BACKGROUND:Neuroinflammation is a key driver of cognitive deficits after surgical menopause, a state commonly triggered by oophorectomy for oncological purposes. This intervention is routinely performed in premenopausal patients with hormone receptor-positive (HR+) breast cancer, constitutes foundational therapy for epithelial ovarian carcinoma, and is indicated for risk reduction in carriers of hereditary mutations such as breast cancer susceptibility gene 1/2 (BRCA1/2). As highly efficient immune cells, microglia play a central role in the onset of neurodegenerative diseases. Our study explored the role of thioredoxin-1 (Trx-1) in suppressing microglial activation and its potential for ameliorating postmenopausal cognitive decline. METHODS:Female C57BL/6J mice underwent ovariectomy (OVX) to model tumor-therapeutic oophorectomy. They were intraperitoneally injected with recombinant human Trx-1 (rhTrx-1) at a dose of 200 μg/30 g or PBS once weekly for five weeks following OVX. A Y-maze active avoidance task and trace fear conditioning were used to assess cognitive function. Levels of neuroinflammation were evaluated through immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR). Trx-1 levels in the hippocampus of OVX mice were measured by western blot and immunohistochemical analysis. Furthermore, the impact of Trx-1 on microglial activation was assessed in vitro. RESULTS:OVX induced the production of inflammatory factors and microglial activation in the brain, resulting in cognitive deficits in mice. However, intraperitoneal injection of rhTrx-1 inhibited these effects by improving cognitive function, reducing inflammatory cytokines, and promoting microglial polarization. In vitro studies also showed that rhTrx-1 attenuated lipopolysaccharide (LPS)-stimulated microglial activation through mitogen-activated protein kinase (MAPK) pathway signaling. DISCUSSION AND CONCLUSION:Due to its inhibitory effect on neuroinflammation and microglial activation, Trx-1 may represent a promising therapeutic candidate for managing cancer therapy-related cognitive impairment, particularly in patients undergoing estrogen-deprivation therapies such as oophorectomy.

Oncolytic virus (OV) therapy constitutes a novel advancement in cancer immunotherapy, with a distinctive dual mechanism of action against gynecological malignancies. These viruses, either genetically engineered or naturally occurring, are designed to selectively replicate within and lyse tumor cells, while eliciting a robust systemic antitumor immune response through the release of tumor-associated antigens and danger signals. This therapeutic strategy shows considerable promise for treating recurrent or treatment-resistant ovarian, cervical, and endometrial cancers, conditions for which conventional therapies are often inadequate. To standardize and enhance its clinical implementation, an expert consensus evaluated and endorsed three primary routes of administration. Intratumoral injection administers the virus directly into accessible tumors, thereby maximizing local viral concentration while minimizing systemic exposure. By contrast, intravenous infusion is useful for addressing disseminated or metastatic disease, as it enables the virus to circulate and target tumor sites throughout the body. Intraperitoneal delivery is particularly significant for gynecologic malignancies, such as ovarian cancer, which predominantly metastasizes within the abdominal cavity. This approach exposes peritoneal surfaces to a high concentration of the therapeutic virus, ensuring direct interaction with both primary and metastatic lesions. By delineating these strategic administration pathways, the consensus provides a practical framework to improve efficacy, inform clinical decision-making, and facilitate the broader integration of OV therapy into the oncological treatment repertoire for gynecological cancers.

