Value Of Tumor Regression Grade Research Articles

The role of MRI after neochemoradiotherapy in predicting pathological tumor regression grade and clinical outcome in patients with locally advanced rectal adenocarcinoma.

To evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC). This was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test. From January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p<0.05). In multivariate analysis, downstaging N was an independent prognostic factor for OS. Meanwhile, downstaging T and downstaging N remained independent prognostic factors for PFS. Although the consistency between mrTRG and pTRG is only fair, favorable mrTRG after neo-CRT may be used as a potential prognostic factor for LARC patients.

Is Tumor Regression Grade Sufficient to Predict Survival in Esophageal Cancer with Trimodal Therapy?

Background This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT). Methods Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan–Meier method and log–rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods. Results From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264–5.566, P < 0.001) and disease-free survival (HR: 2.801, 95% CI: 1.874–4.187, P < 0.001). The modified TRG system combining tumor regression with nodal status stratified patients survival with good discrimination. Conclusions Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systematic therapy of gastric cancer.

e16063 Background: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. However, the consistency of these two methods has not been determined. Therefore, we compared the prognostic value of TRG and RECIST 1.1 for gastric cancer (GC) patients and analyzed their consistency. Methods: Patients with gastric cancer who received preoperative chemotherapy or chemotherapy combined with immunotherapy and had record of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 is considered as consistent with CR or PR in RECIST 1.1 and TRG 2-3 corresponds to SD or PD in RECIST 1.1. The primary endpoints were disease free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Kaplan-Meier method and Cox proportional hazards regression models were used for survival analysis. Results: We enrolled 157 GC patients, including 125 patients with preoperative chemotherapy, and 32 patients with preoperative chemotherapy combined with PD-1 inhibitors. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results of RECIST 1.1 and TRG. The pCR rate was 13.4% and the overall response rate (ORR) was 52.6% according to RECIST 1.1. Preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone, 34.4% vs 8.0%, P&lt; 0.001. TRG was significantly correlated with both OS and DFS (P = 0.0162 and 0.0259, respectively) while response according to RECIST1.1 was not significantly related with OS and DFS ( P= 0.8598 and 0.2288, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. Young patient, peritoneal metastasis or liver metastasis was correlated with TRG 2-3. Conclusions: Our results showed that TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received neoadjuvant therapy.

Tumor regression grade combined with lymph node status in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy

IntroductionWe aimed to elucidate the prognostic value of tumor regression grade (TRG) combined with lymph node status compared with the 8th edition of the ypTNM staging system in patients with advanced esophageal squamous cell cancer (ESCC) after neoadjuvant chemoradiotherapy (nCRT).MethodsWe enrolled 325 patients with ESCC who underwent nCRT followed by complete resection. We adopted the modified Schneider TRG system, with high (ypT0N0), mid (ypT0N+ or ypT + N0), and low (ypT + N+). After developing a multivariable Cox model, the discrimination ability of the ypStage and TRG systems was evaluated using the Akaike Information Criterion (AIC) and R 2 measure.ResultsThe mean duration of follow‐up was 56.7 ± 43.3 months. The survival curves between the adjacent groups of TRG were significantly different for both overall survival (OS) and recurrence‐free survival (RFS). However, there were no significant differences between ypStages II and III for OS (p = 0.683) or RFS (p = 0.760). The TRG system also had a discrimination ability in patients with ypStage I (p < 0.001 for both OS and RFS) and ypStage III (p = 0.045 for OS and 0.042 for RFS). Compared with the ypTNM staging system, the modified TRG had a lower AIC value (1835.99 vs. 1852.02) and a higher R 2 (0.256 vs. 0.177), indicating better discrimination ability and prediction accuracy.ConclusionsFor patients with ESCC who underwent esophagectomy following nCRT, the modified Schneider TRG system may complement the ypStage and help clinicians select the most appropriate postoperative treatment and surveillance.

