Combined Assessment of WT1 and BAALC Expression Levels Improves Risk Stratification in Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5603-5603
Author(s):  
Paola Minetto ◽  
Fabio Guolo ◽  
Marino Clavio ◽  
Laura Mitscheunig ◽  
Raffaella Grasso ◽  
...  
Keyword(s):  
High Risk ◽  
Copy Number ◽  
Who Classification ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Molecular Profile ◽  
Free Survival ◽  
Expression Levels ◽  
Molecular Expression

Abstract BACKGROUND AND AIMS In patients with myelodysplastic syndromes (MDS) several validated prognostic scores, such as IPSS and R-IPSS, are available to assess the risk of AML progression and predict overall survival (OS) as well as leukemia-free survival (LFS). A number of molecular aberrations can be identified in MDS. However, differently from AML, none of the current prognostic indexes takes into account molecular profile at diagnosis. WT1 expression has often been evaluated in acute leukemias and MDS. High WT1 expression levels on bone marrow at diagnosis have been reported to identify MDS patients who are at high risk of progression to AML. BAALC (Brain And Acute Leukemia Cytoplasmic) hyper-expression has been associated with a poor prognosis in AML patients, whereas its prognostic value in MDS is not yet clearly defined. The aim of our study was to determine if combined assessment of WT1 and BAALC expression levels at diagnosis could be predictive of leukemic evolution. MATERIALS AND METHODS We selected 86 patients with available WT1 and BAALC expression levels on BM samples at diagnosis. According to IPSS score, 22 patient were considered low-risk, 27 intermediate-1 and 28 intermediate-2 or high risk. Patients underwent different treatment schedules including supportive care, erythropoietin, hypomethylating and immunomodulating agents, according to their risk group. Median follow-up was 36 months (range 4 -121 months). Leukemia-free survival (LFS) was calculated from the diagnosis until last follow-up or documented leukemic progression as defined in literature. LFS was estimated using the Kaplan–Meier method. All Real-Time PCR were performed on DNA Engine 2 (Opticon®, MJ Research®). WT1 copy number/Abl copy number 1000x104 was used as cut-off value for high WT1 expression, a level of 1000x104 BAALC copy number/Abl copy number was set as cut-off for BAALC hyper-expression. RESULTS After a median time of 32 months, 43 patients died. The main cause of death was leukemic evolution (accounting for 31/43 deaths, 72%), other causes were cardiovascular events and infections (data not shown). The risk of death by any cause was significantly affected by leukemic evolution, diagnosis according to WHO classification and molecular expression profile at diagnosis. Multivariate analysis showed that leukemic evolution was an independent predictor of death (p <0.001). Twenty-nine leukemic evolutions were observed. Median LFS was 34 months. The probability of leukemic evolution was significantly affected by karyotype, IPSS and R-IPSS scores, diagnosis according to WHO classification, and molecular profile at diagnosis. According to our data WT1 and BAALC combined expression levels further enhanced prognostic stratification. In IPSS Int-1, Int-2/high and in R-IPSS high risk groups, low levels of expression resulted in significantly lower probability of leukemic progression, whereas high levels predicted poor outcome. Furthermore, in patients assigned to IPSS unfavorable prognostic groups, low levels of WT1 and BAALC seemed to predict a significantly longer LFS. In the univariate analysis LFS duration was significantly affected by WT1 and BAALC expression levels (fig. 1), IPSS and R-IPSS scores, karyotype and WHO classification at diagnosis. A multivariate Cox Regression model showed that LFS duration was significantly influenced only by molecular profile at diagnosis and R-IPSS risk group (p <0.001 and p <0.01, respectively). Median OS was 32 months. In univariate analysis OS was significantly influenced by diagnosis according to WHO classification, karyotype, R-IPSS score, leukemic evolution and molecular profile expression at diagnosis. The multivariate model disclosed molecular expression profile, R-IPSS score and leukemic evolution as independent predictor of OS (p <0.02, <0.03 and <0.01, respectively). CONCLUSIONS In MDS patients combined WT1 and BAALC expression levels on bone marrow samples at diagnosis is a reliable predictor of risk of AML progression, LFS and OS. This can improve risk stratification especially in intermediate and high risk groups and may lead to a risk tailored therapy. Figure 1: LFS according to molecular profile Figure 1:. LFS according to molecular profile Disclosures No relevant conflicts of interest to declare.

