High-intermediate Risk Group Research Articles

Not all high-intermediate risk endometrial cancers are created equal: recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy in all possible subgroups of early-stage high-intermediate risk endometrial cancer

<h3>Objectives:</h3> Historically, patients with early-stage high-intermediate risk (HIR) endometrioid endometrial cancer (EC) have been known to benefit from improved recurrence-free survival (RFS) with the use of adjuvant therapy. However, specific subgroups of HIR patients may benefit from observation ± vaginal brachytherapy (VB) only. We sought to evaluate RFS and cause-specific survival (CSS) after observation ± VB in the subgroups of early-stage HIR endometrioid EC. <h3>Methods:</h3> We identified patients with early-stage HIR endometrioid EC, who underwent a total hysterectomy, bilateral salpingo-oopho-rectomy, and sentinel lymph node biopsy or pelvic ± paraaortic lymphadenectomy at Mayo Clinic and Cleveland Clinic between 1999 and 2016. HIR group was defined based on revised GOG99 criteria used in the GOG249 trial: age ≥70 with 1 risk factor, age ≥50 with 2 risk factors, or all the 3 risk factors (grade 2-3, ≥50% myometrial invasion, or positive lymphovascular space invasion [LVSI]). HIR subgroups were determined by all possible combinations of risk factors, and 3-year RFS, site-specific RFS, and CSS were estimated. <h3>Results:</h3> Among 1,507 women with stage I or II EC, 447 stage I endometrioid EC patients were identified who fulfilled HIR criteria, and 349 (78.1%) were managed with observation ± VB. Eleven subgroups were defined and evaluated (Table). Among stage IA patients (1-5 subgroups), subgroup 5 (G3 ≥50y LVSI+) had the lowest RFS and CSS of 68.9% (46.6-100.0%) and 86.7% (71.1-100.0%), respectively, whereas the remaining 4 subgroups had 3-year RFS and CSS >90%. In all stage IA subgroups, 3-year lymphatic RFS was >90%; 3-year distant RFS was lowest in subgroup 5 (79.6% [56.9-100.0%] and 97.1% [91.8-100.0%] in subgroup 3 [G2 ≥50y LVSI+]). Additionally, 3-year CSS was <100% in these two subgroups (vs. 100% in subgroups 1, 2, and 4). Among the 6 stage IB subgroups (6-11), 3-year RFS ranged from 68.2% (48.6-95.7%) to 93.6% (87.7-99.9%) and 3-year CSS from 80.0% (58.7-100.0%) to 100.0% (100.0-100.0%). Lymphatic recurrence was observed in subgroup 8 (IB G2 ≥50y LVSI -), but site-specific RFS was >90%. Conversely, all stage IB subgroups experienced distant recurrence; 3-year distant RFS ranged from 73.1% (53.5-99.7%) to 96.5% (91.8-100.0%). 3-year distant RFS lower than 90% was observed in those subgroups with grade 3 or positive LVSI (7, 9, 10, and 11). <h3>Conclusions:</h3> Our results suggest that observation ± VB can be sufficient in some subgroups of stage I endometrioid HIR patients, specifically stage IA endometrioid HIR EC without the concomitant presence of grade 3 and LVSI. Among stage IB endometrioid HIR EC subgroups, particularly those with grade 3 or LVSI, observation ± VB is associated with lower RFS and CSS. Stratifying HIR patients into risk subgroups would alleviate the risk of overtreatment and undertreatment among patients with early-stage endometrioid EC; in this regard, the molecular characterization will provide a further instrument to achieve this objective.

