Rate Of Progression In Patients Research Articles

Abstract 19820: Heterogeneity of Disease Progression Rates in Patients With Bicuspid Aortic Valve: Is There a Suitable Bio-marker?

Introduction: Bicuspid aortic valve (BAV) is associated with inflammatory activation and endothelial dysfunction. Worsening of aortic valve stenosis/regurgitation represents the most common complication of BAV, but clinical and biochemical markers of disease progression are not currently available. Objective: The objective of the current study was to (1) evaluate rates of progression of aortopathy and valve dysfunction, and (2) identify correlates of accelerated progression among BAV patients. Methods: 43 BAV patients aged 45 ± 16 (SD) years were evaluated clinically and with echo/MRI. Inflammatory activation was assessed via hs-CRP and myeloperoxidase (MPO) levels, endothelial function/NO responsiveness via flow-mediated dilatation (FMD), plasma asymmetric dimethylarginine (ADMA) levels, inhibition of platelet aggregation by SNP, and endothelial progenitor cell counts. Follow-up was undertaken after 47 ±16 months to determine rate of progression and of need for valve replacement; some patients did not undergo repeat echo (Figure). Biochemical/physiological correlates of valve dysfunction and aortic dimensions were sought via univariate and multiple linear regression analyses. Results: AV max increased from 2.1 ± 0.6 to 2.5 ± 1.1(m/s), p < 0.05, while ascending aorta (Asc Ao) dimensions increased from 18.2 ± 6.1 to 21.2 ± 4.9 (mm/m 2 ), p < 0.05 over the monitoring period. Although there was a direct correlation (p < 0.01) between baseline AV max and MPO levels on multivariate analysis, this correlation did not extend to progression rates. Indeed neither clinical nor biochemical parameters predicted accelerated progression. Conclusions: (1) Progression of valve disease and aortopathy in BAV is often rapid, with annual mean rate of 0.1 m/s for AV max and 0.4 mm/m 2 for Asc Ao. (2) Despite physiological evidence linking BAV with inflammation and endothelial dysfunction, these biochemical factors did not appear to predict rapid disease progression.

Abstract 16680: Lipoprotein(a) and Progression Rate of Aortic Valve Stenosis - A Pooled-Analysis of Two Prospective Studies

BACKGROUND: Recent studies have reported a single nucleotide polymorphism (i.e. rs10455872) at the LPA gene locus, encoding the lipoprotein(a) [Lp(a)], is associated with the presence of aortic valve calcification and clinical aortic stenosis (AS). The objectives of this study were to examine the association of Lp(a) plasma levels and rs 10455872 with the progression rate of AS. METHODS: Lp(a) plasma levels were measured in 203 patients with AS included in the ASTRONOMER (NCT00800800) trial and 246 patients in the PROGRESSA study (NCT01679431). The polymorphism rs10455872 was genotyped in the PROGRESSA cohort. Hemodynamic progression rate of AS severity was assessed by measuring the annualized increase in peak aortic jet velocity (Vpeak) by Doppler-echocardiography. RESULTS: Twenty-seven (13%) patients of the ASTRONOMER trial and 47 (19%) of the PROGRESSA study had high Lp(a) plasma levels (i.e. >50mg/dL). Baseline AS severity was similar in patients with high vs. low Lp(a) levels (p>0.10). In the pooled-analysis of both cohorts (a total of 449 patients with mean follow-up: 3.0 ±1.4 yrs), AS progression rate was similar in patients with Lp(a)>50 mg/dL compared to those with Lp(a)≤50 mg/dL (annualized change in Vpeak: +0.17±0.21 vs. +0.17±0.21 m/s/yr; p=0.97). Stratified analyses by cohort provided consistent results (ASTRONOMER: +0.20±0.21 vs. +0.25±0.19 m/s/yr; p=0.20; and PROGRESSA: +0.12±0.21 vs. +0.14±0.20 m/s/yr; p=0.46). In the PROGRESSA study, 38 (16%) patients carried at least one rs10455872 risk allele. Carriers of the risk allele had higher Lp(a) levels (58±24 vs. 20±38 mg/dL; p<0.0001). Baseline AS severity was similar in carriers and non-carriers whereas there was a borderline significant association for lower AS progression rate in carriers compared to non-carriers (+0.07±0.17 vs. +0.15±0.21 m/s/yr; p=0.05). Similar results were obtained for baseline and annualized progression rate assessed by aortic valve area. CONCLUSION: This prospective study shows that neither LPA gene variant nor Lp(a) plasma levels are associated with faster AS progression rate. Our findings do not support the notion that Lp(a) levels are related to AS progression rate in patients with AS.

