678 Background: Improved outcomes have been demonstrated with the use of neoadjuvant fluoropyrimidine-based chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer. The addition of oxaliplatin in the adjuvant setting has also resulted in improved disease-free survival (DFS). A meta-analysis was performed to evaluate DFS and overall survival (OS) with the addition of oxaliplatin to standard neoadjuvant chemoradiation for locally advanced rectal cancer. Methods: A systematic literature review was performed. Randomized-controlled trials (RCTs) comparing the addition of oxaliplatin in the neoadjuvant setting (oxaliplatin group) to fluoropyrimidine-based chemoradiation (standard group) were included. The primary outcomes were DFS and OS; secondary outcomes were short-term surgical results, morbidity, and mortality. Results were combined using meta-analysis via linear mixed-effects models. Calculations were performed using R. Results: Of 73 studies identified, 4 reported DFS (n=3829) and 3 reported OS (n=2680). There was no difference in DFS between the standard and oxaliplatin groups amongst RCTs [HR 0.90 (0.64-1.26), p=0.5313]. There was no difference in OS [HR 0.93 (0.59-1.47), p=0.9894]. There was no significant heterogeneity between RCTs for primary outcomes. There was also no difference in pathologic complete response rate [OR 0.93 (0.77-1.14), p=0.4923), resection margin (R0) status [OR 1.01 (0.59-1.72), p=0.9846], circumferential resection margin status [OR 0.84 (0.50-1.41), p=0.5079], sphincter saving surgery rate [OR 0.87 (0.74-1.03), p=0.1103], grade 3-4 toxicity [OR 1.60 (0.88-2.92), p=0.1251], and 60-day mortality [OR 1.27 (0.50-3.25), p=0.6148]. There was significant heterogeneity between RCTs for R0 status, circumferential margin status, and grade 3-4 toxicity. Adjuvant treatment varied across studies. Conclusions: There are no short-term or long-term survival benefits with the addition of oxaliplatin to fluoropyrimidine-based chemoradiation in the neoadjuvant setting for locally advanced rectal cancer.
Abstract Background: Health disparities play a major role in prostate cancer (PCa). African American (AA) compared to European American (EA) men are twice as likely to die of and be diagnosed with PCa. Multilevel factors from societal/neighborhood exposures down to genetics likely contribute to racial disparities, but few PCa risk prediction models include multilevel factors and consider race/ethnic differences. Objective: We sought to: 1) develop a multilevel risk prediction model for time to PCa diagnosis, that includes neighborhood variables, individual-level socioeconomic and clinical factors (education, race, digital rectal exam or DRE), and biologic variables (prostate specific antigen or PSA level, and percent West African genetic ancestry) in men at high risk for prostate cancer (defined as AA men and/or men with a PCa family history); 2) compare our multilevel model to a more standard prediction model that includes only age, race, PSA, and DRE (abnormal/normal). Methods: A total of 443 high risk, cancer-free men between 35 and 69 years of age with complete socioeconomic, racial, and genetic ancestry data were identified from the Prostate Risk Assessment Program (PRAP) at Fox Chase Cancer Center. Their data were geocoded and linked to 17 neighborhood variables at the census tract level (from the Year 2000 U.S. Census) that were previously associated with advanced PCa in EA men in a novel neighborhood-wide association study(NWAS) our study team developed. These variables generally represent neighborhood transportation, poverty, income, social support, immigration, renting/owning a house, and employment. Men were followed from time of program (PRAP) entry to PCa diagnosis or censoring, with annual follow-up visits that included PSA and DRE screening. Men with elevated PSA or other indications for PCa were referred to Urology for evaluation and potential biopsy according to PRAP protocols. Univariate analyses of neighborhood variables, and the interaction of each variable with PSA and race, were evaluated in Cox regression models, using robust standard errors to adjust for clustering by census tract, in order to inform the final multivariate, multilevel model. Harrell's C Index (C Statistic) was used to compare the multilevel risk prediction model to a standard prediction model. Results: With a median follow-up time of 71 months, PCa diagnosis occurred in 69 participants. The final multilevel risk prediction model included 3 neighborhood variables related to transportation, social support, and poverty, along with education, age, race, baseline PSA, baseline DRE, and PCa family history. Significant interactions between the top hit from the NWAS and PSA were noted in the full study population (neighborhood mode of transportation to work X PSA, p-value<0.001) and within racial subgroups (AA, p-value=0.03; EA, p-value<0.001). Genetic ancestry was not significant in multilevel models. Compared to standard prediction models, multilevel prediction models modestly improved for EA men (C-statistic: 0.80 vs 0.83) and remained relatively constant for AA men (0.86 vs 0.85) and the study population as a whole (0.82 vs. 0.83). Conclusion: This study is the first to investigate the role of neighborhood in PCa risk prediction. While risk prediction models show little change, significant neighborhood effects in multilevel models warrant additional study and could inform future health disparity studies. Citation Format: Shannon M. Lynch, Elizabeth Handorf, Elizabeth Blackman, Lisa Bealin, Shiju Daniel, Veda N. Giri, Elias Obeid, Camille Ragin, Mary B. Daly. Testing a multilevel risk prediction model in high risk men enrolled in a prostate cancer early detection program. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B01.
Advanced bladder cancer is largely a lethal disease that has demonstrated little improvement in survival trends over the past 50 years. Five-year survival for advanced bladder cancer has remained at about 8% since 1973; though, as in most diseases, survival outcomes are not evenly distributed among different sociodemographic groups (1).
