scholarly journals P218 Linked colour imaging predicts the risk of the clinical relapse in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S250-S250
Author(s):  
S Kanmura ◽  
Y Komaki ◽  
F Komaki ◽  
A Tanaka ◽  
F Sasaki ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Relapse Rate ◽  
Univariate Analysis ◽  
Additional Treatment ◽  
Chronic Inflammatory Bowel Disease ◽  
Clinical Relapse ◽  
Vascular Pattern ◽  
Endoscopic Observation ◽  
Significant Difference

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown aetiology. Recently, mucosal healing (MH) has emerged as an important therapeutic endpoint in UC. Linked colour imaging (LCI) is a novel endoscopic system that enhances the colour differences of the gastrointestinal mucosa. We aimed to evaluate the correlation between the endoscopic observation using LCI and the clinical relapse rate in UC patients. Methods We retrospectively analysed UC patients who underwent a total colonoscopy between August 2016 and May 2019 at our facility with Mayo endoscopic score (MES) of 0 or 1. We assessed the most relevant endoscopic findings, including erythema, vascular pattern, and friability using white-light imaging (WLI) and LCI observation. We analysed the correlation of clinical relapse rate, which means requiring additional treatment for UC, during the 2-year follow-up period with endoscopic assessment using WLI and LCI. We also evaluated the utility of LCI-observation method for predicting the prognosis in UC patients with clinical remission. Results Forty-seven patients were analysed, and clinical relapse was observed in 10 patients (21%) during the 2-year. Univariate analysis revealed a significant difference in decreased vascular pattern and friability between the clinical relapse and remission groups; multivariate analysis showed decreased vascular pattern observed on LCI as the only variable, which remained significantly associated with clinical relapse (p <0.03). We defined LCI-mucosal score (MS) as LCI-MS 0, distinct vascular pattern and no friability; LCI-MS 1, either indistinct purple/magenta vascular pattern or friability; and LCI-MS 2, both indistinct purple/magenta vascular pattern or friability on LCI observation. The relapse rate in patients with LCI-MS 0 was 10% (3/30), which was significantly lower than in patients with LCI-MS 1 or 2 (36 %; 6/16). Conclusion LCI findings have the diagnostic implications in predicting the risk of clinical relapse in UC during the 2-year follow-up period.

scholarly journals Significance of Linked Color Imaging for Predicting the Risk of Clinical Relapse in Ulcerative Colitis

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Shuji Kanmura ◽  
Akihito Tanaka ◽  
Kazuki Yutsudou ◽  
Kosuke Kuwazuru ◽  
Fukiko Komaki ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Relapse Rate ◽  
Additional Treatment ◽  
Chronic Inflammatory Bowel Disease ◽  
Unknown Etiology ◽  
Clinical Relapse ◽  
Color Imaging ◽  
Significant Difference ◽  
Linked Color Imaging

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown etiology. Recently, mucosal healing has emerged as an important therapeutic endpoint in UC. Linked color imaging (LCI) is a novel endoscopic system that enhances the color differences of the gastrointestinal mucosa. Our previous study emphasized the redness and yellowness of the lesion using LCI observation, which was useful for the evaluation of histological mucosal activity in UC. In this study, we aimed to evaluate the correlation between LCI observation and clinical relapse rate in UC patients. We retrospectively analyzed UC patients who underwent total colonoscopy between August 2016 and October 2018 at our facility with Mayo endoscopic scores of 0 or 1. We assessed the correlation between orange-like color lesion (defined as LCI-scarlet color lesions) and clinical relapse rate (requiring additional treatment for UC) during the 1-year follow-up period. Fifty-eight patients (22 female, 36 male; median age at diagnosis, 47.2 (18–80) years) who underwent colonoscopy were analyzed. During the 1-year follow-up period, clinical relapse was observed in 12 patients (20.1%) among which ten patients (83.3%) had an LCI-scarlet color lesions recognized by LCI. By contrast, 29 patients (63%) had no LCI-scarlet color lesions in the clinical remission group (n=46). There was a significant difference in LCI-scarlet color between the clinical relapse and remission groups, remaining significantly associated with clinical relapse. LCI findings, including an orange-like color lesion, have diagnostic implications for predicting the risk of clinical relapse in UC during the 1-year follow-up period.

