrence were recorded. Sixty-five were in intermediate-risk group, of which 21 were in low intermediate- and 44 in high intermediate-risk group, with 4 patients with positive pelvic node in each group. In patients with low intermediate-risk stage IA, grade III tumors, the nodal involvement was substantial even when the myometrial invasion was less than 50%. All grade 1 tumors did not have pelvic nodal metastasis. Overall percentage of pelvic nodal metastasis in our review of intermediate-risk carcinoma endometrium was 12%, with 19% in stage IA, grade III tumors, and 9% with stage IB, grade I and II tumors. A systematic lymphadenectomy should be done in patients with endometrial cancer who are at intermediate to high risk of lymph node metastases. The grade III histology is more likely to predict for nodal metastasis more than depth of myometrial invasion. It is recommended to stratify patients into risk groups to formulate guidelines for therapeutic lymphadenectomy.

Risk stratification in normotensive acute pulmonary embolism patients: focus on the intermediate-high risk subgroup.

Patients with acute pulmonary embolism are at intermediate-high risk in the presence of imaging signs of right ventricular dysfunction plus one or more elevated cardiac biomarker. We hypothesised that intermediate-high risk patients with two elevated cardiac biomarkers and imaging signs of right ventricular dysfunction have a worse prognosis than those with one cardiac biomarker and imaging signs of right ventricular dysfunction. We analysed the cumulative presence of cardiac biomarkers and imaging signs of right ventricular dysfunction in 525 patients with intermediate risk pulmonary embolism (intermediate-high risk = 237) presenting at the emergency department in two centres. Studied endpoints were composites of all-cause mortality and/or rescue thrombolysis at 30 days (primary endpoint; n=58) and pulmonary embolism-related mortality and/or rescue thrombolysis at 30 days (secondary endpoint; n=40). Patients who experienced the primary endpoint showed a higher proportion of elevated troponin (47% vs. 76%, P<0.001), elevated N-terminal pro-brain natriuretic peptide (67% vs. 93%, P<0.001) and imaging signs of right ventricular dysfunction (47% vs. 80%, P<0.001). Multivariate analysis revealed N-terminal pro-brain natriuretic peptide (hazard ratio (HR) 3.6, 95% confidence interval (CI) 1.3-10.3; P=0.015) and imaging signs of right ventricular dysfunction (HR 2.8, 95% CI 1.5-5.2; P=0.001) as independent predictors of events. In the intermediate-high risk group, patients with two cardiac biomarkers performed worse than those with one cardiac biomarker (HR 3.3, 95% CI 1.8-6.2; P=0.003). Risk stratification in normotensive pulmonary embolism should consider the cumulative presence of cardiac biomarkers and imaging signs of right ventricular dysfunction, especially in the intermediate-high risk subgroup.

Utility of the relative apparent diffusion coefficient for preoperative assessment of low risk endometrial carcinoma

ObjectivesLymphadenectomy is not recommended for low risk stage I endometrial carcinoma (EC) patients. This study was to investigate the predictive value of apparent diffusion coefficient (ADC) values in predicting patients with low risk EC, and to identify an optimum ADC measurement for preoperative assessment. Materials and methodsEighty-one patients with stage I EC who underwent diffusion-weighted imaging (DWI) at 1.5T were included and divided into low group and intermediate-high risk group based on the ESMO-ESGO-ESTRO classification. Clinical indexes, conventional MRI parameters, minimum ADC values (minADC), mean ADC values (meanADC) and relative ADC values (rADC) were compared between those two groups. rADC was calculated using the equation ADC (cancer)/ADC (reference) with the obturator internus muscle as reference. The optimal ADC measurement and cut-off ADC value for low risk EC were calculated using the receiver operating characteristic (ROC) curve. ResultsThe low risk group had significantly higher meanADC, minADC, and rADC values than did the intermediate-high risk group (1.095 vs. 0.902 × 10−3 mm2/s, 0.755 vs. 0.657 × 10−3 mm2/s, 0.754 vs. 0.603, respectively). In assessments of low risk EC patients, the area under the curve (AUC) values for meanADC, minADC, and rADC were 0.840 (95%CI, 0.749,0.931), 0.681 (95% CI: 0.561,0.800), and 0.876(95% CI: 0.798,0.954), respectively. The optimal cut-off rADC value for prediction was 0.669, the maximum Youden index, sensitivity, specificity, and accuracy values were 0.683, 81.8%, 86.5%, and 84.0%, respectively. ConclusionsrADC is superior to minADC and meanADC for predicting patients with low risk EC, and could potentially aid to the surgical management of these patients in avoiding unnecessary lymphadenectomy.

