scholarly journals Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heba Alshaker ◽  
Robert Mills ◽  
Ewan Hunter ◽  
Matthew Salter ◽  
Aroul Ramadass ◽  
...  

Abstract Background Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with PCa. Predicting the risk of PCa is pivotal for making an informed decision on treatment options as the 5-year survival rate in the low-risk group is more than 95% and most men would benefit from surveillance rather than active treatment. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can serve as a disease biomarker. Methods In this prospective study we screened whole blood of newly diagnosed, treatment naïve PCa patients (n = 140) and cancer-free controls (n = 96) for the presence of 14,241 chromosomal loops in the loci of 425 genes. Results We have detected specific chromosome conformation changes in the loci of ETS1, MAP3K14, SLC22A3 and CASP2 genes in peripheral blood from PCa patients yielding PCa detection with 80% sensitivity and 80% specificity. Further analysis between PCa risk groups yielded prognostic validation sets consisting of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes that achieved 80% sensitivity and 93% specificity stratifying high-risk category 3 vs low risk category 1 and 84% sensitivity and 89% specificity stratifying high risk category 3 vs intermediate risk category 2 disease. Conclusions Our results demonstrate specific chromosome conformations in the blood of PCa patients that allow PCa diagnosis and risk stratification with high sensitivity and specificity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 813-813
Author(s):  
R.H. Advani ◽  
H. Chen ◽  
T.M. Habermann ◽  
V.A. Morrison ◽  
E. Weller ◽  
...  

Abstract Background: We reported that addition of rituximab (R) to chemotherapy significantly improves outcome in DLBCL patients (pt) >60 years (JCO24:3121–27, 2006). Although the IPI is a robust clinical prognostic tool in DLBCL, Sehn et al (ASH 2005: abstract 492) reported that a revised (R) IPI more accurately predicted outcome in pt treated with rituximab-chemotherapy. Methods: We evaluated outcomes of the Intergroup study with respect to the standard IPI, R-IPI, age-adjusted (aa) IPI for evaluable pt treated with R-CHOP alone or with maintenance rituximab. We further assessed a modified IPI (mIPI) using age ≥ 70 y as a cutoff rather than age 60 y. Results: The 267 pt in this analysis were followed for a median of 4 y. Pt characteristics were: age > 70 (48%) (median=69), male 52%, stage III/IV 75%, >1 EN site 30%, LDH elevated 60%, PS ≥2 15%. On univariate analysis all of these characteristics were significant for 3 y failure-free survival (FFS) and overall survival (OS). The IPI provided additional discrimination of risk compared to the R-IPI with significant differences in FFS and OS for 3 vs 4–5 factors. The aa-IPI defined relatively few pt as low or high risk. The impact of age was studied using a cut-off of 70 years in a modified IPI, yielding 4 risk groups as shown below. Conclusions: For pt ≥ 60 treated with rituximab-chemotherapy the distinction between 3 vs 4,5 factors in the IPI was significant.The IPI also provided additional discrimination of risk compared to the R-IPI. In this older group of pt, use of an age cutoff ≥70 y placed more patients in the low risk category. It is of interest to apply the mIPI in other datasets with DLBCL pt >60 y. Group # Factors # Pt % 3y FFS* % 3y OS* *All risk groups significantly different; logrank p < 0.001 **95 % CI: FFS (0.46,0.66), OS (0.58,0.78) ***95 % CI: FFS (0.21,0.45), OS (0.31,0.55) L: Low, LI: Low Intermediate, HI: High Intermediate, H; High IPI L 0–1 12 78 83 LI 2 28 70 80 HI 3 33 56** 68** H 4–5 37 33*** 43*** R-IPI Very Good 0 0 - - Good 1–2 40 72 81 Poor 3–5 60 46 57 aa-IPI L 0 12 78 83 LI 1 35 68 78 HI 2 44 47 59 H 3 9 31 35 mIPI (age ≥ 70) L 0–1 27 77 86 LI 2 28 62 74 HI 3 29 47 58 H 4–5 16 28 36


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6098-6098
Author(s):  
Winston Wong ◽  
Joseph Cooper ◽  
Steve Richardson ◽  
Bruce A. Feinberg

