Tao Wang

Background Postoperative radiotherapy (RT) or chemoradiotherapy (CRT) improves outcomes of cervical cancer patients with risk factors. Minimally invasive surgery (MIS) has an inferior survival than open radical hysterectomy (ORH), however, the impact of MIS on postoperative RT remains uncertain. The study compared the impacts of MIS versus ORH on delivering of adjuvant RT or CRT for intermediate- or high-risk early-stage cervical cancer. Methods Data on stage IB1-IIA2 patients who underwent radical hysterectomy and postoperative RT/CRT in our institution, from 2014 to 2017, were retrospectively collected. Patients with high or intermediate-risk factors who met the Sedlis criteria received postoperative pelvic external beam radiotherapy (50Gy/25f) with platinum-based chemotherapy (0–6 cycles) according to guidelines. Disease-free survival (DFS) and overall survival (OS) were compared in the two surgical groups. Results One hundred and twenty-nine patients eligible for the study (68 in ORH; 61 in MIS groups) had similar clinicopathologic features except for the stage (highest in MIS was IB1; IIA1 in ORH) and presence of lymph vascular space invasion (higher in MIS group). The median time interval from surgery to chemotherapy and to RT was shorter in the MIS group. Three-year DFS and OS were similar in both groups. Further sub-analysis indicated that the DFS and OS in intermediate/high-risk groups had no significant difference. Cox-multivariate analyses found that tumor size > 4 cm and time interval from surgery to RT beyond seven weeks were adverse independent prognostic factors for DFS. Conclusions In early-stage (IB1-IIA2) cervical cancer patients with intermediate or high-risk factors who received postoperative RT or CRT, no matter they received ORH or MIS as their primary treatment, the DFS and OS had no significant difference, despite TI from surgery to postoperative adjuvant therapy being shorter in the MIS group than ORH.

Background: The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. Methods: We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. Results: The median total doses in EQD2_{α/β = 3} at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7–392.1) Gy, 56.2 (51.4–82.1) Gy and 2.6 (0.9–7.4) Gy, respectively. The median total doses in EQD2_{α/β = 3} at ICRU-R and ICRU-B were 77.5 (54.8–132.4) Gy and 79.9 (60.7–133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2_{α/β = 3} at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. Conclusions: With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose–effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues. Five miRNAs were sharply downregulated in the cancer tissue, including miR-199a, miR-22, miR-615, miR-3681-3p (miR-3681), and miR-1193. Among them, miR-3681 was uncharacterized. The results from qPCR analysis showed that miR-3681 expression was decreased in patients with cervical cancer compared with the control, and decreased in the human cervical cancer cell lines SiHa, HeLa, C4-1, C-33A and Caski, compared with the normal human cervical epithelial cell line HCerEpic. Then, different concentrations of miR-3681 mimic and miR-3681 inhibitor were respectively transfected into the human cervical cancer cell line C-33A, and the expression of miR-3681, cell proliferation, cell apoptosis and cell migration were measured after 48 h. The results showed that the miR-3681 mimic increased the miR-3681 level, suppressed cell proliferation and migration, and induced cell apoptosis in a dose-dependent manner. In contrast, the miR-3681 inhibitor decreased the miR-3681 level, promoted cell proliferation and migration, and inhibited cell apoptosis in a dose-dependent manner. Moreover, bioinformatics analysis showed that there was a miR-3681 binding site in the mRNA 3′UTR of HGFR, which was robustly upregulated in cervical cancer cell lines compared with HCerEpic cells. In addition, luciferase activity analysis demonstrated that miR-3681 could directly target HGFR, which promoted the proliferation and migration of C-33A cells via activation of the PI3K/Akt pathway in a dose-dependent manner. Furthermore, our results showed that knockdown of HGFR could antagonize the promotion of anti-miR-3681 on the activation of the PI3K/Akt pathway and cell proliferation and migration. In conclusion, MiR-3681 was identified as a negative regulator in the proliferation and migration of cervical cancer cells. This function is associated with the posttranscriptional suppression of HGFR and the deactivation of the PI3K/Akt pathway.

The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy.