Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 695-695
Author(s):  
Javier A. Cienfuegos ◽  
Fernando Rotellar ◽  
Jorge Baixauli ◽  
Carmen Beorlegui ◽  
Iosu Sola ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Factor ◽  
Lymphovascular Invasion ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Tumor Regression Grade ◽  
Grade 3

695 Background: The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. Methods: A total of 324 patients with LARC treated with CRT were operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification, and the presence of PLVI was studied histologically. Results: At a median follow-up of 79.0 months (range 3–250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2% and 74.9% respectively. The 5- and 10-year disease-free survival (DFS) was 75.1% and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p<0.001). The 10-year OS and DFS was 32.7% and 31.8% for grade 1; 63.8% and 58.6% for grade 2; 75.0% and 70.4% for grade 3; 90.4% and 88.4% for grade 3+, and 96.0% and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, TRG was an independent prognostic factor for OS and DFS. Conclusions: The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

scholarly journals Impact of Tumor Regression Grade as a Major Prognostic Factor in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Proposal for a Modified Staging System

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 319 ◽  
Author(s):  
Changhoon Song ◽  
Joo-Hyun Chung ◽  
Sung-Bum Kang ◽  
Duck-Woo Kim ◽  
Heung-Kwon Oh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cox Regression ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Staging System ◽  
Tumor Regression Grade ◽  
C Statistic ◽  
Regression Grade

There is ongoing debate regarding the significance of complete or near-complete response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study assessed the prognostic value of the Dworak tumor regression grade (TRG) following neoadjuvant CRT and surgery primarily in patients with pathological stage (ypStage) II and III rectal cancer. The records of 331 patients who underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and 2015 were retrospectively reviewed. Patients were categorized as having a good response (GR, TRG 3/4, n = 122) or a poor response (PR, TRG 1/2, n = 209). At a median follow-up of 65 months, five-year disease-free survival (DFS) was higher in the GR group than in the PR group (91.3% vs. 66.6%, p < 0.001). Patients with a GR and ypStage II disease had a five-year DFS that was indistinguishable from that of patients with ypStage 0–I disease (92.3% vs. 90.7%, p = 0.885). Likewise, patients with a GR and ypStage III disease had a five-year DFS similar to those with ypStage II disease (76.0% vs. 75.9%, p = 0.789). A new modified staging system that incorporates grouped TRG (GR vs. PR) was developed. The prognostic performance of this modified stage and the ypStage was compared with the Harrell C statistic. C statistic of the modified stage was higher than that of the ypStage (0.784 vs. 0.757, p = 0.012). The results remained robust after multivariate Cox regression analyses. In conclusion, a GR to neoadjuvant CRT is an independent predictor of good DFS and overall survival and further stratifies patients so as to estimate the risk of recurrence and survival among patients with ypStage II and III rectal cancer.

scholarly journals Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Alessandro Del Gobbo ◽  
Stefano Ferrero
Keyword(s):  
Rectal Cancer ◽  
State Of The Art ◽  
Tumor Regression ◽  
Dihydropyrimidine Dehydrogenase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Response To Therapy ◽  
Tumor Regression Grade ◽  
Immunohistochemical Markers ◽  
Rectal Cancers

We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG)). The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers.

Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
Jiaolin Zhou ◽  
Guole Lin ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
Yan-Fang Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lymph Node ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Lymph Node Involvement ◽  
Tumor Regression Grade ◽  
Treatment Intensification

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.

The prognosis valve of tumor regression grade in the same ypStage patients after neoadjuvant treatment in locally advanced rectal cancer: Post-hoc analysis of a prospective trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16129-e16129
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Zehua Wu ◽  
Xiaoyu Xie ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Prospective Trial ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Prognosis Factor

