Is proliferative index (Ki-67) useful to stratify patients (pts) with G2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs)? Clinicopathologic correlation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 255-255
Author(s):  
Martin Angel ◽  
Juan O Connor ◽  
Veronica Pesce ◽  
Guillermo Ariel Mendez ◽  
Claudia Bestani ◽  
...  

255 Background: Grade 2 (G2) Neuroendocrine tumors (NETs), of the digestive tract is a heterogeneous group of tumors. Several treatment options including chemotherapy and target therapy are available, but there is a lack of prospective trials assessing the role of pronostic factors in this population. Aim(s): to analyze prognostic factors and clinical characteristics in a population of patients with G2 GEP-NETs. To determine the role of ki 67 in the stratification of G2 population. Methods: Study population was obtained from our prospective database (Argentum Group). Survival was estimated using the Kaplan-Meier method and compared between Ki-67 quartiles using the log-rank test. Value of Ki-67 to discriminate mortality was assesed with a ROC curve analysis Results: 144 pts were evaluated. Mean age 54.9, 46.7% male. 102 (70.8%) with metastatic disease, mainly hepatic in 97 pts. (67.4%). 67.9 % underwent surgery. 34% received chemotherapy, and 10.9% target therapy. Median Ki-67 value was 6 (IQR 4-10), ROC curve=0.62 (95% CI 0.53 a 0.72 p=0.021. cut-off: 6.5 (sensitivity 62.2%, specificity 57.7%). Median survival was 97, 67, 51 and 27 months according stratification by quartile (p.001), 45 events (31.7%). Conclusions: Our results suggest that in the heterogenous G2 GEP-NETs there are significant differences in survival. This study was underpowered to detect differences between Ki-67 quartiles, we detected that chemotherapy was mostly used in the higher quartiles.

2021 ◽  
Author(s):  
Hong Song ◽  
Pamela L. Kunz ◽  
Benjamin L. Franc ◽  
Farshad Moradi ◽  
Judy Nguyen ◽  
...  

Abstract Lutetium-177 ( 177 Lu)-DOTATATE is an effective systemic therapy for metastatic somatostatin receptor positive neuroendocrine tumors (NETs). Here we report our experience with the use of pre-therapy 68 Ga-DOTATATE PET as prognostic marker for short-term clinical outcomes of 177 Lu-DOTATATE therapy in patients with advanced NETs. Materials and methods: We retrospectively reviewed patients who received at least one dose of 177 Lu-DOTATATE between Dec. 2016 and July 2019 at our institution. 50 patients (63.6 ± 10.0 years) with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who had pre-therapy 68 Ga-DOTATATE PET were included in the analysis. 68 Ga-DOTATATE avid tumor volumes were determined automatically using an SUV thresholding approach. Total and extrahepatic 68 Ga-DOTATATE avid tumor volumes were measured and dichotomized into large and small tumor volume groups. Association with progression free survival (PFS) and overall survival (OS) were determined at median follow up of 32 months by Kaplan-Meier survival analysis with Log-Rank test. Results: During follow up, 38 patients (76%) had disease progression and 15 patients (30%) died. Kaplan-Meier analysis of PFS in GEP-NETs patients showed that smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<140 mL) is associated with significantly longer PFS (Median PFS 29.0 ± 6.7 months vs 9.0 ± 1.7 months, P = 0.0001). This trend in PFS is less prominent when total 68 Ga-DOTATATE avid tumor volume is analyzed. Similarly, Kaplan-Meier analysis of OS found that GEP-NETs patients with smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<150 mL) is associated with significantly longer OS (Median OS not reached vs 44.0 ± 12.3 months, P = 0.002). This association with OS is not statistically significant when total 68 Ga-DOTATATE avid tumor volume is analyzed. When 68 Ga-DOTATATE avid hepatic tumor volume is grouped into low (<500 mL), medium (500-1000mL) and large (> 1000 mL) tumor volumes, no statistically significant difference in PFS is observed, P = 0.19. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate at 58% and 72%. Conclusions: Smaller extrahepatic 68 Ga-DOTATATE avid tumor volumes are associated with longer PFS and OS following 177 Lu-DOTATATE treatment in patients with advanced GEP-NETs. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate, which may limit its clinical application.


