ARTemis Findings Confirm Computational Pathology Lymphocyte Density Linked To pCR

A computational pathology approach to lymphocyte density is validated for prediction of pathological complete response after breast cancer treatment

medwireNews: Computational pathology determination of lymphocyte density can predict the likelihood of a pathological complete response (pCR) in breast cancer patients undergoing chemotherapy, UK researchers confirm.

The team originally used specimens from the Neo-tAnGo trial to develop the approach, where the overall lymphocyte density is calculated by determining the average distance to the next 50 nearest lymphocytes for each lymphocyte on a digitalised slide.

Helena Earl, from the University of Cambridge, and co-workers have now validated their technique in a secondary analysis of specimens from the ARTemis trial . The study compared a docetaxel-based chemotherapy regimen with or without bevacizumab in women with early-stage breast cancer.

Pretreatment lymphocyte density was calculated for 78% of the 781 patients included in the trial’s primary endpoint analysis and density after treatment was determined for 49%; 20% of these patients achieved a pCR.

Analysis showed that pretreatment lymphocyte density assessed as a continuous variable was significantly associated with pCR, with an odds ratio (OR) of 2.93. And after adjusting for confounders, such as tumour grade, size and oestrogen receptor (ER) status, this OR remained a significant 2.13.

Furthermore, patients who showed an increase in lymphocyte density at their post-treatment assessment were significantly less likely to achieve pCR than those who did not, with an adjusted OR of 0.10.

However, neither pretreatment lymphocyte density, nor an increase in lymphocyte density after treatment, were associated with overall or disease-free survival outcomes in the ARTemis patients, regardless of whether they had ER-positive or -negative disease.

“[O]ur finding that an increase in pre-to-post treatment lymphocyte density is associated with residual disease again highlights perturbations in the immune microenvironment secondary to, and presumably caused by, treatment”, the researchers write in the Annals of Oncology.

“We speculate that such a comparative metric could serve as a biomarker to identify patients likely to respond to post-neoadjuvant immunotherapy.”

And they hypothesise: “Patients with low pre-treatment lymphocyte density may benefit from more aggressive therapies or enrolment into clinical trials.

“In addition, immunotherapies may prove more effective following an increase in lymphocyte density following neoadjuvant chemotherapy.”


Ali HR, Dariush A, Thomas J, et al. Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial. Ann Oncol; Advance online publication 19 May 2017. DOI:

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