Local Cervical Cancer Research Articles

Nationwide cohort study on the risk of high-grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ.

Internationally, little consensus exists about the best treatment for cervical adenocarcinoma in situ (AIS). This study aimed to determine the incidence of recurrent high-grade cervical dysplasia and development of local cervical cancer after treatment for AIS. This nationwide, retrospective cohort study included patients with AIS, who were treated by a large loop excision of the transformation zone (LLETZ), cold-knife conization (CKC), or hysterectomy between January 1, 1990 and December 31, 2021 in the Netherlands. Pathology reports were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were the cumulative incidences of high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2 or 3, and AIS) and local cervical cancer up to 20 years after primary treatment. In total, 4243 patients with AIS were included. The primary treatment was a LLETZ, CKC, or hysterectomy in 1593, 2118, and 532 patients, respectively. The incidence of recurrent high-grade cervical dysplasia after LLETZ (10.5%; 95%CI: 8.6-12.3) was higher than after CKC (5.5%; 95%CI: 4.4-6.6, p <.0001). When a radical excision, that is, surgical margins free of dysplasia at end of treatment, was achieved, the incidence of recurrent high-grade dysplasia and local cervical cancer did not differ between LLETZ (5.6% [95%CI: 3.3-7.9] and 1.9% [95%CI: 0-4.4]) and CKC (4.7% [95%CI: 3.5-5.8], p = .631 and 1.5% [95%CI: 0.7-2.3], p = .918). After hysterectomy, none of the patients developed cervical dysplasia or local cervical cancer. Conservative treatment for AIS can be considered a safe and final treatment modality when a radical excision is achieved.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PurposeThis study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy.MethodsPatients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey.ResultsThe responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians’ recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships.ConclusionAlthough several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

BackgroundTumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.MethodsPatient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence.ResultsIn matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010).ConclusionsOur modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer.Trial registrationNCT04766320, Jan 04, 2021.

Metastatic Cervical Cancer Presenting as a Sessile Polyp in the Ascending Colon

Patients with metastatic cervical cancer, particularly hematogenous metastasis, have a worse prognosis compared to those with localized cervical cancer. Gastrointestinal involvement of cervical cancer occurs in approximately 8% of cases and most lesions are located in the recto-sigmoid area due to direct extension of the disease. Here, we present a case of cervical adenocarcinoma spreading to the ascending colon as a sessile polyp and mimicking a hyperplastic polyp. Histopathological evaluation followed by immunohistochemistry analysis is needed to confirm the diagnosis.

Construction and efficacy test of a survival prediction model for locally advanced cervical cancer based on anti-angiogenesis

ObjectiveThis study aimed to develop and evaluate an anti-angiogenesis-based model for predicting the survival and the potential benefits of targeted therapy for patients with localized advanced cervical cancer. MethodsWe collected clinical data from 163 patients with cervical cancer who received paclitaxel and cisplatin (TP) or TP plus bevacizumab during or after radiotherapy from June 2017 to February 2023. We analyzed the clinical measures of recent efficacy and overall survival (OS) using univariate and logistic multivariate and Cox regression methods, respectively. We constructed a nomogram model and evaluated its efficacy using the c-index, the area under the curve (AUC), a calibration curve, and the clinical decision curve (DCA). ResultsWe found that targeted agents and hemoglobin were independent determinants of near-term efficacy (P < 0.05), while targeted agents and stage were independent factors of OS (P < 0.05). We developed a predictive model for an OS prognostic nomogram and performed internal validation 1000 times using the Bootstrap re-sampling method. The c-index was 0.81, and the AUC was 0.84 (P < 0.01).The calibration curves showed a good agreement between the projected and actual values. The DCA curve indicated that the model had a high positive predictive accuracy. ConclusionWe developed a novel anti-angiogenesis-based survival prediction model for patients with locally advanced cervical cancer. This model could estimate the benefit of targeted therapy before treatment, and it had good validation.

MRI Plain Scan: A Tool in the Management of Cervical Cancer during Pregnancy.

