肿瘤-正常组织界面的肿瘤厚度：预测结直肠癌肝转移化疗疗效的新指标

Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases.

机构信息

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Am J Surg Pathol. 2010 Sep;34(9):1287-94. doi: 10.1097/PAS.0b013e3181eb2f7b.

DOI:10.1097/PAS.0b013e3181eb2f7b

PMID:20697255

Abstract

BACKGROUND

Progress in the treatment of hepatic colorectal metastases (HCRM) demands pathologic indicators of therapy response. We observed that a majority of residual tumor cells are seen at the tumor-normal interface (TNI) in resected HCRM specimens and hypothesized that tumor thickness at the TNI correlates with radiologic and pathologic response and recurrence-free survival (RFS).

DESIGN

This study included 103 patients with HCRM resected after preoperative chemotherapy with or without bevacizumab. Imaging response was assessed by response evaluation criteria in solid tumors (RECIST) and recently described CT morphology criteria by Chun et al. The pathologic response was categorized as complete (no tumor cells), major (<50% residual tumor cells), or minor (> or =50% residual tumor cells). The maximum thickness of uninterrupted layers of tumor cells was measured perpendicular to the TNI by 2 pathologists independently, followed by consensus review for discrepant cases. For specimens containing >1 tumor, the average tumor thickness at the TNI was used.

RESULTS

Sixty-five patients received oxaliplatin-based chemotherapy, 38 received irinotecan-based chemotherapy, and 75 received concurrent bevacizumab. A complete pathologic response was seen in 9 patients, a major response in 44, and a minor response in 50. Median tumor thickness at the TNI was 2.8 mm (interquartile range, 0.5 to 6 mm). Tumor thickness correlated better with radiologic response as determined by Chun et al (P<0.0001) than by RECIST criteria (Spearman r=0.35, P<0.001). Tumor thickness correlated with pathologic response (Spearman r=0.80, P<0.0001). Greater thickness predicted shorter recurrence-free survival, and this correlation remained in multivariate analysis (P=0.015). Tumor thickness was smaller in patients treated with bevacizumab than in patients not given bevacizumab (P=0.03).

CONCLUSIONS

Tumor thickness measured at the TNI is potentially a new prognostic factor for therapy response and survival outcome in patients with resected HCRM.

摘要

背景

结直肠癌肝转移（HCRM）治疗的进展需要治疗反应的病理指标。我们观察到，在切除的 HCRM 标本中，大多数残留肿瘤细胞位于肿瘤-正常界面（TNI），并假设 TNI 处的肿瘤厚度与影像学和病理学反应以及无复发生存（RFS）相关。

设计

本研究纳入了 103 例接受术前化疗（联合或不联合贝伐单抗）后切除的 HCRM 患者。影像学反应通过实体瘤反应评估标准（RECIST）和 Chun 等人最近描述的 CT 形态学标准进行评估。病理反应分为完全（无肿瘤细胞）、主要（<50%残留肿瘤细胞）或次要（> =50%残留肿瘤细胞）。由 2 位病理学家独立垂直于 TNI 测量不连续肿瘤细胞层的最大厚度，然后对有分歧的病例进行共识审查。对于包含>1 个肿瘤的标本，使用 TNI 处的平均肿瘤厚度。

结果

65 例患者接受奥沙利铂为基础的化疗，38 例患者接受伊立替康为基础的化疗，75 例患者接受贝伐单抗联合化疗。9 例患者获得完全病理缓解，44 例患者获得主要缓解，50 例患者获得次要缓解。TNI 处肿瘤厚度的中位数为 2.8mm（四分位间距 0.5 至 6mm）。肿瘤厚度与 Chun 等人确定的影像学反应相关性更好（Spearman r=0.35，P<0.001），而与 RECIST 标准的相关性较差（Spearman r=0.35，P<0.001）。肿瘤厚度与病理反应相关（Spearman r=0.80，P<0.0001）。肿瘤厚度越大，无复发生存时间越短，多因素分析显示这种相关性仍然存在（P=0.015）。接受贝伐单抗治疗的患者肿瘤厚度小于未接受贝伐单抗治疗的患者（P=0.03）。