Prognostic Indices in Older DLBCL Patients Receiving R-CHOP: An Analysis of the U.S. Intergroup Study (E4494, CALGB 9793).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 813-813
Author(s):  
R.H. Advani ◽  
H. Chen ◽  
T.M. Habermann ◽  
V.A. Morrison ◽  
E. Weller ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Risk Category ◽  
Free Survival ◽  
Prognostic Tool ◽  
The Impact ◽  
The U.S

Abstract Background: We reported that addition of rituximab (R) to chemotherapy significantly improves outcome in DLBCL patients (pt) &gt;60 years (JCO24:3121–27, 2006). Although the IPI is a robust clinical prognostic tool in DLBCL, Sehn et al (ASH 2005: abstract 492) reported that a revised (R) IPI more accurately predicted outcome in pt treated with rituximab-chemotherapy. Methods: We evaluated outcomes of the Intergroup study with respect to the standard IPI, R-IPI, age-adjusted (aa) IPI for evaluable pt treated with R-CHOP alone or with maintenance rituximab. We further assessed a modified IPI (mIPI) using age ≥ 70 y as a cutoff rather than age 60 y. Results: The 267 pt in this analysis were followed for a median of 4 y. Pt characteristics were: age &gt; 70 (48%) (median=69), male 52%, stage III/IV 75%, &gt;1 EN site 30%, LDH elevated 60%, PS ≥2 15%. On univariate analysis all of these characteristics were significant for 3 y failure-free survival (FFS) and overall survival (OS). The IPI provided additional discrimination of risk compared to the R-IPI with significant differences in FFS and OS for 3 vs 4–5 factors. The aa-IPI defined relatively few pt as low or high risk. The impact of age was studied using a cut-off of 70 years in a modified IPI, yielding 4 risk groups as shown below. Conclusions: For pt ≥ 60 treated with rituximab-chemotherapy the distinction between 3 vs 4,5 factors in the IPI was significant.The IPI also provided additional discrimination of risk compared to the R-IPI. In this older group of pt, use of an age cutoff ≥70 y placed more patients in the low risk category. It is of interest to apply the mIPI in other datasets with DLBCL pt &gt;60 y. Group # Factors # Pt % 3y FFS* % 3y OS* *All risk groups significantly different; logrank p &lt; 0.001 **95 % CI: FFS (0.46,0.66), OS (0.58,0.78) ***95 % CI: FFS (0.21,0.45), OS (0.31,0.55) L: Low, LI: Low Intermediate, HI: High Intermediate, H; High IPI L 0–1 12 78 83 LI 2 28 70 80 HI 3 33 56** 68** H 4–5 37 33*** 43*** R-IPI Very Good 0 0 - - Good 1–2 40 72 81 Poor 3–5 60 46 57 aa-IPI L 0 12 78 83 LI 1 35 68 78 HI 2 44 47 59 H 3 9 31 35 mIPI (age ≥ 70) L 0–1 27 77 86 LI 2 28 62 74 HI 3 29 47 58 H 4–5 16 28 36

A Risk Score Integrating BAALC, ERG and WT1 Expression Can Be Used To Improve Risk Stratification In Acute Promyelocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1323-1323
Author(s):  
Anna Hecht ◽  
Florian Nolte ◽  
Daniel Nowak ◽  
Verena Nowak ◽  
Benjamin Hanfstein ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Expression Levels ◽  
Improve Risk Stratification

