scholarly journals Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

2021 ◽  
Author(s):  
Sara Imboden ◽  
Denis Nastic ◽  
Mehran Ghaderi ◽  
Filippa Rydberg ◽  
Franziska Siegenthaler ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Risk Groups ◽  
Molecular Classification ◽  
Outcome Data ◽  
Molecular Diagnostic ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Clinicopathologic Parameters ◽  
Evidence Based Guidelines ◽  
Risk Grouping

ABSTRACT Introduction In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. Materials and methods We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. In addition, clinical treatment and outcome data were collected from medical records. Results The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 386 (65.0%) cases would need to be analyzed by TP53 IHC, only 44 (7.4%) by MMR IHC and 109 (18.4%) POLE sequencing reactions. Conclusion Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected

Microarray Classification of Myelodysplastic Syndrome (MDS) Identifies Subgroups with Distinct Clinical Outcomes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2426-2426
Author(s):  
Ken I. Mills ◽  
Alex Kohlmann ◽  
Mickey Williams ◽  
Wei-Min Liu ◽  
Rachel Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Cell Signalling ◽  
Bioinformatic Analysis ◽  
Initial Study ◽  
Outcome Data ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Gene Expression Signatures ◽  
Microarray Classification

Abstract The MILE (Microarray Innovations in LEukemia) study has previously shown that gene expression signatures associated with initial leukaemia classifier (LCver7) give an overall cross-validation accuracy of >95% for distinct sub-classes of pediatric and adult leukemias. However, only 50% of the 174 MDS samples in the whole-genome microarray analysis (Stage 1) of the MILE study were correctly identified; the remainder showed AML-like or non-leukemia-like gene profiles. An external morphological review (DB & HL) according to FAB and WHO criteria, of the 174 slides was performed independently (blind) which resulted in 6 samples being reclassified as AML and 4 non-leukemia cases excluded from the study. A recently improved, hierarchical based algorithm correctly identified 100% of the confirmed MDS cases. In this study, using LCver7, the confirmed 164 samples had 50% MDS classifications (Class 17), 23.8% non-leukemia classifications (Class 18), and 22.6% AML classifications (Classes 13 or 14) with the remaining 3.7% having a classification tie between 2 or 3 Classes (due to low confidence). No 5q- syndrome patients had an AML call, whilst 68.3% of RAEB2 patients had an AML classification and none were Class 18. Similarly, 95.6% of Low IPSS patients were classified as Class 17 or 18, whilst all patients (n=5) with High IPSS had an AML call. The classification was independent of blast cells: 10.2% of Class 18 calls had >5% blasts; 28.2% of AML-like cases had <5% blasts. Outcome data (132 MDS patients) was correlated with Class: significant difference (p<0.028, (Kaplan-Meier)) was seen in overall survival; with p <0.004 if AML (Classes 13 & 14) was compared to “non AML” (Classes 17 & 18). Statistically significant differences were seen for time to transformation to AML between the classes (p<0.0001) and between AML and “non AML” (p<0.00007, Kaplan-Meier)) with a probability of transformation of 44% at 18 months for the AML group compared to <8% for the “non-AML” group. A further linear classifier has been used to discriminate patients who transform to AML within 18 months (poor prognosis) with patients with no transformation after >60 months (good prognostic group). Bioinformatic analysis of molecular mapped functions and canonical pathways showed that cell signalling processes were over-represented when comparing de novo AML (n=204) with MDS, from the MILE study, whilst signal transduction pathways were deregulated when comparing non-leukemia samples (n=71) with MDS. Similar pathways and functions were also deregulated when comparing the correctly classified MDS with Class 17 call against MDS with Class 18 call and MDS with AML Classes 13 or 14 calls. In conclusion, the use of microarrays within the initial study, solely intended for diagnostic purposes, has now evolved towards a position in which novel prognostic value may be gained from distinct gene expression signatures. This has also resulted in a better molecular understanding of the progression from non-leukemia, through MDS into full blown AML.

