Prognosis Of Rectal Cancer Patients Research Articles

Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50years and 50-66years groups than in > 66years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66years group (P > 0.05). Multivariate analysis showed age > 66years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5cm was independent risk factors for 5-year OS after LE; age > 66years, perineural invasion, and tumor size 3 to 5cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

Nomograms integrating the collagen signature and systemic immune-inflammation index for predicting prognosis in rectal cancer patients.

This study aimed to develop and validate a model based on the collagen signature and systemic immune-inflammation index to predict prognosis in rectal cancer patients who underwent neoadjuvant treatment. Patients with rectal cancer who had residual disease after neoadjuvant treatment at two Chinese institutions between 2010 and 2018 were selected, one used as a training cohort and the other as a validation cohort. In total, 142 fully quantitative collagen features were extracted using multiphoton imaging, and a collagen signature was generated by least absolute shrinkage and selection operator Cox regression. Nomograms were developed by multivariable Cox regression. The performance of the nomograms was assessed via calibration, discrimination and clinical usefulness. The outcomes of interest were overall survival and disease-free survival calculated at 1, 2 and 3 years. Of 559 eligible patients, 421 were selected (238 for the training cohort and 183 for the validation cohort). The eight-collagen-features collagen signature was built and multivariable Cox analysis demonstrated that it was an independent prognostic factor of prognosis along with the systemic immune-inflammation index, lymph node status after neoadjuvant treatment stage and tumour regression grade. Then, two nomograms that included the four predictors were computed for disease-free survival and overall survival. The nomograms showed satisfactory discrimination and calibration with a C-index of 0.792 for disease-free survival and 0.788 for overall survival in the training cohort and 0.793 for disease-free survival and 0.802 for overall survival in the validation cohort. Decision curve analysis revealed that the nomograms could add more net benefit than the traditional clinical-pathological variables. The study found that the collagen signature, systemic immune-inflammation index and nomograms were significantly associated with prognosis.

P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort study

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD. Methods The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress. Results In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients. Conclusion The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.

Can neoadjuvant chemoradiotherapy before lateral pelvic lymph node dissection improve local control and prognosis in rectal cancer patients with clinically suspected lateral lymph node metastasis? A multicenter lateral node study in China

AimsSelective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients.Materials and methodsData were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared.ResultsPatients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts.ConclusionsLPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.

Advances in rectal cancer: Real-world evidence suggests limited gains in prognosis for elderly patients

BackgroundRectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. Methods20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988–1997), partial (1998–2007), and full implementation (2008–2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. ResultsMedian survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 – 76.6]) to 79.2% (95%CI[77.8 – 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 – 18.8]); 6.7% (95%CI[6.1 – 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 – 73.3] to 67.6% [64.0 – 71.2]; Male 71.7% [65.9 – 77.4] to 74.0% [70.8 – 77.2]). ConclusionsReal-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

Nomogram including tumor deposition count to noninvasively evaluate the prognosis of rectal cancer patients: A retrospective study

To build a nomogram model that includes tumor deposition (TDs) count to noninvasively evaluate the prognosis of patients with rectal cancer (RC). A total of 262 patients between January 2013 and December 2018 were recruited and divided into 2 cohorts: training (n = 171) and validation (n = 91). Axial portal venous phase computed tomography images were used to extract radiomic features, and the least absolute shrinkage and selection operator-Cox analysis was applied to develop an optimal radiomics model to derive the Rad-score. A Cox regression model combining clinicopathological factors and Rad-scores was constructed and visualized using a nomogram. And its ability to predict RC patients’ survival was tested by Kaplan–Meier survival analysis. The time-dependent concordance index curve was used to demonstrate the differentiation degree of model. Calibration and decision curve analyses were used to evaluate the calibration accuracy and clinical usefulness of the nomogram model, and the prediction performance of the nomogram model was compared with the clinical and radiomics models using the likelihood test. Computed tomography-based Rad-score, pathological tumor (pT) stageT4, and TDs count were independent risk factors affecting the prognosis of RC. The whole concordance index of the nomogram model for predicting the overall survival rates of RC was higher than that of the clinical and radiomics models in the training (0.812 vs 0.59, P = .019; 0.812 vs 0.714, P = .014) and validation groups (0.725 vs 0.585, P = .002; 0.725 vs 0.751, P = .256). The nomogram model could effectively predict patients’ overall survival rate (hazard ratio = 9.25, 95% CI = [1.17–72.99], P = .01). The nomogram model also showed a higher clinical net benefit than the clinical and radiomics models in the training and validation groups. The nomogram model developed in this study can be used to noninvasively evaluate the prognosis of RC patients. The TDs count is an independent risk factor for the prognosis of RC.