SAT0368 Tumor Necrosis Factor Inhibitor Has NO Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

ObjectivesTo evaluate the influence of tumor necrosis factor (TNF) blocker on the radiographic damage in ankylosing spondylitis (AS)MethodsA total of 598 TNF blocker naïve AS patients from the Observation Study...

Relative lymphocyte count as a marker of progression of chronic kidney disease

Although low relative lymphocyte count (RLC) is associated with poor outcomes in patients with chronic kidney disease (CKD), the relationship between low RLC and progression of CKD is poorly defined. The aim of this study was to determine the association between low RLC and the progression of CKD. Between January 2003 and December 2009, 288 CKD patients were analyzed. RLC was calculated as the ratio between lymphocyte and total white blood cell counts. The median RLC was 29.1% [interquartile range (IQR) 24.1-34.1]. When the patients were compared according to a level below or above the median value for RLC, the rate of CKD progression to end-stage renal disease (ESRD) was greater in patients with low RLC count than in patients with high RLC (48 vs. 25%, p < 0.001) during the median follow-up of 5.5 years (IQR 3.5-7.6). The variables found to be predictive of progression to the ESRD included younger age, smoking, diabetes, higher systolic blood pressure, no use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lower hemoglobin and serum albumin levels, higher low-density lipoprotein cholesterol concentration, presence of proteinuria, and low RLC in the univariate Cox proportional hazards regression analysis. However, after adjustment, younger age, male, higher systolic blood pressure, no use of ACEIs or ARBs, lower hemoglobin and serum albumin concentrations, higher proteinuria, and lower RLC were significantly associated with progression to ESRD in multivariate analysis. Low RLC is independently associated with increased rate of progression in patients with CKD.

Adjuvant Treatment of Intermediate Risk Non-muscle Invasive Bladder Cancer.

Despite continuous improvement of diagnosis, surgical and adjuvant treatment procedures for non-muscle invasive bladder cancer (NMIBC), their natural development is still influenced by the high rates of tumor recurrence and progression. The study aims at assessing the value of adjuvant intravesical chemotherapy within the therapeutic protocol for operated intermediate risk non-muscle invasive bladder cancers. We analyzed recurrence and progression rates for patients within two samples: group A included 76 patients with intermediate risk NMIBC treated by transurethral resection (TUR) alone between 1995 and 1999 and group B included 89 patients with the same diagnosis with 8 – 12 Farmorubicin 50 mg intravesical instillations associated with the initial TUR between 2000 and 2004. For group A we recorded a 3 months recurrence rate of 27.6% and a general recurrence rate of 38.1% at one year and 51.3% at three years. The recurrence rate was lower for group B at 3 months (14.6%) as well as significantly lower (p<0.05) at one (23.6%) and three years (34.8%). Most NMIBC recurrences were recorded within one year of follow-up (75%), more than 50% of them being present at the first cystoscopy (3 months). Progression rate was unsignificantly 3% lower for group B, probably due to incomplete pathology data.

Abstract P4-12-27: Efficacy and safety of trastuzumab emtansine (T-DM1) vs lapatinib plus capecitabine (XL) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and central nervous system (CNS) metastases: Results from a retrospective exploratory analysis of EMILIA

