Cervical Cancer Therapy Research Articles

Unveiling the multitargeted repurposing potential of taxifolin (dihydroquercetin) in cervical cancer: an extensive MM\GBSA-based screening, and MD simulation study.

Cervical cancer is a significant cause of morbidity and mortality in women worldwide. Despite the availability of effective therapies, the development of drug resistance and adverse side effects remain significant challenges in cervical cancer treatment. Thus, repurposing existing drugs as multitargeted therapies for cervical cancer is an attractive approach. In this study, we extensively screened the complete prepared FDA-approved drugs and identified the repurposing potential of taxifolin, a flavonoid with known antioxidant and anti-inflammatory properties, as a multitargeted therapy for cervical cancer. We performed a computational analysis using molecular docking with various sampling algorithms, namely HTVS, SP, and XP algorithms, for robust sampling pose and filtered with MM/GBSA analysis to determine the binding affinity of taxifolin with potential targets involved in cervical cancer, such as Symmetric Mad2 Dimer, replication initiation factor MCM10-ID, TPX2, DNA polymerase epsilon B-subunit, human TBK1, and alpha-v beta-8. We then conducted MD simulations to investigate the stability and conformational changes of the complex formed between taxifolin and the mentioned proteins. Our results suggest that taxifolin has a high binding affinity ranging from -6.094 to -9.558kcal/mol, indicating its potential as a multitargeted therapy for cervical cancer. Furthermore, interaction fingerprints, pharmacokinetics and MD simulations revealed that the Taxifolin-target complexes remained stable over the simulation period, indicating that taxifolin may bind to the targets for an extended period. Our study suggests that taxifolin has the potential as a multitargeted therapy for cervical cancer, and further experimental studies are necessary to validate our findings.

Planning Target Volume Margin Determination for Volumetric Modulated Arc Therapy Planning in Cervix Cancers Using an Empty Bladder Protocol

OBJECTIVE To evaluate the planning target volume (PTV) margin and bladder volume variation of volumetric modulated arc therapy (VMAT) in cervical cancer using an empty bladder protocol. METHODS Ten patients with cervical cancer who had indications to receive whole pelvic radiotherapy and who had been identified to receive whole pelvic irradiation with a dose of 46-55.2 Gy in 23 fractions planned by VMAT were included. International Commission on Radiation Units and Measurements (ICRU) Report 83 was used to report plan parameters. The empty bladder protocol is designed for use with all patients before simulation and irradiation. From June 2020 to February 2021, 215 fractions from the 10 patients were evaluated. The ‘all fraction’ set-up errors were recorded using cone-beam computed tomography (CBCT) and were interpreted as error margins using the Van Herk Formula. RESULTS The calculated PTV margins were 0.75, 0.84, and 0.98 cm on the X, Y, and Z-axes, respectively. The median volume of the bladder before irradiation was 40.6 cc, with an interquartile range of 31.9 to 59.2 cc. The average change in bladder volume from the planning volume was 23.56%. CONCLUSIONS Using the empty bladder protocol, the clinical target volume (CTV) to PTV margin was 1 cm following the Van Herk formula. No patients experienced side effects of grade 3 or greater. The empty bladder protocol is a method which can reduce target placement error and reduce patient discomfort without causing serious side effects. KEYWORDS PTV margin, VMAT, IGRT, Cervix cancer, Empty bladder

Clinical characteristics of cervical cancer in patients infected with human immunodeficiency virus