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

It is well-established that tumor antigens and molecules expressed and secreted by cancer cells trigger innate and adaptive immune responses. These two types of anti-tumor immunity lead to the infiltration of the tumor's microenvironment by immune cells with either regulatory or cytotoxic properties. Whether this response is associated with tumor eradication after radiotherapy and chemotherapy or regrowth has been a matter of extensive research through the years, mainly focusing on tumor-infiltrating lymphocytes and monocytes and their subtypes, and the expression of immune checkpoint and other immune-related molecules by both immune and cancer cells in the tumor microenvironment. A literature search has been conducted on studies dealing with the immune response in patients with rectal cancer treated with neoadjuvant radiotherapy or chemoradiotherapy, assessing its impact on locoregional control and survival and underlying the potential role of immunotherapy in the treatment of this cancer subtype. Here, we provide an overview of the interactions between local/systemic anti-tumor immunity, cancer-related immune checkpoint, and other immunological pathways and radiotherapy, and how these affect the prognosis of rectal cancer patients. Chemoradiotherapy induces critical immunological changes in the tumor microenvironment and cancer cells that can be exploited for therapeutic interventions in rectal cancer.

High expression of cytoplasmic FOXO3 protein associated with poor prognosis of rectal cancer patients: A study from Swedish clinical trial of preoperative radiotherapy to big database analysis

IntroductionAccumulating evidence has implicated a pivotal role for FOXO3, FOXM1 and SIRT6 in cancer progression. The majority of researches focused on the functions of these proteins in drug resistance, but their relationships with radiotherapy (RT) response remain unclear. In this study, we examined protein expression of FOXO3, FOXM1 and SIRT6 and their clinical significance in a Swedish rectal cancer trial of preoperative RT. MethodsExpression of FOXO3, FOXM1 and SIRT6 protein was examined by immunohistochemistry in patient samples. Genetic analysis of FOXO3, FOXM1 and SIRT6 were performed by cBioportal and MEXPRESS database. Gene-gene network analysis was conducted using GeneMANIA. Functional enrichment analysis was performed based on LinkedOmics and Metascape online software. ResultsFOXO3 and FOXM1were mainly expressed in the cytoplasm in both normal and tumour tissues, and SIRT6 in both the cytoplasm and nucleus in normal and tumour tissues. FOXO3 and FOXM1 expression increased from normal mucosa to primary cancer (P < 0.001), while SIRT6 expression decreased from normal mucosa to primary cancer (P < 0.001). High FOXO3 expression correlated with late TNM stage (P = 0.040), distant metastasis (P = 0.032) and independently with disease free survival (DFS) in the RT patients (HR = 7.948; P = 0.049; 95% CI = 1.002–63.032) but not in non-RT patients (P > 0.05). Genetic analysis indicated that DNA methylation status contributed to FOXO3 overexpression. Functional enrichment analysis demonstrated that FOXO3 was closely related to metabolism-related signalling pathway which in turn associated with cancer radioresistance. Moreover, there were strong gene–gene interactions between FOXO3 and metabolism-related signalling. ConclusionsOur findings suggest that FOXO3 may be a prognostic factor in rectal cancer patients with RT.

Not all Rectal Cancer Patients Could Benefit From the Surgery on the Primary Site.

Previous studies have provided evidence that primary site surgery can improve the prognosis of rectal cancer patients, even in those with advanced age and distant metastasis, though results have been inconsistent. The current study aims to determine if all rectal cancer patients are likely to benefit from surgery in terms of overall survival. This study examined the impact of primary site surgery on the prognosis of rectal cancer patients diagnosed between 2010 and 2019 using multivariable Cox regression analysis. The study also stratified patients by age group, M stage, chemotherapy, radiotherapy, and number of distant metastatic organs. The propensity score matching method was used to balance observed covariates between patients who received and did not receive surgery. The Kaplan-Meier method was used to analyze the data, and the log-rank test was used to determine differences between patients who did and did not undergo surgery. The study included 76,941 rectal cancer patients, with a median survival of 81.0months (95% CI: 79.2-82.8months). Of these patients, 52,360 (68.1%) received primary site surgery, and they tended to be younger, have higher differentiated grade, earlier T, N, M stage, and lower rates of bone, brain, lung, and liver metastasis, chemotherapy, and radiotherapy than those without surgery. Multivariable Cox regression analysis revealed that surgery had a protective effect on the prognosis of rectal cancer patients, including those with advanced age, distant metastasis, and multiple organ metastasis, but not in patients with four organ metastases. The results were also confirmed using propensity score matching. Not all rectal cancer patients could benefit from the surgery on the primary site, especially the patients with more than four distant metastases. The results could help the clinicians to tailor targeted treatment regimens and provide a guideline for making surgical decisions.

