Supplementary Figures 1-11, Methods and Materials from Phosphatase PRL-3 Is a Direct Regulatory Target of TGFβ in Colon Cancer Metastasis

Genomic testing and targeted use of non-steroidal anti-inflammatory drugs (NSAIDs) may mitigate cancer recurrence risks. This study examines colorectal cancer (CRC) survivors' interest and receptivity to these strategies. Patients diagnosed with stage I-III CRC in 2004-2012 were recruited through the New Mexico Cancer Registry to complete a cancer survivorship experiences survey. We assessed interest in genomic testing, daily aspirin (ASA) and NSAID use, and receptivity to future daily ASA/NSAIDs. Descriptive statistics and multivariable logistic regression models estimated factors associated with genomic testing interest. Receptivity to future ASA/NSAIDs use was estimated for non-users of ASA/NSAIDs. Among CRC survivors (n = 273), 83% endorsed interest in genomic testing, 25% were ASA users and 47% ASA/NSAIDs users. In our final model, genomic testing interest was associated with being uncoupled [OR = 4.11; 95% CI = 1.49-11.35], low income [OR = 0.35, 95% CI: 0.14-0.88], smoking history [OR = 0.35, 95% CI: 0.14-0.90], low [OR: 0.33, 95% CI: 0.07-1.43] and moderate [OR: 0.26, 95% CI: 0.11-0.61] health literacy, and personal CRC risk worry [OR: 2.86, 95% CI: 1.63-5.02, p = 0.0002]. In our final model, ASA use was associated with age [OR: 1.05, 95% CI: 1.01-1.10] and cardiovascular disease history [OR: 2.42, 95% CI: 1.23-4.73, p = 0.010]. Among non-users ASA/NSAIDs, 83% reported receptivity to ASA/NSAIDs to reduce cancer risks, and no significant correlates were identified. The majority of survivors' expressed genomic testing interest and endorsed receptivity toward ASA/NSAIDs use for cancer risk management. Further research to optimize ASA/NSAIDs use guided by genomic testing is warranted.

BACKGROUND:Rectal cancer treatment is often multimodal, comprising of surgery, chemotherapy, and radiotherapy. However, the impact of coordination between these modalities is currently unknown. We aimed to assess whether delivery of nonsurgical therapy within same facility as surgery impacts survival in patients with rectal cancer. METHODS:A patient cohort with rectal cancer stages II to IV who received multimodal treatment between 2004 and 2016 from National Cancer Database was retrospectively analyzed. Patients were categorized into three groups: (A) surgery + chemotherapy + radiotherapy at same facility (surgery + 2); (B) surgery + chemotherapy or radiotherapy at same facility (surgery + 1); or (C) only surgery at reporting facility (chemotherapy + radiotherapy elsewhere; surgery + 0). The primary outcome was 5-year overall survival (OS), analyzed using Kaplan-Meier curves, log-rank tests, and Cox proportional-hazards models. RESULTS:A total of 44,716 patients (16,985 [37.98%] surgery + 2, 12,317 [27.54%] surgery + 1, and 15,414 [34.47%] surgery + 0) were included. In univariate analysis, we observed that surgery+2 patients had significantly greater 5-year OS compared to surgery + 1 or surgery + 0 patients (5-year OS: 63.46% vs 62.50% vs 61.41%, respectively; P= .002). We observed similar results in multivariable Cox proportional-hazards analysis, with surgery + 0 group demonstrating increased hazard of mortality when compared to surgery + 2 group (HR: 1.09; P< .001). These results held true after stratification by stage for stage II (HR 1.10; P= .022) and stage III (HR 1.12; P< .001) but not for stage IV (P= .474). CONCLUSION:Greater degree of care coordination within the same facility is associated with greater OS in patients with stage II to III rectal cancer. This finding illustrates the importance of interdisciplinary collaboration in multimodal rectal cancer therapy.

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation – arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.

