High-intermediate Risk Group Research Articles

Syncope as a subject of the risk assessment of pulmonary thromboembolism to be used for: A cross-sectional study.

Syncope is infrequent in pulmonary thromboembolism (PTE) yet might be indicative of haemodynamic instability. The prognostic role of syncope in PTE has not been well documented. In this study, the association between risk classification of the European Society of Cardiology and syncope was investigated in the normotensive PTE patients. We retrospectively screened electronic medical records of patients who were admitted in 2 tertiary care hospital and diagnosis of PTE with computed tomography pulmonary angiography. Patients with hypotension (high risk) at the time of admission were excluded from the study. Of 5% patients (16/322) had syncope with the proportion of 81.3% (13/16) in the intermediate high risky group, 18.7% (3/16) in intermediate low risk group and 0% in low risk group. Mortality rate was higher in subjects with syncope (25% vs 11.1%) although it was not it was not statistically significant (P = NS). In those with syncope, the central venous thrombus was more frequent than those without it (78.6% vs 30.1%, P = .008). Only heart rate and intermediate high-risk group were retained as independent predictors of syncope selection in the multivariate logistic regression. Although syncope is positively correlated with the severity of PTE, it does not predict the prognosis alone. Nonetheless, syncope in patients with PTE can be considered as an important alarming stimulus for clinical course.

Impact of the 21-gene recurrence score assay in clinical treatment and prognosis analysis for patients with hormone receptor positive early-stage breast cancer

Objective: To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer. Methods: The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS). Results: Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04). Conclusions: The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.

Preoperative MR imaging for ESMO-ESGO-ESTRO classification of endometrial cancer.

To retrospectively investigate whether magnetic resonance imaging (MRI) findings could contribute to predict histologic type, tumor grade and lymphovascular space invasion (LVSI) to improve preoperative assessment of endometrial cancer using the European Society for Medical Oncology (ESMO) European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynecological Oncology (ESGO) classification. Between January 2008 and August 2014, 104 women (mean age, 65±11 [SD] years; range, 32-84 years) with International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer underwent preoperative MRI of the pelvis. Two independent readers evaluated tumor heterogeneity and measured tumor size on T2-weighted, diffusion-weighted and T1-weighted images obtained after gadolinium chelate administration at 2minutes. The apparent diffusion coefficient (ADC) was generated from pixel ADC from the whole tumor volume. A short axis>24mm on MRI was associated with histopathologic type 2, grade 3 tumor and presence of LVSI (P<0.01). There were no significant differences in minimum, mean and maximum ADC between presence/absence of LVSI. In 9.1% women (9/99), the accuracy of the ESMO-ESGO-ESTRO classification with the inclusion of the MRI short-axis criterion was higher than that of the conventional ESMO classification to predict high-risk recurrence endometrial cancer (P=0.02). Tumor size reflects histologic type, tumor grade and LVSI in endometrial cancer. FIGO stage 1 endometrial cancer>24mm should be classified preoperatively in the high-intermediate or high-risk recurrence risk groups.

Interim 18F-FDG PET/CT improves the prognostic value of S-IPI, R-IPI and NCCN-IPI in patients with diffuse large B-cell lymphoma.

The current study aimed to explore whether the efficiency of the standard International Prognostic Index (S-IPI), revised-IPI (R-IPI) and enhanced-IPI (NCCN-IPI) in evaluating the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) may be improved by interim 18F-FDG PET/CT. A total of 185 patients with newly diagnosed DLBCL were enrolled in the current study. All patients underwent interim PET/CT following the 4th cycle of chemotherapy. Patients were divided into different risk groups using S-IPI, R-IPI and NCCN-IPI and further subdivided into risk groups using interim PET/CT. Interpretations were evaluated for 2-year progression-free survival (PFS) and overall survival (OS). With a median follow-up time of 44 months, the 2-year PFS and OS were 60% [95% confidence interval (CI) 53–67%] and 81% (95% CI 74–86%), respectively. Analysis of S-IPI and NCCN-IPI identified no significant difference in PFS and OS between high intermediate and high risk groups. However, there were significant differences in the PFS and OS between the low and low intermediate risk groups (P<0.01). Interim PET/CT was used to redistribute patients in the higher risk group into PET negative and positive groups (P<0.01) and arallel results were observed in the lower risk group. In R-IPI, interim PET/CT identified a significant difference between PFS and OS in the good and poor risk groups but not in the very good risk group. Therefore, the results of the current study indicate that S-IPI, R-IPI and NCCN-IPI are three clinically useful prognostic indexes for patients with DLBCL. Interim PET/CT may improve the prognostic value of S-IPI, R-IPI and NCCN-IPI in predicting 2-year PFS and OS, particularly in patients with a high IPI score.

RISK STRATIFICATION BASED ON NCCN‐IPI AT THE TIME OF DIAGNOSIS IN COMBINATION WITH POST‐TREATMENT PET‐CT SCAN FOR THE TREATMENT OF NODAL PERIPHERAL T‐CELL LYMPHOMA

Background: Nodal peripheral T-cell lymphomas (PTCLs) consist of PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large-cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+), and ALCL-ALK−. Clinical assessments before and after treatment are essential to predict survival in nodal PTCL. However, limited data are available regarding the prognostic significance of National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) as a pre-treatment clinical tool and post-treatment PET-CT scan indicating tumor viability in patients with nodal PTCL. The primary aim was to establish a risk model for nodal PTCL based on NCCN-IPI and post-treatment PET-CT scan. Method: In this retrospective, multicenter, cohort study, patients were eligible if they were diagnosed with nodal PTCL from Jan 2005 to June 2016, received systemic chemotherapy, and had the results of PET-CT scan at the time of diagnosis and at the end of treatment, which was assessed using 5-point Deauville score. The study excluded ALCL-ALK+. Results: A total of 396 patients were screened. Seventy patients were excluded from the analysis: unavailable pre- or post-treatment PET scans, no systemic treatment, uncertain histology, and ALCL-ALK+. Thus, 326 patients were analyzed. The median age was 61 years (range, 18–86) and 209 (64%) were male. PTCL-NOS (N = 172, 53%) was the most common subtype, and AITL (N = 111, 34%) and ALCL-ALK− (N = 43, 13%) followed. Patients were categorized into low (N = 42, 13%), low-intermediate (LI, N = 108, 33%), high-intermediate (HI, N = 136, 42%), and high (N = 40, 12%) risk groups according to the NCCN-IPI. Based on the Deauville criteria, post-treatment PET-CT scan was scored as 1 (N = 130, 40%), 2 (N = 47, 14%), 3 (N = 60, 18%), 4 (N = 27, 8%), and 5 (N = 62, 19%). Because the number of progression in Deauville score 3 (40/60, 67%) was significantly different from score 2 (21/47, 45%; P = 0.023) and 4 (24/27, 89%; P = 0.030), we categorized patients into 3 groups: Deauville score 1–2, 3, and 4–5. With a median follow-up of 54.7 months (IQR, 30.2–84.5), 5-year PFS rate was 35.7% (95% CI, 30.0–41.4), and OS rate was 47.1% (95% CI, 40.8–53.4). NCCN-IPI risk and post-treatment PET-CT scan were independently associated with PFS in multivariate analysis (for LI NCCN-IPI, hazard ratio [HR] 1.615, 95% CI 0.838–3.113; HI NCCN-IPI, HR 3.063, 95% CI 1.626–5.769; high NCCN-IPI 4.475, 95% CI 2.231–8.977; P < 0.001: for post-treatment Deauville score 3, HR 1.895, 95% CI 1.281–2.801; score 4–5, HR 6.916, 95% CI 4.948–9.667; P < 0.001). We stratified patients into 5 groups based on risk of progression: low (low NCCN-IPI and Deauville score 1–2), INT-1 (low NCCN-IPI and score 3, or LI NCCN-IPI and score 1–2), INT-2 (HI NCCN-IPI and score 1–2), high (high NCCN-IPI and score 1–2, or LI to high NCCN-IPI and score 3), and very high (score 4–5). The risk model showed a strong association with PFS and OS (Figure 1). Keywords: peripheral T-cell lymphomas (PTCL); positron emission tomography (PET); prognostic indices.

The Enhanced International Prognostic Index for Diffuse Large B-cell Lymphoma

ObjectiveTo explore the prognostic value of the enhanced International Prognostic Index (NCCN-IPI) for Asian patients with diffuse large B-cell lymphoma (DLBCL) treated in the rituximab era. Materials and MethodsWe performed a retrospective analysis of 176 patients with newly diagnosed DLBCL. The estimated overall survival (OS) and progression-free survival (PFS) of the different risk groups were discriminated by the International Prognostic Index (IPI), the revised International Prognostic Index (R-IPI) and the NCCN-IPI. ResultsWith a median follow-up of 18 months, at 3 years, the OS was 73% and the PFS was 65%. The 3-year OS for the 4 NCCN-IPI risk groups were 91% versus 80% versus 57% versus 45% (P < 0.001); the 3-year PFS were 77% versus 72% versus 56% versus 26% (P < 0.001). The 3-year OS of the 4 risk groups discriminated by the IPI ranged from 85-55% (P < 0.001); the 3-year PFS ranged from 81-41% (P < 0.001). The 3-year OS of the 3 distinct prognostic groups by the R-IPI ranged from 86-51% (P < 0.001); the 3-year PFS ranged from 86-47% (P < 0.001). The 3-year OS and PFS of the high-risk group according to the NCCN-IPI were lower than the IPI and R-IPI. Using the NCCN-IPI, the outcomes among the risk groups spanned a large range, and the survival of the high-risk group was significantly different from the high-intermediate risk group. ConclusionsThe NCCN-IPI is a clinically useful prognostic index for patients with DLBCL treated in the rituximab era, especially for high-risk patients.

Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group.

