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Length biased data occurs when a prevalent sampling is used to recruit subjects into a study that investigates the time from an initial event to a terminal event. Such data are usually left-truncated and right-censored. While there have been accurate and efficient methods to estimate the survival function, not much work has been done regarding the estimation of the residual life time distribution or the summary parameters such as the median and quantiles of the residual life. This dissertation proposes to make two new contributions. In the first part of the dissertation, we propose two ways to estimate the quantiles of the residual life time at fixed time points accounting for the length biased and censored nature of the data. We provide the asymptotic properties of these estimators and investigate them through simulation studies. Considering that the variances of these estimators require density estimation, we suggest an alternate approach taken by Jeong and others to obtain the confidence interval for the available residual function. We apply these methods to a breast cancer dataset from the National Surgical Adjuvant Breast and Bowel Project (NSABP). n the second part of the dissertation, we propose a method for testing the equality of quantile residual life times from two different populations under prevalence sampling. This test can also be inverted to construct confidence intervals for the ratio or difference of two quantile residual life between two populations. We compare the performance of two methods, namely, the TPL and Huang and Qin methods via simulation. The results show that the proposed tests maintain Type I error. The test based on Huang and Qin survival estimator is more powerful than that of based on the TPL estimator. We apply our methods to test the equality of median residual life of breast cancer patients having recurrence and undergoing two different treatments. Public health significance of this research is enormous. For a population experiencing certain disease such as cancer, it is important to estimate the quantiles of the residual life time at specific time points to assess the impact of a disease and an intervention strategy on the population. This dissertation will provide accurate and efficient methods for estimating these quantiles.

To examine the relationship between treatment and subsequent functional status among prostate cancer patients.Using Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data, we identified men 65 years or older diagnosed with prostate cancer between 1998 and 2009 (follow-up through 2010) who were treated with conservative management, surgery, or radiation. Our primary outcome was functional status as measured by activities of daily living. Secondary outcomes included physical component summary and mental component summary scores, which are both calculated from the Short Form 36 (SF-36) and the Veterans RAND 12-item health survey (VR-12) questionnaires. We included patients who completed 2 surveys and performed propensity score analyses to match patients 1:5 with noncancer controls. We used generalized linear mixed effects models, accounting for clustering due to insurance plan.We identified 408 patients of whom 143 (35%) underwent conservative management, 59 (14%) underwent surgery, and 206 (51%) underwent radiation. Among conservative management and radiation patients, changes in functional status mirrored that of their noncancer controls (all P.05). Among surgery patients, changes in activities of daily living scores were not significant, but physical component summary (mean difference = 4.5, P.001) and mental component summary (mean difference = 3.3, P = .01) scores declined slightly more than for their noncancer peers.Surgery patients had a slight decline in their general functional status whereas conservative management and radiation patients had no differences in functional status compared with their noncancer peers. Although the functional status of surgery patients declined more than that of their noncancer peers, this difference may not be clinically significant.

OBJECTIVE: To characterize the use of multiparametric magnetic resonance imaging (mpMRI) in male Medicare beneficiaries electing active surveillance for prostate cancer. Multi-parametric resonance imaging (mpMRI) has emerged as a tool that may improve risk-stratification and decrease repeated biopsies in men electing active surveillance. However, the extent to which mpMRI has been implemented in active surveillance has not been established. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims data, we identified men with localized prostate cancer diagnosed between 2008–2013 and managed with active surveillance. We classified men into two treatment groups: active surveillance without mpMRI and active surveillance with mpMRI. We then fit a multivariable logistic regression models to examine changing mpMRI utilization over time, and factors associated with the receipt of mpMRI. RESULTS: We identified 9,467 men on active surveillance. Of these, 8,178 (86%) did not receive mpMRI and 1,289 (14%) received mpMRI. The likelihood of receiving mpMRI over the entire study period increased by 3.7% (p=0.004). On multivariable logistic regression, patients who were younger, white, had lower comorbidity burden, lived in the northeast and west, had higher incomes and lived in more urban areas had greater odds of receiving mpMRI (all p

Large numbers of previously published studies show the importance of Metabolic syndrome (MetS) in the development of endometrial cancer (EC), the most common gynecologic malignancy in the United States. Defining the association between EC and MetS is complicated by inconsistencies among the MetS definitions used in EC. The aim of this study was to identify the MetS definition that is most practical for EC patients, as well as to estimate the prevalence of MetS using each definition in EC patients. A systematic literature search of PubMed and Embase was conducted to identify studies published between 1988 and 2018 and reporting the components of MetS in EC patients. Relevant studies were selected based on the presence of key MetS components, including central obesity, dyslipidemia, elevated blood pressure, and impaired glucose metabolism. Two independent reviewers extracted information from these articles. Our literature search has identified 400 articles, 8 of which were used for the final analyses. In this systematic review, the prevalence of MetS in EC patients varied based on the definition used, ranging from 6% for International Diabetes Federation (IDF) to 62% for Harmonized. IDF and Harmonized of MetS were the most practical definitions for women with EC. While our review included different approaches to diagnosing MetS and linking it to EC, we argue that there is a need for single and practical MetS definition criteria to improve diagnostics, decrease the inconsistencies across the future EC studies, and foster a cohesive understanding of the evidence regarding the association between MetS and EC.

Objectives To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. Patients and methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. Results Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+ , or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. Conclusions Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease-specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.