Background The purpose of this study was to assess the impact of surgical delays on short- and long-term survival among colon cancer patients. Methods Adult patients undergoing surgery for stage I, II, or III colon cancer were identified from the National Cancer Database (2010-2016). After categorization by wait times from diagnosis to surgery (<1 week, 1-3 weeks, 3-6 weeks, 6-9 weeks, 9-12 weeks, and >12 weeks), 30-day mortality, 90-day mortality, and 5-year overall survival were compared between patients both overall and after stratification by pathological disease stage. Results Among 187 394 colon cancer patients, 24.2% waited <1 week, 30.5% waited 1-3 weeks, 29.0% waited 3-6 weeks, 9.7% waited 6-9 weeks, 3.3% waited 9-12 weeks, and 3.3% waited >12 weeks for surgery. Patients undergoing surgery 3-6 weeks after colon cancer diagnosis exhibited the best 30-day mortality (1.3%), 90-day mortality (2.3%), and 5-year overall survival (71.8%) (P < .001 for all). After risk-adjusting for confounders, all wait times beyond 6 weeks were associated with worse 5-year overall survival (6-9 weeks: HR 1.10, 95% CI 1.06-1.15; 9-12 weeks: HR 1.25, 95% CI 1.18-1.33; >12 weeks: HR 1.43, 95% CI 1.35-1.52; P < .001 for all). Subgroup analysis after stratification by disease stage demonstrated that patients with stage III colon cancer were able to wait up to 9 weeks before exhibiting worse 5-year overall survival, compared to 6 weeks for patients with stage I or II disease. Conclusions Colon cancer patients should undergo surgery 3-6 weeks after diagnosis, as all surgical delays beyond 6 weeks were associated with worse 30-day mortality, 90-day mortality, and 5-year overall survival.

Sentinel lymph nodes (SLNs) have for centuries been recognized as reliable and effective filters of foreign material, including tumor cells. Since the mid-20th century, this principle has been applied to oncologic care through sentinel lymph node biopsy (SLNB), which detects and quantifies the extent of regional metastasis. First pioneered in parotid tumors, the technique has since expanded to many branches of oncology including breast, melanoma, head and neck, gastrointestinal, and gynecologic tumors. Across these varied pathologies, SLNB has repeatedly demonstrated non-inferiority to traditionally more extensive lymphatic dissections, which are associated with higher rates of infectious, lymphatic, and neuropathic complications. In an era of ever increasing management options, this technique also provides prognostic and predictive information key to therapeutic selection. This paper reviews the history of the practice of SLNB and its evolution over the decades in a number of oncologic disciplines.

Retrorectal cysts are cystic lesions located in the retrorectal space and are a distinct subset of retrorectal tumours, which are often misdiagnosed due to their rarity and mimicry of symptoms caused by common diseases. We have described the presentation and management of four patients who were diagnosed with retrorectal cysts from a 10-year retrospective chart review at our institute, a tertiary care centre. In middle-aged women, the following should raise suspicion of retrorectal cyst: gastrointestinal or urinary obstructive features, mass or fullness palpable on the posterior wall on digital rectal examination, presacral dimple, perianal fistula and/or recurrent disease. Such features should prompt an MRI evaluation of the pelvis for definitive diagnosis.

BACKGROUND:Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays. PATIENTS AND METHODS:DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral heterogeneity. Response to nCRT was pathologically scored after surgical resection. RESULTS:Biopsy samples from 21 patient tumors were analyzed. Eight patients had disease noted to have complete response, 2 moderate, 4 minimal, and 7 poor. Higher MATH scores correlated with poorer response to treatment, demonstrating significantly increased tumor heterogeneity compared to complete response (P = .039). CONCLUSION:The application of MATH scores as a measure of tumor heterogeneity may provide a useful biomarker for treatment response in locally advanced rectal cancer.

Improvements in colorectal cancer (CRC) prevention, early detection, and treatment have resulted in substantial gains in survival. However, the health-related quality of life (HRQoL) of CRC survivors often depends on access to supportive care, which differs by survivors’ socioeconomic characteristics. The purpose of this study was to investigate the relationship between socioeconomic characteristics and HRQoL in a diverse group of CRC survivors. We conducted a population-based, cross-sectional study to examine the association between socioeconomic factors (household income, health literacy, and insurance status) and HRQoL domains of pain interference, fatigue, physical function, sleep disturbance, anxiety, and depression. PROMIS® Short Forms v.2.0 were used to assess domains of HRQoL. Linear regression modeling was used to estimate the coefficient representing the average HRQoL domain score and its 95% confidence interval (CI). Three hundred one CRC survivors participated in the survey. Low-income (≤ $30,000) CRC survivors had, on average, a 4.70-point (95% CI 1.10–8.28) higher pain interference score, a 7.02-point (95% CI 3.27–10.77) higher fatigue score, a 5.13-point (95% CI − 8.56 to − 1.71) lower physical function score, and a 4.44-point (95% 1.40–7.49) higher depression score than CRC survivors with an income ≥ $70,000. Survivors with Medicaid insurance reported significantly greater pain interference and worse physical function than privately insured survivors. Survivors with low health literacy reported significantly greater pain interference compared with survivors with high health literacy. Substantial socioeconomic disparities in HRQoL were observed in this diverse population of CRC survivors. Designing supportive care interventions to improve HRQoL among low-income and Medicaid-insured CRC survivors is critical for eliminating disparities in CRC outcomes.

