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.
To assess whether chromosomal copy number alterations can assist in predicting lymph node metastasis in patients with locally advanced rectal cancer treated with pre-operative chemoradiation therapy.
Non-randomized, prospective Phase II study.
95 patients with stage II (cT3-4, cN0) or stage III (any cT, cN1-2) rectal cancer.
Patients were treated with pre-operative chemoradiation therapy (CRT) followed by total mesorectal excision. Pretreatment biopsy tumor DNA and surgical margin control DNA was extracted and analyzed by oligonucleotide array-based comparative genomic hybridization. Chromosomal copy number alterations were correlated with lymph node metastasis. Finally, a model for predicting lymph node metastasis was built.
Main outcome measures
To determine if chromosomal copy number alterations are associated with lymph node metastasis in patients with rectal cancer, and to assess the accuracy of oligonucleotide array-based comparative genomic hybridization for predicting lymph node metastasis.
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 lymph node metastasis with 68% sensitivity, 93% specificity, and positive and negative predictive values of 77% and 89%. Using this model lymph node status (positive or negative) after CRT was predicted accurately in 82 out of 95 patients (86%).
The patient cohort was not completely homogeneous which may have influenced their clinical outcome. Additionally, while we performed rigorous statistically sound internal validation, external validation will be important to further corroborate our findings.
Copy number alterations can help identify rectal cancer patients at risk of lymph node metastasis after chemoradiation.