Chemosensitivity and stratification by a five monoclonal antibody IHC test in the NSABP B20 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 529-529 ◽  
Author(s):  
D. T. Ross ◽  
C. Kim ◽  
G. Tang ◽  
O. M. Mejia ◽  
R. A. Beck ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Statistical Power ◽  
Risk Group ◽  
Cox Model ◽  
Small Sample ◽  
Tissue Array ◽  
Rank Test ◽  
P Value ◽  
Ratio Test ◽  
Significant Difference

529 Background: We previously reported the association between a five monoclonal antibody test staining p53, NDRG1, SLC7A5, CEACAM5 and HTF9C and recurrence-free interval (RFI) in 711 ER+ N- breast cancer patients from Tamoxifen (Tam) arm of the NSABP trials B14 and B20 (SABCS 2006). In this study, we examined interaction between the test and chemotherapy in the B20 trial. Subjects and Methods: Tissue array sections from B20 paraffin blocks were stained using standard IHC protocols (N=457). Pre-defined scoring rules and cut- points were applied. RFI was defined as time from entry to any local, regional or distant recurrence. Log-rank test was applied to assess the effect of chemotherapy for each risk stratum pre-defined by this IHC test. Interaction between risk strata and treatment was assessed by the likelihood ratio test in a Cox model with age and clinical tumor size adjusted. Results: The IHC test identified high and low risk groups that both showed significant improvement upon treatment with cytotoxic chemotherapy. The moderate risk group was poorly populated and showed no significant difference between chemo-treated and Tam-only patients. Conclusion: It appears that five monoclonal antibodies may be able to identify groups of ER+, node negative patients who have greater absolute benefit from adjuvant Chemo compared to un-stratified patient populations. However, the formal test for interaction between Chemo and the risk group was not significant (p- value=0.127). This may be due to small sample size and a lack of statistical power. The results suggest that this test deserves further evaluation as a method for identifying subsets of patients who may receive more benefit from Chemo. [Table: see text] No significant financial relationships to disclose.

Prognostic Factors in the UK LRF CLL4 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 299-299 ◽  
Author(s):  
David Graham Oscier ◽  
Rachel Wade ◽  
Jenny Orchard ◽  
Zadie Davis ◽  
Giles Best ◽  
...  
Keyword(s):  
Risk Group ◽  
Univariate Analysis ◽  
Treatment Modalities ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Significant Difference ◽  
Trisomy 12 ◽  
Vh Genes

Abstract The LRF CLL4 trial randomised 777 previously untreated patients with Binet stage progressive A, B or C disease between January 1999 and October 2004 to receive either Chlorambucil, Fludarabine or Fludarabine and Cyclophosphamide. Interphase FISH for deletions of chromosome 6q, 11q, 13q, 17p and trisomy 12, IgVH gene mutational status (98% cut off), CD38 (7% cut off) and ZAP70 (10% cut off) expression were measured at randomisation on 579, 523, 535 and 478 patients respectively. Leukemic cells from 39 patients utilised the VH3-21 gene of whom 33 had homologous CDR3’s. Among the biological markers, log rank analysis showed that >20% p53 loss, del 11q, unmutated VH genes, high CD38 and high ZAP 70 correlated with disease progression or death (Table 1) but not deletion of chromosome 6q, 13q and trisomy 12 (p=0.7, 0.3 and 0.2 respectively). There was no difference in PFS or response duration between the 52 patients with 5–20% p53 loss and the 494 patients with no p53 loss. Multivariate Cox regression analysis showed that >20% p53 loss (p<0.0001), unmutated IgVH genes (p=0.0001), deletion of 11q (p=0.02) and male gender (p=0.03) were independent risk factors for short PFS. The effects of stage and age were overridden by FISH abnormalities. High ZAP70 expression was only significant when VH gene mutation status was not included in the model. CD38 expression was only significant in univariate analysis. Table 1 Variable Progression or Death/N Univariate p-value(log rank test) Gender Male 384/573 0.002 Female 111/204 17q(p53) No 131/546 <0.00005 Yes 21/33 IgVH Unmutated 105/203 <0.00005 Mutated 225/320 del 11q No 288/463 <0.00005 Yes 87/116 ZAP70 Negative 140/242 0.003 Positive 158/236 CD38 Negative 110/201 0.0001 Positive 227/334 Among the 320 unmutated cases there was no significant difference in PFS between those with 100% homology (227 cases) and those with 99% or 98% homology to the germline sequence (93 cases). Mutated VH3-21 cases were more likely to express ZAP70 than other mutated cases, p=0.004. Excluding patients with >20% p53 loss, patients using the VH3-21 gene had similar progression free survival (PFS) to those remaining patients with unmutated VH genes and an inferior PFS to those with mutated VH genes (2p=0.0001). The adverse prognostic significance of 11q deletions was not clearly evident in an interim analysis presented at ASH ‘05. Patients can now be divided into 3 risk groups (Table 2). This risk stratification provides the basis of evaluating differing treatment modalities for each risk group in subsequent clinical trials. Table 2 Risk Group Definition Progression or Death/N Univariate p-value (log-rank test) 3 yr PFS Poor >20%p53 loss 28/33 0% Standard Unmutated VH or 11q deletion or VH3-21 208/292 <0.00001 24.7% Good Mutated VH(excl VH3–21) 79/161 55.0%

