scholarly journals Early recurrence and the need for re-resection following Photodynamic diagnosis–assisted Transurethral Resection of Bladder Tumours: Multi-centre real-world experience of the UK PDD Users Group

2019 ◽  
pp. 205141581989046
Author(s):  
Paramananthan Mariappan ◽  
Colin Bunce ◽  
Jo Cresswell ◽  
Altaf Shamsuddin ◽  
Malcolm Crundwell ◽  
...  
Keyword(s):  
High Risk ◽  
Transurethral Resection ◽  
Residual Disease ◽  
Early Recurrence ◽  
Complete Resection ◽  
Photodynamic Diagnosis ◽  
High Grade ◽  
Risk Patients ◽  
Bladder Tumours

Objective: This study aimed to investigate the association between Photodynamic Diagnosis (PDD) with hexaminolevulinate (HAL) and the rate of complete resection and disease persistence at first follow-up cystoscopy for non-muscle-invasive bladder cancer (NMIBC) in UK real-world practice. Methods: Audit data were pooled from six UK centres where HAL PDD was used in patients with a new NMIBC diagnosis undergoing transurethral resection of bladder tumours (TURBT) since 2008. Patients received adjunctive intra-vesical therapy and surveillance in line with European and UK guidelines, including early re-resection in high-grade NMIBC. Results: PDD-assisted TURBT was done in 837 patients with new NMIBC. The detrusor muscle was present in 69.4% of cases. At early re-TURBT in 207 high-risk patients, 13.0% had residual disease. Multifocal disease was the most significant factor in increasing the rate of residual disease (odds ratio excluding cases of CIS=4.1; 95% confidence interval 1.5–11.3). The recurrence rate at first follow-up cystoscopy (RRFFC) was 10.6% (8.9% in patients with complete initial TURBT). In the historical cohort undergoing good-quality white-light TURBT, RRFFC was 31%; 40.5% of high-risk patients had residual disease at early re-TURBT. Conclusion: HAL PDD may increase the rates of complete resection, reducing the risk of early recurrence and the need for routine re-resection in high-grade NMIBC. Level of evidence: 2b.

Utility of quantitative fluorescent in situ hybridization (FISH) to predict non-muscle-invasive bladder cancer (NMIBC) recurrence.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 286-286
Author(s):  
H. M. Rosevear ◽  
A. J. Lightfoot ◽  
M. A. O'Donnell
Keyword(s):  
High Risk ◽  
First Year ◽  
Fish Analysis ◽  
High Grade ◽  
Intermediate Risk ◽  
Binary Variable ◽  
Risk Patients ◽  
History Of ◽  
Abnormal Cells

286 Background: Urovysion's (Abbot Laboratories, Downers Grove, IL) FISH analysis is used to monitor bladder cancer recurrence in patients with a history of NMIBC and is often reported as a binary variable (normal/abnormal). We investigated whether the percentage of abnormal cells as determined by FISH analysis in patients with a history of NMIBC correlated with risk of recurrence. Methods: At our institution, barbotage FISH analysis is routinely done along with cystoscopy and cytology on both high risk (Ta/T1 high grade or CIS) and low or intermediate risk patients (all others) at every 3-month follow-up for the first year post-resection. We retrospectively reviewed 241 consecutive NMIBC patients and identified 399 FISH analyses for which we had one year follow-up. Normal FISH analyses were defined as 2 or fewer abnormal cells per sample. We calculated the percentage of abnormal cells and correlated that to the number of patients who had a recurrence of NMIBC as defined by positive high grade cytology or tumor on cystoscopy during the first year of follow-up. Results: The sensitivity, specificity, and positive and negative predictive values of FISH analysis if reported as a binary variable was 55, 43, 16 and 89%, respectively. Considering only those patients with abnormal FISH, the average percentage of abnormal cells for patients who were found to have NMIBC recurrence at 1 year was 38% (range 6–100) compared to 21% (range 6–100) for patients who were recurrence-free at 1 year (p<0.0001). High risk patients who recurred within 1 year had a statistically higher percentage of abnormal cells as compared to those who did not recur within 1 year (50% [range 6–100] vs. 25% [range 6– 100], respectively p=0.001). There was no difference in the percentage of abnormal cells for those patients with low or intermediate risk disease based on recurrence within 1 year (22% [range 6–100] vs. 20% [range 6–100], respectively p=0.25). Conclusions: The percentage of abnormal cells in FISH analysis correlates with risk of recurrence for patients with high risk disease and can be used to guide surveillance interval decisions in patients with no other evidence of recurrence. [Table: see text]