Purpose: To assess the response of a 12-week exercise, education, and stress management program on the fatigue levels of a heterogeneous group of fatigued cancer survivors in a community setting. Methods: Peer-reviewed evidence was translated into a community-based exercise and stress management program for cancer-related fatigue. Inclusion criteria were adult with a cancer diagnosis, a score of 4 or more on a 0-10 fatigue scale, and the ability to walk for 10 continuous minutes. The 12-week program included 10 weeks of supervised moderate-intensity aerobic and strength training combined with 2 unsupervised weeks. During the 10 supervised sessions, participants also received education on nutrition, stress management, and sleep. Outcome Measures: Functional Assessment of Chronic Illness Therapy–Fatigue, Hospital Anxiety and Depression Scale (HADS), National Comprehensive Cancer Network Distress Thermometer, Six-Minute Walk Test (6MWT), and Sit-to-Stand Test. Results: Sixteen cancer survivors completed the program (mean age = 68.5 years). Sixty-two percent were female, and 24% had breast cancer. Significant improvements were noted in fatigue ( P = .008), physical well-being ( P = .004), and in the anxiety subscale scores of the HADS ( P = .047). Increases in 6MWT distance ( P = .002) and Sit-to-Stand Test score ( P = .018) were also observed. Significant reductions in psychological distress were found ( P = .003); however, no significant changes were observed in emotional well-being ( P = .855), social well-being ( P = .327), or depression ( P = .221). Limitations: Because of attrition, this pilot study had a modest sample size. Study findings require replication with larger sample sizes. Conclusions: A 12-week exercise, stress management, and education program may be effective in reducing fatigue in a heterogeneous group of cancer survivors in a community setting.
806 Background: Microsatellite instability (MSI) is a marker for hypermutability due to impaired DNA mismatch repair and has been shown to be a favorable prognostic marker in colon cancer. We examined the role of MSI in locally advanced rectal cancer (LARC) as a predictive marker for response to neoadjuvant chemoradiation (CRT). Methods: We identified T3-T4 or ≥ N1 rectal cancer with reported MSI status in the National Cancer Data Base from 2007 – 2012. Patients were eligible if they were treated with CRT followed by surgical resection. Squamous cell and carcinoid histologies were excluded. The primary outcome was neoadjuvant rectal (NAR) score, categorized as low ( < 8), intermediate (8-16), and high ( > 16), representing a good, intermediate, and poor response to CRT, respectively. The secondary outcomes were complete pathologic response (ypCR) rate and overall survival (OS). Chi-square, Fisher’s exact, and independent sample t-tests were used to compare MSI status. Multivariable logistic regression models were used to examine factors associated with increasing level of NAR score and ypCR. OS was examined using multivariable Cox proportional hazards models. Results: A total of 1849 patients were eligible for the study and were classified as MSI-high (n = 52) or MSI-low/stable (n = 1797). Patients in the MSI-high group were younger (median age 50.5 vs 57.0, p = 0.005) and had higher rates of mucinous and signet ring histology (p < 0.001), clinical T4 disease (p = 0.001), and clinically positive lymph nodes (p = 0.049). The two groups did not differ in gender, race, grade, or resection margin status. While clinical T and N stage, histology, LVI, tumor grade, and PNI were correlated with the NAR score groups, MSI-high status was not significantly associated with a higher NAR score group on multivariable analysis (OR 1.168, 95% CI 0.673 – 2.028). The MSI-high group also did not differ significantly from MSI-low/stable group in ypCR rate (OR 0.748, 95% CI 0.179 – 3.115) or OS (HR 1.727, 95% CI 0.864 – 3.453) on multivariable analysis. Conclusions: MSI status in LARC was not associated with NAR score, ypCR rate, or OS. Our results do not support the use of MSI status as a predictive marker for response to CRT in LARC.
594 Background: Higher treatment facility (TF) volume has been linked with improved surgical and hematologic malignancy outcomes. We evaluated the association between TF volume and overall survival (OS) in pts with metastatic renal cell carcinoma (mRCC). Methods: The National Cancer Data Base was queried for all pts with mRCC and survival data available (2004 to 2013, cohort A). We defined high volume TFs as those in the top 20 th percentile of mean number of mRCC pts treated per year ( > 5 pts). The effect of volume on OS was determined using unadjusted Kaplan-Meier curves and Cox regression models (MVA) adjusting for pt (age, sex, race, ethnicity, insurance type, income, Charlson-Deyo Score), facility (location, practice setting) and clinical characteristics (histology, presence or absence of liver and lung metastasis). Increasingly more stringent inclusion criteria were used to confirm the overall cohort association (cohort B = mRCC pts with active treatment; cohort C = mRCC pts with systemic therapy; cohort D = mRCC pts with systemic therapy at the reporting institution; cohort E = mRCC pts with systemic therapy at the reporting institution with liver and lung metastatic status known). Results: There were 44,109 mRCC pts treated at 1,224 TFs. The median age was 65, 66% were men and 75% had clear cell mRCC. Median TF volume was 2.4 pts/year (range 0.1-46.8). High volume TFs treated 54% of all mRCC pts. The unadjusted median overall survival of mRCC patients (cohort A) treated at high vs low volume TFs was 9.2 vs 6.4 months (P < 0.0001). This difference was maintained in all cohorts: cohort B = 13.7 vs 10.9, cohort C = 12.4 vs 10.0, cohort D = 12.5 vs 9.3, and cohort E = 13.4 vs 10.6 months (P < 0.0001 for all cohorts). MVA confirmed that facility volume was associated with all-cause mortality after adjustment: HR = 0.85, [95% CI 0.82-0.88], P < 0.001. These results were consistent regardless of inclusion criteria, e.g. for cohort E: HR = 0.839, [95% CI 0.785-0.897], P < 0.0001. Considering the definition of high volume, all thresholds > 5 pts/year showed a survival benefit, with the largest effects at ≥10 pts/year. Conclusions: Patients with mRCC treated at higher volume facilities had a longer survival compared with those treated at lower volume facilities.
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