Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Peter Grell ◽  
Simona Borilova ◽  
Renata Schwanzerova ◽  
Sabina Kukolikova ◽  
Josef Dvorak ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Median Line ◽  
Free Survival ◽  
Treatment Groups ◽  
Factors Associated ◽  
Patient Will

137 Background: Trifluridine/tipiracil (T) and regorafenib (R) are indicated for patients with refractory mCRC. Currently, no biomarkers are used to select which patient will benefit from which treatment. Methods: We retrospectively evaluated 212 patients who received T and/or R. Different factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results: T received 132, R 52, both drugs 28 patients. Median age was 64 (range 28-83), male 64%, PS 0 37%, median line of treatment 3, characteristic was similar between treatment groups. Median follow-up was 16.5 months. Median OS for T was 10.2, for R 6.9 months, P = 0.03. Factors significantly associated with OS were: ≥ 24 months from diagnosis of mCRC (0.49, P < 0.001), PS 0 (HR 1.54, P = 0.007), baseline WBC < 8 × 109/L (HR 0.47, P < 0.001), normal baseline CRP (HR 0.47, P < 0.001), ≥ 3 months from last therapy (fluoropyrimidine for T, anti-VEGF for R) (HR 0.66, P = 0.006). We developed a scoring system TASREG from these factors, 1 point for each factor, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS for all patients according to risk group was 4.6 for high risk, 7.9 intermediate, 11.8 months favorable risk (P < 0.001). Score was also significant for T and R group evaluated separately. Score was also significant for PFS. Factors associated with OS specific for T were neutropenia G≥2 (HR 0.34, P < 0.001); for R normal baseline LDH (HR 0,40. P < 0.001), no liver metastases (HR 0.45, P = 0.002), non-synchronous disease (HR 0,40, P < 0.001). Conclusions: We could find factors associated with better outcomes for both treatment groups and factors specific for T or R. TASREG is simple prognostic tool for patients with refractory mCRC.

The FLIPI2 SCORE Predicts PROGRESSION-FREE SURVIVAL (PFS) and OVERALL SURVIVAL (OS) IN AN INDEPENDENT SERIES of Follicular LYMPHOMA: A Single Institution EXPERIENCE

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3128-3128 ◽  
Author(s):  
María José Terol ◽  
Ana Isabel Teruel ◽  
Paula Amat ◽  
Danella Elaluf ◽  
Mar Tormo ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Free Survival ◽  
Intermediate Group ◽  
Independent Series

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study

2021 ◽  
pp. JCO.20.03096
Author(s):  
Huyong Zheng ◽  
Hui Jiang ◽  
Shaoyan Hu ◽  
Ning Liao ◽  
Diying Shen ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Patients ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Standard Risk

PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Minimal Residual Disease by Flow Cytometry in Children with Acute Lymphoblastic Leukemia. Single-Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4238-4238
Author(s):  
Marcela Eugenia Soria ◽  
Marcela Ema Gutierrez ◽  
Maria Isabel Gaillard ◽  
Maria Cores ◽  
Gimena Gil ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Residual Disease ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Wbc Count ◽  
Minimal Residual

