Chemotherapy For Cervical Cancer Research Articles

Metachronous Ovarian Cancer after a Radical Hysterectomy with Ovarian Conservation for Early-Stage Cervical Cancer: A Case Report

Introduction: Cervical cancer is the fourth most common disease in women worldwide and the leading cause in Tanzania, with 9,772 new cases and 6,695 deaths annually. Surgery is better than radiation or chemotherapy for early-stage cervical cancer (stages IA2–IIA1). Due to the risks of oophorectomy in young women, ovarian conservation is crucial. Metachronous ovarian cancer is understudied, however, ovarian conservation does not enhance cervical cancer mortality. Clinical presentation: We report a rare case of recurrent metachronous ovarian cancer in a 42-year-old female, Para 3, Living 3, who had her ovaries conserved following a radical hysterectomy and bilateral lymph node dissection for stage IB2 cervical cancer at 37 years old in April 2017. The final biopsy showed a well-differentiated, invasive cervical adenocarcinoma. Stage IV ovarian cancer with significant ascites and pleural effusion was detected in July 2018, 14 months post-surgery. Six chemotherapy treatments and total tumor debulking succeeded. Despite the most effective cytoreduction surgery, the patient experienced two further recurrences in 2020 and 2022. After additional surgeries and chemotherapy, she is currently in complete remission and will be followed up. Conclusion: Young women undergoing radical hysterectomy for early-stage cervical cancer must preserve their ovaries, but metachronous ovarian cancer is a risk. Thus, metachronous ovarian cancer risks, challenges, and outcomes must be understood.

Retracted: Construction of Nursing Practice Model in Case Management of Concurrent Chemotherapy and Radiochemotherapy Treatment in Cervical Cancer.

[This retracts the article DOI: 10.1155/2022/5450575.].

Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer

BackgroundImmunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy. MethodsMultiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC. ResultsThe infiltration rate of the CD8+ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3+ regulatory T cells (Tregs) and IDO+ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3+ T, CD8+ T, and CD4+ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8+ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3+ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC. ConclusionsNACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

Hubungan Jarak Tempuh Dan Efek Samping Terhadap Kepatuhan Kemoterapi Pada Pasien Kanker Serviks

Cervical cancer is a deadly cancer for women but some medication could be applied, such as chemotherapy. Chemotherapy has some side effects on these patients if they do not obey. This research determined the correlation between the distance coverage and the side effects on the obedience of cervical cancer patients with chemotherapy at DR. Moewardi Surakarta regional hospital. This quantitative research applied a cross-sectional design. The population consisted of 102 cervical cancer patients with chemotherapy. The researchers took the sample with purposive sampling. The samples were 49 patients measured with the questionnaire of chemotherapy obedience and chemotherapy side effect; and the observational guideline of distance coverage. The results showed that most respondents had a far category distance, 45 respondents (91.8%) and maladaptive side effect type, 37 respondents (75.5%). The Spearman rank test showed the correlation between the distance coverage and the obedience with a p-value of 0.004, lower than 0.05. The result also showed the correlation between side effects and obedience with a p-value of 0.044, lower than 0.05. The results found a correlation between the distance coverage and side effects toward the obedience of cervical cancer chemotherapy.

Intact glycopeptides identified by LC-MS/MS as biomarkers for response to chemotherapy of locally advanced cervical cancer.

For locally advanced cervical cancer (LACC), patients who respond to chemotherapy have a potential survival advantage compared to nonresponsive patients. Thus, it is necessary to explore specific biological markers for the efficacy of chemotherapy, which is beneficial to personalized treatment. In the present study, we performed a comprehensive screening of site-specific N-glycopeptides in serum glycoproteins to identify glycopeptide markers for predicting the efficacy of chemotherapy, which is beneficial to personalized treatment. In total, 20 serum samples before and after neoadjuvant chemotherapy (NACT) from 10 LACC patients (NACT response, n=6) and NACT nonresponse, n=4) cases) were analyzed using LC-MS/MS, and 20 sets of mass spectrometry (MS) data were collected using liquid chromatography coupled with high-energy collisional dissociation tandem MS (LC-HCD-MS/MS) for quantitative analysis on the novel software platform, Byos. We also identified differential glycopeptides before and after chemotherapy in chemo-sensitive and chemo-resistant patients. In the present study, a total of 148 glycoproteins, 496 glycosylation sites and 2279 complete glycopeptides were identified in serum samples of LACC patients. Before and after chemotherapy, there were 13 differentially expressed glycoproteins, 654 differentially expressed glycopeptides and 93 differentially expressed glycosites in the NACT responsive group, whereas there were 18 differentially expressed glycoproteins, 569 differentially expressed glycopeptides and 99 differentially expressed glycosites in the NACT nonresponsive group. After quantitative analysis, 6 of 570 glycopeptides were identified as biomarkers for predicting the sensitivity of neoadjuvant chemotherapy in LACC. The corresponding glycopeptides included MASP1, LUM, ATRN, CO8A, CO8B and CO6. The relative abundances of the six glycopeptides, including MASP1, LUM, ATRN, CO8A, CO8B and CO6, were significantly higher in the NACT-responsive group and were significantly decreased after chemotherapy. High levels of these six glycopeptides may indicate that chemotherapy is effective. Thus, these glycopeptides are expected to serve as biomarkers for predicting the efficacy of neoadjuvant chemotherapy in locally advanced cervical cancer. The present study revealed that the N-glycopeptide of MASP1, LUM, ATRN, CO8A, CO8B and CO6 may be potential biomarkers for predicting the efficacy of chemotherapy for cervical cancer.

Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1

Cisplatin resistance remains a major obstacle limiting the effectiveness of chemotherapy in cervical cancer. However, the underlying mechanism of cisplatin resistance is still unclear. In this study, we demonstrate that vacuolar protein sorting 13 homolog C (VPS13C) deficiency promotes cisplatin resistance in cervical cancer. Moreover, through an RNA sequencing screen, VPS13C deficiency was identified as negatively correlated with the high expression of glutathione S-transferase pi gene (GSTP1). Mechanistically, loss of VPS13C contributes to cisplatin resistance by influencing the expression of GSTP1 and inhibiting the downstream c-Jun N-terminal kinase (JNK) pathway. In addition, targeting GSTP1 with the inhibitor NBDHEX effectively rescued the cisplatin resistance induced by VPS13C deficiency. Overall, our findings provide insights into the underlying mechanisms of VPS13C in cisplatin resistance and identify VPS13C as a promising candidate for the treatment of chemoresistance in cervical cancer.

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.

A novel predictor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors

ObjectiveFor early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (CONUT) score in guiding the use of concurrent chemotherapy during postoperative radiotherapy. MethodsA total of 969 patients with FIGO stage IB-IIA cervical cancer were retrospectively analyzed. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses. ResultsFor the patients in the high CONUT group (≥3), the addition of concurrent chemotherapy had better 5-year DFS (91.2 % vs. 72.8 %, P = 0.005) and CSS (93.8 % vs. 77.4 %, P = 0.013) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of locoregional recurrence (8.5 % vs 16.7 %, P = 0.034) and distant metastases (11.7 % vs 30.4 %, P = 0.015). The multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (P = 0.011), local control (P = 0.041), distant metastasis (P = 0.005) and CSS (P = 0.023). For the patients in low CONUT group (<3), there was no difference in prognosis between patients. ConclusionPretreatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.

Value of [18F]FDG PET/CT radiomic parameters in the context of response to chemotherapy in advanced cervical cancer

The first-order statistical (FOS) and second-order texture analysis on basis of Gray-Level Co-occurence Matrix (GLCM) were obtained to assess metabolic, volumetric, statistical and radiomic parameters of cervical cancer in response to chemotherapy, recurrence and age of patients. The homogeneous group of 83 patients with histologically confirmed IIIC1–IVB stage cervical cancer were analyzed, retrospectively. Before and after chemotherapy, the advancement of the disease and the effectiveness of the therapy, respectively, were established using [18F] FDG PET/CT imaging. The statistically significant differences between pre- and post-therapy parameters were observed for SUVmax, SUVmean, TLG, MTV, asphericity (ASP, p = 0.000, Z > 0), entropy (E, p = 0.0000), correlation (COR, p = 0.0007), energy (En, p = 0.000) and homogeneity (H, p = 0.0018). Among the FOS parameters, moderate correlation was observed between pre-treatment coefficient of variation (COV) and patients’ recurrence (R = 0.34, p = 0.001). Among the GLCM textural parameters, moderate positive correlation was observed for post-treatment contrast (C) with the age of patients (R = 0.3, p = 0.0038) and strong and moderate correlation was observed in the case of En and H with chemotherapy response (R = 0.54 and R = 0.46, respectively). All correlations were statistically significant. This study indicates the remarkable importance of pre- and post-treatment [18F] FDG PET statistical and textural GLCM parameters according to prediction of recurrence and chemotherapy response of cervical cancer patients.