scholarly journals P125 Histological activity as a predictor of clinical outcome in ulcerative colitis: a 1-year prospective study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S200-S200
Author(s):  
B Neri ◽  
S Romeo ◽  
A Ruffa ◽  
E Calabrese ◽  
G Sena ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Prospective Study ◽  
Univariate Analysis ◽  
Predictive Marker ◽  
Clinical Indication ◽  
Clinical Activity ◽  
Clinical Relapse ◽  
Histological Activity

Abstract Background The role of histological activity in clinical management of ulcerative colitis (UC) is under investigation. Primary aim was, in a prospective study, to assess the role of histological activity as predictor of clinical relapse in a cohort of UC patients (patients) undergoing colonoscopy and followed-up for 1 year. Secondary aim was to assess the correlation between clinical, endoscopic and histological activity scores. Methods From February 2016 to February 2017 consecutive UC patients with clinical indication for colonoscopy were enrolled and clinically followed-up for 1 year. Inclusion criteria: (1) UC diagnosis; (2) Age > 18, ≤ 80 years; (3) regular follow-up; (4) indication for colonoscopy. During colonoscopy ≥2 biopsies was taken from ≥1 macroscopically involved and, possibly, from ≥1 uninvolved area. The day of colonoscopy clinical activity was assessed by the Mayo partial score, endoscopic activity by the Mayo endoscopic score, histological activity by the Geboes Simplified Score (GSS). Scores blindly assessed by three investigators. Statistical analysis: data expressed as mean [range], Spearman’s correlation coefficients, Cox hazards regression model used for univariate and multivariate analyses to identify predictors of clinical relapse at 1 year (HR[95% CI]). Results UC cohort included 77 UC patients. Characteristics of these 77 UC patients: 43 (55.8%) males, age 51 [24–80]; UC duration 14.7 [1–48] years. UC extent included n (%): 33 (42.8%) pancolitis, 24 (31.2%) left-sided, 20 (26%) proctitis. The day of colonoscopy, UC was clinically active in 15 (19.4%), inactive in 62 (80.6%) patients. Endoscopic activity was observed in 39 (50.6%) patients, histological activity (GSS≥ 3.1) in 37(48%) patients. Moderate correlations were observed between clinical and endoscopic scores (r = 0.439;p < 0.0001) clinical and histological scores (r = 0.32;p = 0.0045), endoscopic and histological scores (r = 0.653;p < 0.0001). During the clinical follow-up at 1 year, UC clinical relapse occurred in 24 (31%) patients, while 53 (69%) patients maintained clinical remission. At baseline colonoscopy, 11/24 (46%) UC patients were clinically active, 15/24 (63%) showed endoscopic activity and 16/24 (67%) patients histological activity. Univariate analysis identified clinical activity (HR 4.82 [2.15–10.82]; p < 0.001) and histological activity (HR 2.599 [1.11–6.08]; p < 0.027) as significant predictive factors for clinical relapse at 1 year. Multivariate model confirmed histological activity as predictive marker of clinical relapse (HR 2.44 [1.04–5.75]; p < 0.041). Conclusion Histological activity provided independent information for clinical relapse in a cohort of UC patients prospectively followed up for 1 year. Histological activity had a significant correlation with the endoscopic and clinical activity scores.

scholarly journals POS1189 THE IMPACT OF TELEMEDICINE AND COVID-19 ON A TERTIARY RHEUMATOLOGY SERVICE: A RETROSPECTIVE AUDIT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 876-877
Author(s):  
W. Zhu ◽  
T. De Silva ◽  
L. Eades ◽  
S. Morton ◽  
S. Ayoub ◽  
...  
Keyword(s):  
Immunosuppressive Therapy ◽  
Univariate Analysis ◽  
Diagnostic Delay ◽  
Cohort Differences ◽  
Phone Calls ◽  
Retrospective Audit ◽  
Common Diagnosis ◽  
Significant Difference ◽  
The Impact