scholarly journals Time to viral load suppression and its associated factors in cohort of patients taking antiretroviral treatment in East Shewa Zone, Oromiya, Ethiopia, 2018

2019 ◽  
Author(s):  
Jemal H Ali
Keyword(s):  
Viral Load ◽  
Marital Status ◽  
Associated Factors ◽  
Plasma Viral Load ◽  
Baseline Viral Load ◽  
Rank Test ◽  
P Value ◽  
People Living With Hiv ◽  
Age Group ◽  
Significant Difference

Abstract Background: Human immuno-deficiency virus is a virus that causes Acquired Immuno- Deficiency Syndrome. The key goal of ART is to achieve and maintain durable viral suppression. Thus, the most important use of the viral load is to monitor the effectiveness of therapy after initiation of ART. The main objective of the study was to determine the time for virological suppression and its associated factors among people living with HIV taking antiretroviral treatments in East shewa zone, Oromiya, Ethiopia. Methods: The study was conducted in East Shewa zone, Oromiya, Ethiopia from August 2017 to January 2018. Patients diagnosed with human immunodeficiency virus presenting to the study health centers between October 3, 2011 and March 1, 2013 were included in the study given the following criteria: age 18 years or greater, eligible to start ART. All patients with baseline viral load measurement were included in the study. Interaction between explanatory variables with the response variable was analyzed by using cross tab features of SPSS, IBM Inc. Significance group comparison was done by Kaplan Meier log rank test. Cox proportional hazard model was used to select significant factors to the variability between groups. Data was collected by using structured questionnaires and interview. A total of ETB 81,120.00 was utilized to carry out the study. Result: plasma viral load was suppressed below detection level in 72% of individuals taking different regimen of ART. The median HIV-1 plasma viral load in the cohort was log 5.3111 copies/ml. Survival curve difference were observed in category of marital status (p-value 0.023) and baseline CD4 values (p-value 0.023) whereas no significant difference were observed in Educational status (p-value 0.404), MUAC (p- value 0.407) BMI(p-value 0.335) and BTB(p-value 0.257). Estimated median time to PVL suppression was 181days (CI: 140.5-221.4) with the age group of 30-39years having minimum time to achieve suppression with 92 days (CI: 60.1-123.8) and the maximum time required to reach the level was age group between 50-59 years. Conclusion: Estimated time to achieve PVL after taking ART was found to be 181 days. Factors affecting time to suppression level was marital status and baseline CD4.

scholarly journals Effect of Application Time of Two Different Disinfectants on the Surface Roughness of an Elastomeric Impression Material

2020 ◽  
Author(s):  
Tahir Karaman ◽  
Faruk Oztekin ◽  
Samet Tekin
Keyword(s):  
Surface Roughness ◽  
Sodium Hypochlorite ◽  
Quaternary Ammonium ◽  
Rank Test ◽  
Control Group ◽  
P Value ◽  
Sodium Hypochlorite Solution ◽  
Application Time ◽  
Impression Material ◽  
Significant Difference