Start so young? Defense of the primary HPV test as a screening test for cervical cancer in women aged 25 and over in Brazil.

e17531 Background: Cervical cancer (CC) is the most frequent type of cancer on woman at reproductive age and on the puerperal pregnancy cycle in Brazil. It is a disease that can be prevented with the resources already available at Brazil’s public healthcare system.The most important risk factor for developing cervical cancer is infection with human papillomavirus (HPV). With the covid 19 pandemic, there was an advance in the possibility of carrying out an HPV test by PCR by through the government initiative "uterus is life" and we was asked what age should start the HPV test in the proposed screening organized. Methods: Descriptive, observational, cross sectional study Carried two cancer centers( using an adapted form, between 2020 2021 Sociodemographic data, cancer characteristics. Descriptive statistics were used to analyze the data and evaluation of secondary data from the ministry of health (DATASUS) This study was approved by the institution’s ethics committee. Recife, Brazil. Results: From 2021 -2022, 240 patients with CC mean age 50,48y (SD ± 13.8; range 24-87), 15, 8 % &lt; 35 y, age of first sexual intercourse: mean age 16,7 (SD ± 3.2, range 11- 30) and 79,6 % &lt; 18y. age of first pregnancy mean 18 (SD ± 6.54; range 12- 36) 77,4 % &lt; 18 y.In the year 2019 of the number of patients undergoing treatment in the Brazilian public system (SUS), by age group, 14.076 patients &lt;35 y (58%). $821,000 was spent in 2019 on anticancer chemotherapy for CC in women &lt; 35 y. Conclusions: With a view to establishing an organized screening policy using the HPV test, considering the window of opportunity to diagnose the non-invasive cervical cancer stage, the onset of sexual activity and the age of first pregnancy among patients with invasive cervical cancer and the representativeness of patients with &lt; 35 years undergoing treatment for advanced CC. The "Utero é Vida" initiative recommended starting the screening of the HPV test from the age of 25 y, in addition to intensifying vaccination coverage against HPV.

Efficacy and safety of camrelizumab in combination with radiation and chemotherapy for recurrent or metastatic cervical cancer.

5542 Background: Cisplatin-based concurrent chemoradiation regimens have been suggested to be beneficial in recurrent or metastatic cervical cancer. Immunotherapy has also shown good therapeutic efficacy in recurrent or metastatic cervical cancer. Among them, Pembrolizumab in combination with chemotherapy has been used for first-line treatment of advanced PD-L1-positive cervical cancer. Meanwhile, Camrelizumab has shown good anti-tumor activity and manageable toxicity in patients with locally advanced cervical cancer. The primary objective of this study is to evaluate the efficacy and safety of Camrelizumab in combination with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer. Methods: Patients diagnosed with recurrent or metastatic cervical cancer received Camrelizumab combined with concurrent chemoradiotherapy, radiotherapy:External beam radiotherapy (EBRT) 1.8-2.15 Gy/f, a total of 28 fractions; Brachytherapy: high-risk CTV using image guidance 28 Gy in 4 fractions (18 Gy in 3 fractions for posthysterectomy recurrent patients); chemotherapy regimen used TP regimen (paclitaxel: 175 mg/m2, cisplatin: 75 mg/m2, Q3W 6 cycles); Camrelizumab 200 mg Q3W 6 cycles. The primary endpoint of this trial was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and incidence of adverse reactions. Results: From September 16, 2020 to September 30, 2022, a total of 29 patients were recruited. 27 of these patients completed 6 cycles of planned treatment. 27 patients had a median age of 53 years (33-73 years), ECOG PS 0 (n = 8), ECOG PS 1 (n = 14), ECOG PS 2 (n = 1). The ORR rate was 96.30% (26/27), including 17 patients with CR, 9 patients with PR, and 1 patient with SD Treatment-related AEs were mainly lymphocyte count decreased, anemia, and white blood cell count decreased, with overall safety manageable and no treatment-related deaths. Conclusions: Camrelizumab combined with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer has good efficacy, low side effects and acceptable toxicity. Clinical trial information: NCT04884906 .

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]

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 &lt; 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 &lt; 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.

