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Original Articles
Clinical Impact of Tumor Regression Grade after Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Subset Analyses in Lymph Node Negative Patients
Byung Soh Min, Nam Kyu Kim, Ju Yeon Pyo, Hoguen Kim, Jinsil Seong, Ki Chang Keum, Seung Kook Sohn, Chang Hwan Cho
J Korean Soc Coloproctol. 2011;27(1):31-40.   Published online February 28, 2011
DOI: https://doi.org/10.3393/jksc.2011.27.1.31
  • 6,156 View
  • 47 Download
  • 10 Citations
AbstractAbstract PDF
Background

We investigated the prognostic significance of tumor regression grade (TRG) after preoperative chemoradiation therapy (preop-CRT) for locally advanced rectal cancer especially in the patients without lymph node metastasis.

Methods

One-hundred seventy-eight patients who had cT3/4 tumors were given 5,040 cGy preoperative radiation with 5-fluorouracil/leucovorin chemotherapy. A total mesorectal excision was performed 4-6 weeks after preop-CRT. TRG was defined as follows: grade 1 as no cancer cells remaining; grade 2 as cancer cells outgrown by fibrosis; grade 3 as a minimal presence or absence of regression. The prognostic significance of TRG in comparison with histopathologic staging was analyzed.

Results

Seventeen patients (9.6%) showed TRG1. TRG was found to be significantly associated with cancer-specific survival (CSS; P = 0.001) and local recurrence (P = 0.039) in the univariate study, but not in the multivariate analysis. The ypN stage was the strongest prognostic factor in the multivariate analysis. Subgroup analysis revealed TRG to be an independent prognostic factor for the CSS of ypN0 patients (P = 0.031). TRG had a stronger impact on the CSS of ypN (-) patients (P = 0.002) than on that of ypN (+) patients (P = 0.521). In ypT2N0 and ypT3N0, CSS was better for TRG2 than for TRG3 (P = 0.041, P = 0.048), and in ypN (-) and TRG2 tumors, CSS was better for ypT1-2 than for ypT3-4 (P = 0.034).

Conclusion

TRG was found to be the strongest prognostic factor in patients without lymph node metastasis (ypN0), and different survival was observed according to TRG among patients with a specific histopathologic stage. Thus, TRG may provide an accurate prediction of prognosis and may be used for f tailoring treatment for patients without lymph node metastasis.

Citations

Citations to this article as recorded by  
  • Tumor Regression Grade as a Prognostic Factor in Metastatic Colon Cancer Following Preoperative Chemotherapy
    Yufei Yang, Dakui Luo, Ruoxin Zhang, Sanjun Cai, Qingguo Li, Xinxiang Li
    Clinical Colorectal Cancer.2022; 21(2): 96.     CrossRef
  • Prediction of tumor response of rectal cancer cells via 3D cell culture and in�vitro cytotoxicity assay before initiating preoperative chemoradiotherapy
    Jeonghyun Kang, Min Park, Jina Kim, Hyuk Hur, Byung Min, Seung Baik, Kang Lee, Nam Kim
    Oncology Letters.2019;[Epub]     CrossRef
  • Prognostic significance of tumour regression grade after neoadjuvant chemoradiotherapy for a cohort of patients with locally advanced rectal cancer: an 8‐year retrospective single‐institutional study
    L. Xu, S. Cai, T. Xiao, Y. Chen, H. Qiu, B. Wu, G. Lin, X. Sun, J. Lu, W. Zhou, Y. Xiao
    Colorectal Disease.2017;[Epub]     CrossRef
  • Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression?
    Melanie J. McCoy, Chris Hemmings, Simon Hillery, Cheryl Penter, Max K. Bulsara, Nik Zeps, Cameron F. Platell
    ANZ Journal of Surgery.2017;[Epub]     CrossRef
  • Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales
    Muhammed R S Siddiqui, Jemma Bhoday, Nicholas J Battersby, Manish Chand, Nicholas P West, Al-Mutaz Abulafi, Paris P Tekkis, Gina Brown
    World Journal of Gastroenterology.2016; 22(37): 8414.     CrossRef
  • Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG)
    M.R.S. Siddiqui, K.L. Gormly, J. Bhoday, S. Balyansikova, N.J. Battersby, M. Chand, S. Rao, P. Tekkis, A.M. Abulafi, G. Brown
    Clinical Radiology.2016; 71(9): 854.     CrossRef
  • Controversies in the pathological assessment of colorectal cancer
    Aoife Maguire
    World Journal of Gastroenterology.2014; 20(29): 9850.     CrossRef
  • The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer
    K. I. Abdul‐Jalil, K. M. Sheehan, J. Kehoe, R. Cummins, A. O'Grady, D. A. McNamara, J. Deasy, O. Breathnach, L. Grogan, B. D. P. O'Neill, C. Faul, I. Parker, E. W. Kay, B. T. Hennessy, P. Gillen
    Colorectal Disease.2014;[Epub]     CrossRef
  • Pathological grading of regression: an International Study Group perspective
    Runjan Chetty, P Gill, Adrian C Bateman, David K Driman, Dhirendra Govender, Andrew R Bateman, Y J Chua, Godman Greywoode, Christine Hemmings, I Imat, Eleanor Jaynes, Cheok Soon Lee, Michael Locketz, Corwyn Rowsell, Anne Rullier, Stefano Serra, Eva Szentg
    Journal of Clinical Pathology.2012; 65(10): 865.     CrossRef
  • Pathological grading of regression following neoadjuvant chemoradiation therapy: the clinical need is now: Table 1
    Tom P MacGregor, Tim S Maughan, Ricky A Sharma
    Journal of Clinical Pathology.2012; 65(10): 867.     CrossRef
The Efficacy of UGT1A1 Polymorphism in Chemoradiation Therapy Using Irinotecan in Patients with Locally Advanced Rectal Cancer.
Oh, Seung Yeop , Kim, Young Bae , Chun, Mi Son , Suh, Kwang Wook
J Korean Soc Coloproctol. 2007;23(5):344-349.
DOI: https://doi.org/10.3393/jksc.2007.23.5.344
  • 2,310 View
  • 9 Download
  • 2 Citations
AbstractAbstract PDF
PURPOSE
Irinotecan (CPT-11) is hydrolyzed to an active SN-38, which is further detoxicated to SN-38G through conjugation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzymes. There are many reports that UGT1A1 polymorphisms are associated with irinotecan related dose-limiting toxicity. The aim of the present study is to determine whether UGT1A1 polymorphisms affect individual variations of the toxicity due to and the tumor response to irinotecan via the alteration of bioavailability of SN-38 in Korean patients with locally advanced rectal cancer.
METHODS
Twenty patients with locally advanced rectal cancer, who had received surgery after irinotecan-containing chemoradiation from 2003 to 2006, were enrolled. We analyzed the association of UGT1A1 genotypes with toxicity and tumor response to chemoradiation therapy. A tumor response was assumed when a tumor regression grade I or II was obtained. Toxicity was graded in accordance with the NCI common toxicity criteria.
RESULTS
The frequence of square53(TA)6>7 (UGT1A1*28), 211G>A (UGT1A1*6), 686C>A (UGT1A1*27), square3279T>G (UGT1A1*60), and square3156G>A were 25% (5/20), 25% (5/20), 0% (0/20), 55% (11/20), and 20% (4/20), respectively. There were five grade III neutropenia and one severe diarrhea. Patients with UGT1A1*28 and square3156G>A showed higher complete tumor response rates (40% vs. 6.7%, P=0.07; 50% vs. 6.3%, P=0.08), but there was no differences in toxicity and tumor response between responders and non-responders. Patients with square3279T>G (UGT1A1*60) showed a tendency for lower tumor response in tumor responders, but there was no statistically significant difference (P=0.07).
CONCLUSIONS
This study suggested that square3279T>G (UGT1A1*60) may be useful in predicting tumor response of irinotecan. In the future, further study is warranted using large numbers of cases to reach statistical significance.