The European Society of Medical Oncology (ESMO)/European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy & Oncology (ESTRO) classification for endometrial cancer (EC) now includes a high-intermediate risk (HIR) group of recurrence due to the adverse prognostic role of lymphovascular space involvement (LVSI) and grade 3 for women at intermediate risk. However, optimal surgical staging, and especially the place of lymphadenectomy, remains to be elucidated. We aimed to establish whether systematic nodal staging should be part of surgical staging for women with HIR EC. We abstracted from a prospectively maintained multicentre database the data of 181 women with HIR EC based on uterine factors (endometrioid type 1, grade 1-2 tumors with deep (≥50%) myometrial invasion and unequivocally positive LVSI, and those with grade 3 tumors with <50% myometrial invasion regardless of LVSI status), who received primary surgical treatment between January 2001 and December 2013. We recorded frequency of lymph node (LN) metastases in those who underwent nodal staging. The secondary outcomes were overall survival and recurrence patterns. Overall, 145 (80.1%) women underwent nodal staging consisting of at least pelvic lymphadenectomy. Of these, 62 (42.7%) had LN disease (9.7% with micrometastases). The respective 5-year overall survival rates according to LN status were 85.0% (95% confidence interval [CI] 76.5-91.4), 71.8% (95% CI 61.9-80.4) and 36.0% (95% CI 26.6-46.2) for women with negative LN, positive LN, and unstaged (p=0.047). Unstaged women were more likely to experience nodal recurrence than surgically staged/LN negative women (p=0.05). Systematic nodal staging should be part of surgical staging for women with apparent ESMO/ESGO/ESTRO HIR EC. Sentinel LN biopsy (SLNB) could be an option in this specific setting that may possiblysubstitute comprehensive staging, for the identification of patients with lymphatic dissemination.

Rebounds after discharge from the emergency department for community-acquired pneumonia: focus on the usefulness of severity scoring systems.

Background:Community-acquired pneumonia (CAP) is common cause of hospital admission and leading cause of morbidity and mortality. Severity scoring systems are used to predict risk profile, outcome and mortality, and to help decisions about management strategies.Aim of the work and Methods:To critically analyze pneumonia “rebound” cases, once discharged from the emergency department (ED) and afterwards admitted. We conducted an observational clinical study in the acute setting of a university teaching hospital, prospectively analyzing, in a 1 year period, demographic, medical, clinical and laboratory data, and the outcome.Results:249 patients were discharged home with diagnosis of CAP; 80 cases (32.1%) resulted in the high-intermediate risk class according to CURB-65 or CRB-65. Twelve patients (4.8%) presented to the ED twice and were then admitted. At their first visit 5 were in the high-intermediate risk group; just 4 of them were in the non-low risk group at the time of their admission. The rebound cohort showed some peculiar abnormalities in laboratory parameters (coagulation and renal function) and severe chest X-rays characteristics. None died in 30 days.Conclusions:The power of CURB-65 to correctly predict mortality for CAP patients discharged home from the ED is not confirmed by our results; careful clinical judgement seems to be irreplaceable in the management process. Many patients with a high-intermediate risk according to CURB-65 can be safely treated as outpatients, according to adequate welfare conditions; we identified a subgroup of cases that should worth a special attention and, therefore, a brief observation period in the ED before the final decision to safely discharge or admit. (www.actabiomedica.it)

Improved overall survival with adjuvant radiotherapy for high-intermediate and high risk Stage I endometrial cancer

Background/purposeTo perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. Material/methods132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. Results104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT+VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p<0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731–0.867; p<0.001) and 0.783 (95% CI: 0.693–0.885; p<0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. ConclusionsIn Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival.

NCCN-IPI Is Superior to aaIPI and IPI in Predicting Survival of DLBCL in the Rituximab Era

ObjectiveInternational prognostic index (IPI) has been widely used for predicting outcome in diffuse large B cell lymphoma. Although the introduction of rituximab to chemotherapy has dramatically improved the outcome of DLBCL, it also changed the prognostic value of IPI. The National Comprehensive Cancer Network IPI (NCCN-IPI) and age-adjusted IPI (aaIPI) were used to evaluate the prognosis for DLBCL in the rituximab era. However which one of them is more powerful in predicting survival remains unknown in Chinese patients.Patients and MethodsA total of 334 patients with de novo diffuse large B-cell lymphoma diagnosed from 2003 to 2012 were included. All patients were treated with CHOP with or without rituximab. They were divided into CHOP and R-CHOP groups. IPI, NCCN-IPI and aaIPI score were recorded. Survival was performed according to the Kaplan-Meier (K-M) curves using the log-rank test. The predictive abilities of PI, NCCN-IPI and aaIPI were investigated by Harrell's C-statistics.ResultCompared with the IPI, the NCCN-IPI and the aaIPI had better discrimination in different scores in all patients treated with or without rituximab. Both the NCCN-IPI and aaIPI had power in discriminating low, low-intermediate and high-intermediate risk groups. In comparison, the NCCN-IPI discriminated low-intermediate and high-intermediate risk groups (5-year overall survival [OS]: 74% vs 50%) better than the aaIPI (5-year OS: 80% vs 62%) in all patients and in the R-CHOP group with the NCCN-IPI 5-year OS: 85% vs 67% while the aaIPI: 87% vs 77%. In the CHOP group, the aaIPI discriminated low-intermediate and high-intermediate risk groups better (5-year OS: 70% vs 25%) than the NCCN-IPI (5-year OS: 60% vs 24%). According to the Harrel C statistic, the NCCN-IPI showed higher discrimination of the different scores (C_index: 0.669 ) than the aaIPI (C_index: 0.663 ) in all the patients (C_index: 0.669 vs. 0.663), especially in the R-CHOP group (C_index: 0.681 vs. 0.636). In the CHOP group, the aaIPI had stronger power (C_index: 0.711 ) than the NCCN-IPI (C_index: 0.683 ) in discriminating different scores.ConclusionThe NCCN-IPI is more powerful than the IPI for predicting survival in the rituximab era. In patients aged 60 or younger and treated with CHOP without rituximab, aaIPI is a preferable tool for evaluating prognosis. DisclosuresNo relevant conflicts of interest to declare.