6098 Background: CareFirst BlueCross BlueShield (CFBCBS) insurance network partnered with Cardinal Health Specialty Solutions (CHSS) to develop a cancer care pathway for network physicians in 2008. The program included a recommendation for molecular diagnostic testing with the Oncotype DX assay for pts with early-stage estrogen receptor-positive breast cancer. Based on NCCN guidelines, the pathway suggested adjuvant chemotherapy for all pts with Oncotype DX Recurrence Scores (RS) in the high-risk category. We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using data from CFBCBS, CHSS proprietary claims software, and Genomic Health, we retrospectively identified a cohort of women with breast cancer who were treated on the CFBCBS clinical care pathways program from 8/2008 to 6/2011 and received Oncotype DX testing. We determined the number of pts with a RS value in the low- (RS <18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of 1174 women who received Oncotype DX testing, 53% of pts were in the low-, 35% in intermediate-, and 12% in the high-risk groups. Five percent of low-, 41% of intermediate-, and 74% percent of pts in the high-risk category were treated with chemotherapy. Twenty-six percent of pts in the high-risk group did not receive chemotherapy. Conclusions: The proportionate use of chemotherapy in the low and intermediate risk groups was as expected based on adjuvant chemotherapy guidelines; however, the underuse of chemotherapy in 26% of high-risk pts was an unexpected finding. Further study is needed to determine: (1) why physicians avoided chemotherapy in 26% of high-risk pts; (2) the overall number of appropriate pts who underwent Oncotype DX testing; and, (3) the tumor characteristics that may have driven the underutilization of chemotherapy in the high-risk population.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 177-177
Author(s):  
Takamitsu Inoue ◽  
Norihiko Tsuchiya ◽  
Shigeyuki Matsui ◽  
Tomomi Kamba ◽  
Koji Mitsuzuka ◽  
...  

177 Background: Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. Methods: A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. A prognostic scoring index using selected SNPs was developed by incorporating the difference in their effect sizes to classify high-risk and low-risk groups and its predictive accuracy was assessed. Results: Fourteen SNPs in six genes, XRCC4, PSM1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20×10−8). The predictive model using the 14 SNPs showed a statistically significant cross-validated accuracy in predicting the groups at high and low risk groups for poor survival (P = 0.0050). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). Conclusions: Using a panel of the SNPs, the prediction of the survival and optimization of the individualized treatment for patients with advanced PCa may be possible.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 28-28
Author(s):  
Anusha Kalbasi ◽  
Jiaqi Li ◽  
Abigail T. Berman ◽  
Samuel Swisher-McClure ◽  
Marc C. Smaldone ◽  
...  

28 Background: Infive publishedRCTs, dose-escalated external beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, the question of whether dose escalation improves overall survival (OS) remains unanswered. We examined OS among men with non-metastatic prostate cancer undergoing EBRT in the modern era. Methods: Using the National Cancer Database (NCDB), we conducted non-randomized comparative effectiveness studies of dose-escalated versus standard-dose EBRT in men diagnosed from 2004-2006 in three analytic cohorts defined by NCCN risk category: low- (N=12,848), intermediate- (N=14,966) or high-risk (N=14,587) prostate cancer. We categorized patients in each risk cohort into 2 treatment groups: standard-dose (68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT. The primary outcome was time to death from any cause, measured from diagnosis to NCDB date of death or end of follow-up (December 31, 2011). We compared OS between treatment groups in the three analytic cohorts using Cox proportional hazard models. Inverse probability weighted propensity score methods were used to balance differences between treatment groups in age, race, year of diagnosis, AJCC T- and N-stage, PSA, Gleason score, androgen deprivation therapy, IMRT use, comorbid disease, income, insurance, urban/rural location, facility type and facility volume. In secondary analyses, we evaluated dose response for survival by categorizing dose in approximately 2 Gy increments. Results: Median follow up for survivors was between 73 and 74 months in all three risk cohorts. Dose-escalated EBRT was associated with improved survival in the intermediate-risk (adjusted HR 0.81, 95% CI 0.77 and 0.85, p<0.0001) and high-risk groups (aHR 0.85, 95% CI 0.81 and 0.89, p<0.0001), but not the low-risk group (aHR 0.99, 95% CI 0.92-1.06, p=0.803). For every incremental ~2Gy increase in dose, there was a 9% (95% CI 6% – 11%, p<0.0001) and 7% (95% CI 3% - 10%, p=0.004) reduction in the hazard of death for intermediate- and high-risk patients, respectively. Conclusions: Dose-escalated EBRT is associated with improved survival in men with intermediate- and high-risk, but not low-risk, prostate cancer.


