Outcomes Of Rectal Cancer Patients Research Articles

Outcomes in rectal cancer patients undergoing laparoscopic or robotic low anterior resection compared to open: a propensity-matched analysis of the NCDB (2010-2015).

Minimally invasive resection of rectal cancer is controversial due to concerns of the oncologic efficacy and the difficulties of a laparoscopic total mesorectal excision (TME). Using the National Cancer Database (NCDB), for the period 2010-2015, perioperative outcomes and overall survival (OS) in patients with rectal cancer who underwent laparoscopic or robotic low anterior resection (LLAR or RLAR) were compared to open LAR (OLAR) after propensity score matching. 26,047 patients underwent LAR: 4062 (16%) RLAR, 9236 (35%) LLAR, and 12,749 (49%) OLAR. Patient and clinical tumor characteristics were similar between groups after matching. The conversion rates among patients undergoing LLAR and RLAR were 15% and 8%, respectively. In matched OLAR and LLAR patients, longitudinal and circumferential resection margins (CRM) were positive in 5.4% and 3.2% (p < 0.001) and 5.5% and 4.1% (p < 0.001); length of stay was 6 and 5days, (p < 0.001); readmission was required in 6.5% and 7.0% (p = 0.112); OS at 1, 3, and 5years were 95.5%, 83.7%, and 72.0% and 95.9%, 86.3%, and 76.4%, respectively (p < 0.001). In matched OLAR and RLAR patients, longitudinal and CRM were positive in 5.4% and 3.2% (p < 0.001) and 5.5% and 3.9% (p < 0.001); length of stay was 6 and 5days (p < 0.001); readmission was required in 6.1% and 7.9%, (p = 0.010); and OS at 1, 3, and 5years were 96.2%, 86.5%, and 77.1% and 97.5%, 89.4%, and 79.7%, respectively (p = 0.001). In this national sample of propensity matched patients with rectal cancer who underwent open, laparoscopic, or robotic sphincter-saving rectal resection, only small differences in terms of resection margin status, length of stay, readmission, and overall survival were revealed. With acknowledgement of the limitations introduced by selection bias, our data indicate that each of the evaluated operative techniques results in acceptable outcomes for patients with rectal cancer.

Comparison of surgical data and survival outcome of rectal cancer patients that need upfront surgery after chemoradiotherapy versus salvage surgery after watch-and-wait

Comparison of surgical data and survival outcome of rectal cancer patients that need upfront surgery after chemoradiotherapy versus salvage surgery after watch-and-wait

The effect of time interval from chemoradiation to surgery on postoperative complications in patients with rectal cancer

BackgroundA prolonged time interval between chemoradiation and total mesorectal excision (TME) may render more rectal cancer patients eligible for organ-sparing approaches but may also cause more pelvic fibrosis and surgical morbidity. We estimated the effect of time interval on postoperative complications and other surgical outcomes in rectal cancer patients. MethodsThis is a population-based cohort study using data of the Dutch Colorectal Audit. Rectal cancer patients treated with chemoradiation followed by TME after an interval of 3–20 weeks were selected (n = 6,268). Time interval from completion of chemoradiation to TME was categorized into 3–6, 7–8, 9–10, 11–12 and 13–20 weeks. Outcomes included postoperative complication (any, and stratified by medical and surgical complications), reintervention, intraoperative complication, incomplete resection, positive circumferential margin (CRM) and pathological complete response (pCR). The interval of 7–8 weeks was the reference group. ResultsProlonged time intervals were not associated with a higher risk of a postoperative complication (any, surgical or medical), reintervention, and incomplete resection. Intraoperative complications were however more common after 11–12 weeks than after 7–8 weeks (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.20–2.69). The interval of 9–10 weeks was associated with less CRM positive resections, and 9–10 and 13–20 weeks with more pCR (relative to 7–8 weeks, OR = 0.74, 95%CI = 0.56–0.98; OR = 1.28, 95%CI = 1.04–1.58; and OR = 1.33, 95%CI = 1.04–1.71, respectively). ConclusionsCompared with 7–8 weeks, longer time intervals up to 13–20 weeks between chemoradiation and TME are not associated with more postoperative complications or more positive resection margins. Accordingly, prolonging the interval aiming for organ-sparing treatment is safe.