The purpose of this study was to assess the diagnostic value of magnetic resonance imaging (MRI) in staging and treatment of cervical cancer in pregnancy, and to evaluate the benefit of apparent diffusion coefficient (ADC) during neoadjuvant chemotherapy management. This was a retrospective cohort study. Patients were divided into two groups according to the stage of cervical cancer. The mean term of pregnancy at the time of the diagnosis was the early second trimester (range 10-27 weeks) and the median age was 33 years (range 26-40 years). The abdominal and pelvic MRI images and clinical data of these patients were reviewed. Tumor size, local tumor spread, and nodal involvement were evaluated using an MRI dataset. The treatment and follow-up imaging were analyzed as well, and the ADC was measured before and after the chemotherapy. 16 patients with histopathologically confirmed cervical cancer during pregnancy were retrospectively enrolled. 7 patients were diagnosed with local cervical cancer (FIGO stage IAI) and designated as early stage group, as the lesion was invisible on MRI. In this group, pregnancies were allowed to continue until cesarean delivery (CD) at 38-41 weeks. The other 9 patients presenting with local or extensive cervical cancer (FIGO stage IB2-IIA2) were designated as the advanced-stage group. The lesion could be measured and analyzed on MRI. They were treated with neoadjuvant chemotherapy in pregnancy. Among them, 6 patients underwent TP regimen (paclitaxel 135~175 mg/m2 plus cisplatin 70~75 mg/m2), while 3 patients received TC regimen (paclitaxel 135~175 mg/m2 plus carboplatin AUC=5). NACT was performed for 1 to 2 courses before surgery. ADC demonstrated significant differences before and after chemotherapy administered during pregnancy (1.06 ± 0.12 sec/mm2 vs. 1.34 ± 0.21 sec/mm2). MRI has been found to be helpful in staging cervical cancer in pregnancy. Patients with stage IA confirmed by MRI can choose conservative treatment and continue the pregnancy until term birth. MRI can dynamically monitor the efficacy of chemotherapy for patients with stage IB and above during pregnancy. ADC value can have a potential role in the evaluation of chemotherapy efficacy.

SY05-3 Controversies in the surgical treatment for local recurrent cervical cancer

SY05-3 Controversies in the surgical treatment for local recurrent cervical cancer

Formulation and evaluation of paclitaxel-loaded boronated chitosan/alginate nanoparticles as a mucoadhesive system for localized cervical cancer drug delivery.

Cervical cancer remains a significant global health challenge, and there is a need for innovative drug delivery systems to improve the efficacy of anticancer drugs. In this study, we developed and evaluated boronated chitosan/alginate nanoparticles (BCHIALG NPs) as a localized mucoadhesive drug delivery system for cervical cancer. Boronated chitosan (BCHI) was synthesized by incorporating 4-carboxyphenylboronic acid onto chitosan (CHI), and boronated chitosan/alginate nanoparticles (BCHIALG NPs) with varying polymer ratios were prepared using an ionic gelation method. The physical properties, drug loading capacity/encapsulation efficiency, mucoadhesive properties, and in vitro drug release profile of the nanoparticles were evaluated. The BCHIALG NPs exhibited a size of less than 390 nm and demonstrated high drug encapsulation efficiency (98.1 - 99.8%) and loading capacity (326.9 - 332.7 μg/mg). Remarkably, the BCHIALG NPs containing 0.03% boronated chitosan and 0.07% alginate showed superior mucoadhesive capability compared to CHIALG NPs, providing sustained drug release and they showed the most promising results as a transmucosal drug delivery system for hydrophobic drugs like paclitaxel (PTX). To the best of our knowledge, this is the first report investigating BCHIALG NPs for cervical drug delivery. The new mucoadhesive paclitaxel formulation could offer an innovative strategy for improving cervical cancer treatment.

Approximating missing epidemiological data for cervical cancer through Footprinting: A case study in India.