Objectives To quantify the proportion of patients receiving high-intensity end-of-life care, identify associated risk factors, and assess how receipt of palliative care impact end-of-life care; as the delivery of such care, and how it relates to palliative care, has not been reported in bladder cancer Subjects and Methods We conducted a retrospective cohort study of patients with bladder cancer who died within 1 year of diagnosis using Surveillance, Epidemiology, and End Results linked Medicare data. The primary outcome was a composite measure of high-intensity end-of-life care (>1 hospital admission, >1 ED visit, or ≥1 ICU admission within the last month of life; receipt of chemotherapy within the last 2 weeks of life; or acute care in-hospital death). Secondary outcomes included the use of such care over time and any association with the use of palliative care. A generalized linear mixed model assessed for independent determinants. Results Overall, 45% of patients received high-intensity end-of-life care. This proportion decreased over time. Patients receiving high-intensity care had higher rates of comorbidities, advanced bladder cancer, and nonbladder cancer cause of death. These patients more often received palliative care but, compared to those not receiving high-intensity care, this occurred farther removed from bladder cancer diagnosis and closer to death. Conclusions Nearly half of Medicare beneficiaries with bladder cancer who die within 1 year of diagnosis receive high-intensity care at the end of life. Palliative care was seldom used and only very near the time of death.

Hysterectomy is one of the most common surgical procedures. Same-day discharge (SDD) is increasingly utilized for minimally invasive hysterectomies, but its uptake varies across healthcare systems and surgical specialties. An evidence-based initiative was developed to aid in the incorporation of SDD into the practice of minimally invasive hysterectomy (MIH) in the UPMC Health System. The objective of this study was to identify trends of SDD utilization across various gynecologic specialties at UPMC, as well as evaluate the impact of SDD on length of stay (LOS) and complications after the implementation of SDD initiative.We retrospectively identified 5554 patients who underwent MIH between 2014 and 2017 and were eligible for SDD, as determined by physicians and authorized by patients' insurance plans. Multivariable logistic regression models evaluated the trend of SDD utilization among four specialty types (general gynecologists, urogynecologists, specialized minimally invasive surgeons, and oncologists) and trends in complications. Multivariable logistic and linear regression models were applied to compare complications and LOS between patients with SDD vs. those with overnight admissions.SDD utilization increased from 28.55% to 74.99% during the study period. SDD significantly increased over the study period for all specialty types, with urogynecologists having the highest uptake from 3.9% in 2014 to 95.8% in 2017 (p.01). After adjusting for year, specialty types, MIH procedure type, and total case time, SDD utilization was associated with shorter mean LOS (p.01); such that mean LOS was 764.43 min (95% CI: 735.46-793.40) for SDD patients and 2041.84 min (95% CI: 2015.99-2067.70) for patients with overnight admissions. SDD was also associated with 42% lower odds (95% CI: 0.37-0.93, p=.02) of complications compared with patients with overnight admissions.Same-day discharge uptake increased over years and was associated with lower odds of complications and decreased length of stay. More studies are needed to explore same-day discharge process to improve patient outcomes, patient satisfaction, and value of care.

Objective To investigate whether women with early pregnancy elevated blood pressure (BP) or stage 1 hypertension exhibit increased risk of preeclampsia and maternal or neonatal morbidity. Methods We conducted a clinical cohort study of 18,162 women who delivered a singleton neonate from 2015 to 2018 and attended at least two prenatal appointments before 20 weeks of gestation. Data were collected within the Magee Obstetric Maternal and Infant database, an aggregate of prenatal and delivery health records. Early pregnancy BP was defined as average BP before 20 weeks of gestation, and women were classified with normal, elevated BP, stage 1 or 2 hypertension according to current guidelines. The primary outcome was preeclampsia. Secondary outcomes were severe maternal morbidity, placental abruption, gestational diabetes, and composite neonatal morbidity. Results Overall, 75.2% of the women were categorized with normal BP, 13.9% with elevated BP, 5.4% with stage 1 hypertension, and 5.5% with stage 2 hypertension. Risk of preeclampsia increased in a stepwise fashion with increasing BP category, adjusted for covariates (normal BP, 4.7%, referent; elevated BP, 7.3%, adjusted odds ratio [aOR] 1.29, 95% CI 1.07-1.56; stage 1, 12.3%, aOR 2.35, 95% CI 1.86-2.96), and stage 2, 30.2%, aOR 6.49, 95% CI 5.34-7.89). Results were similar among black and white women. Gestational diabetes was more prevalent among women with stage 1 (11.4%; aOR 1.50, 95% CI 1.18-1.91] and stage 2 hypertension (14.2%; aOR 1.65, 95% CI 1.30-2.10). Severe maternal morbidity and neonatal morbidity were increased only among women with stage 2 hypertension (aOR 2.99, 95% CI 2.26-3.99, and aOR 2.67, 95% CI 2.28-3.12, respectively). Conclusion Women with elevated BP, and stage 1 and 2 hypertension in early pregnancy are at increased risk for preeclampsia. These findings emphasize the importance of applying the 2017 BP guidelines to reproductive-aged women. Strategies to incorporate these guidelines into obstetric care may also be warranted.

