The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype

Abstract The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level—measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3 + 1)—on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML.

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TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01078-2 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Hideyuki Arita ◽

Yuko Matsushita ◽

Ryunosuke Machida ◽

Kai Yamasaki ◽

Nobuhiro Hata ◽

...

Keyword(s):

Cox Regression ◽

Hazard Ratio ◽

Prognostic Impact ◽

Promoter Mutation ◽

Who Grade ◽

Favorable Prognosis ◽

Diffuse Gliomas ◽

Grade Ii ◽

Promoter Mutations ◽

The Impact

AbstractTERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90–100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

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The Prognostic Impact of High EVI1 expression In AML Is Due to Its Close Correlation to Rearrangements Involving EVI1 or MLL, which Are Cytogenetically Cryptic In a Subset of Patients: a Study on 332 Cases.

Blood ◽

10.1182/blood.v116.21.1676.1676 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1676-1676

Author(s):

Claudia Haferlach ◽

Vera Grossmann ◽

Melanie Zenger ◽

Tamara Alpermann ◽

Alexander Kohlmann ◽

...

Keyword(s):

Chromosome Banding ◽

Normal Karyotype ◽

Fish Analysis ◽

Prognostic Impact ◽

Employment Equity ◽

Npm1 Mutation ◽

Banding Analysis ◽

Chromosome Banding Analysis ◽

Equity Ownership ◽

The Impact

Abstract Abstract 1676 Introduction: High EVI1 expression has been proposed as a negative prognostic factor in AML. An association between high EVI1 expression and distinct cytogenetic subgroups, such as 3q26-rearrangements, MLL-rearrangements and -7/7q- have been reported. Both 3q26- and MLL-rearrangements can be difficult to detect by chromosome banding analyses or may even be cytogenetically cryptic in a subset of patients due to limited resolution. Therefore, only studies using FISH for the detection of cryptic EVI1- or MLL-rearrangements can clarify their frequencies in AML with elevated EVI1 expression. Methods/Patients:: The study cohort was composed of 332 AML cases with a) normal karyotype (NK) (n=211), b) -7/7q- (n=77), and for comparison c) 3q26-rearrangements (n=38), and d) MLL-rearrangement (n=6). In all cases EVI1 expression was investigated using quantitative PCR calculating a % EVI1/ABL1 expression. In all cases FISH for EVI1 rearrangement was performed in addition to chromosome banding analysis. Cases with high EVI1 expression were also analyzed for MLL rearrangements by FISH. Results: In the total cohort, EVI1 expression varied between 0 and 1614 (median: 21.1). The highest EVI1 expression was measured in cases with cytogenetically identified 3q26-rearrangements (range: 6.1–566.4; median: 81.9) and in AML with MLL-rearrangements (range: 46.7–831; median: 239). The EVI1 expression was significantly lower in AML with NK (range: 0–1614; median: 0.5, p<0.001) and AML with -7/7q- (range: 0.03–199; mean: 34.5; median: 10.7, p<0.001). In the subgroup of cases with NK 4 MLL-rearrangements (1.9%) were detected by FISH and subsequently verified by fusion gene specific PCR. In addition, 4 cases with cryptic EVI1-rearrangements (1.9%) were identified by FISH analysis. Further genetic analysis revealed that these were due to t(3;8)(q26;q24) (n=2) and t(3;21)(q26;q11) (n=1). In one case, the EVI1-rearrangement could not be further analyzed due to lack of material. In the -7/7q- cohort 14/77 cases (18.2%) with cytogenetically cryptic EVI1 rearrangement including 3 novel recurrent abnormalities were detected: t(3;21)(q26;q11) (n=3), inv(3)(p24q26) (n=4) and t(3;8)(q26;q24) (n=2). In 5 cases FISH analysis revealed that the 7q- was not caused by an interstitial deletion but due to an unbalanced rearrangement between chromosomes 7 and 3: der(7)t(3;7)(q26;q21). In these 5 cases high-resolution SNP microarray were performed and revealed breakpoints in the CDK6 gene and centromeric of the EVI1 gene. Further mutation screening revealed that none of the cases with EVI1- or MLL-rearrangement harboured mutations in NPM1 or CEPBA. In 254 cases clinical follow-up data was available. Different cut-off levels of EVI1 expression were tested, and a cut-off at 30% EVI1/ABL1 expression was the lowest level that had a significant impact on outcome. Separating the cohort at this cut-off into high EVI1 (n=67) and low EVI1 expressors (n=187) showed a shorter EFS in patients with high EVI1-expression (p=0.001; relative risk (RR)=1.87, median EFS 6.2 vs 15.0 months (mo)), while no impact on OS was observed. When the same analyses were performed with respect to EVI1-rearrangements we observed both a significantly shorter EFS in cases with EVI1-rearrangement (n=39) vs all others (n=215) (p=0.001; RR=2.03, median EFS 4.6 vs 15.0 mo) and a significantly shorter OS (p=0.026; RR=1.73, median OS 10.1 vs 26.3 mo). Analyzing the impact of high EVI1 expression separately in the cohort without EVI1 rearrangement revealed no impact of EVI1 expression on EFS. Conclusions: The negative prognostic impact of high EVI1 expression is strongly associated with EVI1- or MLL-rearrangements and is absent in AML without EVI1- and MLL-rearrangement. Applying FISH in addition to chromosome banding analysis we identified cryptic rearrangements in 3.8% of AML with normal karyotype and in 18.2% of AML with -7/7q-, including 3 novel recurrent cytogenetically cryptic EVI1-rearrangements. This data supports the routine performance of FISH screening for EVI1- and MLL-rearrangements in patients with normal karyotype or 7q-/-7 and without NPM1 mutation and CEPBA mutation to assign patients to the correct biologic entity. The postulated independent prognostic impact of EVI1 expression should be tested further including this laboratory workflow as these parameters may have important impact on prognosis and future treatment strategies. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Grossmann:MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)