Validation of the NCCN-IPI and the Geltamo-IPI in a Large Cohort of Patients Diagnosed of Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP/R-CHOP-like in a Single Institution

▪Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the identification of risk groups is important to plan different therapeutic strategies. The International Prognostic Index (IPI) has been an easy and universal prognostic index during the past 20 years. New prognostic indexes are needed to improve the identification of higher risk groups. The objective of this study is to validate and compare the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) and the Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO-IPI) in a large cohort of DLBCL patients treated homogeneously with immunochemotherapy in a single institution.Methods: 371 adults with de novo DLBCL consecutive diagnosed from 2004 to 2016 at Insitut Català d'Oncologia in Barcelona and treated with curative intention based on immunochemotherapy [310(81%) R-CHOP, 61 (19%) R-CHOP-like] were included in the analyses. Prognostic indexes were compared in patients with complete data: NCCN-IPI vs. IPI (371 patients) and GELTAMO IPI vs. IPI (268 patients). All survival curves were obtained by the Kaplan-Meier method, and compared using the log-rank test.Results: The number of patients in the low risk (LR), low-intermediate risk (LIR), High-intermediate risk (HIR) and high risk (HR) groups are shown in table 1. OS curves for each prognostic index are shown in Figure 1. In all the risk indexes, the four risk groups had 5-yearOS and PFS rates with significant differences in the global comparisons. The NCCN-IPI discriminated better low-risk subgroups than IPI (5-year OS: 90.6% vs 75.5%, respectively). The GELTAMO-IPI compared to IPI improved the discrimination of the LR group (5-year OS: 81.8% vs 75.5%, respectively) and the HR group (5-year OS: 26.4% vs 39.4%, respectively).Conclusion: GELTAMO-IPI has been validated in an independent cohort of patients equally treated in a single centre. GELTAMO-IPI is a good prognosis index capable of differentiating a high-risk group with a 5-year OS of 26% unlike NCCN-IPI and IPI. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Absolute Lymphocyte Count Is Associated with the Prognosis in Patients with Peripheral T-Cell Lymphoma, Not Otherwise Specified

IntroductionPeripheral T-cell lymphomas (PTCLs) are a heterogeneous group of tumors that belong to the category of aggressive lymphomas and are roughly subdivided into specified and not otherwise specified (NOS) types. Clinically, the International Prognostic Index (IPI) has been the effective prognostic model to discriminate the prognosis of patients with PTCL-NOS. Also, Prognostic Index for T-cell lymphoma (PIT) has been proposed, which further modified to the Bologna score (modified PIT, mPIT). However, no simple prognostic marker has been satisfactory in predicting treatment outcomes in patients with PTCL-NOS. In this study, we investigate the association between absolute lymphocyte count at diagnosis and the prognosis of patients with PTCL-NOS.MethodsAs a retrospective study, we searched the Lymphoma Registry of Asan Medical Center and Inje University Sanggye Paik Hospital. From April 2001 to Jun 2016, we identified 131 patients diagnosed with PTCL-NOS initially treated with CHOP or CHOP-like regimens. Patients diagnosed with PTCLs other than PTCL-NOS and primary cutaneous lymphoma were excluded. Event-free survival (EFS) was calculated from the date of diagnosis to the date of disease progression, treatment failure, relapse, or death from any cause. Overall survival (OS) was calculated from the date of diagnosis to the date of death from any cause. Lymphopenia was defined as absolute lymphocyte count < 1000 / μL. The association between clinical characteristics and response was analyzed by the Fisher's exact test. Survival curves were analyzed by the Kaplan-Meier method and compared with the log-rank test.ResultsAmong 131 patients, 42 (32.1%) patients showed lymphopenia, 58 (44.3%) patients showed B symptoms, and 46 (35.1%) patients showed bone marrow involvement. The median absolute lymphocyte count was 1392/μL (range, 61-10092/μL). According to the International Prognostic Index (IPI) scores, 33 (25.2%) patients belonged to the low risk group (L), 36 (27.5%) to the low-intermediate risk group (LI), 38 (29.0%) to the high-intermediate risk group (HI), and 24 (18.3%) to the high risk group (H).In univariate analysis, treatment outcomes including CR, EFS, and OS were associated with lymphopenia, B symptoms, performance status, lactate dehydrogenase, extranodal involvement, Ann Arbor stage, IPI risk group, and the Prognostic Index for T-cell lymphoma (PIT) risk groups. After multivariate analysis, lymphopenia was independently associated with CR (≥1000 vs. <1000, odd ratio [OR]: 2.899, 95% confidence interval [CI]: 1.229-6.841, P=0.015), EFS (≥1000 vs. <1000, hazard ratio [HR]: 0.523, 95% CI: 0.339-0.807, P=0.003), and OS (≥1000 vs. <1000, HR: 0.599, 95% CI: 0.375-0.955, P=0.031). IPI risk group was also associated with CR (L/LI vs. HI/H, P <0.001), EFS (P <0.001), and OS (P <0.001).ConclusionsAbsolute lymphocyte count is an independent prognostic factor for the patients with PTCL-NOS. Lymphopenia (<1000/μL) at diagnosis was associated with worse prognosis of patients with PTCL-NOS. Because the absolute lymphocyte count easily obtained from the initial complete blood count, it seems to be simple prognostic factors to estimate the prognosis of patients with PTCL-NOS. The larger scaled study is warranted to confirm our result. DisclosuresNo relevant conflicts of interest to declare.

