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

2020 ◽  
Vol 30 (10) ◽  
pp. 1528-1534
Author(s):  
Agnieszka Rychlik ◽  
Ignacio Zapardiel ◽  
Laura Baquedano ◽  
María Ángeles Martínez Maestre ◽  
Denis Querleu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
European Society ◽  
Risk Group ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Nodal Metastases ◽  
Disease Free

ObjectiveRisk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology (ESMO), the European Society of Gynecologic Oncology (ESGO), and the European Society of Radiotherapy (ESTRO). A high–intermediate risk group was introduced within the intermediate risk group. The purpose of this study was to evaluate the clinical relevance of this subclassification.MethodsA multicenter retrospective study was carried out at five international tertiary institutions. Patients diagnosed with intermediate risk endometrial cancer on the basis of definitive pathology findings were included. Patients were stratified into intermediate and high–intermediate risk groups. Incidence of nodal metastases, and disease free and overall survival were compared between the two risk groups in univariate and multivariate analysis.Results477 patients were included: 325 (68%) patients were identified as intermediate and 152 (32%) as high–intermediate endometrial cancer patients. Nodal metastases were found in 18 patients (11.8%) in the high–intermediate risk endometrial cancer group and 16 patients (4.9%) in the intermediate risk group. Lymphovascular space invasion was found to be a strong predictive factor of lymph node involvement. High–intermediate risk was found to be an independent factor of disease free survival (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00 to 3.08; p=0.050) and overall survival (HR 1.99; 95% CI 1.10 to 3.60; p=0.022) in the multivariate analysis.ConclusionsThe study validates the clinical significance of the intermediate risk endometrial cancer subclassification. Prognosis for high–intermediate risk endometrial cancer was significantly poorer. The prevalence of lymph node metastases was higher in this group of patients.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study

2019 ◽  
Vol 26 (3) ◽  
pp. 619-631
Author(s):  
Abdullah Sakin ◽  
Nurgul Yasar ◽  
Suleyman Sahin ◽  
Serdar Arici ◽  
Saban Secmeler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Risk Group ◽  
Disease Free Survival ◽  
Old Patients ◽  
Free Survival ◽  
Disease Free

Background This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. Methods Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. Results The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70–94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. Conclusion The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.

scholarly journals Additional Gene Mutations Refine the 2017 European Leukemianet (ELN) Classification of Adult Patients (Pts) with De Novo Acute Myeloid Leukemia (AML) Aged <60 Years: An Analysis of Alliance for Clinical Trials in Oncology (Alliance) Studies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2740-2740 ◽  
Author(s):  
Ann-Kathrin Eisfeld ◽  
Jessica Kohlschmidt ◽  
Krzysztof Mrózek ◽  
Alice S. Mims ◽  
Christopher J. Walker ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Genetic Risk ◽  
Risk Group ◽  
Gene Mutations ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Advisory Committees ◽  
Npm1 Mutation ◽  
Disease Free

