Independent Predictors Of Progression Research Articles

ECOG is as independent predictor of the response to chemotherapy, overall survival and progression-free survival in carcinoma of unknown primary site.

The aim of the present study was to determine whether age, gender, functional status, histology, tumor location, number of metastases, and levels of the tumor markers, lactate dehydrogenase (LDH) and albumin, are poor prognostic factors for the response to chemotherapy in patients with carcinoma of unknown primary site. A total of 149 patients diagnosed with carcinoma of unknown primary site that was histologically confirmed, and treated with chemotherapy in the Oncology Hospital, National Medical Center, ‘Century XXI’ IMSS, Mexico City, Mexico during the period between January 2002 to December 2009, were carefully selected for the present study. The analysis of 149 patients diagnosed with carcinoma of unknown primary site revealed that the liver was the organ with the highest frequency of metastases (33.5%). The objective response rates to chemotherapy were ~30.2%. Notably, ECOG was an important predictor of response to chemotherapy (P=0.008). The median progression-free survival was 7.1 months. Upon multivariate analysis, the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status was observed as an independent predictor of progression (P<0.0001). The median overall survival was 14.2 months. The ECOG was also an independent predictor of mortality (P<0.0001). In conclusion, the data from the present study have demonstrated that ECOG is an independent predictor of a poor response to chemotherapy, lower overall survival and progression-free survival in carcinoma of unknown primary site.

PcMab-47: Novel Antihuman Podocalyxin Monoclonal Antibody for Immunohistochemistry.

Podocalyxin (PODXL) is a CD34-related sialomucin and a well-known marker of embryonic stem cells. PODXL is expressed in many types of tumors including colorectal cancers, breast cancers, and brain tumors. Overexpression of PODXL is an independent predictor of progression, metastasis, and poor outcome. PODXL is also expressed in many normal cells such as renal podocytes and endothelial cells (ECs). However, high-sensitive and high-specific anti-PODXL monoclonal antibodies (mAbs) have not been established. Herein, we immunized mice with recombinant human PODXL, which was produced using LN229 glioblastoma cells. The anti-PODXL mAb, PcMab-47, reacted with endogenous PODXL-expressing cancer cell lines and normal cells independently of glycosylation in flow cytometry. Immunohistochemical analysis showed that PcMab-47 detected PODXL-expressing normal cells such as podocytes of kidney or ECs. Furthermore, PcMab-47 stained PODXL-expressing cancer cells of colon or breast cancers. These results suggest that PcMab-47 could be useful for investigating the expression and function of PODXL in cancers and normal tissues.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography.

BackgroundCoronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable.ObjectiveTo identify factors associated with CAD progression in patients undergoing sequential CCTA testing.MethodsWe retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression.ResultsFrom a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression.ConclusionsA history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Dynamic contrast-enhanced MR imaging in predicting progression of enhancing lesions persisting after standard treatment in glioblastoma patients: a prospective study.

To prospectively explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the progression of enhancing lesions persisting after standard treatment in patients with surgically resected glioblastoma (GBM). Forty-seven GBM patients, who underwent near-total tumorectomy followed by concurrent chemoradiation therapy (CCRT) with temozolomide (TMZ) between May 2014 and February 2016, were enrolled. Twenty-four patients were finally analyzed for measurable enhancing lesions persisting after standard treatment. DCE-MRI parameters were calculated at enhancing lesions. Mann-Whitney U tests and multivariable stepwise logistic regression were used to compare parameters between progression (n = 16) and non-progression (n = 8) groups. Mean Ktrans and ve were significantly lower in progression than in non-progression (P = 0.037 and P = 0.037, respectively). The 5th percentile of the cumulative Ktrans histogram was also significantly lower in the progression than in non-progression group (P = 0.017). Mean ve was the only independent predictor of progression (P = 0.007), with a sensitivity of 100%, specificity of 63%, and an overall accuracy of 88% at a cut-off value of 0.873. DCE-MRI may help predict the progression of enhancing lesions persisting after the completion of standard treatment in patients with surgically resected GBM, with mean ve serving as an independent predictor of progression. • Enhancing lesions may persist after standard treatment in GBM patients. • DCE-MRI may help predict the progression of the enhancing lesions. • Mean K trans and v e were lower in progression than in non-progression group. • DCE-MRI may help identify patients requiring close follow-up after standard treatment. • DCE-MRI may help plan treatment strategies for GBM patients.

Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609.

Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.

Abstract 2958: A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity

Abstract Background: Podocalyxin (PODXL) is a CD34-related sialomucin and a well-known marker of embryonic stem cells. PODXL is expressed in many cancers including brain tumors, breast cancers, and colorectal cancers. Overexpression of PODXL is an independent predictor of progression, metastasis, and poor outcome. In contrast, PODXL is highly expressed in normal cells such as vascular endothelial cells (VECs) or renal podocytes. Although many monoclonal antibodies (mAbs) against PODXL have been established, they bind to both cancer and normal cells. We recently established CasMab technology for developing cancer-specific mAbs, which could target only cancer cells, although those membranous proteins are highly expressed in both cancer and normal cells. Methods: We immunized mice with human PODXL, which was overexpressed in a glioblastoma cell line. Cancer-specific mAbs were screened using flow cytometry against PODXL-expressing cancer and normal cells. The cancer specificity was confirmed using immunohistochemistry against breast cancer tissues. A mouse-human chimeric anti-PODXL mAb was produced and antibody-dependent cellular cytotoxicity (ADCC) was investigated in vitro. The in vivo efficacy of anti-PODXL mAbs was evaluated using xenograft models of PODXL-expressing cell lines. Results: One clone of anti-PODXL mAbs, which was established by CasMab technology, reacted with PODXL-expressing many cancer cell lines including breast cancers, brain tumors, and malignant mesotheliomas, whereas it did not bind to VECs in flow cytometry. The anti-PODXL mAb reacted only with PODXL-expressing cancer cells, not with VECs in breast cancer tissues in immunohistochemistry. Furthermore, the anti-PODXL mAb possesses ADCC activity in vitro and anti-tumor effect in vivo. Conclusion: The anti-PODXL mAb established by CasMab technology could be useful for targeting PODXL in cancer, although PODXL is highly expressed in many normal cells. Citation Format: Yukinari Kato, Satoshi Ogasawara, Akiko Kunita, Yuki Fujii, Mika K. Kaneko. A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2958.

Evolving changes in disease biomarkers and risk of early progression in smoldering multiple myeloma.

We studied 190 patients with smoldering multiple myeloma (SMM) at our institution between 1973 and 2014. Evolving change in monoclonal protein level (eMP) was defined as ⩾10% increase in serum monoclonal protein (M) and/or immunoglobulin (Ig) (M/Ig) within the first 6 months of diagnosis (only if M-protein ⩾3 g/dl) and/or ⩾25% increase in M/Ig within the first 12 months, with a minimum required increase of 0.5 g/dl in M-protein and/or 500 mg/dl in Ig. Evolving change in hemoglobin (eHb) was defined as ⩾0.5 g/dl decrease within 12 months of diagnosis. A total of 134 patients (70.5%) progressed to MM over a median follow-up of 10.4 years. On multivariable analysis adjusting for factors known to predict for progression to MM, bone marrow plasma cells ⩾20% (odds ratio (OR)=3.37 (1.30–8.77), P=0.013), eMP (OR=8.20 (3.19–21.05), P<0.001) and eHb (OR=5.86 (2.12–16.21), P=0.001) were independent predictors of progression within 2 years of SMM diagnosis. A risk model comprising these variables was constructed, with median time to progression of 12.3, 5.1, 2.0 and 1.0 years among patients with 0–3 risk factors respectively. The 2-year progression risk was 81.5% in individuals who demonstrated both eMP and eHb, and 90.5% in those with all three risk factors.

