Association between primary tumor site, perioperative CEA ratio, smoking status, and overall survival in patients with colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15156-e15156
Author(s):  
Thomas A Odeny ◽  
Nicole Farha ◽  
Hannah Hildebrand ◽  
Jessica Allen ◽  
Wilfred Vazquez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Tumor Stage ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Primary Tumor Site

e15156 Background: There are differences in the incidence, clinical presentation, molecular pathogenesis and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between tumor location, CEA ratio, smoking status and overall survival (OS) among patients with CRC. Methods: We analysed 323 patients who underwent resection for CRC at KUMC. After excluding those without pre- or post-operative CEA data, 162 patients were classified as either high ( > = 0.5) or low ( < 0.5) ratio. Primary outcomes were: 1) OS stratified by tumor location; 2) OS stratified by CEA ratio; and 3) whether the association between CEA ratio and OS differed by tumor location, after adjusting for stage and smoking status. Kaplan-Meier method was used to estimate survival rates, and Cox proportional hazards models for multivariate analysis. Results: The median age was 63 years (inter-quartile range 53-72), 61% male, 43% smokers, 73% left-sided tumors, median pre-operative CEA was 3.0 (IQR 1.5-7), and 64% had CEA ratio > = 0.5. The OS rates were 85.7% and 91.9% in patients with left-sided vs right-sided tumors respectively (log-rank p-value = 0.9). The OS rates were 83.5% and 91.5% in patients with high vs low CEA ratios respectively (log-rank p-value = 0.3). The effect of CEA ratio on OS was significantly different when stratified by tumor location (p-value for interaction < 0.001). However, in the stratified analysis, the n was too small to permit further inferential analysis. In multivariate analysis, both tumor location (HR 0.6; p = 0.5) and CEA ratio (HR 1.5; p = 0.5) were not significantly associated with OS after adjusting for smoking status and tumor stage. Smoking was significantly associated with higher rates of death (HR 3.9; p = 0.04) when adjusted for tumor location, CEA ratio, and tumor stage. Conclusions: There was no difference in OS between left versus right-sided tumors. The association between CEA ratio and OS was significantly modified by tumor location. However, to attribute this modification to left vs right warrants validation in a larger cohort as our sample size was limited. Smoking increases mortality irrespective of right vs left sided CRC.

Association between primary tumor site, perioperative CEA ratio, and overall survival in patients with colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 518-518
Author(s):  
Thomas A Odeny ◽  
Nicole Farha ◽  
Wilfred Vazquez ◽  
Amna Batool ◽  
Anwaar Saeed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Smoking Status ◽  
Tumor Stage ◽  
Tumor Location ◽  
Effect Modification ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Primary Tumor Site

518 Background: There are differences in the incidence, clinical presentation, molecular pathogenesis and outcome of colorectal cancer (CRC) based on the tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio is a prognostic factor for CRC patients. We aimed to determine the association between tumor location, perioperative CEA ratio, and 5-year survival among patients with CRC. Methods: We analyzed 111 patients who underwent resection for CRC at KUMC. After excluding patients without pre- or post-operative CEA data, 62 patients for whom we could calculate a CEA ratio (post-op/pre-op CEA) were classified as either high ( ≥ 0.5) or low ( < 0.5) ratio. The primary outcomes were: 1) overall survival (OS) stratified by tumor location; 2) OS stratified by CEA ratio; and 3) whether there was effect modification by tumor location, of the association between perioperative CEA ratio and OS, after adjusting for tumor stage and smoking status. Kaplan-Meier method was used to estimate survival rates, and Cox proportional hazards models for multivariate analysis. Results: The median age was 61 years, 54% male, 31% smokers, 74% left-sided tumors, median pre-operative CEA was 3.3, and 60% had CEA ratio ≥ 0.5. The OS rates were 89.1% and 81.3% in patients with left-sided versus right-sided tumors respectively (p-value = 0.4). The OS rates were 83.8% and 92.0% in patients with high versus low CEA ratios respectively (p-value = 0.3). There was effect modification by tumor location on association between CEA ratio and OS, after adjusting for smoking status and tumor stage (p-value < 0.001). However, in the stratified analysis, the n was too small to permit inferential analysis. In multivariate analysis, both tumor location (HR 0.4; p = 0.3) and perioperative CEA ratio (HR 2.7; p = 0.3) were not significantly associated with OS after adjusting for smoking status and tumor stage. Conclusions: There was no difference in OS between left versus right-sided tumors. The association between perioperative CEA ratio and OS was significantly modified by tumor location. However, to attribute this modification to left versus right warrants validation in a larger cohort as our sample size was limited.

