Bias Assessment in Progression-Free Survival Analysis

2012 ◽  
pp. 299-338
Keyword(s):  
Survival Analysis ◽  
Progression Free Survival ◽  
Bias Assessment ◽  
Free Survival

scholarly journals Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma

2020 ◽  
Vol 477 (5) ◽  
pp. 677-685
Author(s):  
Ben Davidson ◽  
Arild Holth ◽  
Hiep Phuc Dong
Keyword(s):  
Stem Cell ◽  
Survival Analysis ◽  
Cancer Stem Cell ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
Stem Cell Marker ◽  
Serous Carcinoma ◽  
High Grade ◽  
Poor Survival ◽  
Free Survival

Abstract The objective of the present study was to perform a quantitative analysis of cancer stem cell (CSC) marker expression in ovarian carcinoma effusions. The clinical role of SSEA1 in metastatic high-grade serous carcinoma (HGSC) was additionally analyzed. CD133, Nanog, SOX2, Oct3/4, SSEA1, and SSEA4 protein expressions were quantitatively analyzed using flow cytometry (FCM) in 24 effusions. SSEA1 expression by immunohistochemistry was analyzed in 384 HGSC effusions. Highly variable expression of CSC markers by FCM was observed, ranging from 0 to 78% of Ber-EP4-positive cells in the case of CD133, with the largest number of negative specimens seen for SSEA4. SSEA1 expression by immunohistochemistry was found in HGSC cells in 336/384 (89%) effusions, most commonly focally (< 5% of cells). SSEA1 was overexpressed in post-chemotherapy disease recurrence specimens compared with chemo-naïve HGSC effusions tapped at diagnosis (p = 0.029). In univariate survival analysis, higher SSEA1 expression was significantly associated with poor overall survival (p = 0.047) and progression-free survival (p = 0.018), though it failed to retain its prognostic role in Cox multivariate survival analysis in which it was analyzed with clinical parameters (p = 0.059 and p = 0.111 for overall and progression-free survival, respectively). In conclusion, CSC markers are variably expressed in ovarian carcinoma effusions. SSEA1 expression is associated with disease progression and poor survival in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

scholarly journals Lenalidomide and Low Dose Dexamethasone Plus Elotuzumab or Carfilzomib for Relapsed or Refractory Multiple Myeloma: A Comparison of Progression-Free Survival with Reconstructed Individual Participant Data

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shuo Li ◽  
Xiang-Yu Meng ◽  
Souraka Tapara Dramani Maman ◽  
Yong-Nong Xiao ◽  
Sheng Li
Keyword(s):  
Multiple Myeloma ◽  
Survival Analysis ◽  
Low Dose ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Baseline Status ◽  
Individual Participant

Background. Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports. Methods. We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated. Results. Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67]). Conclusion. The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.

Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma

2020 ◽  
pp. jclinpath-2020-206868
Author(s):  
Wei Sang ◽  
Jing Xue ◽  
Li-Ping Su ◽  
Abulajiang Gulinar ◽  
Qian Wang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Clinicopathological Parameters ◽  
Low Grade ◽  
Ki 67 ◽  
Free Survival ◽  
Tumour Location ◽  
Spearman Correlation Test ◽  
The Relationship

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.MethodsExpression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.ResultsHigh expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.ConclusionOur research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.

scholarly journals Adverse events during immunotherapy in Slovenian patients with metastatic melanoma reveal a positive correlation with better treatment outcomes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tanja Mesti ◽  
Vid Ceplak Mencin ◽  
Biljana Mileva Boshkoska ◽  
Janja Ocvirk
Keyword(s):  
Survival Analysis ◽  
Adverse Events ◽  
Treatment Outcomes ◽  
Metastatic Melanoma ◽  
Survival Probability ◽  
Progression Free Survival ◽  
Cox Proportional Hazards Model ◽  
Free Survival ◽  
Overall Response ◽  
Significant Difference

Abstract Background Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy. Patients and methods A retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups. Results Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE cohort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort. Conclusions Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall response rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.

scholarly journals Predicting Clear Cell Renal Cell Carcinoma Survival Using Kurtosis of Cytoplasm in the Hematoxylin Channel from Histology Slides

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Jun Wang ◽  
Jianhui Chen ◽  
Liren Jiang ◽  
Qi Wu ◽  
Dawei Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Purpose. Grade-dependent decrease of lipid storage in clear cell renal cell carcinoma (ccRCC) leads to morphology changes in HE sections. This study investigated the role of cytoplasmic features in frozen sections of ccRCC on prognosis using the digital pathology approach. Methods. We established an automatic pipeline that performed tumor region selection, stain vector normalization, nuclei segmentation, and feature extraction based on the pathologic data from Shanghai General Hospital and The Cancer Genome Atlas database. Extracted features were subjected to survival analysis. Results. Kurtosis of the cytoplasm in the hematoxylin channel was correlated with progression-free survival (HR 0.10, 95% CI: 0.04–0.24, p = 6.52 ∗ 10 − 7 ) and overall survival (HR 0.11, 95% CI: 0.05–0.31, p = 1.72 ∗ 10 − 5 ) in ccRCC, which outperformed other texture features in this analysis. Multivariate Cox regression analysis revealed that low kurtosis of cytoplasm in the hematoxylin channel was an independent predictor for a shorter progression-free survival time ( p = 0.044 ) and overall survival time (p = 0.01). Kaplan–Meier survival analysis of progression-free survival and overall survival also showed a significantly worse prognosis in patients with low kurtosis of the cytoplasm in the hematoxylin channel (both p < 0.0001 ). Lower kurtosis of cytoplasm in the hematoxylin channel was associated with higher pathologic grade, less cholesterol ester, and more mitochondrial DNA content. Conclusion. Kurtosis of the cytoplasm in the hematoxylin channel predicts survival in clear cell renal cell carcinoma.