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Is the Extent of Septal Hypertrophy Important?

Hypertrophic cardiomyopathy (HCM) is a cardiac disease associated with a high incidence of atrial fibrillation (AF). Recent studies have suggested that interventricular septum thickness may influence the risk stratification of patients with AF. We evaluated the effects of septal hypertrophy on morbidity and mortality in patients with HCM. Patients were followed for a median of 6.1 years and were divided into two groups according to the extent of septal hypertrophy. A total of 1,360 HCM patients were enrolled: 482 (33%) apical or apicoseptal, 415 (28%) asymmetric septal, 388 (27%) basal septal, 38 (2.6%) concentric, and 37 (2.5%) diffuse and mixed type. Ninety-two all-cause deaths and 21 cardiac deaths occurred. The total event rates were significantly higher for patients with HCM with more extensive septal hypertrophy (group A) compared to those with HCM ± focal septal hypertrophy (group B), regardless of type (p<0.001). Arrhythmias occurred in 502 patients, with a significantly higher incidence in group A than in group B (p<0.001). Among patients with arrhythmias, the incidence of AF was significantly higher in group A than group B (p<0.001). In univariate Cox analysis, a greater extent of septal hypertrophy (p<0.001), E/E´ ratio (p = 0.011), and mitral regurgitation grade (p = 0.003) were significantly associated with developing AF. In multivariate Cox analyses, a greater extent of septal hypertrophy [odds ratio (OR) 5.44 (2.29–12.92), p<0.001] in patients with HCM was significantly associated with developing AF. In conclusion, a greater extent of septal hypertrophy is an independent predictor of progression to AF in patients with HCM.

Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort

Rates of progression to esophageal adenocarcinoma in subjects with Barrett's esophagus (BE) are lower than previously estimated. Identification of predictors of progression will enable risk stratificationofBE subjects, potentially making current surveillance programs more efficient. We aimed to assess the potential ofdemographic and lifestyle factors, obesity, and medications in predicting progression in BE. BE subjects were identified from the General Practice Research Database using validated diagnostic codes. BE subjects developing esophageal cancer (EC) 12 months after their index BE diagnosis were defined as progressors. Time-to-event analysis was used to assess the overall risk of progression to EC. Cox proportional hazards models and time-varying marginal structural models were used to assess predictors of progression. Included in the analysis were 9660 BE patients. The mean age (SD) of the study subjects was 63 (13.5) years; 62.6% were men. One hundred three subjects (1.1%) progressed to EC. The mean (SD) follow-up since initial diagnosis was 4.8 (3.3) years. The incidence of EC was 2.23 per 1000 person-years of follow-up. Increasing age, male gender, and being overweight (body mass index, 25-29.9) were found to be independent predictors of progression. When time-varying models were used, proton pump inhibitor (PPI) and statin use were protective against progression. In this large population-based cohort of patients with BE, increasing age, male gender, and being overweight predicted progression to EC, whereas PPI and statin use were protective against EC development. These factors may aid in developing a risk score to predict the risk of progression and chemopreventive strategies in patients with BE.

Cumulative Incidence and Predictors of Progression in Corticosteroid-Naïve Patients with Sarcoidosis.

