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乳腺癌低危患者单次剂量术前部分乳房照射的肿瘤浸润淋巴细胞。

Tumor-Infiltrating Lymphocytes in Low-Risk Patients With Breast Cancer Treated With Single-Dose Preoperative Partial Breast Irradiation.

机构信息

Department of Radiation Oncology, UMC Utrecht, Utrecht, the Netherlands.

Department of Pathology, UMC Utrecht, Utrecht, the Netherlands.

出版信息

Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1325-1331. doi: 10.1016/j.ijrobp.2020.12.009. Epub 2020 Dec 15.

DOI:10.1016/j.ijrobp.2020.12.009
PMID:33333201
Abstract

PURPOSE

Preoperative partial breast irradiation (PBI) has the potential to induce tumor regression. We evaluated the differences in the numbers of preirradiation tumor infiltrating lymphocytes (TILs) between responders and nonresponders after preoperative PBI in low-risk patients with breast cancer. Furthermore, we evaluated the change in number of TILs before and after irradiation.

METHODS AND MATERIALS

In the prospective ABLATIVE study, low-risk patients with breast cancer underwent treatment with single-dose preoperative PBI (20 Gy) to the tumor and breast-conserving surgery after 6 or 8 months. In the preirradiation diagnostic biopsy and postirradiation resection specimen, numbers of TILs in 3 square regions of 450 × 450 μm were counted manually. TILs were visualized with CD3, CD4, and CD8 immunohistochemistry. Differences in numbers of preirradiation TILs between responders and nonresponders were tested using Mann-Whitney U test. Responders were defined as pathologic complete or near-complete response, and nonresponders were defined "as all other response." Changes in numbers of TILs after preoperative PBI was evaluated with the Wilcoxon signed rank test.

RESULTS

Preirradiation tissue was available from 28 patients, postirradiation tissue from 29 patients, resulting in 22 pairs of preirradiation and postirradiation tissue. In these 35 patients, 15 had pathologic complete response (43%), 11 had a near-complete response (31%), 7 had a partial response (20%), and 2 had stable disease (6%). The median numbers of CD3 TILs, CD4 TILs, and CD8 TILs in the preirradiation tumor tissue were 49 (interquartile range [IQR], 36-80), 45 (IQR, 28-57), and 19 (IQR, 8-35), respectively. The number of preirradiation TILs did not differ significantly between responders and nonresponders. The median numbers of CD3 TILs, CD4 TILs, and CD8 TILs in postirradiation tumor tissue were 17 (IQR, 13-31), 26 (IQR, 16-35), and 7 (IQR, 5-11), respectively.

CONCLUSIONS

After preoperative PBI in this limited cohort, the number of TILs in tumor tissue decreased. No differences in numbers of preirradiation TILs between responders and nonresponders were observed.

摘要

目的

术前局部乳房照射(PBI)有可能诱导肿瘤消退。我们评估了低危乳腺癌患者接受术前 PBI 后,肿瘤浸润淋巴细胞(TILs)数量在应答者和无应答者之间的差异。此外,我们还评估了照射前后 TIL 数量的变化。

方法和材料

在前瞻性 ABLATIVE 研究中,低危乳腺癌患者接受单次剂量术前 PBI(20 Gy)照射肿瘤,6 或 8 个月后行保乳手术。在术前诊断性活检和术后切除标本中,手动计数 3 个 450×450μm 正方形区域的 TIL 数量。用 CD3、CD4 和 CD8 免疫组化检测 TIL。使用 Mann-Whitney U 检验比较应答者和无应答者之间的术前 TIL 数量差异。应答者定义为病理完全或接近完全缓解,无应答者定义为“所有其他反应”。使用 Wilcoxon 符号秩检验评估术前 PBI 后 TIL 数量的变化。

结果

28 例患者有术前组织,29 例患者有术后组织,共 22 对术前和术后组织。在这 35 例患者中,15 例有病理完全缓解(43%),11 例有接近完全缓解(31%),7 例有部分缓解(20%),2 例有稳定疾病(6%)。术前肿瘤组织中 CD3 TIL、CD4 TIL 和 CD8 TIL 的中位数分别为 49(四分位距[IQR],36-80)、45(IQR,28-57)和 19(IQR,8-35)。应答者和无应答者之间的术前 TIL 数量无显著差异。术后肿瘤组织中 CD3 TIL、CD4 TIL 和 CD8 TIL 的中位数分别为 17(IQR,13-31)、26(IQR,16-35)和 7(IQR,5-11)。

结论

在这个有限的队列中,接受术前 PBI 后,肿瘤组织中的 TIL 数量减少。应答者和无应答者之间的术前 TIL 数量无差异。

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