Abstract The ELN recommendations for diagnosis and management of AML in adults, authored by a panel of international experts, have become an important tool to assess pts' prognosis and guide treatment decisions. Following advances in our understanding of the molecular landscape of AML, several gene mutations were added as criteria for assigning pts to genetic risk categories in the 2017 ELN classification. The aim of our study was to apply the 2017 ELN risk groups to a large cohort of 864 AML pts aged <60 years who were similarly treated with intensive cytarabine/daunorubicin based chemotherapy on Cancer and Leukemia Group B/Alliance protocols. In addition, we sought to identify novel gene markers that could refine the ELN classification. Using the 2017 ELN genetic risk-stratification criteria, we assigned 49% of pts to the Favorable-risk group, whereas 22% and 29% of pts belonged to the Intermediate- and Adverse-risk groups, respectively. The complete remission (CR) rate of Favorable-risk pts was 92%, compared with 77% and 48% CR rates of Intermediate-risk and Adverse-risk pts. Fifty-two percent of Favorable-risk pts were disease-free and 63% were alive 3 years after diagnosis, compared with the respective 3-year rates of 22% and 32% for pts belonging to the Intermediate-risk group, and only 10% and 19%, respectively, for pts classified in the Adverse-risk group. Using a targeted 80-gene sequencing panel, we detected 2,354 mutations, with a median of 3 per pt. The frequencies of specific mutations differed between the ELN risk groups. We performed multivariable outcome analyses for the achievement of CR, disease-free (DFS) and overall (OS) survival within each of the ELN groups. Within the Favorable-risk group MVA analyses, the presence of WT1 mutations associated with lower CR rates (P=0.02). Mutations in BCOR (P=0.02), IDH1 (P=0.04), KIT (P<0.001), PTPN11 (P=0.01) and SETBP1 (P=0.02) associated with a shorter DFS; mutated BCOR (P=0.02), IDH1 (P=0.006), SETBP1 (P=0.004), WT1 (P<0.001) and ZRSR2 (P=0.002) associated with a shorter OS. In the Intermediate-risk group MVA analyses, mutations in WT1 associated with lower CR rates (P=0.02). Mutations in DNMT3A and WT1 associated with shorter DFS (DNMT3A, P<0.001; WT1, P=0.01) and OS (DNMT3A, P<0.001; WT1, P=0.005). In the Adverse-risk group MVA analyses, IDH2 mutations associated with lower CR rates (P=0.05). NRAS mutations associated with shorter DFS (P<0.001) and OS (P=0.008). In addition, IDH2- (P=0.03) and TET2-mutated pts (P=0.009) had shorter OS than pts without these mutations. Among FLT3-ITDlow pts, those harboring NPM1 mutation had higher CR rates (P<0.001) and longer OS (P=0.001), but not DFS (P=0.16), than pts with wild-type (wt) NPM1. Within the FLT3-ITDhigh cohort, pts with an NPM1 mutation had higher CR rates than those without (P<0.001). However, there was no difference in either DFS or OS between NPM1 mutated and NPM1 wt pts, indicating that the negative prognostic impact of FLT3-ITDhigh may outweigh the positive prognostic impact of NPM1 mutations with respect to those survival endpoints. We also noted that the negative prognostic impact of WT1 mutations was worsened by co-occurring NPM1 mutations. Similarly, the impact of IDH1 mutations within the Favorable group was influenced by NPM1 mutations, with IDH1/NPM1 co-mutated patients having inferior survival. Based on the results of our multivariable analyses, as well as co-occurring mutations, we provide a possible refinement of the ELN genetic risk stratification in Table 1. DFS and OS of the re-classified pts were comparable to DFS and OS of the original ELN groups (Figure 1). Importantly, the re-classification also changed the percentages of AML patients assigned to specific risk groups, reducing the Favorable-risk group from 49% to 39% and increasing the Adverse-risk group from 29% to 38%, with the Intermediate-risk group remaining almost the same (23% vs 22%). In summary, our study provides a comprehensive analysis of genetic prognostic markers in younger AML pts treated with standard chemotherapy within the framework of the ELN risk classification. Furthermore, we identified several combinations of co-occurring mutations with prognostic significance. Our results provide a refinement of the 2017 ELN risk classification, and identify additional pts that may need more intensive treatment early on. Support: U10CA180821, U10CA180882, U10CA180861, U24CA196171; ClinicalTrials.gov Disclosures Mims: Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Kolitz:Magellan Health: Consultancy, Honoraria. Powell:Rafael Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Varying Importance of Prognostic Factors in Subgroups of Myelodysplastic Syndromes Defined by Blast Count, Cytogenetic Risk Group, or WHO Classification.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2776-2776
Author(s):  
Andrea Kuendgen ◽  
Corinna Strupp ◽  
Kathrin Nachtkamp ◽  
Barbara Hildebrandt ◽  
Rainer Haas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Univariate Analysis ◽  
Risk Groups ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Blast Count

