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Skeletal muscle loss is an independent negative prognostic factor in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.

ABSTRACT: The impact of body composition on the short- or long-term outcomes of patients with surgically treated advanced rectal cancer after neoadjuvant chemoradiotherapy remains unclear. This study examined the correlation between low skeletal muscle mass and morbidity and survival in patients with advanced lower rectal cancer.We enrolled 144 clinical stage II/III patients with advanced lower rectal cancer who underwent neoadjuvant chemoradiotherapy followed by curative resection between 2004 and 2011. The cross-sectional skeletal muscle area at the third lumbar vertebra (L3) level was evaluated by computed tomography before chemoradiotherapy, and this was normalized by the square of the height to obtain the skeletal muscle index. Low skeletal muscle mass was defined as the sex-specific lowest quartile of the L3 skeletal muscle index. The association between low skeletal muscle mass and morbidity, relapse-free survival, or overall survival was assessed.Low skeletal muscle mass was identified in 37 (25.7%) patients. Age and body mass index were associated with low skeletal muscle mass. By multivariate analysis, we found that low skeletal muscle mass was independently associated with poor overall survival (hazard ratio = 2.93; 95%CI: 1.11-7.71; p = 0.031) and relapse-free survival (hazard ratio = 2.15; 95%CI: 1.06-4.21; p = 0.035), but was not associated with the rate of postoperative complications.Low skeletal muscle mass is an independent negative prognostic factor for relapse-free and overall survival in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.

SUBMITTER: Takeda Y

PROVIDER: S-EPMC5890989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Neoadjuvant chemoradiotherapy determines the prognostic impact of anastomotic leakage in advanced rectal cancer

Project description:Purpose The prognostic impact of anastomotic leakage (AL) in rectal cancer remains uncertain. We investigated the prognostic significance of AL in rectal cancer patients who underwent curative surgery, especially in terms of chemoradiotherapy. Methods A total of 1,818 rectal cancer patients who underwent radical surgery from 2011 to 2015 were retrospectively evaluated. We categorized patients according to AL and compared survival outcomes between the groups before and after matching. In locally advanced rectal cancer patients, we classified patients according to neoadjuvant chemoradiotherapy (nCRT) or adjuvant chemotherapy (aCTx) and analyzed survival outcomes according to AL in each group. Results Before matching, overall survival (OS) was significantly worse in the AL (+) group compared to the AL (–) group (P = 0.004). In matched patients, there were no differences in disease-free survival (DFS) and OS between groups (P = 0.423 and P = 0.083, respectively). In subgroup analysis for locally advanced rectal cancer, patients were classified as follows: nCRT (+) and aCTx (+) group; nCRT (+) and aCTx (–) group; nCRT (–) and aCTx (+) group; and nCRT (–) and aCTx (–) group. In the nCRT (–) and aCTx (+) group, patients with AL exhibited significantly worse DFS than patients without AL (P = 0.040). In the other 3 groups, there were no differences in DFS according to AL. Conclusion In locally advanced rectal cancer, AL had an adverse effect on oncologic outcome in patients receiving aCTx without nCRT but not in patients receiving nCRT.

| S-EPMC9582617 | biostudies-literature

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

Project description:PurposeIt 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/methodsIn 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.ResultsOf 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.ConclusionsFor 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

Promises and Challenges of Predictive Blood Biomarkers for Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.

Project description:The treatment of locally advanced rectal cancer (LARC) requires a multimodal approach combining neoadjuvant radiotherapy or chemoradiotherapy (CRT) and surgery. Predicting tumor response to CRT can guide clinical decision making and improve patient care while avoiding unnecessary toxicity and morbidity. Circulating biomarkers offer both the advantage to be easily accessed and followed over time. In recent years, biomarkers such as proteins, blood cells, or nucleic acids have been investigated for their predictive value in oncology. We conducted a comprehensive literature review with the aim to summarize the status of circulating biomarkers predicting response to CRT in LARC. Forty-nine publications, of which forty-seven full-text articles, one review and one systematic review, were retrieved. These studies evaluated circulating markers (CEA and CA 19-9), inflammatory biomarkers (CRP, albumin, and lymphocytes), hematologic markers (hemoglobin and thrombocytes), lipids and circulating nucleic acids (cell-free DNA [cfDNA], circulating tumor DNA [ctDNA], and microRNA [miRNA]). Post-CRT CEA levels had the most consistent association with tumor response, while cfDNA integrity index, MGMT promoter methylation, ERCC-1, miRNAs, and miRNA-related SNPs were identified as potential predictive markers. Although circulating biomarkers hold great promise, inconsistent results, low statistical power, and low specificity and sensibility prevent them from reliably predicting tumor response following CRT. Validation and standardization of methods and technologies are further required to confirm results.

| S-EPMC9913546 | 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

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

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

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

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy.

Project description:The aim of this study was to explore the most powerful systemic inflammation marker of survival in locally advanced rectal cancer (LARC) patients and construct prognostic nomograms. A total of 472 LARC patients undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2011 to 2015 were included. The optimal cutoff points for the systemic immune-inflammation index (SII); and neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios were calculated and determined by using the X-tile program. The cut-off values were 797.6. 2.3, 169.5, and 0.4, respectively. Cox regression analysis demonstrated that higher pathological TNM stage, the AJCC tumor regression grade, and the NLR level were significantly associated with increased overall survival and disease-free survival. High NLR level (? 2.3) was associated with higher pre-NCRT CA19-9 levels, lower hemoglobin, larger tumor size, and more lymph nodes retrieved (p?=?0.012, p?=?0.024, and p?<?0.001; p?<?0.001, respectively). High NRL scores were associated with poorer 5-year disease-free survival and overall survival (p?<?0.001, and p?<?0.001, respectively). Predictive nomograms and time-independent receiver operating characteristic (ROC) curve that included the NLR score group were superior to those without NLR scores. Higher NLR scores (?2 0.3) were associated with poorer DFS and OS in LARC patients. In addition, NLR was identified as the most effective marker for systemic inflammation, and the prognostic value was further confirmed by time-dependent ROC analysis. More intense adjuvant treatment could be considered for higher NLR score patients with LARC following NCRT.

| S-EPMC7228917 | biostudies-literature

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

Project description: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.

| S-EPMC8635484 | biostudies-literature

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