Abstract Introduction: Cancer survivors increasingly report financial hardship as a consequence of the high cost of cancer care, yet the financial experience of traditionally underserved patients, including racial/ethnic minorities, non-English speakers, and rural residents, remains largely unstudied. The purpose of this study was to investigate potential disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy. Methods: In this cross-sectional study, individuals diagnosed with localized or regional colorectal cancer between 2004-2012 were ascertained by the population-based New Mexico Tumor Registry. Participants completed a mailed questionnaire or telephone survey about their cancer survivorship experience, including treatment-related financial hardship and receipt of surveillance colonoscopy. Participants were considered to have experienced treatment-related financial hardship if they reported any debt accumulation, bankruptcy filing, other financial sacrifices, or inability to pay medical bills as a consequence of their illness, its treatment, or its lasting effects. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: In this sample of 277 colorectal cancer survivors, 44% of participants reported financial hardship. Individuals with low health literacy (OR 5.41, 95% CI 1.45-20.1), Spanish-speaking Hispanics (OR 3.09, 95% CI 1.39-6.87), divorced, separated or single survivors (OR 1.94, 95% CI 1.94, 95% CI 1.06-3.54), and rural residents (OR 1.86, 95% CI 1.06-3.28) were more likely to report financial hardship. Nonadherence to surveillance colonoscopy guidelines was two times as likely among participants reporting financial hardship (OR 2.17 95% CI 1.01-4.67) and among rural residents (OR 2.28, 95% CI 1.07-4.48) than those reporting no financial hardship and urban residents, respectively. Conclusions: Substantial disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy exist. Identifying patients at risk of financial hardship and developing interventions to reduce the financial burden of cancer may improve adherence to surveillance recommendations. Citation Format: Jean A. McDougall, Matthew P. Banegas, Charles Wiggins, Ashwani Rajput, Vi K. Chiu, Kristina G. Flores, Anita Y. Kinney. Disparities in treatment-related financial hardship and adherence to surveillance colonoscopy guidelines in ethnically, linguistically, and geographically diverse colorectal cancer survivors [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C52.

Background: Cancer survivors increasingly report financial hardship as a consequence of the high cost of cancer care, yet the financial experience of rural cancer survivors remains largely unstudied. The purpose of this study was to investigate potential rural disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy. Methods: Individuals diagnosed with localized or regional colorectal cancer between 2004 and 2012 were ascertained by the population-based New Mexico Tumor Registry. Participants completed a mailed questionnaire or telephone survey about their colorectal cancer survivorship experience, including treatment-related financial hardship and receipt of surveillance colonoscopy. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Compared with urban colorectal cancer survivors (n = 168), rural colorectal cancer survivors (n = 109) were slightly older; more likely to be married (65% vs. 59%) and have an annual income <$30,000 (37% vs. 27%); and less likely to be employed (35% vs. 41%), have a college degree (28% vs. 38%), or a high level of health literacy (39% vs. 51%). Rural survivors were twice as likely as urban survivors to report treatment-related financial hardship (OR, 1.86; 95% CI, 1.06–3.28) and nonadherence to surveillance colonoscopy guidelines (OR, 2.28; 95% CI, 1.07–4.85). In addition, financial hardship was independently associated with nonadherence to surveillance colonoscopy (OR, 2.17; 95% CI, 1.01–4.85). Conclusions: Substantial rural disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy exist. Impact: Treatment-related financial hardship among rural colorectal cancer survivors may negatively affect adherence to guideline-recommended follow-up care. Cancer Epidemiol Biomarkers Prev; 27(11); 1275–82. ©2018 AACR.

IgG4-related disease (IgG4-RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG4 and tissue IgG4 levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid treatment. The low incidence and the heterogeneous nature of the disease has made consensus on diagnostic criteria for IgG4-RD difficult. Whether sclerosing mesenteritis (SM) is considered a manifestation of IgG4-RD is strongly debated. We present the case of a patient with a history of rheumatoid arthritis who presented with a calcified abdominal mass. She was found to have an isolated, pedunculated mesenteric mass positive for IgG4 and concurrently elevated serum IgG4 levels. Clinical features did not classify her disease as either SM or IgG4-RD as currently described in consensus statements. Concurrent diagnoses of IgG4-RD, SM and other autoimmune disorders, as well as postoperative recommendations for resected isolated IgG4-positive masses, are discussed.

