Prognosis Of Rectal Cancer Research Articles

Lateral node metastasis in low rectal cancer as a hallmark to predict recurrence patterns.

Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.

Prognostic role of platelet-to-lymphocyte ratio in patients with rectal cancer undergoing resection: a systematic review and meta-analysis.

Inflammation plays a pivotal role in tumor growth, with the platelet-to-lymphocyte ratio (PLR) emerging as a promising serum biomarker for prognostic assessment in patients with cancer. However, its specific role in rectal cancer remains controversial. A comprehensive literature review encompassing PubMed, EMBASE, and the Cochrane Library, spanning from their inception to March 2024, was conducted. The systematic review and meta-analysis strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). Quality assessment was conducted using the Newcastle-Ottawa scale (NOS). This study aimed to assess the available literature on the association of PLR with both overall survival (OS) and disease-free survival (DFS) in patients with rectal cancer undergoing resection. Twenty-three observational studies, encompassing 7577 patients, were included in the analysis. These comprised 20 retrospective and 3 prospective cohort studies, with NOS scores ranging from 5 to 8. A significant association was found between high PLR and worse OS (hazard ratio [HR] 1.00; 95% confidence interval [CI] 1.00-1.01; P = 0.01). Conversely, no significant association was observed between PLR and DFS (HR 1.14; 95% CI 0.98-1.32; P = 0.09). PLR serves as an independent clinical predictor of OS in patients with rectal cancer treated with curative surgery, but not of DFS. This easily accessible biomarker appears to be an optimal prognostic index and may aid clinicians in predicting the prognosis of rectal cancer, facilitating the development of individualized treatment strategies.

Recent advances in the diagnosis of rectal cancer and evaluation of clinical treatment efficacy using magnetic resonance imaging

Accurate preoperative tumor staging is essential for precise treatment of rectal cancer, and magnetic resonance imaging (MRI) is the preferred method. In addition to accurately determining tumor (T) and stages node (N), MRI can also be used to evaluate factors related to the prognosis of rectal cancer, such as depth of tumor invasion into the muscular layer, extramural vascular invasion of the tumor, and distance to the circumferential resection margin. MRI is also an important method for evaluating tumor regression after neoadjuvant therapy, and quantitative biomarkers of functional MRI can objectively reflect treatment efficacy. Moreover, MRI can predict response after neoadjuvant therapy, local recurrence rate, and disease-free survival before treatment. The present article reviews recent advances in the preoperative diagnosis and staging of rectal cancer, reassessment after neoadjuvant therapy, and evaluation of clinical treatment efficacy using MRI.

The effect of long-standing lymphopenia after radiation therapy on survival in rectal cancer

BackgroundLymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy. We hypothesized that chronic lymphopenia following radiotherapy might negatively influence the survival of patients, and pre-treatment lymphopenia may be predictive of poor outcomes. MethodsThis retrospective study involved 110 patients treated for rectal cancer between 2015 and 2019. The oncological outcomes are defined as alive without disease (AWOD), alive with disease (AWD), and death. These outcome probabilities tested against variables of lymphopenia before RT, during RT, and at several post-RT follow-up time points. ResultsAt the end of the study, 69 patients were AWOD (63 %), 13 were AWD (12 %) and 28 had died (25 %). Treatment results were assessed with according level of lymphocytes measured one year following RT: 35 out of 39 patients (89.7 %) with normal values were AWOD. In 65 patients with sustained lymphopenia, 52 % were AWOD, 18.5 % AWD and 29 % died. A similar difference was found at all time-points up to 2 years following RT (p < 0.004).The results of our study shows that pre-existing lymphopenia (prior to RT) is associated with a 3 times greater chance of death compared to patients with normal lymphocyte levels prior to RT. The PFS significantly affected by lymphopenia at all time-points after RT. An NLR of more than 4 was associated with a 3-time higher risk of recurrence than lower NLR scores (p = 0.0054). ConclusionOur results support the relevance of lymphopenia and NLR in the prognosis of rectal cancer. We believe this is the first study showing a negative correlation between sustained lymphopenia and OS following RT.

