Prognostic significance of response to preoperative radiotherapy, lymph node metastasis, and CEA level in patients undergoing total mesorectal excision of rectal cancer

Ishihara, Soichiro; Watanabe, Toshiaki; Kiyomatsu, Tomomichi; Yasuda, Koji; Nagawa, Hirokazu

doi:10.1007/s00384-010-1051-1

Cited by 17 publications

(21 citation statements)

References 33 publications

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“…The micro-RNA signature may be of value in predicting pCR [18], but will need further validation. Several studies had focused on the predictive value of pre- and post-CRT CEA levels in patients with rectal cancer receiving pre-operative CRT [12-15,19,20]. In this study, we found not only pre-CRT CEA levels had prognostic significance, “normalization” of these values and CEA ratio also predicted tumor response and may be helpful in the design of individualized treatment for rectal cancer with high CEA levels before treatment.…”

Section: Discussionmentioning

confidence: 51%

“…It was reported that pre-CRT CEA levels >2.5 or >5 ng/ml were associated with poor pCR rates and poor disease-free survival on univariate analysis, but not for both on multivariate analysis [12,13]. However, in other studies, pre-CRT CEA levels were a common predictor of downstaging, pCR and tumor response on multivariate analysis [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic value of serum CEA levels has been widely discussed in the relevant literature: poor tumor response to CRT and an increased risk of recurrence have been observed in patients with elevated CEA levels before or after CRT [12-15]. It has also been reported that the reduction ratio of pre- to post-CRT serum CEA levels may be a prognostic factor for disease-free survival in rectal cancer patients with a pre-CRT CEA of more than 6 ng/ml [16].…”

Section: Introductionmentioning

confidence: 99%

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Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

Yang

Liang

et al. 2013

Radiat Oncol

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BackgroundTo investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT).MethodsBetween 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR).ResultsFive-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%).ConclusionsIn patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

Yang

Liang

et al. 2013

Radiat Oncol

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“…As expected, in this study, the likelihood of 3-year DFS decreased with increased ypTNM stage. However, the ypTNM stage could roughly classify NCRT-treated patients mainly because the key determination was lymph node involvement, whereas the depth of tumor invasion had less impact on DFS [6–9]. In addition, patients with pCR had the most favorable outcome, which might overestimate the difference among a large number of patients with residual disease.…”

Section: Discussionmentioning

confidence: 99%

The combination of early treatment response and ypT stage is a novel metric to stage rectal cancer patients treated with neoadjuvant chemoradiotherapy

et al. 2017

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Rectal cancer patients receiving neoadjuvant chemoradiotherapy (NCRT) are currently classified using the same Tumor-Node-Metastasis staging system as those patients without NCRT. We determined whether the combination of tumor treatment response (TRG) and ypT stage more accurately assesses primary tumors in rectal cancer after NCRT. We analyzed data from 329 rectal cancer patients treated with NCRT followed by radical resection. Cox proportional hazards models were used to evaluate the effects of different staging parameters on disease-free survival (DFS). ypN stage and TRG were independently associated with 3-year DFS, but ypT stage was not. We developed a new modified T stage classification metric (M-TTRG) that categorized patients into 5 subgroups based on ypT stage and TRG, with weighting by β-coefficients from multivariate analyses. The incidence of patients developing local or distant recurrence increased with increasing M-TTRG level. All five M-TTRG classes correlated with 3-year DFS. Improvement was seen in the model with M-TTRG classification compared with ypT stage, based on area under the curve after computing receiver operating characteristic curves. Our modified ypTNM staging system significantly improved prediction of 3-year DFS. This suggests TRG could complement ypT stage, and we propose the new M-TTRG metric could be used to better classify NCRT-treated patients, thereby improving treatment and assessing prognosis. The M-TTRG metric might be applicable to other types of cancer.

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“…Due to the absence of an adequate follow-up but the need for fresh frozen biopsies to perform the genome-wide CpG scan, targets were selected based on tumor regression grading (TRG) and post-therapeutic lymph node status (ypN) after CRT. Both parameters are known to be well-established surrogate parameters for outcome in rectal cancer [15, 44–48]. The study was conducted in accordance with the Helsinki Declaration and was approved by the ethics committee of the University Medical Center Goettingen.…”

Section: Methodsmentioning

confidence: 99%

Identification of a DNA methylation signature to predict disease-free survival in locally advanced rectal cancer

Gaedcke¹,

Leha²,

Claus

et al. 2014

Oncotarget

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In locally advanced rectal cancer a preoperative predictive biomarker is necessary to adjust treatment specifically for those patients expected to suffer relapse. We applied whole genome methylation CpG island array analyses to an initial set of patients (n=11) to identify differentially methylated regions (DMRs) that separate a good from a bad prognosis group. Using a quantitative high-resolution approach, candidate DMRs were first validated in a set of 61 patients (test set) and then confirmed DMRs were further validated in additional independent patient cohorts (n=71, n=42). We identified twenty highly discriminative DMRs and validated them in the test set using the MassARRAY technique. Ten DMRs could be confirmed which allowed separation into prognosis groups (p=0.0207, HR=4.09). The classifier was validated in two additional cohorts (n=71, p=0.0345, HR=3.57 and n=42, p=0.0113, HR=3.78). Interestingly, six of the ten DMRs represented regions close to the transcriptional start sites of genes which are also marked by the Polycomb Repressor Complex component EZH2. In conclusion we present a classifier comprising 10 DMRs which predicts patient prognosis with a high degree of accuracy. These data may now help to discriminate between patients that may respond better to standard treatments from those that may require alternative modalities.

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Prognostic significance of response to preoperative radiotherapy, lymph node metastasis, and CEA level in patients undergoing total mesorectal excision of rectal cancer

Cited by 17 publications

References 33 publications

Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

The combination of early treatment response and ypT stage is a novel metric to stage rectal cancer patients treated with neoadjuvant chemoradiotherapy

Identification of a DNA methylation signature to predict disease-free survival in locally advanced rectal cancer

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