Abstract Introduction With current therapy regimens over 75% of patients with de novo acute promyelocytic leukemia (APL) can be cured. Approaches to further improve patient outcome by stratifying patients at the time of initial diagnosis according to their individual risk and to adjust therapy accordingly have been based on clinical features only. Molecular markers have not been established for risk stratification as yet. Recently, we have shown that high expression levels of the genes brain and acute leukemia, cytoplasmic (BAALC) and ets related gene (ERG) are associated with inferior outcome in APL patients. In addition, data indicate that aberrant expression of the gene Wilms’ tumor 1 (WT1) is a negative prognostic factor with regard to overall survival (OS) after complete remission (CR) and relapse free survival (RFS) in APL. In this study we evaluated the prognostic relevance of a combined score integrating the expression levels of the above mentioned genes to further improve risk stratification in APL patients. Methods Expression levels of BAALC, ERG and WT1 of 62 patients with newly diagnosed APL were retrospectively analyzed in bone marrow mononuclear cells using multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR). Median age of patients was 47 years (range: 19 to 82y). All patients gave informed consent. Patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) study with a treatment of simultaneous ATRA and double induction chemotherapy including high-dose ara-C, consolidation and maintenance chemotherapy. The following gene expression levels were identified as negative risk factors in preceding studies: BAALC expression ≥25th percentile (BAALChigh), ERG expression >75th percentile (ERGhigh) and WT1 expression ≤25th percentile or ≥75th percentile (WT1low/high). A risk score was developed as follows: for the presence of one of the mentioned risk factors one scoring point was assigned to a respective patient, i.e. a maximum of 3 points (one point for BAALChigh, ERGhigh and WT1low/high, respectively) and a minimum of 0 points (i.e. presenting with none of the aforementioned risk factors) could be allocated to one patient. Accordingly, patients were divided into four risk groups: 7 patients scored 0 points (= low risk), 27 patients scored 1 point (= intermediate 1 risk), 19 patients scored 2 points (= intermediate 2 risk) and 9 patients scored 3 points (= high risk). Subsequently, OS, RFS and relapse free interval (RFI) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the four risk groups (p<0.05). Results The integrative risk score divided patients into four groups with significantly different outcome. The low risk group showed a RFS of 100% at 10 years of follow-up compared to the intermediate 1 risk group with 81%, the intermediate 2 risk group with 58% and the high risk group with a RFS of 42% only (median survival: 4.6y) (p=0.02). In accordance, the RFI differed significantly between the four groups: low risk 100%, intermediate 1 risk 100%, intermediate 2 risk 89% and high risk 71% (p=0.049). There was no statistically significant difference between the 4 groups with regard to OS in the entire patient cohort. However, there was a clear trend towards a difference in OS in patients who achieved a CR after induction therapy: low risk 100%, intermediate 1 risk 81%, intermediate 2 risk 68% and high risk 53% survival at 10 years of follow-up (p=0.09). Conclusion Integration of expression levels of the genes BAALC, ERG and WT1 into a scoring system identifies 4 risk groups with significantly different outcome with regard to RFS and RFI. It might be a promising approach to guide therapeutic decisions in patients with APL. However, multivariate analyses and validation of these data in an independent patient cohort is warranted. Disclosures: No relevant conflicts of interest to declare.

Comparison of the international prognostic factors index (IPI) with the absolute monocyte and lymphocyte prognostic index (AMLPI) for patients (Pts) with diffuse large b-cell lymphoma (DLBCL) receiving R-CHOP.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8067-8067
Author(s):  
Nicolas Batty ◽  
Elham Ghonimi ◽  
Lei Feng ◽  
Luis Fayad ◽  
Anas Younes ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Prognostic Effect ◽  
Large B Cell Lymphoma ◽  
High Risk Disease

8067 Background: We studied the value of a proposed prognostic index (PI) generated by baseline absolute monocyte (AMC) and lymphocyte (ALC) counts for pts with DLBCL, using values as previously reported (Leukemia 25:1502-9, 2011). Methods: From 03/07 to 01/09, 245 consecutive pts with untreated DLBCL receiving standard R-CHOP from the MDACC database were evaluated. Baseline AMC and ALC were retrospectively recorded. High AMC (≥610/uL) and a low ALC (≤1000/uL) were examined as dichotomized variables for progression-free (PFS) and overall survival (OS). An AMLPI was generated, stratifying pts into 3 risk groups (RGs): low-(AMC <610/uL and ALC >1000/uL), intermediate-(AMC ≥610/uL or ALC ≤1000/uL), and high-risk(AMC ≥610/uL and ALC ≤1000/uL). The prognostic effect of the AMLPI and the IPI were examined by multivariate analysis (MVA). Results: Ninety (37%) had high AMC and 71 (29%) had low ALC. By univariate analysis, a high AMC was associated with inferior PFS (p=0.01) and OS (p=0.03). The frequencies of AMLPI RGs were: low-105 pts (43%), intermediate-119 (48%), and high risk-21 (9%). With a median follow-up of 22 months (range <1-42), 3-year PFS and OS rates for these RGs were 80%, 61%, and 46% (p=0.007) and 92%, 76%, and 60% (p=0.006), respectively. Three-year PFS rates for IPI 0-2 and 3-5 RGs were 73% and 58%, respectively (p=0.0004); comparable OS rates were 88% and 68%(p<0.0001). For pts with IPI 0-2, 1-year PFS rates for AMLPI low, intermediate, and high RGs were 92%, 89% and 80% (p=0.022); comparable 1-year OS rates were 96%, 95% and 80% (p=0.049). By MVA, AMLPI effect (low vs. high RGs) on PFS was significant (p=0.046) as was IPI effect (0-2 vs 3-5, p=0.005); similar results were observed for OS (p=0.052 and p=0.003, respectively). Conclusions: Baseline AMC and AMLPI are significant variables for PFS and OS for pts with DLBCL receiving R-CHOP. AMLPI can identify pts with low, intermediate, and high-risk disease for PFS and OS, particularly for those with IPI 0-2. AMLPI may also add prognostic value beyond that of the IPI.

Outcome of risk-adapted therapy for pediatric acute lymphoblastic leukemia in Egypt.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10044-10044
Author(s):  
Iman A. Sidhom ◽  
Abir Mokhles ◽  
Sonya Soliman ◽  
Khaled Shaaban ◽  
Sherine Salem ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Response To Therapy ◽  
Cell Phenotype ◽  
Free Survival ◽  
Egyptian Children

10044 Background: With modern risk directed therapy, >80% of children with acute lymphoblastic leukemia (ALL) in western countries are cured. The 5-year event free survival (EFS) and relapse free survival (RFS) of pediatric ALL patients in Egypt were 65% and 75% respectively in a previous study using an intensive treatment protocol for all patients. Aim: To improve cure rates of Egyptian children with ALL using risk adapted therapy. Methods: From July 2007 to December 2010, 706 patients aged 1-18 years with newly diagnosed ALL were treated at Children Cancer Hospital Egypt with a risk directed ALL protocol adopted from St Jude Total Study XV. Results: B-precursor phenotype was encountered in 75.8% and T-cell in 24.2%. Based on initial presentation and response to therapy measured by minimal residual disease (MRD), 42.6%, 45.8% and 11.6% of the patients were classified as low, intermediate and high risk respectively. The 5-year RFS and EFS were 88.2 ± 1.5% and 76.5 ± 1.7% respectively. Adverse events included 4.4% induction deaths, 2.5% failure to achieve induction remission (1.4% remained refractory), 6.8% deaths in remission, 9.2% relapses (3.1% hematological, 1.8% combined hematological and CNS, 4% isolated CNS, 0.3% isolated testicular), 0.9% abandonment of therapy and one patient had secondary myeloid leukemia. The median follow up for patients alive in CR was 43months (range 24–65). The 5-year RFS of the low, intermediate and high risk groups were 92.2 ± 2.4%, 85.3 ± 2.2% and 82.7 ± 4.8% respectively (p=0.001), while the 5-year EFS were 87.6 ± 2.5%, 78.2 ± 2.5% and 57.9 ± 5.7% respectively (p<0.001). Prognostic factors that had statistically significant unfavorable impact on both EFS and RFS by univariate analysis were age ≥10 years, TLC ≥100x109/L, T-cell phenotype, risk groups, MRD d42 ≥1% and MRD W7 ≥0.1%, while MRD d15 ≥1% had statistically significant unfavorable outcome on EFS only. By multivariate analysis, TLC and MRD W7 had prognostic significance on EFS and RFS, MRD d42 on EFS, while MRD d15 had marginal significance on EFS (p=0.055). Conclusions: Risk adapted therapy was effective in improving ALL survival among patients at our institution compared with previous trials, although the outcome remains lower than that in high income countries.

Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

2020 ◽  
Vol 20 (9) ◽  
pp. 681-688
Author(s):  
Nikolai V. Litviakov ◽  
Marina K. Ibragimova ◽  
Matvey M. Tsyganov ◽  
Artem V. Doroshenko ◽  
Eugeniy Y. Garbukov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal B ◽  
Cell Clones ◽  
Genetic Landscape ◽  
Intelligent Approach

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

scholarly journals Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience

2021 ◽  
Author(s):  
Federico Marin ◽  
Simone Fezzi ◽  
Alessia Gambaro ◽  
Francesco Ederle ◽  
Gianluca Castaldi ◽  
...  
Keyword(s):  
High Risk ◽  
Medical Therapy ◽  
Resistant Hypertension ◽  
Univariate Analysis ◽  
Daily Practice ◽  
Renal Sympathetic Denervation ◽  
High Risk Population ◽  
Safety And Efficacy ◽  
Renal Artery Denervation

Abstract Aims To evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy. Methods Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit. Results Forty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by − 19.7 ± 27.1 mmHg and by − 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR < 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline. Conclusion RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months. Graphic abstract

scholarly journals The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 671
Author(s):  
Margherita Rimini ◽  
Pierfrancesco Franco ◽  
Berardino De Bari ◽  
Maria Giulia Zampino ◽  
Stefano Vagge ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Anal Cancer ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
External Validation ◽  
Risk Groups ◽  
Anal Squamous Cell Carcinoma ◽  
Predictors Of Response ◽  
Risk Patients

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

EARLY AND INTERMEDIATE-TERM OUTCOMES WITH DRUG-ELUTING STENTS IN HIGH-RISK PATIENTSWITH SYMPTOMATIC INTRACRANIAL STENOSIS

Neurosurgery ◽  
2006 ◽  
Vol 59 (5) ◽  
pp. 1044-1051 ◽  
Author(s):  
Adnan I. Qureshi ◽  
Jawad F. Kirmani ◽  
Haitham M. Hussein ◽  
Pansy Harris-Lane ◽  
Afshin A. Divani ◽  
...  
Keyword(s):  
High Risk ◽  
Target Lesion ◽  
Intracranial Stenosis ◽  
Drug Eluting Stents ◽  
Free Survival ◽  
Angiographic Restenosis ◽  
Drug Eluting ◽  
Ischemic Events ◽  
Major Stroke

Abstract OBJECTIVE To report the 1-month and intermediate-term results of treatment of symptomatic intracranial stenosis using drug-eluting stents. BACKGROUND Patients with intracranial stenosis who are at high risk because of either high-grade stenosis or medication failure may have an annual risk of recurrent ischemic events in excess of 40%. Drug-eluting stents may reduce the rate of ischemic events in patients with a low restenosis rate. METHODS We determined rates of technical success (defined as reduction of target lesion to stenosis &lt;30%) and 1-month major stroke or death in patients with symptomatic intracranial stenosis (≥70% and/or medication failure). Patients' clinical and follow-up information during a mean period of 14.3 ± 7 months were obtained. Kaplan-Meier analysis was performed to determine the rate of major stroke-free survival during 12 months. RESULTS There were 18 patients (mean age, 58 ± 16 yr; 12 were men) treated with either a sirolimus-eluting stent (n = 14) or a paclitaxel-eluting stent (n = 4) for stenosis located in the: intracranial internal carotid artery (n = 6), proximal middle cerebral artery (n = 4), intracranial vertebral artery (n = 4), vertebrobasilar junction (n = 2), or basilar artery (n = 2). There was one major stroke and no death observed in the 1-month follow-up. At the 6-month follow-up examination, no major stroke or death was observed. Major stroke-free survival was 86% (±standard error of 9%) at 12 months after the procedure. One symptomatic angiographic restenosis was observed during the follow-up period. CONCLUSION A low rate of major stroke or death was observed after treatment of symptomatic intracranial stenosis using drug-eluting stents in high-risk patients.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals Overexpression of the OCT-1 Gene Is a Biomarker Associated with Poor Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) - Data from a Retrospective Cohort from Latin America: Defining a Very High-Risk Clinical-Molecular Subgroup

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Aparecida Coelho de Siqueira ◽  
Abrahão Elias Hallack Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
B Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Molecular Subgroup ◽  
Free Survival ◽  
Very High

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document