Fibrosis signature of anastomotic margins for predicting anastomotic stenosis in rectal cancer with neoadjuvant chemoradiotherapy and sphincter-preserving surgery
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PROVIDER: S-EPMC10950477 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundFew studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage (AL) are available up to now. This study aimed to investigate potential radiation-induced injury left on surgical margins of anterior resection after neoadjuvant chemoradiotherapy (nCRT) and its association with AL.MethodsWe retrospectively identified 161 consecutive patients who underwent anterior resection with nCRT, neoadjuvant chemotherapy without radiation (nCT) or no neoadjuvant therapy between 2014 and 2015. Tissue samples of resection margins were assessed using a specific histopathological score and microvessel density in submucosa. Propensity score matching was used to balance the baseline characteristics. Association between AL and histopathological features was analysed.ResultsAL occurred in 13 of 54 patients undergoing nCRT, 5 of 48 patients undergoing nCT and 7 of 59 patients without neoadjuvant therapy. Comparisons after matching showed median (range) histopathological scores as follows: 3 (0-8) vs 0 (0-3) vs 0 (0-2) for the proximal margin (P < 0.001); 4 (2-9) vs 0 (0-4) vs 0 (0-3) for the distal margin (P < 0.001). Correspondingly, mean (SD) microvessel densities were as follows: 21.7 (7.9) vs 27.2 (8.6) vs 27.3 (9.4) for the proximal margin (P = 0.003); 18.1 (9.3) vs 25.2 (12.9) vs 24.9 (7.4) for the distal margin (P < 0.001). Among patients undergoing nCRT, AL was associated with increased histopathological score (P = 0.003) and decreased microvessel density (P = 0.004) on the proximal margin.ConclusionsSurgical margins of rectal-cancer resection are exposed to certain radiation-induced injury after nCRT. AL is associated with aggravated radiation damage on the proximal margin.
| S-EPMC6454846 | biostudies-literature
Project description:PurposeThe 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.MethodsA 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.ResultsBefore 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.ConclusionIn 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
Project description:BackgroundLocally advanced rectal cancers (LARC) show a highly variable response to neoadjuvant chemoradiotherapy (nCRT), and the impact of the tumor immune response in this process is poorly understood. This study aimed to characterize the immune-related gene expression profiles (GEP), pathways, and cell types associated with response or resistance to neoadjuvant chemoradiotherapy.MethodsThe transcriptomic and clinical data of Rectal carcinoma from the Gene Expression Omnibus database and Immune-related genes (IRGs) from ImmPort were downloaded to identify the differentially expressed immune-related genes (DEIRGs) between responder and non-responder to neoadjuvant chemoradiotherapy. Gene set enrichment analyses were performed to uncover significantly enriched GO terms and KEGG pathways. Immune cell infiltration was estimated from RNA-sequencing data using ImmuCellAI. Afterward, we constructed an immune-related gene-based predictive model (IRGPM) by Support Vector Machine and validated it in an external cohort.ResultA 15-gene signature (HLA-DPB1, HLA-DQA1, CXCL9, CXCL10, TAP2, INHBB, BMP2, CD74, IL33, CCL11, CXCL11, DEFB1, HLA-DPA1, CCN3, STAT1) was identified as DEIRGs and found to be significantly associated with nCRT outcomes. Gene set enrichment analyses indicated that the 15 genes play active roles in inflammation-related biological processes. In addition, ImmuCellAI revealed that CD4 naive T cells, Tex, Th1 were significantly up-regulated (p=0.035, p=0.02, p=0.0086, respectively), while Tfh were significantly down-regulated (p=0.015) in responder subgroup. Finally, a novel predictive model was developed by SVM based on DEIRGs with an AUC of 80% (internal validation) and 73.5% (external validation).ConclusionOur team conducted a genomic study of the relationship between gene expression profile and response to nCRT in LARC. Our data suggested that the DEIRGs signature could help predict the efficacy of nCRT. And a DEIRGs-based SVM model was developed to monitor the outcomes of nCRT in LARC.