Impact of Body Composition on Surgical Outcome in Rectal Cancer Patients, a Retrospective Cohort Study

Obesity is becoming a bigger health problem every year. Current research shows that the obesity-related metabolic problems are strongly associated with visceral fat and not subcutaneous fat. Visceral obesity (VO) is associated with a worse postoperative outcome in multiple fields of abdominal surgery. On the other hand, muscle mass is related to better postoperative outcome. In rectal cancer patients, we studied the influence of visceral obesity and muscle mass on postoperative complications. The visceral fat area (VFA) and skeletal muscle area (SMA) were determined on preoperative CT scans in 406 patients. The preoperative comorbidity, per-operative outcome and postoperative complications were extracted retrospectively from the patient files. VO was defined as a VFA > 100cm2. Correlations between body composition, postoperative complications and LOS were studied. In our study, 67% of the patients were classified as visceral obese. Mean body mass index (BMI) was higher in the VO group (26.6 ± 3.5 vs 23.5 ± 2.8; p < 0.001). Visceral obese patients had a higher prevalence of cardiac comorbidity (29% vs 13% p = 0.001), hypertension (36% vs 20% p = 0.002) and diabetes mellitus (16% vs 5% p = 0.002). In addition, VO patients had more operative blood loss (431 vs 310mL; p = 0.008), longer operating time (166 vs 149min p = 0.003) and more wound infections (14% vs 8% p = 0.048). Visceral obesity was associated with more complications (OR: 1.63 p = 0.043) and longer LOS (risk estimate: 1.18 p = 0.009). VO patients more often had a history of cardiac disease, hypertension and diabetes mellitus. Visceral obesity correlated with a worse outcome after surgery for rectal cancer.

Comprehensive treatment of rectal cancer patients with synchronous distant metastases

Objective : to analyze short-term and long-term outcomes of surgical, combination, and comprehensive treatment in patients with metastatic rectal cancer. Materials and methods . We performed a retrospective analysis of prospectively collected data on the outcomes of rectal cancer patients receiving surgical, combination (surgery + chemotherapy), or comprehensive (chemoradiotherapy + surgery + chemotherapy) treatment in the Department of Proctology at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, between 1999 and 2015. We assessed overall survival, frequency of postoperative complications, postoperative death rates and frequency of complications associated with chemoradiotherapy. Results . The study included 366patients that were divided into 3 groups according to the treatment strategy. The 2-year survival rate was 83 % in group 3 (comprehensive treatment) vs 40 % in groups 1 and 2. Median survival was 43 months in group 3 compared to 18 and 14 months in groups 2 and 1 respectively. The number of postoperative complications was 19 %, 13.4 %, and 15.1 % in groups 1, 2 and 3 respectively. There was one postoperative death (1.1 %) in group 3. Conclusion . Comprehensive treatment significantly improves overall survival of rectal cancer patients without increasing the risk of postoperative complications.

Hospital volume and outcome in rectal cancer patients; results of a population-based study in the Netherlands

BackgroundClinically staged T1-3 rectal cancer (cT1-3) is generally treated by total mesorectal excision(TME) with or without neoadjuvant therapy and sometimes requires beyond TME-surgery, whereas cT4 rectal cancer often requires both. This study evaluates the outcome of cT1-3 and cT4 rectal cancer according to hospital volume. MethodsPatients undergoing rectal cancer surgery between 2005 and 2013 in the Netherlands were included from the National Cancer Registry. Hospitals were divided into low(1–20), medium(21–50) and high(>50 resections/year) volume for cT1-3 and low(1–4), medium(5–9) and high(≥10 resections/year) volume for cT4 rectal cancer. Cox-proportional hazards model was used for multivariable analysis of overall survival (OS). ResultsA total of 14.050 confirmed cT1-3 patients and 2.104 cT4 patients underwent surgery. In cT1-3 rectal cancer, there was no significant difference in 5-year OS related to high, medium and low hospital volume (70% vs. 69% vs. 69%). In cT4 rectal cancer, treatment in a high volume cT4 hospital was associated with a survival benefit compared to low volume cT4 hospitals (HR 0.81 95%CI 0.67–0.98) adjusted for non-treatment related confounders, but this was not significant after adjustment for neoadjuvant treatment. Patients with cT4-tumours treated in high volume hospitals had a significantly lower age, more synchronous metastases, more patients treated with neoadjuvant therapy and a higher pT-stage. ConclusionHospital volume was not associated with survival in cT1-3 rectal cancer. In cT4 rectal cancer, treatment in high volume cT4 hospitals was associated with improved survival compared to low volume cT4 hospitals, although this association lost statistical significance after correction for neoadjuvant treatment.