scholarly journals Nomogram to Predict the Overall Survival of Colorectal Cancer Patients: A Multicenter National Study

2021 ◽  
Vol 18 (15) ◽  
pp. 7734
Author(s):  
Nasrin Borumandnia ◽  
Hassan Doosti ◽  
Amirhossein Jalali ◽  
Soheila Khodakarim ◽  
Jamshid Yazdani Charati ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Family History ◽  
Clinical Decision Making ◽  
Proportional Hazards ◽  
Clinical Decision ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
National Study ◽  
Historical Cohort

Background: Colorectal cancer (CRC) is the third foremost cause of cancer-related death and the fourth most commonly diagnosed cancer globally. The study aimed to evaluate the survival predictors using the Cox Proportional Hazards (CPH) and established a novel nomogram to predict the Overall Survival (OS) of the CRC patients. Materials and methods: A historical cohort study, included 1868 patients with CRC, was performed using medical records gathered from Iran’s three tertiary colorectal referral centers from 2006 to 2019. Two datasets were considered as train set and one set as the test set. First, the most significant prognostic risk factors on survival were selected using univariable CPH. Then, independent prognostic factors were identified to construct a nomogram using the multivariable CPH regression model. The nomogram performance was assessed by the concordance index (C-index) and the time-dependent area under the ROC curve. Results: The age of patients, body mass index (BMI), family history, tumor grading, tumor stage, primary site, diabetes history, T stage, N stage, and type of treatment were considered as significant predictors of CRC patients in univariable CPH model (p < 0.2). The multivariable CPH model revealed that BMI, family history, grade and tumor stage were significant (p < 0.05). The C-index in the train data was 0.692 (95% CI, 0.650–0.734), as well as 0.627 (0.670, 0.686) in the test data. Conclusion: We improved a novel nomogram diagram according to factors for predicting OS in CRC patients, which could assist clinical decision-making and prognosis predictions in patients with CRC.

scholarly journals Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Models ◽  
Proportional Hazards ◽  
Treatment Decision ◽  
Tumor Stage ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
Men And Women ◽  
Logistic Regression Models ◽  
Comorbidity Index

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

scholarly journals Eps15 Homology Domain-Containing Protein 3 Hypermethylation as a Prognostic and Predictive Marker for Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 453
Author(s):  
Yu-Han Wang ◽  
Shih-Ching Chang ◽  
Muhamad Ansar ◽  
Chin-Sheng Hung ◽  
Ruo-Kai Lin
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Uterine Cancer ◽  
Colonic Polyps ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Eps15 Homology Domain

Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, Eps15 homology domain-containing protein 3 (EHD3) had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, EHD3 hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low EHD3 mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, EHD3 hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, EHD3 hypermethylation contributes to the development of CRC in both Asian and Western populations.

scholarly journals A novel nomogram to predict the overall survival in esthesinoeroblastoma

2020 ◽  
Author(s):  
Lijie Jiang ◽  
Tengjiao Lin ◽  
Yu Zhang ◽  
Wenxiang Gao ◽  
Jie Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
P Value ◽  
Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

Neutrophils lymphocyte ratio role in predicting response to checkpoint inhibitors in metastatic non-small lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20646-e20646
Author(s):  
Hosam Hakim ◽  
Ahmed Abdalla ◽  
Tarik H. Hadid
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Immune Therapy ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Lymphocyte Ratio ◽  
Metastatic Nsclc