Abstract Abstract 2776 Poster Board II-752 Introduction: We wondered whether prognostic factors have similar relevance in different subpopulations of MDS patients. Methods: Our analysis was based on patients with primary, untreated MDS, including 181 RA, 169 RARS, 649 RCMD, 322 RSCMD, 79 5q-syndromes, 290 RAEB I, 324 RAEB II, 266 CMML I, 64 CMML II, and 209 RAEB-T. The impact of prognostic variables in univariate analysis was compared in subpopulations of patients defined by medullary blast count, namely <5%, ≥5% (table), ≥10%, and ≥20% (not shown), as well as 3 subpopulations defined by the cytogenetic risk groups according to IPSS (table). Multivariate analysis of prognostic factors was performed for cytogenetically defined subgroups and WHO-subtypes. Results: Strong prognostic factors in all blast-defined subgroups were hemoglobin, transfusion dependency, increased WBC, age, and LDH. However, all variables became less important in patients with ≥20% blasts (RAEB-T) and increased WBC was rare. Platelet count and cytogenetic risk groups were relevant in patients with <5%, ≥5%, and ≥10% marrow blasts, but not in RAEB-T. Marrow fibrosis was important in patients with <5% or ≥5% blasts, but not ≥10%. Gender and ANC <1000/μl were significant only in patients with a normal blast count. Furthermore, we looked for the effect of the karyotypes, relevant for IPSS scoring (-Y, del5q, del20q, others, del7q/-7, complex), and found a comparable influence on survival, irrespective whether patients had < or ≥5% marrow blasts. In subpopulations defined by cytogenetic risk groups, several prognostic factors were highly significant in univariate analysis, if patients had a good risk karyotype. These included hemoglobin, sex, age, LDH, increased WBC, transfusion need, and blast count (cut-offs 5%, 10%, and 20%). In the intermediate risk group only LDH, platelets, WBC, and blasts were significant prognostic factors, while in the high risk group only platelets and blast count remained significant. Multivariate analysis was performed for the cytogenetic risk groups and for subgroups defined by WHO subtypes. The analysis considered blast count (</≥5%), hemoglobin, platelets, ANC, cytogenetic risk group, transfusion need, sex, and age. In the subgroup including RA, RARS, and 5q-syndrome, LDH, transfusion, and age in descending order were independent prognostic parameters. In the RCMD+RSCMD group, karyotype, age, transfusion, and platelets were relevant factors. In the RAEB I+II subgroup, the order was hemoglobin, karyotype, age, and platelets, while in CMML I+II only hemoglobin had independent influence. In RAEB-T none of the factors examined was of independent significance. Looking at cytogenetic risk groups, in the favorable group, several variables independently influenced survival, namely transfusion, blasts, age, sex, and LDH (in this order). Interestingly, in the intermediate and high risk group, only blast count and platelets retained a significant impact. Conclusion: Univariate analysis showed prognostic factors (except ANC) included in IPSS and WPSS are relevant in most subgroups defined by marrow blast percentage. However, they all lose their impact if the blast count exceeds 20%. Regarding cytogenetic risk groups, several prognostic factors lose their influence already in the intermediate risk group. This underscores the prognostic importance of MDS cytogenetics. Multivariate analysis showed MDS subpopulations defined by WHO types also differ with regard to prognostic factors. In particular, CMML and RAEB-T stand out against the other MDS types. Disclosures: Kuendgen: Celgene: Honoraria. Hildebrandt:Celgene: Research Funding. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials. Germing:Novartis, Celgene: Honoraria, Research Funding.

The impact of the metastasis region on patients with metastatic renal cell cancer in the intermediate-risk group.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17091-e17091
Author(s):  
Cengiz Karacin ◽  
Fatma Bugdaycı Basal ◽  
Irem Bilgetekin ◽  
Omur Berna Oksuzoglu
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Lymph Node ◽  
Brain Metastasis ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Group ◽  
Intermediate Risk ◽  
The Impact

e17091 Background: The majority of patients with metastatic renal cell carcinoma (mRCC) are in the intermediate-risk group, according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Some patients in the intermediate-risk group have similar overall survival (OS) with those in the good-risk group, while others with those in the poor-risk group. In our study, we aimed to evaluate the prognostic significance of the region of the metastasis and to classify the intermediate-risk group into two as favorable or unfavorable according to the metastasis region. Methods: We retrospectively analyzed the clinical data of patients with mRCC those in the intermediate-risk group seen at our Oncology Training and Research Hospital from 2010 to 2018. Patients who received at least one line of tyrosine kinase inhibitor (TKI) were included in the study. Overall survival was calculated. The log-rank test was used to check the statistical significance for OS. Results: Of 113 patients, median age 58 (range 34-78) years, 99 (88%) had more than one site of metastasis: 61 (54%) lung, 41 (36%) bone, 21 (18%) lymph node, and 19 (17%) brain metastasis. Nine patients received one, 86 patients received two, and 18 patients received three lines of systemic therapy. Median follow up was 14 (range 4 – 54) months. Median OS for patients with bone and/or brain metastasis was 10 (95% CI = 6.1 – 13.9) months compared to 16 (95% CI = 10.1 – 22.2) months for patients with lung and/or lymph node metastasis (HR = 1.675, p-value = 0.012). Conclusions: Our data suggest that the bone and/or brain metastasis in the intermediate-risk group mRCC patients treated with TKI are unfavorable prognostic factors.

