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Prognostic Value of the Distribution of Lymph Node Metastasis in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy.

ABSTRACT: Background: The objective of this study is to assess the prognostic value of lymph node metastasis distribution (LND) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods: This study included 179 patients with pathological stage III LARC who underwent nCRT followed by radical surgery. LND was classified into three groups: LND1, lymph node metastasis at the mesorectum (140/179, 78.2%); LND2, lymph node metastasis along the inferior mesenteric artery trunk nodes (26/179, 14.5%); LND3, lymph node metastasis at the origin of the IMA (13/179, 7.3%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. Result: LND showed better stratification for 3-year DFS (LND1 66.8, LND2 50, and LND3 15.4%, P < 0.01) compared to the ypN (3-year DFS: N1 59.9 and N2 60.3%, P = 0.34) and ypTNM (3-year DFS: IIIA 68.6%, IIIB 57.5%, and IIIC 53.5, P = 0.19) staging systems. Similar results were found for 3-year LRFS and DMFS. According to multivariate survival analysis, LND was shown to be an independent prognostic factor for DFS, LRFS, and DMFS in patients with positive lymph nodes (P < 0.01, in all cases). Conclusion: LND is an independent prognostic factor in stage III rectal cancer after nCRT. LND can be used as a supplementary indicator for the ypTNM staging system in patients with LARC after nCRT.

SUBMITTER: Chen B

PROVIDER: S-EPMC8635484 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Increased lymph node yield indicates improved survival in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Project description:PURPOSE:It is recommended for colorectal cancer to harvest at least 12 lymph nodes (LNs) during surgery to avoid understaging of the disease. However, it is still controversial whether it is necessary to harvest from locally advanced rectal cancer (LARC) patients who underwent neoadjuvant chemoradiotherapy (neo-CRT). The impact of lymph node yield (LNY) on prognosis in LARC patients was analyzed. MATERIALS/METHODS:In total, 495 LARC patients who underwent neo-CRT in 2006-2015 were analyzed. After examining clinicopathological distribution differences between the LNY subgroups (with the threshold of 12), univariate and multivariate Cox survival analyses were performed. Survival plots were obtained from Kaplan-Meier analyses. Similar subgroup analyses were performed according to the tumor regression grade (TRG) and metastatic status of post-operational LNs. RESULTS:Of the 495 patients, 287 (57.98%) had an LNY of less than 12. Nearly no significant clinicopathological difference was found between the LNY subgroups, including the TRG scores. Multivariate survival analysis demonstrated that at least 12 LNs examined was an independent prognostic feature of good overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS), but not local recurrence free survival (LRFS). However, in the subgroup analyses, no association was found between LNY and prognosis in patients with good TRG scores (0-1) or negative LNs. CONCLUSIONS:For LARC patients treated with neo-CRT, an LNY of at least 12 indicated an improved survival. Decreased LNY was not related to better tumor regression. It suggests that a sufficiently high LNY is still required, especially in those with a potentially poor tumor response.

| S-EPMC6712464 | biostudies-literature

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer.

Project description:According to the American Joint Committee on Cancer, at least 12 lymph nodes are required to accurately stage locally advanced rectal cancer (LARC). Neoadjuvant chemoradiation therapy (NACRT) reduces the number of lymph nodes retrieved during surgery. In this study, we evaluated the effect of NACRT on lymph node retrieval and prognosis in patients with LARC. We performed an observational study of 142 patients with LARC. Although our analysis was retrospective, data were collected prospectively. Half the patients were treated with NACRT and total mesorectal excision (TME) and the other half underwent TME only. The number of lymph nodes retrieved and the number of metastatic lymph nodes were significantly reduced in the NACRT group (P?>?0.001). In the univariate and multivariate analyses, only NACRT and patient age were significantly associated with reduced lymph node retrieval. The number of metastatic lymph nodes and the lymph node ratio (LNR) both had a significant effect on prognosis when the patient population was examined as a whole (P?=?0.003 and P?=?0.001, respectively). However, the LNR was the only significant, independent prognostic factor in both treatment groups (P?=?0.007 for the NACRT group; P?=?0.04 for the no-NACRT group). NACRT improves patient prognosis only when the number of metastatic lymph nodes is reduced. The number of metastatic lymph nodes and the LNR are important prognostic factors. Lymph node retrieval remains an indispensable tool for staging and prognostic assessment of patients with rectal carcinoma treated with NACRT.

| S-EPMC7481149 | biostudies-literature

The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer.