Purpose This study evaluated the safety and efficacy of polyethylene glycol (PEG) hydrogels in reducing rectal radiation dose and complication during cervical cancer radical concurrent chemoradiation therapy. Methods and Materials This phase 3, randomized, parallel-controlled trial (NCT 05690906) conducted across 9 centers in China (July 2022-January 2025). Participants were randomly assigned 1:1 to receive a 10 mL PEG hydrogel injection (experimental group) or no injection (control group) after 50.4 Gy/28 fractions (f) or 45 Gy/25 f external beam radiation therapy. Three-dimensional image guided brachytherapy plans were developed before each brachytherapy session using computed tomography or magnetic resonance imaging (MRI) imaging, delivered in a prescribed dose of 6 Gy × 5 f or 7 Gy × 4 f. Concurrent chemotherapy was administered during the radiation therapy course. Patients were followed up for 72 weeks. The primary endpoint was the cumulative rectal D2cc dose. Secondary endpoints included rectal D0.1cc and D5cc doses and D2cc of the sigmoid, bladder, and small intestine; changes in the perirectal space and hydrogel volume; quality of life (QOL) scores (QLQ-C30 and QLQ-CX24); and incidence of radiation-induced rectal complication. QOL was assessed before brachytherapy, immediately after completing brachytherapy, and at 4, 12, 24, 36, 48, and 72 weeks after brachytherapy. Radiation-induced rectal complication was assessed at each of the aforementioned follow-up timepoints and additionally evaluated on a weekly basis throughout the entire radiation therapy course. Results Of 94 analyzed patients (45 experimental and 49 control), the experimental group showed significant reductions in rectal D2cc (64.23 ± 6.58 Gy vs 69.79 ± 6.10 Gy; P < .001), D0.1cc (74.67 ± 12.22 Gy vs 84.38 ± 9.91 Gy; P < .001), and D5cc (60.23 ± 4.96 Gy vs 63.18 ± 5.04 Gy; P = .003) doses, with no significant changes in doses to other organs The hydrogel increased the cervix-rectum distance during brachytherapy and remained stable until 24 weeks after treatment, with noticeable absorption occurring between weeks 24 and 36. No significant differences were observed between experimental group and control group in acute radiation-induced rectal injuries (55.6% vs 46.9%), chronic injuries (9.5% vs 16.7%), or QOL scores, except for higher constipation scores and symptom experience scores in the experimental group. One case (2.2%) of rectovaginal fistula occurred in the experimental group, with no other grade ≥3 adverse events observed. Conclusions PEG hydrogel injection effectively reduced rectal radiation dose during cervical cancer radical concurrent chemoradiation therapy without increasing doses to other organs, preserving overall safety and QOL despite transient QOL variations and an isolated rectovaginal fistula.

AIM:Surgery (e.g., radical hysterectomy) combined with radiotherapy is the mainstay of treatment strategy for locally advanced cervical cancer. However, the beneficial effects of adjuvant radiotherapy are frequently offset by late-onset toxicities, such as vaginal stenosis (VS), which significantly impact patients' quality of life. Although imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI) are key for both surgical planning and radiotherapy targeting, their ability to predict VS risk before treatment remains limited. This challenge underscores the need for accurate and interpretable predictive models specifically adapted to surgical oncology contexts. This study aims to develop and validate an explainable deep learning framework, integrating Squeeze-and-Excitation (SE) networks and Gradient-weighted Class Activation Mapping (Grad-CAM) visualization, for predicting radiotherapy-induced VS to enable early, personalized intervention strategies. METHODS:Pre-treatment (i.e., post-surgical, pre-radiotherapy) CT images of cervical cancer patients diagnosed between January 2017 and March 2022 were retrospectively collected. These patients underwent radical hysterectomy (or equivalent surgical resection) followed by radiotherapy. Each patient was categorized as either positive or negative for subsequent VS development. Following normalization and augmentation, we employed a Squeeze-and-Excitation enhanced Inception network (SE-Inception) to distinguish between high- and low-risk cases. Model performance was compared to a conventional Random Forest and a deep learning baseline (ResNet50). Additionally, Grad-CAM visualization was integrated to highlight discriminative image regions for enhanced interpretability and clinical validation. RESULTS:Among the 140 patients included in the study, 51 developed VS after treatment, representing an incidence rate of 36.4%. The SE-Inception model yielded superior performance (accuracy: 0.93; area under the receiver operating characteristic curve [AUC]: 0.95), surpassing both ResNet50 (accuracy: 0.85; AUC: 0.90) and Random Forest (accuracy: 0.59; AUC: 0.65). Recall and F1 scores also improved markedly, indicating robust sensitivity and precision. Calibration curves demonstrated excellent agreement between predicted and observed risks, while decision curve analysis (DCA) consistently indicated superior net clinical benefits of the SE-Inception model across various threshold probabilities compared to ResNet50 and Random Forest. Grad-CAM consistently localized to anatomically relevant regions correlating with surgeon- and radiologist-identified risk sites, strengthening the clinical interpretability and trustworthiness of the predictive framework. CONCLUSIONS:Taking the surgical context into account, our SE-Inception framework demonstrated enhanced accuracy and interpretability in identifying patients at risk for postoperative radiotherapy-induced VS. Through alignment with expert clinical assessments and enabling early, personalized intervention strategies, this approach has the potential to improve outcomes and long-term quality of life in cervical cancer survivors, supporting more proactive, surgery-informed treatment planning.

