Analysis of Treatment Response With Proteins Related to Tumor Immunity in Postoperative Irradiated Cervical Cancer Patients.

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

Identification and Quantification of Radiotherapy-related Protein Expression in Cancer Tissues Using the Qupath Software and Prediction of Treatment Response.

BACKGROUND/AIM: Automated measurement of immunostained samples can enable more convenient and objective prediction of treatment outcome from radiotherapy. We aimed to validate the performance of the QuPath image analysis software in immune cell markers detection by comparing QuPath cell counting results with those of physician manual cell counting. PATIENTS AND METHODS: CD8- and FoxP3-stained cervical, CD8-stained oropharyngeal, and Ku70-stained prostate cancer tumor sections were analyzed in 104 cervical, 92 oropharyngeal, and 58 prostate cancer patients undergoing radiotherapy at our Institution. RESULTS: QuPath and manual counts were highly correlated. When divided into two groups using ROC curves, the agreement between QuPath and manual counts was 89.4% for CD8 and 88.5% for FoxP3 in cervical cancer, 87.0% for CD8 in oropharyngeal cancer and 80.7% for Ku70 in prostate cancer. In cervical cancer, the high CD8 group based on QuPath counts had a better prognosis and the low CD8 group had a significantly worse prognosis [p=0.0003; 5-year overall survival (OS), 65.9% vs. 34.7%]. QuPath counts were more predictive than manual counts. Similar results were observed for FoxP3 in cervical cancer (p=0.002; 5-year OS, 62.1% vs. 33.6%) and CD8 in oropharyngeal cancer (p=0.013; 5-year OS, 80.2% vs. 47.2%). In prostate cancer, high Ku70 group had worse and low group significantly better outcome [p=0.007; 10-year progression-free survival (PFS), 56.0% vs. 93.8%]. CONCLUSION: QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice.