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Objective <p>Tumor-infiltrating lymphocytes (TILs) are key immune biomarkers associated with prognosis and treatment response in early-stage breast cancer (BC), particularly in the triple-negative subtype. This study aimed to evaluate whether [18F]FDG PET/CT imaging and routine cell blood count (CBC)-derived biomarkers can serve as non-invasive surrogates for TILs, using machine-learning models.</p> Material and methods <p>We retrospectively analyzed 358 patients with biopsy-proven early-stage invasive BC who underwent pre-treatment [18F]FDG PET/CT imaging. PET-derived biomarkers were extracted from the primary tumor, lymph nodes, and lymphoid organs (spleen and bone marrow). CBC-derived biomarkers included neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). TILs were assessed histologically and categorized as low (0–10%), intermediate (11–59%), or high (≥ 60%). Correlations were assessed using Spearman’s rank coefficient, and classification and regression models were built using several machine-learning algorithms.</p> Results <p>Tumor SUVmax and tumor SUVmean showed the highest correlation with TIL levels (ρ = 0.29 and 0.30 respectively, p &lt; 0.001 for both), but overall associations between TILs and PET or CBC-derived biomarkers were weak. No CBC-derived biomarker showed significant correlation or discriminative performance. Machine-learning models failed to predict TIL levels with satisfactory accuracy (maximum balanced accuracy = 0.66). Lymphoid organ metrics (SLR, BLR) and CBC-derived parameters did not significantly enhance predictive value.</p> Discussion <p>In this study, neither [18F]FDG PET/CT nor routine CBC-derived biomarkers reliably predict TILs levels in early-stage BC. This observation was made in presence of potential scanner-related variability and for a restricted set of usual PET metrics. Future models should incorporate more targeted imaging approaches, such as immunoPET, to non-invasively assess immune infiltration with higher specificity and improve personalized treatment strategies.</p>

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Are [18F]FDG PET/CT imaging and cell blood count-derived biomarkers robust non-invasive surrogates for tumor-infiltrating lymphocytes in early-stage breast cancer?

  • 期刊论文

  • 发表日期：

    2025年8月12日

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  • Romain-David Seban,
  • Louis Rebaud,
  • Lounes Djerroudi,
  • Anne Vincent-Salomon,
  • Francois-Clement Bidard,
  • Laurence Champion,
  • Irene Buvat

摘要

Objective

Tumor-infiltrating lymphocytes (TILs) are key immune biomarkers associated with prognosis and treatment response in early-stage breast cancer (BC), particularly in the triple-negative subtype. This study aimed to evaluate whether [18F]FDG PET/CT imaging and routine cell blood count (CBC)-derived biomarkers can serve as non-invasive surrogates for TILs, using machine-learning models.

Material and methods

We retrospectively analyzed 358 patients with biopsy-proven early-stage invasive BC who underwent pre-treatment [18F]FDG PET/CT imaging. PET-derived biomarkers were extracted from the primary tumor, lymph nodes, and lymphoid organs (spleen and bone marrow). CBC-derived biomarkers included neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). TILs were assessed histologically and categorized as low (0–10%), intermediate (11–59%), or high (≥ 60%). Correlations were assessed using Spearman’s rank coefficient, and classification and regression models were built using several machine-learning algorithms.

Results

Tumor SUVmax and tumor SUVmean showed the highest correlation with TIL levels (ρ = 0.29 and 0.30 respectively, p < 0.001 for both), but overall associations between TILs and PET or CBC-derived biomarkers were weak. No CBC-derived biomarker showed significant correlation or discriminative performance. Machine-learning models failed to predict TIL levels with satisfactory accuracy (maximum balanced accuracy = 0.66). Lymphoid organ metrics (SLR, BLR) and CBC-derived parameters did not significantly enhance predictive value.

Discussion

In this study, neither [18F]FDG PET/CT nor routine CBC-derived biomarkers reliably predict TILs levels in early-stage BC. This observation was made in presence of potential scanner-related variability and for a restricted set of usual PET metrics. Future models should incorporate more targeted imaging approaches, such as immunoPET, to non-invasively assess immune infiltration with higher specificity and improve personalized treatment strategies.