Background. Infection caused by human immunodeficiency virus (HIV) is a slowly developing anthroponosis with a long course and a variety of clinical manifestations, which finally results in acquired immunodeficiency syndrome (AIDS). Over the past 4 decades, the HIV / AIDS pandemic has been considered as one of the world’s most serious public health problems. Globally, there were approximately 38 million people living with HIV in 2022; 53 % of them were women. The number of HIV-infected patients living in Russia reaches 1,168,000. The incidence and prevalence of HIV infectionvaries across different regions of Russia. High prevalence of cervical cancer usually correlates with HIV prevalence, which is associated with the long-term and aggressive persistence of human papillomavirus (HPV) in HIV patients. HIV co-infection is believed to be the main risk factor for HPV-related precancerous lesions to the cervical epithelium and their rapid progression to invasive cancer. Aim. To analyze risk factors for poor prognosis in HIV-infected patients with HPV. Materials and methods. This study included 15 HIV-infected patients with cervical cancer treated in Novosibirsk Regional Clinical Oncology Dispensary or Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of Russia between 2016 and 2021. Results. Median age of the patients was 38 years; all of them were HPV-positive. Their viral load was >400 copies / mL and baseline CD4+ cell count ≥350 cells / mL. All patients were diagnosed with AIDS, given the presence of HPV infection. During the therapy for cervical cancer, patients also received combination antiretroviral treatment, including Lamivudine Advanced at a dose of 300 mg / day. Ten patients received comprehensive treatment, while 8 patients received chemoradiotherapy. Conclusion. Given the more aggressive course of cervical cancer in HIV-infected patients, their treatment plan should be developed by a multidisciplinary team, including an infectious disease specialist, clinical pharmacologist, radiotherapist, and gynecological oncologist. Such patients should receive maximal antitumor treatment, as well as intensive antiretroviral therapy. HIV-positive women with cervical cancer require special attention to ensure treatment completion and to optimize long-term outcomes.

Advance in Nanomedicine for Improving Mucosal Penetration and Effective Therapy of Cervical Cancer.

Insufficient intratumor drug distribution and serious adverse effects are often associated with systemic chemotherapy for cervical cancer. Considering the location of cervical cancer, access to the cervix through the vagina may provide an alternative administration route for high drug amounts at the tumor site, minimal systemic exposure as well as convenience of non-invasive self-medication. Enormous progress has been made in nanomedicine to improve mucosal penetration and enhance the effectiveness of therapy for cervical cancer. This review article first introduce the physiological state of cervicovaginal cavity and the characteristics of intravaginal environment in cervical cancers. Based on introduction to the physiological state of cervicovaginal cavity and the characteristics of intravaginal environment in cervical cancers, both "first mucus-adhering then mucosal penetration" and "first mucus-penetrating then mucosal penetration" strategies are discussed with respect to mechanism, application condition, and examples. Finally, existing challenges and future directions are envisioned in the rational design, facile synthesis, and comprehensive utilization of nanomedicine for local therapy of cervical cancer. This review is expected to provide useful reference information for future research on nanomedicine for intravaginally administered formulations for topical treatment of cervical cancer.

Biosynthetic of Green Zinc Oxide Nanoparticles with Effect on Cancer Cell Line Hela

The cytotoxic impact of biosynthetic zinc oxide nanoparticles (ZnONPs) was investigated using Vitex agnus-castus, which has been shown to have Effective compounds that suppress cancer cell proliferation. Zinc oxide nanoparticles were biosynthesized in the laboratories of the Biology department /College of Education for the Pure Sciences /University of Diyala. The phenotypic and structural characteristics of biosynthetic nanoparticles were identified using scanning electron microscopy (SEM). The majority of ZnONPs are dense and spherical in shape, with diameters ranging from (20-61) nm, and were discovered on the cervical cancer cell line Hela and compared to the normal line Human Foreskin Fibroblast cells (HFF) using the MTT stain test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium ). Cytotoxicity experiments were conducted at the Iraqi Center for Cancer Research / Al-Mustansiriya University. This study showed inhibitory activity on Hela cervical cancer cells, where the highest inhibition rate reached 93.6% at a concentration of 200 µg/ml. This raises the prospect of finding a viable therapy for cervical cancer (Hela) or any other malignancy using nanoparticle manufacturing technologies. Keywords: Biosynthetic, Green nanoparticles, Cancer cell, Hela, GC-MS.

Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12.