scholarly journals Diagnostic Tumor Mirna Profiling Predicts Molecular Relapse in Mantle Cell Lymphoma Patients Prospectively Followed for Minimal Residual Disease. Results from the Nordic MCL2-3 Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2994-2994
Author(s):  
Simon Husby ◽  
Lone Bredo Pedersen ◽  
Ulrik Ralfkiær ◽  
Christian Garde ◽  
Sara Ek ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
High Dose ◽  
Advisory Committees ◽  
Mantle Cell ◽  
Risk Patients ◽  
Minimal Residual

Abstract Background Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin`s lymphoma (NHL) with a variable but often aggressive clinical course. The majority of MCL patients ≤65 years will experience clinical relapse during a 10-year period (Geisler et al. Br J Haematol 2012). Risk-stratification is therefore of great importance in order to identify patients who are eligible for novel or alternative treatment regimens. Minimal residual disease (MRD) monitoring can predict clinical progression in MCL and guide pre-emptive treatment with rituximab as single agent. It has thus far not been possible to predict post-treatment molecular relapse (MRD-positivity). Although some recent studies have shown that aberrant miRNA expression delineate pathogenic molecular pathways and predict survival in MCL patients, miRNA profiling has not been performed in the context of MRD and molecular relapse. Aims We assessed MCL miRNA expression, in a large, prospective, uniformly treated patient cohort followed with molecular markers for MRD to determine if miRNAs could predict molecular relapse. Methods Diagnostic MCL tumor samples from 114 patients in the Nordic MCL2 and MCL3 clinical trials were retrieved. All patients had confirmed CyclinD1 overexpression and 96 patients had Ki-67 expression measurement for use in the MIPI-B predictive score. All patients received almost identical induction treatment with six alternating cycles of maxi-CHOP and high-dose Ara-C in combination with rituximab. Patients in remission were consolidated with high dose chemotherapy followed by autologous stem cell transplantation. All patients had a molecular marker (PCR detectable t(11;14) or clonal IgH rearrangement) for MRD. The median follow-up was 6.4 years for the MCL2 cohort and 3.7 years for the MCL3 cohort. 19 miRNAs, previously found to have prognostic significance in MCL (Husby et al EHA 2014), were measured by qRT-PCR and analyzed in concordance with MRD-data. The main endpoint was first event of molecular relapse (MRD-positive sample). Results Of the 114 patients in the study, 71 (62%) patients became MRD-positive in the follow-up period. Of the 19 examined miRNAs, 10 miRNAs showed unique qPCR melting curves and were analyzed with respect to MRD. Four miRNAs (miR-92a, miR-3687, miR-486-5p and miR-185-5p) were significantly up-regulated in patients who had molecular relapse (t-test; respectively p = 0.010, p = 0.019, p = 0.048, p = 0.043). However miR-18b, previously identified as prognostic marker regarding survival, was not significantly overexpressed. We hereafter investigated if a newly derived prognostic score, the MIPI-B-miR, which incorporates miR-18b with the MIPI-B, could predict molecular relapse. The MIPI-B-miR high-risk patients had significantly shorter time to first molecular relapse than MIPI-B high-risk patients (Figure 1). Functional studies of these aberrantly expressed miRs are ongoing. Conclusion Patients with molecular relapse had significantly increased levels of miR-92a, miR-3687, miR-486-5p and miR-185-5p, and MIPI-B-miR improved MRD prediction compared to MIPI-B. Aberrant miRNA profiles may be able to predict molecular relapse, and may already at diagnosis identify patients eligible to anti-CD20 antibody maintenance or alternative regimens. However validation in other cohorts is needed. Figure 1 Figure 1. Disclosures Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Räty:GlaxoSmithKline Ltd: Honoraria; Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria.