2017 ◽  
Vol 2 ◽  
pp. 115-122 ◽  
Author(s):  
Beata Kos-Kudła ◽  
Jarosław Ćwikła ◽  
Marek Ruchała ◽  
Alicja Hubalewska-Dydejczyk ◽  
Barbara Jarzab ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14598-e14598
Author(s):  
Juan Manuel O'Connor ◽  
Veronica Pesce ◽  
Guillermo Ariel Mendez ◽  
Claudia Bestani ◽  
Fabiana Marmissolle ◽  
...  

e14598 Background: Somatostatin receptor expression (SSTR), mainly subtypes 2 and 5, is a feature of well differentiated GEP-NETs. Such expression has a prognostic and predictive value for the use of somatostatin analogs.Ki 67, present during the cycle phases (G1, S, G2 y M) is a nuclear antigen associated with cell proliferation. The correlation between both clinical and pathological factors is under active investigation in patients with GEP-NETs. Methods: An analysis including 100 patients in the database of the Argentum Group was performed. Consecutive patients were included during the 2006-2007 period. In all cases, a centralized revision of the sample was conducted for diagnosis confirmation.The study of SSTR receptors in tissue and Ki67 was conducted using IHQ.The Kaplan-Meier method was used to analyse survival. Log-rank test was used for the comparative analysis of the variables of interest. Results: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. The univariate analysis showed significant differences in the expression of SSTR2 (a) but not in the expression of SSTR 5.The expression of the proliferative index (Ki 67) was associated with significant differences in relation to OS at 5 years, 84% (Ki 67 under or equal to 2%), 66% (Ki 67 between 3 and 15%) and 13% (Ki 67 over 15%). The OS at 5 years in patients with SSTR 2/5 positive and Ki 67 under 2% was 86%, 64% in pts. with SSTR 2/5 positive and Ki 67 over 2% and 20 % in pts. with SSTR 2/5 negative, independent Ki 67 (p .0023). Conclusions: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. In the population with GEP-NETs under study, a subgroup of patients with a better prognosis was identified in association with the expression of SSTR 2/5 and Ki67 below 2%. The assessment of SSTR 2(a) and 5 in tissues, together with the study of the proliferative index are a useful tool for prognosis assessment in these patients.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Ikeda ◽  
K Iwatsu ◽  
K Matsumura ◽  
H Ashikawa ◽  
K Takabayashi ◽  
...  

Abstract Background Perceived social isolation (SI), the subjective sense of feelings of loneliness or isolation, has a negative impact on health outcomes, particularly in older adults. Although SI may also contribute to poor prognosis in patients with HF, evidence on the relationship between SI and outcomes in patients with HF is limited. Purpose The aim of this study was to investigate the relationship between SI and hospital readmission in patients with HF. Methods This study was a single center prospective cohort study. We consecutively enrolled 203 patients (mean age 72.9±11.7) who admitted for acute HF or exacerbation of chronic HF. At hospital discharge, we assessed perceived SI by using Lubben Social Network Scale - 6 (LSNS-6). Lower scores in LSNS-6 represents greater SI. Study outcome was rehospitalization for worsening HF within 180 days after discharge. We selected the optimal cutoff point of LSNS-6 that predict a worse outcome by the receiver operating characteristic (ROC) curve analysis. We investigate the association between SI and 180-days HF rehospitalization by using Cox proportional-hazard models, controlling for potential confounding factors. Results During follow up, A total of 40events (19.7%) were observed. The optimal cut-off point of LSNS-6 score was 17 points (the area under the ROC curve: 0.62, p<0.05, sensitivity: 82.5%, specificity 42.4%). Kaplan-Meier survival curves showed that those patients with greater SI (LSNS-6≤17) presented significantly higher HF rehospitalization rate (Figure). After adjusting for several pre-existing prognostic factors, LSNS-6≤17 was independently associated with HF rehospitalization (hazard ratio2.15,95% confidence interval 1.00–4.89). Conclusion The present study shows that SI is a independent predictor of HF rehospitalization in patients with HF. Assessing SI in the clinical practice with a brief screening tool may help identify patients with heart failure at greater risk of rehospitalization.


2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e39-e41
Author(s):  
Lilian Kebaya ◽  
Mong Tieng Ee ◽  
Michael Miller ◽  
Soume Bhattacharya