Citations

Citations to this article as recorded by  
  • The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients
    Choong-kun Lee, Hong Jae Chon, Woo Sun Kwon, Hyo-Jeong Ban, Sang Cheol Kim, Hyunwook Kim, Hei-Cheul Jeung, Jimyung Chung, Sun Young Rha
    Genomics & Informatics.2022; 20(3): e29.     CrossRef
  • Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer
    Do Yoon Kim, Tae Yoon Paek, Seung Yeop Oh, Young Bae Kim, Je Hee Lee, Mi Young Lee, Zi Sun Choi, Kwang Wook Suh
    Journal of Surgical Oncology.2014; 109(3): 250.     CrossRef
p53, Bcl-2 and Ki-67 Expression according to Tumor Response after Concurrent Chemoradiation Treatment for Advanced Rectal Cancer.
Kim, Nam Kyu , Park, Jae Kyun , Yang, Woo Ik , Yun, Seong Hyeon , Sung, Jin Sil , Min, Jin Sik
J Korean Soc Coloproctol. 2000;16(6):436-443.
  • 1,334 View
  • 9 Download
AbstractAbstract PDF
PURPOSE
Concurrent chemoradiation treatment (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but its tumor response shows wide spectrum. The aim of study is to investigate any correlation between a related genetic mutations, proliferative index and tumor response after CCRT.
METHODS
A twenty three patients with rectal cancer, which preoperatively staged as over T3N1 or T4 determined by transrectal ultrasonography and MRI. Enrolled patients were given 5 FU 450 mg/m2 and leucovorin 20 mg/m2 intravenously for 5 days during the first and fifth weeks of radiation therapy (45~54 Gy). 4 weeks after completion of scheduled treatment, surgical resection was performed. Tumor response was classified into CR (complete remission), PR (partial response: 50% of diminution of tumor volume and downstaging), NR (no response). Paraffin-embedded tissues obtained before chemoradiation treatment were studied with immunohistochemical staining of p53, Bcl-2 and Ki-67. The extent of tumor response was correlated with proliferative activity as measured by immunostaining of Ki-67 proliferative antigen and expression of p53 and bcl-2 oncoproteins (less than 10%: negative, 10~25%: , 25~50%: , more than 50%: , Ki-67: to count a labeled cells per 1,000 cells).
RESULTS
All patients were resectable. CR was obtained in 4 (17.4%), PR in 10 (43.3%) and NR in 9 (39.2%). p53 mutation was noted in 16 (70%). p53 mutation was found in NR: 5 (31.3%), PR: 9 (56.2%), CR: 2 (12.5%), respectively. Bcl-2 expression was noted in 11 (48%). NR as in 4 (36.3%), PR: 3 (28.4%) and CR: 4 (36.3%), respectively. Ki-67 labeling index was NR: 615.4 446.2, PR: 663.2 296.4, CR: 765.5 188.3, respectively (CR PR Vs NR, p=0.029).
CONCLUSIONS
Immunohistochemical Expression of p53 and bcl-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be useful parameters for good radiosensitive tumor selected for CCRT.
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