e16129 Background: The ypStage after neoadjuvant treatment was an important prognosis factor in locally advanced rectal cancer (LARC). pCR or ypStage 0 showed best prognosis, while ypStage II-III showed poor prognosis and further adjuvant chemotherapy with FOLFOX was recommended. Tumor regression grade (TRG) was another factor to evaluate the response to neoadjuvant treatment. Even in the same ypStage, the TRG could be different. Here, we tried to analyze the prognosis valve of TRG in the same ypStage after neoadjuvant treatment in LARC from a prospective trial (FOWARC study). Methods: Patients with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil plus radiotherapy followed by surgery and seven cycles of infusional fluorouracil as adjuvant treatment, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). Survival analysis was performed on different ypStage and TRG (WHO classification) group. Results: In total, 495 patients were randomly assigned to different neoadjuvant treatment. 444 patients received surgery with a median follow-up of 45.2 months. The 3-year disease free survival (DFS) in ypStage 0, ypStage I, ypStage II and ypStage III was 95.8%, 89.2%, 71.7% and 55.1%, respectively (P < 0.0001). In TRG 0, 1, 2 and 3, the 3-year DFS was 93.3%, 83.2%, 68.4% and 63.6%, respectively (P < 0.0001). In ypStage I subgroup, TRG was not an independent prognosis factor, the 3-year DFS for TRG 1, 2 and 3 was 90.0%, 90.7% and 76.2%, respectively (P = 0.277). In ypStage II population, the 3-year DFS for TRG 1, 2 and 3 was 78.6%, 70.3% and 64.7%, respectively (P = 0.184). The ypStage III group showed great heterogeneity, the 3-year DFS for TRG 0-3 was 60.0%, 70.0%, 41.8% and 59.5%, respectively (P = 0.067). Conclusions: Both ypStage and TRG was strong prognosis factor for rectal cancer after neoadjuvant treatment. However, TRG was not an independent prognosis factor in the same ypStage after neoadjuvant treatment. Clinical trial information: NCT01211210 .

Phase II study of durvalumab plus total neoadjuvant therapy (TNT) in locally advanced rectal cancer: The GEMCAD-1703 DUREC trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4122-TPS4122
Author(s):  
Jaume Capdevila ◽  
Ismael Macias Declara ◽  
Maria Carmen Riesco Martinez ◽  
Joan Maurel ◽  
Jorge Hernando ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cell Death ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Primary Objective ◽  
Tumor Regression Grade ◽  
Open Label ◽  
Post Surgery

TPS4122 Background: In clinical stages II and III (cT3-4 and/or N+), preoperative chemoradiotherapy (CRT) or short-course radiation followed by total mesorectal escision (TME) have been the standard of care for the last 15 years. Induction chemotherapy (CT) before CRT (strategy known as TNT) results in fewer toxic effects and improved compliance. TNT may release tumor-neoantigens with platinum-based induction CT, and radiotherapy has the potential ability to induce an immunogenic cell death and counteract an immune-suppressive tumor microenvironment that provides the rationale for combining with immunotherapies. In addition, the presence of tumor infiltrating lymphocytes has been demonstrated in patients with rectal cancer treated with neoadjuvant CRT, reinforcing the rational for immune check-point inhibitors in this setting. We hypothesize that combining TNT with durvalumab (an optimized monoclonal antibody directed against programmed cell death-1 ligand 1) would improve outcome. Methods: DUREC is a multicenter, single-arm, open-label, phase Ib/II study for patients with magnetic resonance (mr) image middle or distal third, mrT3c-d/T4/N2 rectal adenocarcinoma. Treatment: Patients will receive 6 cycles of modified FOLFOX6 prior to CRT (capecitabine with 50.4 Gy in 28 fractions) and TME, combined with durvalumab 1500 mg every 4 weeks during induction CT, CRT and waiting period until surgery. To assess the tolerability and toxicity profile we plan to perform a run-in treatment phase including the first 6 patients in the study, holding recruitment until all of them will be operated and 30-days post-surgery period completed. If ≤ 2 durvalumab-related dose-limiting toxicities (DLTs) are observed, recruitment will continue. The primary objective is pathological complete response (pCR) rate. Secondary endpoints include toxicity, tumor regression grade, R0 resections, clear circumferential margins, surgical complications, NAR score, disease-free survival and a biomarker program on tumor tissue, blood samples and stool microbiota. Statistical design: 58 evaluable patients (assuming a P0 of 16% and a P1 of 30%, with 0.1 alpha and 0.1 beta); Study started recruitment on December 2019. Clinical trial information: 2018-004835-56 .