In this study, an innovative transdermal peptide, #PKU12, was developed based on transdermal peptide TD-1, and the anti-tumor effect of PKU12-based siRNA against HPV was investigated in vivo. Furthermore, transcriptome differences between PKU12 + siRNA treatment and control groups were compared to assess treatment effects. The top five upregulated and downregulated genes identified by RNA sequencing were further subjected to survival analysis. The present study, for the first time, showed that this novel peptide could enhance the transdermal delivery of the siRNA targeting HPV16 L1, E6, and E7. PKU12-based siRNA delivery significantly repressed the mRNA expression levels of HPV16 L1, E6, and E7 in the SiHa xenograft tumors and attenuated tumor growth as well. The RNA-sequencing results showed that a total of 586 DEGs were detected in the PKU12 + siRNA-treated tumor tissues compared to the control tumor tissues. The GSEA analysis revealed that DEGs were inversely associated with the HIF-1 signaling pathway, the TNF signaling pathway, the AGE-RAGE signaling pathway, the NF-kappa B signaling pathway, ferroptosis, the IL-17 signaling pathway, ovarian steroidogenesis, and rheumatoid arthritis. Further functional enrichment analysis revealed that DEGs were significantly enriched in several key pathways, including cytokine-cytokine receptor interaction, the TNF signaling pathway, and the IL-17 signaling pathway. High expression of MYH1, MYH4, FGG, DEPP1, and ZBTB16 was associated with shorter overall survival of patients with cervical cancer; high expression of SULT1E1, RAB3C, CXCR3, and PROX2 was associated with longer overall survival of patients with cervical cancer. In conclusion, the transdermal peptide PKU12 is potentially a good candidate for a siRNA delivery vehicle for the treatment of cervical cancer.

Maintenance therapy for patients with recurrent or metastatic cervical cancer: A multicentre, cohort study.

e17518 Background: Maintenance therapy with alternative agents after chemotherapy was shown to improve the overall survival in some advanced cancers such as breast cancer, lung cancer, ovarian cancer and so on. However, maintenance therapy is not accepted as the standard treatment for recurrent/metastatic cervical cancer. Aim of this study is to elucidate the efficacy of maintenance therapy in cervical cancer and to explore the factors associated with the prognosis of recurrent or metastatic cervical cancer. Methods: In this multicenter cohort study, we retrospectively collected patients with a diagnosis of either recurrent or stage IVB cervical cancer to receive first-line chemotherapy with or without maintenance therapy. Patients did not have disease progression with chemotherapy and were divided into maintenance therapy group (Arm A) and conventional chemotherapy group (Arm B). Information on clinical characteristics, metastasis information, treatment outcome and survival of patients was collected using an electronic medical record system. The endpoints of the study were OS and PFS. Data were analyzed for general characteristics and survival using SPSS25.0 software, and the results were considered statistically significant at P < 0.05. Results: Between January 2019 and July 2021, a total of 270 patients were enrolled from 6 institutions in China. 26 patients were excluded because of short treatment cycles (less than 3 cycles). Finally, a total of 66 patients in Arm A and 178 patients in Arm B were analyzed for survival. The addition of maintenance significantly prolonged overall survival. Overall survival at 3 year was 50.1% in Arm A and 27.8% in Arm B (median overall survival, ≥36 months vs. 22 months; P < 0. 001). The median progression-free survival was 21 months in Arm A and 14 months in Arm B (P = 0.025). Univariate survival analysis showed that age, maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were associated with PFS. Further multifactorial analysis showed that maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were independent prognostic factors for patients with recurrent or metastatic cervical cancer. Conclusions: The addition of maintenance therapy significantly prolonged overall survival as well as progression-free survival in patients with recurrent or metastatic cervical cancer and did not increase the incidence of serious adverse events. It is time to consider maintenance therapy as the standard treatment after conventional chemotherapy for recurrent or metastatic cervical cancer, rather than waiting for disease progression.

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

BackgroundThe European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. ObjectiveTo develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. MethodsQuality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n = 99). ResultsUsing a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1–6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7–17 are related to treatment indicators. Quality indicators 18 and 19 are related to patient outcomes. DiscussionThis set of quality indicators is a major instrument to standardize the quality of radiation therapy in cervical cancer. A scoring system combining surgical and radiotherapeutic quality indicators will be developed within an envisaged future ESGO accreditation process for the overall management of cervical cancer, in an effort to support institutional and governmental quality assurance programs.

