Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study

2018 ◽  
Vol 107 (4) ◽  
pp. 375-386 ◽  
Author(s):  
Guido Rindi ◽  
Catherine Klersy ◽  
Luca Albarello ◽  
Eric Baudin ◽  
Antonio Bianchi ◽  
...  

Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell’s C statistics, and Royston’s explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

Author(s):  
Philip J. Johnson ◽  
Sofi Dhanaraj ◽  
Sarah Berhane ◽  
Laura Bonnett ◽  
Yuk Ting Ma

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.


Toxics ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 84
Author(s):  
Ying-Tse Yeh ◽  
Chun-Kuei Chen ◽  
Chih-Chuan Lin ◽  
Chia-Ming Chang ◽  
Kai-Ping Lan ◽  
...  

The efficacy of hemoperfusion (HP) in patients with acute paraquat poisoning (PQ) remains controversial. We conducted a multi-center retrospective study to include acute PQ-poisoned patients admitted to two tertiary medical centers between 2005 and 2015. We used the Severity Index of Paraquat Poisoning (SIPP) to stratify the severity of PQ-poisoned patients. The indication to start HP was a positive result for the semiquantitative urine PQ test and presentation to the hospital was within 24 h. Early HP was defined as the first session of HP performed within five hours of PQ ingestion. A total of 213 patients (100 HP group, 113 non-HP group) were eligible for the study. The overall 60-day mortality of poisoned patients was 75.6% (161/213). Multivariate Cox regression analysis showed no statistically significant difference in 60-day survival between HP and non-HP groups (95% confidence interval (CI): 0.84–1.63, p = 0.363). Further subgroup analysis in the HP group showed early HP (95% CI: 0.54–1.69, p = 0.880), and multiple secessions of HP (95% CI: 0.56–1.07, p = 0.124) were not significantly related to better survival. Among acute PQ-poisoned patients, this study found that HP was not associated with increased 60-day survival. Furthermore, neither early HP nor multiple secessions of HP were associated with survival.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 62-62 ◽  
Author(s):  
Emily C. Sturm ◽  
Whitney Zahnd ◽  
John D. Mellinger ◽  
Sabha Ganai

62 Background: Esophageal cancer management has evolved due to improvements in staging and treatment strategies. Endoscopic local excision presents an attractive option for definitive management of T1 cancers, avoiding the morbidity of esophagectomy. We hypothesized that for cT1N0 cancers, patients who underwent local excision would have lower survival compared to esophagectomy due to potential discordant staging. Methods: The National Cancer Database was queried for esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) with AJCC T1N0 clinical stage who underwent local excision (n = 1625) or esophagectomy (n = 3255) between 1998 and 2012. Chi-square analysis was used to compare demographic and clinical characteristics by procedure. Chi-square trend analysis was performed to assess trends in procedure type over time. Cox Regression analysis was performed to assess survival by procedure controlling for demographic and clinical characteristics. Results: Between 1998 and 2012, the proportion of patients who underwent local excision increased from 12% to 50% for all patients (p < 0.001); from 17% to 40% for SCC patients (p < 0.001); and from 9% to 51% for AC patients (p < 0.001). Surgical procedure varied significantly by demographic, socioeconomic status, facility, and tumor-related factors. 65% of cT1N0 cancers had concordant clinical and pathological staging after esophagectomy, with 11% having positive nodal disease; 44% were concordant after local excision. While no significant difference was seen in unadjusted survival, adjusted Cox Regression analysis indicated worse survival after esophagectomy compared to local excision for all cases (HR 1.67; 95% CI, 1.40-2.00) and for ACs with concordant staging (HR 1.54; 95% CI, 1.11-2.14). Conclusions: Local excision for cT1N0 esophageal cancer has increased over time. Staging concordance for esophagectomy is seen in two-thirds of cases. Contrary to our hypothesis, patients undergoing local excision for T1N0 cancers have better overall survival than those undergoing esophagectomy, which may reflect early differences in mortality and/or selection bias. As this study was unable to distinguish T1a from T1b, further analysis is warranted.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11616-e11616
Author(s):  
Barbara Pistilli ◽  
Andrea Marcellusi ◽  
Michele Valeri ◽  
Umberto Torresi ◽  
Dania Nacciarriti ◽  
...  