2021 ◽  
Vol 10 (16) ◽  
pp. 3709
Author(s):  
Paulius Bosas ◽  
Gintaras Zaleskis ◽  
Daiva Dabkevičiene ◽  
Neringa Dobrovolskiene ◽  
Agata Mlynska ◽  
...  

Background: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. Methods: Radical prostatectomy (RP) was performed on 108 PCa stage pT2–pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. Results: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = −2.0% d−1 (AUC = 0.85 (95% CI, 0.78–0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 − CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). Conclusion: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 11-11
Author(s):  
Santino Butler ◽  
Idalid Ivy Franco ◽  
Amandeep R Mahal ◽  
Nina Niu Sanford ◽  
Quoc-Dien Trinh ◽  
...  

11 Background: National guidelines have increasingly supported active surveillance/watchful waiting (AS/WW) in low- and favorable intermediate-risk prostate cancer (PCa). It is unknown how these changes have influenced national management patterns across localized PCa. Therefore, we sought to define the U.S. trends in management of localized PCa across National Comprehensive Cancer Network (NCCN) risk groups. Methods: Using the novel and non-public Surveillance, Epidemiology, and End Results Program Prostate with AS/WW Database, we identified 164,760 men diagnosed with localized PCa and actively treated with either AS/WW, radical prostatectomy [RP], or radiation therapy [RT] from 2010-2015. Rates of initial management type over time, stratified by NCCN risk-category, were determined. Multivariable logistic regression defined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for receipt of each initial management type, with year of diagnosis (2010-2015) as the independent variable of interest (Year 2010 = referent). Results: AS/WW utilization increased from 14.5% to 42.1% from 2010-2015 in low-risk disease (AOR 4.50 [95% CI 4.17–4.86, P < 0.001]); conversely, RT and RP decreased from 38.0% to 26.6% (AOR 0.55 [0.51–0.59, P < 0.001]), and from 47.4% to 31.3% (AOR 0.50, [0.47-0.54, P < 0.001]), respectively (all Ptrends< 0.001). AS/WW increased in intermediate-risk disease from 5.78% to 9.60% (AOR 1.83 [1.67–2.00, P < 0.001]) and RT also decreased from 42.4% to 39.8% (AOR 0.81 [0.77–0.85], P < 0.001; Ptrends< 0.001)—Yet, there was no change in RP (51.8% vs. 50.6%; AOR 1.03 [0.98–1.09, P = 0.254]). Notably, while RP for high-risk disease increased from 38.0% to 42.8% (AOR 1.41 [1.30–1.53, P < 0.001]), RT decreased from 60.1% to 55.0% (AOR 0.71 [0.65–0.77, P < 0.001]; Ptrends< 0.001). Conclusions: These findings capture the rapidly shifting landscape of management for localized PCa and are suggestive of “management migration”—where down-trending RP utilization in low-risk disease (in the setting of up-trending AS/WW) may drive non-evidence based management bias toward RP over RT in higher risk disease. These national patterns serve as a targetable trend that should be addressed.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 87-87 ◽  
Author(s):  
Mustafa Ozguroglu ◽  
Simon Chowdhury ◽  
Anders Bjartell ◽  
Hirotsugu Uemura ◽  
Byung Ha Chung ◽  
...  