Does lymphadenectomy improve survival in patients with intermediate risk endometrial cancer? A multicentric study from the FRANCOGYN Research Group

2018 ◽  
Vol 29 (2) ◽  
pp. 282-289
Author(s):  
Lilia Bougherara ◽  
Henri Azaïs ◽  
Hélène Béhal ◽  
Geoffroy Canlorbe ◽  
Marcos Ballester ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
Survival Rates ◽  
Intermediate Risk ◽  
Nodal Staging ◽  
Relapse Free Survival ◽  
Multicentric Study ◽  
Free Survival ◽  
The Impact

ObjectiveThe role of lymphadenectomy in intermediate risk endometrial cancer remains uncertain. We evaluated the impact of lymphadenectomy on overall survival and relapse-free survival for patients with intermediate risk endometrial cancer.MethodsWe retrospectively reviewed patients from the FRANCOGYN database with intermediate risk endometrial cancer, based on pre-operative and post-operative criteria (type 1, grade 1–2 tumors with deep (> 50%) myometrial invasion and no lymphovascular space invasion), who received primary surgical treatment between November 2002 and August 2013. We compared overall survival and relapse-free survival between staged and unstaged patients.ResultsFrom 1235 screened patients, we selected 108 patients with intermediate risk endometrial cancer. Eighty-two (75.9%) patients underwent nodal staging (consisting of pelvic +/- para-aortic lymphadenectomy). Among them, 35 (32.4%) had lymph node disease. The median follow-up was 25 months (range 0.4 to 155.0). The overall survival rates were 82.5% for patients staged (CI 64.2 to 91.9) vs 77.9 % for unstaged patients (CI 35.4 to 94.2) (P = 0.73). The relapse-free survival rates were 68.9% for staged patients (CI 51.2 to 81.3) vs 68.8% for unstaged patients (CI 29.1 to 89.3) (P=0.67).ConclusionSystematic nodal staging does not appear to improve overall survival and relapse-free survival for patients with IR EC but could provide information to tailor adjuvant therapy. Sentinel lymph node dissection may be an effective and less invasive alternative staging technique and should provide a future alternative for this population.

scholarly journals Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3554
Author(s):  
Taizo Uchimoto ◽  
Kazumasa Komura ◽  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Kazuhiro Takahashi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Model ◽  
Risk Group ◽  
Objective Response ◽  
Collaborative Study ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Neutrophil Lymphocyte Ratio ◽  
Poor Risk ◽  
Metastatic Sites

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

CGE19-065: Number of Somatic Mutations Is an Independent Predictor of Overall Survival in Acute Myeloid Leukemia

2019 ◽  
Vol 17 (3.5) ◽  
pp. CGE19-065
Author(s):  
Zin W. Myint ◽  
Rani Jayswal ◽  
Ranjana Arora ◽  
Gregory P. Monohan ◽  
Amit Goldberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Poor Risk ◽  
Baseline Characteristics ◽  
Clinically Significant