Introduction: Pathogens, such as cytomegalovirus, hepatitis B virus, hepatitis C virus, herpes simplex virus types 1 and 2, and human immunodeficiency virus are transmitted, threatening the health of dental laboratory workers, especially as a result of saliva and blood contact of patients. To prevent cross-infection, impression materials should be disinfected at the end of the impression process in the mouth. Aim: To study the effect of application time of sodium hypochlorite and quaternary ammonium-based disinfectant solution on the surface roughness of an elastomeric impression material. Materials and Methods: In this in-vitro study done during March 2020, 10 disc-shaped samples were used in each group, with a total of 110 samples obtained from a light body elastomeric impression material with dimensions of 15×3 mm. The samples were kept in a sodium hypochlorite solution (Wizard; Rehber Kimya, Istanbul, Turkey) at concentrations of 1% and 5% for 1, 5, 10, and 30 minutes and in a quaternary ammonium-based disinfectant (Zeta 7 Solution, Zhermack SpA, Italy) for 10 and 30 minutes. Surface roughness measurements were taken with a profilometer device. The data obtained were statistically analysed by Kolmogorov-Smirnov test and Wilcoxon signed rank test for dependent/paired groups for the continuous data. The significance level was set to α=0.05. Results: A statistically significant difference was found between the control group and the 1% sodium hypochlorite (30 min p-value 0.037), and 5% sodium hypochlorite (30 min p-value 0.017). The statistical evaluation of the surface roughness of the samples with different concentrations of sodium hypochlorite and the same times was done and found statistically significant at 30 mins, p-value 0.021. Conclusion: The prolonged application of the sodium hypochlorite disinfectant at 1% and 5% concentrations caused a significant increase in the light body elastomeric impression material’s surface roughness

scholarly journals Postural Changes in Measures of Arterial Stiffness in Hypertensive Subjects on Antihypertensive Drug Therapy: A Prospective, Pilot Study

2016 ◽  
Vol 26 (02) ◽  
pp. 078-082
Author(s):  
Du Jun ◽  
Chin Cheong ◽  
Ashish Sule
Keyword(s):  
Arterial Stiffness ◽  
Supine Position ◽  
Enzyme Inhibitor ◽  
Antihypertensive Drug Therapy ◽  
Rank Test ◽  
P Value ◽  
Sitting Position ◽  
Antihypertensive Medications ◽  
Postural Changes ◽  
Significant Difference

AbstractProspective study with a controlled arm to know if there are variations of measures of arterial stiffness with posture in subjects with hypertension on antihypertensive medications.We studied postural variations of measures of arterial stiffness in 21 subjects with diagnosed hypertension on antihypertensive medications and compared them with 21 normotensive subjects. All subjects underwent pulse-wave analysis on SphygmoCor in the morning between 8 am to 10 am initially in supine and then in sitting position after 3 minutes. Summary measures on demographics, and blood pressure characteristics at sitting and supine positions are obtained. Differences between characteristics at supine and sitting position are compared using nonparametric paired test of Wilcoxon signed-rank test. A value of p < 0.05 was accepted as statistically significant.Antihypertensive medications decreased the supine aortic augmentation pressure (AAP) and augmentation index (AI) but not significantly. When subgroups of patients with antihypertensive treatment were analyzed, it was noted that angiotensin-converting enzyme inhibitor and angiotensin receptor blocker group (12) decreased AAP and AI significantly in supine position compared with patients on other antihypertensive medications (9) (p-value 0.034 and 0.038, respectively). There was no significant difference in other groups of calcium channel blockers, β-blockers, or diuretics. However, in normotensive control arm, there was an increase in AAP and AI in the supine position.In hypertensive subjects, on antihypertensive, there was reduction in AAP and AI in supine position compared with those of normotensives. The significance of the decrease in AAP and AI in supine position on antihypertensive needs to be studied further.

Development and Validation of a GC-MS Method for the Quantitation of Nanoformulated Primaquine in Whole Blood and Plasma of Mouse Model

2017 ◽  
Vol 2 (1) ◽  
pp. 44-58
Author(s):  
James Jorum Owuor ◽  
Florence Oloo ◽  
Martin Ongas ◽  
Caroline Kirimi ◽  
Wesley Nyaigoti Omwoyo ◽  
...  
Keyword(s):  
Whole Blood ◽  
Internal Standard ◽  
Small Sample ◽  
Precipitation Method ◽  
Gas Chromatography Mass Spectrometry ◽  
P Value ◽  
Blood Collection ◽  
Significant Difference ◽  
Product Ions ◽  
The Mean