OBJECTIVE:Investigate the efficacy/safety of ociperlimab (anti-TIGIT monoclonal antibody [mAb]) + tislelizumab (anti-PD-1 mAb) in recurrent/metastatic (R/M) cervical cancer (CC). METHODS:Patients had R/M CC, received ≥1 prior chemotherapy, and were not amenable to curative treatment. In stage 1, 80 patients were randomized 1:1 to ociperlimab 900 mg + tislelizumab 200 mg every 3 weeks (cohort 1) or tislelizumab monotherapy (cohort 2). In stage 2, 98 additional patients were enrolled in cohort 1. Primary endpoint was blinded independent review committee-assessed objective response rate (ORR) by RECIST v1.1 for PD-L1+ subgroup and all-comers in cohort 1. RESULTS:Between March 2 and December 15, 2021, 178 patients were enrolled, and all were treated (cohort 1: 138; cohort 2: 40). ORR of cohort 1 PD-L1+ subgroup and all-comers were 27.4% (95% CI 18.2%-38.2%) and 23.2% (16.4%-31.1%), respectively. In cohort 1, median progression-free survival (PFS) was 3.0 months (95% CI 2.6-4.9) (all-comers) and 4.1 months (95% CI 2.7-6.9) (PD-L1+); median overall survival was 12.2 months (95% CI 9.9-16.6) (all-comers) and 16.4 months (95% CI, 10.4 months-not estimable) (PD-L1+). 70.3% of cohort 1 had ≥1 treatment-related adverse event (TRAE); 18.1% experienced ≥1 grade ≥3 TRAE. Immune-mediated AEs occurred in 35.5% of cohort 1. CONCLUSIONS:In patients with R/M CC who had received prior chemotherapy, ociperlimab + tislelizumab has promising antitumor activity in both all-comers and PD-L1+ subgroup, supporting further investigation of immune-modulating agent combinations for R/M CC. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04693234; https://clinicaltrials.gov/study/NCT04693234?term=NCT04693234&rank=1; EudraCT: https://eudract.ema.europa.eu/2020-004657-77.

[Purpose]: To address the issue of low accuracy in dose distribution prediction in radiotherapy, we propose a deep learning-based model for predicting three-dimensional dose distribution in tumor radiation therapy. The model utilizes quantitative evaluation methods to assess the treatment plans. [Methods]: We selected a dataset of 130 cervical cancer patients, including CT images and target region files. A deep learning U-Net model based on convolutional neural networks and residual blocks was employed to automatically extract multi-scale and multi-level feature maps of CT images, target regions, and anatomical structures of critical organs for intensity-modulated radiation therapy (IMRT) treatment plans and perform threedimensional dose distribution prediction. Quantitative analysis methods, including error measures such as maximum dose (Dmax), mean dose (Dmean), V20, and D95, were used. [Results]: For cervical cancer cases, DVH (dose-volume histogram) graphs were generated based on the evaluation results, directly reflecting the differences between the actual and predicted doses. The actual errors met the basic requirements, and a quantitative evaluation approach was used to optimize the dosimetric parameters. The specific quantification results are: DSC: 86.52 +/- 9.31, 95% HD: 3.74 +/- 1.49, JD: 0.112 +/- 0.026, MSD: 0.067 +/- 0.031. [Conclusion]: Through training the deep learning model, we have successfully captured the complex nonlinear relationship between IMRT plan feature map parameters and three-dimensional dose distribution. In practical clinical applications, this trained model can accurately predict personalized three-dimensional dose distribution for new patients and effectively assess treatment plans in a quantitative manner. The source code is available at: https://github.com/xiebw9509/Radiotherapy_dose_prediction.

