■之前的微观肿瘤扩展，放化疗（RCHT）期间或之后及其与肿瘤微环境（TME）的相关性目前尚不清楚。这个信息是,然而,在图像引导的时代至关重要，自适应高精度光子或粒子治疗。
■在这项试点研究中，我们分析了经组织学证实的食管鳞状细胞癌（SCC;n=10）或腺癌（A;n=10）患者的福尔马林固定石蜡包埋（FFPE）肿瘤切除标本，已接受新辅助放化疗，然后进行切除术（NRCHTR）或切除术（R）]。FFPE组织切片通过免疫组织化学分析肿瘤缺氧（HIF-1α），增殖（Ki67），免疫状态（PD1），癌细胞干性（CXCR4），和p53突变状态。HIF-1α亚体积中的标志物表达是亚分析的一部分。使用单侧Mann-Whitney检验和Bland-Altman分析进行统计分析。
■在SCC和AC患者中，五种TME标志物中阳性肿瘤细胞的总百分比，即HIF-1α，NRCHT后Ki67、p53、CXCR4和PD1低于R组。然而,只有SCC中的PD1和AC中的Ki67表现出显著的相关性(Ki67:p=0.03,PD1:p=0.02).在对AC患者缺氧亚体积的亚分析中，在除PD1以外的所有标志物中,NRCHT中缺氧区域内的阳性肿瘤细胞百分比在统计学上显著低于R队列.
■在这项试点研究中，我们显示了在SCC和AC中NRCHT诱导的TME的变化。这些发现将与随后的患者队列中的微观肿瘤延伸测量相关联。
UNASSIGNED: The microscopic tumor extension before, during or after radiochemotherapy (RCHT) and its correlation with the tumor microenvironment (TME) are presently unknown. This information is, however, crucial in the era of image-guided, adaptive high-precision photon or particle therapy.
UNASSIGNED: In this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis.
UNASSIGNED: In both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1.
UNASSIGNED: In this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.
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