Non-metastatic Rectal Cancer Patients Research Articles

Assessing the role of prognostic nutritional index in predicting outcomes for rectal cancer surgery

Background & AimsThe association of Prognostic Nutritional Index (PNI) with prognosis has been established for various cancer types, including rectal cancer. However, the precise relationship between PNI and body composition characteristics in patients with non-metastatic rectal cancer remain unclear. This study aimed to investigate the impact of PNI on overall survival and disease-free survival in non-metastatic rectal cancer patients undergoing total surgical resection. Additionally, it sought to assess the inflammatory status and body composition in patients across different PNI levels. MethodsPatients with non-metastatic rectal cancer who underwent total surgical resection, were consecutively enrolled. PNI was calculated using the formula: PNI = (10 x serum albumin [g/dl]) + (0.005 x lymphocytes/μL). Body composition was assessed using CT-derived measurements and laboratory tests performed at diagnosis were used to calculate inflammatory indices. Univariate and multivariate logistic regression analyses as well as Kaplan-Meier curves were used to determine prognostic values. ResultsA total of 298 patients were included. Patients with low PNI demonstrated significantly reduced overall survival and disease-free survival compared to those with high PNI (Hazard ratio [HR] 1.85; Confidence interval [CI] 1.30-2 .62; p= 0.001). Moreover, patients with low PNI exhibited heightened systemic inflammatory status and reduced skeletal muscle index, increased muscle radiodensity, as well as a decrease in subcutaneous adipose tissue area, subcutaneous fat index, and low attenuation of both subcutaneous and visceral adipose tissue. ConclusionThe PNI, assessed prior to treatment initiation, serves as a prognostic biomarker for non-metastatic rectal cancer patients undergoing total surgical resection and is linked with both inflammation and alterations in body composition.

327 Impact of Adjuvant Chemotherapy/Radiotherapy on the 5 Year Overall Survival of Patients with Non-Metastatic Rectal Cancer in Bulgaria - a Retrospective Population-Wide Observational Study

Abstract Introduction Survival rates of patients with non-metastatic rectal cancer (RC) have increased, due the use of adjuvant chemotherapy/radiotherapy post-surgery, recommended by the National Comprehensive Cancer Network (NCCN) [1–3]. The aim of the study was to analyse the impact of adjuvant chemotherapy/radiotherapy on the 5-year overall survival (OS) of patients diagnosed with non-metastatic RC patients in Bulgaria. Method This is a retrospective population wide observational study of 8968 cases registered with Colorectal cancer in the Bulgarian National Cancer Registry (BNCR) between 2015 and 2016. The mean and median age of patients with left colon (LCC) and right colon (RCC) along with rectal cancer (RC) was analysed. The impact of adjuvant chemotherapy and radiotherapy on the 5-Year OS for non-metastatic RC was analysed. Kaplan-Meier curve with log rank, ANOVA and chi-squared tests were used to estimate the statistical significance. Results The mean age at diagnosis for RCC, LCC and RC was 68.9, 67.41 and 66.4 respectively (p-Value=<0.001). The median age at diagnosis was 69, 68 and 67 for RCC, LCC and RC respectively. Our study showed that patients with non-metastatic RC that received both adjuvant chemotherapy and radiotherapy had a higher 5-year OS compared to patients who received either chemotherapy, radiotherapy or neither therapy (61.4%, 59.5%, 56.2%, 51.8%), p-Value=0.007. Less than 40% of patients received either adjuvant chemotherapy or radiotherapy. Conclusions Adjuvant chemotherapy/radiotherapy improves the 5-Year OS for patients with non-metastatic RC. NCCN guidelines should be implemented in Bulgaria [1–3]. Bulgaria will benefit by implementing an organised screening programme [4].

Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis

BackgroundThe primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection.MethodsConsecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed.ResultsOut of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001).ConclusionPrognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Development and validation of a nomogram to predict overall survival in young non-metastatic rectal cancer patients after curative resection: a population-based analysis

