Bendamustine and Rituximab Achieve a Major Survival Improvement Of Patients With Morbus Waldenström In Routine Care

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5611-5611
Author(s):  
Rudolf Weide ◽  
Stefan Feiten ◽  
Vera Friesenhahn ◽  
Jochen Heymanns ◽  
Kristina Kleboth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Relative Survival ◽  
Routine Care ◽  
Low Risk ◽  
Intermediate Risk ◽  
Number Of Patients ◽  
Made In

Abstract Introduction Progress has been made in diagnosis and treatment of patients with Morbus Waldenström who receive their treatment within prospective clinical trials. Due to necessary inclusion and exclusion criteria only a very limited number of patients are treated in studies. Therefore results from clinical trials can't be transferred into routine care. Little practice data are available how patients with Morbus Waldenström are diagnosed and treated in routine care and whether improvements in survival are achieved. Methods A retrospective analysis of all patients with Morbus Waldenström who were treated in an oncology group practice in Germany between 1995-2012. Relevant clinical data concerning diagnosis, treatment and survival were transferred from clinical files into a database and analyzed statistically using SPSS and SURVSOFT. Results 52 patients with a median age of 67 (36-84) were identified. 67.3% were male and 32.7% female. Distribution according to IPSSWM-stage was: 21.2% low risk, 61.5% intermediate risk, 17.3% not evaluable (in most cases due to lacking β2 microglobulin data). 59.6% needed therapy with a median of 3 therapies (1-12). Regimens most frequently applied were: Bendamustine-containig (74.2%), Rituximab-containing (74.2%), Bendamustine+Rituximab-combinations (61.3%) and Chlorambucil-containing (45.2%). 6.5% of patients were treated within a clinical trial. Median overall survival was 12 years (0-19). Median relative survival was 13.6 years. 10-year relative survival was 86%. 10-year relative survival according to IPSSWM-stage was as follows: low risk 92%, intermediate risk 71%. Median overall survival of the patients who never needed any therapy was 11 years compared to 12 years of those patients who needed therapy. Median relative survival for patients who never needed therapy was not reached yet, median relative survival of the patients who needed therapy was 13.6 years. Conclusions Systemic treatment of patients with Morbus Waldenström in routine care consists mainly of Bendamustine, Rituximab and Bendamustine+Rituximab-combinations. Employment of the most active chemoimmunotherapies leads to a marked prolongation of survival compared to historical controls and registry data. Disclosures: No relevant conflicts of interest to declare.

Sequential Treatment With Bendamustine, Rituximab, Chlorambucil and Fludarabine Leads To a Major Survival Improvement Of Patients With Chronic Lymphocytic Leukemia (CLL) In Routine Care

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5613-5613
Author(s):  
Rudolf Weide ◽  
Stefan Feiten ◽  
Vera Friesenhahn ◽  
Jochen Heymanns ◽  
Kristina Kleboth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Relative Survival ◽  
Routine Care ◽  
Initial Diagnosis ◽  
Lymphocytic Leukemia ◽  
Number Of Patients ◽  
Binet Stage

Abstract Introduction Progress has been made in diagnosis and treatment of patients with CLL who receive their treatment within prospective clinical trials. Due to necessary inclusion and exclusion criteria only a very limited number of patients are treated in studies. Therefore results from clinical trials can't be transferred into routine care. No clinical practice data are available how patients with CLL are diagnosed and treated in routine care and whether improvements in survival are achieved. Methods A retrospective analysis of all patients with CLL who were treated in an oncology group practice in Germany between 1995-2012. Relevant clinical data concerning diagnosis, treatment and survival were transferred from clinical files into a database and analyzed statistically using SPSS and SURVSOFT. Results 580 CLL patients with a median age of 67 (35-92) were identified. At initial diagnosis 446 patients (76.9 %) were in Binet stage A, 69 (11.9%) Binet stage B and 31 (5.3%) Binet stage C. Due to external diagnosis of 34 patients (5.9%) the stage at initial diagnosis couldn't be retrieved. 323 patients (55.7 %) never received any treatment. 257 patients (44.3%) needed therapy with a median of 2 therapy lines (1-11). Regimens most frequently applied were: Bendamustine-containig (66.9%), Rituximab-containing (62.3%), Chlorambucil-containing (61.5%), Bendamustine+Rituximab-combinations (48.2%) and Fludarabine-containing (40.9%). 21.0% of patients were treated within a clinical trial. 5 and 10 year absolute overall survival was 83.6% and 60.9%. Relative survival after 5 and 10 years was 96.1% and 82.3%. Median overall survival according to Binet stage was 16 years for Binet A, 9 years for Binet B and 8 years for Binet C. Median relative survival was 20.8 years for Binet A, 14.0 years for Binet B and 8.6 years for Binet C. Patients who needed therapy had a median overall survival of 11 years (0-41) compared to 18 years (0-23+) of patients who never needed any therapy. Conclusions 55.7% of CLL-patients never needed any therapy. Patients who needed therapy had a much lower life expectancy compared to patients who never needed therapy. Treatment consisted mainly of Bendamustine, Rituximab, Chlorambucil, Bendamustine+Rituximab-combinations and Fludarabine leading to a marked prolongation of survival compared to historical controls and registry data. Disclosures: No relevant conflicts of interest to declare.