Impact of Mucin Proportion in the Pretreatment MRI on the Outcomes of Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

PurposeThe purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer.Materials and MethodsBetween 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed.ResultsAfter neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance.ConclusionPoor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.

Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy.

To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial-mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.

142P - Biological characteristics predict outcome of rectal cancer patients: Data from tertiary care hospital in a low economic country

Background: Management of rectal cancer has been evolved significantly in the last few decades, improvement in disease control were achieved with introduction of neoadjuvant chemoradiation followed by surgical excision. Objective: To determine progression free survival and overall survival of the patients with rectal cancer and various factors that affect survival. Methods: We retrospectively collected data of newly diagnosed patients with rectal cancer presented at Aga Khan University Hospital Karachi, from 2009 to 2016. All the patients with early stage or locally advanced rectal cancer who either underwent upfront surgery or received neoadjuvant chemoradiation followed by surgery were included in the study. Results: From 2009 to 2016, 101 patients with newly diagnosed rectal carcinoma were included in the study. Median age 47 years (21-80), 66.3 % (n = 67) were males whereas 33.6 % (n = 34) female. 9.90% (n = 10) have signet ring cell histology while 90.1 % (n = 91) are adenocarcinoma. 59.4 % (n = 60) were stage III, 26.7% (n = 27) stage II and 13.8% (n = 14) were stage I at the time of diagnosis, 47.5% (n = 48) underwent upfront surgery while 52.4% (n = 53) received neoadjuvant chemoradiation. 31 patients who underwent upfront surgery completed adjuvant chemoradiation. 51 patient after neoadjuvant chemoradiation underwent surgery, 2 had disease progression. Of them 7 %( n = 4) of the patients had pathological complete response (CR) while 92.1% (n = 47) had non CR. Median follow up was 3 years (1-5 yrs.), 37 pts. had disease progression. Median time to progression of all patients was 21 months and overall survival of 24 months. In subgroup analysis patient with adenocarcinoma had better PFS (21 vs. 19 months) and OS (24 vs. 21 months) as compared to signet ring histology. Patient who had pathological CR after neoadjuvant chemoradiation had a PFS and OS of 32 months respectively vs. 16 and 18 months who had no pathological CR. Conclusions: Several factors affect survival of rectal cancer patients, our analysis showed that the patients who had pathological complete response and non-signet ring cell histology had better time to progression as that which was reported in international studies. Legal entity responsible for the study: Aga University Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Predicting Treatment Outcome of Rectal Cancer Patients with Neoadjuvant Chemoradiotherapy by ctDNA: The Potential Use of ctDNA Monitoring as Organ-Sparing Approach

Predicting Treatment Outcome of Rectal Cancer Patients with Neoadjuvant Chemoradiotherapy by ctDNA: The Potential Use of ctDNA Monitoring as Organ-Sparing Approach

C-Reactive Protein Level Predicts Survival Outcomes in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation Therapy.

Systemic inflammatory response, as measured by C-reactive protein (CRP), is associated with prognosis in various types of human malignancies. However, to the best of our knowledge, the clinical significance of CRP in patients with locally advanced rectal cancer that undergo preoperative chemoradiation has not been investigated in detail. This retrospective study validates CRP as a potential predictive marker for survival outcomes in rectal cancer patients. In this study, we enrolled 125 patients that received total mesorectal excision after preoperative chemoradiation for rectal cancer between January 2003 and December 2010. We investigated the association between preoperative CRP and clinicopathological characteristics and assessed the prognostic value of CRP. The median follow-up was 41months. Elevated CRP showed significant correlation with high histological grade (P = 0.009) and cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer-specific survival were significantly lower in the elevated CRP group (P = 0.001). Moreover, CRP was the strongest predictive factor for cancer-specific survival in multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a significant prognostic factor in patients with node-positive disease (P = 0.025) and was associated with poorer tumor regression (TRG4-5; P = 0.011). The results of our study suggest that preoperative CRP level shows prognostic significance in rectal cancer patients that have undergone chemoradiation. Therefore, preoperative CRP may help clinicians to identify patients that need additional therapy to reduce systemic failure.