High and low inferior mesenteric artery ligation in laparoscopic low anterior rectal resections: Aretrospective study.

The high or low inferior mesenteric artery (IMA) ligation in rectal cancer remains a great debate. This study retrospectively discussed the outcomes of the perioperative period, defecation and urinary function and long-term prognosis in rectal cancer patients with high or low IMA ligation. This study enrolled 220 consecutive rectal cancer cases, including 134 with high IMA ligation and 86 with low ligation. A comparison between the two groups was made for anastomotic leakage, low anterior resection syndrome (LARS), international prostate symptom score (IPSS), 5-year disease-free survival (DFS) and 5-year overall survival (OS). Low-ligation group had a longer operative time, and larger intraoperative blood loss. No significant difference was noted in anastomotic leakage incidence. In multivariable analysis, the male gender and tumor located at the lower rectum were identified as risk factors for anastomotic leakage. No significant differences were observed between groups in their LARS and IPSS questionnaire responses. The high-ligation vs. the low-ligation 5-year OS and DFS were 78.3% vs. 82.4% and 72.4% vs. 76.6%, respectively, which were not statistically different. The ligation level of the IMA had no significant effect on the anastomotic leakage incidence, defecation, urinary function, and long-term prognosis.

Computed tomography-measured body composition and survival in rectal cancer patients: a Swedish cohort study

BackgroundThe association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy.MethodsThis retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography scans at the time of diagnosis were used to assess the skeletal muscle index (SMI) and the visceral adipose tissue area (VAT). The patients were divided into a low or high SMI group and a low or high VAT group according to previously defined cutoff values. Endpoints included cancer-specific survival (CSS) and overall survival (OS).ResultsIn all patients, low SMI was associated with worse CSS (HR, 2.63; 95% CI, 1.35–5.12; P = 0.004) and OS (HR, 3.57; 95% CI, 2.01–6.34; P < 0.001) compared to high SMI. The differences remained significant after adjusting for potential confounders (CSS: adjusted HR, 2.28; 95% CI, 1.13–4.58; P = 0.021; OS: adjusted HR, 3.17; 95% CI, 1.73–5.82; P < 0.001). Low SMI was still related to a poor prognosis after stratifying by sex, tumour location, stage and radiotherapy (P < 0.05). High VAT was associated with better CSS (HR, 0.31; 95% CI, 0.11–0.84; P = 0.022) and OS (HR, 0.40; 95% CI, 0.17–0.97; P = 0.044) compared to low VAT among men with rectal cancer ≤ 10 cm from the anal verge. High VAT was associated with worse CSS (HR, 4.15; 95% CI, 1.10–15.66; P = 0.036) in women with rectal cancer ≤ 10 cm from the anal verge.ConclusionsLow SMI was associated with worse survival. High VAT predicted better survival in men but worse survival in women. The results suggest that CT-measured body composition is a useful tool for evaluating the prognosis of rectal cancer patients and demonstrate the need to include the sex and the tumour location in the analyses.

Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients.

Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson’s chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.

Effect of lateral lymph nodes without malignant characteristics on the prognosis of patients with rectal cancer.

Background: Lateral lymph node (LLN) metastasis is a poor prognostic factor for rectal cancer patients. However, the effect of LLNs without malignant characteristics on the prognosis of rectal cancer patients has been uncertain. Methods: Consecutive patients who underwent laparoscopic-assisted low anterior resection were included. Patients with MRI-detected LLNs, but without malignant characteristics, were compared with patients with no MRI-detected LLNs. Results: The local recurrence rate was higher in the LLN-present group than in the LLN-absent group (9.8% vs 2.5%; p=0.056). The overall survival of patients with no MRI-detected LLNs was significantly better than that of patients with MRI-detected LLNs (p=0.021). Conclusion: The presence of LLNs, even without malignant features, may lead to worse local control and overall survival.

Prognostic factors and individualized nomograms predicting overall survival in stage IV rectal cancer patients with different metastatic status: a SEER-based study.

