Survival In Rectal Cancer Patients Research Articles

Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage: A Retrospective Dutch Population-based Study.

Objective:The aim was to evaluate the impact of anastomotic leak (AL) after colon cancer (CC) and rectal cancer (RC) surgery on 5-year relative survival, disease-free survival (DFS), and disease recurrence.Background:AL after CC and RC resection is a severe postoperative complication with conflicting evidence whether it deteriorates long-term outcomes.Methods:Patients with stage I to IV CC and RC who underwent resection with primary anastomosis were included from the Netherlands Cancer Registry (2008–2018). Relative survival, measured from day of resection, and multivariable relative excess risks (RERs) were analyzed. DFS and recurrence were evaluated in a subset with stage I to III patients operated in 2015. All analyses were performed with patients who survived 90 days postoperatively.Results:A total of 65,299 CC and 22,855 RC patients were included. Five-year relative survival after CC resection with and without AL was 95% versus 100%, 89% versus 94%, 66% versus 76%, and 28% versus 25% for stage I to IV disease. AL was associated with a significantly higher RER for death in stage II and III CC patients. Stage-specific 5-year relative survival in RC patients with and without AL was 97% versus 101%, 90% versus 95%, 74% versus 83%, and 32% versus 41%. AL was associated with a significantly higher RER for death in stage III and IV RC patients. DFS was significantly lower in CC patients with AL, but disease recurrence was not associated with AL after colorectal cancer resection.Conclusion:AL has a stage-dependent negative impact on survival in both CC and RC, but no independent association with disease recurrence.

Impact of renin-angiotensin system inhibitors on the survival of patients with rectal cancer

BackgroundRenin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection.MethodsBetween 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan–Meier estimator with the log-rank test and the Cox proportional hazards model.ResultsThe log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p = 0.009) and non-RASI users (p = 0.013). Disease-free survival (DFS) was better in the group of ARB users compared to ACEI users. However, the difference was not statistically significant (p = 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147–0.724, p = 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135–0.850, p = 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016–1.073, p = 0.002), regional lymph node metastasis (ypN +) (HR: 2.157, 95% CI: 1.395–3.334, p = 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799–8.301, p = 0.001). Additional factors affecting DFS included ypN + (HR: 2.310, 95% CI: 1.374–3.883, p = 0.002) and PNI (HR: 4.351, 95% CI: 1.584–11.954, p = 0.004).ConclusionsThe use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.

Abstract 3221: Differences in body composition among rectal cancer patients with neo-adjuvant treatment-related toxicity: Results from the ColoCare Study

Abstract BACKGROUND Neo-adjuvant chemoradiation is standard of care for patients diagnosed with stage II and III rectal cancer. This treatment can cause significant toxicities and may require treatment modifications. Obesity and low muscle mass (=sarcopenia) may portend increased toxicity to chemotherapy and/or radiation and may further affect mortality in rectal patients. The present study investigates associations of pre-treatment body composition parameters with toxicity in prospectively followed rectal cancer patients. METHODS This initial analysis includes data from n=320 stage II and III rectal cancer patients from four study sites of the ColoCare Study. All patients underwent neo-adjuvant treatment. Pre-treatment CT scans were semi-automatically segmented at spinal level L3 vertebrae using SliceOmatic + ABACS software v5.0 rev13 to quantify: subcutaneous and visceral fat area (SFA/VFA, cm2) and skeletal muscle area (SMA, cm2). Information on toxicities was abstracted from medical charts and categorized into gastrointestinal, cardiovascular, and other system-specific toxicities. Median values were calculated for continuous variables (e.g., age at diagnosis, VFA, SFA, and SMA) and compared among patients who did versus did not experience toxicities. Frequencies and percentages were calculated for categorical variables. RESULTS Among n=320 rectal cancer patients, n=48 (15%) patients experienced at least one toxicity that required treatment modification (defined as dose reduction or discontinuation of therapy). Patients who experienced toxicities were older (58 years vs 56 years), more likely to be male (63% vs 59%), and more likely to be diagnosed with stage III cancer (92% vs 69%) compared to patients who did not experience toxicities. Patients who had higher VFA (166 cm2 vs 148 cm2), lower SFA (197 cm2 vs 208 cm2), and lower SMA (144 cm2 vs 147 cm2) were more likely to experience toxicities compared to patients with lower VFA, higher SFA, or higher SMA. CONCLUSIONS Body composition parameters may differ between rectal cancer patients who experience toxicities versus those who do not. Multivariate logistic regression and Cox proportional hazard analyses are underway to investigate in more detail the associations of body composition parameters (VFA, SFA, SMA), sarcopenia, and sarcopenic obesity with toxicity and survival in rectal cancer patients. Citation Format: Jennifer Ose, Jeffrey T. Yap, Daniel Jeong, Simon Ta Van, Matthew F. Covington, Biljana Gigic, Johanna Nattenmueller, Benjamin Haaland, Tengda Lin, Sheetal Hardikar, Caroline Himbert, Anita R. Peoples, Anjelica Ashworth, Juergen Boehm, Petra Schrotz-King, Jane C. Figueiredo, Adetunji T. Toriola, Erin M. Siegel, Christopher I. Li, Alexis B. Ulrich, Martin Schneider, Hans-Ulrich Kauczor, David Shibata, Cornelia M. Ulrich. Differences in body composition among rectal cancer patients with neo-adjuvant treatment-related toxicity: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3221.