Abstract INTRODUCTION: The H1047R mutation is the most frequent cancer-specific mutation in the catalytic subunit p110α of Class 1A PI3K. Our previous reports have shown that the H1047R is a gain-of-function mutation that increases colorectal cancer (CRC) cell migration & cancer metastasis. We have also shown that H1047R mutation may increases CRC HCT116 cell migration via actin cytoskeleton reorganization & cell morphology change. The actin cytoskeleton is a dynamic structure which is controlled or mediated by a number of small molecules & actin-binding proteins. The purpose of this study was to determine the differential gene expression profiles in CRC cells with either wild type (WT) or H1047R mutant (MUT) PIK3CA. METHODS: HCT116 cells engineered to contain either MUT or WT PI3KCA allele were used in this study. Total RNA was extracted from the two isogenic cell lines by commercial isolation reagents. RNA sequencing was used to identify the specific alterations in gene expression profiling of the cells. The raw RNA-seq reads were preprocessed through a customized analysis pipeline & summarized to gene level feature counts. The differential expression gene (DEG) analysis was performed using R & Bioconductor packages including edgeR. RESULTS: At significance levels false discovery rate (FDR) = 0.05, we identified 89 DEGs whose fold changes (FC) are greater than 2. Among the 89 DEGs, 49 are up-regulated & 40 are down-regulated by H1047R mutation. By GO (Gene Ontology) category pathway analysis, the H1047R mutation mediated gene expression alteration are involved in 26 pathways including cell migration, regulation of cell communication, cell surface receptor signaling pathway, morphogenesis, regulation of signaling & cell-cell signaling pathways. For example, the upregulated VCA (Versican) & EPHA4 (EPH Receptor A4) play important roles in controlling cell migration. CTEN/TNS4 was also upregulated, which localizes to focal adhesions & induces cell motility. On the other hand, the downregulated ARHGAP18 is a coding gene of Rho GTPase Activating Protein 18 which suppresses F-actin polymerization by inhibiting Rho, thereby regulating cell shape, spreading, & migration. CONCLUSION: The H1047R mutation induced specific alterations in gene expression profiling of CRC HCT116 cells have been detected. These changes appear to contribute to more aggressive cancer cell behavior. These results will guide further studies on the molecular mechanisms underlying H1047R-p110α mediated CRC metastasis. Understanding these mechanisms may allow for the development of novel therapeutic strategies for patients who bear the H1047R mutation. Citation Format: Guanghua Wan, Huining Kang, Scott Ness, Alissa Greenbam, Ashwani Rajput. H1047R mutation of p110 alpha alters expression level of genes which are associated with cell migration & cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-077. doi:10.1158/1538-7445.AM2017-LB-077