87 Background: TITAN showed that APA + androgen deprivation therapy (ADT) improves radiographic progression-free survival (rPFS) and overall survival (OS) in a broad group of pts with mCSPC (Chi et al. NEJM 2019). This post hoc analysis evaluates APA + ADT based on baseline (BL) prognostic risk as defined in LATITUDE (Fizazi et al. Lancet Oncol 2019). Methods: 1052 pts with mCSPC receiving ADT were randomized 1:1 to APA (240 mg/d; n = 525) or placebo (PBO; n = 527). Treatment cycles were 28 days. Risk included Gleason score ≥ 8, ≥ 3 bone lesions, or visceral metastasis. High risk was ≥ 2 risk factors, low risk was ≤ 1. Cox proportional hazards model was used to estimate HR and 95% CI for rPFS and OS. Results: Pt demographic and BL disease characteristics were similar between treatment groups (high risk: APA n = 289, PBO n = 286; low risk: APA n = 236, PBO n = 241). Median treatment duration was similar in the low-risk group with APA or PBO (21.8 mo and 20.3 mo, respectively). For the high-risk groups, treatment duration was longer with APA (APA 19.5 mo, PBO 14.7 mo). APA significantly reduced the risk of radiographic progression relative to PBO in both groups (Table). Risk of death (OS) was reduced by 38% in high-risk pts and 26% in low-risk pts with APA (Table). 24-mo survival rates: high risk, 76% APA, 63% PBO; low risk, 90% APA, 85% PBO. There were few deaths (≤ 33) in low-risk groups. Second PFS in APA pts: high risk, HR 1.9 (95% CI 1.2-3.0), p = 0.004; low risk, HR 2.2 (95% CI 1.5-3.2), p < 0.0001. Regardless of risk category, the safety profile of APA remained consistent with previously reported overall results. Conclusions: Addition of APA to ADT for pts with mCSPC prolonged rPFS and OS with a consistent safety profile compared with PBO + ADT regardless of BL risk. Clinical trial information: NCT02489318. [Table: see text]


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4459-4459 ◽  
Author(s):  
Dr. Muhammad Irfan Khan ◽  
Catriona O'Leary ◽  
Mary Ann Hayes ◽  
Patricia O'Flynn ◽  
Pauline Suzanne Chappell ◽  
...  

Abstract Background Evidence based consensus guidelines for venous thromboembolism (VTE) prevention are broadly accepted to be effective and safe for more than three decades (Clagett GP et al, 1992). However VTE continues to be associated with a major global burden of disease with 3.9 million cases of HAT during one year among 1.1 billion citizens of high income countries (Jha AK et al, 2013). Therefore prevention is the key to reduce death and disability resulting from VTE (Kahn S et al, Gould MK et al & Falck-Yitter Y et al, 2012). Ireland like many other countries has yet to implement a mandatory risk assessment tool and thromboprophylaxis (TP) policy nationally. Aims The aim of this study was to calculate the proportion of inpatients who had a VTE risk assessment performed and received appropriate TP in a large tertiary referral hospital. This information will be vital for baseline data for implementation of a new national policy for prevention of HAT. Methods This audit was performed at Cork University Hospital on 4 pre specified days between November 2014 to February 2015. All adult inpatients (Medical and Surgical) excluding maternity and psychiatric were included. Patients on therapeutic anticoagulation were also excluded. The patients' medical chart and drug prescription chart were reviewed to determine whether or not a VTE risk assessment was documented for each patient and if they had received appropriate TP. If no risk assessment had been performed, trained researchers applied the National Institute for health and Care Excellence (NICE) guidelines 92 (Jan 2010) for VTE risk assessment and prevention. Following the risk assessment patients were divided into three categories, high risk of VTE with low risk of bleeding; high risk of VTE with significant risk of bleeding and low risk of VTE. From this the proportion of patients in each group that received appropriate TP were calculated. Results A total of 1019 patients were enrolled the majority were medical patients 63.5% (n=648). The mean age of patients was 69 years. Females accounted for 52% of patients. Average length of hospitalisation for each patient at the time of the audit was 6 days (range 1-664 days). Overall, a formal TP risk assessment was documented in only 24% (n=244) of all charts reviewed however TP was prescribed in 43.2% (n=441) of patients. See table.Table 1.High Risk of VTE low risk of bleedingHigh risk of VTE significant risk of bleedingLow risk of VTENo. of pts80.3% (n=819)16.6% (n=170)2.9% (n=30)VTE risk assessment documented21.9% (n=180)28.2% (n=55)30% (n=9)Received TP46.3% (n=380)28.8% (n=49)40% (n=12) Within the high risk category patients, 64.3% (n=526) medical. TP was only administered to 46.3% (n=380) of patients in the high risk category. This was almost evenly distributed between surgical 50.1% (n=147) and medical 43.4% (n=233) patients. Conclusion This audit was done as the initial step to develop a national policy to prevent HAT. As suspected, this audit highlights that a large proportion of hospitalised patients, both surgical and medical, continue to be at high risk for VTE despite the availability of preventative measures. There is clear illustration of under prescription of safe, effective and recommended means of VTE prevention. The current overall figure of less than 50% prescription of VTE thromboprophylaxis in high risk patients is a major patient safety concern. There are numerous recognised international guidelines for prevention of VTE, and an efficient method to implement these guidelines needs to be developed. Beyond developing national guidelines for TP, we need a co-ordinated approach to implement and monitor compliance with guidelines. Once the preliminary results of this audit were available to us in March 2015, urgent measures were taken to reduce the identified risk such as the establishment of a Hospital Thrombosis Group which developed a user friendly VTE risk assessment tool and TP policy. The VTE risk assessment tool was incorporated into the patients drug prescription chart and included a pre printed prescription for TP. It is now mandatory for the all patients to have a VTE risk assessment tool and TP prescribed if appropriate within 24hrs of admission. This was successfully piloted for four weeks in the acute medical assessment unit and is now incorporated into each patients drug chart throughout the hospital. This audit will be replicated in 6 months from introduction of this initiative, with an aim of >90% compliance. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Dominic McGovern ◽  
Jennifer Lees ◽  
Dana Kidder ◽  
James Smith ◽  
Jamie Traynor ◽  
...  