scholarly journals Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Katja Weisel ◽  
Andrew Spencer ◽  
Suzanne Lentzsch ◽  
Hervé Avet-Loiseau ◽  
Tomer M. Mark ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Subgroup Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Sensitivity Threshold ◽  
Risk Patients ◽  
Poor Outcomes

Abstract Background Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). Methods This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10−5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. Results After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21–0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. Conclusion These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. Trial registration ClinicalTrials.gov, NCT02136134. Registered 12 May 2014

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals Implementation of the acutely presenting older patient (APOP) screening program in routine emergency department care

2021 ◽  
Author(s):  
Laura C. Blomaard ◽  
Bas de Groot ◽  
Jacinta A. Lucke ◽  
Jelle de Gelder ◽  
Anja M. Booijen ◽  
...  
Keyword(s):  
Emergency Department ◽  
High Risk ◽  
Older Patients ◽  
Screening Program ◽  
Admission Rate ◽  
Older Patient ◽  
Hospital Admission Rate ◽  
High Risk Patients ◽  
Risk Patients

Abstract Objective The aim of this study was to evaluate the effects of implementation of the acutely presenting older patient (APOP) screening program for older patients in routine emergency department (ED) care shortly after implementation. Methods We conducted an implementation study with before-after design, using the plan-do-study-act (PDSA) model for quality improvement, in the ED of a Dutch academic hospital. All consecutive patients ≥ 70 years during 2 months before and after implementation were included. The APOP program comprises screening for risk of functional decline, mortality and cognitive impairment, targeted interventions for high-risk patients and education of professionals. Outcome measures were compliance with interventions and impact on ED process, length of stay (LOS) and hospital admission rate. Results Two comparable groups of patients (median age 77 years) were included before (n = 920) and after (n = 953) implementation. After implementation 560 (59%) patients were screened of which 190 (34%) were high-risk patients. Some of the program interventions for high-risk patients in the ED were adhered to, some were not. More hospitalized patients received comprehensive geriatric assessment (CGA) after implementation (21% before vs. 31% after; p = 0.002). In 89% of high-risk patients who were discharged to home, telephone follow-up was initiated. Implementation did not influence median ED LOS (202 min before vs. 196 min after; p = 0.152) or hospital admission rate (40% before vs. 39% after; p = 0.410). Conclusion Implementation of the APOP screening program in routine ED care did not negatively impact the ED process and resulted in an increase of CGA and telephone follow-up in older patients. Future studies should investigate whether sustainable changes in management and patient outcomes occur after more PDSA cycles.

Depth of response and minimal residual disease status in ultra high-risk multiple myeloma and plasma cell leukemia treated with daratumumab, bortezomib, lenalidomide, cyclophosphamide and dexamethasone (Dara-CVRd): Results of the UK optimum/MUKnine trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Martin F. Kaiser ◽  
Andrew Hall ◽  
Katrina Walker ◽  
Ruth De Tute ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
Cell Leukemia ◽  
Ultra High Risk ◽  
Grade 3 ◽  
Minimal Residual