| S-EPMC9121132 | biostudies-literature
Project description:BackgroundThe adequate distal resection margin is still controversial in rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). The aim of this study was to assess the impact of a distal margin of ≤1 mm on locoregional recurrence-free survival (LRRFS).MethodsAmong 255 patients treated with nCRT and surgery at the National Cancer Institute of Milan, 83 (32.5%) had a distal margin of ≤1 mm and 172 (67.5%) had a distal margin of >1 mm. Survival analyses were performed to assess the impact of distal margin on 5-year LRRFS, as well as Cox survival analysis. The role of distal margin on survival was analyzed according to different tumor regression grades (TRGs).ResultsThe overall 5-year LRRFS rate was 77.6% with a distal margin of ≤1 mm vs. 88.3% with a distal margin of >1 mm (Log-rank p = 0.09). Only stage ypT4 was an independent predictor of worse LRRFS (HR 15.14, p = 0.026). The 5-year LRRFS was significantly lower in TRG3-5 patients with a distal margin of ≤1 mm compared to those with a distal margin of >1 mm (68.5% vs. 84.2%, p = 0.027), while no difference was observed in case of TRG1-2 (p = 0.77).ConclusionsLow-responder rectal cancers after nCRT still require a distal margin of >1 mm to reduce the high likelihood of local relapse.
| S-EPMC10047023 | biostudies-literature
Project description:Background: Neoadjuvant chemoradiotherapy (NCRT) is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. Methods: Forty-eight candidates for NCRT were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade (TRG).Results: Both Smoothing and Hidden Markov Model (HMM) approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 7q21, 7q36, 13q12, 13q32-34, 16p13, 17p12 chromosomal regions. Conclusion: This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information about response to NCRT and help to optimize therapy in rectal cancer patients. 48 samples included in the study were analyzed on whole genome BAC arrays with the aim to characterize genomic alterations and correlate them with the tumor response to therapy. The case series was composed by 15%,81% and 4% of uT2, uT3 and uT4 tumors, respectively. At the diagnosis 56% of patients had uN0 tumors and 44% uN+. 30%,13%, 23% and 34% of patients reached/mantained respectively ypT0, ypT1, ypT2 and ypT3. With regard to response to NCRT, according to TRG criteria proposed by Dworak, two group were defined: non responders (TRG0-2= 56%) and responders (TRG3-4=44%). Clinical and pathological parameters: uT: pre-therapy stage determined by ultrasounds techniques uN: pre-therapy lymph node status determined by ultrasounds techniques ypT: pathologic stage after a neoadjuvant treatment ypN: pathologic lymph node status after a neoadjuvant treatment
2011-11-17 | E-GEOD-25885 | biostudies-arrayexpress
Project description:The present study explored the benefit of preoperative chemoradiotherapy (PCRT) for sphincter preservation in locally advanced low-lying rectal cancer patients who underwent stapled anastomosis, especially in those with deep and narrow pelvises determined by magnetic resonance imaging.Patients with locally advanced low-lying rectal cancer (≤5 cm from the anal verge) who underwent stapled anastomosis were included. Patients were categorized into two groups (PCRT+ vs. PCRT-) according to PCRT application. Patients in the PCRT+ group were matched to those in the PCRT- group according to potential confounding factors (age, gender, clinical stage, and body mass index) for sphincter preservation. Sphincter preservation, permanent stoma, and anastomosis-related complications were compared between the groups. Pelvic magnetic resonance imaging was used to measure 12 dimensions representing pelvic cavity depth and width with which deep and narrow pelvis was defined. The impact of PCRT on sphincter preservation and permanent stoma in pelvic dimensions defined as deep and narrow pelvis was evaluated, and factors associated with sphincter preservation and permanent stoma were analyzed.One hundred sixty-six patients were one-to-one matched between the PCRT+ and PCRT- groups. Overall, sphincter-saving surgery was performed in 66.3% and the rates were not different between the 2 groups. Anastomotic complications and permanent stoma occurred nonsignificantly more frequently in the PCRT+ group. PCRT was not associated with higher rate of sphincter preservation in all pelvic dimensions defined as deep and narrow pelvis, while PCRT was related to higher rate of permanent stoma in shorter transverse diameter and interspinous distance. On logistic regression analysis, PCRT was not shown to influence both sphincter preservation and permanent stoma, while longer transverse diameter and interspinous distance were associated with lower rate of permanent stoma.PCRT had no beneficial effect on sphincter preservation in patients with locally advanced low-lying rectal cancer who had undergone stapled anastomosis. In patients with deep and narrow pelvis, PCRT had no impact on sphincter preservation but was associated with higher rate of permanent stoma.