Background Intraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore the uptake of IP/IV treatment and to evaluate its impact on survival and recurrence in OC patients. Methods Demographic and clinical information on OC patients (N = 2916) who underwent treatment for OC between 2000 and 2017 was obtained from the large healthcare system cancer registry. Duplicate records, grade 1, rare (eg, gelatinous carcinoma), and non‐epithelial (eg, granulosa cell carcinoma) tumors were excluded. Kaplan‐Meier survival curves were constructed to compare 5‐ and 10‐year survival based on the chemotherapy type, surgery type, and stage. Multivariable Gray's piecewise constant time‐varying coefficient models were fitted to evaluate the effect of IP/IV on adjusted hazard ratio (AHR) of OC survival and recurrence adjusting for potential confounders. Results The final sample consisted of 1846 OC patients, 14% (250/1846) of which received IP/IV chemotherapy. IP/IV was significantly associated with improved 10‐year survival (P, Only one of seven eligible patients underwent intraperitoneal chemotherapy in our large heterogenous health system. Intraperitoneal chemotherapy use has been associated with improved 10‐year survival, but not necessarily recurrence benefit compared to intravenous chemotherapy.

BACKGROUND Several new prostate cancer treatments have emerged since 2000, including 2 radiotherapies with similar efficacy at the time of their introduction: intensity-modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). The objectives of this study were to compare their early adoption patterns and identify factors associated with their use. METHODS By using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, patients who received radiation therapy during the 5 years after IMRT introduction (2001-2005) and the 5 years after SBRT introduction (2007-2011) were identified. The outcome of interest was the receipt of new radiation therapy (ie, IMRT or SBRT) compared with the existing standard radiation therapies at that time. The authors fit a series of multivariable, hierarchical logistic regression models accounting for patients nested within health service areas to examine the factors associated with the receipt of new radiation therapy. RESULTS During 2001 to 2005, 5680 men (21%) received IMRT compared with standard radiation (n = 21,555). Men who received IMRT were older, had higher grade tumors, and lived in more populated areas (P

OBJECTIVE: To develop prostate cancer-specific physician-hospital networks to define hospital-based units that more accurately group hospitals, providers, and the patients they serve. METHODS: Using SEER-Medicare, we identified men diagnosed with localized prostate cancer between 2007 and 2011. We created physician-hospital networks by assigning each patient to a physician and each physician to a hospital based on treatment patterns. We assessed content validity by examining characteristics of hospitals anchoring the physician-hospital networks and of the patients associated with these hospitals. RESULTS: We identified 42,963 patients associated with 344 physician-hospital networks. Networks anchored by teaching hospital (compared to a non-teaching hospital) had higher median numbers of prostate cancer patients (117 (interquartile range [71-189] versus 82 [50-126]) and treating physicians (7 [4-11] versus 4 [3-6]) (both p

To our knowledge it is unknown whether stereotactic body radiation therapy of prostate cancer is a substitute for other radiation treatments or surgery, or for expanding the pool of patients who undergo treatment instead of active surveillance.Using SEER (Surveillance, Epidemiology, and End Results)-Medicare we identified men diagnosed with prostate cancer between 2007 and 2011. We developed physician-hospital networks by identifying the treating physician of each patient based on the primary treatment received and subsequently assigning each physician to a hospital. We examined the relative distribution of prostate cancer treatments stratified by whether stereotactic body radiation therapy was performed in a network by fitting logistic regression models with robust SEs to account for patient clustering in networks.We identified 344 physician-hospital networks, including 30 (8.7%) and 314 (91.3%) in which stereotactic body radiation therapy was and was not performed, respectively. Networks in which that therapy was and was not done did not differ with time in the performance of robotic and radical prostatectomy, and active surveillance (all p0.05). The relationship with intensity modulated radiation therapy did not show any consistent temporal pattern. In networks in which it was performed less intensity modulated radiation therapy was initially done but there were similar rates in later years. Brachytherapy trends differed among networks in which stereotactic body radiation therapy was vs was not performed with a lower brachytherapy rate in networks in which stereotactic body radiation therapy was done (p=0.03).Surgery and active surveillance rates did not differ in networks in which stereotactic body radiation therapy was vs was not performed but when that therapy was done there was a lower brachytherapy rate. Stereotactic body radiation therapy may represent more of an alternative to brachytherapy than to active surveillance.

Background We use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making. Patients and Methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates. Results We identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, “head-to-head” comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57). Conclusion Significant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.

OBJECTIVE Thromboelastography (TEG) is a point-of-care device used to evaluate whole blood coagulation function. The TEG is unique as a test of coagulation function in that it measures the interaction of all components of clot formation, which is different than traditional laboratory-based tests that measure isolated components of coagulation. Little is known about fetal coagulation physiology. We sought to evaluate the impact of severe fetal anemia and intrauterine transfusion (IUT) on fetal coagulation physiology by use of the TEG and to compare fetal TEG values to those of healthy neonates and adults. METHOD One milliliter of fetal blood was collected immediately before (pre) and after (post) IUT of packed red blood cells (PRBCs). Sampling and transfusion were performed for fetal anemia due to hemolytic disease of the fetus and newborn. Samples were run in duplicate. For descriptive summary, duplicate pre-IUT and post-IUT values were averaged. Values for R (initiation of clot in minutes), K (clot firmness in minutes), angle (kinetics of clot development in degrees), and MA (maximum strength in mm) were obtained for each sample and presented using mean ± SE. Pre-IUT values for R, K, angle, and MA were compared with post-IUT values using linear mixed-effect model to account for clustering due to repeated observation from the same fetus. Pre-IUT values are compared with normal healthy term neonates and healthy adults using Wald test. The study was approved by the University of Pittsburgh Institutional Review Board (PRO14050051). RESULTS Four fetuses underwent nine IUTs rendering 17 pre-IUT and 17 post-IUT specimens. The mean gestational age at IUT was 31 weeks 2 days (25 weeks 4 days to 35 weeks 2 days). The mean IUT volume transfused was 69 mL (30-170 mL). The mean estimated percent intravascular volume transfused was 33.4% (19%-52%). Of the four variables analyzed, only R showed a significant difference, with the initiation of clot formation being modestly delayed after transfusion by an estimated 2.87 minutes (95% CI, 0.82-4.92, P = .0480). Pre-IUT values were compared with 100 normal term neonates and 118 healthy adults. Compared with pre-IUT, only R was affected (shorter) compared with term neonates (mean ± SE = 5.46 ± 0.16 minute, P