Abstract Abstract 4238 Introduction: Minimal residual disease (MRD) allows detection of blasts in patients in morphologically complete remission. Detection of MRD in patients with ALL is an independent risk factor associated with lower event-free survival (EFS). Objectives: 1) Evaluate MRD in bone marrowaspirateby flow cytometry at days 15 and 33 of induction in children with ALL. 2) Determine MRD association with hematologic features. 3) To correlate MRD association with overall survival (OS) and event-free survival (EFS). Design and Statistical Analysis: Descriptive, retrospective study. Univariate analysis was performed by T- test for continuous varibles and byχ2or Fisher tests for categorical variables. Survival was estimated with Kaplan Meier method. Regression multiple was used for multivariate analysis. p values < 0.05 were deemed as statistically significant. SPSS 15.0 program was used for the analyses. Patients: From January 2006 to December 2009, 84 patients with newly diagnosed ALL, aged 1 –18 years, were admitted at our institution. They were treated according to ALLIC / BFM / GATLA 2002 protocol. Immunophenotypic studies were performed by standard Four-color flow cytometry (FC) using FACSCalibur BD cytometer, MDR follow up panels were tailored depending on aberrant finding at diagnosis. 300.000–500.000 events were acquired using the CellQuest Pro and Paint -a-gate software for data analysis. MDR status has been defined as positive if at least 30–50 clustered events displaying leukemia –associated immunophenotypic characteristics (0,01%). Results: The mean age at diagnosis was 7.7 years (r: 2.1–18). Mean follow-up 33.9 months (r: 1–66). 38% were female. Immunophenotype: Pro B 5%, common B 87%, Pre B 2%, and T 6%. Good response to prednisone was achieved by 92% of patients. With regard to risk groups, the distribution was: 28% standard, 55% intermediate and 17% high. MRD at day 15 was evaluable in 66 patients (78%), being positive in 35 of them (45%). MRD at day 33 was evaluable in 75 patients (89%), being positive in 10 (12%). Conclusion: Positive MRD at day 15 was associated with: increased WBC count at diagnosis, high-risk group, higher relapse rate, lower EFS and OS. Otherwise, positive MRD at day 33 was associated: increased WBC count at diagnosis, T immunophenotype, poor response to prednisone, high risk group, lower EFS and OS. Our data indicate that positive MRD at days 15 and 33 result an independent variable of poor prognosis in children with ALL. Disclosures: No relevant conflicts of interest to declare.

EUTOS Score Identifies Cases with Poor Outcome in Patients with Early Chronic Phase Chronic Myeloid Leukemia, Though Not Predictive for Optimal Response to Imatinib

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3778-3778 ◽  
Author(s):  
Mario Tiribelli ◽  
Massimiliano Bonifacio ◽  
Elisabetta Calistri ◽  
Gianni Binotto ◽  
Elena Maino ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Low Risk ◽  
Molecular Response ◽  
Free Survival ◽  
Optimal Response ◽  
Risk Patients ◽  
Eutos Score

