Dataset Information

Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer.

ABSTRACT:

Background

Lymph node metastasis is an important indicator of oncologic outcome for patients with rectal cancer. Identifying predictive biomarkers of lymph node metastasis could therefore be clinically useful.

Objective

The aim of this study was to assess whether chromosomal copy number alterations can assist in predicting persistent lymph node metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiation therapy.

Design

This is a nonrandomized, prospective phase II study.

Setting

This study took place in a multi-institutional setting.

Patients

Ninety-five patients with stage II (cT3-4, cN0) or stage III (any cT, cN1-2) rectal cancer were included.

Intervention

Patients were treated with preoperative chemoradiation therapy followed by total mesorectal excision. Pretreatment biopsy tumor DNA and surgical margin control DNA were extracted and analyzed by oligonucleotide array-based comparative genomic hybridization. Chromosomal copy number alterations were correlated with persistent lymph node metastasis. Finally, a model for predicting persistent lymph node metastasis was built.

Main outcome measures

The primary outcomes assessed were whether chromosomal copy number alterations are associated with persistent lymph node metastasis in patients with rectal cancer and the accuracy of oligonucleotide array-based comparative genomic hybridization for predicting lymph node metastasis.

Results

Twenty-five of 95 (26%) patients had lymph node metastasis after chemoradiation. Losses of 28 chromosomal regions, most notably in chromosome 4, were significantly associated with lymph node metastasis. Our predictive model contained 65 probes and predicted persistent lymph node metastasis with 68% sensitivity, 93% specificity, and positive and negative predictive values of 77% and 89%. The use of this model accurately predicted lymph node status (positive or negative) after chemoradiation therapy in 82 of 95 patients (86%).

Limitations

The patient cohort was not completely homogeneous, which may have influenced their clinical outcome. In addition, although we performed rigorous, statistically sound internal validation, external validation will be important to further corroborate our findings.

Conclusions

Copy number alterations can help identify patients with rectal cancer who are at risk of lymph node metastasis after chemoradiation.

SUBMITTER: Chen Z

PROVIDER: S-EPMC3356567 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer.

Chen Zhenbin Z Liu Zheng Z Deng Xutao X Warden Charles C Li Wenyan W Garcia-Aguilar Julio J

Diseases of the colon and rectum 20120601 6

<h4>Background</h4>Lymph node metastasis is an important indicator of oncologic outcome for patients with rectal cancer. Identifying predictive biomarkers of lymph node metastasis could therefore be clinically useful.<h4>Objective</h4>The aim of this study was to assess whether chromosomal copy number alterations can assist in predicting persistent lymph node metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiation therapy.<h4>Design</h4>This is a nonra ...[more]

PMID: 22595848

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Project description:ImportancePatients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited.ObjectiveTo analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes.Design, setting, and participantsThis cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024.ExposuresReceiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial.Main outcome and measuresThe associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed.ResultsA total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001).Conclusions and relevanceIn this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.

Dataset Information

Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer.

Background

Objective

Design

Setting

Patients

Intervention

Main outcome measures

Results

Limitations

Conclusions

Publications

Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer.

Similar Datasets

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