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Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer : secondary analysis of the ARTemis trial
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Ali, H. R., Dariush, A., Thomas, J., Provenzano, E., Dunn, Janet A., Hiller, Louise, Vallier, A.-L., Abraham, J., Piper, T., Bartlett, J. M. S., Cameron, D. A., Hayward, L., Brenton, J. D., Pharoah, P. D. P., Irwin, M. J., Walton, N. A., Earl, H. M. and Caldas, C. (2017) Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer : secondary analysis of the ARTemis trial. Annals of Oncology, 28 (8). pp. 1832-1835. doi:10.1093/annonc/mdx266 ISSN 0923-7534.
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WRAP-lymphocyte-density-determined-computational-pathology-validated-predictor-Hiller-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (734Kb) | Preview |
Official URL: http://dx.doi.org/10.1093/annonc/mdx266
Abstract
Background:
We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown.
Patients and methods:
The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed.
Results:
Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78–4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24–3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033–0.31; P < 0.001).
Conclusions:
Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.
Item Type: | Journal Article | ||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Breast -- Cancer -- Treatment, Breast -- Cancer -- Chemotherapy, Lymphocytes, Immunological adjuvants, Pathology | ||||||||||||
Journal or Publication Title: | Annals of Oncology | ||||||||||||
Publisher: | Oxford University Press | ||||||||||||
ISSN: | 0923-7534 | ||||||||||||
Official Date: | 1 August 2017 | ||||||||||||
Dates: |
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Volume: | 28 | ||||||||||||
Number: | 8 | ||||||||||||
Page Range: | pp. 1832-1835 | ||||||||||||
DOI: | 10.1093/annonc/mdx266 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | Published | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 15 February 2018 | ||||||||||||
Date of first compliant Open Access: | 16 February 2018 | ||||||||||||
RIOXX Funder/Project Grant: |
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