A novel high-risk model identified by epithelial-mesenchymal transition predicts prognosis and radioresistance in rectal cancer.

Many studies have shown that tumor cells that survive radiotherapy are more likely to metastasize, but the underlying mechanism remains unclear. Here we aimed to identify epithelial-mesenchymal transition (EMT)-related key genes, which associated with prognosis and radiosensitivity in rectal cancer. First, we obtained differentially expressed genes by analyzing the RNA expression profiles of rectal cancer retrieved from The Cancer Genome Atlas database, EMT-related genes, and radiotherapy-related databases, respectively. Then, Lasso and Cox regression analyses were used to establish an EMT-related prognosis model (EMTPM) based on the identified independent protective factor Fibulin5 (FBLN5) and independent risk gene EHMT2. The high-EMTPM group exhibited significantly poorer prognosis. Then, we evaluated the signature in an external clinical validation cohort. Through in vivo experiments, we further demonstrated that EMTPM effectively distinguishes radioresistant from radiosensitive patients with rectal cancer. Moreover, individuals in the high-EMTPM group showed increased expression of immune checkpoints compared to their counterparts. Finally, pan-cancer analysis of the EMTPM model also indicated its potential for predicting the prognosis of lung squamous cell carcinoma and breast cancer patients undergoing radiotherapy. In summary, we established a novel predictive model for rectal cancer prognosis and radioresistance based on FBLN5 and EHMT2 expressions, and suggested that immune microenvironment may be involved in the process of radioresistance. This predictive model could be used to select management strategies for rectal cancer.

Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study).

For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

The effects of KRAS Mutations on the Prognosis of Rectal Cancer Following Neoadjuvant Chemoradiotherapy and Surgery.

Rectal cancers with mutations in the KRAS gene have worse prognoses than wild-type malignancies. Variants at codon 12 of KRAS have particularly detrimental effects on prognosis. We aimed to analyze whether KRAS mutations act as adverse prognostic factors following neoadjuvant concurrent chemoradiotherapy (CRT) and surgery for rectal cancer treatment. We analyzed the effects of KRAS mutations on disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) in 125 patients with cT2-4N0-2M0 rectal cancer who underwent surgery following CRT between June 2014 and March 2023 Inje University Busan Paik Hospital. The median follow-up period was 39.7 (range, 7.5-98.2) months. There were 25 patients (20.0%) who harbored KRAS mutations. Among them, 22 patients (17.6%) had codon 12 variants. Overall, 43 patients (34.4%) showed recurrence, of which 10 (8.0%) had locoregional recurrence and 35 (28.0%) had distant metastases (two occurred simultaneously). DFS was significantly reduced in the patients with KRAS mutations (p = 0.005). LRFS was also reduced in patients with KRAS mutations (p = 0.039). DFS and LRFS were also relatively low in the subgroup with KRAS mutations at codon 12 (n = 22) (p = 0.003 and p = 0.017, respectively). However, pathologic complete response rate following CRT was not affected by KRAS mutations (p = 0.197). Overall survival was also not associated with KRAS mutations (p = 0.486). KRAS mutation is related to decreased DFS and LRFS, when surgery is performed following neoadjuvant CRT to treat rectal cancer. These effects are particularly pronounced for KRAS mutations at codon 12.

Prediction models of locally advanced rectal cancer prognosis incorporating perioperative longitudinal clinical data: A retrospective longitudinal cohort study.