BackgroundThe prognosis of rectal cancer patients with different metastatic status was significantly different. Our aim was to identify prognostic factors for metastatic rectal cancer (mRC) patients with different metastatic status and to construct specific nomograms to predict overall survival (OS).MethodsThis study retrospectively analyzed mRC patients from 2010 to 2016 in the Surveillance, Epidemiology, and End Results Program database. All patients were ultimately divided into four groups: synchronous liver metastasis, synchronous lung metastasis, synchronous other organs metastasis and synchronous multiple metastases. Univariate and multivariate cox analyses were performed to screen out independent factors for each group. Individualized nomograms were constructed in different metastatic modes. The concordance index (C-index), decision curve analysis (DCA), time-dependent receiver operating characteristic (ROC) curve and calibration curve were performed to verify these nomograms.ResultsFinally, 10,407 mRC patients were included in this study. Age, tumor grade, surgery of primary tumor, and chemotherapy were identified as common independent prognostic factors for each subgroup (all P<0.05). Other independent prognostic factors specific to each group included radiotherapy and marital status in the liver metastasis group, race, N stage, and the presence or absence of site-specific metastases in the multiple metastases group (all P<0.05). Higher T staging suggested worse OS in the group with liver, lung, and multiple site metastases. Individualized nomograms predicting 1-, 2-, and 3-year OS for each group were constructed by combining all independently significant risk factors in each group. The area under the curve (AUC) values and C-indexes of these nomograms created by each subgroup were greater than 0.7. All calibration curves and DCA curves showed that these nomograms had good clinical application significance.ConclusionsIndividualized prognostic nomograms were constructed for mRC patients with different metastatic status based on different prognostic factors. These nomograms presented satisfactory predictive effects, which helps to provide survival assessment and individualized treatment decision-making for mRC patients with different metastatic status.

Histopathological and Haemogram Features Correlate with Prognosis in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiation without Pathological Complete Response.

Background: Neoadjuvant chemoradiation therapy (NCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC); approximately 80% of patients do not achieve complete response. Identifying prognostic factors predictive of survival in these patients to guide further management is needed. The intratumoural lymphocytic response (ILR), peritumoural lymphocytic reaction (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PtLR) are correlated with the tumour microenvironment and cancer-related systemic inflammation. This study aimed to explore the ability of the ILR, PLR, NLR, and PtLR to predict survival in LARC patients without a complete response to NCRT. Methods: Sixty-nine patients who underwent NCRT and surgery were retrospectively reviewed. The ILR and PLR were assessed in surgical specimens, and the NLR and PtLR were calculated using pre- and post-NCRT blood count data. The Kaplan–Meier method and Cox regression analyses were performed for survival analysis. Results: A high PLR and high post-NCRT NLR and PtLR were significantly associated with better prognosis. Lymphovascular invasion (LVI), post-NCRT neutrophil count, and lymphocyte count were significant predictors of overall survival. LVI and the PLR were independent predictors of disease-free survival. Conclusions: NCRT-induced local and systemic immune responses are favourable prognostic predictors in LARC patients without complete response to NCRT.

Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

The number of cycles of adjuvant chemotherapy in stage III and high-risk stage II rectal cancer: a nomogram and recursive partitioning analysis

ObjectiveThe prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival.MethodsFour hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis.ResultsWe found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61–0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28.ConclusionIn conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient’s risk of death.

Relation between skeletal muscle volume and prognosis in rectal cancer patients undergoing neoadjuvant therapy.

The prognostic role of body composition indexes, and specifically sarcopenia, has recently been explored in different cancer types. However, conflicting results have been reported. Heterogeneity in cancer type, cancer stage or oncological treatments, as well as different methodology and definition of sarcopenia, could be accounted for different conclusions retrieved from literature. When focusing on colorectal cancer, it clearly appears that colon and rectal cancers are often treated as a single entity though they have different behaviors and treatments. Particularly, patients with advanced rectal cancer represent a peculiar group of patients that according to current guidelines are treated with neoadjuvant chemotherapy and radiotherapy followed by radical surgery. This review was restricted to a homogeneous group of patients with advanced lower rectal cancer and the aim of exploring whether there is a correlation between skeletal muscle depletion and prognosis. Literature was searched for articles related to patients with advanced rectal cancer undergoing neoadjuvant chemo-radiotherapy (NCRT) followed by radical surgery, in whom muscle mass and/or change in muscle mass during neoadjuvant treatment were measured. Eight full-text articles were selected and included in the present review. The main findings of our review were: (1) The majority of the studies defined sarcopenia as muscle mass alone over muscle strength or physical performance; (2) There was a great deal of heterogeneity in the definition and measures of sarcopenia, in the definition of cut-off values, and in the method to measure change in muscle mass; (3) There was not full agreement on the association between sarcopenia at baseline and/or after chemo-radiotherapy and prognosis, and only few studies found a significance in the multivariate analysis; and (4) It seems that a loss in skeletal muscle mass during NCRT is associated with the worst outcomes in terms of disease-free survival. In conclusion, analysis of muscle mass might provide prognostic information on patients with rectal cancer, however more robust evidence is needed to define the role of muscle depletion and/or muscle change during neoadjuvant treatments, related to this specific group of patients. If a prognostic role would be confirmed by future studies, the role of preoperative intervention aimed at modifying muscle mass could be explored in order to improve outcomes.