Correlative Significance of Tumor Regression Grade and ypT Category in Patients Undergoing Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

Background: In patients with locally advanced rectal cancer, the treatment response to preoperative chemoradiotherapy (PRCRT) varies, and the ypT stage may change as a result of tumor shrinkage. The purpose of this study was to evaluate the correlative significance and determine the prognostic value of tumor regression grade and ypT category staging systems.Materials and Methods: This retrospective observational study was conducted in a tertiary center. A total of 1240 patients with rectal cancer who underwent curative resection after PRCRT between January 2007 and December 2016 were consecutively included.Results: A significant association was found between the American Joint Committee on Cancer/College of American Pathology tumor regression grading system and ypT category, indicating a potential correlation between worse tumor regression grade and more advanced T stage (Cramer's V = 0.255, P < .001). The ypT stage and tumor regression grade were independent predictors of each other (P < .001). The good response group (tumor regression grades 0-1) had significantly higher 5-year disease-free survival (85.5% vs. 68.2%, P < .001) and overall survival (92.1% vs. 81.0%, P < .001) rates than the poor response group (tumor regression grades 2-3). However, the ypT and ypN categories were the most important independent prognostic factors for disease-free and overall survival.Conclusions: Tumor regression grade and ypT category were significantly correlated. Although tumor regression grade alone is not definitive, it is closely related to the ypT stage and impacts oncologic outcomes. These findings should be taken into consideration when stratifying the prognosis of patients undergoing PRCRT.

Tumor Regression Grade as a Prognostic Factor in Metastatic Colon Cancer Following Preoperative Chemotherapy

BackgroundThe prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported. Materials and MethodsA total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response). ResultsOf the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients’ prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P<0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2). ConclusionTRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.

Prognostic value of tumor regression grade following the administration of neoadjuvant chemotherapy as treatment for gastric/gastroesophageal adenocarcinoma: A meta-analysis of 14 published studies

IntroductionThe efficacy of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) has recently been revealed. The use of tumor regression grade (TRG) has also been reported, where TRG has been positively correlated with prognosis. However, previous studies included several types of GC and treatments. The prognostic value of TRG in a specific population has not been well investigated. Therefore, a meta-analysis of studies on gastric adenocarcinomas treated with NAC that evaluate the prognostic impact of TRG on overall survival (OS) must be conducted to provide more accurate evidence. MethodsA meta-analysis of studies reporting gastric cancer/gastroesophageal junction (GC/GEJ) adenocarcinoma treated with NAC was performed. Studies that calculate the number of responders and non-responders were considered eligible. The risk ratio (RR) was obtained from the eligible studies, and a random-effects model was used for pooled analysis. ResultsFourteen studies, which included a total of 1660 patients, were included in the current study. The responders showed better OS (RR: 0.53, 95% confidence interval (CI): 0.46–0.60, P < 0.001). All subgroup analyses (Asian vs. non-Asian populations, different TRGs, GC/GEJ vs. GC) also revealed the statistical dominance of better TRG over better OS. However, the possibility of some publication bias remained. ConclusionsIn this meta-analysis, better TRG was associated with better OS. However, the histology, configuration, and location of GC varied. Hence, a more subdivided analysis is recommended to obtain more solid evidence.

Prognostic Value of Tumor Regression Grade on MR in Rectal Cancer: A Large-Scale, Single-Center Experience.

ObjectiveTo determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared with pathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserver agreement for evaluating mrTRG.Materials and MethodsBetween 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; mean age, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologists independently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologists graded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models were used for survival analysis. Cohen's kappa analysis was used to determine interobserver agreement.ResultsAccording to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5. By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantly different according to the 5-point grading mrTRG (p = 0.024) and pTRG (p = 0.038). The 5-year disease-free survival (DFS) was significantly different among the five mrTRG groups (p = 0.039), but not among the five pTRG groups (p = 0.072). OS and DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio = 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, k value between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI.ConclusionmrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weighted MRI may improve interobserver agreement on mrTRG.