Purpose: Acute myeloid leukemia (AML) is characterized by multiple somatically acquired mutations that affect genes of different functional categories. It has been well established in myelodysplastic syndrome (MDS) that the cumulative number of somatic mutations has an impact on overall survival. However, no such data exist for AML. In this study, we sought to determine the number of clinically significant somatic mutations for each cytogenetically defined risk group of AML and to determine whether this had an impact on overall survival (OS). Methods: In this retrospective, single-center study, all adult patients diagnosed with AML from August 2016–December 2017 were reviewed. Baseline characteristics, somatic mutations in the diagnostic bone marrow as detected by Next Generation Sequencing (NGS), and survival outcomes were analyzed. NGS panel was done in-house and could identify 94 genes. Patients were divided into favorable, intermediate, and poor risk groups based on cytogenetics, and molecular abnormalities using NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML, version 1.2018. Kaplan-Meier plots and Cox regression analyses were utilized. Results: A total of 105 AML patients were included; baseline characteristics and frequency of identified clinically significant (CS) mutations are described in the presentation. The FLT3 mutation occurred in the highest frequency (22%) followed by DNMT3A & ASXL1 (15%). 17 (16%) patients were favorable risk, 33 (31%) intermediate risk, and 55 (52%) were poor risk. 67.6% of patients were male, and the median age was 64 (20–79) years. There was a difference in the number of CS mutations between the intermediate risk group and favorable risk group (P=.007), but not between the favorable risk and poor risk groups (P=.221) or between the intermediate risk group and poor risk group (P=.093). Increased number of CS mutations (≥ 5) was seen with equal frequency across risk groups and predicted for shorter overall survival in both univariate (HR=2.80; P=.039) and by multivariate Cox regression analysis (P=.001) independently from assigned risk group. There were no differences in age, gender, smoke, geographic, and different risk groups by multivariate analyses. Conclusion: Our study shows that ≥ 5clinically significant somatic mutations were associated with adverse outcomes and decreased survival, independent of risk groups and induction regimen. Thus, it may be a useful prognostic factor. This finding needs to be validated using a larger sample size.

scholarly journals Exploring the Clinical Characteristics of the Lymph Nodal Metastatic Regions in Patients with Endometrial Cancer

2021 ◽  
Author(s):  
Wonkyo Shin ◽  
Sun-Young Kim ◽  
Sangyoon Park ◽  
Sokbom Kang ◽  
Myong Cheol Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Risk Group ◽  
Survival Rates ◽  
Cox Proportional Hazards Model ◽  
Clinical Factors ◽  
Gynecology And Obstetrics ◽  
Overall Survival Rates

Abstract Objective To evaluate clinical factors that can help determine the extent of lymphadenectomy required in endometrial cancer patients and confirm the differences of metastatic lymph node regions based on the risk factors for endometrial cancer patients. Methods The medical records of 468 endometrial cancer patients were retrospectively reviewed between January 2006 and December 2018. Patients were categorized into pelvic lymph node dissection (PLND) and pelvic plus para-aortic lymph nodes dissection (PPALND) groups. Demographics, recurrence-free survival, and 5-year overall survival rates were compared, and the clinical factors affecting survival were evaluated using Cox proportional hazards model. Results The median follow-up period was 55 months (range, 6–142 months). The mean age was higher in the PPALND group than in the PLND group (51.0 vs. 54.5 years; P < 0.001). The PPALND group had a higher International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular invasion, endocervical invasion, and FIGO grade (P = 0.001) than the PLND group. The PPALND group had higher 5-year recurrence-free and overall survival rates than the PLND group. While comparing lymph node (LN) metastasis confirmed pathologically, the group with confirmed metastasis showed a higher number of high-risk group patients than lymph node-negative patients. However, no difference was observed in pelvic LN metastasis, pelvic plus para-aortic LN metastasis, and isolated para-aortic LN metastasis groups. Conclusions When treating patients with endometrial cancer, risk group evaluation is an important factor for determining LN dissection. Our study found no differences in clinical factors of metastatic LN regions.

scholarly journals The Impact of Cytogenetics on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Survey from the Acute Leukemia Working Party (ALWP) of EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4639-4639
Author(s):  
Monica Poiani ◽  
Myriam Labopin ◽  
Dietrich W. Beelen ◽  
Johanna Tischer ◽  
Jürgen Finke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Stem Cell Transplantation ◽  
Research Funding ◽  
Risk Group ◽  
Chronic Gvhd ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Free Survival