Blood ◽

10.1182/blood-2005-08-3167 ◽

2006 ◽

Vol 107 (10) ◽

pp. 4011-4020 ◽

Cited By ~ 452

Author(s):

Christian Thiede ◽

Sina Koch ◽

Eva Creutzig ◽

Christine Steudel ◽

Thomas Illmer ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

Normal Karyotype ◽

Clinical Impact ◽

Prognostic Impact ◽

Npm1 Mutation ◽

Free Survival ◽

High Bone ◽

Acute Myeloid

Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P < .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P < .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment.

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Prognostic impact of miR-196a/b expression in adult acute myeloid leukaemia: a single-centre, retrospective cohort study

Journal of International Medical Research ◽

10.1177/0300060518777399 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3675-3683 ◽

Cited By ~ 2

Author(s):

JunYu Zhang ◽

WeiE Liu ◽

Jing Du ◽

YangJin Jin ◽

MinLei Zhao ◽

...

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Cox Regression ◽

Prognostic Significance ◽

Prognostic Impact ◽

Event Free Survival ◽

Internal Tandem Duplication ◽

Free Survival ◽

Prognostic Effect ◽

Acute Myeloid

Objective The prognostic effect of miR-196a/b expression in adult patients with leukaemia remains unclear. This study aimed to determine whether miR-196a/b expression can serve as a prognostic factor for patients with acute myeloid leukaemia. Methods We enrolled 124 patients with acute myeloid leukaemia. We measured miR-196a/b expression by real-time reverse transcription-polymerase chain reaction. We classified patients into high and low expression groups based on the median expression value. Cox regression analyses were carried out to assess the prognostic significance of miR-196a/b expression in the context of well-established predictors. Results Patients with high miR-196a/b expression were older in age, and had higher white blood cell and platelet counts than did patients with low miR-196a/b expression. Patients with high miR-196a/b expression were associated with the French–American–British classification M5 subtype and with the presence of nucleophosmin and FLT3 internal tandem duplication mutations, but were not associated with the favourable karyotype risk subgroup. Moreover, patients with high miR-196a/b expression had a shorter event-free survival rate compared with those with low miR-196a/b expression in univariate and multivariate analyses. Conclusion High miR-196a/b expression is associated with poor event-free survival.