Abstract Introduction T-DM1 is an antibody–drug conjugate that was recently approved by the FDA for patients with HER2-positive MBC who have received prior treatment with trastuzumab and a taxane. In the phase 3 EMILIA trial, T-DM1 significantly prolonged progression-free survival (PFS) and overall survival (OS) compared with XL in patients with previously treated HER2-positive MBC (Verma 2012). Because the CNS is a common site of progression in HER2-positive MBC, it is of interest to characterize the incidence of CNS metastases in patients treated with TDM1 vs XL and the efficacy of T-DM1 in patients with pre-existing CNS metastases. Methods EMILIA is a multicenter, randomized, open-label trial in which patients with HER2-positive, unresectable, locally advanced or MBC previously treated with trastuzumab and a taxane were randomized (1:1) to T-DM1 (3.6 mg/kg every 21 days) or XL (X: 1000 mg/m2 bid on days 1–14 of each 21-day cycle; L: 1250 mg/day on days 1–21). Treatment continued until disease progression or unacceptable toxicity. All patients underwent brain magnetic resonance imaging or computed tomography at screening, and follow-up scans were performed as clinically indicated. Those with untreated or symptomatic brain metastases and those who required therapy for symptom control ≤2 months before randomization were excluded from the trial. Patients with CNS metastases at baseline or who developed CNS metastases on study were retrospectively identified using independent review committee data, and exploratory analyses were performed on data from these patients. Results Of the 896 patients without CNS metastases at baseline (T-DM1 = 450; XL = 446), 9 (1.8%) and 3 (0.6%), respectively, developed CNS progression on study. Of the 95 patients with CNS metastases at baseline (T-DM1 = 45; XL = 50), 10 (2.0%) and 8 (1.6%), respectively, developed CNS progression on study. Median PFS in patients with CNS metastases at baseline was 5.9 months in the T-DM1 arm and 5.7 months in the XL arm (HR = 1.000; 95% CI: 0.542–1.844; P = 0.9998). Median OS was 26.8 months and 12.9 months in the T-DM1 and XL arms, respectively (HR = 0.382; CI: 0.184–0.795; P = 0.0081). Multivariate analysis adjusting for baseline risk factors produced similar results. Safety profiles of T-DM1 and XL in patients with CNS metastases at baseline (T-DM1 = 43; XL = 49) were consistent with those for the overall study population. Grade ≥3 adverse events (AEs) were reported in 17 (39.5%) patients in the T-DM1 arm and 29 (59.2%) patients in the XL arm. Serious AEs were reported in 5 (11.6%) and 11 (22.4%) patients in the T-DM1 and XL arms, respectively. No new safety signals were identified. Conclusions In this retrospective exploratory analysis of data from EMILIA, the rate of CNS progression in patients with or without baseline CNS metastases was low in both treatment arms. In the subset of patients with brain metastases at baseline, similar to the intent-to-treat population, T-DM1 was associated with significantly improved OS compared with XL. Prospective phase 3 trials are necessary to confirm these results. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-27.

The Effect of Restaging Transurethral Resection on Recurrence and Progression Rates in Patients with Nonmuscle Invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guérin

We determined whether restaging resection before initiating induction intravesical bacillus Calmette-Guérin improves the recurrence-free rate in patients with high risk nonmuscle invasive bladder cancer. We retrospectively analyzed data on 1,021 patients treated at our institution with intravesical bacillus Calmette-Guérin for nonmuscle invasive high risk bladder cancer. All patients underwent a second resection except those already receiving bacillus Calmette-Guérin at the time of initial consultation and those who refused restaging resection. All patients were assessed every 3 to 12 months for a minimum of 5 years. Univariate and multivariate regression was used to identify predictors of 5-year recurrence. Restaging transurethral resection was performed in 894 patients (87.5%). At restaging resection viable tumor was found in 496 patients (55.5%). At 3 months patients with a single resection had a 44.3% recurrence rate compared to 9.6% in those with restaging resection (p <0.01). On multivariate analysis a single transurethral resection was the only predictor of recurrence at 5 years (OR 2.1, 95% CI 1.3-3.3, p = 0.01). Time to recurrence in patients with a single resection was significantly shorter than in those with restaging resection (median 22 vs 36 months, p <0.001). Failure to repeat resection before initiating intravesical bacillus Calmette-Guérin therapy for high risk nonmuscle invasive bladder cancer significantly increases the risk of recurrence. Therefore, we believe that restaging resection should be performed before initiating bacillus Calmette-Guérin therapy in all patients with high risk nonmuscle invasive bladder cancer.

P-313 Response and progression rate of patients with primary MDS and isolated del(5q), IPSS low/int1 under treatment with lenalidomide

P-313 Response and progression rate of patients with primary MDS and isolated del(5q), IPSS low/int1 under treatment with lenalidomide

Citicoline Oral Solution in Glaucoma: Is There a Role in Slowing Disease Progression?