Constructing and Validating a Prognosis Predictive Nomogram for Cancer-Specific Survival in Rectal Cancer Patients Receiving Preoperative Radiotherapy

Background A predictive tool is required to identify the cancer-specific survival in rectal cancer (RC) patients who have opted to receive preoperative radiotherapy. Methods A database containing the data on RC patients’ records of Surveillance, Epidemiology, and End Results (SEER) receiving surgery during 2000–2014 was selected. All patients received neoadjuvant radiotherapy (NR). The correlation of clinicopathological parameters was analyzed using the Chi-square test and the survival risk factors were analyzed using the Cox proportional hazards analysis (univariate and multivariate). Finally, the nomogram was developed and validated to visually represent an accurate prediction of the probability of 3- and 5-year cancer-specific survival (CSS) based on the screened variables of the cohort. Results 11,499 rectal cancer patients were included in our cohort. Patients’ records were randomly allocated to either the development or validation cohorts based on an equal ratio (1:1). Performing the multivariate Cox regression analysis incorporating these variables in the development cohort determined 11 independent prognostic factors. Statistically significant differences were recorded among subgroups using log-rank tests, which confirmed the appropriateness and acceptability of factor stratifications. Then, the nomogram was constructed and its concordance index (C-index) values in the development cohort (0.720) and validation cohort (0.717) were evaluated to be higher (P<0.05) than those of the AJCC stage (0.631 and 0.633 respectively). Also, the 3-year AUC values of this nomogram were higher than those of the AJCC stage in both the development cohort (0.746 vs. 0.631) and the validation cohort (0.745 vs. 0.640). Using DCA curves, the predictive potential of the currently developed nomogram outperformed the conventional AJCC staging system. Conclusion The nomogram model might be a more reliable tool to predict prognosis accurately in rectal cancer patients receiving preoperative radiotherapy.

A new insights of mesorectum

Total mesorectal excision (TME) represents the gold standard for radical resection in rectal cancer. The development in radiology and laparoscopic surgical equipment and the advancement in technology have led to a deepened understanding of the mesorectum and its surrounding structures. Both the accuracy of preoperative staging and the preciseness of the planes of TME surgical dissection have been enhanced. The postoperative local recurrence rate is reduced and the long-term survival of rectal cancer patients is improved. The preservation of the pelvic autonomic nervous system maintains the patient's urinary and sexual functions to the greatest extent possible, which in turn improves the patient's postoperative quality of life. A thorough understanding of the anatomy of the mesorectum and its surrounding structures is a prerequisite for successful TME. Herein, we review the basic concepts and the anatomy of the mesorectum in the current literature. Some important clinical issues are also discussed systematically in terms of imaging, surgery, and pathology.