Prognostic Value of Tumor Regression Grade Based on Ryan Score in Squamous Cell Carcinoma and Adenocarcinoma of Esophagus.

Tumor regression grade (TRG) of the primary tumor after neoadjuvant therapy is one of the most sensitive prognostic factors among patients with locally advanced esophageal cancer, although no TRG system is fully accepted. The Ryan score was proposed in 2005 to evaluate TRG in rectal cancer and could be adaptable for pathological evaluation of esophageal cancer. The objective of this study is to evaluate the prognostic value of the Ryan score for esophageal cancer in the setting of trimodal therapy. We performed a retrospective cohort study in which patients with locally advanced esophageal cancer, submitted to neoadjuvant therapy followed by surgical resection, were selected. One hundred thirty-four patients were selected. All tissue specimens were assessed as per the TRG system proposed by Ryan et al. Survival curves were assessed by the Kaplan-Meier method and log-rank test. Chi-square test or likelihood-ratio test was used for absolute and relative variables. Kruskal-Wallis and analysis of variance tests were used to assess significant differences on a continuous dependent variable by a categorical independent variable. Of the 134 included patients, 94 (70.1%) had squamous cell carcinoma, and 40 (29.9%) adenocarcinoma. Ryan score was correlated with histological type (p < 0.001), and clinical (p = 0.044) and pathological (p < 0.001) staging. Mean follow-up was 31.1months. Multivariate analysis showed that Ryan score can safely predict survival, and systemic and lymphatic recurrence (p < 0.05). Ryan score is an effective system to evaluate TRG and can predict risk for lymph node or distant metastasis, overall survival, and disease-free survival.

PROGNOSTIC VALUE OF POST-RADIATION REGRESSION OF LOCALLY ADVANCED RECTAL CANCER

Currently, combination therapy, including preoperative irradiation of the tumor and areas of regional lymphatic drainage, has become the standard for the treatment of patients with locally advanced rectal cancer. Methods for evaluating neoadjuvant therapy response are increasingly being introduced into the practice of specialized medical centers. However, the prognostic value of tumor regression grade remains unclear. The results of numerous studies presented in modern literature are contradictory, and their comparative analysis is extremely difficult because of the abundance of post-radiation regression classifications used. This review article reflects the current views on the role and ways of assessing the therapeutic pathomorphosis of rectal cancer after radiotherapy/chemoradiotherapy.

Lymph nodes regression grade is a predictive marker for rectal cancer after neoadjuvant therapy and radical surgery.

Neoadjuvant therapy (NT) for rectal cancer (RC) reduces primary tumors and involved lymph nodes. While a prognostic value of tumor regression grade (TRG) has been identified, involved lymph node regression grade (LRG) has not been systematically evaluated. Here, we evaluated the association of LRG with oncologic outcomes of RC patients after NT followed by radical surgery. 347 patients with locally advanced RC who received NT and then underwent radical surgery were retrospectively recruited between 2004 and 2011. Response to NT was evaluated by a 3-tier LRG and TRG based on the ratio of residual tumor to fibrosis. LRG was assessed in all patients (LRG 0, 170 patients [49.0%]; LRG 1, 100 patients [28.8%]; and LRG 2, 77 patients [22.2%]). LRG correlated with 5-year distant metastasis and 5-year disease free survival (p=0.029 and 0.023, respectively). LRG also correlated with TRG (p=0.017). We conclude that the LRG system may be an independent predictive factor of long-term oncologic outcomes of rectal cancer patients after NT and radical surgery.

