Influence of chemoradiation on the immune microenvironment of cervical cancer patients.

PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD­1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC­I were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD­1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD­1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group.

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.