e15624 Background: For locally advanced rectal cancer, neoadjuvant chemoradiation(CCRT) followed by surgery is a standard treatment. Clinical T/N stage, whether pathological complete remission (pCR) after neoadjuvant CCRT or not are well recognized tumor features that predict disease prognosis. Although the parameters that determine pathologic stage are the strongest predictors of postoperative outcome, other clinical, molecular, and histologic features may influence prognosis independent of stage. The aim is to compare the predictive efficiency, between different models for overall survival in rectal cancer patients. Methods: This retrospective study is approved by TMU-JIRB(Protocol Number: N201809032).This is also a single institute study. 175 newly-diagnosed patients with locally advanced rectal cancer were retrospectively enrolled between Jan.2011 and Dec.2016. Basic information include sex, age, body weight, body height, previous medical history were recorded. CEA level, chemotherapy regimen, type of surgery, and distance between tumor and anal verge were also collected. Chemotherapy regimen of CCRT including 5FU+LV, capecitabine (Xeloda), FOLFOX, and FOLFIRI are recorded. Surgical resection was then followed 4-8 weeks after completion of CCRT. The 2010 AJCC tumor response grading (TRG) system was used to report treatment response of proctectomy samples. The progression free survival (PFS) and overall survival (OS) are then calculated. PFS is defined as survival without any recurrence or distant metastasis before Dec 31st, 2023. A comprehensive evaluation was conducted by incorporating all these machine learning models together. The aim was to compare their predictive efficiency, with models such as Random Forest, Naïve Bayes, KNeighbor, SVM, Decision Tree, Logistic Regression, XGBoost, and LightGBM. Results: 175 patients (104 men and 71 women) were enrolled in this study. The median follow up time was 7.1 yrs. The BMI was 24.05 ± 0.03 for men and 24.20 ± 0.07 for women. 32 (17.3%) patients achieved pCR, TRG 0. Clinical staging cT3 (78.8%) and nodal positive (78.8%) are the most common tumor feature in this study group. The median age of male and female patient is 58.6 and 56.1 respectively. Upon applying various machine learning models, different predictive accuracies emerged. The Random Forest, KNeighbor, and SVM models all achieved an accuracy of 0.9250. Naïve Bayes had an accuracy of 0.8620, while the SVC model registered at 0.9310, and XGBoost was slightly behind at 0.9286. SVC model is marking the best-performing model in this evaluation. Conclusions: This multicenter retrospective data-driven deep learning prediction model informed that SVC model yielded the best predictive results. Further prospective clinical trials and external validation of this prediction model are needed to further reinforce our findings.

Predicting rectal cancer prognosis from histopathological images and clinical information using multi-modal deep learning.

The objective of this study was to provide a multi-modal deep learning framework for forecasting the survival of rectal cancer patients by utilizing both digital pathological images data and non-imaging clinical data. The research included patients diagnosed with rectal cancer by pathological confirmation from January 2015 to December 2016. Patients were allocated to training and testing sets in a randomized manner, with a ratio of 4:1. The tissue microarrays (TMAs) and clinical indicators were obtained. Subsequently, we selected distinct deep learning models to individually forecast patient survival. We conducted a scanning procedure on the TMAs in order to transform them into digital pathology pictures. Additionally, we performed pre-processing on the clinical data of the patients. Subsequently, we selected distinct deep learning algorithms to conduct survival prediction analysis using patients' pathological images and clinical data, respectively. A total of 292 patients with rectal cancer were randomly allocated into two groups: a training set consisting of 234 cases, and a testing set consisting of 58 instances. Initially, we make direct predictions about the survival status by using pre-processed Hematoxylin and Eosin (H&E) pathological images of rectal cancer. We utilized the ResNest model to extract data from histopathological images of patients, resulting in a survival status prediction with an AUC (Area Under the Curve) of 0.797. Furthermore, we employ a multi-head attention fusion (MHAF) model to combine image features and clinical features in order to accurately forecast the survival rate of rectal cancer patients. The findings of our experiment show that the multi-modal structure works better than directly predicting from histopathological images. It achieves an AUC of 0.837 in predicting overall survival (OS). Our study highlights the potential of multi-modal deep learning models in predicting survival status from histopathological images and clinical information, thus offering valuable insights for clinical applications.

T1 Mapping and Amide Proton Transfer Weighted Imaging for Predicting Lymph Node Metastasis in Patients with Rectal Cancer.