Background Targeting PD-L1 has become a crucial approach in tumor immunotherapy. Echinacoside (ECH) is a natural compound known for its extensive biological activities, its impact on antitumor immunity remains uncertain. Purpose This work was designed to assess the effects of ECH on the PD-L1/PD-1-mediated tumor immune evasion and its underlying mechanisms. Methods Flow cytometry and RT-qPCR were utilized to explore the influence of ECH on PD-L1 expression. Western blot was employed to examine the mechanism by which ECH might modulate PD-L1 expression. Flow cytometry was conducted to evaluate the influence of ECH therapy, or the synergistic effects of ECH combined with immune checkpoint blockade (ICB) on tumor immune microenvironment (TIME) in tumor-burden mice. Blood biochemistry tests were used to evaluate the safety of ECH treatment. Results ECH downregulated both the protein and mRNA expression levels of IFN-γ-induced PD-L1 through JAK/STAT1/IRF1 signaling pathway. ECH treatment upregulated the infiltration of IFN-γ+CD8+ T cells and Ki-67+CD8+ T cells, lowered the frequency of TIM-3+PD-1+ T cells, promoted the infiltration of effector CD4+ T cells and total CD8+ T cells while suppressed the percentage of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Moreover, the combination of ECH and anti-PD-1 or anti-CTLA-4 therapy exhibited synergistic anti-tumor effects, reshaping TIME. Blood biochemistry tests unveiled that ECH did not show additional toxicity. Conclusion ECH upregulates the expression of inducible PD-L1 through the JAK/STAT1/IRF1 signaling pathway, enhances T cell function, and reshapes the tumor immune landscape into an anti-tumor phenotype. Importantly, ECH markedly enhances the efficacy of ICB treatment, indicating its potential application in anti-tumor therapy.

Background: Endometrial cancer is one of the most common gynecological malignancies in the world. Vaginal brachytherapy is an important postoperative adjuvant treatment for endometrial cancer. However, a common problem with existing applicators is insufficient dose at the vaginal apex. Purpose: This study describes the Hangzhou (HZ) cylinder, a novel 3D printed vaginal intracavity brachytherapy applicator, detailing its characteristics, dose distribution, and clinical applications. Methods and materials: The HZ cylinder is distinguished by its unique structure: a U-shaped channel with a 2 mm diameter, a straight central axis channel of the same diameter, and 10 parallel straight channels. For comparison, standard plans were employed, designed to ensure that a minimum of 95% of the prescribed dose reached 5 mm beneath the mucosal surface. We conducted comparative analyses of mucosal surface doses and doses at a 5 mm depth below the mucosa between the HZ cylinder and a conventional single-channel cylinder across various treatment schemes. Additionally, the study examined dose differences in target volume and organs at risk (OARs) between actual HZ cylinder plans and hypothetical single-channel plans. Results: In the standard plans, mucosal surface doses at the apex of the vagina were 209.32% and 200.61% of the prescribed dose with the HZ and single-channel cylinders, respectively. The doses on the left and right wall mucosal surfaces varied from 149.26% to 178.13% and 142.98% to 180.75% of the prescribed dose, and on the anterior and posterior wall mucosal surfaces varied from 128.87% to 138.50% and 142.98% to 180.75% of the prescribed dose. Analysis of 24 actual treatment plans revealed that when the vaginal tissue volume dose covering 98% (vaginal D98%) was comparable between the HZ cylinder and virtual single-channel plans (6.74 +/- 0.07 Gy vs. 6.69 +/- 0.10 Gy, p = 0.24), rectum doses of HZ cylinder plans were significantly lower than those of single-channel plans (D1cc, 5.96 +/- 0.56 Gy vs. 6.26 +/- 0.71 Gy, p = 0.02 and D2cc, 5.26 +/- 0.52 Gy vs. 5.56 +/- 0.62 Gy, p = 0.02). Conclusions: The HZ cylinder demonstrates a reduction in dose to the rectum and bladder while maintaining adequate target volume coverage. Its mucosal surface dose is comparable to that of the traditional single-channel cylinder. These findings suggest that the HZ cylinder is a viable and potentially safer alternative for vaginal brachytherapy, warranting further investigation with larger sample sizes.