Local cervical cancer epidemiological data essential to project the context-specific impact of cervical cancer preventive measures are often missing. We developed a framework, hereafter named Footprinting, to approximate missing data on sexual behaviour, human papillomavirus (HPV) prevalence, or cervical cancer incidence, and applied it to an Indian case study. With our framework, we (1) identified clusters of Indian states with similar cervical cancer incidence patterns, (2) classified states without incidence data to the identified clusters based on similarity in sexual behaviour, (3) approximated missing cervical cancer incidence and HPV prevalence data based on available data within each cluster. Two main patterns of cervical cancer incidence, characterized by high and low incidence, were identified. Based on the patterns in the sexual behaviour data, all Indian states with missing data on cervical cancer incidence were classified to the low-incidence cluster. Finally, missing data on cervical cancer incidence and HPV prevalence were approximated based on the mean of the available data within each cluster. With the Footprinting framework, we approximated missing cervical cancer epidemiological data and made context-specific impact projections for cervical cancer preventive measures, to assist public health decisions on cervical cancer prevention in India and other countries.

Gold-Enhanced Brachytherapy by a Nanoparticle-Releasing Hydrogel and 3D-Printed Subcutaneous Radioactive Implant Approach.

Brachytherapy (BT) is a widely used clinical procedure for localized cervical cancer treatment. In addition, gold nanoparticles (AuNPs) have been demonstrated as powerful radiosensitizers in BT procedures. Prior to irradiation by a BT device, their delivery to tumors can enhance the radiation effect by generating low-energy photons and electrons, leading to reactive oxygen species (ROS) production, lethal to cells. No efficient delivery system has been proposed until now for AuNP topical delivery to localized cervical cancer in the context of BT. This article reports an original approach developed to accelerate the preclinical studies of AuNP-enhanced BT procedures. First, an AuNP-containing hydrogel (Pluronic F127, alginate) is developed and tested in mice for degradation, AuNP release, and biocompatibility. Then, custom-made 3D-printed radioactive BT inserts covered with a AuNP-containing hydrogel cushion are designed and administered by surgery in mice (HeLa xenografts), which allows for measuring AuNP penetration in tumors (≈100µm), co-registered with the presence of ROS produced through the interactions of radiation and AuNPs. Biocompatible AuNPs-releasing hydrogels could be usedin the treatment of cervical cancer prior to BT, with impact on the total amount of radiation needed per BT treatment, which will result in benefits to the preservation of healthy tissues surrounding cancer.

Patient, disease, and survival outcomes for stage IB to stage IV cervical cancer-A population study.

Factors that impact recurrence in stages IB to IV include larger tumor, high-risk histology, older age, and lymphovascular invasion (LVI); however, local studies on risk factors for recurrence in British Columbia and our local recurrence patterns have not been well studied. Furthermore, the efficacy of treatment modalities including surgery and chemoradiation in the different stages of cervical cancer have not been clarified in this population. The purpose of this study is to determine the disease and treatment characteristics of stages IB to IV cervical cancer which are associated with survival differences within British Columbia. We performed a retrospective population study. A chart review on cervical cancer patients in British Columbia between 1 January 2010 and 31 December 2017 was done. Demographic data and treatment details were collected. Data were analyzed using multivariate Cox regressions, pairwise comparison using the Log-Rank test, and chi-square tests. We included 780 patients (stage I: 31.5%, II: 20.0%, III: 34.5%, and IV: 3.3%). LVI and p16 negativity were associated with decreased overall survival (OS), and multivariate analyses show them to be independent risk factors for poorer survival. Surgical resection in stage I was associated with improved survival, but not with stages II-IV. The use of radical radiation therapy (RT), brachytherapy, and concurrent chemotherapy were independently associated with improved survival in stages II-IV. Peri-RT chemotherapy was not associated with survival benefit in adeno/adenosquamous carcinoma. There were 180 recurrences (23.1%), mostly distant metastases (42.8%). There were fewer recurrences after resection of tumors <2 cm compared to tumors 2 cm or larger (6.49% vs 31.3%, p = 0.00011). Only 37.7% of recurrence/metastases were treated with first-line carboplatin/paclitaxel/bevacizumab, but it was associated with better OS compared to other regimens (median OS 40.1 vs 24.8 months, p = 0.03). A significant portion of patients with localized cervical cancer relapse despite radical therapy, with LVI and p16 negativity associated with poorer survival. Surgical resection may still play a role in stage IB disease, while RT, brachytherapy, and concurrent chemotherapy should be considered first-line therapy in stage II-IV diseases. First-line carboplatin, paclitaxel, and bevacizumab for recurrence shows improved survival.