A Gas chromatography-mass spectrometry (GC/MS) method was developed and validated for the quantitation of the antimalarial drug, nanoformulated Primaquine (PQ), in whole blood and plasma. The analyte was extracted using a protein precipitation method followed by chromatographic separation on a Waters Xterra, RP C8, 2.5µm, 50mm x 4.6mm analytical column with a mobile phase consisting of A: 0.5% Formic acid in 20mM NH4COOH, B: Methanol pH adjusted to 3.0 with FA at a ratio of 3:7 (v/v), delivered at a constant flow rate of 0.5 ml/min. Mefloquine (MEF) was used as the internal standard. Compound reaction monitoring was performed using 260.4 Da for precursor ion and 175. 2 and 379.2 Da for product ions for the quantification of PQ and 379.2 Da for precursor ion and 175.2 and 379.2 Da for product ions for the quantification, respectively. Calibration curves were constructed over the concentration range 16.7–4300 ng/ml. The mean intra- and inter-assay accuracy values for the analysis of PQ in WB was 104% (%CV = 5.6) and 98.6% (%CV = 5.7), respectively. The mean intra- and inter-assay accuracy values for the analysis of PQ in plasma was 92.7% (%CV = 3.7) and 93.7% (%CV = 5.4), respectively. No significant matrix effect was observed during the method validation. The validated method was applied to an absorption study in mice, to determine and compare PQ concentrations in whole blood and plasma samples. Results of the statistical analysis using a linear mixed effects growth curve model concluded that there was no significant difference (p-value = 0.688) between WB and plasma PQ concentrations. This method utilizes a small sample volume of 20 µl, facilitating low blood collection volumes and a short chromatographic run time of 3 min which allows for high sample through put analysis.

A Measure to Detect Sleep Onset Using Statistical Analysis of Spike Rhythmicity

2014 ◽  
Vol 3 (1) ◽  
pp. 27-41 ◽  
Author(s):  
B.R. Purnima ◽  
N. Sriraam ◽  
U. Krishnaswamy ◽  
K. Radhika
Keyword(s):  
Statistical Analysis ◽  
Sleep Onset ◽  
Rank Test ◽  
P Value ◽  
Sleep State ◽  
Statistical Measures ◽  
Plot Analysis ◽  
Significant Difference ◽  
Signed Rank Test ◽  
The Impact

Electroencephalogram (EEG) signals derived from polysomnography recordings play an important role in assessing the physiological and behavioral changes during onset of sleep. This paper suggests a spike rhythmicity based feature for discriminating the wake and sleep state. The polysomnography recordings are segmented into 1 second EEG patterns to ensure stationarity of the signal and four windowing scheme overlaps (0%, 50%, 60% and 75%)of EEG pattern are introduced to study the influence of the pre-processing procedure. The application of spike rhythmicity feature helps to estimate the number of spikes from the given pattern with a threshold of 25%.Then non parametric statistical analysis using Wilcoxon signed rank test is introduced to evaluate the impact of statistical measures such as mean, standard deviation, p-value and box-plot analysis under various conditions .The statistical test shows significant difference between wake and sleep with p<0.005 for the applied feature, thus demonstrating the efficiency of simple thresholding in distinguishing sleep and wake stage .

Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 328-328 ◽  
Author(s):  
Edo Vellenga ◽  
Annelise Notenboom ◽  
Mars van ‘t Veer ◽  
Josée Zijlstra ◽  
Willem E. Fibbe ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Response Duration ◽  
Rank Test ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Post Transplantation ◽  
Free Survival ◽  
Significant Difference ◽  
First Line Treatment

Abstract A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL. Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03

Myeloablative Chemotherapy for T-Cell Lymphoma: a Case for Autologous Stem Cell Transplantatin (Auto) in First Remission.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1141-1141 ◽  
Author(s):  
Issa F Khouri ◽  
Adriana Lopez ◽  
Grace-Julia Okoroji ◽  
Martin Korbling ◽  
Gloria McCormick ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Cox Model ◽  
Performance Status ◽  
Autologous Transplantation ◽  
T Cell Lymphoma ◽  
Cancer Center ◽  
P Value ◽  
Significant Difference ◽  
First Remission