Purpose ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) evaluated pembro + CCRT in patients (pts) with high-risk LACC. Materials and Methods Pts with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB with node-positive disease or stage III‒IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or placebo (pbo) Q3W + CCRT then 15 cycles of pembro 400 mg or pbo Q6W. CCRT was 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 QW + EBRT then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator or histopathologic confirmation and OS. Results 1060 pts were randomized to pembro + CCRT (n = 529) or pbo + CCRT (n = 531). At IA1 (data cutoff: Jan 9, 2023), median follow-up was 17.9 mo. Pts received a median of 11 cycles of pembro or pbo and 5 cycles of cisplatin in both arms. Most pts completed radiation treatment (pembro + CCRT, 97.9%; pbo + CCRT, 98.3%); overall median treatment duration was 52 d in both arms. Table 1 summarizes the CCRT treatment. Pembro + CCRT improved PFS vs pbo + CCRT (HR 0.70 [95% CI 0.55‒0.89]; P = 0.0020). Median PFS was not reached in either arm. PFS benefit was generally consistent across prespecified subgroups. With only 103 events (42.9% maturity), pembro + CCRT had a favorable trend in OS (HR 0.73 [95% CI 0.49‒1.07]). Treatment-related AEs (TRAEs) were less common in the pembro monotherapy phase (72.7%) vs pembro + CCRT combination therapy phase (94.5%); results in the pbo arm were 60.0% vs 95.7%. Safety profiles were consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Conclusions Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS vs pbo + CCRT in pts with high-risk LACC. Pembro + CCRT had manageable safety, with most TRAEs occurring during the combination phase of therapy. Pembro + CCRT has potential as a new standard of care for this high-risk population.

Background To evaluate the clinical benefit of concurrent chemoradiotherapy in combination with H101 injection for the treatment of locally advanced cervical cancer (LACC) patients. Methods The patients, all diagnosed with stage IIB or III cervical cancer according to The International Federation of Gynecology and Obstetrics (FIGO) stage (2009) with tumor length ≥6cm were enrolled at Zhejiang Cancer Hospital from July 2015 to April 2017. All patients received concurrent chemoradiotherapy (CCRT) in combination with intratumoral H101 injection before and during external beam radiotherapy (EBRT). The parameters recorded and analyzed included progression-free survival (PFS), overall survival (OS), tumor regression after EBRT and side effects, which were compared to another group of patients with similar characteristics treated with CCRT alone. Results Twenty patients were treated with CCRT in combination with intratumoral H101 injection and another group of 20 patients treated with CCRT alone was selected as control. The median follow-up time was 38 months (range 10-58 months). The 3-year local, regional, and overall PFS rates were 95% vs 66.6%( p = 0.02), 95% vs 62.5%(p = 0.029), and 65% vs 43.8%( p = 0.19), for H101 group and control group respectively. The 3-year (OS) was 74.3% vs 54.5%( p = 0.098), respectively. The median reduction of tumor length and volume for H101 group and control group were 37.7% vs 28.7%(p = 0.016) and 75.1% vs 62.4%(p = 0.001), respectively. The major adverse event related to H101 was fever. Conclusion CCRT in combination with intratumoral H101 injection is effective in treating LACC, and has an acceptable safety profile. Trial registration The study was registered at Chinese Clinical Trail Registry (ChiCTR-OPC-15006142).

