Prognostic importance of Mandard tumour regression grade following pre-operative chemo/radiotherapy for locally advanced rectal cancer

Dhadda, A.S.; Dickinson, P.; Zaitoun, Abed M.; Gandhi, Nilay; Bessell, E.M.

doi:10.1016/j.ejca.2010.12.006

Cited by 68 publications

(66 citation statements)

References 18 publications

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“…Tumor down-staging, post-operative stage, N, T classification and TRG have been identified as important prognostic factors in rectal cancer patients following pre-operative CRT (3)(4)(5)(6)(7)(8)(27)(28)(29). We observed that advanced post-operative stage, the presence of lymph node metastasis and poor pathological response based on JSCCR and Rödel TRGs were significantly associated with recurrence-free survival in this study of 52 patients (log-rank test; post-operative stage, P=0.0137; presence of lymph node metastasis, P=0.0244; JSCCR, P=0.0464; Rödel, P=0.0338) (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Tumor regression grade (TRG) following preoperative CRT is determined by quantifying the proportion of residual cancer cells to the stroma of the entire tumor bed. In rectal cancer, several studies have found that TRG or pathologic response is a predictor of clinical outcome, including disease recurrence and survival (3)(4)(5)(6)(7)(8). Hence, it is possible that gene expression correlated with TRG might reflect the characteristics, including resistance to CRT, of residual cancer cells and might be associated with prognosis in patients with rectal cancer after pre-operative CRT.…”

Section: Introductionmentioning

confidence: 99%

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Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

et al. 2012

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“…Hundred and twenty six patients (29%) were treated with surgery only while 282 were treated with long-course preoperative chemo-radiotherapy before surgery for rectal cancer as described previously [14]. The latter group had locally advanced rectal cancer, cT3/4 and/or N+ and were considered inoperable or of borderline resectability due to potential circumferential resection margin (CRM) involvement.…”

Section: Patient Datamentioning

confidence: 99%

Factors Influence Lymph Node Retrieval after Resection for Rectal Cancer

Elsheikh¹,

M²

2016

J Adenocarcinoma

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Introduction: Total lymph node (TLN) count is an important qualifier of cancer evaluation and extensive nodal resection has been associated with lower rates of cancer recurrence; allows for more accurate cancer staging and improved survival following resection for rectal cancer. Aim:To examine the adequacy of lymph node sampling in rectal cancer and the influence of the clinicopathological factors and treatment modalities on the total lymph node yield.Methods: This is a retrospective study includes 409 cases of rectal cancer treated by surgical intervention only (126 cases), or surgery after short or long course chemotherapy (75 and 208 cases respectively).Results: TLN count range from (2-50, mean 12.38). Twelve lymph nodes were found in 49.4% of the specimens with or without neoadjuvent chemo radiatherapy (CRT). Patient treated with surgery only have a significant high total LN yield (mean is 15.53) in comparison with (12.99 and 10.25 for short course CRT and long course CRT respectively, P value <0.001). The number of lymph nodes was significantly correlated with the modality of treatment, anterior quadrant involvement, vascular and perineural invasion, pathological staging, Duke's and Mandard staging. On multivariate only perineural invasion, high tie lymph node involvement, Dukes stage, and tumour load were found to be the main predictors of the number of lymph node yield. Conclusion:The neoadjuvent CRT has a significant effect on the adequacy of lymph node sampling and a negative impact on the lymph nodes retrieved. This negative effect was more prominent with the long term rather than the short term CRT. This should be taken in consideration at the N staging of the tumour to avoid down-staging.

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“…However, the majority of patients have mid to advanced stage CRC at the time of diagnosis. Neoadjuvant radiochemotherapy improves the survival and anus-preservation rates by shrinking tumors, decreasing the clinical stage and reducing the pathological grade (4). While patients with local CRC have a more favorable outcome, with a 5-year survival rate of 90%, patients with metastatic CRC have a poor 5-year survival rate of 12%, despite the good therapeutic regimens that are available, including surgical resection, adjuvant radiotherapy and chemotherapy (5).…”

Section: Introductionmentioning

confidence: 99%

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

et al. 2016

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Abstract. The aim of the present study was to investigate the effect of hepatocyte growth factor receptor (c-MET) inhibition on the viability of colon cancer cells and xenografts exposed to irradiation using short hairpin (sh)RNA or the c-MET inhibitor PHA665752. The underlying mechanisms were also investigated. Human colorectal adenocarcinoma HT-29 cells were infected with a lentivirus expressing shRNAs against c-MET and were irradiated at 0, 2, 4, 6 and 8 Gy. The viability of the cells was assessed by alamarBlue ® assays. Mice bearing human colon carcinoma SW620 xenografts were randomly selected to receive 2.5% dimethyl sulfoxide (DMSO), 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks, irradiation at 10 Gy, or 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks followed 24 h later by irradiation at 10 Gy. The mean tumor volume (MTV) was measured. The apoptotic rate of cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays, and double stranded break marker antibody γ-H2AX and hypoxia inducible factor (HIF)-1α expression was examined by immunohistochemistry. alamarBlue assays revealed that c-MET downregulation by shRNA markedly accentuated the irradiation-induced reduction in the viability of HT-29 cells compared with HT-29 cells irradiated at the same doses (P<0.05). A combination of irradiation and PHA665752 caused an additional reduction in the MTV (382.8±42.4 mm 3 ; P<0.01 vs. irradiation and PHA665752, 998.0±180.6 and 844.8±190.0 mm 3 , respectively). TUNEL assays revealed that irradiation and PHA665752 alone caused significant apoptosis of the SW620 cells in the tumor xenografts (P<0.01 vs. DMSO). The apoptotic index in the tumor xenografts of mice treated with a combination of irradiation and PHA665752 was significantly increased compared with mice treated with either agent alone (P<0.01). The combination of irradiation and PHA665752 was also associated with a marked increase in γ-H2AX levels and a significant decrease in HIF-1α expression in the xenografts (P<0.01). In conclusion, c-MET inhibition sensitizes colorectal cancer cells to irradiation by enhancing the formation of DNA double strand breaks and possibly alleviating tumor hypoxia. IntroductionWorldwide, colorectal cancer (CRC) is the third most common cancer (1). Currently, the standard regimen for newly diagnosed patients with locally advanced rectal cancer (grade, cT3/T4 and cN + ) is surgery in combination with neoadjuvant radiochemotherapy (2,3). However, the majority of patients have mid to advanced stage CRC at the time of diagnosis. Neoadjuvant radiochemotherapy improves the survival and anus-preservation rates by shrinking tumors, decreasing the clinical stage and reducing the pathological grade (4). While patients with local CRC have a more favorable outcome, with a 5-year survival rate of 90%, patients with metastatic CRC have a poor 5-year survival rate of 12%, despite the good therapeutic regimens that are available, including surgical resection, ad...

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Prognostic importance of Mandard tumour regression grade following pre-operative chemo/radiotherapy for locally advanced rectal cancer

Cited by 68 publications

References 18 publications

Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

Factors Influence Lymph Node Retrieval after Resection for Rectal Cancer

c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo

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