PO28: Overview on Adjuvant Vaginal Brachytherapy in Stage I to II Endometrial Carcinoma According to ESMO-ESGO-ESTRO Risk Classification: Long-Term Data from a Multi-Institutional Analysis in China

Purpose: This research aimed to perform an overview on adjuvant vaginal brachytherapy (VBT) in stage I to II endometrial carcinoma (EC) according to ESMO-ESGO-ESTRO risk group consensus in China from multi-institutional analysis.Materials and Methods: We retrospectively analyze patients with stage I to II EC at 13 institutions in China treated between 2003 and 2015. All patients underwent adjuvant radiotherapy and were divided into low-risk (LR), intermediate-risk (IR), high-intermediate risk (HIR) and high-risk (HR) groups according to ESMO-ESGO-ESTRO risk group consensus.

Venous thromboembolism associated with combined oral contraceptive use: a single-institution experience.

ObjectiveCombined oral contraceptives (COCs) are used for various reasons. However, venous thromboembolism (VTE), a significant side effect, can be fatal. This study reports the first case series in Korea involving patients with COC-associated VTE registered at a university hospital.MethodsThis study recruited 13 patients diagnosed with COC-associated VTE between June 2006 and May 2018. Risk factors, including age, body mass index, smoking habits, estrogen dosage, type of progestin, and duration of COC use, were evaluated.ResultsAmong patients with VTE, 9 showed pulmonary embolism (PE) concomitant with deep vein thrombosis (DVT). However, the remaining patients showed DVT (1 patient), PE (1 patient), and cerebral venous thrombosis (2 patients). The median duration between the onset of symptoms and a hospital visit was 3 days, and it sometimes took as long as 32 days. Among the 10 patients with PE, 1 high-risk group and 2 intermediate-high risk groups were treated with tissue plasminogen activators before anticoagulants. There were no cases of recurrence among patients who continued to take anticoagulants for 3 months.ConclusionThese findings emphasize that healthcare professionals who prescribe or dispense COCs to women must inform them of the risk of VTE, including the risk factors, differences in risk depending on the type of progestin present in the product, and pertinent signs and symptoms. Efforts should also be made to inform patients of VTE, even through information campaigns such as brochures. Most importantly, women should remain alert for signs and symptoms of VTE when using COCs.

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer.

Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.

Evaluation of GELTAMO-IPI for Patients with Diffuse Large B-cell Lymphoma

To evaluate the prognostic value of GELTAMO-IPI for patients with diffuse large B-cell lymphoma (DLBCL). The clinical data of 238 newly diagnosed DLBCL patients treated in Shanxi Cancer Hospital from September 2011 to March 2016 were collected retrospectively, the risk stratification and prognostic evaluation of the patients were analyzed according to GELTAMO-IPI. Progression-free survival (PFS) and overall survival (OS) of the patients were analyzed by the Kaplan-Meier method, COX regression analysis was used to compare the risk of death and progress in each risk group. Harrell's C statistics was used to compare the prognostic stratification ability of each model. The 3-year OS rate statistics showed that both IPI and GELTAMO-IPI could distinguish low risk group and Low-intermediate risk group, but the prognosis stratification ability of IPI was better (IPI: HR=5.085, P<0.05; GELTAMO-IPI; HR=4.639, P>0.05). GELTAMO-IPI could distinguish High-intermediate risk group from high risk group (GELTAMO-IPI: HR=2.966, P<0.05; 3 years OS rate was 34.5%), but the ability of IPI to identify high risk groups was weak (3 years OS>50%). The results of Harrell's C statistics showed the C-index of IPI and GELTAMO-IPI was 0.687 and 0.721 (P<0.001); the C-index of the predicted PFS was 0.672 and 0.700 (P<0.001). It was suggested that the prognostic stratification ability of GELTAM0-IPI be superior to that of IPI, R-IPI, NCCN-IPI. GELTAMO-IPI can make a clear distinction between DLBCL patients with different prognosis, especially for high-risk patients, and the prognostic stratification ability of GELTAMO-IPI is significantly better than that of IPI.