Bendamustine + Rituximab-Combinations and R-CHOP Achieve a Major Survival Improvement Of Patients With Follicular Lymphoma In Routine Care

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5584-5584
Author(s):  
Rudolf Weide ◽  
Stefan Feiten ◽  
Vera Friesenhahn ◽  
Jochen Heymanns ◽  
Kristina Kleboth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Stage Iv ◽  
Relative Survival ◽  
Routine Care ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Number Of Patients

Abstract Introduction Progress has been made in diagnosis and treatment of patients with follicular lymphoma who receive their treatment within prospective clinical trials. Due to necessary inclusion and exclusion criteria only a very limited number of patients are treated in studies. Therefore results from clinical trials can't be transferred into routine care. Little practice data are available how patients with follicular lymphoma are diagnosed and treated in routine care and whether improvements in survival are achieved. Methods A retrospective analysis of all patients with follicular lymphoma who were treated in an oncology group practice in Germany between 1995-2012. Relevant clinical data concerning diagnosis, treatment and survival were transferred from clinical files into a database and analyzed statistically using SPSS and SURVSOFT. Results 174 patients with a median age of 60 (27-87) were identified. 43.7% were male and 56.3% female. Stage distribution at initial diagnosis was as follows: Stage I 45 patients (25.9%), stage II 23 patients (13.2%), stage III 32 patients (18.4%), stage IV 62 patients (35.6%), in 12 patients (6.9%) initial stage could not be retrieved. 90.8% needed therapy with a median of 2 different therapies (1-12). Regimens most frequently applied were: Rituximab-containing (67.1%), Bendamustine-containig (41.8%), Bendamustine+Rituximab-combinations (39.9%) and R-CHOP (27.8%). 15 patients (9.5%) received radiotherapy only. 13.3% of patients were treated within a clinical trial. 5 and 10 year absolute overall survival was 88.9% and 73.9%. Relative survival after 5 and 10 years was 94.4% and 86.6%. Median overall survival according to stage was 28 years for stage I, median not reached for stage II, 21 years for stage III and 16 years for stage IV. Median relative survival was 17.4 years for stage IV and has not been reached for stages I-III. Conclusions Systemic treatment of patients with follicular lymphoma in routine care consisted mainly of Bendamustine+Rituximab-combinations and R-CHOP. Employment of the most active chemoimmunotherapies leads to a marked prolongation of survival compared to historical controls and registry data. Disclosures: No relevant conflicts of interest to declare.

Early Mortality in Acute Promyelocytic Leukemia May Be Higher Than Previously Reported.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1015-1015 ◽  
Author(s):  
Ash A Alizadeh ◽  
James S. McClellan ◽  
Jason R. Gotlib ◽  
Steven Coutre ◽  
Ravindra Majeti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
High Risk ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either <=3 or <=7 days) tended to be older than APL patients with non-early deaths (>7d), or APL patients alive as of their last follow-up (median age 54 years vs. 50 years vs. 39 years), and were more likely to have higher risk disease, though coagulopathy appeared not significantly different amongst the groups. Median fibrinogen, PTT and INR for each individual group are presented on Table 1. The 3-year overall survival (% +/- SE) of the low, intermediate, and high risk patients was 90+/-7, 74+/-7, and 64+/-8, respectively, though early mortality (death within 7 days) was a major determinant of this stratification (p=0.045). Conclusions: Risk of early death in APL patients appears to be higher than previously reported in clinical trials, where trial registration may exclude patients requiring urgent therapeutic interventions. In this cohort, 25% and 13% patients with high- and intermediate-risk APL died within 7 days of presentation, respectively. Risk group stratification was very predictive of risk of early death. Disclosures: No relevant conflicts of interest to declare.