Abstract Introduction: Diagnostic karyotype is one of the most important determinants of initial response to treatment, remission duration and overall survival in Acute Myelogenous Leukemia (AML). Moreover, risk stratification of AML based on cytogenetic abnormalities is a key parameter for the success rate and outcome of allogeneic stem cell transplantation (allo-SCT) in AML. However, while the prognostic significance of chromosomal abnormalities is well established during frontline therapy, its influence at time of salvage therapy in Primary Refractory (Ref) and Relapsed (Rel) AML and the role of allo-SCT in this subset, remains uncertain. Patients and methods: This was a survey from the EBMT registry which included adult AML patients undergoing allo-SCT for Ref/Rel AML from HLA-matched related or 9/10 - 10/10 unrelated donor (UD) between 2000 and 2017. Patients were stratified according to cytogenetic risk as defined by Grimwade et al. (Blood 2010). Primary endpoint was Leukemia-Free Survival (LFS). Secondary endpoints were relapse cumulative incidence (RI), non-relapse mortality (NRM), overall survival (OS), acute and chronic GVHD and GVHD-relapse-free Survival (GRFS). Results: 2089 patients with Ref AML (n=972) and Rel AML (n=1117) were analyzed: 154 patients had a favorable risk, 1283 were in intermediate risk and 652 had an adverse cytogenetic risk. Median follow-up was 49 months. Patients and transplant characteristics are summarized in table 1. Patients in the favorable risk group were younger and transplanted more frequently in first or second relapse. Patients in the adverse risk group received more frequently transplants from 9/10 UD. FLT3-ITD mutation was present in 18%, 43% and 16% of the favorable, intermediate and adverse risk groups, respectively (p<10-3). The 3 groups were not significantly different in terms of Karnosfky score, patient and CMV serology status and conditioning intensity (myeloablative or reduced). Outcome correlated with cytogenetic category, with a percentage of complete remission within 100 days after transplant of 79%, 69% and 61% (p<10-3), RI at 2 years were 42%, 51% and 61% (p<10-5), LFS and OS rates were 34%, 27%, 18% and 41%, 33%, 22% in favorable, intermediate and adverse risk group (p<10-5 for both LFS and OS), respectively. Non-relapse mortality, on the contrary, did not differ among the three groups (24%, 21% and 21%, respectively; p=NS). We performed a multivariate analysis adjusting for all factors differing between risk groups and factors known as influencing outcome of AML patients after allograft. Compared to the favorable risk group, intermediate risk group was associated with a higher RI (HR=1.58; 95% CI: 1.17-2.14; p=0.003), lower LFS (HR=1.39; 95% CI: 1.09-1.77; p=0.008), lower OS (HR=1;47; 95% CI: 1.14-1.90; p=0.003) and lower GRFS (HR=1;29; 95% CI: 1.03-1.61; p=0.03). The adverse risk group was associated with a higher RI (HR=2.27; 95% CI: 1.65-3.10; p<10-5), lower LFS (HR=1.86; 95% CI: 1.44-2.40; p<10-5), lower OS (HR=1.89; 95% CI: 1.44-2.47; p<10-5) and lower GRFS (HR=1.62; 95% CI: 1.28-2.06; p<10-4; Figure1). In a subgroup analysis of patients in intermediate or adverse risk groups with available information on FLT3-ITD status, adverse cytogenetics remained an important prognostic factor for RI (HR=1.55; 95% CI: 1.22-1.97; p=0.0004), LFS (HR=1.37; 95% CI: 1.12-1.68; p=0.002), OS (HR=1.38; 95% CI: 1.11-1.70; p=0.003) and GRFS (HR=1.31; 95% CI: 1.08-1.59; p=0.006) compared to the intermediate risk group. Other poor prognostic factors in this population were presence of FLT3-ITD mutation, Rel vs Ref status at transplant, Karnofsky score <80%, use of bone marrow as stem cell source and patient CMV serology positivity. In vivo T cell depletion was associated with a lower risk of acute and chronic GVHD and a better GRFS. Conclusion: In Rel and Ref AML karyotype remains an important prognostic factor for those patients undergoing allo-SCT in active disease phase, allowing to separate patients into different risk groups. Moreover, FLT3-ITD mutation remains a negative prognostic factor in this population. Disclosures Beelen: Medac: Consultancy, Other: Travel Support. Tischer:Jazz Pharmaceuticals: Other: Jazz Advisory Board. Finke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Mohty:MaaT Pharma: Consultancy, Honoraria.

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