The role of PP2A variants to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and TRIBE trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3581-3581
Author(s):  
Jingyuan Wang ◽  
Joshua Millstein ◽  
Fotios Loupakis ◽  
Sebastian Stintzing ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Progression Free Survival ◽  
Snp Markers ◽  
Discovery Cohort ◽  
Increased Risk ◽  
Phosphatase 2A ◽  
Cell Signaling Networks ◽  
Risk Of Cancer ◽  
The Impact

3581 Background: Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase with functions that counter-balance kinase-mediated phosphorylation throughout cell signaling networks. PP2A was reported to upregulate the angiogenesis, while negatively regulate the pathways downstream of receptor tyrosine kinases at multiple nodes. Previous studies showed PP2A variants were associated with the increased risk of cancer. Therefore, we hypothesized that PP2A variants may predict first-line treatment outcome in mCRC pts treated with bevacizumab (bev)/cetuximab (cet)-based chemotherapy. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, TRIBE (bev arm, n=215, as discovery cohort) and FIRE-3 (bev arm, n=107, as validation cohort; cet arm, n=129, as control cohort), was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 17 selected SNPs in 3 main PP2A core subunits (PPP2CA, PPP2R1B, PPP2R1A), one phosphatase activator (PPP2R4) and 2 endogenous inhibitors (TIPRL, CIP2A) was analyzed. Results: In the discovery cohort, pts with PPP2R4 rs2541164 A/A (N=16) showed significantly shorter overall survival (15.3 vs 27.3 months) compared to carriers of any G allele (N=198) in both univariate (hazard ratio [HR]=1.8; 95% confidence interval [CI]: 1.1-3.1; p=0.02) and multivariate (HR=2.4; 95%CI: 1.4-4.4; p=0.006) analysis. These data were validated in the FIRE-3 bev cohort in both univariate (A/A vs. Any G: 17.3 vs 39.9 months, HR=2.8, 95%CI: 1.4-5.9, p=0.004) and multivariate (HR=4.3, 95%CI: 1.5-12.2, p=0.0095) analysis. Conversely, pts carrying CIP2A rs13069780 C/C (N=24) only showed significantly longer progression-free survival (17.7 vs 12.3 months) than carriers of any T allele (n=105) in the FIRE-3 cet cohort in both univariate (HR=0.6; 95%CI 0.4-0.99; p=0.04) and multivariate (HR=0.5; 95%CI 0.3-0.94; p=0.02) analysis, but no association were observed in the bev cohort of TRIBE and FIRE-3. Conclusions: Our study demonstrated for the first time that PPP2R4 polymorphisms could predict outcomes of bev-based treatment in mCRC patients; Meanwhile CIP2A polymorphism could predict outcomes of cet-based treatment in mCRC patients. These findings support a possible role of the PP2A variants in contributing to resistance to anti-VEGF/EGFR treatment.

Genetic variants involved in the lipid metabolism pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and MAVERICC trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 118-118
Author(s):  
Jingyuan Wang ◽  
Joshua Millstein ◽  
Fotios Loupakis ◽  
Sebastian Stintzing ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Genetic Variants ◽  
Progression Free Survival ◽  
Snp Markers ◽  
Acid Oxidation ◽  
Metabolism Pathway ◽  
Increased Risk ◽  
In Fire ◽  
The Impact