Endothelial cell-specific molecule 1 drives cervical cancer progression

The expression, biological functions and underlying molecular mechanisms of endothelial cell-specific molecule 1 (ESM1) in human cervical cancer remain unclear. Bioinformatics analysis revealed that ESM1 expression was significantly elevated in human cervical cancer tissues, correlating with patients’ poor prognosis. Moreover, ESM1 mRNA and protein upregulation was detected in local cervical cancer tissues and various cervical cancer cells. In established and primary cervical cancer cells, ESM1 shRNA or CRISPR/Cas9-induced ESM1 KO hindered cell proliferation, cell cycle progression, in vitro cell migration and invasion, and induced significant apoptosis. Whereas ESM1 overexpression by a lentiviral construct accelerated proliferation and migration of cervical cancer cells. Further bioinformatics studies and RNA sequencing data discovered that ESM1-assocaited differentially expressed genes (DEGs) were enriched in PI3K-Akt and epithelial-mesenchymal transition (EMT) cascades. Indeed, PI3K-Akt cascade and expression of EMT-promoting proteins were decreased after ESM1 silencing in cervical cancer cells, but increased following ESM1 overexpression. Further studies demonstrated that SYT13 (synaptotagmin 13) could be a primary target gene of ESM1. SYT13 silencing potently inhibited ESM1-overexpression-induced PI3K-Akt cascade activation and cervical cancer cell migration/invasion. In vivo, ESM1 knockout hindered SiHa cervical cancer xenograft growth in mice. In ESM1-knockout xenografts tissues, PI3K-Akt inhibition, EMT-promoting proteins downregulation and apoptosis activation were detected. In conclusion, overexpressed ESM1 is important for cervical cancer growth in vitro and in vivo, possibly by promoting PI3K-Akt activation and EMT progression. ESM1 represents as a promising diagnostic marker and potential therapeutic target of cervical cancer.

The Prognostic Value of Systemic Immune-Inflammation Index (SII) and Red Cell Distribution Width (RDW) in Cervical Cancer Patients Treated with Radiotherapy

<h3>Purpose/Objective(s)</h3> To assess the association of pre-treatment systemic immune-inflammation index (SII) and red cell distribution width (RDW) with overall survival (OS) in patients treated for primary localized cervical cancer with radiotherapy. <h3>Materials/Methods</h3> The study cohort includes retrospectively collected data of 249 consecutive cervical cancer patients treated with radical intent between 2011 and 2017. The database was based on medical history of the patients and survival data from National Cancer Registry. The statistical analysis included Kaplan-Meier method, log-rank testing and Cox proportional hazards regression model. The cut-off values for log-rank testing were based on available literature data. <h3>Results</h3> The median age of the patients was 57.2 (IQR 49.2-64.5). The patients undergone a combination of external beam radiotherapy (100%), brachytherapy (98%) and concurrent chemotherapy (90%). The 5-year OS was 69.9% and 60.2% patients were alive at the time of the analysis. The results of the Cox model are presented in Table 1. Both SII and RDW were associated with survival in univariate analysis and remained independent prognostic factors in stepwise selection multivariate analysis. The OS was significantly higher in low SII (≤1000 and >1000; p=0.006) and low RDW (≤14.5% and >14.5%; p=0.002) groups. The 5-year OS was 73.5% and 60.2% for SII, and 74.3%, and 52.7% for RDW respectively. <h3>Conclusion</h3> SII and RDW are significantly associated with overall survival and could be used to improve the accuracy of pre-treatment prognostic assessment, in patients treated with radiotherapy for cervical cancer. Table: Univariate and multivariate Cox Regression analysis of HR for OS in patients with cervical cancer

A novel point-of-care ethyl cellulose ethanol ablative therapy for the enhancement of paclitaxel in local recurrent cervical cancer treatment (308.5)