Over 2.1 million Native Americans (NA) reside in the United States and 5.2 million people identify as NA in combination with other ethnicities. NA population numbers were noted to increase 18 per cent from 2000 to 2010. Recent studies have revealed significant health disparities and inferior surgical outcomes in this small but growing U.S ethnic minority.1 The high incidence of both benign and malignant gallbladder disease in NA populations, specifically those living in the southwest United States, is widely known. Studies performed before the laparoscopic era suggested that NA may experience increased postoperative complications after cholecystectomy compared to non-Hispanic Whites (NHW), though rates of bile duct injury (BDI) were not examined during this time.2 Major BDI presents a rare though devastating complication of laparoscopic cholecystectomy (LC). The presence of acute cholecystitis, male sex, aberrant biliary anatomy, and older age are associated with an increased risk of BDI during LC. One study to date has explored ethnicity as a possible risk factor for BDI.3 NA were not analyzed as a separated ethnic group and their BDI risk remains unknown. We observed a high number of NA patients referred to our academic center for major BDI after LC. New Mexico is a tricultural and mostly rural state with a high incidence of gallbladder disease, presenting a unique opportunity to study major BDI in NA, Hispanic, and NHW populations. We hypothesized that the risk of BDI is higher in NA populations compared to NHW and Hispanics. The Hospital Inpatient and Discharge Data (HIDD), a state database maintained by the New Mexico Department of Health, was queried to obtain the total number of LCs occurring from 2010 to 2014. LCs were identified by ICD-9 code and sorted by race/ethnicity (as defined by patient self-reporting). The HIDD did not yield any results in a query for ICD-9 codes for common BDI, though 18 patients had ICD-9 codes consistent with additional biliary procedures that may indicate the occurrence of BDI. Secondary to the small sample size, the Department of Health could not release the ethnicities of these patients due to confidentiality concerns. Therefore, we could not determine ethnic distribution of BDI solely through the HIDD. To estimate the incidence of major BDI occurring in the state by ethnicity, a retrospective cohort analysis of all patients referred to our institution during the study period was performed. We are the only tertiary referral center in the state with a hepatobiliary unit established in 2009, receiving transfers from all types of facilities, both public and private, metropolitan and rural, for major BDI after LC. We examined patient demographics, LC indications, injury characteristics, and subsequent interventions. Exact Wilcoxon rank sum tests were used to compare continuous variables. Chi-squared tests examined categorical variables and determined odds ratios with 95 per cent confidence intervals and P values (<0.05 considered significant). A total of 12,608 patients underwent LC in New Mexico from 2010 to 2014. NHW compromised 39.3 per cent of the cohort (n 4 4952), Hispanic patients 41.0 per cent (n 4 5105) and NA 10.5 per cent (n 4 1313). Other ethnicities (8.7%) were excluded from analysis. A retrospective chart review revealed 23 patients (10 NA, 9 Hispanic, and 4 NHW) were referred to our hepatobiliary surgeon. We compared NA to nonNative American (non-NA) patients including NHW and Hispanics. Patient cohort characteristics are shown in Table 1. NA were disproportionately represented in our BDI cohort compared to the New Mexico state population (43 vs 10.4%; P < 0.0001). NA had significantly higher BMIs than non-NA patients. NA underwent LC in a rural setting more often, had increased incidence of acute cholecystitis and experienced one Address correspondence and reprint requests to Alissa Greenbaum, M.D., Department of Surgery, University of New Mexico, MSC 10 5610, Albuquerque, NM 87131. E-mail: agreenbaum@salud.unm.edu.

e18067 Background: The high cost of cancer care creates adverse financial consequences for cancer patients, impacting adherence to treatment, clinical outcomes, and quality of life. Prior studies estimate that 40% of colorectal cancer (CRC) patients experience treatment-related financial burden. This study aims to identify factors associated with financial burden and evaluate its relationship with cancer recurrence. Methods: This cross-sectional study identified individuals diagnosed with stages I-III CRC between 2001 and 2012 through the statewide New Mexico Tumor Registry. A comprehensive survey was administered in 2014. Participants were considered to have experienced financial burden if they reported any treatment-related debt accumulation, bankruptcy filing, other financial sacrifices, or inability to pay medical bills. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Among the 277 CRC survivors who participated in this study, 40% identified as Hispanic and 39% lived in a rural area. Financial burden was reported by 43% of CRC survivors. In a model adjusted for age at diagnosis, sex, race, ethnicity, education, and years since diagnosis, participants who spoke a mixture of English and Spanish (OR: 3.5, 95% CI: 1.3-9.5), those with low health literacy (OR: 2.4, 95% CI: 1.2-4.7), and those with public insurance (OR: 2.2, 95% CI: 1.2-4.4) were more likely to report financial burden. Ethnicity and rural status were not independently associated with financial burden. Six percent (n = 16) of participants experienced a CRC recurrence. Survivors who reported financial burden were 4-times as likely to experience a recurrence (OR: 4.3, 95% CI 1.1-17.7) as those who did not report financial burden. Conclusions: Language, low health literacy, and public insurance may increase the likelihood that CRC survivors experience financial burden. These disparities are alarming given the observed association between financial burden and CRC recurrence. Larger, prospective studies are needed to confirm the association between financial burden and recurrence and to identify potential intervention targets.

LESSONS LEARNED:Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single-agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential. BACKGROUND:Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase-2 (COX-2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX-2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity. METHODS:Patients with resectable (T3-4, N1-2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m2 b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions. RESULTS:Thirty-two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%-50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%-89%) and sphincter-sparing surgery (SSS): 56% (95% CI: 38%-74%). Common grade >3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease-free survival and overall survival (OS) were 84% (95% CI: 65%-93%) and 94% (95% CI: 77%-98%), respectively. CONCLUSION:Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%-78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.