BackgroundAssessment of the clinical course of sarcoidosis requires long-term observation. However, the appropriate period of follow-up for sarcoidosis remains unclear, especially in patients without indication of corticosteroid therapy at the time of diagnosis.ObjectiveThis study aimed to clarify the cumulative incidence and identify risk factors for disease progression in corticosteroid-naïve sarcoidosis patients.MethodsThe clinical courses of 150 Japanese patients with sarcoidosis, who were followed for more than 2 years and had no indication for corticosteroid therapy at diagnosis, were retrospectively reviewed. Disease progression was defined as worsening of pulmonary sarcoidosis, development of new organ involvement, or extrapulmonary organ damage. The cumulative incidence of progression was estimated by generating a cumulative incidence curve with the Fine and Gray method.ResultsThe median follow-up duration was 7.7 years (interquartile range, 4.7–13.6 years). Thirty-two (21%) patients experienced disease progression. New organ involvement appeared in 16 patients (11%). The 6-month, and 1-, 5-, 10-, and 15-year cumulative incidence of progression was 2%, 5%, 15%, 28%, and 31%, respectively. The number of organs involved at diagnosis was an independent predictor for progression with a multifactorial adjusted hazard ratio of 1.71 (95% confidence interval, 1.11–2.62). The optimal cut-off of the number of organs involved at diagnosis to identify future progression was three.ConclusionsIn corticosteroid-naïve sarcoidosis patients, the risks of disease progression are comparable from 0–5 years and 5–10 years after diagnosis. The number of organs involved at diagnosis is a useful predictor for progression of sarcoidosis.

Predicting progressive hemorrhagic injury from isolated traumatic brain injury and coagulation

Progressive hemorrhagic injury (PHI) in traumatic brain injury (TBI) patients is associated with poor outcomes. Early prediction of PHI is difficult yet vital. We hypothesize that TBI subtype and coagulation would be predictors of PHI. This was a retrospective analysis of highest level activation adult trauma patients with evidence of TBI (head Abbreviated Injury Scale ≥3). Coagulopathy was determined using rapid thrombelastography (r-TEG), complete blood counts, and conventional coagulation tests obtained on arrival. Patients were dichotomized into PHI and stable groups based on head computerized CT. Subtypes of TBI included subdural hematoma, intraparenchymal contusions (IPC), subarachnoid hemorrhage, epidural hematoma, and combined. Data are reported as median values with interquartile range (IQR). Multivariate logistic regression was used to assess the effect of subtype and coagulation on PHI. We included 279 isolated TBI patients who met study criteria. There were 157 patients (56%) who experienced PHI; 122 (44%) were stable on repeat CT. Patients with PHI were older, had fewer hospital-free days, and higher mortality (all P<.001). No differences were noted in r-TEG parameters between groups; however, coagulopathy and age were independent predictors of progression in all subtypes (odds ratio [OR], 1.81; 95% CI, 1.09-3.01 [P=.021]; OR, 1.02, 95% CI, 1.01-1.04 [P=.006]). Controlling for age, Glasgow Coma Scale score, and coagulopathy, patients with IPC were more likely to experience PHI (OR, 4.49; 95% CI, 2.24-8.98; P<.0001). This study demonstrates that older patients with coagulation abnormalities and IPC on admission are more likely to experience PHI, identifying a target population for earlier therapies.

Percutaneous Coronary Intervention Rates and Associated Independent Predictors for Progression of Nontarget Lesions in Patients With Diabetes Mellitus After Drug-Eluting Stent Implantation.

Little is known about clinically driven percutaneous coronary intervention (PCI) rates and predictors for progression of nontarget lesions in diabetic patients who have undergone drug-eluting stent (DES) implantation. We retrospectively analyzed the clinical and angiographic data of 2187 diabetic patients undergoing DES implantation. The cumulative rate of nontarget lesion PCI was 6.3% at 1 year, 14.3% at 2 years, and 19.8% at 3 years. The independent predictors of need for clinically driven PCI in patients with diabetes mellitus after DES implantation included obesity (odds ratio [OR] 2.303, 95% confidence interval [CI] 1.657-3.199, P < .001), low levels of high-density lipoprotein cholesterol (OR 1.412, 95% CI 1.114-1.789, P = .004), statin use (OR 0.669, 95% CI 0.454-0.986, P = .042), insulin use (OR 1.310, 95% CI 1.030-1.665, P = .027), and Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (OR 1.061, 95% CI 1.045-1.077, P < .001) at baseline PCI. These findings may facilitate prediction of the risk of repeat revascularization and improve repeat revascularization rates in diabetic patients after DES implantation.