Thrombolysis in Acute Pulmonary Embolism: Are we overdoing it?

Aim and Methods:We aimed to study the clinical data and outcome of patients admitted in our center with acute pulmonary embolism (PE) over a 5-year period from May 2013 to April 2018. The main outcome data included were: in - hospital bleeding, in - hospital right ventricular (RV) function improvement, pulmonary arterial hypertension improvement, duration of hospital stay, and 30- and 90-day mortality.Results:A total of 114 (69 m, 55 f) patients with the mean age of 55 ± 15 years were included. Patients who had involvement of central pulmonary trunk called as “Central PE” group (n = 82) and others as “Peripheral PE” group (n = 32). There were more women in the peripheral PE group (53.1% vs. 34.1%, P = 0.05), while RBBB (22% vs. 3.1%, P = 0.02) and RV dysfunction (59.8% vs. 25%, P = 0.002) were noted more in the central PE group. Systemic thrombolysis was done in 53 patients (49 central, 4 peripheral), of which only 3 had hypotension and 28 patients were in the Intermediate-high risk group. The overall inhospital, 30-day, and 90-day mortalities were 3.6, 13.2, and 22.8%, respectively. Bleeding was significantly higher in the thrombolysis group compared to the nonthrombolysis group (18.9% vs. 0, P = 0.0003). However, improvement in pulmonary hypertension was noted more in thrombolysis group compared to nonthrombolytic group (49% vs. 21.2%, P = 0.01).Conclusion:This retrospective data from a tertiary center in South India showed that short- and mid-term mortality of patients with PE still remains high. The high nonguideline use of thrombolysis has been reflected in the increased bleeding noted in our study.

L1CAM is not a reliable predictor for lymph node metastases in endometrial cancer, but L1CAM positive patients benefit from radiotherapy.

Purpose: Several studies evidenced the potential of L1CAM as a prognostic marker in endometrial cancer. The aim of this study was to investigate whether L1CAM can predict lymph node metastasis and could therefore be used preoperatively to identify patients with low to high-intermediate risk endometrial cancer who would profit from a lymphadenectomy and an adjuvant treatment. To avoid unnecessary morbidity, de-escalating strategies are still required.Methods: Immunohistochemistry for L1CAM was performed on curettage or hysterectomy specimens from 212 patients diagnosed with endometrial cancer who were treated at the University Hospital Basel during 2011-2019. L1CAM expression was correlated with clinicopathological features such as histological subtype, FIGO stage, lymph node metastasis, lymphadenectomy, adjuvant treatment and outcome.Results: Using a cut off ≥10%, L1CAM was positive in 41/212 patients (19.3%) and negative in 171/212 patients (80.7%). L1CAM was associated with high-risk features such as non-endometrioid histology, high tumour grade, and high FIGO stage. There was no significant correlation between L1CAM expression and lymph node metastasis. However, patients with L1CAM positive tumours showed improved disease-specific survival if treated with adjuvant radiotherapy.Conclusion: Although L1CAM expression pointed towards aggressive tumour biology, preoperative L1CAM analysis did not add any substantial predictive information regarding lymph node metastasis in low to high-intermediate risk groups. Therefore, L1CAM status is not suitable to tailor the surgical algorithm for lymph node staging. Nevertheless, our results suggest that L1CAM could be used as a predictive biomarker to select patients who may benefit the most from adjuvant radiotherapy.

Serum solubleB7-H3is a prognostic marker for patients with non-muscle-invasivebladder cancer.