The accumulation of metabolic syndrome components is associated with higher risk of positive surgical margin among patients with localized prostate cancer after radical prostatectomy.

ObjectiveTo evaluate the association between metabolic syndrome (MetS) and the accumulation of its components with prostate cancer (PCa).Patients and methodsPatients undergoing radical prostatectomy were retrospectively included. Patients were grouped by low risk and intermediate-high risk according to International Society of Urological Pathology grade. Multivariable logistic regression and Cox hazard regression model were utilized to assess the association of MetS with overall survival, biochemical recurrence, upgrading, upstaging, and positive surgical margin (PSM) after prostatectomy. Besides, trend test was also performed to evaluate the impact of the accumulation of MetS components on postoperative pathological feature.ResultsA total of 1,083 patients were eventually enrolled. With a median follow-up of 40.45 months, 197 patients were diagnosed with MetS. No significant association between MetS and survival outcomes and pathological features was found. However, we did notice that the accumulation of the MetS components could lead to an elevated gradient of the PSM risk in the entire cohort (one component: OR=1.46; two components: OR=1.89; ≥3 components: OR=2.07; P for trend=0.0194) and intermediate-high risk group (one component: OR=1.4; two components: OR=1.85; ≥3 components: OR=2.05; P for trend=0.0127).ConclusionThe accumulation of MetS components could lead to increasing risk of PSM on the entire PCa cohort and patients with intermediate-high risk PCa after prostatectomy, but not for the low-risk patients.

Impact of vaginal brachytherapy in intermediate and high-intermediate risk endometrial cancer: a multicenter study from the FRANCOGYN group.

ObjectiveAccording to recent European Society of Medical Oncology, European Society of Gynaecological Oncology and European Society of Radiotherapy and Oncology guidelines, adjuvant vaginal brachytherapy (VB) is optional in patients with intermediate risk (IR) and high-intermediate risk (HIR) endometrial cancer (EC). The aim of this French retrospective, multicenter study was to assess the impact of VB in these groups on local recurrence rate, local recurrence-free survival (RFS) and overall survival (OS).MethodsData of 191 patients with IR and HIR EC who underwent primary surgery with or without VB and no other adjuvant treatment between 2000 and 2016 were extracted from the FRANCOGYN database. Rate of local recurrence, OS and local RFS in these two groups were compared using the Kaplan-Meier method.ResultsThe number of patients with IR and HIR EC were 118 and 73 respectively. VB was used in 92 patients in IR group and 43 in HIR group. Median follow-up was 22 months. In the HIR group, the local recurrence rate was significantly higher in the no adjuvant therapy group in comparison with the VB group (16.7% and 0% respectively, p=0.02). There was also a significant improvement in local RFS (p=0.01) in VB group. In IR EC, there is no significant difference on local recurrence rate (4.2% and 3.2%, respectively, p=1.00) or local RFS (p=0.54) between the two groups.ConclusionsVB is an efficient adjuvant treatment for patients with HIR EC. VB is not associated with an improvement of RFS or OS in IR EC patient.

Prognostic significance of tumor grade in early-stage endometrioid endometrial cancer

Aim: Although tumor grade has no impact on endometrial cancer stage, it carries prognostic and therapeutic importance. Surgical management and adjuvant treatment following surgery in certain patients depends on a number of factors including tumor grade. Although grade 3 tumors are included in the high-intermediate risk group, there are data demonstrating that there is a slight difference in survival between patients with grade 1 and 2 tumors in early-stage disease. In this study, we aimed to investigate the association of grade with clinicopathological characteristics, recurrence-free and disease-specific survival in patients treated at our clinic and diagnosed with endometrioid endometrial cancer. Material and Methods: 279 patients with early FIGO Stage endometrioid endometrial cancer treated between 2009-2018 in a University hospital were included in the study. The associations between tumor grade with stage, lymphovascular space invasion (LVSI), myometrial invasion, tumor size, and survival were analyzed. Results: LVSI, ≥50% myometrial invasion, advanced stage and > 2 cm tumor size were significantly higher in grade 3 tumors compared to patients with grade 1 tumors. Recurrence-free and disease-specific survival were significantly lower in patients with grade 2 and 3 tumors compared to patients with grade 1 tumors. In multivariate analysis of RFS and DSS, tumor grade, LVSI and stage were independent prognostic factors. Conclusion: According to this study, grade 2 tumors may not differ significantly from grade 3 tumors in terms of survival. Therefore, due to the potential adverse prognosis associated with grade 2 and 3 tumors, vigilance for recurrence is warranted.