118 Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches the glucose-dependent metabolism to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer. Previous reports suggested that polymorphisms of the lipid metabolism-related genes are associated with the increased risk of CRC and poor clinical outcome in CRC. Therefore, we hypothesized that genetic variants in the lipid metabolism pathway may predict first-line treatment outcome in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, FIRE-3 and MAVERICC, was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 25 selected SNPs in 10 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1, LPCAT2, PPARG, CPT1A, ACSS2, SREBF1, FASN, ACACA) was analyzed. Those treated with FOLFIRI/ bevacizumab (bev) in FIRE-3 (n = 107) and MAVERICC (n = 163) served as discovery and validation cohorts respectively, while FIRE-3 FOLFIRI/ cetuximab (cet) (n = 129) arm was used as the control. Interaction between each SNP and treatment was evaluated in FIRE-3 (FOLFIRI/bev arm vs. FOLFIRI/cet arm). Results: In the discovery (FIRE-3 bev) cohort, pts with FASN rs4485435 any C allele (N = 21) showed significantly shorter progression-free survival (PFS) (8.69 vs 13.48 months) compared to carriers of G/G (N = 62) in both univariate (hazard ratio [HR] = 2.88; 95% confidence interval [CI]: 1.57-5.29; p = 0.00037) and multivariate (HR = 2.87; 95%CI 1.4-5.9; p = 0.00675) analyses. These data were validated in the MAVERICC bev cohort in multivariate analysis (11.17 vs 14.06 months; HR = 2.07; 95%CI: 1.15-3.74; p = 0.02). Pts carrying any T allele in PPARG rs3856806 (N = 36) showed significantly longer overall survival (OS) (Not reached vs 42 months) than carriers of C/C (n = 93) in the FIRE-3 cet cohort in both univariate (HR = 0.4; 95%CI 0.17-0.92; p = 0.03) and multivariate (HR = 0.37; 95%CI 0.15-0.93; p = 0.02) analyses, but the association was not observed in the bev cohort of MAVERICC and FIRE-3. In the comparison of bev arm vs cet arm in FIRE-3, interactions were shown with FASN rs4485435 (p = 0.017) on PFS and PPARG rs3856806 (p = 0.059) on OS. Conclusions: Our study demonstrates for the first time that FASN polymorphism could predict outcomes of bev-based treatment in mCRC patients; Meanwhile PPARG polymorphism could predict outcomes of cet-based treatment in mCRC patients. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF/EGFR treatment.

scholarly journals Emerging Role of Microbiome in the Prevention of Urinary Tract Infections in Children

2022 ◽  
Vol 23 (2) ◽  
pp. 870
Author(s):  
Anna Kawalec ◽  
Danuta Zwolińska
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urinary Tract Infections ◽  
Pediatric Population ◽  
Urologic Diseases ◽  
Increased Risk ◽  
Tract Infections ◽  
The Impact

The microbiome of the urinary tract plays a significant role in maintaining health through the impact on bladder homeostasis. Urobiome is of great importance in maintaining the urothelial integrity and preventing urinary tract infection (UTI), as well as promoting local immune function. Dysbiosis in this area has been linked to an increased risk of UTIs, nephrolithiasis, and dysfunction of the lower urinary tract. However, the number of studies in the pediatric population is limited, thus the characteristic of the urobiome in children, its role in a child’s health, and pediatric urologic diseases are not completely understood. This review aims to characterize the healthy urobiome in children, the role of dysbiosis in urinary tract infection, and to summarize the strategies to modification and reshape disease-prone microbiomes in pediatric patients with recurrent urinary tract infections.

scholarly journals CANCER OF THE ORGANS OF THE REPRODUCTIVE SYSTEM IN WOMEN WITH TYPE 2 DIABETES. EFFECTS OF ANTIDIABETIC THERAPY

2020 ◽  
Vol 73 (5) ◽  
pp. 967-971
Author(s):  
Tamara S. Vatseba
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Postmenopausal Women ◽  
Reproductive System ◽  
Uterine Cancer ◽  
Antidiabetic Therapy ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
The Impact

The aim: to investigate the prevalence of cancer of the reproductive system in women with type 2 diabetes, and to examine the impact of antidiabetic therapy on cancer risk of this localization. Materials and methods: The study included a retrospective analysis of medical records of women with T2D with first diagnosed cancer during 2012-2016. The bases for the study were specialized medical institutions in Ivano-Frankivsk region. The obtained results were processed using statistical programs “Microsoft Excel” and “Statistika-12”. Results: Breast, uterine, and ovarian cancer were detected in 202 postmenopausal women, 63.92% from the total number of cancer cases in women. An increased risk of breast [OR = 1.24; 95% CI (1.04 – 1.50) P = 0.019] and uterine cancer [OR = 1.32; 95% CI (1.02 – 1.69) P = 0.040] has been identified. Most often, before the detection of cancer, women received combination therapy with sulfonylurea and metformin (83 patients (57.64%)) with BMI 32.64 ± 3.69 kg/m2. The difference between risk of cancer on metformin monotherapy and on sulfonylurea monotherapy [OR = 2.17; 95% CI (0.88 – 5.36) P = 0.141] or on combination therapy [OR = 1.68; 95% CI (0.76 – 3.74) P = 0.276] was not found. Conclusions: Postmenopausal women have an increased risk of breast and uterine cancer and are recommended to be screened for these diseases

Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 425-425
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle
Keyword(s):  
Palliative Therapy ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Molecular Profiling ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Ctdna Analysis ◽  
Chemotherapy Initiation ◽  
The Impact

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.

scholarly journals Cancer Risk in Children and Young Adults (Offspring) Born after Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

J ◽  
2019 ◽  
Vol 2 (4) ◽  
pp. 430-448
Author(s):  
Manuela Chiavarini ◽  
Andrea Ostorero ◽  
Giulia Naldini ◽  
Roberto Fabiani
Keyword(s):  
Cancer Risk ◽  
Health Outcomes ◽  
Childhood Cancer ◽  
Assisted Reproduction ◽  
Meta Analysis ◽  
Cancer Data ◽  
Medically Assisted Reproduction ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
The Impact

Many studies have investigated the relationship between medically assisted reproduction (MAR) and health outcomes, particularly cancer, in the offspring. This meta-analysis investigated the association between MAR and childhood cancer. Data sources were PubMed, Scopus, and Web of Science up until June 2018. From the selected studies, we extracted the cancer risk estimates of the exposure of interest (MAR, assisted reproductive technology—ART, and in fitro fertilization—IVF). We conducted the meta-analysis using a random effects model. The outcomes of interest were childhood cancers, classified according to the international classification of childhood cancer (ICCC-3). In our meta-analysis (18 cohort and 15 case-control studies) the overall cancer risk was significantly increased in children conceived by MAR, ART, or IVF. MAR and ART significantly increased the risk for hematological tumors, hepatic tumors, and sarcomas (odds ratio (OR) 1.54; 95% CI 1.18–2.02 and OR 1.92; 95% CI 1.34–2.74, respectively). MAR increased acute myeloid leukemia risk (OR 1.41; 95% CI 1.02–1.95) and ART increased neural cancer risk (OR 1.21; 95% CI 1.01–1.46). Our results suggest an increased risk of cancer in children conceived by MAR. Further studies are needed to investigate the impact of fertility treatments, parental subfertility status, and their association on health outcomes in the offspring.

scholarly journals Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Julie Abildgaard ◽  
Magnus Glindvad Ahlström ◽  
Gedske Daugaard ◽  
Dorte Lisbet Nielsen ◽  
Anette Tønnes Pedersen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Rate Ratio ◽  
Bilateral Oophorectomy ◽  
Family History Of Cancer ◽  
Increased Risk ◽  
History Of ◽  
Risk Of Cancer ◽  
The Impact ◽  
History Of Cancer

Abstract Background Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. Methods A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. Results Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). Conclusions Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

scholarly journals Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

2021 ◽  
Author(s):  
Valentina Gambardella ◽  
Pasquale Lombardi ◽  
Juan Antonio Carbonell-Asins ◽  
Noelia Tarazona ◽  
Juan Miguel Cejalvo ◽  
...  
Keyword(s):  
Early Phase ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Prior Therapy ◽  
Early Phase Trials ◽  
Molecular Tumor Board ◽  
Early Phase Clinical Trials ◽  
The Impact ◽  
To Receive

Abstract Introduction Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution. Methods Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1). Results Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008). Discussion We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 124-124 ◽  
Author(s):  
Kareem Rayn ◽  
Samuel Gold ◽  
Graham R. Hale ◽  
Joey Baiocco ◽  
Jonathan Bloom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factor ◽  
Active Surveillance ◽  
Progression Free Survival ◽  
Normal Weight ◽  
Fusion Biopsy ◽  
Patient Demographics ◽  
Increased Risk ◽  
Risk Of Progression ◽  
The Impact

124 Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.

scholarly journals The Potential Role of Human Papillomavirus Infection in Bell's Palsy: A Hypothesis-Generating Study Based on a Nationwide Cohort

2021 ◽  
Vol 8 ◽  
Author(s):  
Kuan-Ying Li ◽  
Mei-Chia Chou ◽  
Renin Chang ◽  
Hei-Tung Yip ◽  
Yao-Min Hung ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Index Date ◽  
Hpv Infection ◽  
Bell’S Palsy ◽  
Sensitivity Analyses ◽  
Chronic Obstructive ◽  
Bell's Palsy ◽  
Increased Risk ◽  
The Impact