The sub-molecular characterization identification for cervical cancer

BackgroundThe efficacy of therapy in cervical cancer (CESC) is blocked by high molecular heterogeneity. Thus, the sub-molecular characterization remains primarily explored for personalizing the treatment of CESC patients. MethodsDatasets with 741 CESC patients were obtained from TCGA and GEO databases. The NMF algorithm, random forest algorithm, and multivariate Cox analysis were utilized to construct a classifier for defining the sub-molecular characterization. Then, the biological characteristics, genomic variations, prognosis, and immune landscape in molecular subtypes were explored. The significance of classifier genes was validated by quantitative Real-Time PCR, cell transfection, cell colony formation assay, wound healing assay, cell proliferation assay, and Western blot. ResultsThe CESC patients were classified into two subtypes, and the high classifier-score patients with significant differences in ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway showed a poorer prognosis in OS (p < 0.001), DFI (p = 0.016), PFI (p < 0.001) and DSS (p < 0.001), and with high the M0 Macrophage and resting Mast cells infiltration and low HLA family gene expression. Moreover, the constructed classifier owns a high identified accuracy in the tumor/normal groups (AUC: 0.993), the tumor/CIN1–CIN3 groups (AUC: 0.963), and normal/CIN1–CIN3 groups (AUC: 0.962), and the total prediction performance is better than currently published signatures in CESC (C−index: 0,763). The combined prediction performance further indicated that Nomogram (AUC = 0.837) is superior to the classifier (AUC = 0.835) and Stage (AUC = 0.568), and the C−index of calibration curves is 0.784. The potential biological function of classifier genes indicated that silencing GALNT2 inhibited the cancer cell's proliferation, migration, and colony formation; Conversely, the cancer cell's proliferation, migration, and colony formation were increased after the upregulation of GALNT2. The Epithelial-Mesenchymal Transition Experiment showed that GALNT2 knockdown might reduce the levels of Snail and Vimentin proteins and increase E-cadherin; Conversely, the levels of Snail and Vimentin proteins were increased, E-cadherin was reduced by GALNT2 upregulation. ConclusionThe classifier we constructed may help improve our understanding of subtype characteristics and provide a new strategy for developing CESC therapeutics. Remarkably, GALNT2 may be an option to directly target drivers in CESC cancer therapy.

EE500 Cost-Effectiveness Analysis of Cemiplimab As Second-Line Therapy for Recurrent Cervical Cancer in Japan

Patients with recurrent cervical cancer have a poor response to standard chemotherapy. Although cemiplimab, new anti-PD-1 drug, showed superiority over chemotherapy in improving overall survival, its cost-effectiveness is not necessarily clarified. This study aimed to evaluate the cost-effectiveness of cemiplimab for recurrent cervical cancer from the payer’s perspective in Japan.

Curcumin-reduced gold nanoparticles facilitate IL-12 delivery to a cervical cancer in vitro cell model.

Aim: To synthesize curcumin-reduced gold nanoparticles (AuNPs) for the efficient delivery to and expression of the IL-12 gene in cervical cancer (HeLa) cells in vitro. Methods: Curcumin-reduced AuNPs were synthesized, stabilized with poly-L-lysine and PEG, conjugated to IL-12 DNA and physicochemically characterized. Cytotoxicity and IL-12 expression were accessed in vitro. Results & discussion: Stable, spherical AuNPs effectively compacted and protected the IL-12 DNA and tolerated well in vitro. Real-time quantitative PCR and ELISA confirmed the successful delivery and expression of the IL-12 gene in HeLa cells. Conclusion: The favorable attributes of this AuNP-delivery system and the significant IL-12 expression obtained augur well for cytokine-based therapy or immunotherapy in cervical cancer.

