Background

Tumor development is critically dependent on the supporting stroma consisting of inflammatory cells and fibroblasts. This study intended to improve prognostic prediction for early colorectal cancer (CRC) by combined estimation of T-lymphocyte and stroma fractions with conventional markers.

Methods

In total 509 and 1041 stage II/ΙΙΙ CRC from the VICTOR and QUASAR 2 trials were included as a training set and a validation set, respectively. Intratumoral CD8⁺ T-lymphocytes and stroma were identified and quantified by machine-based learning on digital sections. The primary endpoint was to evaluate the prognostic value of the combined marker for time to recurrence (TTR).

Findings

For low-risk patients (n = 598; stage Ⅱ, and stage ΙΙΙ pT1-3 pN1 with neither lymphatic (L⁻) nor vascular (V⁻) invasion), low stroma fraction (n = 511) identified a good prognostic subgroup with 5-year TTR of 86% (95% CI 83–89), versus the high stroma subgroup TTR of 78% (HR = 1.75, 95% CI 1.05–2.92; P = 0.029). For high-risk patients (n = 394; stage ΙΙΙ pT3 pN1 L⁺/V⁺, pT4, or pN2), combined low CD8⁺ and high stroma fraction identified a poor prognostic subgroup (n = 34) with 5-year TTR of 29% (95% CI 17-50), versus the high CD8⁺ fraction and low stroma fraction subgroup (n = 138) of 64% (HR = 2.86, 95% CI 1.75–4.69; P < 0.001).

Interpretation

Quantification of intratumoral CD8⁺ T-lymphocyte and stroma fractions can be combined with conventional prognostic markers to improve patient stratification.

中文翻译：

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CD8+ T 淋巴细胞和基质组分的自动评估补充了结直肠癌的常规分期

背景

肿瘤的发展严重依赖于由炎症细胞和成纤维细胞组成的支持基质。本研究旨在通过将 T 淋巴细胞和基质分数与常规标志物相结合来改善早期结直肠癌 (CRC) 的预后预测。

方法

来自 VICTOR 和 QUASAR 2 试验的总共 509 个和 1041 个 II/IIII 期 CRC 分别被包括作为训练集和验证集。通过基于机器学习的数字切片识别和量化肿瘤内CD8 ⁺ T 淋巴细胞和基质。主要终点是评估联合标志物对复发时间 (TTR) 的预后价值。

发现

对于低风险患者（n  = 598；Ⅱ期和 Ⅲ期 pT1-3 pN1，既没有淋巴（L ^-）也没有血管（V ^-）侵犯），低基质分数（n  = 511）确定了一个良好的预后亚组5 年 TTR 为 86% (95% CI 83–89)，而高基质亚组 TTR 为 78% (HR = 1.75, 95% CI 1.05–2.92; P  = 0.029)。对于高危患者（n  = 394；III 期 pT3 pN1 L ⁺ /V ⁺、pT4 或 pN2），结合低 CD8 ⁺和高基质分数确定了一个预后不良的亚组（n  = 34），5 年 TTR 为29% (95% CI 17-50)，与高 CD8 ⁺分数和低基质分数亚组 ( n  = 138) 为 64% (HR = 2.86, 95% CI 1.75–4.69; P  < 0.001)。

解释

^{肿瘤内 CD8 +} T 淋巴细胞和基质部分的量化可以与传统的预后标志物相结合，以改善患者分层。