HER2 status and prediction of extended endocrine benefit with breast cancer index (BCI) in HR+ patients in the adjuvant tamoxifen: To offer more? (aTTom) trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 522-522
Author(s):  
John Bartlett ◽  
Dennis C. Sgroi ◽  
Kai Treuner ◽  
Yi Zhang ◽  
Tammy Piper ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Predictive Performance ◽  
Predictive Biomarker ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Significant Benefit ◽  
Her2 Status ◽  
Free Interval ◽  
Likelihood Ratio Testing ◽  
Extended Endocrine Therapy

522 Background: BCI is a validated gene expression-based assay that stratifies patients based on risk of overall (0-10y) and late (post-5y) distant recurrence (DR) and predicts likelihood of benefit from extended endocrine therapy (EET). The Trans-aTTom study established Level1B validation for BCI (H/I) to predict benefit from EET.1 In this updated Trans-aTTom analysis including HER2 status, BCI (H/I) and prediction of endocrine benefit were further characterized. Methods: Centralized HER2 was determined for all cases according to current ASCO/CAP guidelines. Kaplan-Meier and Cox proportional hazards regression were conducted to assess primary and secondary endpoints of Recurrence-Free Interval (RFI) and Disease-Free Interval (DFI), respectively. A three-way interaction using likelihood ratio testing, which included treatment, BCI (H/I) and HER2, was performed to assess the effect of HER2 on BCI (H/I) prediction of EET benefit. Results: Of 789 N+ patients, 90% (N = 711) and 9% (N = 72) were HR+/HER2- and HR+/HER2+, respectively. In the HER2- subset, BCI (H/I)-High (48%) showed significant benefit from 10y vs. 5y of tamoxifen (9.4% RFI: HR = 0.35 [95% CI 0.15-0.81]; P = 0.047) while BCI (H/I)-Low patients did not (-2.1% RFI; HR = 1.15 [95% CI 0.78-1.69]; P = 0.491). For DFI, BCI (H/I)-High patients also showed significant benefit (10.3% DFI; HR = 0.41 [95% CI 0.18-0.91]; P = 0.047) while BCI (H/I)-Low patients did not (-1.7% DFI; HR = 1.10 [95% CI 0.75-1.62] P = 0.612). As demonstrated in the overall N+ cohort, significant interaction between BCI (H/I) and treatment was shown in the HER2- subset (RFI P = 0.045; DFI P = 0.044). Notably, three-way interaction evaluating BCI (H/I), treatment and HER2 status was not statistically significant (P = 0.85), indicating the ability of BCI (H/I) to predict benefit of EET activity was not significantly affected by HER2 status. Conclusions: In this updated Trans-aTTom analysis with HER2 data, BCI (H/I) showed similar predictive performance for EET response in the HER2- subset when compared to the overall N+ cohort. These data further support the clinical utility of BCI (H/I) as a predictive biomarker for informing EET benefit in HR+/HER2- and HR+/HER2+ disease. Clinical trial information: NCT00003678 . [Table: see text]

Concordance of HER2+ status by IHC/ISH and ERBB2 status by NGS in a real-world clinicogenomic database and analysis of outcomes in patients (pts) with metastatic breast cancer (mBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1036-1036
Author(s):  
Cheryl D. Cho-Phan ◽  
Jeremy Snider ◽  
Liangliang Zhang ◽  
Kimberly McGregor ◽  
Alexa Betzig Schrock ◽  
...  
Keyword(s):  
Real World ◽  
Clinical Characteristics ◽  
Proportional Hazards ◽  
Metastatic Breast ◽  
Cox Proportional Hazards ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Testing ◽  
Specimen Collection ◽  
Testing Patterns