Validation of the AJCC staging system (7th edition) in Asian patients with localized prostate cancer undergoing radical radiotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 112-112
Author(s):  
M. Wong ◽  
C. Yip ◽  
X. Hou ◽  
P. Tan ◽  
H. Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Univariate Analysis ◽  
Staging System ◽  
Risk Groups ◽  
Radical Radiotherapy ◽  
Seventh Edition ◽  
Delivery Technique ◽  
Significant Difference ◽  
Risk Grouping

112 Background: The epidemiology of prostate cancer (PCa) varies widely internationally. Although prostate cancer is usually regarded as uncommon in Asia, dramatic rises in recent years have resulted in it being ranking third by incidence in Singapore. Conventional prognostic parameters derived from Western populations have been integrated into systems such as the new AJCC seventh edition staging system, the validity of which is unclear in Asia. We thus sought to validate its performance, alongside other prognostic factors in a large Asian series of radiotherapy patients. Methods: A retrospective review of 404 consecutive Singaporean patients receiving radical radiotherapy between 1997 and 2005 at the National Cancer Centre was performed. The primary outcome was biochemical relapse free survival (BRFS), defined by the Phoenix criteria. Prognostic risk groups were defined using AJCC seventh edition. Univariate analysis (UVA) and multivariate analysis (MVA) was performed for other putative risk factors: age, race, Gleason score, prognostic risk grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy (HT) and initial PSA. Results: Median age was 69; median BRFS was 55 months with 71 biochemical relapses. 4 risk factors showed univariate association with BRFS: AJCC risk groups (p=0.038), T-stage (p=0.018), RT dose (p=0.025) and initial PSA value (p=0.013) with AJCC risk groups and initial PSA value remaining significant after MVA ( Table ). Harrell's c-index for AJCC risk grouping was 0.56, with no significant difference seen in outcomes between AJCC risk group II and III. Conclusions: Our results validate the new AJCC seventh edition prostate cancer prognostic risk grouping in an Asian radiotherapy population for the first time; the actual association however is relatively weak possibly due to differences in biology, screening or epidemiology. [Table: see text] No significant financial relationships to disclose.

scholarly journals Oseltamivir, Lopinavir/ritonavir and Reduning May Improve Survival of COVID-19 Patients With High-risk

2020 ◽  
Author(s):  
zhiyong zeng ◽  
Chaohui Wu ◽  
Zhenlv Lin ◽  
Yong Ye ◽  
Shaodan Feng ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Lasso Regression ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Reduning Injection ◽  
Total Point

Abstract Background No therapeutics have demonstrated specific efficacy for patients with COVID-19. Methods We retrospectively evaluated 351 patients with COVID-19 admitted to the Third People's Hospital of Yichang from 9 January to 25 March, 2020.Univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were employed to identify risk factors associated with progression, which were then incorporated into the nomogram. Survival of patients between high-risk and low-risk groups was compared by kaplan-Meier analysis. Moreover, we assessed the effects of existing common drugs on survival of patients with high-risk. Results Based on the LASSO, four variables (white blood cell, C-reactive protein, whether lymphocyte ≥ 0.8 × 109/L, and whether lactate dehydrogenase ≥ 400 U/L) were selected for construction of the nomogram. Patients in the total cohort were stratified into low-risk group (total point < 160) and high-risk group (total point ≥ 160). Kaplan-Meier analysis demonstrated that there was significant difference in survival of patients between high-risk and low-risk groups (8-week survival rate: 71.41% vs 100%, P < 0.0001). Among the common drugs, we found that patients with high-risk received oseltamivir, lopinavir/ritonavir or Reduning injection exhibited better survival. The combination of these three drugs showed the effect of improving survival, although single drug may have no effect in different grouping analysis. Conclusions The combination of oseltamivir, lopinavir/ritonavir and Reduning injection may improve survival of COVID-19 patients with high-risk identified by our simple-to-use nomogram.

scholarly journals The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1478
Author(s):  
Matthias Alexa ◽  
Annette Hasenburg ◽  
Marco Johannes Battista
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Treatment ◽  
Copy Number ◽  
Histological Grade ◽  
Treatment Decision ◽  
Risk Groups ◽  
Molecular Classification ◽  
Treatment Decisions ◽  
P53 Expression

Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry and mutation analysis: Polymerase Epsilon exonuclease domain mutated (POLE EDM), mismatch repair deficient (MMRd), p53 wild-type/copy-number-low (p53 wt), and p53-mutated/copy-number-high (p53 abn). Patients allocated to the POLE or abnormal p53 expression subtype are faced with a significantly altered outcome possibly requiring a modified adjuvant treatment decision. Within this review, we summarize the development of ProMisE, characterize the four molecular subtypes, and finally discuss its value in terms of a patient-tailored therapy in order to prevent significant under or overtreatment.

scholarly journals Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment

2021 ◽  
Vol 11 ◽  
Author(s):  
Camilla Nero ◽  
Francesca Ciccarone ◽  
Antonella Pietragalla ◽  
Simona Duranti ◽  
Gennaro Daniele ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Copy Number ◽  
Early Stage ◽  
Tumor Grade ◽  
Risk Groups ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Histologic Subtype

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient’s risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Everolimus (E) versus axitinib (A) as second-line therapy (2L) in metastatic renal cell carcinoma (mRCC): Retrospective experience at Gustave Roussy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
Annalisa Guida ◽  
Laurence Albiges ◽  
Yohann Loriot ◽  
Christophe Massard ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Patient Characteristics ◽  
Outcome Data ◽  
Rank Test ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Large Center ◽  
Third Line

527 Background: Currently both E and A are standard treatments for patients (pts) with mRCC after failure of first line therapy (1L)with VEGF-targeted therapy. There is no comparative study reported so far, and this study aims to evaluate these 2 drugs in a large center. Methods: Patient characteristics, safety and outcome data from all mRCC pts who received E or A as 2L at Gustave Roussy from April 2007 to May 2015 have been compared. Progression-free Survival (PFS) and Overall Survival (OS) were assessed by the Kaplan-Meier method and compared with the log-rank test. Results: 81 pts were treated with E and 45 pts with A. The table shows patient characteristics. The 2 groups were similar. The most common 1L was sunitinib (79% in E group and 82.2% in A group). Median follow up was 29 mo (95%CI 26 – 31), 26 mo for A and 33 mo for E (p=0.046). Median OS was 21.5 mo for E and 14.9 mo for A (p = 0.23). Median PFS was 5.3 and 7.7 mo for E and A respectively (p = 0.39). Disease control rate was 69% and 73% (p=0.31) and partial response was achieved in 4% and in 24% of pts (p=0.002), respectively in E and A cohort. At time of analysis E is ongoing in 3 pts (4%) and A in 9 pts (20%) (p=0.008). Third-line therapy (3L) was administrated in 62% of pts after E and in 33% after A (p=0.003). The most common 3L after E is A (48%) and vice versa the most common after A is E (71%). Median PFS of 3L after E is 9.1 mo (12.1 mo for A and 8 mo when 3L is not A (p=0.17)). Median PFS of 3L after A is 7.8 mo (95%CI 4-12). Conclusions: No statistically significant difference for PFS and OS were observed. Nevertheless, A showed more PR than E, while more pts received 3L after E. A remains very active in 3L. [Table: see text]

Novel risk stratification criteria of metastatic renal cell carcinoma (mRCC) patients (pts) treated with immune checkpoint inhibitors (ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16068-e16068 ◽  
Author(s):  
Dylan J Martini ◽  
Yuan Liu ◽  
Julie M. Shabto ◽  
Bradley Curtis Carthon ◽  
Greta Russler ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Checkpoint Inhibitors ◽  
Recursive Partitioning ◽  
Multivariable Analysis ◽  
Regression Tree ◽  
Progression Free Survival ◽  
Risk Groups ◽  
C Statistic ◽  
Kaplan Meier ◽  
Risk Grouping