Abstract Abstract 3778 Introduction. The EUTOS score has recently been developed by the European Leukemia-Net (ELN) to predict the achievement of an 18-month complete cytogenetic response (CCyR) and progression-free survival in imatinib-treated early chronic phase (ECP) chronic myeloid leukemia (CML) patients. The score uses the percentage of basophils and spleen size to divide patients in 2 groups of low- and high-risk. Since its publication in 2011, however, there have been conflicting reports about the efficacy of EUTOS score. Moreover, scanty data are available on the power of this scoring system to foresee optimal response to imatinib, as defined by ELN recommendations. Aims and Methods. To test the power of EUTOS score in predicting achievement of optimal response to imatinib, as defined by ELN, time to imatinib failure (TTF) and progression-free survival (PFS), we evaluated 265 ECP CML patients treated with front-line standard dose imatinib (400 mg daily) at 5 major hematology centres in the north-eastern area of Italy. Partial cytogenetic response (PCyR) and CCyR were defined as 1–35% and 0% Ph+ metaphases, respectively; major molecular response (MMR) was defined as BCR-ABL <0.1%IS. TTF was measured from the start of imatinib to the date of any of the following events: progression to accelerated or blastic phase, death for any cause at any time, imatinib dose increase (≥ 600 mg/day) for primary or secondary hematologic or cytogenetic resistance. PFS was measured from the start of imatinib to the date of progression to accelerated or blastic phase or death for any cause at any time. Survival probabilities were estimated by the Kaplan-Meier method and compared by log rank test; differences among variables were evaluated by the Fisher's exact test or by Student's t-distribution. Results. A total of 265 consecutive patients with ECP CML were included in this study. The median age was 55 years (range 19–84), with 149 males and 116 females. The median follow-up was 61 months (range 6–136). The median time from diagnosis to imatinib therapy was 0.7 months (range 0 – 7.6). The distribution according to the EUTOS score was: 248 patients (93.6%) in the low risk group and 17 patients (6.4%) in the high risk group. The “optimal response” endpoints to imatinib (i.e. PCyR at 6th months, CCyR at 12th months and MMR at 18th months) were higher in low-risk patients, but did not achieve statistical significance. Specifically, the values were as following: PCyR 86% vs 67% (p=0.055), CCyR 80% vs 63% (p=0.117) and MMR 61% vs 36% (p=0.126). Cumulative incidence of CCyR was comparable in the two groups (88%% in low-risk and 80% in high risk), but time to CCyR was shorter in low-risk patients (6 months) compared to the one in high-risk patients (9 months) (p=0.048) [figure 1]. More importantly, EUTOS score was able to predict long term response to therapy. Indeed, 59% of patients in the high-risk group experienced imatinib failure, compared to 30% in the low-risk group (p=0.027). Moreover also TTF was significant shorter in the high-risk group [figure 2]. Fifty-three patients in the low-risk group (21%) were switched to 2nd-generation TKIs (29 dasatinib, 22 nilotinib, 1 bosutinib, 1 ponatinib), compared to six (35%) in the high-risk group (4 dasatinib, 2 nilotinib). Also PFS rate was significantly worse in patients with high EUTOS score, with 11/248 events (4%) in the low-risk group and 4/17 (23%) in the high-risk cases (p=0.01) [figure 3]. Conclusions. In our study group, the EUTOS score was predictive for long-term outcome of imatinib therapy, both in terms of treatment failure and of progression-free survival. Taking into consideration the ELN definitions of optimal response, there was a trend toward better cytogenetic and molecular response in low-risk patients; the lack of statistical significance could be due to the relatively small number of high-risk cases. Disclosures: No relevant conflicts of interest to declare.

The efficacy of EORTC risk tables in Japanese patients with non-muscle invasive bladder cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 331-331
Author(s):  
Satoru Muto ◽  
Takeshi Ieda ◽  
Syou-ichiro Sugiura ◽  
Akiko Nakajima ◽  
Akira Horiuchi ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Time ◽  
Risk Group ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Low Risk ◽  
Progression Rate ◽  
Intermediate Risk ◽  
Free Survival ◽  
Muscle Invasive

331 Background: To predict recurrence and progression of non-muscle invasive bladder cancer (NMIBC), EORTC risk tables are widely used worldwide. EORTC risk tables were, however, developed on the basis of individual data from 2,596 NMIBC patients included in seven special European Organization for Research and Treatment of Cancer trials. Therefore, it is not clear the efficacy of these risk tables in clinical practice, especially in Japan. I will report the recurrence and progression rate on the basis of EORTC risk tables in Japanese NMIBC patients. Methods: A retrospective analysis of 619 patients with NMIBC treated between January 1998 and 2012 was performed. Patients were divided into three groups on the basis of EORTC risk tables. We compared recurrence- and progression-free survival rates between groups. Recurrence- and progression-free survival was estimated using the Kaplan-Meier method. Results: We evaluated the clinical outcome of 1,032 TUR-Bt. The recurrence rate is 32.3% in low risk group (n=31), 44.5% in intermediate risk group (n=757), and 49.4% in high risk group (n=85). The median recurrence free survival time is 87 months in low risk group, 35 months in intermediate risk group, and 25 months in high risk group. Although there are significant differences in recurrence free survival time between low risk group and intermediate risk group (p=0.0351), there are no significant differences between intermediate risk group and high risk group (p=0.1871). On the other hand, the progression rate is 1.6% in low risk group (n=128), 5.8% in intermediate risk group (n=451), and 18.0% in high risk group (n=294). The median progression free survival time is 176 months in low risk group, 131 months in intermediate risk group, and 109 months in high risk group. There are significant differences in progression free survival time between low risk group and intermediate risk group (p=0.0138), and between intermediate risk group and high risk group (p=<0.0001). Conclusions: There is an urgent need to establish the standard of recurrence risk classification in Japan.

