Dataset Information

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial).

ABSTRACT:

Background

The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial).

Methods

The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration.

Results

The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell's C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding.

Conclusions

Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.

SUBMITTER: Ueno H

PROVIDER: S-EPMC7960987 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial).

Ueno Hideki H Ishiguro Megumi M Nakatani Eiji E Ishikawa Toshiaki T Uetake Hiroyuki H Murotani Kenta K Matsui Shigeyuki S Teramukai Satoshi S Sugai Tamotsu T Ajioka Yoichi Y Maruo Hirotoshi H Kotaka Masahito M Tsujie Masaki M Munemoto Yoshinori Y Yamaguchi Takashi T Kuroda Hisashi H Fukunaga Mutsumi M Tomita Naohiro N Sugihara Kenichi K

British journal of cancer 20210107 6

<h4>Background</h4>The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial).<h4>Methods</h4>The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. A ...[more]

PMID: 33414540

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Project description:BackgroundExisting high-risk factors are insufficient to accurately predict the postoperative recurrence risk of stage II colorectal cancer (CRC). The discovery of additional prognostic markers may be the key to improving the current status of stage II CRC treatment. The present study aimed to evaluate the relationship among desmoplastic reaction (DR), tumor budding (TBd), the tumor-stroma ratio (TSR) and their prognostic value for relapse-free survival (RFS).MethodsIn this study, 207 patients with histologically confirmed stage II CRC from January 2012 to August 2018 were retrospectively reviewed from a single center; the cohort was divided into subgroups based on low or high TSR, and low, intermediate or high DR and TBd. Kaplan-Meier curve analysis and log-rank test were applied to examine RFS among subgroups. Univariate and multivariate Cox proportional hazards analyses were used to identify independent factors associated with RFS, and a nomogram was subsequently developed.ResultsAbnormal CA242, CEA, T4 stage, presence of hypertension, internal obstruction or perforation (IOP), lymphovascular or/and perineural invasion (PNI), number of nodes examined less than 12, low-frequency microsatellite instability (MSI-L), higher Ki-67 and immature DR were associated with a lower RFS. In multivariable analysis, DR (HR =2.111; 95% CI: 1.184-3.766; P=0.011), LVI (HR =1.919; 95% CI: 1.004-3.669; P=0.049) and PNI (HR =2.724; 95% CI: 1.362-5.448; P=0.005) were prognostic factors for RFS. On this basis, a nomogram that integrated DR and clinicopathologic predictors for predicting RFS passed the calibration and had an area under the curve of 0.826.ConclusionsThe prognostic significance of DR outperformed TBd and TSR, therefore, we recommend adding DR as a biomarker in routine pathological reports. The novel nomogram combining these factors may be used as a reliable and effective tool for the prediction of RFS in stage II CRC, thus helping optimize therapeutic regimens under cooperation of oncologists and surgeons. Further multicentric studies are required for validation of this novel, simple and cost-effective prognostic model.

Project description:The current staging method is inadequate to identify high-risk recurrence patients with stage II colon cancer (CC). Using a systematic and comprehensive-biomarker discovery and validation method, we aimed to construct a lncRNA-based signature to improve the prognostic prediction of stage II CC. We identified 1,377 differently expressed lncRNAs by analyzing 16 paired stage II CC tumor tissue and adjacent normal mucosal tissue from the TCGA dataset. Subsequently, using a univariable and step multivariable Cox regression model, we trained an 11-lncRNA signature in the training cohort (n = 141), which could divide patients into high-risk and low-risk groups (AUC at 3 years = 0.801, 95% CI: 0.724-0.877; AUC at 5 years = 0.801, 95% CI: 0.718-0.885). Significantly, patients in the high-risk group had poorer recurrence-free survival (RFS) compared with the low-risk group (log-rank test, P < 0.001 in the training cohort). This lncRNA-based signature was further confirmed in the validation cohort (P < 0.001). Multivariate Cox regression and stratified survival analyses showed that the prognostic value of this signature was independent of other clinicopathological risk factors (CEA, T stage, and chemotherapy). Time-dependent receiver operating characteristic (ROC) analysis demonstrated that this signature had better prognostic ability than any other clinical risk factors or single lncRNAs (all P < 0.05). A nomogram was constructed for clinical use, which integrated both the lncRNA-based signature and clinical risk factors (CEA and T stage) and performed well in the calibration plots. Altogether, our lncRNA-based signature was an independent prognostic factor and possessed a stronger predictive power compared with the currently used clinicopathological risk factors when predicting the recurrence of patients with stage II CC. Collectively, this lncRNA-based signature might facilitate individualized treatment decisions and postoperative counseling, ultimately contributing to improved survival.

Project description:Purpose: The primary objective of the current study was to validate biomarkers to identify the 10% to 27% of patients with stage I and 35% of patients with stage IIA squamous cell carcinoma of lung (SC) who are likely to recur following surgical resection, so that these patients may be offered enrollment in clinical trials evaluating directed ACT. A secondary objective was to identify patients with stage IIB SC who are unlikely to develop recurrences and might thereby be spared the potential significant toxicity and expense of ACT. Methods: Two-stage validation used independent core laboratories, objective quality control standards, locked test parameters, and large multi-institutional specimen/data sets. First stage validation confirmed a signature’s ability to stratify patient survival. Second stage validation determined which signature(s) optimally improved risk discrimination when added to baseline clinical predictors. Participants were prospectively enrolled on institutional (Cohort I) or cooperative group (Cohort II) biospecimen/data collection protocols. All cases underwent central review of clinical, pathologic and biospecimen parameters using objective criteria to determine final inclusion (Cohort I: n=249; Cohort II: n=234). Primary selection required that a signature significantly predict 3-years survival after surgery in Cohort I. Signatures meeting this criterion were further tested in Cohort II, comparing risk prediction using baseline risk factors alone versus in combination with the signature. Results: Male sex, advanced age, and higher stage were associated with shorter survival in Cohort I and established a baseline clinical model. Of three signatures validated in Cohort I, one signature was validated in Cohort II and statistically significantly enhanced prognosis relative to the baseline model (C-index difference 0.122; p<0.05). Conclusions: These results represent the first rigorous validation of a test appropriate to direct adjuvant treatment or clinical trials for patients with lung squamous cell carcinoma.

Dataset Information

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial).

Background

Methods

Results

Conclusions

Publications

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial).

Similar Datasets

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