PurposeThis study aimed to establish and validate a nomogram for predicting overall survival (OS) in young non-metastatic rectal cancer (RC) patients after curative resection.MethodsYoung RC patients (under 50 years of age) from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Those patients randomly assigned to a training cohort and a validation cohort at a ratio of 7:3. The independent prognostic factors for OS were identified by univariate and multivariate Cox regression analysis. A nomogram model was built based on the independent prognostic variables and was evaluated by concordance index (C-index), receiver operating characteristics (ROC) curves, calibration plot, and decision curve analysis (DCA).ResultsA total number of 3026 young RC patients were extracted from SEER database. OS nomogram was constructed based on race, histological type, tumor grade, T stage, N stage, carcinoembryonic antigen (CEA) level, and number of lymph nodes (LN) examined. C-index, ROC curves, calibration plot, and DCA curves presented satisfactory performance of the above nomogram in predicting the prognosis of young non-metastatic RC patients after curative resection. The nomogram can identify three subgroups of patients at different risks, which showed different prognostic outcomes both in the training cohort and validation cohort.ConclusionWe successfully established a reliable and insightful nomogram to predict OS for young non-metastatic RC patients after curative resection. The nomogram may provide accurate prognosis prediction to guide individualized follow-up and treatment plans.

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors

This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

Modifications to Treatment Plan of Rectal Cancer in Response to COVID-19 at the Philippine General Hospital.

Purpose The coronavirus disease 2019 (COVID-19) pandemic has strained healthcare resources worldwide. Despite the high number of cases, cancer management should remain one of the priorities of healthcare, as any delay would potentially cause disease progression.Methods This was an observational study that included nonmetastatic rectal cancer patients managed at the Philippine General Hospital from March 16 to May 31, 2020, coinciding with the lockdown. The treatment received and their outcomes were investigated.Results Of the 52 patients included, the majority were female (57.7%), belonging to the age group of 50 to 69 years (53.8%), and residing outside the capital (59.6%). On follow-up, 23.1% had no disease progression, 17.3% had local progression, 28.8% had metastatic progression, 19.2% have died, and 11.5% were lost to follow up. The initial plan for 47.6% patients was changed. Of the 21 patients with nonmetastatic disease, 2 underwent outright resection. The remaining 19 required neoadjuvant therapy. Eight have completed their neoadjuvant treatment, 8 are undergoing treatment, 2 had their treatment interrupted, and 1 has yet to begin treatment. Among the 9 patients who completed neoadjuvant therapy, only 1 was able to undergo resection on time. The rest were delayed, with a median time of 4 months. One has repeatedly failed to arrive for her surgery due to public transport limitations. There was 1 adjuvant chemotherapy-related mortality.Conclusion Delays in cancer management resulted in disease progression in several patients. Alternative neoadjuvant treatment options should be considered while taking into account oncologic outcomes, acceptable toxicity, and limitation of potential COVID-19 exposure.

Prognostic value of pretreatment tumor-to-blood standardized uptake ratio (SUR) in rectal cancer.

The prognostic value of SUV on pretreatment F-18 FDG PET/CT imaging in patients with rectal cancer is a matter of debate. SUR is of prognostic value for survival in different cancers. In this study, we aimed to examine the potential prognostic value of SUR and other parameters in pretreatment F-18 FDG PET/CT for non-metastatic rectal cancer. One hundred four non-metastatic rectal cancer patients who underwent pretreatment PET/CT between March 2012 and January 2018 were included in the study. Firstly, SUVmax, SUVmean, MTV, and TLG were calculated semi-automatically at the workstation. SUR was calculated as the ratio of tumor SUVmax to thoracic aorta blood SUVmean. Univariate Cox regression and Kaplan-Meier analysis were used to evaluate overall survival (OS), progression free survival (PFS), and local recurrence (LR). Then, multivariate Cox regression analysis, which included the parameters that were significant in the univariate analysis, was performed. Multivariate Cox regression analysis revealed that SUR was a prognostic factor for PFS. Age and T stage were prognostic factors for both OS and PFS. MTV was found to be independent risk factors for OS. In our study, SUR was the only F-18 FDG PET/CT parameter found to be significant for PFS. The development of new parameters can increase the prognostic value of F-18 FDG PET/CT.