Comprehensive Analysis of miRNA-Mediated Regulatory Network and Identification of Prognosis Biomarkers in Rectal Cancer.

Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.

Pre-Treatment and Post-Treatment Neutrophil-to- Lymphocyte Ratio Predict Pathological Tumor Response and Survival in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

Pre-Treatment and Post-Treatment Neutrophil-to- Lymphocyte Ratio Predict Pathological Tumor Response and Survival in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

Estimating short-term and long-term survival in rectal cancer patients using cure model.

A large number of rectal cancer patients are cured after treatment. In such cases, cure models are used for survival analysis. This study aims to investigate factors that affect survival in rectal cancer using the Cox mixture cure model. Following a retrospective design, medical documents and pathological findings of newly diagnosed rectal cancer cases hospitalized at Imam Hossein Hospital, Tehran, Iran, from 2005 to 2013 were reviewed. The patients were followed up with until May 2018. The Cox mixture cure model was used. Data analysis was carried out using Statistical Analysis System (SAS) version 9.4. The statistical significance level was considered to be 0.05. Four hundred nine patients were included in this study. The mean of disease-free survival was 87.08 ± 3.2 months. The hazard of the event for the patients who were drug abusers was 2.37 (95% CI: 1.30-4.31) times more than the other cases (P = 0.005). The odds ratio of the event for patients of stage III was 3.04 (95% CI: 1.51-6.12) times more than the cases of stage I (P = 0.002), and for the patients of stage IV, it was 12.42 (95% CI: 4.17-37.01) times more than patients of stage I (P < 0.001). The results of this cure model indicate that the tumor stage, tumor grade, and history of drug abuse are the risk factors for the survival of patients with rectal cancer. These results can attract the attention of doctors and patients who want to be aware of their physical status and prognosis.

Long-term conditional disease-free survival for rectal cancer patients underwent neoadjuvant chemoradiotherapy

Objective: To explore the application value of the conditional disease-free survival (cDFS) analysis in predicting prognosis of stage-specific rectal cancer patients underwent neoadjuvant chemoradiotherapy (nCRT). Methods: Clinicopathologic data of 436 patients with rectal cancer received nCRT and radical operation in Cancer Hospital, Chinese Academy of Medical Sciences between January 2004 and December 2016 were retrospectively reviewed. With reference to conditional probability, the 3-year cDFS of patients at different ypTNM stage after completion of nCRT was estimated using the Kaplan-Meier method. Results: There were 66 patients of ypTNM stage 0 (pathological complete response), 87 patients of ypTNM stage Ⅰ, 135 patients of ypTNM stage Ⅱ and 148 patients of ypTNM stage Ⅲ. The 3-year accumulated DFS of patients with ypTNM stage 0, ypTNM stage Ⅰ, ypTNM stage Ⅱ, and ypTNM stage Ⅲ were 97.0%, 93.1%, 85.2%, and 64.2%, respectively. On the condition of postoperactive disease-free survival for 1 year, 2 years, 3 years, 4 years, and 5 years, the corresponding 3-year cDFS of patients at ypTNM stage 0 were 97.0%, 95.5%, 96.9%, 98.4%, 100.0%, respectively. The corresponding 3-year cDFS of patients at ypTNM Ⅲ were 68.2%, 79.3%, 86.3%, 92.1%, 96.4%, respectively. The more advanced ypTNM staging resulted in the more improvement of 3-year cDFS being acquired. Conclusion: cDFS is a better method to reflect the dynamic changes of the prognosis of rectal cancer patients with nCRT in different ypTNM stage, and it is useful to guide the clinicians to assess the prognosis and propose appropriate surveillance.

CTSE Overexpression Is an Adverse Prognostic Factor for Survival among Rectal Cancer Patients Receiving CCRT.