1036 Background: HER2 overexpression/amplification measured by IHC or ISH is a predictive biomarker for HER2-targeted therapies. Next-generation sequencing (NGS) can identify ERBB2 amplification (amp) and mutations. We examined clinical characteristics, NGS testing patterns, and outcomes of pts treated with 1L HER2 therapy with HER2+ mBC based on ERBB2 amp status using a real-world (RW) clinico-genomic database (CGDB). Methods: Pts with mBC (HER2+ by IHC and/or ISH) treated with 1L HER2 therapy who had undergone NGS and were treated within the Flatiron Health (FH) network were eligible. Clinical characteristics and HER2 testing results were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports and linked to genomic data from Foundation Medicine (FMI) in the nationwide (US-based), de-identified FH-FMI CGDB. Demographic, clinical and genomic characteristics were summarized and stratified by concordance between HER2+ (IHC 3+ or ISH amp+) and ERBB2amp+ status [copy number (CN) ≥ 5]. NGS testing patterns and 1L HER2 therapy were characterized and stratified by concordance status. Concordance was assessed based on contemporaneous timing of paired test specimen collection dates (FMI NGS ≤ 30 days of HER2+ status). RW overall survival (rwOS) stratified by HER2+/ ERBB2 amp concordance was estimated with Kaplan-Meier analysis and adjusted Cox proportional hazards models. Results: Among 268 eligible pts, HER2+/ ERBB2amp+ concordance was 66% (176/268); concordance among contemporaneous paired specimens was 73% (106/145). Demographic and clinical features were overall well-balanced with most pts treated at community sites [94%, (252/268)]; the discordant (HER2+/ ERBB2amp-) group (95/268) had more pts with hormone receptor positive disease (73% vs 62%). Concordance by assay type varied; IHC+ only, IHC+/ISH+, and ISH+ only agreement was 72% (95/132), 76% (26/34) and 52% (50/96), respectively. A higher proportion of discordance (35% vs 19%) was seen in pts treated at community vs. academic sites. Median rwOS was 32.9 months (IQR 25.9-38.9) among concordant (HER2+/ ERBB2amp+) and 15.5 months (IQR 8.9-30.1) among discordant (HER2+/ ERBB2amp-) pts, aHR = 0.71 [95% CI: 0.48-1.03; p = 0.073]. Conclusions: Among RW pts with HER2+ mBC receiving 1L HER2 therapy, discordance between ERBB2amp and IHC/ISH HER2 testing methods was observed. Pts with tumors HER2+ by IHC and/or ISH but negative for ERBB2amp had a trend towards worse rwOS following receipt of HER2 therapy compared to concordant cases. Contemporaneous timing of specimen collection was associated with greater concordance. Future analyses on the additive value of ERBB2 CN as a predictive marker, and assessing factors that may affect discordance such as intratumor HER2 heterogeneity, tumor content, and biopsy site are warranted.

Application of a time-varying covariate model to the analysis of CA 19–9 as a biomarker for time-to-progression (TTP) and overall survival (OS) in patients with advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
S. Boeck ◽  
R. P. Laubender ◽  
M. Haas ◽  
C. Klose ◽  
F. Kullmann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Pre Treatment

e15545 Background: It remains unclear whether baseline CA 19–9 or CA 19–9 kinetics during chemotherapy may serve as predictive biomarker in patients (pts) with pancreatic cancer (PC). Methods: Main inclusion criteria for this retrospective multicenter analysis: histologically confirmed diagnosis of PC, treatment with first-line therapy, pre-treatment CA 19–9 level of > 5.2 U/ml. Analysis of CA 19–9 was exclusively performed using the Elecsys® assay (Roche Diagnostics). The effect of the pre- treatment CA 19–9 level on TTP and OS was modelled by Cox proportional hazards regression. The effect of CA 19–9 kinetics was also modelled by Cox proportional hazards regression where CA 19–9 was treated as time-varying covariate. When modelling CA 19–9 we developed univariate and multivariate Cox models where we selected additional predictors (e.g. performance status) using backward elimination performing likelihood ratio tests on a significance level of 0.05. Results: One-hundred and fifteen pts from 5 German centers were included. Median age was 63 years, 12% had locally advanced and 88% metastatic disease; 73 % of the pts were treated within prospective clinical trials. Median baseline CA 19–9 was 1059 U/ml (range 9.5–100000), median pre- treatment bilirubin 0.6 mg/dl. The median TTP in the study population was 4.4 months, median OS 9.4 months. Univariate analysis showed that the pre-treatment CA 19–9 level (as continuous variable, log [CA 19–9]) was significantly associated with TTP (HR 1.24, 95% CI 1.12–1.37, p<0.001) and OS (HR 1.16, 95% CI 1.06–1.28, p=0.002). These associations remained significant also within a multivariate analysis. For CA 19–9 kinetics during chemotherapy, data from 69 pts (TTP) and 84 pts (OS) were available, respectively; log [CA 19–9] kinetics were found to be a significant predictor for TTP in univariate (HR 1.44, 95% CI 1.25–1.67, p<0.001) and multivariate (HR 1.39, 95% CI 1.19–1.62, p<0.001) analyses, and also for OS (univariate: HR 1.34, 95% CI 1.20–1.49, p<0.001; multivariate: HR 1.39, 95% CI 1.23–1.57, p<0.001). Conclusions: According to this new statistical model, CA 19–9 may serve as a useful predictive biomarker in advanced PC. [Table: see text]