Exploration of risk factors predicting outcomes for primary T1 high-grade bladder cancer and validation of the Spanish Urological Club for Oncological Treatment scoring model: Long-term follow-up experience at a single institute.

To determine the prognostic factors of primary T1 high-grade bladder cancer and to validate the Spanish Urological Club for Oncological Treatment model in Japanese patients with T1 high-grade bladder cancer treated at a single institution. Records of 106 patients with T1 high-grade bladder cancer treated from 1998 to 2013 were retrospectively reviewed. Variables included various clinicopathological parameters, including lymphovascular invasion and tumor growth pattern at the invasion front. Recurrence-free survival and progression-free survival were analyzed. Multivariate Cox proportional regression analysis was used to verify the prognostic significance of the variables. Scores for recurrence and progression were calculated using the Spanish Urological Club for Oncological Treatment model. Of 106 patients, 44 (42%) had recurrence and 16 (15%) developed progression after a median (interquartile range) follow-up period of 54 months (range 32-81 months). Non-papillary shape was the only independent predictor for recurrence, while broad-based tumor stalk and infiltrative tumor growth pattern at the invasion front were determined to be independent predictors for progression. Stratification of patients according to the number of progression risk factors yielded hazard ratios of 10.1 and 13.1 in patients having one and two risks, respectively, compared with those without any risks. The Spanish Urological Club for Oncological Treatment model successfully stratified our patients with a trend toward different probabilities of recurrence and progression. The results of the present study might be helpful for counseling certain patients towards intensive treatment, such as radical cystectomy and/or platinum-based systemic chemotherapy. In addition, the Spanish Urological Club for Oncological Treatment model might be applicable to Japanese patients with T1 high-grade bladder cancer.

Stratification based on methylation of TBX2 and TBX3 into three molecular grades predicts progression in patients with pTa-bladder cancer

The potential risk of recurrence and progression in patients with non-muscle-invasive bladder cancer necessitates followup by cystoscopy. The risk of progression to muscle-invasive bladder cancer is estimated based on the European Organisation of Research and Treatment of Cancer score, a combination of several clinicopathological variables. However, pathological assessment is not objective and reproducibility is insufficient. The use of molecular markers could contribute to the estimation of tumor aggressiveness. We recently demonstrated that methylation of GATA2, TBX2, TBX3, and ZIC4 genes could predict progression in Ta tumors. In this study, we aimed to validate the markers in a large patient set using DNA from formalin-fixed and paraffin-embedded tissue. PALGA: the Dutch Pathology Registry was used for patient selection. We included 192 patients with pTaG1/2 bladder cancer of whom 77 experienced progression. Methylation analysis was performed and log-rank analysis was used to calculate the predictive value of each methylation marker for developing progression over time. This analysis showed better progression-free survival in patients with low methylation rates compared with the patients with high methylation rates for all markers (P<0.001) during a followup of ten-years. The combined predictive effect of the methylation markers was analyzed with the Cox-regression method. In this analysis, TBX2, TBX3, and ZIC4 were independent predictors of progression. On the basis of methylation status of TBX2 and TBX3, patients were divided into three new molecular grade groups. Survival analysis showed that only 8% of patients in the low molecular grade group progressed within 5 years. This was 29 and 63% for the intermediate- and high-molecular grade groups. In conclusion, this new molecular-grade based on the combination of TBX2 and TBX3 methylation is an excellent marker for predicting progression to muscle-invasive bladder cancer in patients with primary pTaG1/2 bladder cancer.