Incidence of low volume metastases after retrospective ultrastaging of patients with early stage, node negative cervical cancer and receipt of post-operative adjuvant therapy.

e17506 Background: Nodal positivity directs receipt of adjuvant post-operative therapy in early stage cervical cancer; the significance of low-volume metastases (LVM) is unclear. We hypothesized patients with early stage cervical cancer with high risk factors on pathology and negative nodes would have a higher incidence of LVM on retrospective ultrastaging. Methods: This retrospective cohort study collected clinicopathologic data via chart review on early stage cervical cancer patients treated at our institution from January 2011 - June 2021. The study was approved by the IRB. Inclusion criteria included patients &gt;18 years old who underwent a radical hysterectomy/trachelectomy with pathology-proven negative nodes who went on to be recommended for post-operative adjuvant therapy, due to factors defined under Sedlis or Peters criteria. Patients were excluded for rare histology or prior pelvic radiation. Resected nodes were ultrastaged, performed by 4 re-cuts at 20 microns on each lymph node staging, stained with H&amp;E and one level with CK AE1/AE3 to identify presence of any LVM. Analysis was performed via descriptive statistics with Microsoft Excel. Results: 199 patients were treated with radical hysterectomy between 2011-2021; 20 met study criteria. The average age at diagnosis was 51 years: 65% Caucasian, 25% Black, 10% Latino. 75% had Squamous cell carcinoma, 85% (n=17) of the cohort were a 2009 FIGO pathologic Stage 1B. 35% of the cohort underwent a minimally invasive hysterectomy. Tumor size varied: 25% (n=5) of tumors were less than 2 cm, 35% (n=7) of tumors measured greater than or equal to 2 cm, 30% (n=6) measured greater than or equal to 3 cm, and 10% (n=2) measured greater than or equal to 4 cm. Lymphovascular space invasion was noted in 75% (n=15) of samples. Superficial stromal invasion was noted in 5% (n=1), deep stromal invasion was noted in 65% (n=13). 5% (n=1) of patients had parametrial invasion, and 5% (n=1) had positive margins. A full bilateral pelvic lymphadenectomy was performed on every patient, with 245 nodal blocks ultrastaged. 80% (n=16) received adjuvant therapy: 3 chemoradiation, 13 radiation, 4 declined. LVM was identified in 5% (n=1) patients; a macrometastases was identified as missed in the initial pathologic evaluation of another. 10% (n=2) patients developed recurrence, one at the pelvic brim and one distant (lung). The patient with the newly identified LVM received adjuvant radiation, and developed recurrence at the pelvic brim. Conclusions: The results of this small study suggest traditional “high risk” factors in surgically managed cervical cancer is associated with positive ultrastaged nodes in 5% of cases. This finding suggests that utilization of sentinel node identification with associated ultrastaging will accurately identify patients who will benefit from adjuvant therapy.

Penpulimab plus platinum-based chemotherapy combined with anlotinib in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, open-label phase Ⅱ study (ALTN-AK105-II-06).

e17512 Background: Penpulimab is a novel human immunoglobulin G1 (IgG1) anti-programmed cell death-1 (PD-1) antibody. Anlotinib is a novel oral multi-target tyrosine kinase inhibitor and primary targeted to VEGFR, FGFR, PDGFR and c-Kit. ALTN-AK105-II-06 (ChiCTR2200062897) is a single-arm, open phase Ⅱ clinical trial aimed to assess the effiacy and safety of penpulimab plus chemotherapy combined with anlotinib as fist-line therapy for persistent, recurrent, or metastatic cervical cancer. Methods: Eligible adults with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy and not amenable curative treatment, with CPS more than 1% PD-L1 expression, and ECOG 0-1 were considered eligible for enrolment. Patients received 2 cycles of penpulimab 200mg Q3W + chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) + anlotinib 10mg, following with penpulimab and anlotinib for maintenance therapy. Patients were treated on continuous 3 weeks of penpulimab for up to 2 years, until disease progression, or unacceptable toxicities. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), 6-month PFS, safety and quality of life. Results: From Sep 2022 to Feb 2023, 9 patients were recruited with a median age of 56.4 years (range: 45-66), FIGO histopathological stage IIB (33.3%), III (44.5%) and IV (22.2%) were enrolled. 22.2% patients had ECOG PS 0. At data cutoff date (Feb 02, 2023), 8 patients had at least one post treatment anti-tumor assessment. 1 (12.5%) patient achieved CR, 6 (75%) patients achieved PR and 1 (12.5%) patient NE. The ORR was 87.5%. Median PFS and OS were not reached. Grade ≥3 TRAEs incidence was 44.44%. The most common grade ≥3 TRAEs were hypertension (22.22%), leukopenia (11.11%), neutropenia (11.11%) and hypertriglyceridemia (11.11%). Conclusions: This chemo-less therapy of only 2 cycles of chemotherapy combined with penpulimab + anlotinib in first-line treatment, maintaining with penpulimab and anlotinib showed promising efficacy with a favourable toxicity profile for patients with persistent, recurrent, or metastatic cervical cancer. We will report more data in the future. Clinical trial information: ChiCTR2200062897 .