Correlation of DPC4 status with outcomes in pancreatic adenocarcinoma patients receiving adjuvant chemoradiation.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 168-168
Author(s):  
J. M. Herman ◽  
C. C. Hsu ◽  
E. K. Fishman ◽  
R. H. Hruban ◽  
S. H. Lin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Local Recurrence ◽  
Proportional Hazards ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Liver Recurrence ◽  
Patterns Of Recurrence

168 Background: In an autopsy series of patients with advanced pancreatic cancer (PCA), loss of DPC4 was highly correlated with disseminated metastasis. The purpose of this study was to determine if DPC4 gene status predicts for survival and patterns of recurrence following adjuvant (adj) chemoradiation (CRT). Methods: 101 patients who underwent surgery followed by adjuvant 5-FU or gemcitabine-based CRT were studied. Imaging studies were reviewed to assess patterns of recurrence and tumor tissue obtained to determine DPC4 immunolabeling status. DPC4 status was graded as intact or lost/mutated. Kaplan-Meier estimates were used to compute survival and Cox proportional hazards were used to compare risk factors. Results: Median overall (mOS) and progression-free survival (PFS) was 22.6 mos (95% CI 18.8 to 31.6) and 14.0 mos (95% CI 11.5 to 18.4). The mOS and 1-yr OS for patients with DPC4 intact vs. lost status was 21.9 mos (95% CI 16.8-32.4) and 78.4% vs. 22.6 mos (95% CI 18.4-32.6) and 78.2%, respectively (HR: 1.05, p=0.82). After adjusting for node, margin status, tumor grade, tumor size, and age, DPC4 status did not predict for mOS (RR 1.04, 95% CI: 0.62-1.74, p=0.89). Time to first progression at any site for PCA with DPC4 intact vs. lost status was 13.8 vs. 14.0 mos (p=0.79). Local recurrence was more common in PCA with DPC4 loss than with intact status (34.4% vs. 13.7%, p=0.012). There was no difference in the rates of distant recurrence in PCA with intact vs. loss of DPC4 expression (62.8% vs. 55.7%, p=0.45); however, DPC4 loss was more commonly associated with liver recurrence (27.9% vs. 19.6%, p=0.31). Conclusions: In pancreatic cancer patients receiving adj CRT, loss of DPC4 labeling in their resected PCA indicates a greater likelihood of developing local recurrence despite having received adj CRT. Efforts to improve loco-regional control are therefore needed for these patients following surgery and adj CRT. No significant financial relationships to disclose.

Tumor IGF-1 expression as a predictive biomarker for IGF1R-directed therapy in advanced pancreatic cancer (APC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4054-4054 ◽  
Author(s):  
Milind M. Javle ◽  
Rachna T. Shroff ◽  
Gauri R. Varadhachary ◽  
Robert A. Wolff ◽  
David R. Fogelman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Primary Study ◽  
Study Objective ◽  
Log Rank Test ◽  
Hazards Model