The introduction of preoperative concurrent chemoradiotherapy (CCRT) increases the rate of anal preservation and allows tumor downstaging for clinical stage T3/T4 or node-positive rectal cancer patients. However, there is no precise predictive tool to verify the presence of residual tumor apart from surgical resection. The gastrointestinal (GI) tract not only digests nutrients but also coordinates immune responses. As the outermost layer of the GI tract, mucus plays a key role in mediating the interaction between the digestive and immune systems, and aberrant mucus mesh formation may cause chemoresistance by impeding drug delivery. However, the correlations among digestion-related genes, mucin synthesis, and chemoresistance remain poorly understood. In the present study, we evaluated genes related to digestion (GO: 0007586) and identified cathepsin E (CTSE), which is involved in immune regulation, as the most significantly upregulated gene associated with CCRT resistance in rectal cancer in a public transcriptome dataset (GSE35452). We recovered 172 records of rectal cancer patients receiving CCRT followed by surgical resection from our biobank and evaluated the expression level of CTSE using immunohistochemistry. The results revealed that tumors with CTSE overexpression were significantly correlated with pre-CCRT and post-CCRT positive nodal status (both p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p < 0.001 and p = 0.002), perineural invasion (p = 0.023), vascular invasion (p < 0.001), and a lesser degree of tumor regression (p = 0.003). At the univariate level, CTSE overexpression was an adverse prognostic factor for all three endpoints: disease-specific survival (DSS), metastasis-free survival (MeFS) (both p < 0.0001), and local recurrence-free survival (LRFS) (p = 0.0001). At the multivariate level, CTSE overexpression remained an independent prognostic factor for poor DSS, MeFS (both p = 0.005), and LRFS (p = 0.019). Through bioinformatics analysis, we speculated that CTSE overexpression may confer CCRT resistance by forming a defensive mucous barrier. Taken together, these results suggest that CTSE overexpression is related to CCRT resistance and inferior survival in rectal cancer patients, highlighting the potential predictive and prognostic value of CTSE expression.

High FRMD3 expression is prognostic for worse survival in rectal cancer patients treated with CCRT.

Rectal cancer patients can conceivably obtain relief from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before resection, but the stratification of risk and clinical outcomes remains challenging. Therefore, identifying effective predictive biomarkers offers clinicians the opportunity to individually tailor early interventions, which would help optimize therapy. Using a public rectal cancer transcriptome dataset (GSE35452), we focused on cytoskeletal protein binding (GO: 0008092)-related genes and identified FERM domain containing 3 (FRMD3) as the most significant differentially expressed gene associated with CCRT resistance. We gathered 172 tumor samples from rectal cancer patients treated with neoadjuvant CCRT accompanied by curative resection and estimated the expression level of FRMD3 using immunohistochemistry. The results revealed that high FRMD3 immunoexpression was remarkably associated with advanced pre-CCRT and post-CCRT tumor status (p = 0.004 and p < 0.001), pre-CCRT and post-CCRT lymph node metastasis (both p < 0.001), more perineurial invasion (p = 0.023), and a smaller extent of tumor regression (p = 0.018). High FRMD3 immunoexpression was remarkably correlated with inferior disease-specific survival (DSS) (p = 0.0001), local recurrence-free survival (LRFS) (p = 0.0003), and metastasis-free survival (MeFS) (p = 0.0023) at the univariate level. Furthermore, in multivariate analysis, high FRMD3 immunoexpression remained independently predictive of inferior DSS (p = 0.002), LRFS (p = 0.005), and MeFS (p = 0.015). These results suggest that high FRMD3 expression is related to advanced clinicopathological features and inferior therapeutic responses in rectal cancer patients treated with CCRT, validating the promising prognostic value of FRMD3 expression.

Morphometric assessment of the mesorectal fat in Chinese Han population: A clinical MRI study.