Abstract Background and Aims Outcomes in ANCA vasculitis remain difficult to predict and therapeutic decision-making can be challenging. We aimed to establish if a renal risk score (RRS) could predict outcomes in this population. Method The Scottish Renal Biopsy Registry is a complete national dataset of all renal biopsies performed in Scotland. Those who had a first renal biopsy between 01/01/2014 and 31/12/2017 with evidence of ANCA vasculitis were included. Demographic data, treatment regimens, episodes of relapse and patient and kidney survival were recorded, retrospectively. The RRS was calculated using the system proposed by Brix et al (1). Each patient was categorised according to % of normal glomeruli (N0 &gt;25%, N1 10 to 25%, N2 &lt;10%), % of tubular atrophy/interstitial fibrosis (T0 ≤25%, T1 &gt;25%) and eGFR (CKD-EPI) at time of biopsy (eGFR: G0 &gt;15 mL/min/1.73 m2, G1 ≤15 mL/min/1.73 m2). Individual scores were summated and patients defined as low, medium or high risk. Cox proportional hazard models were created for survival to ESKD, relapse and death, stratified by risk category. Analyses were conducted using R statistical software. Results Two-hundred and forty-six patients with biopsy proven ANCA vasculitis were identified. Fifty percent (n=123), 46% (n=112) and 5% (n=11) were stratified as low, medium and high risk respectively. Fifty-two percent (n=129) were male and mean age at biopsy was 66.7±12.2 years. This was similar across the risk categories. Mean eGFR was lower in the high-risk category (High risk 8.6±6.1 ‘v’ Low risk 45.7±26.0 ml/min/1.73m2, p&lt;0.001) and proteinuria was higher (High risk 405 (IQR 170-767) ‘v’ Low risk 81 (IQR 41-155) mg/mmol, p&lt;0.001). Thirty-seven percent (n=91) were PR3 antigen positive, 2% (n=5) had dual positivity. In the high risk category, 8 (73%) were PR3 or dual positive. Eighteen (n=7%) patients experienced pulmonary haemorrhage; representation similar across all risk categories. Those categorised as medium or high risk were more likely to receive plasma exchange and/or haemodialysis at presentation (p&lt;0.001) compared with the low risk category. Overall, 16% (n=40) of patients relapsed with a trend to higher risk of relapse in the low risk group (27% of these patients, p=0.05). Thirty seven (15%) patients developed ESKD. Cox proportional hazard model for development of ESKD (Figure 1) shows that those in high risk ‘v’ low risk category were more likely to reach ESKD (HR 124.8, 95% CI 26.4-590.3, p&lt;0.001). Patient survival was similar between risk categories. Conclusion A simple RRS, using routinely reported data, in patients with renal biopsy proven ANCA vasculitis can help to predict development of ESKD. It may also be predictive of future relapse in those with a lower RRS, most likely explained by reduced irreversible damage in this group. The RRS could inform monitoring and treatment decisions. Whilst the numbers are small, a unique strength of this data is that it is based on a complete national dataset making it less susceptible to bias from regional variations in diagnostic and therapeutic practice.


Sign in / Sign up

Export Citation Format

Share Document