INTRODUCTION AND OBJECTIVES:In the United States, there is significant variation in the aggressiveness and quality of end-of-life care. Up to 50% of Medicare beneficiaries dying with cancer receive...

BACKGROUND There are several effective treatments for prostate cancer. To what extent a patient's functional status influences the treatment decision is unknown. This study examined the association between functional status and treatment among older men with prostate cancer. METHODS Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey data were used to identify men who were 65 years old or older and were diagnosed with prostate cancer between 1998 and 2009. The primary outcome was treatment choice: conservative management, surgery, or radiation within 1 year of the diagnosis. The exposure was the functional status assessed as 4 measures within 3 domains: 1) physical function (activities of daily living [ADLs] and physical component summary score), 2) cognitive function (survey completer: self vs proxy), and 3) emotional well-being (mental component summary score). A multivariate, multinomial logistic regression was fitted with adjustments for several patient, tumor, and regional characteristics. RESULTS This study identified 508 conservative management patients, 195 surgery patients, and 603 radiation patients. Compared with men with no ADL dependency, those with any ADL dependency had lower odds of receiving surgery (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.38-0.99) or radiation (OR, 0.58; 95% CI, 0.43-0.78) versus conservative management. ADL dependency did not differ when surgery and radiation were compared. Patients with a proxy survey response were less likely to receive surgery or radiation versus conservative management. CONCLUSIONS Functional status is associated with treatment choice for men with prostate cancer. Future research should examine whether this is due to physician recommendations, patient preferences, or a combination. Cancer 2016. © 2016 American Cancer Society.

Background: Endometrial cancer (EC) is the 6th most common cancer worldwide. However, only few studies addressed dietary factors influencing EC risk in Asia. We explored the association between dietary risk factors and endometrial cancer in the prospective Singapore Chinese Health Study. Methods: A population of 34,028 ethnically Chinese women aged 45-74 residing in Singapore were enrolled in a longitudinal prospective cohort study between 1993 and 1998, and followed up to Dec 31, 2010. Data on baseline demographics, dietary, and reproductive factors were collected via a structured questionnaire. Endometrial cancer cases were identified from the Singapore Cancer Registry. Poisson regression was used to estimate the incidence rate ratio (IRR) on established and dietary risk factors. Results: 166 EC cases were identified (age 53.6±7.2; BMI 24.1±3.3). Obesity (IRR=1.84, 95%CI 1.06-3.06) and having a higher number of live births (IRR=0.43, 95%CI 0.24-0.79, 5+ vs nulliparous) were associated with EC. Overall, compared with the lowest quartile, elevated risk of EC was observed for the highest quartile of dietary thiamine (IRR 1.74, 95%CI 1.02-2.58), riboflavin (IRR 1.58, 95%CI 1.01-2.53), vitamin B6 (IRR 1.71, 95%CI 1.07-2.80), and folate (IRR1.56, 95%CI 1.00-2.47). The highest quartiles of riboflavin (IRR 1.74, 95%CI 1.00-3.12), vitamin B6 (IRR 1.91, 95%CI 1.04-3.65), and folate (IRR 1.89, 95%CI 1.01-3.64) were associated with elevated EC risk in postmenopausal women, but not among premenopausal women. Conclusion: Obesity, parity, and higher intake of dietary vitamin B were associated with elevated EC risk in our analysis. More studies are needed to evaluate the association of supplementary vitamin B complex and EC risk. Citation Format: Ming Lei, Shalkar Adambekov, Robert Edwards, Renwei Wang, Jianmin Yuan, Samia Lopa, Faina Linkov. Association between dietary vitamin B intake and risk of endometrial cancer in the prospective Singapore Chinese Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4646.