8001 Background: Patients with ultra high-risk (UHiR) newly diagnosed multiple myeloma (NDMM) and patients with plasma cell leukemia (PCL) continue to have dismal outcomes and are underrepresented in clinical trials. Recently, improved responses with anti-CD38 monoclonal antibody combination therapy have been reported for NDMM patients. We report here outcomes for NDMM UHiR and PCL patients treated in the OPTIMUM/MUKnine (NCT03188172) trial with daratumumab, cyclophosphamide, bortezomib, lenalidomide, dexamethasone (Dara-CVRd) induction, augmented high-dose melphalan (HDMEL) and ASCT. With final analysis follow-up surpassed in Feb 2021, we report here early protocol defined endpoints from induction to day 100 post ASCT. Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM by central trial genetic (≥2 high risk lesions: t(4;14), t(14;16), t(14;20), gain(1q), del(1p), del(17p)) or gene expression SKY92 (SkylineDx) profiling, or with PCL (circulating plasmablasts > 20%) were included in OPTIMUM across 39 UK hospitals. Patients received up to 6 cycles of Dara-CVRd induction, HDMEL and ASCT augmented with bortezomib, followed by Dara-VR(d) consolidation for 18 cycles and Dara-R maintenance. Primary trial endpoints are minimal residual disease (MRD) status post ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. Data is complete but subject to further data cleaning prior to conference. Results: Median follow-up for the 107 patients in the safety population was 22.2 months (95% CI: 20.6 – 23.9). Two patients died during induction due to infection. Bone marrow aspirates suitable for MRD assessment by flow cytometry (10-5 sensitivity) were available for 81% of patients at end of induction and 78% at D100 post ASCT. Responses in the intention to treat population at end of induction were 94% ORR with 22% CR, 58% VGPR, 15% PR, 1% PD, 5% timepoint not reached (TNR; withdrew, became ineligible or died) and at D100 post ASCT 83% ORR with 47% CR, 32% VGPR, 5% PR, 7% PD, 10% TNR. MRD status was 41% MRDneg, 40% MRDpos and 19% not evaluable post induction and 64% MRDneg, 14% MRDpos and 22% not evaluable at D100 post ASCT. Responses at D100 post ASCT were lower in PCL with 22% CR, 22% VGPR, 22% PR, 22% PD, 12% TNR. Most frequent grade 3/4 AEs during induction were neutropenia (21%), thrombocytopenia (12%) and infection (12%). Grade 3 neuropathy rate was 3.7%. Conclusions: This is to our knowledge the first report on a trial for UHiR NDMM and PCL investigating Dara-CVRd induction and augmented ASCT. Response rates were high in this difficult-to-treat patient population, with toxicity comparable to other induction regimens. However, some early progressions highlight the need for innovative approaches to UHiR NDMM. Clinical trial information: NCT03188172.

Minimally Invasive Direct Coronary Artery Bypass in High-Risk Patients with Multivessel Disease

2021 ◽  
Author(s):  
Grischa Hoffmann ◽  
Christine Friedrich ◽  
Katharina Huenges ◽  
Rainer Petzina ◽  
Astrid-Mareike Vogt ◽  
...  
Keyword(s):  
Coronary Artery ◽  
High Risk ◽  
Minimally Invasive ◽  
Coronary Artery Bypass ◽  
Artery Bypass ◽  
Multivessel Disease ◽  
Complete Revascularization ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background High-risk patients with multivessel disease (MVD) including a complex stenosis of the left anterior descending coronary may not be ideal candidates for guideline compliant therapy by coronary artery bypass grafting (CABG) regarding invasiveness and perioperative complications. However, they may benefit from minimally invasive direct coronary artery bypass (MIDCAB) grafting and hybrid revascularization (HCR). Methods A logistic European system for cardiac operative risk evaluation score (logES) >10% defined high risk. In high-risk patients with MVD undergoing MIDCAB or HCR, the incidence of major adverse cardiac and cerebrovascular events (MACCEs) after 30 days and during midterm follow-up was evaluated. Results Out of 1,250 patients undergoing MIDCAB at our institution between 1998 and 2015, 78 patients (logES: 18.5%; age, 76.7 ± 8.6 years) met the inclusion criteria. During the first 30 days, mortality and rate of MACCE were 9.0%; early mortality was two-fold overestimated by logES. Complete revascularization as scheduled was finally achieved in 64 patients (82.1%). Median follow-up time reached 3.4 (1.2–6.5) years with a median survival time of 4.7 years. Survival after 1, 3, and 5 years was 77, 62, and 48%. Conclusion In high-risk patients with MVD, MIDCAB is associated with acceptable early outcome which is better than predicted by logES. Taking the high-risk profile into consideration, midterm follow-up showed satisfying results, although scheduled HCR was not realized in a relevant proportion. In selected cases of MVD, MIDCAB presents an acceptable alternative for high-risk patients.

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