e20646 Background: There have been numerous advances in the management of metastatic lung cancer, including targeted therapy against certain mutations in cancer cells and later developing immune therapy with check point inhibitors.From the pre-immune therapy era, a simple blood test allowing the calculation of the neutrophil-to-lymphocyte ratio (NLR) was established as a strong prognostic marker associated with worse overall survival (OS) in several tumor types including non-small cell lung cancer (NSCLC). Methods: We have retrospectively reviewed electronic medical records for patients with Metastatic NSCLC whom received at least one dose of Checkpoint Inhibitors from January 2014 till January 2019 in Van Eslander Cancer Center.The analysis was done using SPSS v. 25.0 and a p-value of 0.05 or less was considered to indicate statistical significance. A univariant analysis was done using Student’s t-test, the Mann-Whitney U test and the chi-squared test. Survival analysis was conducted using Kaplan Meier methodology as well as Cox proportional hazards models. Results: There were 80 patients with metastatic NSCLC received at least one dose of a checkpoint inhibitor. Median age was 63.9 ± 9.3; Males were 45%; Whites were 62.5%. 67.5% of patient had adenocarcinoma and 24% had squamous cell carcinoma. Twenty patients had brain metastasis (25%) and nineteen patients had liver metastasis (24.6%). Eleven patients (13.8%) had PDL-1 greater than 50% and 11 patients (13.8%) had PDL-1 between 1%-50% and 22 patients (27.5%) had negative PD-L1 status. 18.8% received immunotherapy as a first-line treatment and 65% got immunotherapy on their second line and 16.3% had immunotherapy as the third line of treatment or more. Sixty-one patients (76.2%) received Nivolumab and nineteen patients (23.8%) received pembrolizumab. Mean duration of immunotherapy was 13.7 months ± 20.7. Mean NLR was 6.1 ± 5. Patient with NLR > 5:1 had statistically significant higher progression-free survival (PFS) 27.5 months compared to 12 months P = 0.02. Also, Patients with baseline NLR > 5:1 had a trend toward higher median overall survival (OS) but was not statistically significant 41 months compared to 12 months P = 0.08. Conclusions: Our data showed similar finding to Bagley et al and other retrospective analysis from multiple institutes showing that NLR could be a good predictor of response to checkpoint inhibitors And a cutoff of NLR higher than 5.1 was associated with statistically significant better PFS and a trend towards a better OS.

scholarly journals Racial disparity in survival of patients diagnosed with early-onset colorectal cancer

2020 ◽  
Vol 9 (3) ◽  
pp. CRC32
Author(s):  
Kristin Wallace ◽  
Hong Li ◽  
Chrystal M Paulos ◽  
David N Lewin ◽  
Alexander V Alekseyenko
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Age Groups ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Study Materials ◽  
Caucasian Americans

Background: Survival is reduced in African–Americans (AAs) diagnosed with colorectal cancer (CRC), especially in those <50 years old, when compared with Caucasian Americans (CAs). Yet, the role of clinicopathologic features of CRCs on racial differences in survival needs further study. Materials & methods: Over 1000 individuals (CA 709, AA 320) diagnosed with CRC were studied for survival via the Cox proportional hazards regression analysis based on race and risk of death in two age groups (<50 or 50+). Results: Risk of death for younger AAs (<50) was elevated compared with younger CAs (hazard ratio [HR] 1.98 [1.26–3.09]). Yet no racial differences in survival was observed in older cohort (50+ years), HR 1.07 (0.88–1.31); p for interaction = 0.01. In younger AAs versus CAs only, colonic location attenuated the risk of death. Conclusion: The tumor location and histology influence the poorer survival observed in younger AAs suggesting these may also influence treatment responses.

scholarly journals Survival Analysis and Prognostic Predictor Study of Colorectal Cancer Patients with Single-Site Metastasis

2021 ◽  
pp. 1-18
Author(s):  
Jaydutt V. Vadgama ◽  
Wenhong Deng ◽  
Katrina M Schrode ◽  
Magda Shaheen ◽  
Jaydutt V. Vadgama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Proportional Hazards ◽  
Regional Lymph Node ◽  
Measurement Data ◽  
Gene Mutations ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
P Value ◽  
Term Survival

Metastatic colorectal cancer (mCRC) patients have various metastasis patterns, which reflect diverse biological characteristics of different patient subgroups. We analyse the prognosis of mCRC patients according to the metastatic site and clarify the relationship between tumor or patient characteristics and the metastatic sites. The whole sequencing and clinical data of 2329 CRC patients were obtained from TCGA and a database of the MSKCC. Kruskal Wallis Tests were used to analyse measurement data. Survival was illustrated by Kaplan-Meier curves, with P value determined by Log-rank Test. Hazard’s ratio was determined through the univariate and multivariate COX proportional hazards regression model. The mortality rate of CRC patients with liver-only metastasis (mCRC-liver) did not increase versus nonmetastatic patients. The survival rate of patients with non-regional lymph node-only metastasis (mCRCNRLN) was lower versus mCRC-liver. Mutations of KRAS and TCF7L2 genes were associated with mortality of mCRC-liver. APC mutation was associated with reduced mortality in mCRC-lung and mCRCNRLN. BRAF mutation was associated with increased mortality of mCRC-peritoneum. In a multivariate COX analysis, gender affected the survival rate of mCRC-liver. Age and the number of gene mutations affected the survival rate of mCRC-lung and mCRC-NRLN respectively. Receiving chemotherapy is an unfavourable factor for prognosis of mCRC-liver, but the length of chemotherapy treatment is an advantageous prognosis factor. This study depicts the long-term survival features of a group of mCRC patients. These findings promoted our understanding of the prognosis characteristics of CRC and have positive guiding significance for clinical management of CRC patients.