Prognostic Value of NCCN-IPI and Interim PET/CT Based on Visual Assessment in the Treatment of Peripheral T Cell Lymphomas

BackgroundIt has been well known that peripheral T cell lymphoma (PTCL) has undergone poor prognosis compared with other non-Hodgkin lymphomas (NHL). Although the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) has been proposed to determining prognosis for patients with diffuse large B-cell lymphoma (DLBCL) at 2014, there is no study examines whether NCCN-IPI could apply to the T-cell NHLs. In addition, a few studies suggest prognostic utility of interim PET/CT in PTCL, but the role of interim PET/CT is not clear.PurposeWe evaluate the predictive efficacy of the NCCN-IPI and interim PET/CT based on visual assessment in patients with newly diagnosed PTCLs.MethodsThis study included 153 patients with de novo peripheral PTCLs, diagnosed from January 2010 to August 2015. The NCCN-IPI was calculated as following the original references. Survival outcomes were compared with a matched result of IPI and/or Prognostic Index for peripheral T cell lymphoma, unspecified (PIT). Visual assessment of interim PET/CT based on Deauville five point scales was performed at the time of diagnosis, mid-treatment and completion of CHOP/CHOP-like or other non-anthracycline chemotherapy.ResultsThe subtypes of PTCLs included PTCL, not otherwise specified (PTCL-NOS) (26%), angioimmunoblastic T cell lymphoma (20%), anaplastic large cell lymphoma (13%), extranodal NK/T cell lymphoma, nasal type (35%), and the others (6%). The NCCN-IPI showed better risk-based prognostic discrimination than IPI and PIT, especially between high-intermediate and high risk subgroups (3-year overall survival 40% vs. 27% vs. 26% among the high-intermediate risk group, respectively; 3-year overall survival 15% vs. 33% vs. 32% among the high risk group, respectively) with a median follow-up of 25.1 months (Figure 1). The absolute difference of survival rates between the low and high risk groups was 75% based on the NCCN-IPI stratification compared with 45% on the IPI stratification or 54% on the PIT stratification, respectively. When divided into two histologic subgroups (nodal vs. extra-nodal type), the NCCN-IPI showed considerable discriminatory capacity in both histologic groups. However, the IPI or PIT classification could not have discrimination in extra-nodal PTCLs. The interim PET-CT was significantly predicting for progression free survival in all PTCL patients, however, it also showed no predictive value in the patients with extranodal PTCLs, especially NK/T cell lymphoma.ConclusionsThe NCCN-IPI is a powerful prognostic model in PTCLs predicting overall survival among high-intermediate and high risk patients. Also, interim PET/CT response based on visual assessment could be a valuable prediction tool in nodal PTCLs, however, it should be carefully interpreted in the treatment of extranodal subtypes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Serum Albumin and Peripheral Blood Neutrophils at Diagnosis May Provide Additional Prognostic Information in Primary Nodal Diffuse Large-B-Cell Lymphoma Patients Treated with R-CHOP