scholarly journals Both the Subtypes of Kit Mutation and Minimal Residual Disease Are Associated with Prognosis in Core Banding Factor Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Wenbing Duan ◽  
Xiaohong Liu ◽  
Jinsong JIA ◽  
Jing Wang ◽  
Lizhong Gong ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Risk Group ◽  
High Risk Group ◽  
Consolidation Chemotherapy ◽  
Kit Mutation ◽  
Free Survival ◽  
Group A ◽  
Group B

B ackground: No consensus has been reached on the relationship between kit mutation and prognosis in core banding factor acute myeloid leukemia(CBF-AML). Our preverious analysis of kit mutation subtypes in patients with RUNX1-RUNX1T1 suggested poor prognosis associated with D816/D820 mutation. Objective: To investigate further risk stratification according to different subtypes of kit mutations and minimal residual disease (MRD) in CBF-AML. Methods: A total of 205 patients aged 16-70 years old with CBF-AML, who were diagnosed in our hospital, were analyzed retrospectively from January 2014 to April 2019. The effects of kit mutation subtypes and MRD on the overall survival (OS) and relapse free survival(RFS) were analyzed. Results: Of all, 118 males and 87 females were included. The median age were 38 (15-70) years old. Patients with RUNX1-RUNX1T1 and patients with CBFB-MYH11 accounted for 71.1% (147/205) and 28.3% (58/205) respectively. The ratio of kit mutation was 33.2% (68/205), of which, 52/147(35.4%) patients were RUNX1-RUNX1T1 positive, and 16/58 (27.6%) patients were CBFB-MYH11 positive. Of 68 patients with kit mutation, patients with D816/D820 mutation accounted for 50.0%(34/68) and the rest 34 cases were non D816/D820 mutation. The rate of D816/D820 mutation was 50% (26/52) and 50% (8/16) respectively in Patients with RUNX1-RUNX1T1 and patients with CBFB-MYH11. During the median follow-up time 28 (7-72) months, 10 patients were lost and a total of 195 patients were available. 42.6% (83/195) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). 112 patients who did not received allo-HSCT were divided into three group: 85 patients without kit mutation(group A) , 15 patients with D816/D820 nutation(group B), 12 patients with non-D816/D820 nutation(group C). The 3-year overall survival(OS) and 3-year relapse free survival(RFS) between group A and B did not have significance(P=0.603, 0.601). Both the 3-year OS and 3-year RFS of group B were superior to group C(65.5% VS 8.3%; 73.3% VS 14.4%, P=0.002, 0.003), and the 3-year OS and 3-year RFS of group A were superior to group C(68.1% VS 8.3%; 75.2% VS 14.4%, P=0.000; 0.000). So group A and B were defined as low risk group (97 patients), group C defined as high risk group(15 patients). The 3-year OS and 3-year RFS of high risk group were significantly lower than those of low risk group(14.4% VS 75.4%、8.3% VS 68.4%, P=0.000、0.000). After 2 cycles of consolidation, MRD (the transcript of RUNX1-RUNX1T1 or CBFB-MYH11) &gt; 0.1% could predicted disease recurrence(P=0.000). Patients who got MRD &lt; 0.1%(49 patients) after two cycles of consolidation chemotherapy could have higher 3-year OS and 3-year RFS than those who did not (63 patients) (94.1%VS 49.9%; 96.3% VS 36.4%, P=0.000; 0.000). During the follow-up time, patients who achieved MRD &lt; 0.1%(81patients) also had higher 3-year OS and 3-year RFS than those did not(31 patients)(81.8% VS 6.7%; 75.7% VS 12.9%, P=0.000, 0.000). Multivariate analysis showed D816/D820mutation, MRD &gt; 0.1% after two cycles of consolidation chemotherapy, MRD &gt; 0.1% during the follow-up time were poor prognosis on OS and RFS, and kit mutation had not effect on OS and RFS. A total of 91 patients out of 195 patients had D816/D820 mutation (30 patients) or MRD &gt; 0.1% after two cycles of consolidation chemotherapy and MRD &gt; 0.1% (61 patients) during the follow-up time, the 3-year OS and 3-year RFS significantly increased in the group of 57 patients who received allo-HSCT than the group of 34 patients who did not(91.0% VS 22.1%; 91.2% VS 15.9%, P=0.000, 0.000). Conclusion: The real high risk patients must be recognized during the treatment of CBF-AML: D816/D820mutation, MRD &gt; 0.1% after two cycles of consolidation chemotherapy and MRD &gt; 0.1% during the follow-up time. Allo-HSCT can improve the survival of patients who were distinguished under the accurate stratification. Disclosures No relevant conflicts of interest to declare.