e11616 Background: Continuing T beyond progression has become a common strategy in the treatment of human epidermal growth receptor 2- overexpressing (HER2) MBC. However, T administered for several years with concomitant chemotherapy elicits concern about cardiac safety especially in patients (pts) with risk factors. Methods: Cardiac events (CEs) and survival of HER2 MBC pts treated with T +/- chemotherapy at our institution from Dec 2003 to Jun 2012 were evaluated. CEs were graded by NCI-CTCAE v 3.0. Risk factors assessed for cardiotoxicity were: age, body mass index, antihypertensive therapy, history of cardiac disease, diabetes, hypothyroidism, smoking, prior radiotherapy on the chest wall, prior cumulative dose of anthracycline(A), interval between last A dose and first T dose, baseline LVEF, continued/interrupted T exposure, concomitant chemotherapy. Chi-square test was used to compare distribution of CEs over different times of T exposure (p≤ 0.05). Univariate and multivariate Cox regression analysis were used to assess the effect of risk predictors. Results: Sixty-two pts assessable. Median age 52 years (range, 29 to 76), median cumulative time receiving T 29.5 months (range, 3 to 99 months); 40 pts (64.5%) received T without interruption and 19 pts (30.6%) were treated for more than 36 months. CEs occurred in 11 out of all pts (17.7%): grade 1 in 3 pts (4.8%), grade 2 in 5 (8.1%) and grade 3 in 3 (4.8%). The rate of CEs showed no statistically significant difference in pts receiving T for up to 36 months and over: 7/43 (16.3%) and 4/19 (21%), respectively, (p =0.724). In univariate Cox regression analysis significant risk factors were: history of cardiac disease (HR 6,814, 95% CI: 1,384-33,542) and smoking (HR 5,228, 95% CI: 1,403-19,491). In multivariate analysis smoking was the only independent predictor (HR 5,886, 95% CI: 1,479-23,247). Median survival from MBC diagnosis was 50 months (range, 6 to 101 months). Conclusions: Despite the limited sample size, our analysis suggests that cardiotoxicity does not hamper a long-term use of T, since the rate of CEs did not increase in pts treated over 36 months. Moreover, smoking appears to be a predictive factor of T cardiotoxicity.


2020 ◽  
Author(s):  
Zhuomao Mo ◽  
Shaoju Luo ◽  
Hao Hu ◽  
Ling Yu ◽  
Zhirui Cao ◽  
...  

Abstract Background Many different signatures and models have been established for patients with hepatocellular carcinoma (HCC), but no signature based on m6A related genes was developed. The objective of this research was to establish the signature with m6A related genes in HCC. Methods Data from 377 HCC patients from The Cancer Genome Atlas (TCGA) database was downloaded. The included m6A related genes were selected by Cox regression analysis and the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, the nomogram was constructed and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the four m6A related genes (YTHDF2, YTHDF1, METTL3 and KIAA1429). Under the grouping from signature, patients in high risk group of showed the poor prognosis than those in low risk group. And significant difference was found in two kinds of immune cells (T cell gamma delta and NK cells activated) between two groups. The univariate and multivariate Cox regression analysis indicated that m6A related signature can be the potential independent prognosis factor in HCC. Finally, we developed a clinical risk model predicting the HCC prognosis and successfully verified it in C-index, calibration and ROC curve. Conclusion Our study identified the m6A related signature for predicting prognosis of HCC and provided the potential biomarker between m6A and immune therapy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yutaka Miyawaki ◽  
Hiroshi Sato ◽  
Shuichiro Oya ◽  
Hirofumi Sugita ◽  
Yasumitsu Hirano ◽  
...  

Abstract Background Surgery is still the mainstay of radical treatment for resectable esophageal cancer (EC). It is apparent that the presence or spread of lymph node metastasis (LNM) is a powerful prognostic factor in patients with EC who are eligible for curative treatment. Although the importance and efficacy of lymph node dissection in radical esophagectomy have been reported, the clinical or prognostic relevance of specific metastatic patterns within the mediastinal cavity and abdomen remains unclear. Methods We retrospectively analyzed the association of postoperative survival with clinical mediastinal LNM (cMLNM) and abdominal LNM (cALNM) in 157 patients who underwent radical EC surgery at our hospital between May 2012 and March 2018. Results A significant difference in cause-specific survival (CSS) was observed between patients with and without cALNM (log-rank p = 0.000). A multivariate Cox regression analysis revealed that cALNM and thoracic surgery (mediastinal lymphadenectomy via conventional open right thoracotomy or video-assisted thoracoscopic surgery) independently predicted CSS (p = 0.0007 and 0.021, respectively). Moreover, a significant difference in systemic recurrence-free survival was observed between those with and without cALNM (log-rank p = 0.000). Multivariate Cox regression analysis revealed that cALNM and sex independently predicted systemic recurrence-free survival (p = 0.000 and 0.015, respectively). Conclusion cALNM was an independent poor prognostic factor for CSS after EC surgery. It may also be an independent prognostic factor for postoperative systemic recurrence, which can shorten the CSS. For patients with cALNM-positive EC who have a high potential risk of systemic metastases, more extensive treatment besides the conventional perioperative systemic chemotherapy may be necessary.