<b>Objectives:</b> Cervical cancer is a leading cause of global cancer mortality. Low- and middle-income countries (LMICs) suffer nearly 90% of the disease burden; this is largely due to the unavailability of technologies for cervical cancer treatment. A local ablation is a promising option for patients with recurrent localized cervical cancer who are not surgical candidates and progress despite systemic therapy and radiation. We developed a low-cost polymer-assisted ethanol ablative therapy, ethyl-cellulose ethanol (ECE) ablation, which overcomes the main shortcoming of traditional ethanol ablation: off-target ethanol leakage. The effectiveness of ECE ablation has been previously demonstrated in pre-clinical head and neck and breast cancer models. Here, we investigated the effects of paclitaxel, either locally or systemically administered, and local ablation with ECE in a preclinical model of cervical cancer. <b>Methods:</b> A syngeneic cervicovaginal tumor model was established in C57BL/6 mice using TC1-Luc, HPV16 E6/E7+ cells expressing luciferase. To determine whether ECE enhances the antitumor effect of paclitaxel, tumor-bearing mice were randomized for treatment with systemic intraperitoneal paclitaxel (P_ip) alone, local intratumoral paclitaxel (P_it) alone, P_ip + ECE, or P_it + ECE therapy (<i>n</i> = 5 per group). Tumors were monitored with calipers and bioluminescence imaging via a Perkin-Elmer <i>in vivo</i> imaging system (IVIS); tumors were imaged on days 1, 2, 3, 7, and 14. Paclitaxel therapy was administered one day prior to ECE at a 20 mg/kg dose either intraperitoneally or intratumorally. ECE was performed via intratumoral injection of 100 µL ethanol ethyl cellulose under IVIS image guidance. Mice were monitored until day 60 at the end of the study. Fig. 1 <b>Results:</b> Representative IVIS images of TC-1 Luc tumors treated with ECE + P_ip, ECE+ P_it, P_ip, and P_it on days 1 (pre-treatment), 7, and 14 post-implantation are shown in Figure 1A. Tumor growth measured by total radiance intensity (integral of light signal intensity throughout the tumor area) showed that both ECE + P_ip and ECE + P_it had significantly decreased tumor growth compared to P_ip, and P_it groups, as shown in Figure 1B (p < 0.05). Overall, mice treated with ECE + P_it performed best with significantly lower total radiance compared to ECE + P_ip, P_ip, and P_it groups. Mice in the ECE + P_ip, ECE+ P_it, P_ip, and P_it groups were observed until tumor burden was reached or the end of the study (day 60). Tumor volumes were significantly decreased in both ECE + P_ip and ECE + P_it compared to P_ip and P_it groups, as shown in Figure 1C. Additionally, mice treated with the ECE + P_it group lived significantly longer than ECE + P_ip, P_ip, and P_it groups. Survival was significantly improved with P_it compared to P_ip and with ECE + P_it compared to ECE + P_ip (p < 0.05). Mice treated with ECE + P_ip lived significantly longer than mice treated with P_ip (p < 0.05), as shown in Figure 1D. At the end of the study, fewer mice had tumors detectable via IVIS after treatment in the ECE + P_it (1 out of 5 mice), compared to ECE + P_ip (5 out of 5 mice), P_ip (5 out of 5 mice), and P_it (5 out of 5 mice) groups. <b>Conclusions:</b> The antitumor effect of paclitaxel is enhanced when paired with ECE ablation in a pre-clinical model of HPV-positive cancer. This proof-of-concept study lays the groundwork for future translational work using paclitaxel in combination with ECE ablation to increase the accessibility of low-cost treatment for recurrent cervical cancer.