| S-EPMC4863762 | biostudies-literature
Project description:AimSphincter-preserving operations for ultra-low rectal cancer include low anterior and intersphincteric resection. In low anterior resection, the distal rectum is divided by a transabdominal approach, which is technically demanding. In intersphincteric resection, a perineal approach is used. We aimed to evaluate whether robotic-assisted surgery is technically superior to laparoscopic surgery for ultra-low rectal cancer. We compared the frequency of low anterior resection in cases of sphincter-preserving operations.MethodWe investigated 183 patients who underwent sphincter-preserving robotic-assisted or laparoscopic surgery for ultra-low rectal cancer (lower border within 5 cm of the anal verge) between April 2010 and March 2020. The frequency of low anterior resection was compared between laparoscopic and robotic-assisted surgeries. The clinicopathological factors associated with an increase in performing low anterior resection were analyzed by multivariate analyses.ResultsOverall, 41 (22.4%) and 142 (77.6%) patients underwent laparoscopic and robotic-assisted surgery, respectively. Patient characteristics were similar between the groups. Low anterior resection was done significantly more frequently in robotic-assisted surgery (67.6%) than in laparoscopic surgery (48.8%) (P = 0.04). Multivariate analyses showed that tumor distance from the anal verge (P < 0.01) and robotic-assisted surgery (P = 0.02) were significantly associated with an increase in the performance of low anterior resection. The rate of postoperative complications or pathological results was similar between the groups.ConclusionCompared with laparoscopic surgery, robotic-assisted surgery significantly increased the frequency of low anterior resection in sphincter-preserving operations for ultra-low rectal cancer. Robotic-assisted surgery has technical superiority over laparoscopic surgery for ultra-low rectal cancer treatment.
| S-EPMC9444857 | biostudies-literature
Project description:Background: Neoadjuvant chemoradiotherapy (NCRT) is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. Methods: Forty-eight candidates for NCRT were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade (TRG).Results: Both Smoothing and Hidden Markov Model (HMM) approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 7q21, 7q36, 13q12, 13q32-34, 16p13, 17p12 chromosomal regions. Conclusion: This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information about response to NCRT and help to optimize therapy in rectal cancer patients.
2011-11-17 | GSE25885 | GEO
Project description:BackgroundColorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance.MethodsFrom twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups.ResultsWe have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440.ConclusionsFrom these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer. These results will pave the way for a larger cohort for better sensitivity and specificity of the signature to guide decisions in the choice of treatment.
| S-EPMC5898006 | biostudies-literature
Project description:PurposeWhether radiomics methods are useful in prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) is unclear. This study aimed to investigate multiple magnetic resonance imaging (MRI) sequence-based radiomics methods in evaluating therapeutic response to nCRT in patients with locally advanced rectal cancer (LARC).MethodsThis retrospective study enrolled patients with LARC (06/2014-08/2017) and divided them into nCRT-sensitive and nCRT-resistant groups according to postoperative tumor regression grading results. Radiomics features from preoperative MRI were extracted, followed by dimension reduction using the minimum redundancy maximum relevance filter. Three machine-learning classifiers and an ensemble classifier were used for therapeutic response prediction. Radiomics nomogram incorporating clinical parameters were constructed using logistic regression. The receiver operating characteristic (ROC), decision curves analysis (DCA) and calibration curves were also plotted to evaluate the prediction performance.ResultsThe machine learning classifiers showed good prediction performance for therapeutic responses in LARC patients (n=189). The ROC curve showed satisfying performance (area under the curve [AUC], 0.830; specificity, 0.794; sensitivity, 0.815) in the validation group. The radiomics signature included 30 imaging features derived from axial T1-weighted imaging with contrast and sagittal T2-weighted imaging and exhibited good predictive power for nCRT. A radiomics nomogram integrating carcinoembryonic antigen levels and tumor diameter showed excellent performance with an AUC of 0.949 (95% confidence interval, 0.892-0.997; specificity, 0.909; sensitivity, 0.879) in the validation group. DCA confirmed the clinical usefulness of the nomogram model.ConclusionThe radiomics method using multiple MRI sequences can be used to achieve individualized prediction of nCRT in patients with LARC before treatment.
| S-EPMC8136527 | biostudies-literature