Background:Telemedicine was widely utilised to complement face-to-face (F2F) care in 2020 during the COVID-19 pandemic, but the impact of this on patient care is poorly understood.Objectives:To investigate the impact of telemedicine during COVID-19 on outpatient rheumatology services.Methods:We retrospectively audited patient electronic medical records from rheumatology outpatient clinics in an urban tertiary rheumatology centre between April-May 2020 (telemedicine cohort) and April-May 2019 (comparator cohort). Differences in age, sex, primary diagnosis, medications, and proportion of new/review appointments were assessed using Mann-Whitney U and Chi-square tests. Univariate analysis was used to estimate associations between telemedicine usage and the ability to assign a diagnosis in patients without a prior rheumatological diagnosis, the frequency of changes to immunosuppression, subsequent F2F review, planned admissions or procedures, follow-up phone calls, and time to next appointment.Results:3,040 outpatient appointments were audited: 1,443 from 2019 and 1,597 from 2020. There was no statistically significant difference in the age, sex, proportion of new/review appointments, or frequency of immunosuppression use between the cohorts. Inflammatory arthritis (IA) was a more common diagnosis in the 2020 cohort (35.1% vs 31%, p=0.024). 96.7% (n=1,444) of patients seen in the 2020 cohort were reviewed via telemedicine. In patients without an existing rheumatological diagnosis, the odds of making a diagnosis at the appointment were significantly lower in 2020 (28.6% vs 57.4%; OR 0.30 [95% CI 0.16-0.53]; p<0.001). Clinicians were also less likely to change immunosuppressive therapy in 2020 (22.6% vs 27.4%; OR 0.78 [95% CI 0.65-0.92]; p=0.004). This was mostly driven by less de-escalation in therapy (10% vs 12.6%; OR 0.75 [95% CI 0.59-0.95]; p=0.019) as there was no statistically significant difference in the escalation or switching of immunosuppressive therapies. There was no significant difference in frequency of follow-up phone calls, however, patients seen in 2020 required earlier follow-up appointments (p<0.001). There was also no difference in unplanned rheumatological presentations but significantly fewer planned admissions and procedures in 2020 (1% vs 2.6%, p=0.002). Appointment non-attendance reduced in 2020 to 6.5% from 10.9% in 2019 (OR 0.57 [95% CI 0.44-0.74]; p<0.001), however the odds of discharging a patient from care were significantly lower in 2020 (3.9% vs 6%; OR 0.64 [95% CI 0.46-0.89]; p=0.008), although there was no significance when patients who failed to attend were excluded. Amongst patients seen via telemedicine in 2020, a subsequent F2F appointment was required in 9.4%. The predictors of needing a F2F review were being a new patient (OR 6.28 [95% CI 4.10-9.64]; p<0.001), not having a prior rheumatological diagnosis (OR 18.43 [95% CI: 2.35-144.63]; p=0.006), or having a diagnosis of IA (OR 2.85 [95% CI: 1.40-5.80]; p=0.004) or connective tissue disease (OR 3.22 [95% CI: 1.11-9.32]; p=0.031).Conclusion:Most patients in the 2020 cohort were seen via telemedicine. Telemedicine use during the COVID-19 pandemic was associated with reduced clinic non-attendance, but with diagnostic delay, reduced likelihood of changing existing immunosuppressive therapy, earlier requirement for review, and lower likelihood of discharge. While the effects of telemedicine cannot be differentiated from changes in practice related to other aspects of the pandemic, they suggest that telemedicine may have a negative impact on the timeliness of management of rheumatology patients.Disclosure of Interests:None declared.

Endovascular versus surgical treatment for improvement of oculomotor nerve palsy caused by unruptured posterior communicating artery aneurysms

2020 ◽  
Vol 12 (10) ◽  
pp. 964-967
Author(s):  
Francesco Signorelli ◽  
Raoul Pop ◽  
Mario Ganau ◽  
Helene Cebula ◽  
Antonino Scibilia ◽  
...  
Keyword(s):  
Nerve Palsy ◽  
Univariate Analysis ◽  
Oculomotor Nerve ◽  
Posterior Communicating Artery ◽  
Oculomotor Nerve Palsy ◽  
Surgical Clipping ◽  
Unruptured Aneurysms ◽  
Significant Difference ◽  
Complete Treatment