Survival Improvement of Patients with Chronic Lymphocytic Leukemia (CLL) in Routine Care. a Retrospective Analysis of All Patients with CLL Who Were Treated in an Oncology Group Practice in Germany Between 1995-2015

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5961-5961
Author(s):  
Rudolf Weide ◽  
Stefan Feiten ◽  
Geothy Chakupurakal ◽  
Vera Friesenhahn ◽  
Kristina Kleboth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Retrospective Analysis ◽  
Median Overall Survival ◽  
Routine Care ◽  
Initial Diagnosis ◽  
Group Practice ◽  
Routine Practice ◽  
Oncology Group ◽  
Binet Stage

Abstract Introduction:Progress has been made in the diagnosis and treatment of patients with CLL who receive their treatment within prospective clinical trials. Clinical trials only include patients who fulfill the selection criteria and hence do not reflect outcomes in routine practice. Data with regards to the diagnosis, treatment and survival of patients in routine care reflecting the improvements in survival following implementation of newer therapy strategies and agents are not available. Methods: A retrospective analysis of all patients with CLL who were treated in an oncology group practice in Germany between 1995-2015. Relevant clinical data concerning diagnosis, treatment and survival were transferred from clinical files into a database and analysed statistically using SPSS. Results:676 CLL patients with a median age of 67 (35-92) were identified. At initial diagnosis 521 patients (77.1%) were in Binet stage A, 83 (12.3%) Binet stage B and 36 (5.3%) Binet stage C. Due to external diagnosis of 36 patients (5.3%) the stage at initial diagnosis couldn't be retrieved. 361 patients (53.4%) never received any treatment. 315 patients (46.6%) needed therapy with a median of 2 therapy lines (1-13). Regimens most frequently applied were: Bendamustine-containing (68.9%), Rituximab-containing (65.4%), Chlorambucil-containing (55.9%), Bendamustine+Rituximab combinations (48.3%) and Fludarabine-containing (39.4%). Regimens containing recently approved drugs could be found as well. 5.1% received Ibrutinib, 2.9% Obinutuzumab and 2.2% Idelalisib. 17.8% of patients were treated within a clinical trial. 5 and 10 year overall survival was 84.5% and 60.4%. Median overall survival according to Binet stage was 13 years for Binet A, 9 years for Binet B and 9 years for Binet C. Patients who needed therapy had a median overall survival of 11 years (0-42) compared to 17 years (0-27) of patients who never needed any therapy. Conclusions: 53.4% of CLL-patients never needed any therapy. Patients who needed therapy had a much lower life expectancy compared to patients who never needed therapy. Treatment consisted mainly of Bendamustine, Rituximab, Chlorambucil, Bendamustine+Rituximab combinations and Fludarabine leading to a marked prolongation of survival compared to historical controls and registry data. Disclosures No relevant conflicts of interest to declare.

Real-World Ibrutinib Validation of the Ball Score to Predict Overall Survival: A Filo Group Study in RR CLL Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1741-1741
Author(s):  
Loic Ysebaert ◽  
Anne-Sophie Michallet ◽  
Fontanet Bijou ◽  
Aline Clavert ◽  
Anne Quinquenel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
High Risk ◽  
Risk Score ◽  
Real World ◽  
Low Risk ◽  
The Other ◽  
Intermediate Risk ◽  
Second Cancer ◽  
Other Hand