Project description:PURPOSE:This study was conducted to investigate the potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer. PATIENTS AND METHODS:Surgical specimens of 128 ypUICC (Union for International Cancer Control) stage 0-III mid-to-low rectal cancer patients were identified from a prospectively maintained colorectal cancer database and classified into two groups using the 10 high-power field average method: none/mild tumor budding (BD-0) and moderate/severe tumor budding (BD-1). Overall survival, relapse-free survival (RFS), and recurrence estimates were calculated using the Kaplan-Meier method and compared with the log-rank test. For RFS, a multivariable Cox's proportional hazards regression analysis was performed. RESULTS:No (n?=?20) or mild (n?=?27) tumor budding (BD-0) was identified in 47 (37%) and moderate (n?=?52) or severe (n?=?29) tumor budding (BD-1) in 81 (63%) surgical specimens. Positive tumor budding (BD-1) was associated with significantly reduced T?level downstaging (P?<?0.001) and tumor regression (P?<?0.001). After a median follow-up time of 7 years (range 2.9-146.7 months), BD-0 patients had more favorable 5?year RFS (90 vs. 71%, P?=?0.02) and distant recurrence (2 vs. 12%, P?=?0.03) estimates. Multivariable analyses confirmed BD-1 as a negative predictive parameter for RFS (hazard ratio?=?3.44, 95% confidence interval 1.23-9.63, P?=?0.018). CONCLUSIONS:Our data confirm tumor budding as a strong prognostic factor and its potential predictive value for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients. This provides the opportunity to modify and individualize neoadjuvant therapy regimens for non-responders.

| S-EPMC6208929 | biostudies-literature

Poor prognostic and staging value of tumor deposit in locally advanced rectal cancer with neoadjuvant chemoradiotherapy.

Project description:Tumor deposit (TD) was associated with poor survival in colorectal cancer. However, its prognostic and staging value in locally advanced rectal cancer (LARC) patients following neoadjuvant chemoradiotherapy (neo-CRT) is controversial. Four hundred and ninety-five LARC patients following neo-CRT and surgery were retrospectively analyzed. Univariate and multivariate analyses were performed using Kaplan-Meier method and Cox proportional hazards regression in all lymph node (LN) -negative and LN-positive patients. Next, we used three methods to classify the counts of LNs and TDs (oN, only LN counts; n1N, counts according to the N1c standards; n2N, total counts of LNs and TDs) to evaluate the impact of TD on N staging. TD-positive patients were associated with more aggressive clinicopathological features. In multivariate analyses, TD was an independent poor prognostic factor of overall survival (OS), disease-free survival (DFS), and local recurrence-free survival in all patients. In LN-negative patients, TD was an independent poor prognostic factor of OS, DFS and distant metastasis-free survival (DMFS). In LN-positive patients, TD has poor prognostic value only in patients with one positive LN. Three multivariate analyses according to three N staging methods showed that oN was not an independent prognostic factor, whereas n1N and n2N were independently associated with poor survival in OS, DFS and DMFS. The n2N method seemed to be better than n1N method. TD is an independent poor prognostic factor in LARC patients following neo-CRT, especially in patients with no more than one positive LN. TD probably should be considered as one positive LN when performing N staging.

| S-EPMC6488131 | biostudies-literature

Radiomics-Based Preoperative Prediction of Lymph Node Status Following Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

Project description:Background and Purpose: Lymph node status is a key factor for the recommendation of organ preservation for patients with locally advanced rectal cancer (LARC) following neoadjuvant therapy but generally confirmed post-operation. This study aimed to preoperatively predict the lymph node status following neoadjuvant therapy using multiparametric magnetic resonance imaging (MRI)-based radiomic signature. Materials and Methods: A total of 391 patients with LARC who underwent neoadjuvant therapy and TME were included, of which 261 and 130 patients were allocated to the primary cohort and the validation cohort, respectively. The tumor area, as determined by preoperative MRI, underwent radiomics analysis to build a radiomic signature related to lymph node status. Two radiologists reassessed the lymph node status on MRI. The radiomic signature and restaging results were included in a multivariate analysis to build a combined model for predicting the lymph node status. Stratified analyses were performed to test the predictive ability of the combined model in patients with post-therapeutic MRI T1-2 or T3-4 tumors, respectively. Results: The combined model was built in the primary cohort, and predicted lymph node metastasis (LNM+) with an area under the curve of 0.818 and a negative predictive value (NPV) of 93.7% were considered in the validation cohort. Stratified analyses indicated that the combined model could predict LNM+ with a NPV of 100 and 87.8% in the post-therapeutic MRI T1-2 and T3-4 subgroups, respectively. Conclusion: This study reveals the potential of radiomics as a predictor of lymph node status for patients with LARC following neoadjuvant therapy, especially for those with post-therapeutic MRI T1-2 tumors.

| S-EPMC7233118 | biostudies-literature

Meta-analysis of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Project description:Background and purposeWith the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.Materials and methodsEligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).ResultsSix studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).ConclusionWe concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.

| S-EPMC8101236 | biostudies-literature

Outcomes of neoadjuvant chemoradiotherapy in Japanese locally advanced rectal carcinoma patients.

