Dataset Information

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma.

ABSTRACT:

Purpose

This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma.

Methods

Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, University Hospital Erlangen, Germany. Patient-, tumour- and treatment-related factors with a potential impact on the downstaging of rectal carcinoma to pathological T category (pT) ≤ ypT2 and ypT0 were analysed in univariate and multivariate logistic regression analyses. The prognosis of patients with and without downstaging of the primary tumour was compared.

Results

A total of 288 (51.9%) patients showed downstaging to ≤ ypT2. Eighty-six (15.5%) patients achieved clinical complete regression (ypT0). In the multivariate logistic regression analysis, the factors cT category, BMI, ECOG score, CEA, histological type, extension in the rectum and year of the start of treatment were found to be independent factors for predicting downstaging to ≤ ypT2 after neoadjuvant chemoradiotherapy. The year of treatment initiation also remained an independent significant predictor for pathological complete regression. The prognosis was superior in patients with downstaging to ≤ ypT2 in terms of locoregional and distant recurrence as well as disease-free and overall survival.

Conclusion

Factors predicting downstaging after long-term nCRT could be identified. This may be helpful for counselling patients and selecting the optimal treatment for patients with advanced rectal carcinoma.

SUBMITTER: Kohl VKB

PROVIDER: S-EPMC9167202 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma.

Kohl Valerie K B VKB Weber Klaus K Brunner Maximilian M Geppert Carol I CI Fietkau Rainer R Grützmann Robert R Semrau Sabine S Merkel Susanne S

International journal of colorectal disease 20220511 6

<h4>Purpose</h4>This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma.<h4>Methods</h4>Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, Unive ...[more]

PMID: 35545701

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Project description:BackgroundLocally advanced rectal cancers (LARC) show a highly variable response to neoadjuvant chemoradiotherapy (nCRT), and the impact of the tumor immune response in this process is poorly understood. This study aimed to characterize the immune-related gene expression profiles (GEP), pathways, and cell types associated with response or resistance to neoadjuvant chemoradiotherapy.MethodsThe transcriptomic and clinical data of Rectal carcinoma from the Gene Expression Omnibus database and Immune-related genes (IRGs) from ImmPort were downloaded to identify the differentially expressed immune-related genes (DEIRGs) between responder and non-responder to neoadjuvant chemoradiotherapy. Gene set enrichment analyses were performed to uncover significantly enriched GO terms and KEGG pathways. Immune cell infiltration was estimated from RNA-sequencing data using ImmuCellAI. Afterward, we constructed an immune-related gene-based predictive model (IRGPM) by Support Vector Machine and validated it in an external cohort.ResultA 15-gene signature (HLA-DPB1, HLA-DQA1, CXCL9, CXCL10, TAP2, INHBB, BMP2, CD74, IL33, CCL11, CXCL11, DEFB1, HLA-DPA1, CCN3, STAT1) was identified as DEIRGs and found to be significantly associated with nCRT outcomes. Gene set enrichment analyses indicated that the 15 genes play active roles in inflammation-related biological processes. In addition, ImmuCellAI revealed that CD4 naive T cells, Tex, Th1 were significantly up-regulated (p=0.035, p=0.02, p=0.0086, respectively), while Tfh were significantly down-regulated (p=0.015) in responder subgroup. Finally, a novel predictive model was developed by SVM based on DEIRGs with an AUC of 80% (internal validation) and 73.5% (external validation).ConclusionOur team conducted a genomic study of the relationship between gene expression profile and response to nCRT in LARC. Our data suggested that the DEIRGs signature could help predict the efficacy of nCRT. And a DEIRGs-based SVM model was developed to monitor the outcomes of nCRT in LARC.

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Dataset Information

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma.

Purpose

Methods

Results

Conclusion

Publications

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma.

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