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

2009 ◽  
Vol 101 (03) ◽  
pp. 541-546 ◽  
Author(s):  
Andreas Scorilas ◽  
Sonia Markakis ◽  
Diane Kowalski ◽  
Robert L. Camp ◽  
Eleftherios P. Diamandis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma

2018 ◽  
Vol 60 (4) ◽  
pp. 516-525 ◽  
Author(s):  
Adam Blomstergren ◽  
Anna Rydelius ◽  
Kasim Abul-Kasim ◽  
Jimmy Lätt ◽  
Pia C Sundgren ◽  
...  
Keyword(s):  
Decision Making ◽  
Overall Survival ◽  
Survival Analysis ◽  
Progression Free Survival ◽  
Volume Estimation ◽  
Estimation Methods ◽  
Rater Agreement ◽  
Entire Study ◽  
Free Survival ◽  
Cox Regression Analysis

Background Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period. Purpose The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR by comparing QRA with subjective visual estimation and with objective volume estimations. The second aim was to clarify whether QRA of RTV and EOR would provide accuracy in predicting progression-free survival (PFS) and overall survival (OS) in GB patients. Material and Methods Seventy GB patients were studied retrospectively. Reproducibility of QRA was compared to conventional visual analysis. Intra-rater agreement between two repeated measurements of 25 patients was calculated. QRA for RTV and EOR was made for the entire study population. Survival analysis was performed by multivariate cox-regression analysis. Results QRA of RTV and EOR gave superior intra-rater agreement compared to subjective evaluation. Multivariate survival analysis showed prognostic significance on 18 months PFS (hazard ratio [HR] = 0.44, P = 0.003) and OS (HR = 0.42, P = 0.012) at RTV < 1.6 mL and with EOR > 96% on PFS (HR = 2.152, P = 0.005) but not on OS (HR = 1.92, P = 0.053). Conclusion QRA of tumor volumes is more robust compared to standard evaluation methods. Since EOR and RTV are correlated to the prognosis in GB, quantitative analysis of tumor volumes could aid decision-making and patient management postoperatively.

Genetic Variations Associated with Overall and Progression-Free Survival in Multiple Myeloma Patients Treated with Thalidomide Combinations.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 426-426 ◽  
Author(s):  
David C Johnson ◽  
Walter M Gregory ◽  
Nicholas J Dickens ◽  
Brian A Walker ◽  
Alex J Szubert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Strand Break ◽  
Individual Response ◽  
Nucleotide Polymorphisms ◽  
Free Survival ◽  
Disease Response

Abstract Abstract 426 It is anticipated that inherited single nucleotide polymorphisms (SNPs) in genes involved in drug absorption, distribution, metabolism and excretion influence individual response to thalidomide therapies in Multiple Myeloma. We extracted peripheral blood DNA from 631 myeloma patients of European descent enrolled in the MRC Myeloma IX trial who had received induction thalidomide (50-200mg). We genotyped 3404 SNPs selected in 983 candidate genes that may influence myeloma disease response, toxicity, and/or survival, on a “Bank on a Cure” (BOAC) Affymetrix® true-tag array. The BOAC array is a custom genotyping chip focused on coding and predicted regulatory SNPs. Quality control (QC) measures were applied on the resulting genotype data such that individual samples failing a chip call rate (> 95%), and SNP assays with missing data (< 0.05%) or with extreme departures from Hardy-Weinberg equilibrium (p > 10-5) were excluded from the statistical analysis. We then performed 2-way log rank tests under recessive, dominant and trend genetic models for each SNP which passed QC for both overall survival and PFS on the training and validation sets. Our training set consisted of 379 myeloma patients from the intensive pathway of the Myeloma IX trial who received CTD (cyclophosphamide, thalidomide, dexamethasone), with a validation set of 252 myeloma patients from the non-intensive pathway who received an attenuated CTD regime. Although the overall and progression-free survival is shorter for individuals in the non-intensive arm in comparison to the younger and fitter patients in the intensive arm, we expected variants influencing overall survival and PFS related to thalidomide to associate with outcome, if both pathways were analysed separately. We looked for significant associations (log-rank chi-squares > 6.5, p > 10-3) across both the training and validation sets, and discounted associations where the number of cases in any one genotype group <10. We detected significant cross validating associations in the survival analysis with genes involved in double-strand break repair: BLM, LIG1, MRE11A, SHFM1 and RAD51L3, and also saw associations with genes important in response to DNA damage stimulus: CYP19A1, GSTA4 and MGST1, along with other notably associations in genes NFKBIE, NFKB1 and SELL. We saw cross validating SNP associations in the progression-free survival analysis in genes including the cytokines: IL10, IL13, as well as NFATC1. In this large study we have seen results indicating that genetic variation plays a role in both overall and progression free survival following thalidomide treatment in multiple myeloma patients, and in doing so we have highlighted SNPs and pathways that may be important and informative in predictive classification of patients for overall survival and PFS following treatment with thalidomide containing regimes. Disclosures: No relevant conflicts of interest to declare.

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