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.

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.

scholarly journals Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1894 ◽  
Author(s):  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Cosmin Caraiani ◽  
Diana Sorina Feier ◽  
Florin Graur ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Imaging Biomarkers ◽  
Tumor Regression Grade ◽  
Pre Treatment

Locally advanced rectal cancer (LARC) response to neoadjuvant chemoradiotherapy (nCRT) is very heterogeneous and up to 30% of patients are considered non-responders, presenting no tumor regression after nCRT. This study aimed to determine the ability of pre-treatment T2-weighted based radiomics features to predict LARC non-responders. A total of 67 LARC patients who underwent a pre-treatment MRI followed by nCRT and total mesorectal excision were assigned into training (n = 44) and validation (n = 23) groups. In both datasets, the patients were categorized according to the Ryan tumor regression grade (TRG) system into non-responders (TRG = 3) and responders (TRG 1 and 2). We extracted 960 radiomic features/patient from pre-treatment T2-weighted images. After a three-step feature selection process, including LASSO regression analysis, we built a radiomics score with seven radiomics features. This score was significantly higher among non-responders in both training and validation sets (p < 0.001 and p = 0.03) and it showed good predictive performance for LARC non-response, achieving an area under the curve (AUC) = 0.94 (95% CI: 0.82–0.99) in the training set and AUC = 0.80 (95% CI: 0.58–0.94) in the validation group. The multivariate analysis identified the radiomics score as an independent predictor for the tumor non-response (OR = 6.52, 95% CI: 1.87–22.72). Our results indicate that MRI radiomics features could be considered as potential imaging biomarkers for early prediction of LARC non-response to neoadjuvant treatment.

scholarly journals Comparison of the Diagnostic Performance of Changes in Signal Intensity and Volume From Multiparametric MRI for Assessing Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy

2021 ◽  
Author(s):  
Zhengwu Tan ◽  
Lan Zhang ◽  
Lan Cheng ◽  
Lingling Xie ◽  
Zhenyu Lin Lin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Signal Intensity ◽  
Diagnostic Performance ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Area Under The Curve ◽  
Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Change Rate

Abstract Background: Tumor regression grade (TRG) correlates with prognosis in patients with locally advanced rectal cancer (LARC), but there is controversy regarding the use of magnetic resonance imaging (MRI) for determining TRG. This study to evaluate the diagnostic value of change rate in signal intensity (SI) and volume (V) from MRI to TRG following preoperative chemoradiotherapy (CRT) in patiens with LARC.Materials and methods: This retrospective analysis examined 82 LARC patients who were admitted to our institution between Oct 2017 and Oct 2019. Patients underwent pre- and post-CRT T2-weighted (T2W), diffusion-weighted (DW)/apparent diffusion coefficient (ADC), and contrast-enhanced T1-weighted (ceT1W) MRI. Change rate of volume and relative SI ratio(%△V and %△SIR) from each sequence were determined. All LARCs were confirmed pathologically and classified into TRG 0, 1, 2 and 3. Descriptive statistics and receiver operating characteristic (ROC) analysis, with calculation of area under the curve (AUC), were used to compare the diagnostic performances. Results: Sixteen patients had TRG-0, 15 had TRG-1, 35 had TRG-2, and 16 had TRG-3. Except for ADC-%△SIR, the remaining%△V and %△SIR on T1W, DWI, and ceT1W had significant differences among the four groups. %△V and/or %△SIR did not distinguish TRG-1 from TRG-2 nor TRG-2 from TRG-3, but differences between other TRGs were identified by %△V and/or %△SIR on T2W, DWI, and ceT1W. The combined use of DW-%△V and T2W-%△SIR provided the best diagnostic performance in distinguishing of TRG-0 from TRG-2 (AUC: 0.954) and from TRG-3 (AUC: 1.000).Conclusions: Preoperative MRI of LARC patients can determine TRG and may improve selection of the preoperative therapy.

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.

Next-generation expression analysis (NanoString) to develop prognostic and predictive gene signatures for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 700-700
Author(s):  
Annalisa Milano ◽  
Marina Borro ◽  
Emanuela Pilozzi ◽  
Andrea Montori ◽  
Marco Mazzotta ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Wide Spectrum ◽  
Expression Profiles ◽  
Geometric Mean ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade

700 Background: The standard of care for locally advanced rectal cancer (RC) is neoadjuvant chemoradiotherapy (CRT) with 5FU aimed to tumor downstaging prior to radical resection but there is a wide spectrum of responses to it, from none to complete. The aim of this project is to validate top candidate genes previously identified by microarray studies as prognostic and predictive classifiers of locally advanced RC, using the NanoString nCounter Platform. Methods: Two cohorts of RC patients were identified according to tumor regression grade (TRG) of AJCC Staging Manual (7th) system: 1) good prognosis: patients that after neoadjuvant CRT obtained TRG0 (complete response); 2) poor prognosis: patients with TRG1 (moderate response), patients with TRG2 (minimum response rate) and patients with TRG3 (poor response). Pre-treatment biopsies tissues from ten TRG0 patients (ID TRG0bio) and thirteen TRG1-3 patients (ID TRG1-3bio) were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of a 305 genes custom code set consisting of 12 normalizer genes, 101 prognostic genes (markers of stemness, invasiveness, proliferation, drug-resistance), 192 predictive genes (involved in response to 5-FU, to radiation therapy and in the response to CRT). All samples were normalized using the geometric mean of the housekeeper genes. P-values were calculated by student’s t-test and was consider significance if was less than 0.05. Gene-specific RNA expression profiles were compared using Spearman's correlation. The heat map was generated using MeV 4.9.0. Results: When we compared TRG0bio to TRG1-3bio tissues, among the 305 genes assayed, changes in expression levels of 18 genes (SSB, GAPDH, TXNDC9, DUT, PKM, STAT1,SLC28A3, DAG1, TYMS, FERMT1, ARNT,SLC6A6, SMAD3, SCRN1, POU5F1, GNG4, PDRG1, ATP5E) were statistically significant. Conclusions: Results suggest that TRG0 RC is characterized by distinct molecular events compared TRG1-3 disease. Next steps will be: to amplify sample size, to understand signaling pathways of top differentially expressed genes and to validate prospectively our gene signature.

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