BackgroundThere is no consensus regarding the best treatment option for unruptured aneurysms of the posterior communicating artery (PCom) presenting with oculomotor nerve palsy (ONP). We aimed to assess predictors of ONP recovery in a multicenter series of consecutive patients.Materials and methodsA retrospective review of prospective databases in three tertiary neurosurgical centers was carried out, selecting patients with ONP caused by unruptured PCom aneurysms, treated by surgical clipping or embolization, between January 2006 and December 2013. Patient files and imaging studies were used to extract ophthalmological assessments, treatment outcomes, and follow-up data. Predictors of ONP recovery during follow-up were explored using univariate and multivariate analyses.ResultsWe identified 55 patients with a median ONP duration before treatment of 11 days (IQR 4.5–18); the deficit was complete in 27 (49.1%) and incomplete in 28 (50.9%) cases. Median aneurysm size was 7 mm (IQR 5–9). Twenty-four (43.6%) patients underwent surgical clipping and 31 (56.4%) embolization as the primary treatment. Overall, ONP improved in 40 (72.7%) patients and persisted/recurred in 15 (27.3 %). Surgery, interval to complete treatment <4 weeks, aneurysm recurrence during follow-up, and retreatment during follow-up were significantly correlated with ONP outcome in the univariate analysis. In the multivariate analysis, independent predictors of ONP improvement were interval to complete treatment <4 weeks (OR 5.15, 95% CI 1.37 to 23.71, p=0.015) and aneurysm recurrence during follow-up (OR 0.1, 95% CI 0.02 to 0.47, p=0.003).ConclusionThere was no significant difference in ONP recovery between surgical clipping and embolization. The best predictor for ONP recovery was timely, complete, and durable aneurysm exclusion.

ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3946-3946 ◽  
Author(s):  
Antony Ceraulo ◽  
Aminetou Mint-Mohamed ◽  
Delphine Maucort-Boulch ◽  
Etienne Paubelle ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Relapse Rate ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Gemtuzumab Ozogamicin ◽  
Small Sample ◽  
Control Group ◽  
Prognostic Impact ◽  
Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

Long-term cardiopulmonary mortality after radiation for locally advanced esophageal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Abigail Berman Milby ◽  
Andrzej Pawel Wojcieszynski ◽  
Smith Apisarnthanarax ◽  
James M. Metz ◽  
John Peter Plastaras
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Carcinoma ◽  
Background Radiation ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Rank Test ◽  
Trimodality Therapy ◽  
Significant Difference

99 Background: Radiation (RT) is considered an integral component of trimodality therapy for locally-advanced esophageal carcinoma to improve locoregional control and potentially survival. However, the long-term risk of cardiopulmonary mortality (CPM) is not well-understood in this population. Methods: Patients age 20-85 with esophageal carcinoma with T3, T4 or node positive (N+) disease who underwent esophagectomy were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988-2006. Patients with metastatic disease or <6 mo follow up were excluded. CPM was calculated for patients receiving vs not receiving RT and compared by the Kaplan-Meier method. The log-rank test was used for univariate associations and Cox proportional hazards model was used for multivariate analysis (MVA). Results: A total of 4,079 patients met the defined selection criteria of whom 2,408 were treated with RT, and 1,671 were not. Median age was 62.2 yrs (22-84) and follow-up was 22 mos (6-248). There was no significant difference in CPM in patients who received RT versus those who did not (p=0.8). At 10 yr, the majority of deaths were from esophageal cancer (73 with vs 78% without RT) compared to CPM (13.7 with vs 11.6% without RT). On univariate analysis ( table ), age <60, diagnosis era, and histology were significant independent predictors of CPM. On MVA, age <60 (HR 0.36) and diagnosis era (0.63 for 1994-2000 and 0.55 for 2000-2006) remained statistically significant for CPM. Conclusions: RT for esophageal cancer is not associated with an increased long-term risk of CPM in the overall population. Older age and earlier diagnosis era predict for CPM. Although survival in esophageal cancer is dominated by cancer deaths, advances in RT are still needed to prevent excess treatment-related mortality. [Table: see text]