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Prognostic value of CD8+ tumor-infiltrating lymphocyte density and PD-L1 expression in tumor cells in thymic epithelial tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.21 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 21-21

Author(s):

Yuki Katsuya ◽

Hidehito Horinouchi ◽

Yasushi Goto ◽

Shintaro Kanda ◽

Yutaka Fujiwara ◽

...

Keyword(s):

Patient Outcome ◽

Cox Regression ◽

Prognostic Significance ◽

Average Density ◽

Hazard Ratio ◽

Related Factor ◽

Prognostic Impact ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

The Impact

21 Background: The prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in thymic epithelial tumors (TETs; thymoma [TM] and thymic carcinoma [TC]) is unknown. We examined whether the density of CD8+ TILs and the PD-L1 expression level in TETs were correlated with patient outcome. Methods: Immunohistochemistry and a semi-automated software quantification analysis were used to examine formalin-fixed paraffin-embedded specimens from patients with TET who had been treated with chemotherapy. The density of CD8+ TILs was evaluated at two representative sites: within the tumor nest (intratumoral CD8), and at the invasive margin (stromal CD8, if evaluable). The average density of CD8+ TILs was used as the cut-off value, while an H-score of 5% was used as the cut-off for PD-L1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate prognostic factors. Results: Twenty-six patients (TM/TC 9/17) were evaluated. A high intratumoral CD8 density was correlated with a superior outcome in terms of both PFS (median, 7.6 vs 27.7 months; P = 0.002) and OS (median, 54.3 months vs not reached; P = 0.022) among the patients with TM, and a similar tendency was seen among the patients with TC, although the correlations were not statistically significant. PD-L1 expression was not significantly correlated with patient outcome in the TM and TC groups. Univariate and multivariate analyses demonstrated that a high intratumoral CD8 density was a significant predictive factor for PFS (Hazard ratio, 0.25 [95%CI 0.08–0.75]; P = 0.014) and OS (Hazard ratio, 0.06 [95%CI 0.007–0.44]; P= 0.006), whereas PD-L1 expression was not. The tendency for a change in the intratumoral CD8 density in pre/post-chemotherapy TM specimens was not consistent. The proportion of stromal CD8 density to intratumoral CD8 density in the TC specimens was not correlated with survival. Conclusions: A high intratumoral CD8 density had a positive prognostic impact for patients with TETs, especially those with TMs. The impact of this immune-related factor should be validated in a larger cohort.

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Cytogenetic Risk Stratification in Primary Versus Post-Essential Thrombocythemia / Post-Polycythemia Vera Myelofibrosis

Blood ◽

10.1182/blood.v128.22.4250.4250 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4250-4250 ◽

Cited By ~ 1

Author(s):

Lucia Masarova ◽

Prithviraj Bose ◽

Naval G. Daver ◽

Naveen Pemmaraju ◽

Kate J Newberry ◽

...

Keyword(s):

Overall Survival ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Research Funding ◽

