(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.

Rationale: Cervical metastasis of breast cancer is rare and its clinical manifestations are similar to those of primary cervical cancer. It is thus easy to misdiagnose, with diagnosis mainly depending on pathology and immunohistochemistry. There have been few studies on its treatment and there is thus no standard treatment plan. Patient concerns: This is a 64-year-old female patient presented with a 2-month history of abnormal postmenopausal vaginal discharge, who had previous history of breast cancer. Diagnoses: Based on the gynecological examination, imaging results, pathology, and immunohistochemical results, a diagnosis of metastatic carcinoma of the cervix and breast cancer was confirmed. Interventions: She received computed tomography-guided 3-dimensional high-dose-rate brachytherapy in combination with chemotherapy. Outcomes: She achieved complete response locally. This case provides a new local treatment option for patients with inoperable localized cervical metastases. Lessons: We hope that this report and the accompanying review help to enrich the literature pertaining to the treatment of rare cervical metastases, providing a foundation for the improved survival of affected patients.

Cervical squamous cell carcinoma (CSCC) represents a significant global health concern among females. Identifying new biomarkers and therapeutic targets is pivotal for improving the prognosis of CSCC. This study investigates the prognostic relevance of CCZ1 in CSCC and elucidates its downstream pathways and targets using a combination of bioinformatics analysis and experimental validation. Transcriptomic analysis of 239 CSCC and 3 normal cervical samples from The Cancer Genome Atlas database reveals a marked upregulation of CCZ1 mRNA levels in CSCC, and elevated CCZ1 mRNA levels were associated with poor prognosis. Immunohistochemical analysis of clinical samples also confirmed these findings. Furthermore, functional assays, including Cell Counting Kit-8, colony formation, Transwell, and flow cytometry, elucidated the influence of CCZ1 on CSCC cell proliferation, migration, invasion, and cell cycle progression. Remarkably, CCZ1 knockdown suppressed CSCC progression both in vitro and in vivo. Mechanistically, CCZ1 knockdown downregulated MMP2 and MMP17 expression. Restoring MMP2 or MMP17 expression rescued phenotypic alterations induced by CCZ1 knockdown. Hence, CCZ1 promotes CSCC progression by upregulating MMP2 and MMP17 expression, emerging as a novel biomarker in CSCC and presenting potential as a therapeutic target in CSCC.

Objective: Inadequate radiation delivery to recurrent pelvic and abdominal tumors is frequently attributable to the dose limitations of surrounding normal structures, particularly the intestines. Radiotherapy guided by magnetic resonance imaging (MRI) significantly enhances the accuracy of soft-tissue delineation. The purposes of this study were to demonstrate the feasibility and effectiveness of MR-Linac Adaptive stereotactic body radiotherapy in patients with pelvic–abdominal recurrent or metastatic gynecological malignancies with or without systemic therapies. Methods: Patients with pelvic–abdominal recurrent or metastatic gynecological malignancies are eligible for MR-Linac Adaptive stereotactic body radiotherapy. Systemic therapies, including chemotherapy, immunotherapy, and targeted therapy, are considered acceptable treatment options. The safety, tolerability, and efficacy of MR-Linac Adaptive stereotactic body radiotherapy were assessed. Results: Between October 2019 and May 2025, 15 patients were subjected to MR-Linac Adaptive stereotactic body radiotherapy. With a median follow-up period of 4.67 months (range, 0.73–20.10 months), the 6-month overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 93.3%, 66.0%, and 92.3%, respectively. The 12-month OS, PFS, and LC rates were 83.8%, 37.7%, and 70.5%, respectively. The best objective response rate (ORR = CR + PR) for the irradiated lesions was 73.3% (11/15 patients). MR-Linac Adaptive stereotactic body radiotherapy led to objective responses in 73.3% (11/15) of the patients. As of the data cutoff (28 May 2025), one patient experienced dose-limiting toxicity (an enteric fistula). Another patient developed grade 4 thrombocytopenia during treatment; it was considered chemotherapy-induced. Conclusions: These findings suggest that MR-Linac Adaptive stereotactic body radiotherapy is relatively effective and safe and can be an important treatment option for patients with pelvic–abdominal recurrent or metastatic gynecological malignancies. MR-Linac Adaptive stereotactic body radiotherapy exhibited acceptable tolerability, promising efficacy, and a favorable local control rate with regard to heavily pretreated advanced solid tumors.

A conventional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival (OS) with five years of follow-up. The primary hypothesis was that progression-free survival (PFS) with three years of follow-up (PFS36) would be an appropriate primary surrogate endpoint. The primary hypothesis, which was developed from our data, was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS. A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. However, patients who achieved PFS36 had a 5-year OS rate of 98.2%. Further data were extracted from 26 randomized phase III trials on LACC. The trials included 55 arms, with a pooled sample size of 7,281 patients. Trial-level surrogacy results revealed that PFS36 (r², 0.732) was associated with 5-year OS. The correlation between PFS36 and OS was externally validated using independent retrospective data. A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens.

Objective: This study aimed to elucidate the association between hematologic toxicity (HT) and pelvic bone marrow (PBM) dosimetric parameters in patients with cervical cancer (CC) undergoing radiotherapy (RT) combined with artificial intelligence (AI)-assisted organ at risk (OAR) delineation (Software Copyright Registration Number 2023SR0150365). Accurate delineation of bone marrow (BM) regions and analysis of radiation doses may provide a theoretical foundation for the application of AI in predicting HT. Methods: This retrospective study included 141 patients with CC who received chemotherapy (sequential or concurrent) and/or pelvic volumetric modulated arc therapy (VMAT) at the Department of Gynecology, Cancer Hospital of the Chinese Academy of Medical Sciences, between March 2019 and December 2019. PBM and its subregions (ilium, lower pelvis, lumbosacral spine, and femoral heads) were delineated using AI-based automatic segmentation of CT images. The volumes receiving 10–40 Gy (V10, V20, V30, V40) were calculated, and baseline clinical characteristics were assessed. HT endpoints included grade ≥ 2 (HT2+) and grade ≥ 3 (HT3+) leukopenia, neutropenia, anemia, or thrombocytopenia. Associations between dosimetric parameters and HT were evaluated using logistic regression models. Results: Of the 141 patients, 107 (75.8%) developed HT2+ and 33 (23.4%) developed HT3+. Univariate analysis showed that chemotherapy and age were correlated with HT2+. Multivariate analysis identified femoral head V30, femoral head V40, and chemotherapy as independent predictors of HT3+. Conclusions: This study highlights the potential of AI-based OAR delineation for assessing PBM dosimetric parameters in patients with CC. Optimizing RT to minimize BM dose and volume may mitigate HT and enhance treatment tolerance. In our cohort, receipt of combined neoadjuvant and concurrent chemotherapy (NACT+CCRT) was a stronger predictor of HT than most BM dosimetric parameters, suggesting that the systemic effect of chemotherapy may dominate the hematologic toxicity profile in this setting. Consequently, patients receiving this combined modality treatment are at particularly high risk for HT and warrant close hematologic monitoring.