The study aimed to analyze morphometric assessment of the mesorectal fat thickness and its correlation with body mass index in Chinese Han population. The anterior, posterior, right lateral, and left lateral mesorectal fat thickness were measured using MRI T2-weighted images. The mean distance from the rectal wall to the mesorectal fascia were 3.8, 8.4, 11.3, and 11.7 mm in anterior, posterior, right lateral, and left lateral portion, respectively. The mesorectal area, rectal area, mesorectal fat thickness area, and rectal height were 2395.3 ± 691.1 mm2, 709.6 ± 403.5 mm2, 1685.7 ± 525.3 mm2, and 9.1 ± 0.8 cm. BMI was found to be directly proportional to and statistically significant to the mesorectal fat area (p = 0.01). Since the mean mesorectal fat thickness was found to be <12 mm, T3d staged rectal cancer is less likely to be found in an average Chinese population that may affect the overall-survival and progression-free survival in rectal cancer patients. Anterior portion of the rectum was least thick compared to all other sides. Therefore, extra-caution should be taken in handling tumors on the anterior part of the rectum.

Baseline liver steatosis has no impact on liver metastases and overall survival in rectal cancer patients

BackgroundThe liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients.MethodsPatients diagnosed with stage II to IV rectal cancer between 2010 and 2016 in our province with suitable baseline CT scan were included. Data on cancer diagnosis, staging, therapy, outcomes and liver function were collected. CT scans were retrospectively reviewed to assess baseline steatosis (liver density < 48 HU and/or liver-to-spleen ratio < 1.1). Among patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was defined as steatosis appearance, ≥ 10% liver volume increase, or significant increase in liver function tests.ResultsWe included 283 stage II to IV rectal cancer patients with suitable CT scan (41% females; mean age 68 ± 14 years). Steatosis was present at baseline in 90 (31.8%) patients, synchronous liver metastasis in 42 (15%) patients and metachronous liver metastasis in 26 (11%); 152 (54%) deaths were registered. The prevalence of synchronous liver metastasis was higher in patients with steatosis (19% vs 13%), while the incidence of metachronous liver metastasis was similar. After correcting for age, sex, stage, and year of diagnosis, steatosis was not associated with metachronous liver metastasis nor with overall survival. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was associated with higher incidence of metachronous liver metastasis and worse survival, results which need to be confirmed by larger studies.ConclusionsOur data suggest that rectal cancer patients with steatosis had a similar occurrence of metastases during follow-up, even if the burden of liver metastases at diagnosis was slightly higher, compatible with chance.

Persistent extramural vascular invasion positivity on magnetic resonance imaging after neoadjuvant chemoradiotherapy predicts poor outcome in rectal cancer

BackgroundIn rectal cancer, extramural vascular invasion (EMVI) is the presence of tumour cells in blood vessels outside the muscular layer, which is associated with poor prognosis. Regression of EMVI on MRI following neoadjuvant chemoradiotherapy or its persistence may have prognostic implications. MethodsThis retrospective study included 52 patients with rectal cancer who underwent total mesorectal excision following long-course neoadjuvant chemoradiotherapy (CRT). EMVI assessments were done on previous pelvic MRIs obtained before neoadjuvant CRT and eight weeks after the completion of neoadjuvant chemoradiotherapy in initially EMVI positive cases. ResultsPersistently EMVI positive patients had worse overall survival and disease-free survival compared to initially EMVI negative patients and patients who returned to negative (p < 0.001 for both). Multivariate analysis identified persistent EMVI positivity after neoadjuvant treatment (HR, 102.9; p = 0.003) as significant independent predictor of worse overall survival; and persistent EMVI positivity (HR, 17.0; p = 0.002), mesorectal fascia involvement after neoadjuvant treatment (HR, 8.0; p = 0.017), and poor differentiation (HR, 10.3, p = 0.012) as significant independent predictors of worse disease-free survival. ConclusionPersistent EMVI positivity after neoadjuvant therapy appears to be an independent factor for poor overall survival; and persistent EMVI positivity as well as mesorectal fascia involvement on post neoadjuvant therapy MRI and poor differentiation appears to be important predictors of poor disease-free survival in rectal cancer patients.

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy.