Cox Regression ◽

International System ◽

Normal Karyotype ◽

Prognostic Impact ◽

Number Of Patients ◽

The Impact

Abstract Introduction: The Dynamic International Prognostic Scoring System-Plus (DIPPS-Plus) for primary myelofibrosis (PMF) categorizes cytogenetic abnormalities as "favorable" and "unfavorable." Abnormalities (Abn) -7/7q-; -5/5q-; i(17q), +8; inv(3); 12p-; 11q23; and complex karyotype (CK; >3 Abn) are considered unfavorable. More recently monosomal karyotype (MK), defined as 2 autosomal monosomies or a single monosomy with at least one additional structural Abn, was also recognized as unfavorable (Vaidya, Blood 2011). While the prognostic impact of cytogenetic Abn has been studied in patients with PMF, almost no data exist in patients with post-essential thrombocythemia/polycythemia vera myelofibrosis (PET/PV-MF). Objective: To identify the impact of cytogenetic Abn on prognosis in patients with PMF and PET/PPV-MF referred to our center between 1984 and 2013. Methods: We retrospectively reviewed the charts of 1100 patients with MF. Cytogenetic analysis performed at the time of referral to our institution was reported according to the International System for Human Cytogenetic Nomenclature. Overall survival (OS) was calculated and compared using the Kaplan-Meier method with the log rank test. The impact of each cytogenetic Abn on OS was measured by stepwise Cox regression model by comparing them against patients with diploid karyotype. Analyses were conducted separately for patients with PMF and PET/PPV-MF. Results: Cytogenetic data (≥ 10 metaphases) were available in 981 patients (660 with PMF and 321 with PET/PPV-MF). Median age was similar in both groups (66 years; range, 27-90), and 61% of patients were male. The distribution of DIPSS scores were similar in both groups (overall 7% low, 37% int-1, 41% int-2 and 15% high). OS in each DIPSS category were 134, 65, 33, 19 months in patients with PMF; and 160, 73, 48, 36 in patients with PET/PPV-MF (in both groups P<0.001). The JAK2 mutation was present in 65% of patients in both groups. Overall, 621 (63%) patients had diploid karyotype (DK), 17% had CK (n=62), and 7% had MK (n=26). Abnormal karyotypes present in >10% of patients were single 20q- (n=75, 21%), single 13q- (n=38, 11%), and CK (n=62, 17%). Others Abn (single +8, +9, single -7/7q-, -5/5q-, or various combinations of the two Abn) occurred less frequently. Importantly, Abn of chromosome (chr) 17 occurred only in patients with PMF, while all other Abn were similarly distributed among PMF and PET/PPV-MF. Ninety nine patients (10%) developed AML, 44% of whom had cytogenetic Abn, similar in PMF and PET/PPV-MF. After a median follow-up of 31 months (range, 0.5-251), 548 (56%) of patients have died, with similar rates in both groups. Impact of different cytogenetic Abn on OS is presented in Table 1 and Graph 1 for PMF, and Graph 2 for PET/PPV-MF. We have identified 4 different risk categories in PMF patients with respective median OS of 86, 46, 14 and 6 months (P<0.001, Graph 1A). Only 2 different categories were identified in patients with PET/PPV-MF, with the corresponding OS of 70 and 14 months (P<0.001, Graph 1B); further separation of these patients was not possible due to smaller number of patients with specific Abn. Conclusions: Results from our cohort of 691 PMF and 321 PET/PPV-MF patients differ from those described in DIPSS-Plus. First, we showed that OS in patients with PMF and single +8 Abn, and 1-3 abnormalities (excluding chromosomes 5, 7, 12p and MK) is no different than in those with normal karyotype. Second, OS was the best in patients with single 20q- Abn, which was significantly better than in patients with normal karyotype. Third, we report cytogenetic stratification on the largest cohort of PET/PPV-MF patients, with findings different than in PMF (Table 1). Further validation in larger multicenter studies is warranted. Table Table. Figure Overall survival in PMF [1A] and PET/PPV-MF [1B] patients stratified by cytogenetic groups. Figure. Overall survival in PMF [1A] and PET/PPV-MF [1B] patients stratified by cytogenetic groups. Disclosures Cortes: ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

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H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

10.21203/rs.3.rs-949930/v1 ◽

2021 ◽

Author(s):

Huy Gia Vuong ◽

Hieu Trong Le ◽

Tam N.M. Ngo ◽

Kar-Ming Fung ◽

James D. Battiste ◽

...