Use of hypnotics among women diagnosed with cervical cancer – A population-based cohort study

ObjectivePrevious studies suggest that sleeping problems are frequent after cervical cancer. However, the evidence on the use of hypnotics is sparse. We investigated if women diagnosed with cervical cancer have an increased risk of using hypnotics and identified risk factors for prolonged use. MethodsIn this nationwide register-based cohort study, 4264 women diagnosed with cervical cancer from 1997 to 2013 and 36,632 cancer-free women were followed in registers until 2016. Prolonged use of hypnotics was defined as more than three prescriptions with no more than three months in between. Data were analysed using Cox proportional hazards regression models and multistate Markov models separately for women with localized and advanced cervical cancer. ResultsThe rate of first use of hypnotics was substantially increased during the first year after cervical cancer diagnosis compared to cancer-free women (HRlocalized 4.4, 95% CI 3.9–5.1; HRadvanced 8.9, 95% CI 7.5–10.6) and remained markedly increased for up to five years after diagnosis. Dependent on stage of disease and age, 1.4 to 4.7 excess women per 100 with cervical cancer were prolonged users of hypnotics compared to cancer-free women one year after diagnosis. Risk factors for prolonged use of hypnotics were higher age, short education, previous use of antidepressants or anxiolytics, and advanced disease. ConclusionsWomen diagnosed with cervical cancer are at increased risk of prolonged use of hypnotics. For the majority, treatment with hypnotics is initiated within the first year after cancer diagnosis, but the rate of first use is increased for up to five years.

Efficacy and Side Effects of Irinotecan Combined with Nedaplatin versus Paclitaxel Combined with Cisplatin in Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer and Tumor Marker Analysis: Based on a Retrospective Analysis.

Objective A case-control study was adopted to investigate the efficacy and side effects of irinotecan combined with nedaplatin (NP) versus paclitaxel combined with cisplatin for locally advanced cervical cancer (CC) neoadjuvant chemotherapy (NACT) and to analyze the changes in tumor marker levels. Methods A total of 96 patients with locally advanced CC who were treated from October 2019 to October 2021 were enrolled in our hospital as the research subjects, and their clinical data were collected for retrospective analysis and grouped according to their treatment regimens. Among them, 53 patients received paclitaxel combined with cisplatin as the control group, and the other 43 patients received irinotecan combined with NP as the observation group. The clinical effectiveness of neoadjuvant chemotherapy and alterations in tumor markers (CEA, AFP, CA125, and SCCA) were compared between the two groups. The incidence of common chemotherapy side effects was observed and compared between the two groups, including nausea and vomiting, abdominal pain and diarrhea, liver function impairment, bone marrow suppression, transient hyperglycemia, rash, ECG abnormalities, peripheral neurotoxicity, and muscle aches and pains. Results The clinical efficiency of neoadjuvant chemotherapy was 97.67% in the observation group and 81.13% in the control group, with no statistically significant difference between the groups (P > 0.05). There was no significant difference in CEA, AFP, and CA125 between the two groups before and after chemotherapy, but the decrease of SCCA before and after chemotherapy was statistically significant. There was no significant difference in the incidence of liver function damage, myelosuppression, abnormal ECG, and rash between the two groups (P > 0.05). There are statistically significant differences in the incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches between the observation and control groups (P < 0.05). The incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches was higher in the control group than in the observation group, with statistically significant differences (P < 0.05). The difference in the incidence of diarrhea and abdominal pain between the observation group and the control group was statistically significant (P < 0.05), and the incidence of diarrhea and abdominal pain in the observation group was higher than that in the control group. Conclusion Irinotecan in combination with nedaplatin can be an effective neoadjuvant chemotherapy regimen for advanced localized cervical cancer, particularly in patients with combined diabetes.

Propensity Score Matched Study of Tri-Weekly vs. Weekly Platinum-Based Chemotherapy Concurrent with Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

Objective: To compare tumor control and toxicity between tri-weekly chemotherapy and weekly platinum-based chemotherapy in locally advanced cervical cancer using the propensity score matching method.Material and Methods: DESIGN: Retrospective cohort with propensity score matched population. SETTING: Four university hospitals. PARTICIPANTS: 781 advanced local cervical cancer patients. INTERVENTION: tri-weekly platinum-based chemoradiotherapy versus weekly chemoradiotherapy OUTCOMES: Overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and toxicity, including hematological and renal toxicity.Results: Overall median follow-up time was 59.5 months. After the propensity score matching process was completed, 326 patients were analyzed (163 in each group). The five-year OS was 66% and 64% (p 0.630); five-year LRFS was 85% and 81% (p 0.209); five-year RRFS was 89% and 94% (p 0.307); and five-year DMFS was 75% and 79% (p 0.420) in the tri-weekly and weekly groups, respectively. The patients in the tri-weekly and the weekly group had grade 2-3 neutropenia (10.5% vs 2.5%). The other toxicities appeared to be similar in both groups in terms of white blood count, platelet and creatinine.Conclusion: There was a potential small benefit of local control (4%) and overall survival (2%) with the tri-weekly regimen but we could not demonstrate statistical significance. However, this came at the price of an increase of 7% to 8% in grade 2-3 neutropenia.