Background. Although Pipelle biopsy plays a significant role in diagnosis of endometrial cancer and benign gynecologic disease, it has a significant failure rate, with multiple reasons for failure not well characterized. Few studies have distinguished between biopsy failures due to inability to obtain a sample at all (sampling failure) and failures due to having samples with insufficient tissue for histopathological diagnosis (tissue failure). Methods. Women undergoing a Pipelle biopsy in a tertiary care center (August 2017 to June 2019) were recruited and signed informed consent. Biopsy sampling failures were assessed by surveys administered to the clinicians immediately after procedures. Reasons for failure included: stenotic cervix, body habitus, and procedure intolerance. Biopsy tissue failures were determined by extraction of patients' pathology reports from electronic health records, which also provided data regarding demographic factors, personal history, and clinical indications for biopsy (i.e., abnormal bleeding, postmenopausal bleeding, other indications). Overall failure of Pipelle biopsy was defined as failures due to sampling failure and tissue failure. Descriptive statistics and univariate logistic regression analyses were used to identify risk factors associated with each type of biopsy failure. Two-sided P≤0.05 was considered significant. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Results. A total of 121 patients were included in the study. A majority were white (84.03%) and obese (median BMI = 31.70). The overall failure incidence was 29% (18% sampling failure and 11% tissue failure). Overall failure was significantly associated with patients': age (OR=1.10, P Conclusions. Overall Pipelle failure was found to be due to both failures to obtain a sample at all, and to failures to obtain enough tissue for histopathological diagnosis. Interestingly, these two reasons for overall failure were found to have different sets of predictors, suggesting that providers may want to pursue alternative approaches in high risk patients for Pipelle biopsy failure. Citation Format: Shalkar Adambekov, Samia Lopa, Esther Elishaev, Noah Rindos, Suketu Mansuria, Robert P. Edwards, Dana H. Bovbjerg, Nicole Donnellan, Faina Linkov. Risk factors associated with Pipelle endometrial biopsy failure [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5777.

Introduction: Office-based endometrial biopsy (Pipelle) is an important minimally invasive diagnostic modality for endometrial cancer and benign gynecologic disease but does have a substantial failure rate. Little is known about trajectories of care following failure of Pipelle procedures, as studies in this area have been almost exclusively based on review of medical records, which may not include information on failures due to inability to obtain samples to send to pathology. Methods: Women undergoing a Pipelle biopsy in a tertiary women's care center (n= 121) were recruited from August 2017 to June 2019 with post-menopausal and abnormal bleeding as a biopsy indication in the majority of cases. Patients' relevant demographic and clinical data were extracted from their medical records and from surveys administered to providers immediately after attempted procedures. Overall failure of their Pipelle biopsy was defined by either a failure to obtain a sample at all (sampling failure) or a failure due to having a sample with insufficient tissue for histopathological diagnosis (tissue failure). Participants' medical records are currently being abstracted for a period of one year after the date of the Pipelle procedure to prospectively track their follow-up care trajectories. Descriptive statistics and tests of dichotomous relationships were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Results: The study sample included 35 women (29% of the original cohort) for whom there was an overall failure of Pipelle biopsy (mean age=56, SD=8; mean BMI=33, SD=10). Among women with overall biopsy failures, 63% were due to sampling failures (attributed by providers to stenotic cervix, body habitus, and procedure intolerance), while 37% were due to having insufficient tissue acquired for pathological diagnosis. Follow-up procedures and/or counseling have already been conducted in the majority of patients and found to include: hysteroscopy/D&C (51%), another Pipelle (3%), Pipelle and D&C (3%), hysterectomy without additional endometrial sampling (3%), ultrasound (3%), and CT scan/referral to gynecologic oncologist for cancer care (3%). Among women with follow-up, approximately one third had pathological findings, which included endometrial polyps (29%) and cancer (6%). Participants with sampling failure had a higher likelihood (76%) of D&C follow-up compared to those with tissue failure (24%) (P=0.055). Conclusions: This study is one of the first to prospectively track follow-up care for women who experienced Pipelle biopsy failures due to sampling failure as well as tissue failure. Considering that D&Cs are invasive and costly, but were used for a majority of the follow-up care for women with Pipelle failures, it is particularly important in future research to determine whether repeat Pipelle, perhaps with supportive care, might prove more successful and reduce the need for invasive procedures. Citation Format: Faina Linkov, Shalkar Adambekov, Samia Lopa, Robert P. Edwards, Noah Rindos, Suketu Mansuria, Nicole Donnellan, Dana H. Bovbjerg. If at first you don't succeed: Follow-up care trajectories for women with failed endometrial biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2303.

Background: Ovarian cancer (OC) is the deadliest gynecologic cancer, with varying incidence across geographic regions. Asian population is underrepresented in etiologic and epidemiologic investigations in the area of ovarian cancer. We explored association between ovarian cancer incidence and several lifestyle, dietary, reproductive, and hormonal risk factors in the Singapore Chinese cohort study. Methods: A population of 34,028 Singaporean Chinese women aged 45-74 were enrolled in the Singapore Chinese Health Study between 1993 to 1998, and followed through Dec. 31, 2010. Data on demographics, tobacco use, dietary and reproductive factors were collected. Cases of OC were determined via linkage to Singapore Cancer Registry. Poisson regression model was performed and hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each variable. Established risk factors and variables showing a significant result in univariate analysis were included in the multivariate analysis. Results: 128 cases of OC were identified. No dietary factors were associated with OC incidence in this population, nor was tobacco/alcohol use. In univariate analysis, significant results included later age of menopause (RR=2.38, 95%CI 1.23-4.30), later age of first birth (RR=0.43, 95%CI 0.17-0.93) and longer period of menstruating (RR=1.48, 95%CI 1.02-2.18), parity (RR=0.37, 95%CI 0.22-0.65), and oral contraceptives use (RR=0.54, 95% CI 0.33-0.84). In multivariate analysis, higher number of children was associated with decreased ovarian cancer risk (1-2, 3-4, 5+ vs nulliparity: RR=0.45, 95%CI 0.26-0.8; RR= 0.35, 95%CI 0.20-0.51 RR= 0.32, 95%CI 0.18-0.60, respectively). Conclusions: Parity, contraceptive use, and later age of first birth decreased the risk of OC incidence, while later age at menopause and longer menstruating period increased ovarian cancer risk in Singaporean Chinese cohort. This finding is consistent with findings in Western populations. Future studies are needed to determine risk factors associated with ovarian cancer histologic types and identify markers of elevated risk, especially in Asian populations. Citation Format: Ming Lei, Shalkar Adambekov, Renwei Wang, Jianmin Yuan, Samia Lopa, Faina Linkov. Reproductive factors and risk of ovarian cancer: The Singapore Chinese Health Study [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B33.

Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment.We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P0.05).From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Background Recent studies suggest that anesthetic technique during radical prostatectomy for prostate cancer may affect recurrence or progression. This association has previously been investigated in series that employ epidural analgesia. The objective of this study is to determine the association between the use of a multimodal analgesic approach incorporating paravertebral blocks and risk of biochemical recurrence following open radical prostatectomy. Patients and methods Using a prospective database of 3,029 men undergoing open radical prostatectomy by a single surgeon, we identified 2,909 men who received no neoadjuvant androgen deprivation and had at least 1 year of follow up. We retrospectively compared patients who received general analgesia with opioid analgesia (1999–2003, n = 662) to those who received general analgesia with multimodal analgesia incorporating paravertebral blocks (2003–2014, n = 2,247). The primary outcome was time to biochemical recurrence. Biochemical recurrence-free interval was assessed using the Kaplan-Meier technique and compared using a multivariate Cox-proportional hazards regression model. Results In total, 395 patients (14%) experienced biochemical recurrence following radical prostatectomy, including 265 (12%) who received multimodal analgesia and 130 (20%) who did not (adjusted P = 0.27). After adjusting for age, race, body mass index, preoperative prostate specific antigen, grade, stage, perineural invasion, margin status, percent of tumor in the gland, and diameter of the dominant nodule, there was no difference in recurrence-free interval between groups (HR = 0.92, 95% CI: 0.73–1.17). Conclusion Use of a multimodal analgesic approach incorporating paravertebral blocks is not associated with a reduced risk of biochemical recurrence following radical prostatectomy.

Introduction Technology availability and prior experience with novel cancer treatments may partially drive their use. We sought to examine this issue in the context of stereotactic body radiation therapy (SBRT) by studying how its use for an established indication (lung cancer) impacts its use for an emerging indication (prostate cancer). Methods Using SEER-Medicare from 2007 to 2011, we developed prostate cancer-specific physician-hospital networks. Our primary dependent variable was SBRT use for prostate cancer and our primary independent variable was SBRT use for lung cancer, both at the network level. To assess the influence of SBRT availability and experiential use, we generated predicted probabilities of SBRT use for prostate cancer stratified by a network's use of lung cancer SBRT, adjusting for network characteristics. To assess intensity of use, we examined the correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT within a network. Results We identified 316 networks that served 41,034 prostate cancer and 83,433 lung cancer patients. A network was significantly more likely to use SBRT for prostate cancer if that network used SBRT for lung cancer (e.g., in 2011, odds ratio [OR] 12.7; 95% confidence interval [CI] 3.9-41.8). The Pearson's correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT in a network was 0.34, which was not statistically significant (P = 0.12). Conclusions SBRT availability and experiential use for lung cancer influences its use for prostate cancer, but intensity of use for one does not relate to intensity of use for the other.

The MOSAIC trial showed that the use of adjuvant oxaliplatin and an infusional regimen of 5-FU/LV in the treatment of stage II/III colon cancer improved disease-free survival (DFS). The NSABP's C-07 trial evaluated the addition of oxaliplatin to a weekly Roswell Park regimen of bolus 5-FU/LV and found a similar improvement in DFS. The benefit of oxaliplatin appears to be independent of the 5-FU/LV regimen used. This paper reviews the efficacy and toxicities of these two regimens and is meant to serve as a guide for clinical practice.

ObjectiveNational Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS).MethodsTo obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, sex, stage, intended surgery, and randomly assigned chemoradiotherapy.ResultsOf 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at 1 year. For the EORTC QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P = 0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS patients reported worse gastrointestinal tract symptoms than did the APR patients (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002).ConclusionsSymptoms and functional problems were detected at 1 year by EORTC QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer.

Purpose The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time. Patients and Methods Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point. Results Of 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value Conclusion Bevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.

Purpose Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. Patients and Methods Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. Results Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). Conclusion This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.

Purpose The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and efficacy of adding bevacizumab to modified FOLFOX6 (mFOLFOX6; ie, infusional/bolus fluorouracil, leucovorin, and oxaliplatin) for the adjuvant treatment of patients with stages II to III colon cancer. Methods Patients received mFOLFOX6 every 2 weeks for 26 weeks alone or modified as FOLFOX6 + bevacizumab (5 mg/kg every 2 weeks for 52 weeks [ie, experimental group]). The primary end point was disease-free survival (DFS). Results Among 2,672 analyzed patients, demographic factors were well balanced by treatment. With a median follow-up of 35.6 months, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.89; 95% CI, 0.76 to 1.04; P = .15). The point estimates for 3-year DFS for the overall population were 77.4% and 75.5% for the experimental and control arms, respectively. For patients with stages II and III diseases, these same estimates were 87.4% and 84.7%, respectively, for stage II and 74.2% and 72.4%, respectively, for stage III. Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 15-month landmark (time-by-treatment interaction P value < .0001). Bevacizumab had a strong effect before the landmark (HR, 0.61; 95% CI, 0.48 to 0.78; P < .001) but no significant effect after (HR, 1.22; 95% CI, 0.98 to 1.52; P = .076). Conclusion Bevacizumab for 1 year with mFOLFOX6 does not significantly prolong DFS in stages II and III colon cancer. However, a significant but transient effect during bevacizumab exposure was observed in the experimental arm. We postulate that this observation reflects a biologic effect during bevacizumab exposure. Given the lack of improvement in DFS, the use of bevacizumab cannot be recommended for use in the adjuvant treatment of patients with colon cancer.

