Dear Editor
Thank you for your interest in our study1. We have not stratified our analyses by treatment because the initial statistical analysis showed no significant treatment interaction for chromosomal instable (CIN) status and overall survival. The KCCH gastric cancer (GC) patients were either treated with surgery or surgery plus adjuvant chemotherapy. Therefore, pathological or radiological tumour regression grade could not be assessed. For the palliatively treated patients, information on radiological tumour response was not available and survival time was used as the surrogate measure of ‘chemotherapy response’.
Although others suggested that patients with CIN GC experienced the greatest benefit from adjuvant chemotherapy, formal statistical analyses for treatment interaction were not conducted in previous studies. Therefore, it remains to be clarified whether the improved survival in CIN patients treated with adjuvant chemotherapy is due to the prognostic effect of CIN or a potential predictive effect of CIN.
Another study demonstrated, in biopsies before patient treatment with neoadjuvant chemotherapy followed by resection, that a high ‘global LOH rate’ was related to tumour response. This study used a different methodology (fractional allelic loss) to establish ‘chromosomal instability’ and investigated a different clinical setting. Therefore, their results cannot be directly compared. Finally, in patients receiving neoadjuvant chemotherapy, the CIN classification as reported was close to our methodology; unfortunately, a formal statistical analysis for treatment interaction was not conducted. Our results suggested a higher CIN frequency in stage IV GC. We, therefore, included the TNM stage in our multivariable Cox regression model and demonstrated that CIN was a poor prognostic biomarker independent of TNM staging. We agree that there are conflicting results about the potential relationship between CIN and response to chemotherapy which deserves further exploration ideally by a large multicentre series of patients undergoing the same clinical treatment, using the same molecular assay and an appropriate statistical methodology.
Contributor Information
Arnaldo N S Silva, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK; Department of Surgery, University of Cambridge, Cambridge University Hospitals, Addenbrookes, Cambridge, UK; Cancer Research UK, Cambridge Institute, Cambridge, UK.
Yuichi Saito, Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Takaki Yoshikawa, Department of Gastric Surgery, National Cancer Centre Hospital, Tokyo, Japan.
Takashi Oshima, Department of Gastrointestinal Surgery, Kanagawa Cancer Centre Hospital, Yokohama, Japan.
Jeremy D Hayden, Department of Upper Gastrointestinal Surgery, Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Jan Oosting, Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Sophie Earle, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK.
Lindsay C Hewitt, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Hayley L Slaney, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK.
Alex Wright, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK.
Imran Inam, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK.
Ruth E Langley, MRC Clinical Trials Unit, University College London, London, UK.
William H Allum, Department of Surgery, Royal Marsden Hospital, London, UK.
Matthew G Nankivell, MRC Clinical Trials Unit, University College London, London, UK.
Gordon Hutchins, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK.
David Cunningham, Department of Medicine, Royal Marsden NHS Trust, London and Sutton, UK.
Heike I Grabsch, Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Reference
- 1. Silva ANS, Saito Y, Yoshikawa T, Oshima T, Hayden JD, Oosting J et al. Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma. Br J Surg 2022;109:291–297 [DOI] [PMC free article] [PubMed] [Google Scholar]