Albumin Improves Stratification in the Low IPI Risk Patients with Diffuse Large B-Cell Lymphoma

Our previous study showed albumin at diagnosis can be used to predict survival in diffuse large B-cell lymphoma (DLBCL) patients, but whether albumin could improve the international prognostic index (IPI) risk stratification in DLBCL remains unknown. Herein, we retrospectively analyzed 440 de novo DLBCL patients treated with R-CHOP in this study. The cutoff value of albumin for survival analysis was 34.4 g/L with an area under the curve value of 0.642±0.0037 (p<0.001) by receiver operating characteristic curve. Patients with low serum albumin showed worse overall survival (OS) and event-free survival (EFS) (p<0.001 and p=0.002, respectively). Multivariate analysis revealed that low serum albumin, independent of IPI, indicated different survival in both OS(relative ratio [RR] .0481; 95% confidence interval [CI], 0.294 - 0.789, p=0.004) and EFS (RR, 0.617; 95% CI, 0.419 - 907, p=0.014) in DLBCL patients.According to IPI, there were 170 patients (40.2%) in low risk group, 101patients (23%) in low-intermediate risk group, 97(22.0%) patients in high-intermediate risk group and 65 patients (14.8%) in high-risk group. Low IPI risk patients showed favorable survival (p<0.05). However, there were no significant survival difference in low-intermediate, high-intermediate and high-risk group (p>0.05). Especially low albumin could identify a subgroup of patients with poorer overall survival in low/ low-intermediate IPI risk patients (p = 0.003). In conclusion, our study suggests that albumin at diagnosis is a simple and effective prognostic factor in DLBCL patients,allowing the identification of an inferior outcome subgroup in low/ low-intermediate DLBCL patients, which may help to guide treatment. DisclosuresNo relevant conflicts of interest to declare.

Impact of Total Dose Intensity and Relative Dose Intensity (RDI) of R-CHOP on Survival in Patients with DLBCL

Background: The standard chemotherapy for diffuse large B-cell lymphoma (DLBCL) is CHOP combined with rituximab (R-CHOP). The guidelines (e.g. NCCN or ESMO) recommend six to eight courses of R-CHOP and the optimal number of courses is still unclear. The relative dose intensity (RDI) was proposed as an indicator for both dose intensity and interval. The previous studies have reported the relation between RDI of CHOP or R-CHOP and treatment outcomes. However, little is known about the low threshold of RDI that affects survival and few studies have compared between RDI and total dose of R-CHOP in the effect on survival. In this study, we evaluated the effect of total dose and RDI of R-CHOP on survival in patients with DLBCL.Patients and methods: We retrospectively analyzed 190 patients with newly diagnosed DLBCL who completed more than 6 courses of R-CHOP between January 2013 and December 2016 at our center. Dose reduction of the CHOP regimen was considered in patients over 70 years of age. RDI was calculated as the ratio of delivered dose intensity (mg/m2/week) to the planned dose intensity (mg/m2/week) and was shown as a percentage. The average of RDI in each drug of R-CHOP was used for the analyses. Risk factors for overall mortality were analyzed using Cox proportional hazards models.Results: Among the 190 patients, median age was 70.0 years (range, 34-91). The numbers of patients were 15, 55, 46, and 66 in low, low-intermediate, high-intermediate, and high risk groups based on the International Prognostic Index (IPI), respectively. Three-year overall survival (OS) was 88%, 100%, and 83% in the patients with 6 (N=64), 7 (N=3), and 8 (N=123) courses of R-CHOP, respectively (p = 0.55). Median RDI was 92% (range, 32 to 117) and the lower quartile of RDI was 72%. Probabilities of OS by the quartile of RDI were shown in Figure 1 and OS was significantly worse in the patients with <72% of RDI than those with ≥72% of RDI (3-year OS, 66% vs 90%; p = 0.001). Subgroup analysis by age (<70 or ≥70 years) showed the similar trend toward worse survival in patients with <72% of RDI in both age groups (<70 years, p=0.001; ≥70 years, p = 0.054). In multivariable analysis, RDI less than 72% (HR, 2.94; 95% CI, 1.25-6.90, p = 0.014) was a significantly important risk factor for mortality, while IPI (HR, 3.2; 95% CI, 0.9-11.4, p = 0.07) or the number of courses of R-CHOP (HR, 1.66; 95% CI, 0.59-4.64, p = 0.34) was not. When analyzing RDI as a continuous variable, RDI (HR, 1.03; 95% CI, 1.01-1.05, p = 0.009) and IPI (HR, 1.49; 95% CI, 1.05-2.12, p = 0.027) were identified as significant risk factors for mortality. Similarly, patients with <72% of RDI had significantly worse progression-free survival (PFS) than those with ≥72% of RDI (Figure 2, 3-year PFS, 59% vs 80%; p = 0.001). However, RDI was not a significantly important risk factor for PFS after adjusting for several factors. Among 190 patients in our cohort, 24 patients died and 17 patients died from recurrence of DLBCL. There is no difference in the number of recurrence between the patients with <72% (N=6) and ≥72% (N=11) of RDI (p = 0.18).Conclusions: Higher RDI of R-CHOP was significantly associated with a higher survival rate in patients with DLBCL, although it did not reach statistical significance in patients over 70 years of age. More than 72% of RDI should be maintained to obtain better OS and PFS. Increase of total dose of R-CHOP was not related to better survival, resulting from the analysis using the number of treatment courses. We conclude that 6 courses of R-CHOP therapy with higher RDI would be recommended for all ages. Further studies are needed to validate our findings. [Display omitted] DisclosuresMinami:Novartis Pharma K.K.: Consultancy; Takeda Pharmaceutical Company Limited.: Consultancy; ONO PHARMACEUTICAL CO., LTD: Research Funding.

