scholarly journals A 41-Gene Pair Signature for Predicting the Pathological Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhengfa Xue ◽  
Shuxin Yang ◽  
Yun Luo ◽  
Hao Cai ◽  
Ming He ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Gene Pair ◽  
Expression Profiles ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathological Response ◽  
Gene Pairs

Background and Purpose: Pathological response status is a standard reference for the early evaluation of the effect of neoadjuvant chemoradiation (nCRT) on locally advanced rectal cancer (LARC) patients. Various patients respond differently to nCRT, but identifying the pathological response of LARC to nCRT remains a challenge. Therefore, we aimed to identify a signature that can predict the response of LARC to nCRT.Material and Methods: The gene expression profiles of 111 LARC patients receiving fluorouracil-based nCRT were used to obtain gene pairs with within-sample relative expression orderings related to pathological response. These reversal gene pairs were ranked according to the mean decrease Gini index provided by the random forest algorithm to obtain the signature. This signature was verified in two public cohorts of 46 and 42 samples, and a cohort of 33 samples measured at our laboratory. In addition, the signature was used to predict disease-free survival benefits in a series of colorectal cancer datasets.Results: A 41-gene pair signature (41-GPS) was identified in the training cohort with an accuracy of 84.68% and an area under the receiver operating characteristic curve (AUC) of 0.94. In the two public test cohorts, the accuracy was 93.37 and 73.81%, with AUCs of 0.97 and 0.86, respectively. In our dataset, the AUC was 0.80. The results of the survival analysis show that 41-GPS plays an effective role in identifying patients who will respond to nCRT and have a better prognosis.Conclusion: The signature consisting of 41 gene pairs can robustly predict the clinical pathological response of LARC patients to nCRT.

Analysis of recurrence pattern and survival in locally advanced rectal cancer treated with neoadjuvant chemoradiation and surgery: 25 years of experience.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 744-744
Author(s):  
Javier A. Cienfuegos ◽  
Jorge Baixauli ◽  
Fernando Rotellar ◽  
Iosu Sola ◽  
Jorge Arredondo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathological Response ◽  
Upper Third

744 Background: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (CRT) followed by total mesorectal excision (TME). Despite the significant reduction (~ 40%) in local recurrence, the overall survival (OS) and disease free survival (DFS) remain stable during last decade. We aimed to study the pattern of recurrence and it’s relationship with clinico-pathological data in 356 patients with LARC treated with CRT and TME in last 25 years. Methods: From a total of 621 patients, 356 with LARC were analyzed. In 55 (15.4%) the tumor was localized in upper third, in 120 (33.7%) in middle third and in 181 (50.8%) in distal third. The median dose of radiotherapy for the 3 groups was between 47.5 - 48.52 Gy. Chemotherapy was based on 5-FU or capecitabine combined with oxaliplatin. Type of surgery, pathological response grade, circumferential resection margin, lymphovascular invasion, colloid response, local recurrence incidence, distal relapse, OS and DFS were analyzed. Results: The median interval between the end of CRT and surgery was 40 days. 52 low anterior resection were carried-out in upper third (94.5%), 112 (93.3%) in middle third and 92 (50.8%) in distal third. Four patients from the middle third (3.3%) underwent abdominoperineal resection and 72 (39.8%) in the distal location. No differences were observed in number of lymphoid nodes, vascular perineural invasion, and pathological response grade. A pathological complete response was assessed in 5 patients (9.1%) in upper third, in 12 (10%) in middle third, as well in 32 (17.7%) in distal third. Median follow-up of 187 months. The 5-10 year DFS for the 3 groups was 75%, 76%, and 69%, and 75%, 71%, and 66% respectively. The local recurrence rate was 3.6%, 4.2%, and 6.1%. The distal recurrence was more frequent in the lung, 10.9%, 16.7%, 23.8%, with tendency to be significant (p<0.007) in distal third. Conclusions: In spite of the good local control with the association of preoperative CRT and TME in treatment of LARC, the development of distant metastases, especially in distal third, gives rise to new therapeutics schemes. Further research is warranted as to the benefits of adjuvant chemotherapy.