BACKGROUNDColorectal cancer is a common digestive cancer worldwide. As a comprehensive treatment for locally advanced rectal cancer (LARC), neoadjuvant therapy (NT) has been increasingly used as the standard treatment for clinical stage II/III rectal cancer. However, few patients achieve a complete pathological response, and most patients require surgical resection and adjuvant therapy. Therefore, identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIMTo establish effective prognostic nomograms and risk score prediction models to predict overall survival (OS) and disease-free survival (DFS) for LARC treated with NT.METHODSNomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017. The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors, which were validated by the Cox regression method. Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves, and that of the two nomograms was conducted by calculating the concordance index (C-index) and calibration curves. The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTSSeven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model: Vascular_tumors_bolt, cancer nodules, yN, body mass index, matchmouth distance from the edge, nerve aggression and postoperative carcinoembryonic antigen. The nomogram showed good predictive value for OS, with a C-index of 0.91 (95%CI: 0.85, 0.97) and good calibration. In the validation cohort, the C-index was 0.69 (95%CI: 0.53, 0.84). The risk factor prediction model showed good predictive value. The areas under the curve for 3- and 5-year survival were 0.811 and 0.782. The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77 (95%CI: 0.69, 0.85). In the validation cohort, the C-index was 0.71 (95%CI: 0.61, 0.81). The prediction model for DFS also had good predictive value, with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSIONWe established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

Baseline Lymphocyte Counts Do Not Predict Oncologic Outcomes and Survival in Patients Receiving Short Course Total Neoadjuvant Therapy for Rectal Cancer

Total neoadjuvant therapy (TNT) is increasingly utilized for patients with locally advanced rectal cancer. Prior studies have suggested that markers of systemic inflammation at baseline may predict treatment outcomes for patients receiving neoadjuvant long-course chemoradiation (LC-CRT). However, this has not been evaluated in patients receiving TNT with short-course radiation (SC-RT). We evaluated the prognostic value of baseline neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) in rectal cancer patients receiving SC-TNT. Between 2010 and 2019, we identified 186 patients with rectal cancer who received SC-TNT at our institution. Of these, 141 patients had a pre-treatment complete blood counts available within 2 months prior to initiating therapy. All patients received neoadjuvant SC- RT 25 Gy/5 Fx to the pelvis followed by chemotherapy followed by delayed surgery +/- adjuvant chemotherapy based on pathologic features. Primary clinical outcomes of interest were pathologic complete response (pCR), loco-regional control (LRC), distant control (DC), disease-free survival (DFS), and overall survival (OS). Cox regression analysis was performed to determine potential associations between NLR, PLR, and MLR with clinical outcomes. NLR, PLR, and MLR were analyzed as both continuous and dichotomized variables. Multiple cutoff values were evaluated based on cohort mean, cohort median, and previously published values. Statistical analyses were performed using SPSS version 26. P <0.05 was considered statistically significant. The median baseline NLR was 2.5 (interquartile range 1.36). The median baseline PLR was 142.73 (interquartile range 82.11). The median baseline MLR was 2.56 (interquartile range 2.26). Median follow-up was 2.44 years (range 0.11 – 9.59 years). pCR was achieved in 34 patients (24.1%). Three-year actuarial LRC, DC, DFS, and OS were 93%, 84.2%, 78.9%, and 87.7%, respectively. NLR as a continuous variable was significantly associated with LRC, DFS, and OS on univariate analysis but not multivariate analysis. There was no other association found between NLR, PLR, or MLR with any other clinical outcomes of interest when analyzed as either continuous or dichotomous variables. In our SC-TNT cohort, baseline NLR, PLR, and MLR did not predict tumor response, oncologic outcomes, or overall survival in rectal cancer patients. Our data contrasts prior studies for LC-CRT, possibly due to differences in neutrophil or lymphocyte depletion with hypo-fractionated RT. Further studies are warranted to compare post-RT immune markers between LC-CRT and SC-RT. As hypo-fractionated RT use increases, identification and validation of biomarkers in rectal cancer patients undergoing neoadjuvant SCRT will become increasingly important.