Background and Aim: Diffuse large B-cell lymphoma (DLBCL) can present both as a primary nodal or extranodal neoplasm. Some studies claimed a separate origin for nodal and extranodal lymphomas and it has been even suggested that these could be regarded as separate nosological entities. However, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP), and the prognostic stratification is performed by the Enhanced Revised International Prognostic Index (NCCN-IPI), identifying 4 distinct [low (L), low-intermediate (LI), high-intermediate (HI) and high (H)] risk groups (RGs). A lot of new prognostic markers such as serum albumin (SA), serum β2-microglobulin (B2M), hemoglobin level (Hb), absolute neutrophil (ANC), lymphocyte (ALC), monocyte (AMC) and platelet counts etc. have been introduced into the clinical practice to perform better pts' stratification. However, data on the importance of these factors particularly in primary nodal (PN) DLBCL pts are still limited. Therefore, we aimed to access the prognostic impact of these markers regarding overallsurvival (OS) across the different NCCN-IPI RG of R-CHOP treated PN-DLBCL pts.Patients and Methods: We retrospectively reviewed the clinical outcome of 174 R-CHOP treated PN-DLBCL pts at a median age 58.4 years. Pts were stratified using NCCN-IPI into L (24.1%), LI (43.1%), HI (24.7%) and H (8.1%) RGs. Laboratory levels of SA, B2M, Hb, ANC, ALC, AMC and PC were recorded, and LMR and NLR - calculated. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, Hb, ANC, ALC, AMC, PC, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models.Results: The estimated 5-year OS was 79.4%, 51.5%, 20.1% and 16.2% for NCCN-IPI L, LI, HI and H-risk pts, respectively (p<0.001). Univariate analysis showed that inferior OS was associated significantly with decreased SA (≤39.4 g/L), elevated B2M (>3.2 mg/L), elevated ANC (>5.19 x 109), reduced ALC (≤1.38 x 109), elevated AMC (>0.515 x 109), decreased LMR (≤1.77), increased NLR (>2.97), lower Hb level (≤134 g/L), presented as dichotomized variables. Multivariate analysis confirmed the independent prognostic impact only for SA (p<0.001) and ANC (p=0.011).Based on the dichotomized SA and ANC values a SA/ANC prognostic index (PI) was created stratifying pts into 3 RG: favorable (F) [SA >39.4 g/L and ANC ≤5.19 x 109], intermediate (I) [SA ≤39.4 g/L or ANC >5.19 x 109] and poor (P) - risk [SA ≤39.4 g/L and ANC ≤5.19 x 109] populations. The estimated 5-year OS differed significantly in SA/ANC PI RG, as follows: 92.8% in F-RG, 48.4% in I-RG, and 0% in P-RG (p<0.001). Median OS for I- and P- SA/ANC PI RG was 2.54 and 1.13 years, respectively and not reached for the F-risk pts.We sought to determine whether the SA/ANC PI may provide additional prognostic information within the NCCN-IPI RG. No statistics could be calculated within the L-RG due to the low number of deaths - 9.5% (4/42), and in the H-RG due to the low number of patients (n=14), respectively. However, within the LI-RG the SA/ANC PI allowed us to discriminate 3 subgroups, characterized by significant differences in the OS (p<0.001): no patient within the P-RG was alive at 5years and the median OS was only 1.13 years; while 5-years OS was 77% and 87.7% in the I-RG and F-RG, respectively, and the median was not reached in both RG. Similarly, within the NCCN-IPI HI-RG the application of SA/ANC PI allowed us to discriminate 3 subgroups, characterized by significant differences in OS: no patient within the P-RG was alive at 5 years and the median OS was 1.29 years; while 5-years OS was 30.6% (median OS - 1.66 yrs) in the I-RG and 100% (median OS not reached) in the F-RG. The introduction of the SA/ANC PI allowed for defining favorable subgroups within the IPI LI- and HI RGs with 5-yrs OS comparable to IPI L-RG.Conclusion: The present study provided evidence for the independent prognostic significance ofSA and ANC in regard to survival in patients with PN-DLBCL. Adding these variables to prognostic models such as the NCCN-IPI score might improve the predictive ability, particularly within the NCCN-IPI LI and HI risk groups, where the introduction of SA/LMR PI allowed for identifying favorable subgroups comparable to the NCCN-IPI L-RG in terms of OS. DisclosuresNo relevant conflicts of interest to declare.

Preliminary Report for Outcome of Treatment with Differentiation Agents Plus Combination Chemotherapy during Induction Phase in High Risk Acute Promyelocytic Leukaemia

BACKGROUND: With the advent of differentiating agents like all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), acute promyelocytic leukemia (APL) nowadays has achieved highest cure rate among acute myeloid leukemias worldwide. However, in Myanmar, remission rate is relatively low (less than 60%) due to high early deaths from coagulopathy, infection and differentiation syndrome (DS). Resource constraints in molecular diagnosis also delay the treatment. High abandonment is also a major problem. As beneficial effects of ATO and ATRA as well as anthracycline and cytarabine on outcome of APL have been reported in recent literatures, they all are combined in local protocol developed to achieve maximum benefit during induction particularly for high risk patients. This preliminary study report the induction outcome of combination of both ATRA and ATO plus two chemotherapeutic agents in high risk APL patients treated at North Okkalapa General Hospital of Myanmar.METHODS: Molecularly or cytogenetically confirmed newly diagnosed APL patients presented during January 2014 to June 2016 were stratified into high and low or intermediate risk groups according to the Sanz’s risk score. High risk patients were treated with oral ATRA 45mg/m2 /day started once diagnosis was suspected together with combined chemotherapy (IV Daunorubicin 45mg/m2 /day x 3 days plus IVI Cytarabine 100mg/m2 /day for 7 days). After receiving molecular or cytogenetic confirmation of PML-RARA fusion transcript, IVI ATO 0.15mg/kg/day was added until complete remission (CR). Low and intermediate risk patients were considered as high risk and chemotherapy was added when WBC count was rapidly raised above 10 x 109/L during first 10 days of induction. Prednisolone 0.5mg/kg/day was added during first 10 days in all patients. Transfusion support was given according to standard transfusion guidelines. Remission assessment by morphology and RT-PCR for molecular remission (mCR) was done at the end of induction. Second induction was repeated if there was no molecular remission after first induction.RESULTS: Among21 APL remained after 4 early deaths, 18 were treated with high risk protocol where 8 cases (44%) were classified as high risk at entry and 10 intermediate patients (56%) were added due to rapid rise in white cell counts. Median age was 29 years (range 12 to 56 years). Male to female ratio was 1.6:1. Five (28%) were variant form and 13 (72%) were typical APL. Median white cell and platelet count were 21.8 x 109/L and 31 x 109/L respectively. The most common grade 3 or 4 complication during induction period was infection, especially blood stream and catheter related infection (9 patients) and respiratory tract infection (7 patients) followed by differentiation syndrome (6 patients).Fourof 18 high risk APL patients (22%) died during induction period due to documented severe respiratory tract infection. Remaining 14 patients who completed induction achieved CR (77.78%). Of 14 who achieved haematologic remission at the end of first induction, 10 (71.43%) had molecular remission. The remaining 4 patients who were also in morphologic CR achieved mCR after second induction. All proceeded to consolidation without chemotherapy and remained in remission till the time of this report.CONCLUSION: Although induction mortality rate of 22% is still high in this combination treatment due to limitation in intensive care support, there were no mortality from coagulopathy or DS. All high risk APL who completed induction in this study achieved high rate of early molecular remission (mCR). As the molecular remission status is documented to be associated with lower relapse, those patients are still hopeful of prolonged survival even if they are unable to attend follow-up frequently. By improving supportive care, and survival could be improved with minimal chemotherapy in even in high risk disease. DisclosuresNo relevant conflicts of interest to declare.