PD17-07 IMPACT OF BLADDER NECK INVOLVEMENT ON PROGRESSION IN PATIENTS WITH PRIMARY NON-MUSCLE-INVASIVE BLADDER CANCER: A MULTICENTER VALIDATION STUDY

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2015PD17-07 IMPACT OF BLADDER NECK INVOLVEMENT ON PROGRESSION IN PATIENTS WITH PRIMARY NON-MUSCLE-INVASIVE BLADDER CANCER: A MULTICENTER VALIDATION STUDY Yasuhisa Fujii, Shingo Moriyama, Minato Yokoyama, Junji Yonese, Akira Noro, Chizuru Arisawa, Shinji Morimoto, Tetsuo Okuno, Satoshi Kitahara, Fumitaka Koga, Yasuyuki Sakai, Masahito Suzuki, Katsushi Nagahama, Toshifumi Izutani, Kazutaka Saito, and Kazunori Kihara Yasuhisa FujiiYasuhisa Fujii More articles by this author , Shingo MoriyamaShingo Moriyama More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , Junji YoneseJunji Yonese More articles by this author , Akira NoroAkira Noro More articles by this author , Chizuru ArisawaChizuru Arisawa More articles by this author , Shinji MorimotoShinji Morimoto More articles by this author , Tetsuo OkunoTetsuo Okuno More articles by this author , Satoshi KitaharaSatoshi Kitahara More articles by this author , Fumitaka KogaFumitaka Koga More articles by this author , Yasuyuki SakaiYasuyuki Sakai More articles by this author , Masahito SuzukiMasahito Suzuki More articles by this author , Katsushi NagahamaKatsushi Nagahama More articles by this author , Toshifumi IzutaniToshifumi Izutani More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , and Kazunori KiharaKazunori Kihara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.664AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously reported that bladder neck involvement (BNI) as well as tumor grade and stage was an independent risk factor for progression in primary non-muscle-invasive bladder cancer (NMIBC) in retrospective and prospective cohorts at a single institute (TMDU), and proposed a simple predictive scoring model for progression, consisting of tumor grade, stage and BNI, all of which were scored as one point, contributing equally to the model (Fujii et al., Eur Urol 1998; Kobayashi and Fujii et al., Urol Oncol 2014). In this study, we externally validated the impact of BNI on progression in NMIBC and the predictive ability of the scoring model using a large multicenter cohort. METHODS A total of 1335 Japanese patients who underwent transurethral resection for primary bladder tumors at 11 institutions not including TMDU between 2006 and 2010 and were pathologically diagnosed with Ta and T1 NMIBC were enrolled. We excluded patients with primary carcinoma in situ and patients with tumors located in the prostate urethra. Multivariate Cox proportional hazards regression models were used to identify the independent predictors for progression. The predictive ability of our model was assessed using Harrell's c-index. RESULTS Over a median follow-up of 48 months, 64 patients (4.8%) progressed. Progression probabilities at one and five years were 2.0% and 6.0%, respectively. Multivariate analysis revealed that tumor grade (HR 2.40, P=0.0012), stage (HR 2.69, P=0.0008) and BNI (HR 1.82, P=0.0315) were independent predictors of progression. Of the 248 patients with BNI, 21 (8.5%) progressed. When the patients were divided into three groups according to their score on our predictive model (0, 1 and 2–3 points), the groups had significantly different progression rates (P<0.0001). The c-index of the model was 0.597. CONCLUSIONS In this multicenter validation study, BNI is confirmed as a significant prognostic factor for progression in primary NMIBC. Our scoring model incorporating BNI is an easy means of estimating progression risk and can be used to determine the appropriate adjuvant treatment and follow-up procedures for individual patients. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e383-e384 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhisa Fujii More articles by this author Shingo Moriyama More articles by this author Minato Yokoyama More articles by this author Junji Yonese More articles by this author Akira Noro More articles by this author Chizuru Arisawa More articles by this author Shinji Morimoto More articles by this author Tetsuo Okuno More articles by this author Satoshi Kitahara More articles by this author Fumitaka Koga More articles by this author Yasuyuki Sakai More articles by this author Masahito Suzuki More articles by this author Katsushi Nagahama More articles by this author Toshifumi Izutani More articles by this author Kazutaka Saito More articles by this author Kazunori Kihara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prognostic significance of lymphovascular space invasion in epithelial ovarian cancer.