Abstract Ibrutinib has revolutionized the management of RR CLL in the past 5 years, improving overall survival (OS) over standard chemo-immunotherapies (CIT) in the registration trials HELIOS and RESONATE. Recently, based on these two studies, a score has been validated able to predict 3 groups with different OS (acronym BALL, further validated in cohorts of patients treated with CIT or other targeted agents) (1). The BALL model consists of four factors with 1 point each (serum ß2-microglobulin>5mg/dL, lactate dehydrogenase >upper limit of normal, hemoglobin <110g/L for women or <120g/L for men, and time from initiation of last therapy <24 months). It separates patients into low (score 0-1), intermediate (score 2-3), and high risk (score 4) groups. Yet, BALL score has never been validated in large cohorts of ibrutinib patients. Methods We collected survival data and causes of death across 10 FiLO centers, in patients treated with ibrutinib monotherapy as per label for RR disease. We included patients across performans statuses, irrespective of previous line of therapies (LOT) or age, with 3 (n=329) or 4 (n=250) available BALL criteria at the time of initiation. Results Median FU was 29.3 months. Stratification of BALL scores in 250 patients (with 4 parameters known) was as follows: low risk (n=88, 35.2%), intermediate risk (n=122, 48.8%), and high risk (n=40, 16%), with estimated 2-years OS rates of 87.3%, 82.3% and 58.8%, respectively (Figure 1A, C-statistics index 0.64). These results are very similar (all 3 groups) to what Soumerai J et al.reported in their ibrutinib/CIT training dataset of 581 patients (1). Causes of 60/250 deaths were as follows: CLL 28.3%, Richter transformation 15%, infectious (33.3%) or cardiovascular (18.3%) toxicity, second cancer (5%). High risk score was significantly associated to deletion 17p/TP53 mutational status (69.4% vs47%, p<0.001), LOT3+ (65.8% vs33.8%, p=0.02), but not age or gender. We also calculated a "worse BALL score" by adding 1 point to 79 more patients with 3 known parameters (n=329 in total). Stratification was as follows: low risk (6.7%, 2y-OS 100%), intermediate risk (45.6%, 2y-OS 82.9%), and high risk (47.7%, 2y-OS 74.6%) (Figure 1B). The latter results were very comparable to the internal validation dataset of ibrutinib/CIT in 242 patients. Causes of 79/329 deaths were as follows: CLL 27.8%, Richter transformation 17.7%, infectious (35.4%) or cardiovascular (15.2%) toxicity, second cancer (3.8%). Altogether, the BALL score was useful to delineate 3 risk-groups with statistically different survivals in real-world ibrutinib patients, despite 50% of deaths were due to toxicity. By Cox univariate analysis for OS (n=227, events=57), variables with significant impact on prognosis were: age>79y (HR 2.09, p=0.003), male gender (HR 1.5, p=0.046), del17p/TP53 mutation (HR 1.45, p=0.049), previous lines of therapy (LOT1-2 vs 3+, HR 2.17, p<0.0001), and BALL score (2-3 vs0-1 HR 1.8, and 4 vs0-1 HR 5.69, p<0.0001). By multivariate analysis, only LOT3+ (HR 2.6, p=0.003) and BALL score (2-3 vs0-1 HR 2.16, p=0.05, and 4 vs0-1 HR 5.2, p<0.001) were shown as independent factors significantly associated with shorter OS. These results further advocated for the use of BALL score in our practice, because we validated its use even in elderly RR patients. In the clinical trials used for model building, median age was <65y, and we included 23.1% of patients >79y. On the other hand, LOT was excluded from the model, and so its impact left unanswered by the first publication. Our data suggested that OS of multi-relapsing patients (3 or more previous lines of therapy) was not adequately predicted by the BALL score. On the other hand, we confirmed that deletion 17p/TP53mutational status was not an independent factor for OS, because predicted by the BALL score parameters (1). Conclusions In our series, the BALL score also identified a well-defined cohort of real-world RR CLL patients with an unmet clinical need despite the use of ibrutinib (median OS 27 months). We suggest that patients in the high-risk group should be thoroughly monitored, or even proposed clinical trials with drug combinations, or even cellular therapies approaches (CAR-T cells, bispecific antibodies) due their shorter OS. (1) Soumerai J, et al. Risk Model for Overall Survival in Relapsed or Refractory Chronic Lymphocytic Leukaemia in the Era of Targeted Therapies. Lancet Haematol 2019. Disclosures No relevant conflicts of interest to declare.

scholarly journals Are survival and mortality rates associated with recruitment to clinical trials in teenage and young adult patients with acute lymphoblastic leukaemia? A retrospective observational analysis in England

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017052 ◽  
Author(s):  
Rachael Hough ◽  
Sabrina Sandhu ◽  
Maria Khan ◽  
Anthony Moran ◽  
Richard Feltbower ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Relative Survival ◽  
Data Repository ◽  
Trial Participation ◽  
Patient Benefit ◽  
Cancer Data