Abstract In order to determine the long-term impact of AUTO in patients (pts) with T-cell lymphoma, we examined the outcome of 79 pts transplanted at the MD Anderson Cancer Center, in first partial or complete remission (CR) (AUTO1, n=20) or for relapsed / refractory disease (AUTO2, n=59) between 06/91 and 05/08. &lt;&lt;&lt;PATIENTS&gt;&gt;&gt; Median age (range) at transplantation was 49 (22–65) and 51 (16–77) for the AUTO1 and AUTO2 groups respectively (p=0.35); other baseline characteristics including gender, stage, B-symptoms, LDH, IPI, PET/Gallium status, history of marrow involvement, and performance status at transplantation were similar. There was a statistically significant difference between AUTO1 and AUTO2 with respect to histology {peripheral t-cell, angioimmunoblatic, and anaplastic/large cell were present in 80%, 5%, 15%, respectively in AUTO1, and 42%, 10%, and 45%, respectively in AUTO2 (p=0.02); one pt in AUTO2 had small lymphocytic and one had hepatosplenic T cell lymphoma}. Statistically significant differences were also noted with respect to B2-microglobulin (P=0.02; favoring AUTO1), number of prior chemotherapy regimens received {median 1 vs 3 for AUTO1 and AUTO2, respectively (p &lt;0.001)}, disease status at transplantation {18% of AUTO2 had stable or progressive disease at transplant vs 0% in AUTO1 (P &lt; 0.001)}, and # of CD34+cellsx10 6/Kg infused {median 9 vs 5 for AUTO1 and AUTO2, respectively}. Most pts in both group received BEAM as conditioning. Median follow-up time in months was 64 (95%CI, 31–87), and 47(95%CI29–121) for AUTO1 and AUTO, respectively. Median overall survival (OS) was 43.5 months (95%CI:30–70 for AUTO2 and the median OS was not reached for AUTO1 (P=0.01)(Figure). The median progression-free survival (PFS) was 16 months (95%CI:8–56) and 95 months (95%CI:6.94-NA) for the pts in the AUTO2 and AUTO1 groups, respectively (P=0.06). Univariate Cox models for OS showed that AUTO2 vs AUTO1 (HR 3.4, P=0.02), high LDH level (HR 2.6. P=0.01), PET/Gallium+ (HR 2.8, P=0.01), IPI2–4 (HR 3.4, P=0.002), marrow involvement (HR 6.3, P=0.02), and marrow vs peripheral blood as source of graft (HR 2.1, P=0.048) were important determinants of outcome. The univariate Cox model for PFS showed that only AUTO2 vs AUTO1, hi LDH, IPI and PET/gallium were statistically significant. A multivariate analysis that included the covariates with the lowest P value showed that AUTO2 vs AUTO1 remained the only important factor for OS (HR 4.79, P=0.035) while PET/ Gallium status at transplantation was the most important determinant of PFS (HR 3.13, P=0.006). &lt;&lt;&lt;CONCLUSION&gt;&gt;&gt; Autologous transplantation has the potential to cure a proportion of pts with t-cell lymphoma if performed during the first remission. Alternative strategies are needed for pts transplanted beyond first remission especially if they continue to have avid functional imaging at transplantation. Figure Figure

The IC50 Assay Is Predictive of Molecular Response, and Indicative of Optimal Dose in De-Novo CML Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1109-1109
Author(s):  
Deborah L White ◽  
Verity A Saunders ◽  
Thea Kalebic ◽  
Timothy P Hughes
Keyword(s):  
De Novo ◽  
Statistical Significance ◽  
Continuous Variable ◽  
Rank Test ◽  
P Value ◽  
Molecular Response ◽  
Optimization Strategy ◽  
Log Reduction ◽  
Significant Difference ◽  
The Impact