Clinical Significance and Radiation Response of miR-302a, miR-105 and miR-888 Expression in Rectal Cancer

Differential expressions of micoRNA (miRNA or miR) were intensively evaluated in colorectal cancer. However, the value of certain miRNAs on radiation response and clinical outcome in rectal cancer patients remains to be elucidated. Here, the expression of miR-302a, miR-105 and miR-888 was determined using Real-time PCR in normal mucosa and rectal cancer from 39 patients with and 41 patients without radiotherapy (RT) before surgery. The relationship of miR-302a, miR-105 and miR-888 expression with biological factors and prognosis was analyzed and identified by The Cancer Genome Atlas (TCGA) database. miR-105 expression in rectal cancer was higher than that in normal mucosa in RT (P=0.042) and non-RT cases (P=0.003), which was associated with mucinous histological type (P=0.004), Cox-2 (P=0.042) and p73 expression (P=0.030). miR-302a expression was more frequently in tumors with necrosis (P=0.033) and cytoplasmic Wrap53 expression (P=0.030), and miR-888 expression occurred more frequently in tumors with Survivin (P=0.015), AEG-1 (also known as MTDH, P=0.003) and SATB1 expression (P=0.036). TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. TCGA database demonstrated that miR-105 expression was associated with high CEA level (P=0.048). RT reduced miR-302a, miR-105 and miR-888 expression. miR-888 expression was independently related to worse survival of rectal cancer patients without RT (OS, P=0.001; DFS, P=0.009). Thus, our findings suggest the involvement of miR-105 in pathogenesis and of miR-888 in prognosis, and imply potential value of miR-302a, miR-105, and miR-888 on radiation response in rectal cancer. Funding: This work was supported by the grants from the Swedish Cancer Foundation, Swedish Research Council and the Health Research Council in the South-East of Sweden. Declaration of Interest: The authors have no conflicts of interest. Ethical Approval: Informed consent was obtained from all patients, and the study protocol was approved by the Institutional Review Board of Linkoping University, Sweden. All experiments were performed in accordance with relevant guidelines and regulations.

Predicting treatment outcome of rectal cancer patients underwent neoadjuvant chemoradiotherapy by ctDNA: The potential use of ctDNA monitoring as organ-sparing approach.

3608Background: Neoadjuvant chemoradiotherapy (nCRT) is widely accepted for the treatment of locally advanced rectal cancer (LARC). Watch & wait (W&W) strategy can improve life quality, but needs s...

Marital status and survival in patients with rectal cancer: An analysis of the Surveillance, Epidemiology and End Results (SEER) database

BackgroundMarital status has been validated as an independent prognostic factor for survival in several cancer types, but is controversial in rectal cancer (RC). The objective of this study was to investigate the impact of marital status on the survival outcomes of patients with RC. MethodsWe extracted data of 27,498 eligible patients diagnosed with RC between 2004 and 2009 from the Surveillance, Epidemiology and End Results (SEER) database. Patients were categorized into married, never married, divorced/separated and widowed groups.We used Chi-square tests to compare characteristics of patients with different marital status.Rectal cancer specific survival was compared using the Kaplan–Meier method,and multivariate Cox regression analyses was used to analyze the survival outcome risk factors in different marital status. ResultsThe widowed group had the highest percentage of elderly patients and women,higher proportion of adenocarcinomas, and more stage I/II in tumor stage (P < 0.05),but with a lower rate of surgery compared to the married group (76.7% VS 85.4%). Compared with the married patients, the never married (HR 1.40), widowed (HR 1.61,) and divorced/separated patients (HR 1.16) had an increased overall 5-year mortality. A further analysis showed that widowed patients had an increased overall 5-year cause-specific survival(CSS) compared with married patients at stage I(HR 1.92),stage II (HR 1.65),stage III (HR 1.73),and stage IV (HR 1.38). ConclusionOur study showed marriage was associated with better outcomes of RC patients, but unmarried RC patients, especially widowed patients,are at greater risk of cancer specific mortality.