B7-H3 is a member of the B7 family of immune-regulatory ligands and is a costimulatory molecule promoting the T cell response in vitro. We herein investigated the clinical utility of serum soluble B7-H3 (sB7-H3) in patients with non-muscle invasive bladder cancer (NMIBC). We analyzed 555 patients in whom NMIBC was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum sB7-H3 (sB7-H3) level using the enzyme-linked immunosorbent assay (ELISA) and evaluated the utility of sB7-H3 as a prognostic biomarker for NMIBC. We used the Cox proportional hazards regression model to assess recurrence-free survival (RFS) and progression-free survival (PFS) with the sB7-H3 level. We detected high levels of sB7-H3 in the sera of 47% of patients with NMIBC versus only 8% in healthy donors. The increase of sB7-H3 was significantly associated with poor RFS and PFS. Multivariate analysis showed that elevated sB7-H3 was an independent prognostic factor of RFS and PFS. According to the European Organization for Research and Treatment of Cancer (EORTC), in intermediate-low and intermediate-high risk groups, the presence of sB7-H3 significantly determined the rate of recurrence and progression. Our data suggested that evaluating serum sB7-H3 expression is a useful tool for predicting the prognosis of patients with NMIBC.

Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

A New Risk Stratification Model (R2-ISS) in Newly Diagnosed Multiple Myeloma: Analysis of Mature Data from 7077 Patients Collected By European Myeloma Network within Harmony Big Data Platform

A New Risk Stratification Model (R2-ISS) in Newly Diagnosed Multiple Myeloma: Analysis of Mature Data from 7077 Patients Collected By European Myeloma Network within Harmony Big Data Platform

Pre-operative physical performance as a predictor of in-hospital outcomes in older patients undergoing elective cardiac surgery

ObjectiveRisk stratification of cardiac surgery patients is usually based on the Society of Thoracic Surgeons (STS) score, that has limited predictive value in older persons. We aimed assessing whether the Short Physical Performance Battery (SPPB) improves, beyond the STS score, assessment of hospital prognosis in older patients undergoing elective cardiac surgery. MethodsAll patients aged 75+ years referred for elective cardiac surgery to Careggi University Hospital (Florence, Italy) from April 2013 to March 2017 were evaluated pre-operatively. Participants were classified according to the STS-Predicted Risk Of Mortality (STS-PROM): low (<4%), intermediate (4 to 8%), and high risk (>8%). Primary study outcomes were hospital mortality and STS-defined major morbidity. Length of hospital stay was an additional outcome. ResultsOut of 235 participants (females: 46.5%; mean age: 79.6 years), 144 (61.3%) were at low, 67 (28.5%) at intermediate and 24 (10.2%) at high risk, based on the STS-PROM. SPPB (mean±SEM) was 8.8 ± 0.2, 7.0 ± 0.5, and 6.0 ± 0.8 in participants at low, intermediate, and high risk, respectively (p<0.001). The primary outcome occurred in 62 participants (26.4%). In low-risk participants, the SPPB score predicted the primary endpoint (adjusted OR 0.77, 95% CI 0.66–0.89 per each point increase; p<0.001) controlling for STS-Major Morbidity or Operative Mortality (STS-MM) score. This result was not observed in the intermediate-high risk group. ConclusionsSPPB predicts mortality and major morbidity in older patients undergoing elective cardiac surgery, classified as low risk with the STS risk score. The SPPB, applied preoperatively, might improve risk stratification in older patients undergoing elective cardiac surgery.

Value of 18F-FDG PET/CT for prognostic stratification in patients with primary intestinal diffuse large B cell lymphoma treated with an R-CHOP-like regimen.