Accurate preoperative judgment of lymph node (LN) metastasis is a critical step in creating a treatment strategy and evaluating prognosis in rectal cancer (RC) patients. This study aimed to explore the value of T1 mapping and amide proton transfer weighted (APTw) imaging in predicting LN metastasis in patients with rectal cancer. In a retrospective study, twenty-three patients with pathologically confirmed rectal adenocarcinoma who underwent MRI and surgery from August 2019 to August 2021 were selected. Then, 3.0T/MR sequences included conventional sequences (T1WI, T2WI, and DWI), APTw imaging, and T1 mapping. Patients were divided into LN metastasis (group A) and non-LN metastasis groups (group B). The intra-group correlation coefficient (ICC) was used to test the inter-observer consistency. Mann-Whitney U test was used to compare the differences between the two groups. Spearman correlation analysis was performed to evaluate the correlation between T1 and APT values. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the differential performance of each parameter and their combination. The difference between AUCs was compared using the DeLong test. The APT value in patients with LN metastasis was significantly higher than in those without LN metastasis group (P=0.020). Also, similar results were observed for the T1 values (P=0.001). The area under the ROC curve of the APT value in the prediction of LN metastasis was 0.794; when the cutoff value was 1.73%, the sensitivity and specificity were 71.4% and 88.9%, respectively. The area under the ROC curve of the T1 value was 0.913; when the cutoff value was 1367.36 ms, the sensitivity and specificity were 78.6% and 100.0%, respectively. The area under the ROC curve of T1+APT was 0.929, with a sensitivity of 78.6% and specificity of 100.0%. APT and T1 values show great diagnostic efficiency in predicting LN metastasis in rectal cancer.

A study on the radiomic correlation between CBCT and pCT scans based on modified 3D-RUnet image segmentation.

The present study is based on evidence indicating a potential correlation between cone-beam CT (CBCT) measurements of tumor size, shape, and the stage of locally advanced rectal cancer. To further investigate this relationship, the study quantitatively assesses the correlation between positioning CT (pCT) and CBCT in the radiomics features of these cancers, and examines their potential for substitution. In this study, 103 patients diagnosed with locally advanced rectal cancer and undergoing neoadjuvant chemoradiotherapy were selected as participants. Their CBCT and pCT images were used to divide the participants into two groups: a training set and a validation set, with a 7:3 ratio. An improved conventional 3D-RUNet (CLA-UNet) deep learning model was trained on the training set data and then applied to the validation set. The DSC, HD95 and ASSD were calculated for quantitative evaluation purposes. Then, radiomics features were extracted from 30 patients of the test set. The experiments demonstrate that, the modified model achieves an average DSC score 0.792 for pCT and 0.672 for CBCT scans. 1037 features were extracted from each patient's CBCT and pCT images, 73 image features were found to have R values greater than 0.9, including three features related to the staging and prognosis of rectal cancer. In this study, we proposed an automatic, fast, and consistent method for rectal cancer GTV segmentation for pCT and CBCT scans. The findings of radiomic results indicate that CBCT images have significant research value in the field of radiomics.

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.

Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

Predicting tumor deposits in rectal cancer: a combined deep learning model using T2-MR imaging and clinical features

BackgroundTumor deposits (TDs) are associated with poor prognosis in rectal cancer (RC). This study aims to develop and validate a deep learning (DL) model incorporating T2-MR image and clinical factors for the preoperative prediction of TDs in RC patients.Methods and methodsA total of 327 RC patients with pathologically confirmed TDs status from January 2016 to December 2019 were retrospectively recruited, and the T2-MR images and clinical variables were collected. Patients were randomly split into a development dataset (n = 246) and an independent testing dataset (n = 81). A single-channel DL model, a multi-channel DL model, a hybrid DL model, and a clinical model were constructed. The performance of these predictive models was assessed by using receiver operating characteristics (ROC) analysis and decision curve analysis (DCA).ResultsThe areas under the curves (AUCs) of the clinical, single-DL, multi-DL, and hybrid-DL models were 0.734 (95% CI, 0.674–0.788), 0.710 (95% CI, 0.649–0.766), 0.767 (95% CI, 0.710–0.819), and 0.857 (95% CI, 0.807–0.898) in the development dataset. The AUC of the hybrid-DL model was significantly higher than the single-DL and multi-DL models (both p < 0.001) in the development dataset, and the single-DL model (p = 0.028) in the testing dataset. Decision curve analysis demonstrated the hybrid-DL model had higher net benefit than other models across the majority range of threshold probabilities.ConclusionsThe proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.Critical relevance statementThe proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.Key points• Preoperative non-invasive identification of TDs is of great clinical significance.• The combined hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.• A preoperative nomogram provides gastroenterologist with an accurate and effective tool.Graphical

Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics

BackgroundRadiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level.MethodsmRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue.ResultsWe found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different.ConclusionFive radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.

Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy

IntroductionMismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy. Materials and methodsTumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed. ResultsThe TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis. ConclusionsDense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.

Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions

BackgroundExtramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD.MethodsFrom 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared.ResultsThe NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047).ConclusionsWe defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.

The impact of mesorectal fat area on recurrence following total mesorectal excision for lower rectal cancer.

The mesorectal fat area (MFA) at the tip of the ischial spines on magnetic resonance imaging has been used to characterize mesorectal morphology. Recent studies reported that a larger MFA correlated with difficulties in rectal cancer surgery. However, the relationship between MFA and rectal cancer prognosis remains unclear. This study evaluated the impact of MFA on recurrence following robotic total mesorectal excision (TME) for rectal cancer. Patients who underwent robotic TME for lower rectal cancer from December 2011 to December 2016 were enrolled. Cox regression analysis was performed to determine variables associated with relapse-free survival (RFS). Patients were divided into groups based on MFA, and RFS was compared. Of 230 patients, 173 (75.3%) were male. The median age was 63years, and median MFA was 19.7 cm2. In multivariate analysis, smaller MFA (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.88-0.97; p < 0.01), p/yp stage II (HR, 3.81; 95% CI, 1.40-10.35; p < 0.01), and p/yp stage III (HR, 5.35; 95% CI, 1.88-15.27; p < 0.01) were independently associated with worse RFS. Sex, body mass index, and visceral fat area were not correlated with RFS. In the median follow-up period of 60.8months, patients with MFA < 19.7 cm2 had a significantly lower 5-year RFS rate (72.7%) than those with MFA ≥ 19.7 cm2 (85.0%). Smaller MFA was associated with worse RFS in patients undergoing robotic TME for lower rectal cancer. MFA is considered to be a prognostic factor in rectal cancer.

Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.

Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial. A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection. Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively). NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.

Examined lymph node numbers influence prognosis in rectal cancer treated with neoadjuvant therapy

BackgroundThe number of lymph nodes examined (LNe) is often insufficient in patients with rectal cancer (RC) treated with neoadjuvant therapy; however, its prognostic value remains controversial. Thus, we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy. MethodsData were collected from seven prospective hospital databases in China from July 2002 to May 2018. Binary logistic regression models were used to predict lymph node metastasis. The cut-off value for LNe was determined using X-tile 3.6.1. Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model. ResultsA total of 482 patients were included, of whom 459 had complete overall survival (OS) information. Using the percentile method, the total number of lymph nodes examined (TLNe) was 14–16 (40th–60th percentile), and the proportion of patients with lymph node metastasis reached a maximum of 48.1%. Cox multivariate analysis showed that the odds ratio (OR) remained the highest when TLNe was 14–16 (OR = 3.379, P = 0.003). The 3-year and 5-year OS were 85.4% and 77.8%, respectively. Negative lymph nodes examined (NLNe) of ≤6 was an independent risk factor for 3-year and 5-year OS (3-year OS 71.1% vs. 85.9%, P = 0.004; 5-year OS 66.3% vs. 74.3%, P = 0.035). Subgroup analysis for patients with ypN + showed that higher 3-year and 5-year OS were achieved when the TLNe was >10, 78.8% vs. 54.0% (P = 0.005), and 60.8% vs. 36.0% (P = 0.012), respectively. Patients with ypN0M0 had a higher 5-year OS when the TLNe was >19 (P = 0.055). ConclusionThe TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.