P-0297 Predictive/Prognostic Value of TS, KI-67, Egfr, MLH-1, MSH-2 and Trg in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation (Bmg-B1-Study)

ABSTRACT Introduction Preoperative 5-fluorouracil/capecitabine based chemoradiation (CRT) is standard treatment in locally advanced rectal cancer (LARC) patients (pts). The aim of this Bologna Multidisciplinary Group (BMG-B1) study was to evaluate the predictive and prognostic value of Tumor Regression Grade (TRG) and pathological biomarkers (thymidylate synthetase/TS, epidermal growth factor receptor/EGFR, Ki-67, p53, Bcl-2, MLH1 and MSH2). Methods Between December 2001 to January 2011 we evaluated 149 pts with cT3-T4 N-/+ rectal adenocarcinoma and location ≤12 cm from the anal margin. Preoperative CRT consisted of radiotherapy 50.4 Gy in 28 daily fractions in combination with 5-fluorouracil continuous infusion or capecitabine +/- oxaliplatin. Rectal surgery with total mesorectal excision was performed 6-8 weeks after neoadjuvant treatment. Pathological examination of surgical specimens included the TRG according to Dworak (TRG0=no regression, TRG1=minor regression, TRG2=moderate regression, TRG3=good regression TRG4=complete regression). TS, EGFR, Ki-67, p53, Bcl-2, MLH1 and MSH2 were immunohistochemically determined in pretreatment biopsies and surgical specimens. Serial sections of formalin-fixed, paraffin-embedded tissues were stained with anti-TS (clone TS106/4H4B1, Zymed Lab. Inc., Invitrogen USA), anti-EGFR (clone DAK-H1-WT, DakoCytomation USA), anti-Ki-67 (clone MM1, Novocastra Lab.UK), anti-p53 (clone BP53-12, Novocastra Lab. UK), anti-Bcl-2 (clone 124, DakoCytomation. USA), anti-MLH1 (clone G168-15, Pharmingen, USA), anti-MSH2 (clone FE11, Zymed Lab. Inc., Invitrogen USA) using a biotin free ready-to-use amplification system (Dako Advance HRP, DakoCytomation DK). Results Immunohistochemistry results of 100 biopsies and 97 surgical specimens were available. After a median follow-up of 60.3 months (2-122) we observed 4.7% local recurrences, 12.7% distant recurrences, and 13.4% deaths. TRG grade 1, 2, 3, and 4 were observed respectively in 22.6%, 35.4%, 25.5%, 16.5% of patients. Patients with TRG grade 0-1 compared to patients with TRG grade 2-4 had significant worse disease free survival (DFS) (p=0.008) and overall survival (p=0.04). High TS expression in biopsy specimens is related with TRG grade 0-1 (p=0.009). High EGFR expression in surgical specimen is related with low DFS (p=0.01). The high decrease in Ki-67 expressions between biopsy and surgical specimen is related with TRG grade 3-4 (p=0.001). The others evaluated biomarkers did not showed clinical correlations. Conclusion In BMG-B1 Study TRG grade and EGFR expression in operative specimen after CRT showed a prognostic value. High TS expression in biopsy before CRT was related to worse pathological response, and high Ki-67 decrease after CRT is related to best response.

Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer

Aims The histological modification produced by neoadjuvant chemoradiation on primary rectal cancer has been investigated by many authors, and a prognostic value of tumor regression grade (TRG) has been identified. Tumor regression grade on metastatic mesorectal lymphnodes has been never evaluated. The purpose of this study is to analyse the TRG on mesorectal lymphnodes (lymphnode regression grade, LRG) after preoperative chemoradiation in rectal cancer patients and to determine the correlation with TRG of primary tumor. Methods Surgical specimens from 35 patients who underwent chemoradiation were included. LRG on mesorectal lymphnodes was assessed by immunohistochemistry. Response to treatment was evaluated by a 5-point LRG based on the ratio of residual tumor to fibrosis. Results Complete pathologic response (LRG 1) was observed in 18 patients (51%). In 4 patients (11%) no regression was observed (LRG 5). In 4 cases only reactive lymphnodes were found. LRG on lymphnodes significantly correlated with TRG on primary tumor ( p < 0.05). Conclusions Neoadjuvant chemoradiation determines a tumor regression on mesorectal lymphnodes as on primary tumor; further studies are needed to evaluate the prognostic value of LRG.