4054 Background: IGF-1 up-regulates PC proliferation and invasiveness through activation of PI3K/Akt signaling pathway and down-regulates PTEN. We investigated IGF-1 expression in tissue and blood as potential predictive markers in phase II study of IGF1R-directed monoclonal antibody, MK-0646 in APC. Prior phase I established the MTD of MK0646 at 5 mg/kg with gemcitabine (G) and erlotinib (E) and 10 mg/kg with G alone. Methods: Patients (pts) with stage IV, previously untreated APC, ECOG PS 0-1, adequate hematologic and organ function were enrolled. Arm A: G 1,000 mg/m2 over 100 min, weekly x 3, MK-0646 weekly x 4; Arm B: G 1000 mg/m2 and MK-0646 + E 100 mg daily. Arm C (control) was G 1,000 mg/m2 + E 100 mg. Cycles were repeated every 4 weeks. Pts were equally randomized in the 3 arms. Primary study objective was progression-free survival (PFS). Pre-treatment peripheral blood samples were measured for IGF-1 level by ELISA; archival core biopsies were analyzed for IGF-1 mRNA expression. RNA extraction from FFPE samples used Roche Transcriptor First Strand cDNA Synthesis Kit. TaqMan PreAmp technique was used to amplify target cDNA prior to TaqMan RT-PCR analysis. Cox proportional hazards model for PFS analyzed the interaction between tissue IGF-1 expression and treatment. Results: 50 pts were enrolled (A=15, B=16,C=16 pts, 3 ineligible). Median PFS of arms A, B and C were 5.5 months (95% CI: 3.9 – NA), 3.0 months (95% CI:1.8 – 5.6) and 2.0 months (95% CI: 1.8 – NA), respectively (log-rank test; p = 0.17). Median OS of A was 11.3 months (95% CI: 8.9 – NA), B 8.9 months (95% CI: 5.3 – NA) and C 5.7 months (95% CI: 2.0 – NA) (log-rank test; p = 0.44). 35 archival core biopsies were analyzed, 21 had adequate tissue for analysis. Using a Multivariable Cox proportional hazards model for PFS, where IGF-1 was dichotomized at the median, there was a 76% reduction in the risk of disease progression or death in arm A as compared with the control (arm C) at high IGF-1 level (p = 0.16). When IGF-1 was fitted as a continuous variable, this reduction was 96% (p = 0.08). There was no correlation between tissue and serum IGF-1. Conclusions: Tissue expression of IGF-1 level may represent a promising predictive biomarker for IGF1R-directed therapy in APC.

scholarly journals Decrease in Blood Neutrophil-to-Lymphocyte Ratio Indicates Better Survival After Neoadjuvant Chemotherapy in Patients With Advanced Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Ziyi Liu ◽  
Yahang Liang ◽  
Xiaolong Tang ◽  
Hui Qu
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Curative Surgery ◽  
Lymphocyte Ratio

Introduction: Gastric cancer is the fifth most commonly diagnosed tumor and is the fourth leading cause of cancer-related mortality, worldwide. Due to the low rate of early diagnosis, approximately two-thirds of patients are first diagnosed at an advanced stage. Neoadjuvant chemotherapy (NAC) is recommended for patients with advanced gastric cancer (AGC). The neutrophil-to-lymphocyte ratio (NLR), a combined inflammatory and immunogenic factor, has been universally used for predicting outcomes in AGC patients. Given that NLR is a dynamic process, in this study, we investigated the value of NLR change for the prediction of chemotherapeutic responses and prognosis in patients with AGC.Methods: We retrospectively enrolled 111 patients with AGC who underwent NAC following curative surgery. Patients were divided into two groups according to the NLR change after chemotherapy into the increased and decreased groups. Outcome measures were overall survival (OS) and disease-free survival (DFS). Univariate was calculated by Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model.Results: Post-chemotherapy, NLR increased in 36 patients and decreased in 75 patients. After a median follow-up time of 19 months, six patients developed local recurrence, 23 developed distant recurrence, and 34 died. Patients with reduced post-chemotherapy NLR showed significantly longer OS (p &lt; 0.001) and DFS (p &lt; 0.001). A decrease in the NLR after NAC was an independent indicator associated with better OS (p &lt; 0.001) and DFS (p &lt; 0.001).Conclusions: In patients with AGC, a decrease in NLR after NAC indicated better survival. NLR change could serve as a robust indicator for the efficiency of NAC and prognostic prediction in patients with AGC.

scholarly journals Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival

2019 ◽  
Vol 8 (2) ◽  
pp. 241 ◽  
Author(s):  
Joshua Yang ◽  
Stijn Verleden ◽  
Arya Zarinsefat ◽  
Bart Vanaudenaerde ◽  
Robin Vos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bronchoalveolar Lavage ◽  
Lung Transplant ◽  
Proportional Hazards ◽  
Predictive Performance ◽  
Cox Proportional Hazards ◽  
Superior Performance ◽  
Cell Free Dna ◽  
Free Dna ◽  
Restrictive Allograft Syndrome

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure.