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

KAI-1 Expression in Pediatric High-Grade Osteosarcoma

2006 ◽  
Vol 9 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Patrick J. Leavey ◽  
Charles Timmons ◽  
William Frawley ◽  
Donald Lombardi ◽  
Raheela Ashfaq
Keyword(s):  
Prognostic Markers ◽  
Clinical Phenotype ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Surface Proteins ◽  
High Grade ◽  
Free Survival ◽  
Treatment Groups ◽  
High Grade Osteosarcoma

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.

scholarly journals Clinical and Biological Prognostic Factors in Follicular Lymphoma Patients During Treatment

2021 ◽  
Author(s):  
Ádám Jóna ◽  
Anna Kenyeres ◽  
Sándor Barna ◽  
Árpád Illés ◽  
Zsófia Simon
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Pet Ct ◽  
Significant Difference ◽  
Biological Prognostic Factors

Abstract Introduction: Follicular lymphoma (FL) is an indolent yet heterogeneous B-cell lymphoproliferative disorder. Most people respond to treatment well. However, a particular group of patients has a poor prognosis, and these patients are difficult to define.Patients and methods: We retrospectively analyzed FL patients treated at the University of Debrecen in the past 20 years. We investigated prognostic factors that may influence the survival of FL patients.Results: We found a standardized uptake value (SUV)max cut-off value of 9.85 at the staging PET/CT to significantly separate FL patients’ progression-free survival (PFS) (p=0.0003, HR: 0.2560, 95%CI: 0.1232-0.5318). Lymphocyte/ monocyte (Ly/Mo) ratio of 3.45 drawn at diagnosis also significantly predicted PFS (p=0.0324, HR: 1.806, 95% CI: 1.051-3.104). Combining patients’ with staging SUVmax >9.85 and Ly/Mo < 3.45 a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1033, 95%CI: 0.03719-0.2868). Similarly, a significant difference was shown with a SUVmax cut-off of 3.15 at the interim PET/CT (p<0.0001, HR: 0.1535, 95%CI: 0.06329-0.3720). Combining patients with staging SUVmax >9.85 and interim SUVmax >3.15, a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1037, 95%CI: 0.03811-0.2824). The PFS difference is translated into overall survival advantage (p=0.0506, HR: 0.1187, 95%CI: 0.01401-1.005).Discussion: Biological prognostic factors, such as the Ly/ Mo ratio, may improve the prognostic assessment of staging PET/CT. Nevertheless, PFS difference is translated into OS when using a combination of staging and interim SUVmax. We consider investigating additional biological prognostic factors while currently highlighting PET/CT's role in FL.

Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yoshitaka Ito ◽  
Kazuhiro Naito ◽  
Katsuhisa Waseda ◽  
Hiroaki Takashima ◽  
Akiyoshi Kurita ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Stent Implantation ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk

Background: While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT. Methods: A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score<4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion. Results: Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score. Conclusion: High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.

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