Association between single nucleotide polymorphisms (SNPs) of genes involved in spindle assembly checkpoint (SAC) and clinical outcomes in advanced gastric cancer (AGC) patients (pts) treated with taxane-based chemotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 79-79
Author(s):  
Shinichi Yamauchi ◽  
Satoshi Okazaki ◽  
Afsaneh Barzi ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Spindle Assembly Checkpoint ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Nucleotide Polymorphisms ◽  
Tissue Samples ◽  
Significant Difference ◽  
Validation Set ◽  
The Impact

79 Background: Taxanes which disrupt the microtubule function and inhibit the process of cell division have shown encouraging activity in the treatment of AGC. Resistance to these agents often becomes a problem in clinical settings and its mechanism hasn’t been dissolved conclusively. SAC is a safety device ensures the proper chromosome segregation in mitosis and is required for taxane-induced cell death. We hypothesized genetic variants in SAC genes may be associated with clinical outcomes in pts with AGC treated with taxane. Methods: Genomic DNA was isolated from blood or tissue samples of 39 U.S. pts (median age 57; median follow-up 6.4 months) for evaluation set and 39 Japanese (JPN) pts (median age 63; median follow-up 9.4 months) for validation set, with AGC treated with taxane. Twenty-five functionally significant SNPs in SAC genes (MAD1, MAD2, BUB3, BUBR1, RAN, TPX2, CDC20, AURKA, AURKB, RCC1, ANAPC10, ANAPC13) were analyzed by PCR-based direct sequencing and evaluated for association with outcomes. Results: In univariate analysis, rs4236271 (MAD1), rs6954673 (MAD1), and rs2064863 (AURKA) showed a significant difference in 6-month (mo) progression-free survival (PFS) rate [(C/C 42%, C/T 12%; HR 2.66, P=0.008), (C/C 75%, C/T or T/T 24%; HR 5.10, P=0.008), and (T/T 50%, T/G 15%, G/G 57%; HR1.55, P=0.046), respectively] and 18-mo overall survival (OS) rate [(C/C 40%, C/T 8%; HR3.69, P<0.001), (C/C 56%, C/T or T/T 19%; HR3.60, P=0.004), and (T/T 59%, T/G 15%, G/G 29%; HR 2.02, P=0.047), respectively] in evaluation set. In multivariate analysis, rs4236271 and rs6954673 remained significant in PFS (HR 7.24, P=0.005, HR 14.49, P=0.015, respectively) and OS (HR 7.39, P=0.001, HR 6.37, P=0.002, respectively). In validation set, rs6954763 showed a significant difference in 18-mo OS rate (C/C 16%, C/T or T/T 47%, HR 3.55, P=0.014), but the impact of C/C genotype on OS in the JPN pts was the opposite to the U.S. pts. Conclusions: These results suggest that MAD1 polymorphisms may serve as a prognostic marker in pts with AGC. Further studies using larger population are needed to corroborate our results.

Polymorphism of the chemokine CXCR4 to predict treatment benefit of first-line bevacizumab-based chemotherapy in patients with metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 635-635
Author(s):  
Satoshi Matsusaka ◽  
Fotios Loupakis ◽  
Wu Zhang ◽  
Shu Cao ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Candidate Snps ◽  
First Line ◽  
Significant Difference

635 Background: The chemokine receptor CXCR4 and its ligand CXCL12 promote angiogenesis and the migration of tumor cells into the metastatic sites in many cancers. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor. Therefore, we analyzed the association between CXCR4/CXCL12 polymorphisms and prognosis in metastatic colorectal cancer (mCRC) patients underwent bevacizumab-based chemotherapy. Methods: This study included 144 Japanese patients (pts) for evaluation set and 424 patients from two clinical trials (204 of TRIBE arm A and 220 of PROVETTA) for validation set, with mCRC treated with bevacizumab-based chemotherapy as first line. A total of 144 Japanese pts with (male/female; 81/63, median age 61 years, median follow-up 4.2 years) and 424 pts (male/female; 252/172, median age 62 years; median follow-up time; 2.8 years) were enrolled in a pharmacogenomics translational study. Genomic DNA was extracted from the pts’ blood or tissue. One CXCR4 single nucleotide polymorphisms (SNP) (rs2228014) and two CXCL12 SNPs (rs1801157, rs3740085) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with the clinical outcome. Results: In univariate analysis, CXCR4 rs2228014 showed a significant difference in PFS [(G/G 15.3 months, any A allele 13.7 months, HR (95% CI) 1.64 (1.01-2.68), p=0.036)]. After multivariate analysis, CXCR4 rs2228014 remained to be a significant for PFS [HR (95% CI) 1.67 (1.01-2.78), p =0.046]. However, this polymorphism was not associated with tumor response and survival. In the validation cohort, pts with GG genotype had significantly longer PFS compared to those with any A allele (10.5 vs 9.6 months, HR (95% CI) 1.40 (1.02-1.93), p =0.035). CXCL12 polymorphisms were not associated with the clinical outcome. Conclusions: This study shows for the first time that CXCR4 rs2228014 may serve as a predictive marker in patients with mCRC treated with bevacizumab-based chemotherapy.

