The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer

Vecchio, Fabio Maria; Valentini, Vincenzo; Minsky, Bruce D.; Padula, Gilbert D. A.; Venkatraman, Ennapadam; Boccadoro, Mario; Miccichè, Francesco; Ricci, Riccardo; Morganti, Alessio Giuseppe; Gambacorta, Maria Antonietta; Maurizi, Francesca; Coco, Claudio

doi:10.1016/j.ijrobp.2004.11.017

Cited by 373 publications

(228 citation statements)

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“…In the phase II study, we have analysed the pathologic response using the TRG score, because it has been shown to be more accurate in defining the tumour regression after primary therapy, and to predict the long-term outcome (Bouzourene et al, 2002;Rödel et al, 2005;Vecchio et al, 2005). Notably, the number of TRG1 or 2 required by our statistical design had already been reached in the first 31 treated patients, with an overall activity (71%) by far greater than that hypothesised.…”

Section: Discussionmentioning

confidence: 99%

“…Phase II We have chosen as primary end point the achievement of a complete or nearly complete pathologic response, because it has been repeatedly reported to predict the long-term survival of patients (Bouzourene et al, 2002;Rödel et al, 2005;Vecchio et al, 2005). To define the sample size, a Simon's two-stage design was utilised (Simon, 1989), setting a and b errors as 0.05 and 0.20, and defining as minimum activity of interest (p0) a TRG1 -2 rate ¼ 30%.…”

Section: Methodsmentioning

confidence: 99%

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Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I–II study

et al. 2006

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Oxaliplatin (OXA), raltitrexed (RTX), 5-fluorouracil (FU) and folinic acid (FA) have shown activity in metastatic colorectal cancer, radioenhancing effect and synergism when combined. We evaluated a chemotherapy (CT) combination of OXA, RTX and FU/FA during preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC) patients. Fifty-one patients with LARC at high risk of recurrence (T4, N þ or T3N0 p5 cm from anal verge and/or circumferential resection margin p5 mm) received three biweekly courses of CT during pelvic RT (45 Gy). Surgery was planned 8 weeks after CT-RT. Recommended doses (RDs) determined during phase I were utilised in the subsequent phase II trial, where the rate of tumour regression grade (TRG) 1 or 2 was the main end point. No toxic deaths occurred, and severe toxicity was easily managed. In phase II, RDs delivered in 31 patients were OXA 100 mg m À2 and RTX 2.5 mg m À2 on day 1, and FU 900 mg m À2 and LFA 250 mg m À2 on day 2. Main severe toxicities by patients were grade 4 neutropenia (23%) and grade 3 diarrhoea (19%). In 71% (95% confidence limits, 52 -86%) of patients, TRG1 (13) or TRG2 (9) was obtained. All patients are alive and recurrence-free after a median follow-up of 29 months. Combination of OXA, RTX and FU/FA with pelvic RT has an acceptable toxicity and a high clinical activity in LARC and should be studied further in patients at high risk of recurrence.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I–II study

et al. 2006

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“…But the overall 5-year survival rate hovers around 50% (Kockerling et al, 1998). The local recurrence of rectal cancer is the main reason for the failure of rectal cancer treatment (Rodel et al, 2005;Vecchio et al, 2005). With the equipment of radiotherapy update, the development of the radiation technology and the radiation biology was rapid (Camma et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Guo

Yang²,

Pei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: : A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

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“…9,10 In addition, the tumor regression grade (TRG) characterization of the pathologic response has shown to be a prognostic factor for local failure, metastasis-free and overall survival with significant better outcome for patients reporting TRG 1-2 (absence or scattered residual isolated cancer cells) compared with those reporting TRG 3-5 (increase in the number of residual cancer cells). 11,12 Nonetheless, TRG 3 could be considered an intermediate prognostic status and some investigators suggested a three-point classification system (TRG 1-2, TRG 3 and TRG 4-5) as a good predictor of pCRT outcome in rectal cancer. 13 For patients with pathologic complete response after pCRT, some investigators advocate an observational approach without any surgical treatment, 14 and others suggest that the transanal local excision may be appropriate.…”

Section: Introductionmentioning

confidence: 99%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

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The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer

Cited by 373 publications

References 22 publications

Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I–II study

Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I–II study

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

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