Incidence of neonatal hyperbilirubinemia in low, intermediate-low, and intermediate-high risk group infants

Background Neonatal hyperbilirubinemia is commonly found in newborns. Assessment of the risk of hyperbilirubinemia and information on the average time of the occurrence of hyperbilirubinemia are important to prevent the development of severe hyperbilirubinemia.Objective To find out the incidence of and the time of the development of hyperbilirubinemia in healthy-term newborns.Method A cohort prospective study was done on healthy-term newborns born at Hasan Sadikin Hospital between November and December 2009. Subjects were divided into 4 groups of risk at discharged, based on Bhutani nonnogram. A serial bilirubin level measurement were perfonned within 6 days.Resu l ts One of 14 newborns at low risk group developed hyperbilirubinemia but did not need phototherapy. Six of 14 newborns at intermediate-low risk group developed hyperbilirubinemia, 2 of them needed phototherapy with total serum bilirubin level of 14.7 mg/dL at 57 hours and 19.8 mg/dL at111 hours. Nine of 15 newborns of intennediate-high risk group developed hyperbilirubinemia, 1 of them needed phototherapy with total serum bilirubin level of 16.6 mg/dL at 76 hours. There was no newborn cathegorized as high risk group in this study. The median time the occurrence of hyperbilirubinemia in intennediate-low and intennediate-high risk group was 140 hours and 82 hours, respectively. There was no significant difference in survival curve between intennediate-high and intennediate-low risk groups (95% CI 108.1 to 1 2 5.4).Conclusion The incidence of hyperbilirubinemia was not different between intennediate-low and intermediate-high risk babies.

Patterns of recurrence and outcomes in surgically treated women with endometrial cancer according to ESMO-ESGO-ESTRO Consensus Conference risk groups: Results from the FRANCOGYN study Group

ObjectivesThe purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO classification. MethodsData of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test). ResultsData from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients (p<0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), (p<0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), (p<0.001). ConclusionsWe report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Outcome of Patients with Diffuse Large B Cell Lymphoma Treated in a Tertiary Care Centre in Uae; A Retrospective Review

Background:Diffuse large B cell lymphoma is the most frequent Haematological Malignancy in UAE. DLBC lymphoma treatment and outcome are well established. Most of reported outcome data is from North America or Europe. Because of lack of reported literature from Middle East, a retrospective data collection and review was performed in Tawam Hospital to evaluate the outcome of DLBC lymphoma.Methods:Retrospective chart review of all diffuse large B cell lymphoma patients treated from January 1, 2008 till December 30, 2012 at Tawam Hospital, a Tertiary Care Oncology Centre in UAE.Results:A total of 99 patients were identified with diffuse large B cell lymphoma. The median age was 48 (17 to 85). 59% of patients were male with a male to female ratio of 1.4. There were 17 (17%) stage I cases, 27 (27%) stage II cases, 23 (23%) stage III cases, and 30 (30%) stage IV cases. The stage was not documented in 2 (2%) patients. International Prognostic Index (IPI) score was documented in 80 (80%) patients. 28 (35%) of patients had low IPI score (0 or 1 risk factor), 33 (41%) patients had low intermediate IPI score (2 risk factor), 8 (10%) patients had high Intermediate IPI score (3 risk factors) and 11 (14%) patients had high IPI score (4 and 5 risk factors). 88 (89%) patients completed planned treatment: either R-CHOP or R-CHOP like chemotherapy. Involved field radiation therapy (IFRT) was given in limited stage and bulky disease. 11 (11%) patients didn't have a complete treatment. 3 patients received only R-CVP, 4 patients received only 1 cycle R-CHOP, 1 patient did not receive any treatment, 1 patient received only palliative Radiotherapy, 1 patient received Rituximab and palliative RT and 1 patient received only Dexamethasone and Rituximab.Relapse-free patients had median follow up of 31 months (1 to 67). 19 (26%) had less than 12 months follow up after completion of chemotherapy. Patients with documented relapses or primary refractory disease had relapse or progression at a median follow up of 14 month (1 to 43). There were 3 (10%) relapses in Low IPI score, 8 (24%) in low intermediate group, 4 (50%) in high intermediate group and 6 (54%) in high risk group.Discussion:Our data showed more young patients, median age 48, as compared to SEER data median age 65 and male predominance (59%), slightly higher as compared to SEER data (55%). These findings may be related to the demographics of UAE. UAE relatively have young and male predominance partly due to large number of expatriate population.Distribution of IPI score in our data is different as compared to the reported data; low risk 35% vs 52%, low intermediate 41% vs 21%, high intermediate 10% vs17%, and high risk 14% vs10%. Our data is missing reporting of IPI score in 20% of cases, may explain party the above difference.As median follow up of patient without relapse was 34 months, so comparison was made with 3 years progression free survival data reported in literature. Relapse free survival in the Low risk group 90% is comparable to reported 3 years progression free survival of 87% , low intermediate 76% as compared to reported 75%, in High intermediate and High risk group 50% and 46% are close to reported 59% (3) and 50% . The difference in high intermediate and high risk group as compared to reported survival in literature may be due to small number of patients in these groups.Conclusion:Outcome of DLBC lymphoma in our single centre retrospective review is relatively similar to reported outcome in literature. Median age is lower as compared to SEER data. DisclosuresNo relevant conflicts of interest to declare.