scholarly journals Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1124-1124
Author(s):  
Jiang Ji ◽  
Ziqi Wan ◽  
Jing Ruan ◽  
Yali Du ◽  
Miao Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aplastic Anemia ◽  
Median Time ◽  
Relapse Rate ◽  
Real World ◽  
Reticulocyte Count ◽  
Efficacy And Safety ◽  
Overall Response ◽  
Significant Difference

Abstract Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P&gt;0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

scholarly journals P377 Inadequate response with advanced therapies in real-world patients with Ulcerative Colitis – Results of a German claims database study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S392-S392
Author(s):  
B Bokemeyer ◽  
N Picker ◽  
T Wilke ◽  
L Rosin ◽  
H Patel
Keyword(s):  
Ulcerative Colitis ◽  
Median Time ◽  
Real World ◽  
Index Date ◽  
Sickness Fund ◽  
Inadequate Response ◽  
Advanced Therapy ◽  
Advanced Therapies ◽  
Significant Difference

Abstract Background Therapeutic management of Ulcerative Colitis (UC) is challenging, and clinicians are often obliged to attempt a variety of therapies in sequence until an adequate clinical response is achieved. However, real-world data regarding response rates in UC treatment are rare, particularly for later lines of therapy. Thus, this study aimed to investigate the incidence of inadequate response to advanced therapies in patients with UC. Methods This retrospective study was based on claims data from a regional German sickness fund covering the period from 01/2014-06/2019. Patients were included if they had at least two outpatient diagnoses in two different quarters or one inpatient diagnosis of UC (ICD-10: K51) and started a newly introduced advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) in 01/2015-06/2019. Patients were followed from treatment initiation (index date) until the end of the study period or loss to follow-up (median = 23.4 months). Proxies of inadequate response included: discontinuation (a supply gap of &gt;60 days), switch, escalation (as dose increase exceeding 1.5 times the recommended maintenance dose), augmentation with 5-ASA, corticosteroid (CS) dependency (two CS prescriptions were observed starting more than 14 weeks after the index date), UC-related hospitalization, or UC-related surgery. CS dependency and treatment escalation were only assessed in the maintenance phase. Inadequate response in the analyzed sample was evaluated by means of Kaplan-Meier survival analysis. Results Among 574 UC patients (median age: 39 years; female: 53.5%), in whom an advanced therapy was initiated, 458 (79.8%) received an anti-TNF therapy, 113 (19.7%) vedolizumab and 3 (0.5%) tofacitinib. According to the available baseline period, 72 (12.4%) patients were identified as biologic-experienced. Most patients received CS (86.4%) and/or 5-aminosalicylic acids (81.7%) in the 12-month pre-index period. The median time to inadequate response to the initiated advanced therapy was 4.8 months (IQR: 2.6-11.9; Figure 1) with an inadequate response over 12 months in 75% (Figure 2). There was no significant difference in median time to inadequate response between biologic-naïve and biologic-experienced patients (4.9 vs. 4.7 months; p-value = 0.285). During the observable follow-up period, 172 (61%) patients switched from their index agent to another advanced therapy. Conclusion From the real-world settings in Germany, we found an inadequate response in UC-patients starting an advanced therapy in 75% of patients over 12 months. There is a need for more effective therapies among these patients.

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