ObjectiveParticipation rates in clinical trials are low in teenagers and young adults (TYA) with cancer. Whilst the importance of clinical trials in informing best practice is well established, data regarding individual patient benefit are scarce. We have investigated the association between overall survival and trial recruitment in TYA patients with acute lymphoblastic leukaemia (ALL).DesignRetrospective.SettingNational (England) TYA patients treated for ALL.Participants511 patients aged 15–24 years diagnosed with ALL between 2004 and 2010 inclusive, of whom 239 (46.7%) participated in the UKALL2003 trial.Outcome measuresPatients were identified using National Clinical Trial (UKALL2003) and Cancer Registry (National Cancer Data Repository, English National Cancer Online Registration Environment) Databases. Relative survival rates were calculated for trial and non-trial patients and observed differences were modelled using a multiple regression approach. The numbers and percentages of deaths in those patients included in the survival analysis were determined for each 3-month period, p values were calculated using the two-tailed z-test for difference between proportions and 95% CIs for percentage deaths were derived using the binomial distribution based on the Wilson Score method.ResultsPatients treated on the trial had a 17.9% better 2-year survival (85.4% vs 67.5%, p<0.001) and 8.9% better 1-year survival (90.8% vs 81.9%, p=0.004) than those not on the trial. 35 (14.6%) patients recruited to the trial died in the 2 years following diagnosis compared with 86 (32.6%) of those not recruited (p<0.001).ConclusionsTYA patients recruited to the clinical trial UKALL 2003 in England had a lower risk of mortality and a higher overall survival than contemporaneous non-trial patients. These data underline the potential for individual patient benefit in participating in a clinical trial and the importance of international efforts to increase trial participation in the TYA age group.Trial registration numberISRCTN07355119.

scholarly journals Mutational Characteristics and Changing Pattern from Idiopathic Cytopenia of Undetermined Significance to High-Risk Myelodysplastic Syndrome Stratified By IPSS-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3009-3009
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-jeoung Park ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Rna Splicing ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
Sequencing Data ◽  
Undetermined Significance

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

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

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

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

scholarly journals Cancer drug development: The missing links

2019 ◽  
Vol 244 (8) ◽  
pp. 663-689 ◽  
Author(s):  
Ajaikumar B Kunnumakkara ◽  
Devivasha Bordoloi ◽  
Bethsebie Lalduhsaki Sailo ◽  
Nand Kishor Roy ◽  
Krishan Kumar Thakur ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Drug Development ◽  
Targeted Therapies ◽  
Science And Technology ◽  
Development Cost ◽  
Phase I Clinical Trials ◽  
Drug Benefits ◽  
Number Of Patients ◽  
Pharmaceutical Industries

Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

Timing of Adjuvant Radioactive Iodine Therapy Does Not Affect Overall Survival in Low- and Intermediate-Risk Papillary Thyroid Carcinoma

2016 ◽  
Vol 82 (9) ◽  
pp. 807-814 ◽  
Author(s):  
Paritosh Suman ◽  
Chi-Hsiung Wang ◽  
Tricia A. Moo-Young ◽  
Richard A. Prinz ◽  
David J. Winchester
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Radioactive Iodine ◽  
Low Risk ◽  
Intermediate Risk ◽  
Radioactive Iodine Therapy ◽  
Papillary Thyroid ◽  
Risk Patients

There is no consensus regarding the timing of adjuvant radioactive iodine therapy (RAI) therapy in low- and intermediate-risk papillary thyroid carcinoma (PTC). We analyzed the impact of adjuvant RAI on overall survival (OS) in low- and intermediate-risk PTC. The National Cancer Data Base was queried from 2004 to 2011 for pN0M0 PTC patients having near/subtotal or total thyroidectomy and adjuvant RAI. Tumors ≤1 cm with negative margins were low risk while 1.1- to 4-cm tumors with negative margins or ≤1 cm with microscopic margins were termed intermediate risk. RAI in ≤3 months and between 3 and 12 months was termed as early and delayed, respectively. Survival analysis was performed after adjusting for patient and tumor-related variables. There were 7,306 low-risk and 16,609 intermediate-risk patients. Seventeen per cent low-risk and 15 per cent intermediate-risk patients had delayed RAI. Kaplan-Meier analysis did not show a difference in OS for early versus delayed RAI administration in low- (10-year OS 94.5% vs 94%, P = 0.627) or intermediate-risk (10-year OS 95.3% vs 95.9%, P = 0.944) patients. In adjusted survival analysis, RAI timing did not affect OS in all patients (hazard ratios = 0.98, 95% confidence interval = 0.71–1.34, P = 0.887). In conclusion, the timing of postthyroidectomy adjuvant RAI therapy does not affect OS in low- or intermediate-risk PTC.

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