Background: Patients (pts) with advanced cervical cancer who progressed on first-line treatment have no standard therapy and derive limited benefit from currently available treatment. More effective therapeutic strategies are required. This phase II trial was conducted to evaluate the efficacy and safety of IBI310 (anti-CTLA-4 mAb) plus sintilimab (sint) versus sint in pts with recurrent/metastatic cervical cancer. Here we present the efficacy and safety results for pts in sint plus placebo group. Methods: Pts aged 18-75 years, with histologically or cytologically confirmed cervical cancer who had progressed on or been intolerant to first-line or above platinum-based chemotherapy were enrolled. Pts in sint plus placebo group received sint (200mg) plus placebo IV Q3W for 4 cycles followed by sint monotherapy till disease progression, intolerable toxicity, withdrawal of informed consent, death, or for up to 24 months. The primary endpoint was objective response rate (ORR) assessed by IRRC per RECIST V1.1. The data cutoff date was April 20, 2022. Results: Overall, 101 pts were enrolled and received at least one dose of assigned treatment (median age of 53.0 years, 71.3% pts with PD-L1 CPS ≥1, 91.0% pts with squamous-cell carcinoma, and 36.6% pts with ≥2 lines of prior systemic therapy). The median treatment exposure was 18.0 weeks. The IRRC-assessed confirmed objective response rate (ORR) was 24.5% (95%CI: 16.4%-34.2%), disease control rate was 56.1% (95%CI: 45.7%-66.1%), and median duration of response was not reached. Pts with PD-L1 CPS ≥1 showed numerically higher ORR versus those with CPS <1 (32.9% vs 17.2%). With a median follow-up of 8.3 months, median PFS was 2.7 months (95%CI: 1.5-4.3). Median overall survival (OS) was not reached; OS rate was 89.6% (95%CI: 80.9%-94.5%) at 6 months and 65.5% (95%CI: 50.9%-76.7%) at 12 months. Treatment-related adverse events (TRAEs) occurred in 75.2% pts, with the most common being anaemia (13.9%), hypothyroidism (12.9%), white blood cell count decreased (12.9%), and hyperthyroidism (10.9%). 18.8% pts experienced CTCAE Grade 3 or higher TRAEs (no TRAE leading to death occurred). TRAEs leading to drug discontinuation occurred in 1 pt (myocarditis, grade 2). Conclusion: This study demonstrated favorable antitumor activity and acceptable safety with sintilimab alone over available therapies in ≥2 line advanced cervical cancer. ClinicalTrials.gov identifier: NCT04590599 Citation Format: Qinglei Gao, Jing Wang, Qin Xu, Ying Tang, Jieqing Zhang, Baoping Chang, Bairong Xia, Wei Duan, Danbo Wang, Lijing Zhu, Ruifang An, Guonan Zhang, Yaling Tang, Jianli Huang, Xiang Zhang, Hui Qiu, Wenting Ji, Li Li, Jianqing Zhu, Ding Ma. Efficacy and safety of sintilimab (anti-PD-1 mAb) for advanced cervical cancer: Results from a Phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT079.

Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis. Recently, immunotherapy plus chemotherapy has demonstrated clinical activity in ES-SCLC in previous phase III trials. Envafolimab is a novel recombinant protein of a humanized camel-derived single-domain anti-PD-L1 antibody fused with a human IgG1 Fc fragment designed for subcutaneous (SC) injection, which can be conveniently administered. This study aims to investigate the efficacy and safety of first-line treatment with envafolimab plus carboplatin and etoposide in patients with ES-SCLC.

Background No standard treatment exists for patients with recurrent cervical cancer. This study aimed to determine the role of surgery, followed by concurrent radiochemotherapy, as a treatment for recurrent pelvic cervical cancer without previous radiotherapy. Methods The current study identified patients diagnosed with vaginal and/or pelvic sidewall recurrent cervical cancer after primary surgery without radiotherapy in Zhejiang Cancer Hospital from May 2012 to November 2016. These enrolled patients underwent surgery, followed by concurrent radiochemotherapy and data were analyzed. Results This study enrolled 27 patients, including 11 with central (vaginal) and 16 with noncentral (pelvic sidewall with or without vaginal) recurrences. The median follow-up time after recurrence was 64 months (range, 5–110 months). All patients underwent surgery to resect the tumor as completely as possible and pelvic external beam radiotherapy (EBRT) with a median equivalent dose in 2 Gy fractions (EQD2) of 45.1 Gy (range, 44.3–47.8 Gy) with concurrent weekly cisplatin chemotherapy. The median EQD2 dose for the tumor bed/residual tumor was 51 Gy (range, 44.3–73.4 Gy), including 18 patients with a boost dose by EBRT or vaginal brachytherapy (VBT). The 5-year overall survival (OS) rates were 77.1% (central) and 65.7% (noncentral) without a statistically significant difference (P=0.246). Progression-free survival (PFS) rates were 81.8% (central) and 34.4% (noncentral), respectively, with a statistically significant difference (P=0.047). Three patients with noncentral recurrence experienced grade ≥3 complications associated with surgery. Conclusions Surgery followed by concurrent radiochemotherapy was a feasible and effective treatment with acceptable complications for locally recurrent cervical cancer, which markedly improved the survival of pelvic sidewall recurrence.