PET/MRI and PET/CT Radiomics in Primary Cervical Cancer: A Pilot Study on the Correlation of Pelvic PET, MRI, and CT Derived Image Features.

To evaluate the correlation of radiomic features in pelvic [2-deoxy-2-18F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging and computed tomography ([18F]FDG PET/MRI and [18F]FDG PET/CT) in patients with primary cervical cancer (CCa). Nineteen patients with histologically confirmed primary squamous cell carcinoma of the cervix underwent same-day [18F]FDG PET/MRI and PET/CT. Two nuclear medicine physicians performed a consensus reading in random order. Free-hand regions of interest covering the primary cervical tumors were drawn on PET, contrast-enhanced pelvic CT, and pelvic MR (T2 weighted and ADC) images. Several basic imaging features, standard uptake values (SUVmean, SUVmax, and SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and more advanced texture analysis features were calculated. Pearson's correlation test was used to assess the correlation between each pair of features. Features were compared between local and metastatic tumors, and their role in predicting metastasis was evaluated by receiver operating characteristic curves. For a total of 101 extracted features, 1104/5050 pairs of features showed a significant correlation (ρ ≥ 0.70, p < 0.05). There was a strong correlation between 190/484 PET pairs of features from PET/MRI and PET/CT, 91/418 pairs of CT and PET from PET/CT, 79/418 pairs of T2 and PET from PET/MRI, and 50/418 pairs of ADC and PET from PET/MRI. Significant difference was seen between eight features in local and metastatic tumors including MTV, TLG, and entropy on PET from PET/CT; MTV and TLG on PET from PET/MRI; compactness and entropy on T2; and entropy on ADC images. We demonstrated strong correlation of many extracted radiomic features between PET/MRI and PET/CT. Eight radiomic features calculated on PET/CT and PET/MRI were significantly different between local and metastatic CCa. This study paves the way for future studies to evaluate the diagnostic and predictive potential of radiomics that could guide clinicians toward personalized patients care.

Magnetoencephalographic Signatures of Hierarchical Rule Learning in Fetuses and Newborns

To analysis the clinical curative effect on bladder function recovery after radical hysterectomy with acupuncture and acu-physiotherapy.A total of 564 cervical cancer patients in the gynecology department who received radical hysterectomy from January 2011 to December 2017 in Qilu Hospital of Shandong University were collected. According to the inclusion and exclusion criteria, we studied 360 case records at last, with 120 cases respectively. Patients got treatment of acupuncture [acupuncture at Zhōngwǎn (中脘 CV12), Tiānshū (天枢 ST25), Shuǐdào (水道 ST28), Tàichōng (太冲 LI3), Sānyīnjiāo (三阴交 SP6), Zúsānlǐ (足三里 ST36) and Yīnlíngquán (阴陵泉 SP9)], or acu-physiotherapy with two large-size electrodes placed on the bladder area above the pubic symphysis besides acupuncture, from the 3rd day after operation once a day till the 14th day that removing the indwelling catheter. And the blank group got no other auxiliary treatment except scrubbed the meatus orifice with iodophor twice a day. We tested the residual urine volume 6 h later after removement of indwelling catheter. Residual urine volume more than 100 mL was defined as urinary retention, and the volume less than 50 mL was defined as adequate bladder emptying.We analyzed patients’ age, the International Federation of Gynecology and Obstetrics (FIGO) stage, operation duration, amount of hemorrhage, depth of myometrium infiltration, cancer embolus, parametrium invasion, lymphatic metastasis, treating methods and residual urine volume recorded in case records, and there was no significant difference between every two groups (P >0.05). The incidences of urinary retention of the acupuncture group, the acu-physiotherapy group and the blank group were 24.17%, 21.67%, and 44.17%, indicating that both treating methods have significant effects (P <0.05), and acupuncture group was a little better than acu-physiotherapy group. The bladder function recovery rates of the 3 groups were 44.17%, 56.67%, and 40.83% correspondingly, which had significant difference between acu-physiotherapy group and blank group (P <0.05). Both acupuncture and acu-physiotherapy could reduce the incidence of urinary retention for the patients of Ib1 and IIa1 stages (P <0.01), whilst for patients of Ib2 and IIa2 stages, neither of the two methods was effective (P >0.05).Both acupuncture and acu-physiotherapy could prevent urinary retention after radical hysterectomy for local early cervical cancer (Ib1 and IIa1 stages) effectively, and acupuncture was a little more effective than acu-physiotherapy group. Acupuncture together with modulated medium frequency eletro-therapy could improve the cure rate of bladder function and minimize the residual urine volume.