Glucocorticoid receptor (GR) expression in circulating tumor cells (CTCs) to prognosticate overall survival (OS) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with androgen receptor signaling inhibitors (ARSi).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 194-194 ◽  
Author(s):  
David Wise ◽  
James Kelvin ◽  
Ryon Graf ◽  
Nicole A. Schreiber ◽  
Brigit McLaughlin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
Hazards Model ◽  
Kaplan Meier ◽  
The Impact

194 Background: Upregulation of GR protein expression in metastatic biopsies from pts with CRPC has previously been shown to correlate with resistance to enzalutamide and has been validated as a therapeutic target in pre-clinical studies. We sought to determine whether upregulated GR protein expression in CTCs from pts with progressing mCRPC predicted clinical outcomes following treatment with enzalutamide (E) or abiraterone (A). Methods: Pre-therapy blood samples from 54 pts with progressing mCRPC were subjected to CTC analysis using the Epic Sciences platform. Samples were examined to identify CK+ (CK+, CD45- cells, with intact nuclei, morph distinct) CTCs for GR protein expression. GR+ CTCs were defined as having expression greater than the 95th percentile of GR expression in the GR negative LNCAP cell line. Kaplan-Meier analysis was used to test the impact of GR+ CTCs on OS following treatment with A or E. A Cox proportional hazards model with CTC number and GR positivity was used in a multivariate analysis. Results: 37 out of 54 pts (69%) had detectable and viable CK+ CTCs. 28 out of 37 pts (76%) had CTCs with upregulated GR staining with a median of 6 GR+/CK+ cells/ml per patient (range 0.7 – 244 cells/ml). The OS of patients with GR+ CTCs treated with ARSi was significantly worse than that of patients without detectable GR+ CTCs (11.4 mo. vs NA, p < 0.01), an effect independent and additive to the presence of viable CTCs, a previously described prognostic biomarker (see Table). Conclusions: GR protein upregulation in CTCs can be detected in a significant percentage of pts with progressing mCRPC and the presence of GR+ CTCs predicts worse OS in response to ARSi. The data supports previously reported pre-clinical data proposing a pathogenic role for GR in mediating resistance to ARSi therapy. Detection of GR in patient CTCs may be a useful predictive biomarker to guide GR-directed therapies. [Table: see text]

Neutrophil extracellular traps (NETs) and thrombosis (Thr) in pancreaticobiliary cancer (PBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16230-e16230
Author(s):  
Christos Fountzilas ◽  
Han Yu ◽  
Anm Nazmul Khan ◽  
Thejaswini Giridharan ◽  
Alok A. Khorana ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Stage Iv ◽  
Information Criterion ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Specific Marker ◽  
Patients At Risk ◽  
Poor Outcomes

e16230 Background: NETs are linked to tissue damage, Thr and cancer progression. Detection of NETs in pancreatic cancer (PC) tissue and NET products in plasma, such as citrullinated Histone 3 (cit-H3) and myeloperoxidase (MPO), can predict survival. A robust biomarker to identify PC patients that may benefit from prophylactic antithrombotic interventions is still lacking. We hypothesized that NET products can predict PC patients at risk of poor outcomes. Methods: Frozen plasma collected on diagnosis from a cohort of 117 patients with HPBC (69% with PC) with known tissue factor (TF) levels was analyzed for MPO and cit-H3 by ELISA. Plasma MPO is a marker of neutrophil degranulation while cit-H3 is a more specific marker of NETosis. Univariate association of clinical variables, TF, cit-H3, MPO with overall survival (OS) was performed. For multivariable analysis, Cox proportional hazards regression model and backward stepwise selection based on the Bayesian information criterion (BIC) were used. Results: We observed a strong correlation between MPO and cit-H3. MPO also correlated with TF. Only TF showed a trend with association with the risk of Thr (p=0.053). Results of the multivariable model for OS are presented in the table (all patients and stratified by Thr status). High absolute neutrophil count (ANC) predicted worse OS only in patients without Thr. Increased cit-H3 was associated with worse OS. Higher MPO predicted worse OS in stage IV patients, which is in contrast to their relationship in stage I-III patients, where increased MPO was associated with improved OS. This interaction effect is stronger in patients with thrombosis. Conclusions: Plasma cit-H3, a systemic marker of NETosis, was associated with worse OS in PBC. Significant MPO by stage interaction implies a differential association of MPO with the OS among patients in different cancer stages. The activation status of neutrophils, including degranulation and NETosis, may be an important predictive biomarker for OS in patients with HPBC with interactions with both stage and Thr. Prospective studies to confirm and extend our findings are ongoing.[Table: see text]

scholarly journals Glioblastoma: Patterns of Recurrence and Efficacy of Salvage Treatments