The prognostic value of 18F-FDG PET/CT for primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) patients has not been determined. This prompted us to explore the value of 18F-FDG PET/CT for prognostic stratification in patients with PI-DLBCL treated with an R-CHOP-like regimen. Seventy-three PI-DLBCL patients who underwent baseline PET/CT between January 2010 and May 2019 were included in this retrospective study. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were computed using the 41% SUVmax thresholding method. Progression-free survival (PFS) and overall survival (OS) were used as endpoints to evaluate prognosis. During the follow-up period of 3-117months (29.0 ± 25.5months), high TLG, non-germinal center B-cell-like (non-GCB) and high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) were significantly associated with inferior PFS and OS. TLG, cell-of-origin and NCCN-IPI were independent predictors of PFS, and both TLG and NCCN-IPI were independent predictors of OS. The grading system was based on the number of risk factors (high TLG, non-GCB, high NCCN-IPI) and patients were divided into 4 risk groups (PFS: χ2 = 33.858, P < 0.001; OS: χ2 = 29.435, P < 0.001): low-risk group (none of the 3 risk factors, 18 patients); low-intermediate risk group (1 risk factor, 24 patients); high-intermediate risk group (2 risk factors, 16 patients); and high-risk group (all 3 risk factors, 15 patients). High TLG, non-GCB and high NCCN-IPI can identify a subset of PI-DLBCL patients with inferior survival outcomes. Furthermore, the grading system can identify PI-DLBCL patient groups with markedly different prognoses, which might contribute to the adjustment of the therapeutic regime.

Recurrence- and progression-free survival in intermediate-risk non-muscle-invasive bladder cancer: the impact of conditional evaluation and subclassification.

To assess the change in rates of recurrence-free survival (RFS) and progression-free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS. A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study. The conditional RFS rate at 1, 2, 3, 4 and 5years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence-free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC. Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.

Clinical relevance of high–intermediate risk endometrial cancer according to European risk classification

ObjectiveRisk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology...

Incorporating molecular markers in standard prognostic models for DLBCL patients using real-world data.

e19251 Background: NCCN-IPI is a prognostic scoring system that outperforms other risk classification mechanisms in diffuse large B-cell lymphoma (DLBCL) but does not consider the molecular profile of patients. We evaluated the predictive value of NCCN-IPI and clinically relevant molecular markers on the overall survival (OS) of patients with diagnosed DLBCL in real-world data (RWD). Methods: Patients diagnosed with DLBCL were identified in the COTA RWD population, and then subset to those with sufficient attributes to calculate NCCN-IPI at diagnosis (age, stage, LDH ratio, performance status, extranodal disease) and those who received a monoclonal antibody targeting CD20 (n = 383). This population was further filtered to patients tested for BCL-2, BCL-6, and C-MYC (n = 176). Disease characteristics were summarized using descriptive statistics and chi-square tests of independence were performed to assess the relationship between NCCN-IPI Risk-Group and molecular marker results. A Cox proportional hazard model was used to identify prognostic features of OS. Results: There were statistically significant relationships between NCCN-IPI Risk-Group and both BCL-2 (p = 0.007) and C-MYC (p &lt; 0.001) after Bonferroni correction for the number of molecular markers tested. A Cox proportional hazard model with the three molecular markers as covariates revealed a statistically significant correlation between the presence of C-MYC alteration and decreased OS (HR = 2.02, CI: 1.24-3.32, p = 0.005). However, when NCCN-IPI Risk-Group was added as a covariate, the relationship between C-MYC and OS was no longer significant. The hazard ratios associated with high-intermediate and high risk groups were larger than that of the low-intermediate group. All three of these risk groups were statistically significant in the model (p &lt; 0.038). Conclusions: The inclusion of molecular markers to the NCCN-IPI prognostic model did not increase predictive power in this RWD cohort. We validated the NCCN-IPI model and found it to be a robust tool for classifying risk and estimating OS in patients who have received a CD20 monoclonal antibody. A larger sample size would increase power to further explore the impact of molecular markers on overall survival. [Table: see text]

Malignant peritoneal cytology and decreased survival of women with stage I endometrioid endometrial cancer

BackgroundTo examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. MethodsThis is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. FindingsMalignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56–2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16–1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high–intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20–2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01–2.68). In the high–intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14–0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53–1.14). InterpretationMalignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.