Specific Identification of High Risk Disease Using Molecular Profiling By Mymap (Myeloma MLPA and translocation PCR) of 1,036 Cases

IntroductionIdentifying molecular high risk myeloma remains a diagnostic challenge. We previously reported co-segregation of >1 adverse lesion [t(4;14), t(14;16), t(14;20), gain(1q), del(17p)] by iFISH to specifically characterise a group of high risk patients (Boyd et al., Leukemia 2012). However, implementation of this approach is difficult using FISH because of its technical limitations. We recently developed and validated a novel high-throughput all-molecular testing strategy against FISH (MyMaP- Myeloma MLPA and translocation PCR; Kaiser MF et al., Leukemia 2013; Boyle EM et al., Gen Chrom Canc 2015). Here, we molecularly characterised 1,036 patients from the NCRI Myeloma XI trial using MyMaP and validated the co-segregation approach.Materials, Methods and PatientsRecurrent translocations and copy number changes were assayed for 1,036 patients enrolled in the NCRI Myeloma XI (NCT01554852) trial using CD138+ selected bone marrow myeloma cells taken at diagnosis. The trial included an intensive therapy arm for younger and fitter and a non-intense treatment arm for elderly and frail patients. Analysis was performed using MyMaP, which comprises TC-classification based multiplex qRT-PCR and multiplex ligation-dependent probe amplification (MLPA; MRC Holland). Median follow up for the analysis was 24 months.ResultsAdverse translocations [t(4;14), t(14;16), t(14;20)] were present in 18.2% of cases, del(17p) in 9.3%, gain(1q) in 34.5% and del(1p32) in 9.4% of cases. All adverse lesions were associated with significantly shorter PFS and OS by univariate analysis (P <0.05 for all).Of the 1,036 analysed cases, 13.5% carried >1 adverse lesion, 33.9% had one isolated adverse lesion and 52.6% had no adverse lesion. Presence of >1, 1 or no adverse lesion was associated with a median PFS of 17.0, 23.9 and 30.6 months (P =3.0x10-9) and OS at 24 months of 67.9%, 75.0% and 86.0% (P =1.8x10-7), respectively.Del(1p) was associated with shorter PFS and OS for the intensive, but not for the non-intensive therapy arm and was independent of the co-segregation model by multivariate analysis regarding OS (P =0.006). We thus included del(1p) as an additional adverse lesion in the model for younger patients. The groups with >1 (19.4% of cases), 1 (31.1%) and no adverse lesions (49.5%) were characterised by median PFS of 19.4, 29.4 and 39.1 months (P =1.2x10-10) and median 24-months survival of 73.8%, 86.4% and 91.5% (P =1.4x10-6), respectively. Hazard Ratio for >1 adverse lesion was 3.0 (95% CI 2.1-4.1) for PFS and 3.8 (95% CI 2.2-6.5) for OS.By multivariate analysis, co-segregation of adverse lesions was independent of ISS for PFS/OS in the entire group of 1,036 cases and in the intensive treatment arm. We integrated adverse lesions and ISS into a combined model defining High Risk (>1 adv les + ISS 2 or 3; 1 adv les + ISS 3) and Low Risk (no adv les + ISS 1 or 2; 1 adv les + ISS 1) and the remainder as Intermediate Risk. The High Risk, Intermediate Risk and Low Risk groups of the total cohort included 11.2%, 41.2% and 41.6% of cases with median PFS of 15.8, 19.8 and 35.2 months (P <2.2x10-16) and median OS at 24 months of 62.9%, 73.7%, and 90.7% (P =4.0x10-14), respectively. Integration of ISS into the model for younger patients resulted in highly specific identification of a High Risk group (15.6% of cases) with HR 3.8 (CI 2.6-5.4) for PFS and 6.2 (CI 3.3-11.6) for OS.ConclusionsCo-segregation analysis of adverse genetic lesions is a specific molecular risk stratification tool which has now been validated in two large independent trials including a real-world population of all age groups (UK MRC Myeloma IX; NCRI Myeloma XI; total 1,905 patients). MyMaP is a validated all-molecular analysis approach that makes the otherwise technically challenging assessment of multiple genetic regions by FISH accessible using standard laboratory equipment without bioinformatics requirements. DisclosuresKaiser:BristolMyerSquibb: Consultancy; Chugai: Consultancy; Janssen: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Jones:Celgene: Other: Travel support, Research Funding. Savola:MRC Holland: Employment. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Gregory:Celgene: Honoraria; Janssen: Honoraria. Davies:Takeda-Milenium: Honoraria; Onyx-Amgen: Honoraria; Celgene: Honoraria; University of Arkansas for Medical Sciences: Employment. Jackson:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Morgan:Weisman Institute: Honoraria; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; MMRF: Honoraria.