2011 ◽  
Vol 38 (4) ◽  
pp. 621-625 ◽  
Author(s):  
Jiwon Oh ◽  
Arjun Sahgal ◽  
Paul Sanghera ◽  
May N. Tsao ◽  
Phil Davey ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Continuous Dose ◽  
Newly Diagnosed Glioblastoma

Abstract:Background:It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.Methods:We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.Results:58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).Conclusion:The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

scholarly journals POS1434 WHICH PROGNOSTIC FACTORS MIGHT PREDICT THE NEED FOR TREATMENT ADAPTATION IN EARLY RHEUMATOID ARTHRITIS? A COMPARISON OF MACHINE LEARNING, SURVIVAL ANALYSIS AND REGRESSION METHODS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1001.2-1002
Author(s):  
G. Verhavert ◽  
T. Verdonck ◽  
S. Pazmino ◽  
V. Stouten ◽  
D. Bertrand ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Statistical Model ◽  
Proportional Hazards ◽  
Predictive Performance ◽  
Cox Proportional Hazards ◽  
Data Driven ◽  
Treat To Target ◽  
Clinical Factors ◽  
Patient Reported ◽  
Random Survival Forest

Background:Current EULAR guidelines recommend treating RA early, intensively and to-target. A data-driven tool for planning the optimal moment for subsequent visits might adapt visit schedules more to the patient’s needs, without losing treatment quality.Objectives:To determine the optimal statistical model and clinical factors to predict the time to a treatment adaptation in early RA patients.Methods:This study included 379 patients from the treat-to-target Care in Rheumatoid Arthritis (CareRA) trial. The CareRA protocol included 2 predefined treatment adaptation steps for patients not reaching low disease activity (DAS28CRP<3.2). The 1st adaptation was an MTX dose increase and the second one was adding/increasing the dose of a 2nd csDMARD. Three predictive models (Cox Proportional Hazards, Linear Multi-Task Regression and Random Survival Forest) were trained and validated to predicting time until these 2 adaptations. Factor selection for these models was performed by applying Cox Proportional Hazards with LASSO penalty to each set of demographic and clinical variables recorded at baseline, w4 and w8. Models used these factors at these 3 time points to predict future treatment adaptations. Model performance was estimated by the Uno Concordance Index with five-fold cross-validation. Missing data were imputed by interpolation or mean score.Results:Factors selected to predict the first per protocol change included TJC, SJC, HAQ, CRP, pain and morning stiffness>15min. Factors selected to predict the second per protocol change included TJC, SJC, PGA, PhGA. Uno Concordance indices showed similar scores per different statistical model but higher scores at w4 and w8 compared to baseline indicating a better predictive performance (Table 1. next page).Table 1.Uno Concordance Scores. Format ‘mean (min-max)’.BaselineWeek 4Week 8Cox Proportional HazardsChange 10.63 (0.59-0.69)0.72 (0.68-0.80)0.75 (0.69-0.82)Change 20.58 (0.50-0.66)0.75 (0.65-0.87)0.78 (0.65-0.93)Linear Multi-Task RegressionChange 10.65 (0.62-0.68)0.72 (0.68-0.78)0.75 (0.69-0.79)Change 20.58 (0.51-0.68)0.72 (0.67-0.82)0.77 (0.68-0.89)Random Survival ForestChange 10.64 (0.58-0.67)0.71 (0.66-0.78)0.76 (0.68-0.80)Change 20.56 (0.50-0.68)0.72 (0.60-0.82)0.77 (0.64-0.92)Conclusion:Our data-driven approach identified predictive clinical factors with a high face validity including joint counts, functionality scores and global health indicators. The different model approaches did not seem to increase the predictive capacity performance. However, our results underline that not so much the baseline disease status but rather the early response to initial treatment reflected in the selected predictive factors can be used for prediction of the need for further treatment adaptation. These models will have to be enriched with patient reported outcomes to further improve predictive performance.Disclosure of Interests:None declared

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