Purpose: To assess the effect of citicoline on visual field rates of progression in patients with progressing glaucoma. Patients and Methods: Forty-one patients with a diagnosis of progressing glaucoma received citicoline in oral solution for 2 years. Included were patients with a disease progression of at least -1 dB/year (at MD, mean deviation) for at least 3 years before entering the study despite controlled intraocular pressure (IOP). Patients were followed with 4 visual field examinations per year for 2 years. Results: At baseline, the mean rate of progression was -1.1 (±0.7) dB/year despite the fact that the IOP had been below 18 mm Hg for at least 3 years. At study inclusion, the mean IOP was 15.5 (±2.6) mm Hg and the mean MD was -9.2 (±6.7) dB in the worst eye. Starting from the first cycle of treatment with citicoline, the mean rate of progression significantly changed to -0.15 (±0.3) dB/year at the end of the study (p = 0.01). Conclusions: This study seems to indicate that supplementation with citicoline might significantly slow down glaucomatous rates of progression.

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, recurrence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ(2) and I(2) tests were first calculated to assess the heterogeneity of the included trials. For P < 0.05 and I(2) > 50%, the assumption of homogeneity was deemed invalid, and the random-effects model was used; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted using Review manager (version 4.2.2.) from the Cochrane collaboration. Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a significantly higher overall survival rate (OR1-year = 2.96, 95%CI: 1.84-7.74, P < 0.001; OR2-year = 3.72, 95%CI: 1.24-11.16, P = 0.02; OR3-year = 2.65, 95%CI: 1.81-3.86, P < 0.001) and recurrence-free survival rate (OR3-year = 3.00, 95%CI: 1.75-5.13, P < 0.001; OR5-year = 2.26, 95%CI: 1.43-3.57, P = 0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR = 0.60, 95%CI: 0.42-0.88, P = 0.008) and there was no significant difference on major complications between two different kinds of treatment (OR = 1.20, 95%CI: 0.31-4.62, P = 0.79). Additionally, the meta-analysis data of subgroups revealed that the survival rate was significantly higher in patients with intermediate- and large-size HCC underwent RFA plus TACE than in those underwent RFA monotherapy; however, there was no significant difference between RFA plus TACE and RFA on survival rate for small HCC. The combination of RFA with TACE has advantages in improving overall survival rate, and provides better prognosis for patients with intermediate- and large-size HCC.

EFFICACY OF SEQUENTIAL BCG AND MITOMYCIN VERSUS MITOMYCIN ALONE FOR TREATMENT OF SUPERFICIAL BLADDER CANCER

A study to compare the efficacy and local toxicity of combining anticancer drugs immunotherapy and chemotherapy (Sequential BCG and mitomycin c) versus mitomycin alone in the treatment of superficial bladder cancer after complete transurethral resection. The study was designed as a prospective study done in Al-hussain Teaching Hospital in Thiqar from July 2007 to August 2010. After transurethral resection and multiple biopsies, eighty-three patients (62m, 21f) from 38-75 years old, suffering from primary superficial (Ta-T1) TCC of the bladder, were randomly assigned to receive intravesical instillations of Mitomycin C (MMC) alone for 41 patients, and the sequential BCG and Mitomycin c, for 42 patients (81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg Mitomycin c once a week for four weeks. The patients evaluated for complications and recurrence and progression rate, they have follow up cystoscope every 3 months for the 1st year then every 6 months for the 2nd year and then yearly . Mean follow-up time was 36 months. The main object of the study were evaluation of recurrence and progression rate and estimate the safety with evaluation of subjective and objective side effects and clinical complications. Of the 83 randomly assigned patients, the analysis demonstrated a significant statistical difference in the recurrence rate. Patients assigned sequential BCG and Mitomycin c had lower recurrence rate 16.6 % (7 patients) versus 29.2% (12 patients) in those assigned for Mitomycin c alone, the difference between groups 12.6%; The progression rate in patients assigned sequential BCG and Mitomycin c about 7 % (3 patients) versus 17 % (7 patients) in those assigned for Mitomycin c alone, the difference between groups 10%. However the side-effects were mainly localized to the bladder, the complications after the treatment more common in patients receive sequential BCG and Mitomycin c than in those receive Mitomycin c alone. Cystitis occur in about 35 patients (83%) in those receiving sequential BCG and Mitomycin c, and two patient 4.7 % developed fever and chills. While in patients receive Mitomycin alone the complications were less cystitis in 4 patients 10%, rash in about 3 patients (7%) and myelosuppression two patients 5%. Conclusion: In this series, sequential BCG and Mitomycin c appears to be more effective than Mitomycin c alone in the treatment of superficial bladder tumors at 36-month follow-up, despite an increased but acceptable local toxicity.This probably because the BCG-induced inflammation might increase the permeability of the bladder mucosa such that Mitomycin c can reach the target tissue more easily and exert its anticancer effect.

Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that a tertiary Gleason grade pattern 4 or 5 found in RP specimens has a negative impact on recurrence rate regarding biochemical relapse after radical prostatectomy. This is the first publication addressing clinical outcome in patients with a tertiary Gleason grade pattern 4 or 5 showing a negative influence on clinical failure rates. To investigate the impact of a tertiary Gleason grade (TGG) pattern 4 or 5 on clinical failure, as the presence of a TGG pattern 4 or 5 in radical prostatectomy (RP) specimens has been associated with biochemical failure. In all, 151 consecutive patients undergoing RP between 1985 and 2006 were reviewed, and 148 patients met study inclusion criteria. The RP specimens were pathologically re-examined and the presence of a TGG pattern 4 or 5 was recorded. The endpoint was clinical failure defined as local recurrence and/or development of metastasis at a mean follow-up of 108 months. Univariate analyses were performed using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Clinical failure was more likely among men with presence of a TGG pattern 4 or 5 than in men without a TGG pattern 4 or 5 (P= 0.006). In the subgroup of patients with Gleason score 7 the presence of a TGG 5 was significantly associated with clinical failure rate (P= 0.002). In patients with Gleason score <7 or >7, a TGG pattern 4 or 5 was not associated with increased failure rates. Multivariate Cox regression analyses in patients with Gleason score 7 showed that a TGG pattern 5 was a statistically significant predictor of clinical failure when adjusting for pathological stage, surgical margin status, extraprostatic extension and seminal vesicle invasion (hazard ratio 4.03, 95% confidence interval 1.72-9.46; P= 0.001). Further subgroup analyses showed that a TGG pattern 5 was associated with statistically higher clinical progression rates in patients with Gleason score 3 + 4 (P= 0.03). In patients with Gleason score 4 + 3, a TGG pattern 5 was associated with a trend towards a higher clinical progression rate, although this was not statistically significant (P= 0.189). A TGG pattern 4 or 5 is associated with decreased clinical recurrence-free survival in Gleason score 7.

Effect of Dose Fractionation on Pulmonary Complications during Total Body Irradiation

Total body irradiation (TBI) is an important component of conditioning regimens for Allogeneic bone marrow transplantation (BMT). Interstitial pneumonitis (IP) and other pulmonary disorders are known regimen-related complications. The incidence of IP is related to the dose rate and dose fractionation; however, there is a paucity of clinical data regarding the optimal dose fractionation. This retrospective study evaluated patients to determine the influence of dose fractionation during TBI in preparation for allogeneic BMT on the subsequent development of IP and other pulmonary complications. Fifty-six patients were treated with TBI followed by BMT at our institute. All patients received a total TBI dose of 12 Gy given in 6 fractions over 3 days or in 4 fractions over 2 days. The prevalence of unrelated donors in the 4-fraction group was higher than that in the 6-fraction group. The overall and freedom from progression rates for patients in the 4-fraction group were better than those for patients in the 6-fraction group, but the difference did not reach significance. Clinically significant lung complications occurred in 19 (10: infectious and 9: non-infectious diseases) of 33 patients in the 6-fraction group and 12 (7: infectious and 5: non-infectious diseases) of 23 in the 4-fraction group. There was no significant difference between the two groups. There was no significant difference in pulmonary complications between patients treated with a TBI dose of 12 Gy in 6 fractions over 3 days and patients treated with a TBI dose of 12 Gy in 4 fractions over 2 days.

Is There Any Difference in Target Intraocular Pressure for Exfoliative Glaucoma Patients with Cardiovascular Disease History?

To investigate if patients with exfoliation glaucoma (XFG) with cardiovascular disease (CVD) require different target intraocular pressure (IOP) compared to patients with XFG with no CVD for long-term stability. A retrospective, multicenter, observational cohort analysis included consecutive patients with XFG from 9 European academic centers, with a minimum of 5 years follow-up. In 201 patients, there was a statistical difference between progressed and non-progressed patients in mean (p=0.0049) and peak (p=0.015) IOP, variance of IOP (p=0.028), and number of medicine changes/year (p=0.0037). At a mean IOP ≥22 mmHg, patients progressed in 84% (32/38), between 14 and 21 mmHg in 54% (81/151), and at ≤13 mmHg in 33% (4/12). There was no difference in the rate of progression between groups based on CVD history (p=0.65). However, IOP that allowed ≤50% progression rate for patients with mild or no CVD was ≤20-21 mmHg and ≤18 mmHg for patients with severe disease. Further, at IOP ≥20 mmHg, 8% (1/12) of patients with severe CVD remained stable in contrast to 38% (16/42) of patients with mild and 21% (4/19) with no CVD history (p=0.0093). By multivariant regression analysis of the IOP and CVD measures, mean IOP was a risk factor for progression (p=0.0097). Although IOP is the main determinant of progression in XFG under treatment, history of severe CVD should be further investigated as potential risk factor for glaucomatous progression.