Predictive value of IABP SHOCK II risk score on in-hospital mortality of patients with cardiogenic shock after ST segment elevation myocardial infarction

Objective To evaluate the predictive value of IABP SHOCKⅡ risk score in in-hospital mortality of patients with ST segment elevation myocardial infarction complicated with cardiogenic shock (CS). Methods From August 2011 to August 2013, the clinical data of 89 patients with cardiogenic shock after STEMI treated with primary PCI and then supported by using IABP were retrospectively analyzed. The IABP SHOCKⅡ risk score were calculated from the data at admission and primary PCI. Comparisons of general information, medication and intervention, pre/post IABP vital life signs and in-hospital death were carried out among patients with different risk stratifications. Results The area under ROC curve of risk stratification was 0.723. The patients were categorized into low risk group (score 0-2, n=71) and intermediate-high risk group (score 3-9, n=18).The patients in intermediate-high risk group were with advanced age, high rate of diabetes mellitus, history of stroke, renal insufficiency, higher serum lactate and glucose at admission compared with low risk group. And more patients in intermediate-high risk group had impaired post-PCI coronary flow (TIMI flow grade<3). Conclusions The IABP SHOCKⅡ risk score is a simple and useful risk score for predicting in-hospital mortality of STEMI patients complicated with CS. Though the patietns are treated with primary PCI and then supported by IABP, the in-hospital mortality of patients with IABP SHOCKⅡ risk score≥3 increases significantly. Key words: Intra-aortic balloon pump; ST segment elevation myocardial infarction; Cardiogenic shock; Primary percutaneous intervention; IABP SHOCKⅡ risk score; In-hospital mortality

Comparison of International Guidelines for Assessment of Suspected Stable Angina: Insights From the PROMISE and SCOT-HEART

ObjectivesThis study sought to compare the performance of major guidelines for the assessment of stable chest pain including risk-based (American College of Cardiology/American Heart Association and European Society of Cardiology) and symptom-focused (National Institute for Health and Care Excellence) strategies. BackgroundAlthough noninvasive testing is not recommended in low-risk individuals with stable chest pain, guidelines recommend differing approaches to defining low-risk patients. MethodsPatient-level data were obtained from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test probability was determined and patients dichotomized into low-risk and intermediate-high–risk groups according to each guideline’s definitions. The primary endpoint was obstructive coronary artery disease on coronary computed tomography angiography. Secondary endpoints were coronary revascularization at 90 days and cardiovascular death or nonfatal myocardial infarction up to 3 years. ResultsIn total, 13,773 patients were included of whom 6,160 had coronary computed tomography angiography. The proportions of patients identified as low risk by the American College of Cardiology/American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%, 19.8%, and 38.4% within SCOT-HEART. All guidelines identified lower rates of obstructive coronary artery disease in low- versus intermediate-high–risk patients with a negative predictive value of ≥0.90. Compared with low-risk groups, all intermediate-high–risk groups had greater risks of coronary revascularization (odds ratio [OR]: 2.2 to 24.1) and clinical outcomes (OR: 1.84 to 5.8). ConclusionsCompared with risk-based guidelines, symptom-focused assessment identifies a larger group of low-risk chest pain patients potentially deriving limited benefit from noninvasive testing. (Scottish Computed Tomography of the Heart Trial [SCOT-HEART]; NCT01149590; Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)