Abstract 53: Implementing Equitable Cancer Support Program: Lessons From Cervical Cancer Chemotherapy Access Program (C3AP)

Abstract Purpose: There is an inverse relationship between diagnosis to initiation of treatment interval and outcome of cancer treatment. A significant number of diagnosed cervical cancer patients don’t receive timely treatment in low resource settings. The Cervical Cancer Chemotherapy Access Program (C3AP) is one of End Cervical Cancer Nigeria Initiative’s interventions to IMProve Access to Cervical Cancer Treatment (IMPACT) in low resource settings. This report provides documentary evidence of the evolution of the implementation of the C3AP and highlights best practices that can be scaled up. Methods: The C3AP was conceptualized to increase the proportion of diagnosed cervical cancer patients that receive timely treatment by exploring adjuvant and neoadjuvant role of chemotherapy in the management of cervical cancer patients in settings where access to radiotherapy services can not be guaranteed. We instituted Plan Do Study and Act (PDSA) quality improvement cycle for the C3AP and used RE-AIM framework to study the implementation processes to be acted upon as part of the PDSA quality improvement process towards improving reach of the program. Results: The C3AP supported treatment of only 4 patients over the reporting period of 5months. Poor referral to the program is a major hurdle the program is battling. Only 2(17%) of the 12 confirmed cases of cervical cancer diagnosed in the facility within the 5month study period were able to access chemoradiation, suggesting a missed opportunity for 6/10(60%) that couldn’t afford chemoradiation. The program evolved over a PDSA cycle to eliminate social eligibility in the criteria to access the support thereby able to shorten application -support interval to same day with potential positive impact on prognosis. Conclusion: Providing equitable support for indigent cancer patients should be beyond the emotion to help humanity. We recommend the use of structured quality improvement for all programs providing support to indigent cancer patients to ensure implementation fidelity. Citation Format: Qudus Lawal, Kasimu Umar Adoke, Jummai Jimeta Tuko, Aminu Magashi Garba, Ishak K. Lawal. Implementing Equitable Cancer Support Program: Lessons From Cervical Cancer Chemotherapy Access Program (C3AP) [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 53.

The efficacy of Mecapegfilgrastim therapy in the primary prevention of concurrent chemoradiotherapy-induced neutropenia

ObjectiveTo evaluate the efficacy and safety of mecapegfilgrastim therapy in primary prevention of neutropenia after concurrent chemoradiotherapy for cervical cancer. MethodsThis study was a single-center, open, one-arm clinical observation, and analyzed the effectiveness of mecapegfilgrastim primary prevention of neutropenia after concurrent chemoradiotherapy in 25 cervical cancer patients undergoing concurrent chemoradiotherapy in Tianjin Medical University Cancer Institute and Hospital from 2019 to 2021. ResultsDuring the whole concurrent chemorrhotic cycle, chemotherapy delay occurred in 8 patients, (16%). The completion rate of chemotherapy cycle was 84% (42/50). There were only 4 (8%) cases of delayed concurrent chemotherapy due to leukopenia or neutropenia. Radiotherapy delay occurred in 10 patients, (20%). None of the patients delayed radiotherapy due to leukopenia or neutropenia. The incidence of febrile neutropenia (FN) was 0%. Subgroup analysis found that after completing 1 cycle of concurrent chemoradiotherapy, 6(12%) patients with grade 3–4 leukocyte or neutropenia. After completing 2 cycles of concurrent chemoradiotherapy, 14(29%) patients with grade 3–4 leukocyte or neutropenia. ConclusionDuring the chemoradiation in patients with cervical cancer, primary prevention use of mecapegfilgrastim can significantly reduce the incidence of FN, effectively reduce the incidence of grade III-Ⅳ leukopenia or neutropenia, beneficial to ensure the smooth progress of concurrent chemoradiotherapy,and provide a new direction for primary prevention of cervical cancer chemotherapy.

EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1.EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

Real-world efficacy and safety of bevacizumab single-maintenance therapy following platinum-paclitaxel chemotherapy plus bevacizumab in patients with advanced cervical cancer.

Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer. We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups. Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death. Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.

Retraction: A novel TMTP1-modified theranostic nanoplatform for targeted in vivo NIR-II fluorescence imaging-guided chemotherapy for cervical cancer.

Retraction of 'A novel TMTP1-modified theranostic nanoplatform for targeted in vivo NIR-II fluorescence imaging-guided chemotherapy for cervical cancer' by Nuernisha Alifu et al., J. Mater. Chem. B, 2022, 10, 506-517, https://doi.org/10.1039/D1TB02481G.

Relationship between Circulating Plasma Galectin-3 Levels and T-Cell Activation during Cervical Cancer Chemotherapy

Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731; p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05; rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+CD69+ cells in cervical cancer.