A novel treatment for recurrent localized cervical cancer using point-of-care ethyl cellulose ethanol ablation with concurrent cytotoxic therapy.

e17507 Background: Historically, the only curative option for patients with recurrent localized cervical cancer after platinum-based chemotherapy and radiation is pelvic exenteration. For non-surgical candidates, treatment options include systemic therapy with chemotherapy, bevacizumab or pembrolizumab. However, these therapies are not curative. Addition of local ablative therapy to systemic therapy is a promising option, as this combination can induce a more robust local antitumor immune response. We developed a polymer-assisted ethanol ablative therapy, Point-of-care Ethanol Ethyl Cellulose (PEEC), that overcomes the main shortcoming of traditional ethanol ablation: off-target ethanol leakage. We previously demonstrated the success of PEEC in pre-clinical head and neck and breast cancer models. Here, we hypothesized that combination of reduced tumor acidity using sodium bicarbonate (bicarb) and decreased regulatory T cells using systemic or local chemotherapy would prime the tumor immune microenvironment for PEEC as a novel treatment strategy for recurrent localized cervical cancer. Methods: An HPV16 E6/E7+ TC1-Luc cell line was used to establish a syngeneic cervicovaginal tumor model in C57BL/6 mice. First, intratumoral PEEC was compared to sham ablation (saline). Tumor bearing mice were randomized to receive either PEEC or sham (n = 5 each) 2 days after tumor inoculation. Tumor volume and growth were measured with calipers and a Perkin Elmer in vivo imaging system (IVIS) respectively; tumors were imaged on days 1, 2, 3, 7, 14 and 28. Tumor weight was measured by weighing reproductive tracts. Next, we tested whether local and/or systemic cyclophosphamide (cyclo) with bicarb improved response to PEEC. Tumor bearing mice were randomized to receive systemic or local cyclo+bicarb and/or PEEC. The same ablation and tumor monitoring schedule was used, with bicarb (200 mM) added to the drinking water and cyclo (50 mg/kg) given either intraperitoneally or locally on day 1 following tumor inoculation. Results: Tumors treated with PEEC had significantly smaller volumes by day 7 and onward compared to sham (p &lt; 0.005). Tumors treated with PEEC also had significantly decreased tumor weights (at necropsy) compared to sham (p &lt; 0.0002). The PEEC groups showed prolonged survival compared to sham (p &lt; 0.05). Local cyclo+bicarb+PEEC therapy was superior to all other treatment groups with no measurable tumor luminescence signal (via IVIS) in all five mice (5/5) on day 14 and onward. Systemic cyclo+bicarb+PEEC resulted in 4/5 mice with no signal. PEEC alone led to no signal in 3/5 mice. Sham alone showed tumor progression in all 5 mice. Conclusions: PEEC ablation is enhanced by concurrent cytotoxic therapy and significantly controls HPV16 E6/E7+ cervicovaginal tumor growth, supporting future clinical translation for treatment of recurrent localized cervical cancer.