e16068 Background: IMDC risk criteria is the gold standard for predicting outcomes for mRCC pts. We developed novel risk groups for mRCC pts treated with ICI. Methods: We performed a retrospective review of 100 ICI-treated mRCC pts at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression-free survival (PFS) were used to measure outcomes; OS was the primary outcome. We obtained baseline monocyte-to-lymphocyte ratio (MLR), body mass index (BMI), and metastatic (met) sites. We created a new variable (D_met) that combines number and sites of met: 0 = < 2 met sites; 1 = ≥ 2 met sites without liver metastases (mets); 2 = ≥ 2 met sites with liver mets. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS. Recursive partitioning and regression tree analyses were used for risk stratification. Discrimination of the risk score was measured by Uno C-statistics. Results: The pts were 66% males, 78% clear cell RCC (ccRCC), and 71% received anti-PD-1 monotherapy. Very poor risk pts (MLR ≥ 0.93 or MLR < 0.93, BMI < 24, and D_Met = 2) had significantly shorter OS and PFS than good risk pts (MLR < 0.93, BMI ≥ 24, and D_Met = 0) in univariable and multivariable analysis (UVA and MVA, Table). The Uno C-statistic for our risk grouping criteria compared to IMDC is 0.687 vs 0.566 (p = 0.061) for OS and 0.594 vs 0.541 (p = 0.78) for PFS. Conclusions: Risk grouping using MLR, BMI, and number and sites of mets may predict survival in mRCC pts treated with ICI. These results should be validated in a larger, prospective study. [Table: see text]

Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

1994 ◽  
Vol 72 (01) ◽  
pp. 033-038 ◽  
Author(s):  
N Schinaia ◽  
A M G Ghirardini ◽  
M G Mazzucconi ◽  
G Tagariello ◽  
M Morfini ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
National Registry ◽  
Factor Ix ◽  
Clotting Factor ◽  
Coagulation Disorders ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Congenital Coagulation Disorders ◽  
Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

Regional Cervical Plexus Blockage for Carotid Endarterectomy in Patients with Cardiovascular Risk Factors

2015 ◽  
Vol 18 (4) ◽  
pp. 140 ◽  
Author(s):  
Mehmet Taşar ◽  
Mehmet Kalender ◽  
Okay Güven Karaca ◽  
Ata Niyazi Ecevit ◽  
Salih Salihi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Carotid Endarterectomy ◽  
Regional Anesthesia ◽  
Carotid Artery Disease ◽  
Risk Groups ◽  
Cardiac Risk ◽  
Cervical Plexus ◽  
Cardiac Risk Factors ◽  
Significant Difference

Background: Carotid artery disease is not rare in cardiac patients. Patients with cardiac risk factors and carotid stenosis are prone to neurological and cardiovascular complications. With cardiac risk factors, carotid endarterectomy operation becomes challenging. Regional anesthesia is an alternative option, so we aimed to investigate the operative results of carotid endarterectomy operations under regional anesthesia in patients with cardiac risk factors. <br />Methods: We aimed to analyze and compare outcomes of carotid endarterectomy under regional anesthesia with cardiovascular risk groups retrospectively. Between 2006 and 2014, we applied 129 carotid endarterectomy ± patch plasty to 126 patients under combined cervical plexus block anesthesia. Patients were divided into three groups (high, moderate, low) according to their cardiovascular risks. Neurological and cardiovascular events after carotid endarterectomy were compared.<br />Results: Cerebrovascular accident was seen in 7 patients (5.55%) but there was no significant difference between groups (P &gt; .05). Mortality rate was 4.76% (n = 6); it was higher in the high risk group and was not statistically significant (P = .180). Four patients required revision for bleeding (3.17%). We did not observe any postoperative surgical infection.<br />Conclusion: Carotid endarterectomy can be safely performed with regional cervical anesthesia in all cardiovascular risk groups. Comprehensive studies comparing general anesthesia and regional anesthesia are needed. <br /><br />

scholarly journals Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy

2021 ◽  
Author(s):  
Satoe Fujiwara ◽  
Ruri Nishie ◽  
Shoko Ueda ◽  
Syunsuke Miyamoto ◽  
Shinichi Terada ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Laparoscopic Surgery ◽  
Retrospective Study ◽  
Prognostic Significance ◽  
Low Risk ◽  
Peritoneal Cytology ◽  
Chi Square ◽  
Significant Difference ◽  
Chi Square Test ◽  
Positive Peritoneal Cytology

Abstract Background There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. Methods From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan–Meier log rank. Results A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. Conclusion This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

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