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Genetic Assay May Help Predict Disease Relapse in Patients With Gastroesophageal Cancer

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Key Points

  • The median overall survival of the high- and low-risk groups was 10.2 and 80.9 months, respectively.
  • Risk groups were independently prognostic of lymph node metastasis by multivariate analysis and not prognostic in surgery-only patients.

A seven-gene assay could improve care for patients with gastroesophageal cancer by predicting their likelihood of relapse after chemotherapy and surgery. These findings were published by Smyth et al in Annals of Oncology.

A team at The Institute of Cancer Research (ICR), London, and The Royal Marsden NHS Foundation Trust developed the test after finding that assessing seven genes together from neoadjuvant chemotherapy–treated resection specimens from patients with gastroesophageal cancer could be used to define prognostic risk groups to identify patients at risk for relapse. The researchers analyzed samples from patients who took part the phase III MAGIC trial, in which patients received either neoadjuvant chemotherapy or surgery alone, as well as data from a separate Cancer Research UK–funded follow-up study.

Scientists at the ICR linked seven genes to the survival outcome of patients who had undergone both chemotherapy and surgery, including whether they were likely to relapse or not. They then created a seven-gene test for these patients who received both chemotherapy and surgery, and used it to place them in groups at high or low risk of relapse. The patients were profiled for a custom gastric cancer gene panel using the NanoString platform.

Two of the genes—epidermal growth factor receptor (EGFR) and CD44—have been previously associated with drug resistance and worse survival in patients with gastric cancer treated with chemotherapy.

Study Findings

The median overall survival of the high- and low-risk groups was 10.2 (95% confidence interval [CI] = 6.5–13.2 months] and 80.9 months (CI = 43.0 months–not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (hazard ratio [HR] = 3.6 in node-positive group, P=.02; HR = 3.6 in high-risk group, P=.0002), and not prognostic in surgery-only patients (n = 118; log rank P=.2). 

Lead researcher Anguraj Sadanandam, PhD, Team Leader in Systems and Precision Cancer Medicine at The Institute of Cancer Research, London, said: “By analyzing the genetic profile of tumors in patients who have received chemotherapy followed by surgery, we developed an exciting new test which indicates their risk of relapse. Our test could help select patients who are at high risk of relapse after surgery, to allow new therapies to be developed for this set of patients, with the potential to change the future standard of care for this subset. If it works on a wider scale, this approach to treating gastroesophageal cancer could personalize standard clinical treatment and improve quality of life after treatment.”

Co–first author Elizabeth Smyth, MB, BCh, MSc, who was a clinical research fellow at The Royal Marsden NHS Foundation Trust at the time of this study and is currently a consultant oncologist at Cambridge University Hospital NHS Foundation Trust, said, “The next step is to validate these findings in patients treated with the most common type of chemotherapy—docetaxel/oxaliplatin/fluorouracil. Analyzing the risk of relapse following chemotherapy brings us one step closer to personalized treatments in this group of patients, and in the United Kingdom, we hope to provide a national framework of genetically powered clinical trials in patients with gastroesophageal cancer.”

Disclosure: The study authors’ full disclosures can be found at academic.oup.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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