Коагуляційні властивості cистеми зсідання крові при гострій тромбоемболії легеневої артерії та їх зміни на тлі проведеної системної тромболітичної терапії в пацієнтів з різним ризиком госпітальної летальності

Мета роботи – оцінити динаміку змін коагуляційних властивостей крові в пацієнтів з гострою тромбоемболією легеневої артерії (ТЕЛА) до і після проведення системної тромболітичної терапії (ТЛТ), порівнюючи групи з високим і проміжним-високим ризиком.Матеріали і методи. Проведене ініціативне контрольоване проспективне нерандомізоване дослідження результатів лікування 45 пацієнтів з первинним епізодом гострої ТЕЛА, яким здійснено ТЛТ у відділенні інтенсивної терапії. Досліджувану вибірку становили 29 (64 %) чоловіків і 16 (36 %) жінок віком у середньому (55,6±13,6) року. Відповідно до рекомендацій Європейського товариства кардіологів (2014) проведена стратифікація на нестабільних пацієнтів з високим ризиком з гіпотонією або епізодом синкопе (1-ша група, 28 (62 %) осіб) і пацієнтів з нормальним артеріальним тиском з проміжним-високим ризиком (2-га група, 17 (38 %) осіб) і значним двобічним емболічним навантаженням, верифікованим мультидетекторною спіральною комп’ютерною томографією в ангіорежимі (U1-2=2,2; р=0,33), ознаками дисфункції правого шлуночка і позитивними біомаркерами пошкодження міокарда. Ризик 30-денної летальності за PESI відповідає V (ІV) класу: в 1-й групі – (152±19) балів, у 2-й – (138,0±9,7) бала (p1-2&lt;0,01).Результати та обговорення. В обох групах виявлена подібна (р1-2&gt;0,25) первинна прокоагуляційна спрямованість змін за показниками тромбіноутворення обох ланок активації гемокоагуляції: протромбіновий час збільшений до 19,8 [16; 23] с, протромбіновий індекс – до 96,1 [86; 106] %. Зменшення активованого часткового тромбопластинового часу (АЧТЧ) до 23,5 [21; 24] с підтвердило визначену спрямованість гемостазу шляхом контактної коагуляції. Виявлено збільшений вміст основного коагуляційного субстрату фібриногену – до 4,3 [4,1; 4,5] г/л (р1-2=0,25) і маркерів тромбінемії: розчинного фібрину – до 17,0 [16; 18] мг, D-димеру – до 5214 [3605; 5643] нг/мл. Початково пригнічена системна фібринолітична активність – значення спонтанного фібринолізу зменшені до 9,5 [6,0; 12,2] %, власна ретракція – до 31,9 [26,1; 36,1] %. На 5-ту добу після проведеної ТЛТ на тлі базисної терапії динаміка виявилася насамперед підвищенням (Z=5,62; р&lt;0,00001) значень АЧТЧ до (46,1±6,0) с (р1-2=0,36), протромбінового часу – до 22,9 (18–26) с, рівень фібриногену зменшився до 3,5 г/л. Незважаючи на сприятливі зміни, залишалися збільшеними маркери тромбінемії – значення фібрину зменшилися (Z=3,03; р&lt;0,001) до 13,7 мг, але перевищували верхню межу референтного діапазону в обох групах (р1-2=0,21). Збільшилися значення спонтанного фібринолізу до 11,9 % [9,9; 12,4], власної ретракції (Z=2,64; р&lt;0,01) – до 32,0 % [27,9; 33,0], при цьому залишаючись значно зниженими за референтні, що засвідчує збереження високого ризику рецидиву тромбоемболічних подій.Висновки. У пацієнтів з гострою ТЕЛА, незалежно від наявності високого або проміжного-високого ризику, за даними коагулограми спостерігається однаковий за силою та спрямованістю прокоагулянтний стан гемостазу, пригнічення фібринолітичної активності, зменшення щільності згустка in vitro. На 5-ту добу після ТЛТ на тлі базисної антикоагулянтної терапії: попри певний рівень «терапевтичної» антикоагуляції, зберігається достатньо високий рівень маркерів тромбінемії, пригнічення фібринолізу та ретракції. Наявність однакових за силою та спрямованістю коагуляційних змін, особливо виснаження фібринолітичних механізмів гемостазу, позитивний клінічний вплив ТЛТ у групі з проміжним-високим ризиком засвідчують доцільність проведення ТЛТ у цій групі хворих.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB – grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group. Impact statement What is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous. What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups. What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.