SHR-1701 in combination with platinum-based chemotherapy and BP102 (a bevacizumab biosimilar) for persistent, recurrent, or metastatic cervical cancer: Data from a phase 1b/3 study.

5529 Background: Platinum-based chemotherapy (chemo) ± bevacizumab is the standard first-line therapy for cervical cancer, regardless of PD-L1 expression. SHR-1701 is a novel bifunctional fusion protein targeting PD-L1 and TGF-βRII, and shows promising efficacy and controllable safety in pretreated patients (pts) with cervical cancer. This ongoing phase 1b/3 study aims to assess the addition of SHR-1701 to standard first-line therapy. Methods: In the phase 1b part, eligible pts had persistent, recurrent, or metastatic squamous-cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix not previously treated with systemic chemo for recurrence or metastasis and not amenable to curative treatment. Prior chemo-radiotherapy was permitted for recurrence, if mono-chemo was used as sensitizer. Pts were given SHR-1701 (30 mg/kg), paclitaxel (175 mg/m2), cisplatin (50 mg/m2) / carboplatin (AUC 5), and BP102 (15 mg/kg) every 3 weeks. The primary endpoints were safety and ORR. Results: From Feb 26 to Aug 12, 2022, 31 pts were enrolled. Median age was 55 years (range, 27-71). 24 (77.4%) had squamous-cell carcinoma, and 7 (22.6%) had adenocarcinoma. 20 (64.5%) had metastatic disease, 7 (22.6%) had recurrent cervical cancer, and 4 (12.9%) had persistent cervical cancer. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 25 (80.6%) pts, with the most common being decreased neutrophil count (n=16, 51.6%), decreased white blood cell count (n=12, 38.7%), and anemia (n=8, 25.8%). TRAEs led to discontinuation of any study agent in 8 (25.8%) pts; of note, only 2 (6.5%) pts discontinued SHR-1701 due to TRAEs (grade 3 infusion reaction and grade 3 immune-mediated rash). No treatment-related deaths occurred. Efficacy outcomes are summarized in Table. ORR was 77.4%, with 4 CRs and 20 PRs; responses were ongoing in all 24 responders. DCR was 93.5%. Shrinkage in target lesions was observed in 30 (96.8%) pts. PFS rate at 6 months reached 93.5%. Conclusions: SHR-1701 plus platinum-based doublet chemo and BP102 provided a manageable safety profile and potent antitumor activity in pts with persistent, recurrent, or metastatic cervical cancer, supporting the subsequent randomized, double-blind, placebo-controlled phase 3 part. Clinical trial information: NCT05179239 . [Table: see text]

Advanced cervical cancer therapy: Comparison of contemporary expert and healthcare professional recommendations from an online treatment decision tool.

5528 Background: Practice patterns for the management of advanced cervical cancer are rapidly evolving given the emergence of novel treatment options. We developed an online Interactive Decision Support Tool (IDST) for advanced cervical cancer to provide expert guidance to healthcare professionals (HCPs). Methods: With input from 5 experts, an IDST was developed for patient scenarios with newly diagnosed (ND) and recurrent/second-line (2L) advanced cervical cancer. The IDST included expert insights on 352 scenarios based on criteria such as adenopathy, disseminated disease status, previous therapy, and actionable biomarkers (PD-L1, MMR/MSI, TMB). Users were asked to enter specific patient criteria and their intended management approach. The IDST then showed the 5 expert recommendations for that specific scenario and HCPs were asked to indicate whether the recommendations changed their intended treatment plan. Expert recommendations vs user-selected therapy for different scenarios were analyzed. We present self-reported practice patterns in this disease setting and the impact of expert recommendations on treatment choice. Results: At this interim analysis, 141 unique learners used the IDST, entering 232 unique patient scenarios. Data from the IDST also showed areas of consensus and controversy in treating patients with advanced cervical cancer. For locally advanced, ND, no adenopathy and no metastases, all experts recommended pelvic chemoradiation with or without brachytherapy vs only 61% of HCPs; 16% and 3% of those entering cases for the locally advanced ND setting indicated expert recommendation changed their treatment choice and that barriers impeded the recommendations, respectively. For advanced ND, with adenopathy, metastatic, PD-L1–positive cervical cancers, all experts vs 50% of HCPs chose an immunotherapy-containing platinum-based chemotherapy regimen with/without bevacizumab; 9% of those indicated barriers to implementing expert recommendations. In 2L recurrent disease, all experts chose either single-agent immunotherapy (if PD-L1 positive) or tisotumab vedotin (if PD-L1 negative) vs 45% and 40% of HCPs, respectively; 19% of those selecting 2L therapy in the recurrent setting said the expert recommendations had changed their intended choice. Conclusions: Analysis from this IDST indicates differences in practice patterns between experts and HCPs for various case scenarios of advanced cervical cancer. Online decision support tools may increase the number of HCPs making optimal treatment decisions for advanced cervical cancer, particularly when new data, indications, and guideline updates must be considered. Updated and detailed analyses from the IDST will be presented.

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

BackgroundThe European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort...

Dosimetric Comparative Analysis of Volumetric Modulated Arc Therapy and Intensity-Modulated Radiation Therapy in Cervical Cancer

Objective: To carry out dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in cervical cancer. Methods: 50 postoperative cervical cancer patients were included in this study. The patients were admitted for treatment from January 2021 to January 2022. VMAT and IMRT plans were designed for each patient to analyze the dose distribution in the target area of the two treatment techniques. Results: Comparing the monitor unit for single treatment (638.21 ± 116.21 MU) and time of single treatment (143.21 ± 23.14 s) in the observation group and the monitor unit for single treatment (932.14 ± 74.11 MU) and time of single treatment (223.14 ± 17.26 s) in the control group, there was significant difference (P &lt; 0.05); there was also significant difference (P &lt; 0.05) between the normal tissue (bladder and rectum) of the observation group and that (bladder and rectum) of the control group. Conclusion: VMAT is more effective in cervical cancer, and it has a certain protective effect on normal tissues in patients and can reduce the radiation dose.

Design and Synthesis of Brefeldin A-Isothiocyanate Derivatives with Selectivity and Their Potential for Cervical Cancer Therapy.

Brefeldin A has a wide range of anticancer activity against a variety of tumor cells. Its poor pharmacokinetic properties and significant toxicity seriously hinder its further development. In this manuscript, 25 brefeldin A-isothiocyanate derivatives were designed and synthesized. Most derivatives showed good selectivity between HeLa cells and L-02 cells. In particular, 6 exhibited potent antiproliferative activity against HeLa cells (IC50 = 1.84 μM) with no obvious cytotoxic activity to L-02 (IC50 > 80 μM). Further cellular mechanism tests indicated that 6 induced HeLa cell cycle arrest at G1 phase. Cell nucleus fragmentation and decreased mitochondrial membrane potential suggested 6 could induce apoptosis in HeLa cells through the mitochondrial-dependent pathway.

Microwave assisted cisplatin-loaded CeO2/GO/c-MWCNT hybrid as drug delivery system in cervical cancer therapy

Microwave assisted cisplatin-loaded CeO2/GO/c-MWCNT hybrid as drug delivery system in cervical cancer therapy

PO-1430 Re-irradiation with intensity-modulated radiation therapy for pelvic recurrent cervical cancer

PO-1430 Re-irradiation with intensity-modulated radiation therapy for pelvic recurrent cervical cancer