Abstract We have previously demonstrated significant interpatient variability in the IC50imatinib, a measure of the intrinsic sensitivity of a patient to imatinib induced kinase inhibition. Furthermore, this measure is predictive of the achievement of major molecular response (MMR &gt; 3 log reduction in BCR-ABL) in de-novo CML patients treated with imatinib (n=60)1. In an expanded patient pool (n=116) we now perform an evaluation of the IC50 as a predictor of response, and address the IC50imatinib as a guide to dose selection. Samples were obtained with informed consent from de novo CML patients enrolled to either the TIDEL (600mg imatinib) or TOPS (randomised 400mg vs 800mg imatinib) trials. Blood was collected pre therapy, and the IC50 was performed as previously1. Outcome data was assessed using Kaplan Meier Analysis and the log rank test was used to assess statistical significance. In our previous analysis the IC50imatinib was divided about the median value for the cohort (0.6μM) into low and high IC50, with a significantly greater proportion of patients with low IC50imatinib achieving MMR by 12 months. In this expanded patient pool, we confirm this finding (&lt;median of 0.7μM for this patient group) (low IC50 65% of patients achieve MMR by 12 mo vs high IC50 39% of patients p=0.014) Dividing the IC50’s into quartiles we now demonstrate that the IC50imatinib is a continuous variable with a greater proportion of patients in the lower quartile achieving MMR than those in the higher (Table 1 Total). Addressing the issue of dose we demonstrate that no patients with IC50&gt;0.95uM achieve MMR on 400mg, and that this is statistically significantly when compared to all other groups. At 600mg while there is no overall significant difference there is a statistically relevant difference between groups 1, 2 and 4 as indicated. In contrast, at 800 mg the effect of IC50imatinib is overcome. MMR by 12 months Total 400mg 600mg 800mg p value Group1 &lt;0.5μM 67% (27) 83% (12)* 50% (8)* 86% (7) 0.470 Group 2 &gt;0.5&lt;0.7μM 63% (30) 67% (6)* 53% (17)* 71% (7) 0.337 Group 3 &gt;0.7&lt;0.95μM 45% (31) 40%(5)* 30% (10) 56% (16) 0.139 Group 4&gt;0.95μM 32% (28) 0% (7)* 22% (9)* 58% (12) 0.016 P value 0.042 0.018 0.108 0.778 Table 1: Dividing the patients into quartile based on the IC50 imatinib and assessing the Impact of dose on the achievement of MMR by 12 month. *p value &lt;0.05 between groups (n). The failure to achieve a Complete Cytogenetic Response by 12 months is considered a suboptimal response. Assessing the molecular equivalent (≥2 log reduction in BCR-ABL) we demonstrate that a significantly greater proportion of patients with IC50imatinib&gt;0.7μM fail to achieve a 2 log reduction when treated with 400mg (IC50 &lt;0.7μM 11%: &gt;0.7μM 33% p=0.034), and 600mg (IC50 &lt;0.7μM 12%: &gt;0.7μM 22% p=0.036). However, there is no significant difference in the 800mg patient cohort (IC50 &lt;0.7μM 7%: &gt;0.7μM 14% p=0.79). This analysis confirms that the IC50imatinib, is predictive of imatinib response. Patients with an IC50imatinib &lt;0.7μM are likely to respond well to doses of 400mg imatinib, as suggested by evaluation of statistically relevant outcome benefit. In contrast patients with higher IC50imatinib (&gt;0.7μM) may benefit from higher dosing regimens (p=0.012). Thus, the accurate assessment of IC50imatinib could support dose optimization strategy for patients with a suboptimal response.

Changing treatment paradigms in the era of targeted therapies.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 518-518
Author(s):  
Philipp Marius Papavassilis ◽  
Edwin Herrmann ◽  
Laura-Maria Krabbe ◽  
Lothar Hertle ◽  
Martin Boegemann ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Rank Test ◽  
P Value ◽  
Line Treatment ◽  
New Agents ◽  
Exact Test ◽  
Significant Survival ◽  
Significant Difference ◽  
The University

518 Background: Our goal was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since targeted therapy became available in 2006. Methods: In this cohort population study we retrospectively investigated all mRCC patients who were treated with targeted therapy between 06/2006 and 06/2012 in the Department of Urology of the University of Münster. To distinguish nominal variables Fisher's exact test was used, in other respects Pearson's χ² test. For metrical variables the Mann-Whitney-U-Test was used. The log-rank test was chosen to derive differences between two or more groups with regard to survival. A p value <0,05 was considered statistically significant. Results: 50/158 (31.6%) patients with a median follow-up of 362 days were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0%). As first line treatment sunitinib was chosen most frequently (68 patients, 63.0%). There was no statistically significant difference in survival between the patients who were treated with immunotherapy and those who were not (572 vs. 554 days, p=0,745). 134 (84.4%) patients received cytoreductive nephrectomy before systemic treatment start. Comparing the survival curves there was a significant survival benefit in favor of nephrectomized patients (632 vs. 169 days, p<0,0001). Conclusions: After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductve nephrectomy should continue to be regarded as standard treatment.

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