Predicting pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using FDG PET/CT.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 505-505
Author(s):  
S. Shanmugan ◽  
R. Arrangoiz ◽  
J. R. Nitzkorski ◽  
J. Q. Yu ◽  
T. Li ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pet Ct ◽  
Fdg Pet Ct

505 Background: Pathologic complete response (pCR) after neoadjuvant chemoradiation has been observed in 15% to 30% of patients with locally advanced rectal cancer. The utility of FDG PET/CT scans in the management of patients with stage II or III rectal cancer is not well defined. The objective of this study is to determine if FDG PET/CT can be used to predict pCR and disease-free survival in patients receiving neoadjuvant chemoradiation with locally advanced rectal cancer. Methods: A retrospective chart review was conducted in patients with endorectal ultrasound-staged T3 to T4 rectal tumors who underwent preoperative and postoperative FGD PET/CT imaging. All patients were treated with neoadjuvant chemoradiotherapy (CRT). Maximum standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, % SUV change, and time between therapy and surgery in comparison to pathological complete response. Kaplan-Meier estimation was used to look for significant predictors of survival. Results: Seventy patients (mean age 62; 42M:28F) with preoperative stage T3Nx (n = 60) and T4Nx (n = 10) underwent pre-CRT and post-CRT FDG PET/CT scans between November 2002 and March 2009. All patients underwent definitive surgery after therapy with standard pathologic evaluation.The pCR rate was 26%. Median pre-CRT SUV was 10.5 while the median post-CRT SUV was 4.05. Patients with pCR had a lower mean post-CRT SUV compared to those without pCR (2.7 vs. 4.5, p = 0.02). Median SUV decrease was 61% (range 6% to 95%) and was significant in predicting pCR (p = 0.004). Patients with a pCR had a greater time interval between neoadjuvant therapy and surgery (median 57 days vs. 50 days) than those without (p = 0.05). Furthermore, patients with post-CRT SUV < 4 had a lower local recurrence rate compared to those with post-CRT SUV > 4 (p = 0.03). Patients with SUV decrease > 61% had improved overall survival at mean follow-up of 39 months than those without (p = 0.01). Conclusions: PET/CT can predict response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Pre-CRT SUV was the only predictor of disease-free survival. No significant financial relationships to disclose.

Predicting Outcomes for Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation With CT-Based Radiomics

2021 ◽  
Author(s):  
Fuqiang Wang ◽  
Boon Fei Tan ◽  
Sharon Shuxian Poh ◽  
Tian Rui Siow ◽  
Faye Lynette Wei Tching Lim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cox Regression ◽  
Primary Tumour ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Survival Models ◽  
Free Survival

Abstract A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR>16 and NAR<8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR>16 and NAR<8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model.

scholarly journals Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 758-758
Author(s):  
Shaan Dudani ◽  
Horia Marginean ◽  
Patricia A. Tang ◽  
Jose Gerard Monzon ◽  
Soundouss Raissouni ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Stage ◽  
Performance Status ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Neoadjuvant Radiotherapy ◽  
Negative Predictor

758 Background: A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. Methods: We performed a review of patients with LARC undergoing nCRT followed by surgery with curative intent from 2005-2013 in 3 academic cancer centers from 2 Canadian provinces. Data regarding demographics, staging, baseline hematologic variables (<4 weeks prior/up to 2 weeks after initiating nCRT) and treatment details were collected. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for an association between baseline hematologic variables and outcomes. Results: Of 1081 identified patients, 845 were included in the DFS/OS analysis. Median age was 61 (range 23-87), 70% male, 85% performance status (PS) 0-1. 31% and 67% had clinical stage II and III disease, respectively. 25% had elevated NLR (≥ 4), and 64% had elevated PLR (≥ 150). 98% of patients received FP-based nCRT, with 96% receiving ≥ 44 Gy (median 50 Gy [range 20-74]). 80% completed neoadjuvant chemotherapy and 94% completed neoadjuvant radiotherapy, with a pCR rate of 23%. After a median follow up time of 64 months, 6% developed local recurrence, 20% developed distant recurrence and 19% have died. 5-year OS and DFS were 78% (95% CI 74-81%) and 76% (95% CI 73-79%), respectively. In multivariate analyses, elevated baseline NLR and PLR were not prognostic for OS or DFS. Elevated NLR was a negative predictor of pCR (OR 0.61, p=0.037, 95% CI 0.38-0.97); there was no association with elevated PLR. Conclusions: Elevated NLR was a negative predictor of pCR, but not prognostic for DFS and OS. PLR was neither predictive nor prognostic.

scholarly journals Tumor Regression Grades: Can They Influence Rectal Cancer Therapy Decision Tree?

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Marisa D. Santos ◽  
Cristina Silva ◽  
Anabela Rocha ◽  
Eduarda Matos ◽  
Carlos Nogueira ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Disease Recurrence ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Tumor Regression Grade ◽  
Survival Difference

Background. Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC).Materials and Methods. We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence.Results. Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS ; DFS ).Conclusions. Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC.

scholarly journals Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Enrichment Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Cytolytic Activity ◽  
Gene Set Enrichment Analysis ◽  
Preoperative Treatment ◽  
Rna Seq

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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