scholarly journals Characteristics and Prognostic Factors of Patients With Osteosarcoma Older Than 60 Years From the SEER Database

2019 ◽  
Vol 26 (1) ◽  
pp. 107327481988889 ◽  
Author(s):  
Yue Pan ◽  
Daqi Chen ◽  
Taobo Hu ◽  
Guohua Lv ◽  
Zhehao Dai
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Distant Metastasis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Disease Stage ◽  
Data Set ◽  
Primary Tumor Site ◽  
Histologic Subtype ◽  
Axial Location

Osteosarcoma is predominant in the adolescent and the elderly population, but few studies have described the characteristics and prognostic factors of patients older than 60 years. In this study, the Surveillance, Epidemiology, and End Results registry database was used to identify all patients diagnosed with primary osteosarcoma from 1973 to 2014. We utilized Cox proportional hazards regression analysis to evaluate the association between patient overall survival and relevant characteristics, including gender, race, disease stage, treatment methods, primary tumor site, differentiation grade, and histologic subtype. In the data set, a total of 1139 patients with osteosarcoma older than 60 years old were identified. The overall rate of distant metastatic cases was 28.6%. Osteosarcoma occurred equally in men and women (49.5% vs 50.5%). Of all, 41.3% of tumors were located in axial location (pelvis, spine, and ribs), 34.1% of tumors were located in extremity (long or short bones of the upper or lower extremity), and 24.6% in other location (mandible, skull, and other atypical locations). Male (hazard ratio [HR] = 1.201; 95% confidence interval [CI]: 1.056-1.366), axial location (HR = 1.342; 95% CI: 1.157-1.556), distant metastasis (HR = 2.369; 95% CI: 2.015-2.785), non-surgery perform (HR = 2.108; 95% CI: 1.814-2.451) were independent risk factors for 5-year overall survival. This study revealed distinct clinicopathological features of patients with osteosarcoma older than 60 years. Male gender, tumor in axial site, nonsurgery perform, and distant metastasis indicated worse prognosis survival. Performing surgery is still an effective and reliable treatment method for patients older than 60 years.

Phenotypic expression of Bax is a predictive marker of 5-fluorouracil treatment in colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3605-3605
Author(s):  
U. Manne ◽  
C. Suarez-Cuervo ◽  
N. C. Jhala ◽  
J. Posey ◽  
C. B. Herring ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Proportional Hazards ◽  
Phenotypic Expression ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Nuclear Accumulation ◽  
Adjuvant Therapies ◽  
Post Surgery ◽  
Significant Difference

3605 Background: The anti-tumor activity of 5-fluorouracil (5-FU) has been related to its ability to induce apoptosis. Therefore, we assessed the predictive value of phenotypic expression of key apoptotic molecules in colorectal adenocarcinomas (CRC) of patients treated with 5-FU-based adjuvant therapies. Methods: Archival tissues of CRCs from 56 patients who received a complete regimen of 5-FU-based chemotherapy after surgery, and 56 age, gender, ethnicity, tumor stage, tumor location, and tumor differentiation matched patients who had undergone only surgery (without any pre- or post-surgery chemo- or radiation therapy), were evaluated for immunophenotypic expression of Bax, Bcl-2 and nuclear accumulation of p53 (p53nac). Immunophenotypic expression of these markers was categorized into low and high expressors and cut-point values were determined based on their expression in benign epithelium. These tumors Ability of these markers in predicting the efficacy of 5-FU-based treatment was assessed by estimating overall survival utilizing the Kaplan-Meier and Cox proportional hazards methods. Results: There was no significant difference in overall survival rates between the two patient categories (logrank P=0.487). However, a better survival was observed for patients who received chemotherapy when their CRCs lacked Bax expression; in contrast, patients with high Bax expression CRCs had worse survival when they received chemotherapy (logrank P=0.016). Surgically treated patients with CRCs lacked Bax expression had 5.33 times higher mortality than those with high Bax expression (HR, 5.33; CI: 1.78–15.94), when controlled for tumor stage and other confounding variables. Bcl-2 or p53nac had no predictive value in either patient group. Conclusions: These preliminary findings are the first to provide good evidence to suggest that patients with CRCs lacking Bax phenotypic expression benefit from 5-FU-based adjuvant therapies but not those with high Bax expression (Supported by NIH/NCI R01-CA98932–01). No significant financial relationships to disclose.

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