Background The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies.

Purpose The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer. We present safety information in advance of the planned analysis of efficacy. Patients and Methods Among 2,710 randomly assigned patients, demographic factors were balanced. Patients received modified FOLFOX6 every 2 weeks × 12 or modified FOLFOX6 plus bevacizumab (5 mg/kg every 2 weeks × 26, experimental group). Results Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms (15.2% and 15.0%, respectively). Six-month mortality rates were 0.96% and 0.90% for the control and experimental groups, respectively. Grade 3+ toxicities that occurred more often in the experimental arm versus control arm included hypertension (12% v 1.8%, respectively), wound complications (abdominal incisional hernia or infusion port dehiscence/inflammation; 1.7% v 0.3%, respectively), pain (11.1% v 6.3%, respectively), and proteinuria (2.7% v 0.8%, respectively). Grade 2+ neuropathy was increased in the experimental arm versus the control arm (grade 2, 33% v 29%, respectively; grade 3, 16% v 14%, respectively; and grade 4, < 1% each). In the experimental arm versus control arm, significantly less thrombocytopenia (1.4% v 3.4%, respectively) and fewer allergic reactions (3.1% v 4.7%, respectively) were observed. Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment. Conclusion Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients. No significant increase in GI perforation, hemorrhage, arterial or venous thrombotic events, or death with the addition of bevacizumab to modified FOLFOX6 has been observed. Follow-up for potential delayed adverse effects and efficacy is ongoing.

3603 Background: The two primary aims of NSABP R-04 were 1) Can the oral fluoropyrimidine, Cape be substituted for the standard of care in the curative setting of Stage II & III rectal cancer namely, CIV 5-FU, during neoadjuvant RT; and 2) Can the addition of Ox enhance the activity of fluoropyrimidine sensitized RT? Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint was local-regional (L-R) tumor control that included L-R tumor recurrence, less than a complete surgical resection, and no surgery for any reason. Results: From July 2004 to August 2010, 1,608 patients were randomly assigned and 99.2% were eligible for analysis. There were n...

384 Background: Valentini, et al. (J Clin Oncol 29: 2011, 3163-72) developed nomograms for predicting overall survival (OS) based on clinical factors available after neoadjuvant therapy (tx). Pathologic T-stage (pT), N-stage (pN), and clinical T (cT) were the most important independent predictors of OS. We developed a neoadjuvant RC score (NAR score) using pN and downstaging of T (cT – pT) based on relative weights suggested by the nomograms. NSABP’s R-04 trial presents an opportunity for independent validation of the NAR score. Methods: Pts with clinical stage II/III RC undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540-1,080cGy in 3-6 daily fractions) were randomized to one of four regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without oxaliplatin (Ox) (50mg/m2 /wk x 5) or oral capecitabine (825 mg/m2 BID 5 days/wk), with or without Ox. The NAR score is computed as [5 pN – 3 (cT – pT) + 12]2/ 9.61 where: cT in {1, 2, 3, 4}, pT in {0, 1, 2, 3, 4}, and pN in {0, 1, 2}. The NAR score takes values from 0 to 100; higher scores indicate poorer prognosis. Analyses based on the score should be stratified by cT. NAR score is compared to pathologic complete response (ypCR) by Akaike’s information criterion (AIC) to determine the better predictor of OS. Results: 1,479 pts had data for the NAR score and follow-up for OS. Continuous NAR score was significantly associated with OS (HR/unit 1.04 95% CI 1.03-1.05, p

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.

468 Background: Surgical resection of asymptomatic primary colon tumor for pts presenting with synchronous yet unresectable metastatic disease is controversial. We published results for the primary endpoint in JCO in September 2012. Here we update the primary endpoint and present definitive survival results. Methods: Eligible pts had ECOG Performance 0 or 1, an asymptomatic colon tumor and unresectable distant metastases. Primary endpoint (PE) was major morbidity, defined as surgical resection or death related to the intact primary tumor. Major morbidity rate of 25% was considered acceptable and the trial had 85% power to rule out a rate of 40%. Secondary endpoints were overall survival and morbidity related to the intact primary requiring hospitalization, transfusion, or interventional procedure. Results: Between March 2006-June 2009, 90 pts were registered and 86 eligible pts with follow-up comprise this analysis. 52% were female and 47% were age 60+. Median follow-up was 61.5 mos. There were 15 (17.4%) major morbidity events, 12 (14.0%) required surgery: obstruction (9), perforation (2), and pain (1). Three (3.5%) resulted in pt death: perforation (2), obstruction (1). Cumulative incidence of major morbidity at 42 mos was 17.7% (95% CI 9.5-26.0%). Fourteen other primary tumor resections were performed: attempted cure (11), other reasons (3). There were 6 secondary endpoint events: 4 obstructions (2 required stents, 2 resolved with conservative management), 2 pts with suspected perforation required percutaneous drainage (1) and hospitalization and antibiotics (1). Median survival was 18.3 mos (95% CI 15.2-24.2). Two year OS rate was 38.7% and 3 year OS rate was 15.1%. Conclusions: The primary endpoint holds with the updated analysis justifying observation for asymptomatic primary colon cancers even in patients with a good clinical response of distant metastases. Clinical trial information: NCT 00321828.