Risk factor analysis for inaccurate pre-operative MRI staging in rectal cancer

BackgroundVarious tumor characteristics might lead to inaccurate local MRI-defined stage of rectal cancer and the purpose of this study was to explore the clinicopathological factors that impact on the precision pre-treatment MRI-defined stage of rectal cancer.MethodsA retrospectively analysis was conducted in non-metastatic rectal cancer patients who received radical tumor resection without neoadjuvant treatment during 2007–2015 in the Sixth Affiliated Hospital of Sun Yat-sen University. Clinical T stage and N stage defined by pelvic enhanced MRI and pathological stage were compared and patients were subdivided into accurate-staging, over-staging and under-staging subgroups. Logistic regressions were used to explore risk factors for over-staging or under-staging.ResultsFive hundred fifty-one cases of patients were collected. Among them, 109 cases (19.4%) of patients were over-T-staged and 50 cases (8.9%) were under-T-staged, while 78 cases (13.9%) were over-N-staged and 75 cases (13.3%) were under-N-staged. Logistic regression suggested that pre-operative bowel obstruction was risk factor for over-T-staging (OR = 3.120, 95%CI: 1.662–5.857, P < 0.001) as well as over-N-staging (OR = 3.494, 95%CI: 1.797–6.794, P < 0.001), while mucinous adenocarcinoma was a risk factor for under-N-staging (OR = 4.049, 95%CI: 1.876–8.772, P < 0.001). Patients with larger tumor size were at lower risk for over-T-staging (OR = 0.837, 95%CI: 0.717–0.976, P = 0.024) and higher risk for over-N-staging (OR = 1.434, 95%CI: 1.223–1.680, P < 0.001).ConclusionBowel obstruction, mucinous adenocarcinoma and tumor size might have impact on the pre-operative MRI T staging or N staging of rectal cancer. Our results reminded clinicians to assess clinical stage individually in such rectal cancer patients.

Gray areas and evidence gaps in the management of rectal cancer as revealed by the comparison of recommendations from national and international clinical guidelines.

74 Background: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. Methods: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence according to the Oxford CEBM Levels of Evidence guidelines by using the χ2 statistic test. Results: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 2/10 cases (20%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 4.4726, p = 0.034). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. Conclusions: Substantial variation exists across national and international clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.

Association of Body Composition with Long-Term Survival in Non-metastatic Rectal Cancer Patients.

PurposeWe evaluated the association of body composition with long-term oncologic outcomes in non-metastatic rectal cancer patients.MethodsWe included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Center between January 2005 and December 2012. Body composition at diagnosis was measured using abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), and sarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscle index (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatory status was defined as a neutrophil-lymphocyte ratio of ≥3. Obesity was categorized by body mass index (≥ 25 kg/m2).ResultsAmong the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The 5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopenia vs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) rate was not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS (79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO, and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatory status, and tumor stage were confirmed as independent factors associated with OS on multivariate analysis. In subgroup analysis, association of SO with OS was more prominent in patients with (y)p stage 0-2 and no inflammatory status.ConclusionThe presence of SO and a low body mass index at diagnosis are negatively associated with OS in non-metastatic rectal cancer patients.

Predictors and Risk Factors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Population-Based Analysis.

Background: Patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) may have a better prognosis and may be eligible for non-operative management. The aim of this research was to identify variables for predicting pCR in rectal cancer patients after nCRT and to define clinical risk factors for poor outcome after pCR to nCRT and radical resection in rectal cancer patients.Methods: A retrospective review was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Non-metastatic rectal cancer patients who received radical resection after neoadjuvant chemoradiotherapy were included in this study. Multivariate analysis of the association between clinicopathological characteristics and pCR was performed, and a logistic regression model was used to identify independent predictors for pCR. A nomogram based on the multivariate logistics regression was built with decision curve analyses to evaluate the clinical usefulness.Results: A total of 6,555 patients were included in this study. The proportion of patients with pCR was 20.5% (n = 1,342). The nomogram based on multivariate logistic regression analysis showed that clinical T4 and N2 stages were the most significant independent clinical predictors for not achieving pCR, followed by mucinous adenocarcinoma and positive pre-treatment serum CEA results. The 3-year overall survival rate was 92.4% for those with pCR and 88.2% for those without pCR. Among all the pCR patients, mucinous adenocarcinoma patients had the worst survival, with a 3-year overall survival rate of 67.5%, whereas patients with common adenocarcinoma had an overall survival rate of 93.8% (P < 0.001). Univariate and multivariate analyses showed that histology and clinical N2 stage were independent risk factors.Conclusion: Mucinous adenocarcinoma, positive pre-treatment serum CEA results, and clinical T4 and N2 stages may impart difficulty for patients to achieve pCR. Mucinous adenocarcinoma and clinical N2 stage might be indicative of a prognostically unfavorable biological tumor profile with a greater propensity for local or distant recurrence and decreased survival.

Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines

BackgroundPre-operative radiotherapy (RT) or chemoradiotherapy (CRT) is frequently used prior to rectal cancer surgery to improve local control and survival. The treatment is administered according to guidelines, but these recommendations vary significantly between countries. Based on the stage distribution and risk factors of rectal cancers as determined by magnetic resonance imaging (MRI) in an unselected Swedish population, the use of RT/CRT according to 15 selected guidelines is described. Materials and methodsSelected guidelines from different countries and regions were applied to a well-characterized unselected population-based material of 686 primary non-metastatic rectal cancers staged by MRI. The fraction of patients assigned to surgery alone or surgery following pre-treatment with (C)RT was determined according to the respective guideline. RT/CRT administered to rectal cancer patients for other reasons, for example, for organ preservation or palliation, was not considered. ResultsThe fraction of patients with a clear recommendation for pre-treatment with (C)RT varied between 38% and 77% according to the different guidelines. In most guidelines, CRT was recommended to all patients who were not operated directly, and, in others, short-course RT was also recommended to patients with intermediate risk tumours. If only non-resectable or difficult to resect tumours were recommended pre-treatment, as stated in many Japanese publications, 9% would receive CRT followed by a delay to surgery. ConclusionsAccording to most guidelines, well over 50% of primary non-metastatic rectal cancer patients from a general population, in which screening for colorectal cancer is not practised, are recommended treatment with pre-operative/neo-adjuvant therapy.

Prognostic significance of sarcopenia and skeletal muscle mass change during preoperative chemoradiotherapy in locally advanced rectal cancer

The aim of this study was to investigate the prognostic impact of sarcopenia and skeletal muscle change in rectal cancer patients who underwent preoperative chemoradiotherapy (preop-CRT). From April 2004 to June 2013, we identified non-metastatic rectal cancer patients who underwent preop-CRT. Sarcopenia was evaluated according to previous cut-off value by computed tomography measured before starting preop-CRT (sarcopenia_pre) and 4-6 weeks after cessation of preop-CRT (sarcopenia_post). The severe muscle loss was defined as change in muscle mass<-4.2%/100 days. The hazard ratio (HR) and 95% confidence interval (CI) of sarcopenia and muscle change were estimated using a Cox proportional hazards model adjusted for potential confounders. Among 93 patients who underwent both pre and post-CRT CTs, 48 (51.6%) and 51 (54.8%) were identified as sarcopenia_pre and sarcopenia_post respectively. Twenty-three patients (24.7%) were included in the severe muscle loss group. Multivariable analysis identified sarcopenia_post (HR 2.6, 95% CI 1-6.2, p=0.023), and severe muscle loss (HR 2.8, 95% CI 1.2-6.2, p=0.011) along with age and ypStage as independent risk factors for overall survival. Clinical T4 stage was the only factor that can predict severe muscle loss (OR 3.4, 95% CI 1.2-9.4, p=0.016). Sarcopenia identified after the completion of preop-CRT and change in muscle mass<-4.2%/100 days during preop-CRT are promising parameters to predict overall survival in patents with locally advanced rectal cancer and should be investigated more rigorously.

Evaluating Surveillance Patterns after Chemoradiation-Only Compared with Conventional Management for Older Patients with Rectal Cancer

Upfront chemoradiation with omission of surgery (CR-only) is increasingly being used to treat rectal cancer. When CR-only is used with curative intent, intense surveillance is recommended. We hypothesized that in practice, few patients treated with CR-only receive intensive post-treatment surveillance. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare, all nonmetastatic rectal cancer patients (≥66 years old) diagnosed from 2004 to 2012, who received upfront chemoradiation, were included. Patients who received CR-only were compared with patients receiving neoadjuvant therapy plus proctectomy. In the 24 months after treatment, markers of surveillance, including carcinoembryonic antigen testing (CEA), endoscopy, and imaging, were compared between groups. A total of 2,482 individuals met the inclusion criteria: 21% (n= 514) had CR-only and 79% had conventional treatment (ie chemoradiation plus proctectomy). Only 2.5% and 3.4% of those in the CR-only and conventional treatment groups, respectively, were in complete compliance with NationalComprehensive Cancer Network surveillance guidelines during the first 2 years post-treatment (p < 0.01). The CR-only group was less likely than the conventional treatment group to receive: CEA (adjusted risk ratio [aRR] 0.57; 95% CI 0.50 to 0.65), endoscopy (aRR 0.76; 95% CI 0.66 to 0.87), and office visits (aRR 0.88; 95% CI 0.84 to 0.92), respectively. However, there were similar rates of cross-sectional imaging between groups (aRR 1.31; 95% CI 0.93 to 1.85). Adherence to guideline-recommended surveillance was poor for all Medicare patients with rectal cancer. Despite recommendations for closer follow-up, patients treated with CR-only were less likely to receive surveillance than those treated with conventional treatment. Efforts should be made to increase adherence to surveillance guidelines for all rectal cancer patients treated with curative intent, but particularly for those with higher risk of recurrence, such as those treated with CR-only.

Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey

This retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatment characteristics with univariate and multivariate analyses. Data of 593 consecutive non-metastatic rectal cancer patients were analyzed. Median follow-up was 41 months. Median OS was 9 years. Radiotherapy was delivered in pre-operative (n = 477, 80.5%), post-operative (n = 75, 12.6%) or exclusive (n = 41, 6.9%) setting. In the whole set of patients, age, nutritional condition, tumor stage, tumor differentiation, and surgery independently influenced OS. For patients experiencing surgery, OS was influenced by age, tumor differentiation and nodal status. Surgical resection is the cornerstone treatment for locally-advanced rectal cancer. Poor tumor differentiation and node involvement were identified as major predictive factor of poor OS. The research in treatment intensification and in identification of radioresistance biomarkers should therefore probably be focused on this particular subset of patients.

The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature

BackgroundColorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance.MethodsFrom twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups.ResultsWe have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440.ConclusionsFrom these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer. These results will pave the way for a larger cohort for better sensitivity and specificity of the signature to guide decisions in the choice of treatment.

Evaluating the Current Status of Rectal Cancer Care in the US: Where We Stand at the Start of the Commission on Cancer's National Accreditation Program for Rectal Cancer

In an effort to improve the quality of rectal cancer care in the US, the American College of Surgeons Commission on Cancer has developed the National Accreditation Program for Rectal Cancer (NAPRC). We aimed to describe the current status of rectal cancer care before implementation of the NAPRC. The 2011-2014 National Cancer Database was queried for non-metastatic rectal cancer patients who underwent proctectomy. The NAPRC process measures evaluated included clinical staging completion, treatment starting fewer than 60 days from diagnosis, CEA level drawn before treatment, tumor regression grading, and margin assessment. The NAPRC performance measures included negative proximal, distal, and circumferential margins, and ≥12 lymph nodes harvested during resection. There were 39,068 patients identified (mean age 62 years, 61.6% male sex). In >85% of patients, clinical staging was completed, treatment was started within 60 days, and all tumor margins were assessed. Pretreatment CEA level (64.6% complete) was the process measure most often omitted. However, completion of all included process measures occurred in only 28.1% of patients. All pathologic margins were negative in 79.8% of patients and 73.2% of specimens reported ≥12 lymph nodes. Overall, 56.3% of patients achieved all performance measures. Patients treated at high-volume centers (>30 cases/year) had higher odds of meeting all performance measures (odds ratio 1.42; p < 0.001). Overall, very few patients achieved all of the proposed quality measures for rectal cancer care. It will be important to re-evaluate these data after the implementation of the NAPRC.

Endoscopic ultrasound for rectal cancer staging: A population-based study of utilization, impact on treatment patterns, and survival.

Optimal rectal cancer (RC) outcomes depend on accurate locoregional staging. The study sought to describe the impact of endoscopic ultrasound (EUS) on RC treatment patterns and survival. Using the Surveillance, Epidemiology, and End Results-Medicare database, the study identified patients with RC between 2005 and 2007. The study excluded patients with stage IV disease, those not enrolled in Medicare parts A and B, those enrolled in managed care, and those staged with pelvic magnetic resonance imaging (because of low numbers). The study then compared outcomes between patients who received EUS and computed tomography of the abdomen and pelvis (CTAP) to those staged with CTAP alone after propensity score matching. Between 2005 and 2007, we identified 3,408 nonmetastatic RC patients. Compared with patients staged with CTAP alone, those who received EUS and CTAP were younger (median age: 75 vs 76years, P<0.0001), more likely men (57.6% vs 48.7%, P<0.0001), with a lower Charlson comorbidity index (P<0.0001). Predictors of EUS included socioeconomic status (highest vs lowest) (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.4-2.5), care by a gastroenterologist (OR 1.713, 95% CI 1.38-2.13), and care in a teaching hospital (OR 1.68, 95% CI 1.35-2.08). Receipt of neoadjuvant chemoradiation was higher in EUS-staged patients (50.3% vs 16.0%, P<0.0001). EUS-staged patients had longer overall survival compared with those staged with CTAP alone (60 vs 57months), but this was not statistically significant (P=0.24). Endoscopic ultrasound in RC staging is associated with higher utilization of neoadjuvant chemoradiation without a significant difference in overall survival.

EP-1270: Clinical outcome of non-metastatic rectal cancer patients with extremely high CEA level

EP-1270: Clinical outcome of non-metastatic rectal cancer patients with extremely high CEA level