Second primary malignancies after high-dose-rate 60Co photon or 252Cf neutron brachytherapy in conjunction with external-beam radiotherapy for endometrial cancer

PurposeSecond primary malignancies (SPMs) may occur in organs after radiotherapy (RT). This study aimed to determine the rate and distribution of SPMs for photon- or neutron-emitting radiotherapy sources for patients treated for primary endometrial cancer. Methods and MaterialsThe cohort comprised 426 patients with 5334 patient-years of observation. Patients were treated by different methods of RT from 1990 to 2000. Patients received postoperative 60Co external-beam radiotherapy (43.4%), external-beam radiotherapy + high-dose-rate (HDR) intracavitary brachytherapy with 60Co or 252Cf (42.3%), or HDR intracavitary brachytherapy alone with 60Co or 252Cf (14.3%). ResultsOver a 25-year period, 47 SPMs were observed (21 for HDR 60Co and 26 for HDR 252Cf). SPMs were observed for 13 patients in the high-intermediate risk group for each radiation source. Patients treated with 60Co developed SPMs in the urinary tract (1.2%) and in lymphoid/hematopoietic tissues (1.2%). Only three SPM cases (0.7%) were observed in digestive tract. In comparison, the patient group treated with 252Cf developed SPMs in the digestive tract (1.4%) with the majority in the colon (1.2%), urinary tract (0.9%) primarily the kidneys, and vulva (0.7%). All other SPMs (4.9%) were in the low-risk group. Of these, SPMs in the skin were most prevalent (1.6%) for 60Co, and breast (1.6%) for 252Cf, but believed to be caused by factors other than treatment. SPM incidence in the digestive and urinary tracts were similar (2.1%), regardless of radiation source. ConclusionsFor followup at 25 years, 47 SPMs were observed with no differences in the high-intermediate risk group depending on the RT source.

Risk stratification of acute pulmonary embolism based on clinical parameters, H-FABP and multidetector CT

IntroductionRisk stratification of normotensive patients with acute pulmonary embolism (PE) includes the assessment of right ventricular dysfunction (RVD), biomarker levels, and a clinical score as suggested by the 2014 guidelines of the European Society of Cardiology (ESC). We performed an external validation of the prognostic performance of Heart-type Fatty Acid Binding Protein (H-FABP) and incorporated it into the new ESC algorithm. Material and methodsH-FABP was measured by fully-automated immunoturbidimetry in 716 patients from the PROTECT study (PROgnosTic valuE of CT scan in haemodynamically stable patients with acute symptomatic PE). ResultsH-FABP ranged from 0.7 to 123.6 ng/ml (median 4.13; IQR, 2.53–6.61) and was above the cut-off of 6 ng/ml in 209 patients (29.2%). A complicated course within 30 days (death, catecholamine administration, mechanical ventilation, resuscitation) occurred in 1.1% (n = 3) of the 271 low risk patients with a simplified Pulmonary Embolism Severity Index (sPESI) of 0 and was particular low (0.4%), if H-FABP levels were normal. In the case of elevated H-FABP, 4.3% of patients suffered complications despite sPESI of 0. The risk for an adverse 30-day outcome increased for patients of the intermediate-low and intermediate-high risk group and was highest for the combination of sPESI ≥1 with RVD on MDCT and elevated H-FABP (odds ratio 12.3, 95% confidence interval, 3.49–43.32; P < 0.001). ConclusionsH-FABP is suitable for risk stratification of normotensive PE patients if integrated in the new ESC algorithm and may help to identify patients with higher risk for adverse clinical events.

Significance of abnormal peritoneal cytology on survival of women with stage I–II endometrioid endometrial cancer

ObjectiveTo examine survival of women with stage I–II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). MethodsThis is a multi-center retrospective study examining 1668 women with stage I–II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. ResultsMalignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P<0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P<0.001) and cause-specific survival (hazard ratio 3.42, P=0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P=0.001) but not local-recurrence (5.2% versus 3.0%, P=0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P<0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P=0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P=0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P=0.63). ConclusionOur study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I–II endometrioid endometrial cancer, particularly for low-risk group.