Keyword(s):

Cox Regression ◽

Fatal Outcome ◽

Extent Of Resection ◽

Tumor Location ◽

Genetic Alterations ◽

Integrated Analysis ◽

Prognostic Impact ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

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G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study

Gerontology ◽

10.1159/000520328 ◽

2021 ◽

pp. 1-10

Author(s):

Katharina Anic ◽

Sophie Birkert ◽

Mona Wanda Schmidt ◽

Valerie Catherine Linz ◽

Anne-Sophie Heimes ◽

...

Keyword(s):

Ovarian Cancer ◽

Global Health ◽

Screening Tool ◽

Prognostic Index ◽

Progression Free Survival ◽

Assessment Tools ◽

Prognostic Impact ◽

Free Survival ◽

Geriatric Screening ◽

The Impact

Background: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). Methods: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Results: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056–3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. Conclusions: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

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Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001184 ◽

2018 ◽

Vol 28 (3) ◽

pp. 586-593 ◽

Cited By ~ 8

Author(s):

Mette Calundann Noer ◽

Sofie Leisby Antonsen ◽

Bent Ottesen ◽

Ib Jarle Christensen ◽

Claus Høgdall

Keyword(s):

Cox Regression ◽

Type I ◽

Prognostic Impact ◽

Type Ii ◽

Regression Analyses ◽

Differential Impact ◽

Kaplan Meier ◽

Prediction Of Survival ◽

Comorbidity Index ◽

The Impact

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

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124Impact of intimal tracking for recanalization of CTO lesions on long-term clinical outcomes

European Heart Journal ◽

10.1093/eurheartj/ehz747.0040 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Kano ◽

K Nasu ◽

M Habara ◽

T Shimura ◽

M Yamamoto ◽

...

Keyword(s):

Clinical Outcomes ◽

Cox Regression ◽

Target Lesion ◽

Hazard Ratio ◽

Rank Test ◽

Total Occlusion ◽

Significant Difference ◽

The Impact

Abstract Background For recanalization of coronary chronic total occlusion (CTO) lesions, subintimal guidewire tracking in both antegrade and retrograde approaches are commonly used. Purpose This study aimed to assess the impact of subintimal tracking on long-term clinical outcomes after recanalization of CTO lesions. Methods Between January 2009 and December 2016, 474 CTO lesions (434patients) were successfully recanalized in our center. After guidewire crossing in a CTO lesion, those lesions were divided into intimal tracking group (84.6%, n=401) and subintimal tracking group (15.4%, n=73) according to intravascular ultrasound (IVUS) findings. Long-term clinical outcomes including death, target lesion revascularization (TLR), target vessel revascularization (TVR) were compared between the two groups. In addition, the rate of re-occlusion after successful revascularization was also evaluated. Results The median follow-up period was 4.7 years (interquartile range, 2.8–6.1). There was no significant difference of the rate of cardiac death between the two groups (intimal tracking vs. subintimal tracking: 7.0% vs. 4.1%; hazard ratio, 0.61; 95% confidence interval [CI], 0.19 to 2.00; p=0.41), TLR (14.3% vs. 16.2%; hazard ratio, 1.34; 95% CI, 0.71 to 2.53; p=0.37), and TVR (17.5% vs. 20.3%; hazard ratio, 1.27; 95% CI, 0.72 to 2.23; p=0.42). However, the rate of re-occlusion was significantly higher in the subintimal tracking group than intimal tracking group at 3-years re-occlusion (4.2% vs. 14.5%; log-rank test, p=0.002, Figure). In the multivariate COX regression, subintimal guidewire tracking was an independent predictor of re-occlusion after CTO recanalization (HR: 5.40; 95% CI: 2.11–13.80; p<0.001). Figure 1 Conclusions Subintimal guidewire tracking for recanalization of coronary CTO was associated with significantly higher incidence of target lesion re-occlusion during long-term follow-up period.

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