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Hypoxic-ischemic encephalopathy (HIE) is a major contributor to morbidity and mortality. Therapeutic hypothermia (TH) is the standard of care for neonates with moderate to severe HIE. Brain magnetic resonance imaging (MRI) is the imaging modality of choice for confirmation of HIE, assessment of injury severity, and prognostication. Reliable, inexpensive and widely available laboratory measures for early identification of risk for neurological injury can play a critical role in the optimal management of neonatal HIE, especially in the resource-limited setting. Our study examined whether derangements in early routine laboratory measures (acid-base, haematological, metabolic) were worse in neonates with MRI findings of neurological injury. Objectives Primary objective: To evaluate the role of early laboratory measures in predicting neurological injury as detected by MRI at 72 hours. Secondary objective: To evaluate the role of early laboratory measures in predicting survival to NICU discharge in patients with HIE. Design/Methods This single-centre, retrospective cohort study included neonates ≥ 35 weeks gestation with moderate to severe HIE, who had undergone therapeutic hypothermia. Based on findings of brain MRI completed within 72 hours of life, our cohort was divided into 2 groups: neonates with, and without, evidence of neurological injury consistent with HIE. Baseline characteristics, as well as laboratory measures, were compared between groups, and a receiver operating characteristic (ROC) curve analysis was conducted to determine the cut-off for prediction of neurological injury based on the highest sensitivity and specificity values. Results 104 neonates were analyzed. Baseline characteristics (Table 1) were similar between both groups, except for cord venous pH and base excess (BE), which were significantly lower in the abnormal MRI group (p = 0.02). In bivariate analysis, pH (at 1 h of age, p = 0.027), BE (at 1 h, p = 0.001, and 6 h of age, p = 0.004), ionized calcium (at 6 h of age, p = 0.02), and platelets (at 1 h of age, p = 0.004) were significantly different in neonates with abnormal MRI. In ROC curve analysis, BE at 1 h of life was the best predictor of abnormal MRI (AUC = 0.71, p = 0.002), with a cut-off value of ≤ -14.95, sensitivity of 67% and specificity of 66% (Figure 1). Conclusion Among neonates with HIE undergoing TH, early laboratory measures such as acid-base status, ionized calcium, and platelet count were worse in neonates with abnormal MRI, in comparison to neonates with normal MRI. Base excess at 1 h of life is a good predictor of abnormal MRI. Future prospective studies to validate these findings are needed


2018 ◽  
Vol 30 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Fatih Mert Dogukan ◽  
Banu Yilmaz Ozguven ◽  
Rabia Dogukan ◽  
Fevziye Kabukcuoglu

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 376-376
Author(s):  
Rachel M Lee ◽  
Danielle K DePalo ◽  
Alexandra G Lopez-Aguiar ◽  
Mohammad Yahya Zaidi ◽  
Flavio G. Rocha ◽  
...  

376 Background: The prognostic value of pathologic variables is not consistent for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We previously demonstrated a limited prognostic role of lymph node (LN) positivity in small bowel NETs (SBNET) compared to pancreatic NETs (panNET). Although minority race is often associated with worse cancer outcomes, the interaction of race with pathologic and oncologic outcomes of pts with GEP-NETS is not known. Methods: Pts with GEP-NETs who underwent curative intent resection at eight institutions of the US NET Study Group from 2000-16 were included. Given few pts of other races, only Black and White race pts were analyzed. Results: Of 2,182 pts, 1,143 met inclusion criteria. Median age was 58 yrs, median follow up was 3 yrs, 48% were male, 14% (n = 157) were Black, and 86% (n = 986) were White. Black pts were more likely uninsured (7 vs 2%, p = 0.005), had symptomatic bleeding (13 vs 7%, p = 0.006), required emergency surgery (7 vs 3%, p = 0.003), and had LN positive disease (47 vs 36%, p = 0.016). Despite this, Black pts had improved 5 yr recurrence free survival (RFS) compared to White pts (90 vs 80%, p = 0.008). The quality of care received was comparable between both groups, demonstrated by similar LN yield at surgery, neg margin resection rate, post-op complications, and need for reoperation or readmission (all p > 0.05). Black pts were more likely to have SBNET (22 vs 13%) and less likely to have panNET (43 vs 68%) compared to White pts (p < 0.001). Consistent with prior data, pts with LN pos panNET had decreased 5yr RFS (67 vs 83%, p = 0.001); however, for SBNET, LN involvement was not prognostic (77 vs 96%, p = 0.08). The prognostic value of LN pos disease was similar between Black and White pts in both SBNET (p = 0.34) and panNET (p = 0.95). Conclusions: Black pts with GEP-NET present with more advanced disease, including higher LN positivity. Despite this, Black pts have improved RFS compared to White pts. Although there may be delays in seeking or reaching care, Black pts received similar quality of care compared to White pts. The improved RFS seen in Black pts may be attributed to the epidemiologic differences in the site of presentation of GEP-NETs and variable prognostic value of LN pos disease.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p&lt;0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p&lt;0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p&lt;0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p&lt;0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p&lt;0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p&lt;0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p&lt;0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p&lt;0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p&lt;0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p&lt;0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.


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