Prognostic Nomogram for Rectal Cancer Patients With Tumor Deposits.

AimTumor deposits (TDs) are an aggressive hallmark of rectal cancer, but their prognostic value has not been addressed in current staging systems. This study aimed to construct and validate a prognostic nomogram for rectal cancer patients with TDs.MethodsA total of 1,388 stage III–IV rectal cancer patients who underwent radical surgical resection from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed to identify the clinical value of TDs. TD-positive rectal cancer patients in the SEER database were used as the training set to construct a prognostic model, which was validated by Fujian Cancer Hospital. Three models were constructed to predict the prognosis of rectal cancer patients with TDs, including the least absolute shrinkage and selection operator regression (LASSO, model 1), backward stepwise regression (BSR, model 2), and LASSO followed by BSR (model 3). A nomogram was established among the three models.ResultsIn the entire cohort, TD was also identified as an independent risk factor for overall survival (OS), even after adjusting for baseline factors, stage, other risk factors, treatments, and all the included variables in this study (all P < 0.05). Among patients with TDs, model 3 exhibited a higher C-index and area under the curves (AUCs) at 3, 4, and 5 years compared with the American Joint Committee on Cancer staging system both in the training and validation sets (all P < 0.05). The nomogram obtained from model 3 showed good consistency based on the calibration curves and excellent clinical applicability by the decision curve analysis curves. In addition, patients were divided into two subgroups with apparently different OS according to the current nomogram (both P < 0.05), and only patients in the high-risk subgroup were found to benefit from postoperative radiotherapy (P < 0.05).ConclusionWe identified a novel nomogram that could not only predict the prognosis of rectal cancer patients with TDs but also provide reliable evidence for clinical decision-making.

A glycolysis-related two-gene risk model that can effectively predict the prognosis of patients with rectal cancer

BackgroundAerobic glycolysis is an emerging hallmark of cancer. Although some studies have constructed glycolysis-related prognostic models of colon adenocarcinoma (COAD) based on The Cancer Genome Atlas (TCGA) database, whether the COAD glycolysis-related prognostic model is appropriate for distinguishing the prognosis of rectal adenocarcinoma (READ) patients remains unknown. Exploring critical and specific glycolytic genes related to READ prognosis may help us discover new potential therapeutic targets for READ patients.ResultsThree gene sets, HALLMARK_GLYCOLYSIS, REACTOME_GLYCOLYSIS and REACTOME_REGULATION_OF_GLYCOLYSIS_BY_FRUCTOSE_2_6_BISPHOSPHATE_METABOLISM, were both significantly enriched in both COAD and READ through glycolysis-related gene set enrichment analysis (GSEA). We found that six genes (ANKZF1, STC2, SUCLG2P2, P4HA1, GPC1 and PCK1) were independent prognostic genes in COAD, while TSTA3 and PKP2 were independent prognostic genes in READ. Glycolysis-related prognostic model of COAD and READ was, respectively, constructed and assessed in COAD and READ. We found that the glycolysis-related prognostic model of COAD was not appropriate for READ, while glycolysis-related prognostic model of READ was more appropriate for READ than for COAD. PCA and t-SNE analysis confirmed that READ patients in two groups (high and low risk score groups) were distributed in discrete directions based on the glycolysis-related prognostic model of READ. We found that this model was an independent prognostic indicator through multivariate Cox analysis, and it still showed robust effectiveness in different age, gender, M stage, and TNM stage. A nomogram combining the risk model of READ with clinicopathological characteristics was established to provide oncologists with a practical tool to evaluate the rectal cancer outcomes. GO enrichment and KEGG analyses confirmed that differentially expressed genes (DEGs) were enriched in several glycolysis-related molecular functions or pathways based on glycolysis-related prognostic model of READ.ConclusionsWe found that a glycolysis-related prognostic model of COAD was not appropriate for READ, and we established a novel glycolysis-related two-gene risk model to effectively predict the prognosis of rectal cancer patients.