2021 ◽  
Author(s):  
Haisheng Qian ◽  
Xin Gao ◽  
Rui Ma ◽  
Wenjie Li ◽  
Zhen Yang ◽  
...  

Abstract Background: Stemness is described as the potential for self-renewal and differentiation from the cell-of-origin. A previous study calculated the mRNA expression-based stemness index (mRNAsi) based on a one-class logistic regression machine learning algorithm for describing stemness features of cancer. We aim to identify stemness-related prognostic genes in gastric cancer (GC) based on mRNAsi using bioinformatics analysis.Methods: The WGCNA analysis was performed to find the relevant gene modules to mRNAsi. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways annotation analysis were performed on genes in blue module. The overall survival analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were used to identify prognostic genes highly associated with survival. The multivariate Cox regression analysis was performed to analysis prognostic factors. The nomogram was constructed according to the result of multivariate analysis. qPCR, Western Blot and IHC staining were appliedResults: The mRNAsi of tumors is higher than normal tissues, and there was a significant difference in overall survival (OS) between the high and low mRNAsi GC groups. TCEAL7 was selected to be the key gene associated with mRNAsi and prognosis according to the result of least absolute shrinkage and selection operator (LASSO) Cox regression. The expression level of TCEAL7 was lower in tumors than in normal tissues, but high TCEAL7 level group showed a worse OS than low TCEAL7 level group in GC. Based on the result of multivariable Cox regression analysis which including TCEAL7 and clinical characteristics, a nomogram for predicting GC 1-, 3-, and 5-year survival was established. The C-index and the AUC (Area Under Curve) of the model indicated that the model has a good discrimination ability. Additionally, the calibration curves of 3- and 5-year OS rates showed the model fits well. The experimental validation of the expression of TCEAL7 in GC and normal tissues were consistent with the above.Conclusions: In summary, we verified mRNAsi was associated with the prognosis of GC patients. And TCEAL7 was finally identified as the key gene correlated with stemness features and prognosis in GC.


2021 ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  

Abstract Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in age, histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95 % CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95 % CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17032-e17032
Author(s):  
Katrin Schlack ◽  
Konstantin Seitzer ◽  
Verena Humberg ◽  
Neele Wüstmann ◽  
Norbert Grundmann ◽  
...  

e17032 Background: Biomarkers predicting response to mCRPC treatment are rare. CTCs and AR-V7 status have been discussed as potential prognosticators. Methods: We evaluated 64 patients (pts.) treated with abiraterone (n=47) or enzalutamide (n=17), determined CTCs and analyzed AR-V7 status in correlation with survival using Kaplan-Meier-estimates and Cox-regression-models. Results: For PSA response, CTC- vs. CTC+ were not different (p=0.25) whereas AR-V7 status was predictive (68.2% AR-V7- and 33.3% AR-V7+ pts. (p=0.01)). Median PSA PFS was 17 mo. (CI 9.5-24.5) for CTC- and 6 (CI 5.2-6.9) for CTC+ pts. (p<0.01) with 9 mo. (CI 4.2-13.8) for CTC+/AR-V7- and 5 (CI 3.0–7.0) for CTC+/AR-V7+ pts. (p=0.04). In univariate cox regression analysis (UV), prior abiraterone or enzalutamide (A/E) (p=0.01), bone metastases (p=0.03), CTC+ (p=0.01), AR-V7+ (p=0.01), Hb ≤12 g/dl (p=0.01) and PSA decline ≥50% (p<0.01) were significant prognosticators. Within the CTC+ subgroup, AR-V7+ (p=0.02) and PSA decline ≥50% (p=0.03) showed a relevant difference. In multivariate analysis (MV), for CTC+ pts, AR-V7+ (p=0.02), PSA decline ≥50% (p=0.02) and visceral metastases (p=0.02) remained independent prognosticators. The analysis for PFS resulted in 22 mo. (CI NA) for CTC- compared to 9 (CI 7.7-10.3) for CTC+ (p=0.01) and 10 mo. (CI 8.2-11.8) for CTC+/AR-V7- vs. 6 (CI 1.9-10.1) for CTC+/AR-V7+ (p=0.07). Performing UV, prior A/E (p<0.01), CTC+ (p=0.01), AR-V7+ (p=0.01), Hb ≤12 (p<0.01), PSA decline ≥50% (p<0.01) and ALP elevated at baseline (p=0.03) showed statistically significant differences. Within the CTC+ subgroup, prior A/E (p=0.01), visceral metastases (p=0.02), Hb ≤12 (p=0.01) and PSA decline ≥50% (p=0.03) were significant prognosticators, whereas AR-V7+ was not. In MV of CTC+ pts, visceral metastases (p=0.02), PSA decline ≥50% (p=0.02) and Hb ≤12 (p=0.05) remained independent prognosticators. Median OS was not reached for CTC- and 17 mo. (CI 9.8–24.2) for CTC+ (p<0.01) with 27 (CI 10.6-43.4) vs. 14 (CI 10.4-17.7) mo. for AR-V7- and AR-V7+, respectively (p=0.06). UV resulted in statistically relevant differences for prior docetaxel (p=0.01), prior A/E (p<0.01), visceral metastases (p=0.02), CTC+ (p=0.01), AR-V7+ (p<0.01) and Hb ≤12 (p< 0.01). Within CTC+, prior docetaxel (p<0.01), prior A/E (p=0.01), visceral metastases (p<0.01) and Hb ≤12 (p<0.01) were statistically relevant parameters. UV for AR-V7 status did not result in a significant difference for OS either. In MV, CTC status as well as Hb ≤12 remained independent prognosticators (p=0.04 and p<0.01, respectively). For MV of CTC+, visceral metastases (p=0.01), Hb ≤12 (p<0.01) and prior docetaxel (p=0.01) were independent prognosticators of OS. Conclusions: Presence of CTCs seems to prognosticate PFS and OS in mCRPC patients undergoing Androgen-deprivation while presence of AR-V7 does not despite its predictive potential.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4703-4703
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Luigi Marcheselli ◽  
Alessia Bari ◽  
Stefano Luminari ◽  
...  