Rates of CNS progression in patients with advanced NSCLC harboring somatic EGFR mutations and treated with gefitinib or erlotinib.

7543 Background: Gefitinib and erlotinib can penetrate into the CNS and elicit intracranial responses. However, there is incomplete data about their impact on the development and control of CNS metastases. The experience at DFCI was reviewed to determine the risk of CNS progression in patients with somatic EGFR mutations and advanced NSCLC treated initially with gefitinib or erlotinib. Methods: We identified patients with stage IIIB or IV NSCLC with somatic EGFR mutations treated with gefitinib or erlotinib as their initial therapy for advanced NSCLC between 1/01 and 2/09. The cumulative risk of brain relapse was calculated using death as a competing risk. Results: Of the 100 eligible patients, 19 had brain metastases (BM) at the time of diagnosis of advanced NSCLC; 17 of them received CNS therapy before initiating gefitinib or erlotinib. To date, 83 patients have progressed after a median potential follow-up of 41.3 months. The median progression-free survival for the entire cohort was 13.2 months. 28 pa...

The Role of Tumor-Free Status in Repeat Resection Before Intravesical Bacillus Calmette-Guerin for High Grade Ta, T1 and CIS Bladder Cancer

We evaluated the outcome of repeat transurethral bladder tumor resection for high risk nonmuscle invasive bladder cancer before induction and maintenance bacillus Calmette-Guerin. Included in the study were 151 consecutive patients with a mean age of 68.6 years (range 32 to 86) with primary high grade, nonmuscle invasive (Ta, T1 or CIS) bladder cancer. All patients underwent repeat transurethral bladder tumor resection and were shown by repeat resection to be tumor-free or have residual tumor before bacillus Calmette-Guerin. The bacillus Calmette-Guerin response was evaluated by disease recurrence and progression. A total of 70 tumor-free patients and 47 with residual tumor received bacillus Calmette-Guerin induction and maintenance therapy after repeat transurethral bladder tumor resection, of whom 84 (71.8%) were disease-free during followup. In the tumor-free group 11.4% of tumors recurred compared with 27.7% in the residual tumor group (p <0.05). Progression was noted in 5.7% of tumor-free cases vs 17.0% of residual tumor cases (p <0.05). Time to recurrence was significantly less in the residual tumor group than in the tumor-free group (17.8 vs 23.9 months, p <0.001). Tumor-free status at repeat transurethral bladder tumor resection improves the bacillus Calmette-Guerin response rate and delays tumor recurrence. During followup recurrence in residual tumor-free patients develop more likely as low grade lesions than in patients with residual tumor at repeat transurethral bladder tumor resection.

Impact of Routine Second Transurethral Resection on the Long-Term Outcome of Patients with Newly Diagnosed pT1 Urothelial Carcinoma with Respect to Recurrence, Progression Rate, and Disease-Specific Survival: A Prospective Randomised Clinical Trial