3545 Background: R-04 is a trial of pre-surgical RT and either capecitabine or 5-FU with or without oxaliplatin in patients (Pts) with resectable rectal cancer. PROs were measured before treatment, post-RT, and 1 yr post-op. We compare PROs at 1 yr by type of surgery with hypothesis that APR Pts would have worse quality of life (QOL). Methods: Pts completed the FACT-C and EORTC-CR38 at all times. Baseline and 1 yr were compared within groups (SSS and APR) with paired t-test, and between groups at 1 yr, with adjustment for covariates of age, gender, clinical stage, baseline score, and surgery intent in a general linear model. These secondary/exploratory hypotheses were significant if p < 0.05. Results: 1,608Pts were randomized and 1405 completed baseline QOL form after consent, prior to treatment. 1,003 completed QOL form 1 yr post-op: 6 were ineligible, 10 did not have surgery, leaving 987 Pts. 615 had SSS and 372 had APR. 66.6% were male, 61.5% stage II, and almost all had post-surgical adjuvant chemotherapy. SSS Pts were significantly younger (60.3% vs. 53.5% < 59 yr, p=0.04). FACT-C total and subscale scores were not significantly different by surgery type at 1 yr, with only minimal decline from baseline in both groups. For SSS Pts, EORTC-CR38 scores significantly worsened for body image, sexual function, sexual enjoyment (all p

391 Background: Preliminary results of NSABP R-04 indicated that 5-FU and cape have similar pathologic complete response (pCR) outcomes and that the addition of oxaliplatin did not improve pCR. We present PROs comparing 5-FU and cape treatments on quality of life (QoL), convenience of care (CoC), and symptoms. Methods: Clinical stage II or III rectal cancer patients were randomized to receive 5-FU (225mg/m2 5 days/wk) or cape (825 mg/m2 5 days/wk) along with RT (4,500cGy in 25 fractions over 5 wk + boost of 540-1080cGy in 3-6 daily fractions). About half of these patients were also randomized to receive oxaliplatin (50 mg/m2 /wk). QoL was assessed by the functional assessment of cancer therapy–colorectal (FACT-C) trial outcome index (TOI) and symptoms were assessed by the fluoropyrimidine specific symptom checklist (SCL) collected at baseline, after chemoradiation before surgery (post therapy), and at 1 year. CoC was assessed by the modified ECOG CoC scale post therapy. Primary hypotheses were to compare 5-FU and cape on the endpoints of change in TOI and SCL baseline to post therapy and CoC at post therapy. P-values, means, and confidence intervals (CI) are adjusted for clinical stage, sex, and intent for sphincter-saving surgery. Results: 625 5-FU and 650 cape patients completed baseline and post therapy data forms. Patient characteristics were similar by treatment. Change in TOI was similar by treatment post therapy (p = .21). Change in SCL post therapy was greater for cape patients than for 5-FU patients (mean difference 1.02, 95% CI 0-2.04, p = .05). CoC was superior with cape compared to 5-FU post therapy (mean difference 3.07, 95% CI 1.31-6.01, p = .002). The change from baseline to post therapy for all FACT-C subscales was similar by treatment. Change in TOI, SCL, and all FACT-C subscales were similar by treatment at the 1-year assessment. Conclusions: PROs indicate that patients treated with 5-FU and cape have similar QoL. Cape provides significantly greater convenience of care but slightly increased symptoms compared to 5-FU. NCI PHS grants U10CA37377, U10CA69974, U10CA12027, and U10CA69651, support from sanofi-aventis and Hoffmann La-Roche.

3507 Background: The use of adjuvant chemotherapy in patients (pts) with stage II colon cancer who lack “high-risk” features ([HiR] perforation, T4 disease and/or less than 12 lymph nodes examined ...

3503 Background: The optimal chemotherapy regimen to be given concurrently with preop radiation therapy (RT) in patients with resectable adenocarcinoma of the rectum is unknown. NSABP R-04 compared the efficacy of 4 chemotherapy regimens administered concomitantly with preop RT. Methods: Patients with clinical stage II or III rectal cancer undergoing preop RT (4,500cGy in 25 fractions over 5 wk + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous IV infusion (CVI) 5-FU (225mg/m2 5 days/wk), with or without IV oxaliplatin (OX) (50mg/m2 /wk x 5); oral capecitabine (CAPE) (825 mg/m2 BID 5 days/wk), with or without OX (50mg/m2/wk x 5). Prior to random assignment the surgeon indicated if the patient was eligible for sphincter-saving surgery (SSS) based on clinical staging. The endpoints were complete pathologic response (pCR), SSS, and surgical downstaging (SD, conversion to SSS). Results: From July 2004 to August 2010, 1,608 patient...

3527 Background: Surgical resection of asymptomatic primary colon tumor for pts presenting with synchronous yet unresectable metastatic disease is controversial. Concerns remain about combining cyt...