Background <p>The current tumor-node-metastasis (TNM) staging system is insufficient for predicting the prognosis and chemotherapeutic benefits in stage II-III colorectal cancer (CRC) patients. We aimed to evaluate whether tertiary lymphoid structures (TLS) density and tumor stroma percentage (TSP) allow the prediction of stage II-III CRC survival and chemotherapy benefits.</p> Methods <p>The intratumoral TLS (In-TLS) density, peritumoral TLS (P-TLS) density, and TSP were assessed via whole-slide imaging with hematoxylin and eosin in the training and validation cohorts. The prognostic value of the TLS density and TPS as well as their association with chemotherapy response were assessed. Furthermore, two nomograms for predicting disease-free survival (DFS) and overall survival (OS) were developed and validated.</p> Results <p>We found that low density P-TLS and high TSP were significantly associated with poor prognosis (<i>P</i> &lt; 0.001). Two nomograms based on depth of invasion, lymph node metastasis, CEA level, P-TLS, and TSP were subsequently developed. The nomograms outperformed the TNM stage in prognosis estimation (C-index: training cohort - DFS, 0.747 vs. 0.649; OS, 0.763 vs. 0.635; validation cohort - DFS, 0.733 vs. 0.641; OS, 0.736 vs. 0.649; <i>P</i> &lt; 0.05 for all). The nomograms could add more net benefit than the TNM stage by decision curve analysis in the two cohorts. Moreover, chemotherapy had no impact on prognosis for patients with low density P-TLS and high TSP in both high-risk stage II disease [DFS, hazard ratios (HR): 0.844 (95% CI: 0.410–1.740), <i>P</i> = 0.647; OS, HR: 0.719 (95% CI: 0.328–1.577), <i>P</i> = 0.410] and stage III disease [DFS, HR: 0.846 (95% CI: 0.520–1.375, <i>P</i> = 0.500; OS, HR: 0.845 (95% CI: 0.504–1.417), <i>P</i> = 0.524]. For the remaining patients, adjuvant chemotherapy was associated with improved survival outcomes [high-risk stage II: DFS, HR: 0.367 (95% CI: 0.173–0.781), <i>P</i> = 0.009; OS, HR: 0.344 (95% CI: 0.149–0.790), <i>P</i> = 0.012; stage III: DFS, HR: 0.432 (95% CI: 0.265–0.706), <i>P</i> = 0.001; OS, HR: 0.374 (95% CI: 0.213–0.659), <i>P</i> = 0.001].</p> Conclusion <p>The P-TLS and TSP could improve prognostic prediction and serve as potential tools for identifying patients who could benefit from chemotherapy in stage II-III CRC patients.</p>

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Combining tertiary lymphoid structures and tumor stroma percentage for predicting prognosis and chemotherapy benefits in stage II-III colorectal cancer

  • Kun Yang,
  • Honghao Li,
  • Xiaoyu Dong,
  • Jiaqing Lin,
  • Zhaopu Li,
  • Wei Jiang,
  • Jun Yan

摘要

Background

The current tumor-node-metastasis (TNM) staging system is insufficient for predicting the prognosis and chemotherapeutic benefits in stage II-III colorectal cancer (CRC) patients. We aimed to evaluate whether tertiary lymphoid structures (TLS) density and tumor stroma percentage (TSP) allow the prediction of stage II-III CRC survival and chemotherapy benefits.

Methods

The intratumoral TLS (In-TLS) density, peritumoral TLS (P-TLS) density, and TSP were assessed via whole-slide imaging with hematoxylin and eosin in the training and validation cohorts. The prognostic value of the TLS density and TPS as well as their association with chemotherapy response were assessed. Furthermore, two nomograms for predicting disease-free survival (DFS) and overall survival (OS) were developed and validated.

Results

We found that low density P-TLS and high TSP were significantly associated with poor prognosis (P < 0.001). Two nomograms based on depth of invasion, lymph node metastasis, CEA level, P-TLS, and TSP were subsequently developed. The nomograms outperformed the TNM stage in prognosis estimation (C-index: training cohort - DFS, 0.747 vs. 0.649; OS, 0.763 vs. 0.635; validation cohort - DFS, 0.733 vs. 0.641; OS, 0.736 vs. 0.649; P < 0.05 for all). The nomograms could add more net benefit than the TNM stage by decision curve analysis in the two cohorts. Moreover, chemotherapy had no impact on prognosis for patients with low density P-TLS and high TSP in both high-risk stage II disease [DFS, hazard ratios (HR): 0.844 (95% CI: 0.410–1.740), P = 0.647; OS, HR: 0.719 (95% CI: 0.328–1.577), P = 0.410] and stage III disease [DFS, HR: 0.846 (95% CI: 0.520–1.375, P = 0.500; OS, HR: 0.845 (95% CI: 0.504–1.417), P = 0.524]. For the remaining patients, adjuvant chemotherapy was associated with improved survival outcomes [high-risk stage II: DFS, HR: 0.367 (95% CI: 0.173–0.781), P = 0.009; OS, HR: 0.344 (95% CI: 0.149–0.790), P = 0.012; stage III: DFS, HR: 0.432 (95% CI: 0.265–0.706), P = 0.001; OS, HR: 0.374 (95% CI: 0.213–0.659), P = 0.001].

Conclusion

The P-TLS and TSP could improve prognostic prediction and serve as potential tools for identifying patients who could benefit from chemotherapy in stage II-III CRC patients.