BackgroundTransurethral resection (TUR) of bladder tumours is not only mandatory for adequate staging but also crucial in delaying or preventing tumour recurrence and progression. ObjectiveTo evaluate the impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma. Design, setting, and participantsTwo hundred ten newly diagnosed T1 bladder cancer patients were prospectively randomised to two groups between January 2001 and January 2005. Second TUR was performed within 2–6 wk after the initial resection for the patients of group 1. Second TUR was not done in group 2. All patients (groups 1 and 2) received the first instillation of intravesical chemotherapy within 24h after the initial resection. Urine cytology and follow-up cystoscopy were performed at 3-mo intervals for the first year, biannually for the second year, and annually thereafter. All patients were followed until death or a minimum of 54 mo. MeasurementsThis study recorded recurrence, progression rate, and disease-specific survival. Results and limitationsThe mean follow-up period was 66.1 mo without a significant difference between the groups. Residual tumour was detected histopathologically in 35 of 105 patients in group 1. Of these patients, eight had upper-stage (pT2) disease. Recurrence was observed in 37 of the 93 patients in group 1 and 70 of the 98 patients in group 2. Median recurrence-free survival was 47 mo for group 1 compared with 12 mo for group 2. Progression was observed in 6.5% of patients for group 1 compared to 23.5% of patients for group 2 (p=0.001). Median progress-free survival was 73 mo for group 1 compared to 53.5 mo for group 2. The overall survival rate was 67.7% and 64.3% in groups 1 and 2, respectively (log-rank test result: 0.363). Only 5 of the 30 patients in group 1 died of cancer compared to 11 of the 35 patients in group 2 (p=0.038). ConclusionsWe have clearly shown that second TUR, which is performed only after complete first TUR, has significantly decreased the recurrence and progression rates in patients with newly diagnosed T1 disease compared to patients with T1 disease but with no second TUR. This study once more underscores the effect of TUR, which is usually underappreciated.

Progression markers of Spinocerebellar Ataxia 2. A twenty years neurophysiological follow up study

Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20 years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5 years prior disease onset and in the last 4 years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents.

Is T1G3 Bladder Cancer Having a Definite Muscle Layer in TUR Specimens a Highly Progressive Disease?

Patients with T1G3 bladder cancer are at high risk of progression to muscle-invasive cancer, and early cystectomy is considered as a treatment option in this particular situation. On the other hand, understaging of T1G3 bladder cancer has been gradually proven as second or repeat transurethral resection (TUR) has been widely applied. To evaluate the real rate of progression, we investigated the prognosis of T1G3 bladder cancer in which a muscle layer was histologically confirmed in the TUR specimens. We retrospectively reviewed 48 patients with primary T1G3 bladder cancer in which a muscle layer in the TUR specimens was confirmed between 1990 and 2006 in our institute. We investigated recurrence and progression in 45 patients, excluding 3 who were immediately treated with radical cystectomy. Fifteen and 12 patients received intravesical treatment with bacillus Calmette-Guérin (BCG) and anticancer agents just after TUR, respectively. The remaining 18 did not have any such treatment. Recurrence and progression were observed in 21 (47%) and 3 patients (6.7%), respectively, during a median follow-up period of 42.1 months. The 3-year recurrence-free and progression-free survival rates were 54% and 91%, respectively. No significant differences were observed in the rates between the patients with and without BCG treatment in the study. There is a possibility that the progression rate in patients with T1G3 bladder cancer is not as high as previously reported when only patients whose muscle layer was histologically confirmed were analyzed. An adequate technique for TUR that unmistakably collects the muscle layer may be important to predict the outcome accurately.

Analysis of the rate of non-target disease progression in patients with stable or responding target disease by the Response Evaluation Criteria in Solid Tumors (RECIST)

6603 Background: RECIST suggests progression of non-target disease is rare in patients with stable or responding target disease. We reviewed outcomes by RECIST to determine the rate of non-target (NT) progressive disease (PD). Methods: Outcomes of RECIST-based blinded independent central review (BICR) of 962 breast and colon cancer patients were used to identify 514 patients that had a progression event in order to determine the incidence of NT-PD. The radiographs of the 55 patients that had NT-PD were further reviewed by the authors (KB, RF) to confirm the NT-PD was “unequivocal.” To be considered unequivocal, there had to be a definite, substantial increase in the size of one or more metastatic NT lesions that was clearly not related to differences in imaging technique. To confirm the subjective nature of the “unequivocal progression,” the lesion(s) upon which PD was assessed was measured and a 20% increase in the lesion(s) since nadir was required. Results: Of the patients with PD, 11% (55/514) progressed only on worsening of NT disease. In 82% (45/55) of cases where the NT-PD was unequivocal, either the target disease was increasing but had not met the quantitative requirement for progression or the increase in NT disease would have resulted in target progression had the NT site(s) of disease been included with the baseline target lesions. Of the remaining 18% (10/55) where the two criteria described above did not apply, and an additional evaluation was performed, the next evaluation confirmed PD. Conclusions: Progression on the basis of NT disease can be reliably assessed if the target disease has started to increase from the nadir or if the increase in NT disease is significant enough to have resulted in target disease progression if classified as such. If one of the above criteria is not met, it is recommended that treatment continue until progression can be confirmed at the next evaluation. No significant financial relationships to disclose.