Background: FOXF1 acts a crucial part to tumor initiation and progression. In this study, we aimed to analyzed FOXF1 in ovarian cancer from different databases which showed diagnosis and targeted therapeutic values. Results: The expression of FOXF1 in ovarian cancer tissue was markedly lower than that in normal tissue. Among different tumor subgroups, FOXF1 expression was conspicuously lower in higher grade stage. Additionally, FOXF1 expression and genetic variations were significantly correlated with various immune infiltrating cells. Altogether, 2594 co-expressed genes evidently pertinent to FOXF1. These genes were correlated with cell adhesion, NADH dehydrogenase complex and cytokine binding in results of enrichment analysis. In addition, FOXF1 was associated with gene networks regulated by PRKG1, miR-151, and SRF respectively. CMap analysis screened several potential small molecules for ovarian cancer treatment. Conclusions: FOXF1 has been shown to be a vital biomarker for the diagnosis of ovarian cancer and the immune infiltrating levels. The small molecules screened here supply rationale for new drug development for ovarian cancer.

Objective:To introduce the workflow of individualized 3D-printed intracavitary/interstitial vaginal template design. Dosimetric parameters and operation safety were investigated to evaluate the performance of 3D-printed template and freehand implantation.Methods:Forty patients previously treated with intracavitary/interstitial Ir-192 HDR brachytherapy were enrolled in this study. All patients were randomly divided into the treatment ( n=20) and control groups ( n=20). In the treatment group, twenty patients were treated with individualized 3D-printed template. CT-based preplan was carried out to determine the needle implantation cannels. Template with customized shape and implantation cannels was then produced by a 3D printer. Finally, the template was inserted under CT guidance. In the control group, twenty patients received freehand implantation. Needle insertion was decided empirically without the preplan process. Results:The difference of D 90 for high risk CTV was found to be minor, while the D 2cm 3 in the rectum, bladder and sigmoid was significantly improved in the treatment group. Meanwhile, the high dose region and conformal index were also improved in the treatment group. A total of 273 needles were inserted and one (0.3%) not-used needle was found. No normal tissues were penetrated during needle insertion in the treatment group. In the control group, a total of 203 needles were inserted and 4(2.0%) not-used needles were observed, and normal tissue penetration occurred in 3(1.5%) needle insertion. Conclusions:The individualized 3D-printed template implantation approach has advantages in terms of dosimetry and safety compared with freehand implantation. The actual treatment can achieve the dosimetric design requirements of the preplan.

BACKGROUND:The high-mobility group A1 gene (HMGA1) plays a major role in the development of malignant cancers. However, the mechanisms underlying the correlation between HMGA1 expression level and patients' overall survival rate in various malignant cancers is unclear.METHODS:We used The Cancer Genome Atlas (TCGA) database (https://genome-cancer.ucsc.edu/) to search for mRNA expression levels of HMGA1 in tumor patients and grouped them by receiver operating characteristic (ROC) curve. This divided patients into a high expression cohort and low expression cohort, and Kaplan-Meier analysis revealed the overall survival of the cancer patients. We also used real-time quantitative PCR (qPCR) to detect the expression of HMGA1, CBX7, E-cadherin, and β-catenin gene was detected by normalized to the expression of β-actin in colorectal cancer cell lines.RESULTS:High expression group correlated with worse survival prognosis statistically significant (P<0.05), and scatter plots showed HMGA1 high expression in the different cancers (lung cancers; lung adenocarcinoma and lung squamous cell carcinoma; stomach and colorectal cancers; liver and pancreatic cancer; kidney papillary cell carcinoma; kidney clear cell carcinoma, brain lower grade glioma; adrenocortical cancer; acute myeloid leukemia; and sarcoma; head and neck squamous cell carcinoma, cholangio and bladder urothelial cancers). Further, we also found that the mRNA expressions of HMGA1, CBX7, E-cadherin, and β-catenin genes significantly in colorectal cancer cell lines (P value: 0.0005), consistent with the results of HMGA1 in TCGA database.CONCLUSIONS:HMGA1 is highly expressed in various cancers than normal tissues, and high expression levels of HMGA1 correlated with a worse prognosis. The gene expressions and the TCGA data clearly supports that targeting HMGA1 in the management of cancers increases the survival rate of cancer patients.