Extracapsular Extension Does Not Decrease Overall Survival in Rectal Cancer Patients with Lymph Node Metastasis Following Neoadjuvant Chemoradiotherapy

Background. The Tumor-Node-Metastasis system does not include additional prognostic factors present in the Lymph Node Metastasis (LNM) such as extra-capsular extension (ECE), which is associated with decreased survival. There are not studies addressing this topic in rectal cancer patients with preoperative chemoradiotherapy (nCRT) and total mesorectal excision (TME). Aim. We aimed to examine the survival influence of ECE in patients with stage III rectal cancer who received nCRT followed by surgery. Methods. A retrospective study of 126 patients prospectively collected with rectal cancer in clinical stage III rated with nCRT and TME from 2010 to 2015 was performed. Results. In total, 71.6% of cases had 1 to 3 lymph node metastases, most tumors were grade 2 (52.4%), 25.4% had good pathologic response, 77.8% had a good quality TME, and the median tumor budding count was 4/0.785 mm2. Forty-four (34.9%) patients had ECE+, which was associated with a higher nodal stage (pN2), perineural invasion and a higher lymph node retrieval. The factors associated with the survival were a higher pathologic T stage, higher pathological N stage, high-grade tumors, and perineural invasion. The ECE did not decrease the 5–year survival with a similar median survival (86.5 months for the ECE+ group vs. 84.1 for the ECE–). Conclusion. Our results demonstrate that ECE has no impact on overall survival in rectal cancer patients who received nCRT and this was independent of nodal stage or number of lymph nodes examined.

Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients.

The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10-2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group (P = 0.149). Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.

Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant CRT at the Department of Internal Medicine III of the Paracelsus Medical University Salzburg (Austria) between January 2003 and October 2012 were included. PD-L1 scoring was performed according to the tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC). PD-L1 TPS prior to neoadjuvant CRT had a statistically significant impact on survival (median: ≤1%: 95.4 months (95% CI: 51.8—not reached) vs. >1%: not reached, p = 0.03, log-rank). Patients with a PD-L1 TPS ≤1% prior to and after CRT showed an inferior survival compared to all other patients (median: 56.7 months (95% CI: 51.4—not reached) vs. not reached, p = 0.005, log-rank). In multivariate analysis, PD-L1 TPS prior to neoadjuvant CRT (>1% vs. ≤1%, hazard ratio: 0.29 (95% CI: 0.11–0.76), p = 0.01) remained independently associated with survival. In conclusion, low PD-L1 TPS was associated with inferior survival in rectal cancer patients undergoing neoadjuvant CRT. A prospective validation of the prognostic value of PD-L1 expression in rectal cancer patients within a clinical trial is necessitated.

Omission of Adjuvant Chemotherapy in Rectal Cancer Patients with Pathologic Complete Response: a National Analysis

BackgroundAn increasing number of patients achieve a pathologic complete response (pCR) after neoadjuvant chemoradiation for locally advanced rectal cancer. Consensus guidelines continue to recommend oncologic resection followed by adjuvant chemotherapy in these patients. We hypothesize that there is significant variability in compliance with this recommendation. MethodsThe National Cancer Database was queried from 2006 to 2015 for patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by oncologic resection with a pCR (ypT0N0). Hierarchical logistic regression models were used to generate risk and reliability-adjusted rates of adjuvant chemotherapy utilization in patients with pCR at each hospital. ResultsIn total, 2421 pCR patients were identified. Five-year overall survival was improved in pCR patients who received adjuvant chemotherapy compared with those who did not (92 vs. 85%, p < 0.01). Multivariate analysis indicated that improvement in overall survival remained associated with adjuvant chemotherapy (HR 0.60, 95% CI 0.44–0.82, p < 0.01). The mean adjuvant chemotherapy utilization rate among hospitals was 32%. There was an upward trend in use over the past decade, but two-thirds still do not receive the recommended therapy. High chemotherapy utilizer hospitals were more likely to be academic centers (54.9 vs. 45.9%, p < 0.01) when compared with low chemotherapy utilizers. ConclusionAdjuvant chemotherapy is associated with improved survival in rectal cancer patients with pCR following neoadjuvant chemoradiation and oncologic resection. However, utilization among centers in the USA was only 32% with significant variability across centers. National efforts are needed to standardize treatment patterns according to national guidelines.