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP).Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection (n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities (n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups.Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03–1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37–2.52], hypertension (aHR = 1.65; 95% CI = 1.17–2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups.Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention.

scholarly journals Leukocyte Subtypes As Predictors for Venous Thromboembolism in Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 495-495
Author(s):  
Jahnavi Gollamudi ◽  
Gouri Dharmavaram ◽  
Petra Martin ◽  
Kirsten Marie Boughan ◽  
Brenda Cooper ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Bulky Disease ◽  
Free Survival ◽  
Increased Risk ◽  
Baseline Characteristics

Abstract Introduction: Venous thromboembolic events (VTE) are a frequent complication of patients diagnosed with diffuse large B -cell lymphoma (DLBCL). Development of VTE portends poor prognosis. Previous studies have identified use of anthracyclines, advanced stage at presentation, obesity, and development of neutropenia and anemia after first cycle of chemotherapy as risk factors for VTE. Recent studies suggest leukocyte subpopulations may affect the risk of VTE; elevated neutrophil and monocyte counts have been associated with increased risk of VTE in solid malignancy patients. The role of leukocyte subpopulations in VTE risk in DLBCL patients has not yet been evaluated. We conducted a retrospective study to identify risk factors for VTE and specifically address the role of leukocytes and their subtypes in VTE risk assessment in DLBCL. Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics, baseline laboratory and disease information, as well as treatment details. Patient records were reviewed for the presence of VTE, including radiographic confirmation. Progression free survival and overall survival were calculated from time of diagnosis using Kaplan Meier methodology, comparisons were done with log rank. Cumulative incidence of VTE was calculated considering death as competing risk. Univariate Cox regression analysis was conducted for baseline characteristics, risk factors and baseline laboratory parameters. Variables with a univariate p value lower than 0.1 were included in multivariate Cox regression. All analyses were performed using XLSTAT (Addinsoft, NY). Results: A total of 542 patients were included in the study. Baseline characteristics are described in Table 1. At a median follow up of 48 months, 93 patients developed VTE, with 1 and 2 -year cumulative incidence of VTE of 13.5% (95% CI 10.9-16.8) and 20.5% (95% CI 17.3-24.3). In subsequent years, VTE risk increased more modestly, reaching 23.6% at 4 years (95% CI 20.2-27.7). Eighty percent of VTE occurred in patients with active disease. Sixteen percent of VTE were pulmonary embolism (PE), 53% were lower extremity deep vein thrombosis (DVT), and 31% upper extremity DVTs. Approximately 55% of upper extremity DVTs were line - related. On univariate analysis (table 2), the risk factors with statistically significant odds for increased hazard of VTE included previous history of VTE, albumin less than 3 gm/dl, leukocyte count greater than 11,000/mcl, hemoglobin less than 12 gm/dl, absolute neutrophil count (ANC), ANC to absolute lymphocyte ratio (ANC: ALC) higher than 2.5 and presence of bulky disease at the time of diagnosis. In multivariate analysis, BMI > 35, bulky disease and ANC/ALC ratio ≥ 2.5 remained statistically significant risk factors for development of VTE. Presence of VTE at any time after DLBCL diagnosis was also associated with worse overall survival (OS) and progression free survival (PFS) rates. Patients with VTE after diagnosis had an estimated 4 - year OS of 50.6 % (95% CI 39.7-61.6) vs. 71.3% (95% CI 66.9-75.7) in patients without VTE (p<0.0001) (figure 1). Four-year PFS estimates were 37.5% (95 % CI 27.1-48) and 60% (95 % CI 55.3-64.7), respectively (p<0.0001) (figure 2). Conclusion: VTE is a frequent complication in DLBCL patients and is associated with increased mortality and risk of progressive disease. The first 24 months after DLBCL diagnosis appear to be the time of highest VTE risk, likely a consequence of active disease, treatment and other risk factors such as indwelling catheters. Leukocyte subpopulations appear to have a correlation with VTE risk; the ANC: ALC ratio is a measure of systemic inflammatory response, and in DLBCL patients, a ratio above 2.5 is correlated with increased risk of VTE. Incorporation of this laboratory measurement to currently available VTE risk assessment tools may help more precisely identify the at highest risk of VTE. Disclosures Malek: Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau. Tomlinson:Foundation Medicine: Consultancy. Caimi:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees.

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