Project description:We investigated the efficacy and prognosis of neoadjuvant chemoradiotherapy (NACRT) for Japanese locally advanced rectal carcinoma patients.Fifty-seven patients diagnosed with cT3-4 or any cT/cN+ disease using enhanced computed tomography or magnetic resonance imaging from 2002 to 2014 were enrolled. The male/female ratio was 42/15, and the median age was 67 years. Ra/Rb/Rb-P/P was expressed by 6/35/14/2 patients. Histological tumor types were tub1/tub2/por/muc in 22/30/4/1 patients. For NACRT, radiotherapy doses were 40-50.4 Gy chemotherapy consisted of 5'-DFUR, capecitabine, or S1.All 57 patients received curative surgical treatment. The anal preservation rate was 65.0%. The ypStage of 0/I/II/IIIa/IIIb was 7/10/25/11/4 cases. The histological antitumor effect (HATE) was ?grade (G) 2 and G3 in 31 (54.4%) and 7 (12.3%) cases, respectively. Postoperative complications occurred in 17 patients and exceeded GIII (Clavien-Dindo classification) in four patients. Recurrence was observed in 19 patients; the primary local recurrence rate was 5.3%. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 64.8 and 95.5%, respectively; the 5-year RFS and OS rates were 60.2 and 61.0%, respectively. In multivariate analysis, ypN+ was a high-risk factor for distant organ recurrence. As predictive factors regarding the efficacy of NACRT, a neutrophil concentration <70% and a neutrophil/lymphocyte ratio <3.0 in peripheral blood prior to treatment indicated that NACRT would be significantly more effective.NACRT was effective in reducing local recurrence but did not suppress distant organ recurrence in Japanese locally advanced rectal carcinoma patients. A further investigation of an extension of the NACRT regimen is required.

| S-EPMC4851776 | biostudies-other

Organ Preservation Strategies After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

Project description:Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while preserving quality of life. Driven by patient demand and interest in preserving quality of life, numerous organ preservation treatment strategies for managing rectal cancer are rapidly evolving. Herein, the flow of research in organ preservation strategies and counter arguments are discussed.

| S-EPMC6529751 | biostudies-literature

Locally advanced rectal cancer transcriptomic-based secretome analysis according to neoadjuvant chemoradiotherapy response

Project description:Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. Here, we performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies carefully selected and collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between cases with complete (pCR) and incomplete response to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome Database and Plasma and Proteome Database). Seventeen potentially secreted candidates (pCR=1, pIR=13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC. The potential secreted biomarkers were also confirmed as associated with the nCRT response (GSE68204). These putative proteins are candidates to be assessed in liquid biopsies aiming a personalized treatment in LARC patients.

2019-07-01 | GSE123390 | GEO

Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy.

Project description:Purpose:To assess the role of the expression levels of FOXK family members, FOXK1 and FOXK2, in predicting response to neo-chemoradiotherapy (NCRT) and prognosis in locally advanced rectal cancer (LARC). Methods:A total of 256 LARC patients who underwent NCRT and radical resection between 2011 and 2017 were enrolled in the present study. The patients were divided into a training dataset (n=169, 2011-2015) and a validation dataset (n=87, 2016-2017). Tumor tissues were collected before NCRT and post-surgery and were used for immunohistochemical analysis. Results:Oncomine database analysis revealed that FOXK1 and FOXK2 were overexpressed in most cancers especially in colorectal cancer. Additionally, overexpression of FOXK1 and FOXK2 was associated with poorer prognosis by the R2 database. In both our training and validation datasets, the expression of FOXK1 and FOXK2 was lower in the pathological complete response (pCR) group compared with the non-pCR group (P<0.05). Cox regression analysis demonstrated that pathological N stage (HR=1.810, 95% CI 1.159-2.827, P=0.009), FOXK1 expression (HR=5.831, 95% CI 2.925-11.625, P<0.001), and FOXK2 expression (HR=2.390, 95% CI 11.272-4.491, P=0.007) were independent predictors of disease-free survival (DFS). Based on the Cox multivariate analysis, we constructed a risk score model that served as a prognostic biomarker and had a powerful ability to predict pCR in LARC patients upon NCRT in both training and validation groups. Conclusion:Expression levels of FOXK family members were associated with chemoradiotherapy resistance and prognosis of LARC patients following NCRT and were used to construct a risk score model that is a promising biomarker for LARC.

| S-EPMC7505718 | biostudies-literature

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