Expression of Programmed Cell Death 1 and Programmed Cell Death Ligand 1 in Extranodal NK/T-Cell Lymphoma, Nasal Type

BackgroundProgrammed cell death ligand 1 (PD-L1) is expressed on extranodal NK/T-cell lymphoma, nasal type (ENKL) tumor cells. The programmed cell death 1 (PD-1) and PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in ENKL. The aim of this study was to investigate the expression of PD-1 and PD-L1 and to determine the clinicopathological impact of PD-1 and PD-L1 positivity in ENKL.MethodsWe performed PD-1 and PD-L1 immunostaining in 79 ENKL biopsy samples and retrospectively analyzed medical records of all 79 patients from 4 tertiary referral hospitals. The demographic features, performance status, stage, LDH, primary sites, nodal sites, hemoglobin, white blood cell, platelet, creatinine, international prognostic index (IPI), and prognostic index for T-cell lymphoma (PIT) were recorded.ResultsThe expression rates of PD-1-positive and PD-L1-positive ENKL were 7.6% and 88.6%, respectively (Figure 1A & 1B). PD-L1-negative ENKL (n=9) was significantly associated with high intermediate or high risk IPI (n=7, P=0.002) and group 3 or 4 PIT (n=6, P=0.043). Patients with PD-1-positive ENKL (n=6) had a trend toward better overall survival (OS) compared with that in patients with PD-1-negative ENKL (P = 0.090, Figure 2A). In contrast, there was no significant difference in OS between PD-L1-positive and -negative ENLK (P = 0.428, Figure 2B).ConclusionsThis is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKL. PD-1 expression rate is very low, and PD-L1 negativity is associated with poor risk groups of IPI and PIT in ENKL [Display omitted] [Display omitted] DisclosuresKim:Alexion Pharmaceuticals: Research Funding; Il-Yang: Research Funding; Celgene: Research Funding; Novartis: Research Funding.

Risk stratification of normotensive pulmonary embolism: prognostic impact of copeptin.

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (high-sensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)).We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study.Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6-90.8) versus 13.2 (5.9-39.3) pmol·L(-1); p=0.020). Patients with copeptin levels above the calculated optimal cut-off value of 24 pmol·L(-1) had a 5.4-fold increased risk for an adverse outcome (95% CI 1.68-17.58; p=0.005). We developed a strategy for risk stratification based on biomarkers. None of 141 patients (52.6%) with hsTnT <14 pg·mL(-1) or NT-proBNP <600 pg·mL(-1) had an adverse outcome (low risk). Copeptin ≥24 pmol·L(-1) stratified patients with elevated hsTnT and NT-proBNP as intermediate-low and intermediate-high risk (5.6% and 20.0% adverse outcome, respectively). Compared to the algorithm proposed by the 2014 European Society of Cardiology guideline, more patients were classified as low risk (52.8% versus 17.5%, p<0.001) and more patients in the intermediate-high risk group had an adverse outcome (20.0% versus 11.6%).Copeptin might be helpful for risk stratification of normotensive patients with pulmonary embolism, especially if integrated into a biomarker-based algorithm.

Early-Stage Endometrial Cancer: Recurrence Pattern and Survival Analysis from a Tertiary Cancer Centre in South India

The incidence of endometrial cancer is rising in India possibly due to the change in lifestyle and urbanization. Recent years have also shown a change in the adjuvant therapy for endometrial cancer. We evaluated the pattern of recurrence and survival of stage I and II carcinoma endometrium treated at our institution during a 5-year period. This was a single-institution retrospective analysis where all patients with early (Stage I and II) endometrial cancers treated from January 2004 to December 2008 were included. Data were retrieved from the hospital electronic medical records and hospital-based cancer registry. Details regarding the disease, initial treatment, follow-up, recurrence, and present status of the patient were collected. During the study period, 103 women with early endometrial cancer were identified. Patients were classified into low-risk, low-intermediate risk (LIR), high-intermediate risk (HIR), and high-risk (HR) groups according to the risk stratification used by the PORTEC study group. There were no recurrences in the low-risk group, whereas 9 % of LIR, 13.7 % of HIR, and 66 % of high-risk group recurred. The recurrence pattern was also distinctive between the groups with LIR having more vault recurrences, HIR and HR groups having distant recurrences. The local recurrences were salvageable whereas the distant recurrences were not. Overall and disease-free survival were 96.35 and 86.6 %, respectively. Endometrial carcinoma is mostly detected in early stages and has an excellent prognosis. Risk stratification is a prognostic indicator and also deciding factor in offering adjuvant therapy. Majority of uterus confined disease falls under intermediate risk group. Recurrences in LIR are locoregional and are salvageable with RT, while recurrences in HIR and HR are distant and not salvageable. EBRT with VBT improved DFS in both LIR and HIR groups when compared with no adjuvant treatment.