Outcomes of Rectal Cancer Patients With Low Sphincter-Preserving Operations Compared to Patients With Abdominoperineal Resection

The surgical management for low rectal cancer patients has evolved as a result of the introduction of preoperative chemoradiotherapy and innovative technical developments. As a result, abdominoperineal resection (APR) for low rectal cancer has decreased over time. Further, the introduction of intersphincteric resection and preoperative chemoradiotherapy has made it possible to proceed with sphincter preservation. However, the oncologic and functional outcomes of intersphincteric resection have been questioned because of the narrow radical margin and sphincter excision. We review the literature to evaluate the oncologic outcomes of sphincter-preserving surgery in low rectal cancer compared to abdominoperineal resection. The oncologic outcome of extended abdominoperineal resection, which was developed to improve result of surgical outcome for low rectal cancer, is also discussed. The present manuscript addresses the evidence that shows oncologic safety and acceptable functional outcomes of intersphincteric resection. Our review shows that intersphincteric resection should be considered as an established acceptable operation for the management of low rectal cancer. On the other hand, APR results in frequent positive circumferential margins, higher local recurrence rate compared to sphincter-preserving resection. Nonetheless, abdominoperineal resection was inevitable for some subset of patients; therefore, efforts to improve oncologic outcomes after abdominoperineal resection have to be made. Extended APR which considers tumor extensiveness and standardizes perineal surgical extent has been proposed and oncologic benefits as well as overall outcomes are being evaluated. The current trend appears to indicate that the rate of intershincteric resection is increasing while APR decreasing. However, a multidisciplinary approach to low rectal cancers should emphasize oncologic and overall outcomes independent of sphincter preservation.

Robot-assisted surgery for rectal cancer: where do we stand?

The use of robotic technology in rectal cancer surgery has gained wide adoption worldwide during the last ten years. However, the scientific evidence in support of such an approach is limited and the potential benefits of this technology are advocated based on the results of small and low-quality studies. The aim of this manuscript is to review the literature and to update the current knowledge of the impact of robot-assisted resection on the outcomes of rectal cancer patients.

Radiotherapy of rectal cancer in elderly patients: Real-world data assessment in a decade

Background and purposeThere is paucity of data on the efficacy and toxicity of radiotherapy in rectal cancer (RC) elderly patients. The objective was to identify management strategies and resulting outcomes in RC patients ≥70 years undergoing radiotherapy. Material and methodsA retrospective study included consecutive RC patients ≥70 years undergoing rectal radiotherapy. ResultsFrom 2004–2015, 340 RC patients underwent pre-operative (n = 238; 70%), post-operative (n = 41, 12%), or exclusive (n = 61, 18%) radiotherapy, with a median age of 78.5 years old (range: 70–96). Radiotherapy protocols were tailored, with 54 different radiotherapy programs (alteration of the total dose, and/or fractionation, and/or volume). Median follow-up was 27.1 months. Acute and late grade 3–4 radio-induced toxicities were reported in 3.5% and 0.9% of patients. Metastatic setting (OR = 6.60, CI95% 1.47–46.03, p = 0.02), exclusive radiotherapy (OR = 5.08, CI95% 1.48–18.21, p = 0.009), and intensity-modulated radiotherapy (OR = 6.42, CI95% 1.31–24.73, p = 0.01) were associated with grade ≥3 acute toxicities in univariate analysis. Exclusive radiotherapy (OR = 9.79, CI95% 2.49–43.18, p = 0.001) and intensity-modulated radiotherapy (OR = 12.62, CI95% 2.05–71.26, p = 0.003) were independent predictive factors of grade ≥3 acute toxicities in multivariate analysis. A complete pathological response was achieved in 12 out of 221 pre-operative patients (5.4%). Age, tumor stage, and surgery were independent predictive factors of survival in multivariate analysis. At end of follow-up, 7.1% of patients experienced local relapse. ConclusionRadiotherapy for RC in elderly patients appeared safe and manageable, perhaps due to the tailoring of radiotherapy protocols. Tailored management resulted in acceptable rate of local tumor control.

The influence of hospital and surgeon volume on survival and local control in rectal cancer: Long-term results of the CAO/ARO/AIO-94 trial.

