Purpose: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti–programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. Patients and Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1–positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%–24.5%]. Median PFS was 4.44 months (95% CI, 2.37–5.75 months), and the median OS was 14.72 months (95% CI, 9.59–NE months). ORR of PD-L1–positive patients was 16.7%, and the ORR of PD-L1–negative patients was 17.9%. No treatment-related deaths occurred. Conclusions: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 mAbs.

To investigate potential predictive factors and assess the utility of systemic inflammatory and nutritional indexes as prognostic indicators for survival in patients with FIGO stage III-IVA squamous cervical cancer (squamous HR-LACC) treated with concurrent chemoradiotherapy. We included consecutive patients with PET-CT diagnosed squamous HR-LACC undergoing curative chemoradiotherapy from November 2016 to April 2024. We systematically reviewed data pertaining to pretreatment clinicopathologic characteristics, hematological parameters, and treatment specifics. A range of composite inflammatory and nutritional indices were calculated, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, pan-immune-inflammation value, and prognostic nutritional index (PNI). X-Tile software was utilized to establish optimal cut-off values based on progression-free survival (PFS). Both univariate and multivariate Cox regression analyses were conducted to identify factors associated with PFS and overall survival (OS). Among 157 patients (median age 55) included, 136 had lymph node involvement, and 45 had para-aortic metastasis. After a median follow-up of 35 months, 47 patients had disease progression, and 22 died, yielding 3-year PFS and OS rates of 66.2% and 82.0%, respectively. Multivariate analysis revealed that low SCC-Ag (HR: 1.518, 95% CI: 1.067–2.159, p = 0.020), para-aortic lymph node involvement (HR: 1.864, 95% CI: 1.020–3.408, p = 0.043), and low PNI (HR: 1.477, 95% CI: 1.105–1.975, p = 0.009) were independently associated with worse PFS, whereas low PNI emerged as the sole independent risk factor for diminished OS (HR = 1.525, 95% CI: 1.002–2.323, p = 0.049). PNI, a readily obtainable metric based on albumin and lymphocyte count, can serve as a predictor of survival in HR-LACC patients undergoing concurrent chemoradiotherapy. Further research is necessary to ascertain whether optimizing pretreatment nutritional status, a modifiable factor, can enhance outcomes in these high-risk patients.

Background: 5-Methylcytidine (m5C) is the most common RNA modification and plays an important role in multiple tumors including cervical cancer (CC). We aimed to develop a novel gene signature by identifying m5C modification subtypes of CC to better predict the prognosis of patients.Methods: We obtained the expression of 13 m5C regulatory factors from The Cancer Genome Atlas (TCGA all set, 257 patients) to determine m5C modification subtypes by the “nonnegative matrix factorization” (NMF). Then the “limma” package was used to identify differentially expressed genes (DEGs) between different subtypes. According to these DEGs, we performed Cox regression and Kaplan-Meier (KM) survival analysis to establish a novel gene signature in TCGA training set (128 patients). We also verified the risk prediction effect of gene signature in TCGA test set (129 patients), TCGA all set (257 patients) and GSE44001 (300 patients). Furthermore, a nomogram including this gene signature and clinicopathological parameters was established to predict the individual survival rate. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, colony formation, migration and invasion assays.Results: Based on consistent clustering of 13 m5C-modified genes, CC was divided into two subtypes (C1 and C2) and the C1 subtype had a worse prognosis. The 4-gene signature comprising FNDC3A, VEGFA, OPN3 and CPE was constructed. In TCGA training set and three validation sets, we found the prognosis of patients in the low-risk group was much better than that in the high-risk group. A nomogram incorporating the gene signature and T stage was constructed, and the calibration plot suggested that it could accurately predict the survival rate. The expression levels of FNDC3A, VEGFA, OPN3 and CPE were all high in cervical cancer tissues. Downregulation of FNDC3A, VEGFA or CPE expression suppressed the proliferation, migration and invasion of SiHa cells.Conclusions: Two m5C modification subtypes of CC were identified and then a 4-gene signature was established, which provide new feasible methods for clinical risk assessment and targeted therapies for CC.

Establishment of a molecular risk model for the prognosis of cervical cancer based on microRNA expression Jian Li, Leilei Liang, Lin Xiu, Jia Zeng, Yunshu Zhu, Jusheng An, Lingying Wu

To evaluate the efficacy and safety of concurrent chemo-radiotherapy with weekly nedaplatin for the treatment of advanced squamous cell carcinoma of the uterine cervix.

(1) Purpose: Challenges remain in dose accumulation for cervical cancer radiotherapy combined with external beam radiotherapy (EBRT) and brachytherapy (BT) as there are many large and complex organ deformations between different treatments. This study aims to improve deformable image registration (DIR) accuracy with the introduction of multi-metric objectives for dose accumulation of EBRT and BT. (2) Materials and methods: Twenty cervical cancer patients treated with EBRT (45–50 Gy/25 fractions) and high-dose-rate BT (≥20 Gy in 4 fractions) were included for DIR. The multi-metric DIR algorithm included an intensity-based metric, three contour-based metrics, and a penalty term. Nonrigid B-spine transformation was used to transform the planning CT images from EBRT to the first BT, with a six-level resolution registration strategy. To evaluate its performance, the multi-metric DIR was compared with a hybrid DIR provided by commercial software. The DIR accuracy was measured by the Dice similarity coefficient (DSC) and Hausdorff distance (HD) between deformed and reference organ contours. The accumulated maximum dose of 2 cc (D_2cc) of the bladder and rectum was calculated and compared to simply addition of D_2cc from EBRT and BT (ΔD_2cc). (3) Results: The mean DSC of all organ contours for the multi-metric DIR were significantly higher than those for the hybrid DIR (p ≤ 0.011). In total, 70% of patients had DSC > 0.8 using the multi-metric DIR, while 15% of patients had DSC > 0.8 using the commercial hybrid DIR. The mean ΔD_2cc of the bladder and rectum for the multi-metric DIR were 3.25 ± 2.29 and 3.54 ± 2.02 Gy_EQD2, respectively, whereas those for the hybrid DIR were 2.68 ± 2.56 and 2.32 ± 3.25 Gy_EQD2, respectively. The multi-metric DIR resulted in a much lower proportion of unrealistic D_2cc than the hybrid DIR (2.5% vs. 17.5%). (4) Conclusions: Compared with the commercial hybrid DIR, the introduced multi-metric DIR significantly improved the registration accuracy and resulted in a more reasonable accumulated dose distribution.