Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2300 RC, Leiden, Netherlands.
Department of Medical Oncology, Leiden University Medical Centre, Leiden, Netherlands.
Cell Oncol (Dordr). 2019 Oct;42(5):717-725. doi: 10.1007/s13402-019-00449-9. Epub 2019 May 17.
Intra-tumoral stroma has become increasingly important in understanding tumor biology, tumor progression and clinical outcome. The amount itself, quantified as the tumor-stroma ratio (TSR), has proven to be prognostic in stage I-III colon cancer. Also, alterations in stromal organization have been found to provide prognostic and predictive information in certain cancers. Here, we evaluated the predictive value of stromal organization in high-risk stage II and III colon cancer with respect to adjuvant bevacizumab and chemotherapy.
In a post-hoc analysis, stromal organization was microscopically determined in hematoxylin and eosin-stained primary tumor tissue samples of 1226 patients enrolled in the AVANT trial.
We found that patients with tumors with a disorganized stroma showed different survival rates after the addition of bevacizumab compared to standard oxaliplatin-based chemotherapy regimens. However, overall this difference was not significant with a HR of 0.94 (95% CI 0.57-1.55; p = 0.80) for disease-free survival (DFS) and 1.01 (95% CI 0.51-1.99; p = 0.99) for overall survival (OS). Subgroup analysis, however, revealed that stromal organization combined with TSR allowed the identification of stroma-high patients with absolute cumulative survival benefits up to 15% when bevacizumab was added to oxaliplatin-based chemotherapy regimens.
In high-risk stage II and stage III colon cancer, we found that subgroup analysis of the combined parameters stromal organization and TSR allows for the identification of patients with absolute cumulative DFS and OS benefits of up to 15%, when adding bevacizumab to the currently recommended oxaliplatin-based chemotherapy. Stromal organization itself does, however, not serve as an independent prognostic or predictive parameter.
肿瘤内间质在理解肿瘤生物学、肿瘤进展和临床结局方面变得越来越重要。其数量本身，以肿瘤间质比（TSR）来量化，已被证明在 I-III 期结肠癌中具有预后意义。此外，在某些癌症中，间质组织的改变已被发现提供预后和预测信息。在这里，我们评估了间质组织在高危 II 期和 III 期结肠癌中的预测价值，涉及辅助贝伐单抗和化疗。
在 AVANT 试验的 1226 名患者的组织学样本中，对苏木精和伊红染色的原发性肿瘤组织进行了间质组织学分析。
我们发现，与标准奥沙利铂为基础的化疗方案相比，贝伐单抗联合治疗后，间质组织紊乱的肿瘤患者的生存结果不同。然而，总体而言，这种差异并不显著，无病生存期（DFS）的风险比（HR）为 0.94（95%置信区间 0.57-1.55；p=0.80），总生存期（OS）为 1.01（95%置信区间 0.51-1.99；p=0.99）。然而，亚组分析显示，间质组织与 TSR 相结合，可以确定间质高的患者，当贝伐单抗添加到奥沙利铂为基础的化疗方案中时，绝对累积生存率提高了 15%。
在高危 II 期和 III 期结肠癌中，我们发现，联合参数（间质组织和 TSR）的亚组分析可以确定患者的无病生存和总生存绝对累积获益高达 15%，当添加贝伐单抗到目前推荐的奥沙利铂为基础的化疗中。然而，间质组织本身并不是一个独立的预后或预测参数。