738 Background: The association of hospital and surgeon volume with the outcome of rectal cancer patients is under debate. In this study the long-term influence of the hospital as well as the surgeon volume on overall survival and local recurrence were investigated. Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with locally advanced rectal cancers were evaluated. Survival and local recurrence rates were stratified by the hospital recruitment volume (≤20 vs. 21-90 vs. &gt; 90 patients) and by the surgeon volume (≤10 vs. 11-50 vs. &gt; 50 procedures). Results: Patients treated in „high-volume“ hospitals had a longer overall survival than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was significantly associated with decreased local recurrences (p = 0.01) but had no influence on overall survival. The effect of neoadjuvant chemoradiation on local control was the strongest in patients being operated by medium-volume surgeons. Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on local control.

High chloride channel accessory 1 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy.

Background: Concurrent chemoradiotherapy (CCRT) has now become the standard of treatments for advanced rectal cancer before surgery. To search the biological molecules with prognostic and therapeutic potential of CCRT could be beneficial for these patients. Recently, aberrant expression of chloride channels has been linked to radio-resistance in glioblastoma; however, its clinical implication has not been well-studied in rectal cancers. Therefore, we examined the clinical significance of targetable drivers associated with chloride channel activity in patients with rectal cancer receiving CCRT.Methods: After datamining from a published transcriptome of rectal cancers, upregulation of CLCA1 gene was recognized to be significantly correlated with non-responders of CCRT. In validation cohort of rectal cancers, the expression levels of CLCA1 were accessed by using immunohistochemistry assays in 172 tumor specimens that were obtained before any treatment. Expression levels of CLCA1 were statistically analyzed with principal clinicopathological features and survival outcomes in this substantial cohort.Results: In validation cohort, high expression of CLCA1 was significantly associated with higher pre-treatment tumor nodal stages (P=0.032), vascular invasion (P=0.028), and inferior tumor regression grade (P=0.042). In survival evaluations, high expression of CLCA1 was significantly correlated with worse local recurrence-free survival (LRFS; P=0.0012), metastasis-free survival (MeFS; P =0.0114), and disease-specific survival (DSS; P=0.0041). Furthermore, high expression of CLCA1 remained an independent prognosticator of shorter LRFS (P=0.029, hazard ratio=2.555), MeFS (P=0.044, hazard ratio=2.125) and DSS (P=0.044, hazard ratio=2.172).Conclusions: High expression of CLCA1 is significantly associated with poor therapeutic response and survival outcomes in rectal cancer patients with CCRT treatment before surgery. With the development of specific inhibitors, our findings indicate not only prognostic but also therapeutic potential of CLCA1 in rectal cancers.

Are pathological high-risk features in locally advanced rectal cancer a useful selection tool for adjuvant chemotherapy?

BackgroundSeveral histological high-risk factors are used as an indication for adjuvant therapy in stage II colon cancer. Those and other factors, including lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding are associated with decreased outcome. In this study, we evaluated the prognostic and predictive values of these biomarkers in a cohort of rectal cancer patients. Materials and methodsThe trial-based cohort consisted of 221npTNM stage II–III rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre randomised phase III trial. Patients treated with neoadjuvant radiotherapy and TME surgery were randomised between adjuvant chemotherapy or observation. Lymphatic invasion, PNI, extramural venous invasion, intramural venous invasion and tumour budding were determined in standard tissue slides. ResultsThe presence of PNI (HR 3.36; 95% CI 1.82–6.21), extramural vascular invasion (HR 1.93; 95% CI 1.17–3.19) and tumour budding (HR 1.83, 95% CI 1.11–3.03) was associated with a significant worse overall survival. The presence of ≥2 adverse biomarkers resulted in a stronger prediction of adverse outcome in terms of overall survival (HR 2.82; 95% CI 1.66–4.79), disease-free survival (HR 2.27; 95% CI 1.47–3.48), and distant recurrence (HR 2.51; 95% CI 1.56–4.02). None of these markers alone or combined predicted a beneficial effect of adjuvant chemotherapy. DiscussionWe confirmed that several stage-independent biomarkers were significantly associated with a decreased outcome in rectal cancer patients. More importantly, these markers did not have predictive value and are thus not useful to select for adjuvant therapy in rectal cancer.