Abstract Some data suggest that there are been no improvement in survival of FL Pts in the last three decades of the 20th century. However that review ended in 1992, before the introduction of R treatment. Most recently reported data, show that evolving chemotherapies, including the incorporation of R has led to outcome improvement. Between 1994 and 2004, 344 Pts with FL were enrolled in different GISL Trials. For the purpose of this study we considered 270 Pts with similar characteristics enrolled in trials including or not R. The first group accounts for 176 naive Pts treated with Antracycline plus Fludarabine containing regimens (Cohort #1: 125 Pts) or plus R (Cohort #2: 51Pts). The second group accounts for 99 relapsed Pts treated with Antracycline plus Fludarabine containing regimens (Cohort #3: 40 Pts) or plus R (Cohort #4: 59 Pts). To evaluate the impact of the incorporation of R in front line and salvage therapies we assessed the patients OS, FFS, TTF, SAR in these different Cohorts of Pts. Descriptive analysis of prognostic features showed differences in the distribution among groups. To compensate for these variations we also performed Cox regression analysis. Previously Untreated patients. Regarding group #1 and #2 that enrolled Pts with clinical stage IIB, III and IV, FFS and OS according to treatment did not show any statistical differences. The univariate analysis of baseline clinical features showed an impact on OS and FFS for clinical stage, LDH level, involvement of more than 4 nodal sites and presence of extranodal involvement. The prevalence of this characteristics were higher in group #2 than group #1. Thus the FFS from group #2 vs. group #1 was adjusted for variation in prognostic features by Cox regression analysis, that shows a failure Hazard Radio reduction (HR) of 40 % in Pts who received R. Because of difference in follow up (FU) (49 months in Cohort #1 vs 21 months in Cohort #2), to evaluate differences in OS we utilized exact Log Rank test for unequal FU. So far, a trend exists for better OS in R treated patients, although the difference is not statistically significant. Relapsed Patients. Clinical characteristics were similar in the two Cohorts of pts. TTF was better in R treated Pts and the difference was statistically significant (66% vs. 53% at 3 yrs, p=0.023) The analysis of SAR demonstrated a better result for R Cohort with a statistically significant difference (88% vs. 68% at 3 yrs, p=0.022). OS according to treatment protocol, showed advantage for patients in R Cohort and the difference was statistically significant (92% vs. 70% at 5 yrs, p=0.004). Conclusion. In naïve patients our retrospective analysis showed a reduction of HR for FFS and a trend toward better OS in R treated Pts. In relapsed Pts all outcome parameters as OS, TTF and SAR had significant improvement in the Cohort treated with R. Although any conclusions between nonrandomized groups maybe subject to differences in observed and unobserved prognostic features, we believe that improvement have occurred in the management of FL Pts with the introduction of combined chemotherapy with R.


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