LincRNA-p21 as predictive response marker for preoperative chemoradiotherapy in rectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15534-e15534
Author(s):  
Jose Carlos Benitez ◽  
Tania Diaz ◽  
Carme Ferrer ◽  
Melissa Acosta ◽  
Mariano Monzo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Preoperative Chemoradiotherapy ◽  
University Hospital ◽  
Stage Iii ◽  
Tumor Regression Grade ◽  
Binary Logistic Regression Analysis ◽  
Crt Response

e15534 Background: Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients (pts). Despite the benefits of CRT, its use in non-responder pts can be associated with increased toxicities and resection delay. The identification of CRT response biomarkers, such as long non-coding RNAs (lncRNA), could improve the management of these pts. LincRNA-p21 is a lncRNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. We aim to study lincRNA-p21 expression in pretreatment samples from RC pts treated with CRT to evaluate whether lincRNA-p21 can act as a predictive biomarker for CRT response. Methods: RNA from pretreatment endoscopy biopsies from 58 RC pts treated with preoperative CRT at Mutua Terrassa University Hospital were analyzed. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR and was correlated with CRT response and, time to relapse (TTR), disease-free survival (DFS) and overall survival (OS). Results: Samples from 58 pts were analyzed. Most of them males (n = 40, 69%). Median age at diagnosis of 67 (44-82) years. Fifty (86.2%) pts reported stage III and, 42 (72.4%) pts assessed TRG 0-3 with a 70.7% of downstaging reported. LincRNA-p21 was upregulated in stage III tumors (p < 0.0001) and also in tumors with worst response to CRT regarding TRG, TGR0-3 (TRG0-3, n = 42 vs TRG4, n = 16, p = 0.019). In this line, the ROC curve analysis showed that lincRNA-p21 expression had capacity to distinguish pts with maximum response (TRG4) from others (AUC:0.7; p = 0.02). The binary logistic regression analysis validated its independence as response biomarker. LincRNA-p21 levels correlated with pts relapse after surgery. When the pts were classified in 3 groups, high, medium and low, according to lincRNA-p21 levels, RC pts with highest lincRNA-p21 expression had the shortest TTR. TTR for pts with high levels was 74.5 months (m) (95% CI:31-117), while it was 114 m (95% CI:95-133) for those with Medium levels and 123 m (95% CI:111-134) for those with low levels (p = 0.047). Conclusions: LincRNA-p21 is a marker of advanced disease and worse response to CRT. LincRNA-p21 may add valuable information for individualizing pre-operative CRT in locally advanced RC pts.

scholarly journals DPYD,TYMS,TYMP,TK1, andTK2Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ming-Yii Huang ◽  
Chan-Han Wu ◽  
Chun-Ming Huang ◽  
Fu-Yen Chung ◽  
Ching-Wen Huang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
High Sensitivity ◽  
Response Prediction ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Genetic Biomarkers

This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction. We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, andTK2) and 3 radiotherapy response-related genes (GLUT1,HIF-1α, andHIF-2α) as targets for gene expression identification in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT. After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade2~4). Using a panel of multiple genetic biomarkers (chip), includingDPYD,TYMS,TYMP,TK1, andTK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991). Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P=0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis). Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P=0.0001). We suggest that a chip includingDPYD,TYMS,TYMP,TK1, andTK2genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT.

scholarly journals Evaluating treatment response to neoadjuvant chemoradiotherapy in rectal cancer using various MRI-based radiomics models

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihui Li ◽  
Xiaolu Ma ◽  
Fu Shen ◽  
Haidi Lu ◽  
Yuwei Xia ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Response ◽  
Nearest Neighbor ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Principal Component ◽  
Tumor Regression Grade ◽  
K Nearest Neighbor

Abstract Background To validate and compare various MRI-based radiomics models to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal cancer. Methods A total of 80 patients with locally advanced rectal cancer (LARC) who underwent surgical resection after nCRT were enrolled retrospectively. Rectal MR images were scanned pre- and post-nCRT. The radiomics features were extracted from T2-weighted images, then reduced separately by least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA). Four classifiers of Logistic Regression, Random Forest (RF), Decision Tree and K-nearest neighbor (KNN) models were constructed to assess the tumor regression grade (TRG) and pathologic complete response (pCR), respectively. The diagnostic performances of models were determined with leave-one-out cross-validation by generating receiver operating characteristic curves and decision curve analysis. Results Three features related to the TRG and 11 features related to the pCR were obtained by LASSO. Top five principal components representing a cumulative contribution of 80% to overall features were selected by PCA. For TRG, the area under the curve (AUC) of RF model was 0.943 for LASSO and 0.930 for PCA, higher than other models (P < 0.05 for both). As for pCR, the AUCs of KNN for LASSO and PCA were 0.945 and 0.712, higher than other models (P < 0.05 for both). The DCA showed that LASSO algorithm was clinically superior to PCA. Conclusion MRI-based radiomics models demonstrated good performance for evaluating the treatment response of LARC after nCRT and LASSO algorithm yielded more clinical benefit.

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