Object: To assess the effects of lymphovascular space invasion (LVSI) on cancer recurrence and survival in patients with primary epithelial ovarian cancer.Methods: A retrospective study was conducted of patients with stage I-IV primary epithelial ovarian cancer who underwent cytoreductive surgery. LVSI is defined as the presence of tumor cells within an endothelium-lined space, and the patients' pathologic slides were reevaluated by gynecological pathologists. Survival analysis was performed to compare risk factors.Results: A total of 492 patients were included in the analysis. The incidence of LVSI was 58.5% in our cohort (288 cases), and it was significantly associated with advanced stage, high-grade serous histology, high grade, and lymph node metastasis (P<0.001). Kaplan-Meier analysis demonstrated that LVSI was only correlated with decreased PFS (5-year rate, 39% vs. 66%, P<0.001) and OS (5-year rate, 44% vs. 78%, P<0.001) in patients at early stage but not at advanced stage (5-year rate, PFS: 14% vs. 11%, P<0.001; OS: 29% vs. 29%, P=0.141). Multivariate analysis showed that LVSI remained a significant variable with PFS and OS in early-stage ovarian cancer (PFS: HR 2.29, 95% CI 1.45-3.57; OS: HR 2.20, 95% CI 1.59-3.44, both P<0.001).Conclusion: LVSI is an independent predictor of progression and survival in patients with primary epithelial ovarian cancer at early stage but not at advanced stage.

Multicenter evaluation of the role of UroVysion FISH assay in surveillance of patients with bladder cancer: does FISH positivity anticipate recurrence?

The significance of a positive UroVysion FISH assay is uncertain in patients with normal cystoscopy. This multicenter study evaluates the clinical significance of a positive FISH assay in patients with no visible tumor and excluding those with a positive cytology. A multi-institutional, retrospective study of patients with a history of urothelial carcinoma of the bladder identified 664 patients with a FISH assay after excluding those with cystoscopic evidence of a tumor and/or positive cytology. Our primary end point was cancer recurrence, defined by biopsy. Progression was defined as recurrence with a tumor stage ≥T2. Statistical analyses were performed using Fisher's exact test as a one-tailed test and Chi-square test with significance at 0.05, using SPSS(®) version 19.0 (SPSS Inc., Chicago, IL, USA). Of the 664 patients in this study, tumor stage was Ta (363, 55 %), T1 (183, 28 %), and CIS (109, 16 %) and most were high grade (440 pts, 66 %). The median follow-up was 26 months (3-104 months), and 277 (41.7 %) patients were recurred. In patients who were FISH positive, mean time to recurrence was 12.6 months, compared to 17.9 months if FISH negative (p = 0.03). In univariate analysis, atypical cytology, positive FISH, cystoscopic findings (atypical vs. normal), and previous intravesical therapy were associated with recurrence (p < 0.05). On multivariate analysis, pathologic stage, cystoscopic findings, and cytology were independently associated with recurrence (p < 0.05). Progression to ≥T2 disease occurred in 34 (5.1 %) patients in this cohort. On multivariate analysis, only initial T stage and FISH result were found to be independent predictors of progression (p < 0.05). Patients with a positive FISH and atypical cytology are more likely to recur even in the absence of visible tumor. FISH positivity may portend a higher risk for progression. These findings require prospective validation.

Molecular subtyping of bladder cancer using Kohonen self-organizing maps.

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering.

Thromboembolic events in patients with urothelial carcinoma undergoing neoadjuvant chemotherapy and radical cystectomy

ObjectivesPatients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy. Methods and materialsWe analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival. ResultsOf 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39–8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92–6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34–11.45). The main limitations of our study are its retrospective data collection and small absolute number of events. ConclusionsTEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.