bluuebunny/crossref_metadata_2025_split huggingface dataset:
18F-FDG PET/CT parameters in precision treatment planning for locally advanced squamous cell carcinoma of the uterine cervix.
Authors: Lai Chyong-Huey , Liu Feng-yuan , Chen Wei-Chun , Yang Lan-Yan , Wang Chun-Chieh , Chao Angel 
Published: June 2023

e17508 Background: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. We aimed to analyze pretreatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and clinicopathological characteristics in patients with locally advanced cervical squamous cell carcinoma (SCC) to establish a scoring system for prognostic stratification. Methods: Cohort 1 consisted of patients with cervical SCC with FIGO (2009) stage III-IVA or stage I-II with positive nodes on PET/CT recruited in AGOG09-001 trial. Cohort 2 consisted of institutional patients treated in 2016-2020 with similar inclusion criteria. Pretreatment clinical characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of cervical tumor and nodal SUVmax were assessed for outcomes using the stepwise multivariable Cox regression. Results: With two cohorts combined (Cohort 1, n= 55, Cohort 2, n= 120), the median follow-up for 175 patients was 55 months (range, 2-164). Age (≥66 years old), MTV (≥87.1 mL) of cervical tumor and PET/CT-defined para-aortic lymph node (PALN) metastasis were independent significant adverse predictors for cancer-specific survival (CSS) ( P<0.001, P=0.002, and P=0.033, respectively). Counting each risk predictor as score one, patients with risk score sum 0, 1, 2, 3 had a 5-year CSS of 85.8%, 68.5%, 29.7%, and 0%, respectively ( P<0.001). Conclusions: Age, cervical tumor MTV and PET/CT-defined PALN metastasis are independent risk predictors in locally advanced cervical SCC. Patients with risk score sum 0 may receive CCRT with single-agent cisplatin, while patients with risk score sum ≥1 may consider receiving novel combination therapies or entering clinical trials.
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).
Authors: Xu Qin , Liu Jing , Li Li , Lin Yibin , Chen Ying , Song Yanwen , Luo Lan 
Published: June 2023

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 .
Circulating exosomal PD-L1 to predict response with immunotherapy in patients with advanced cervical cancer.
Authors: Tang Wenjie , Guo Qiufen , Chen Jinlong , Wu Qian , Zhang Tingting , Wang Qian , Zhang Xueliang , Xie Peng 
Published: June 2023

e17514 Background: Programmed death ligand 1 (PD-L1) expression was wildly used to predict immune Check-Point Inhibitors (ICIs) efficiency. However, emerging results showed that PD-L1 was of great heterogeneity in sampling time and site. Recently, some studies found that exosomal PD-L1(ExoPD-L1) was related to ICIs response. In this study, we aimed to explore the predictive value of ExoPD-L1 in ICIs treatment of cervical cancer (CC) for the first time. Methods: 40 primarily diagnosed CC patients who accepted radical radiotherapy (RT) were included. The consecutive tumor sample were collected before and during RT. Another 37 advanced CC patients who accepted ICIs combination therapy were collected. Blood samples were collected from each participant before and during treatment. Exosomes were derived by differential centrifugation, which was further identified by Western blot (CD9/TSG101/Calnexin), transmission electron microscope analysis and nanoparticle tracking analysis. ExoPD-L1 detection was conducted by enzyme-linked immuno-sorbent assay (ELISA). The knockout of PD-L1 was conducted via CRISPR/Cas9 assay and the overexpress of PD-L1 was conducted by lentiviral transfection. CD8+ T cells were extracted from murine spleen by CD8+ T Cell Isolation Kit. Immune cells and cytokines markers were detected by multicolor flow cytometry. Results: The consecutive detection of PD-L1 showed a dynamic change during RT. Compared with the level before RT, PD-L1 expression elevated in most patients (87.5%, 35/40) after RT. And the responders (n = 18) had elevated ExoPD-L1 level at the first two circles in the ICIs combination therapy (P < 0.001). Whereas the level of pre-treatment ExoPD-L1 couldn’t stratified clinical responders and non-responders (P = 0.181). The median follow-up time was 14.13 months. The mPFS in increased group vs. decreased group: not reach vs.11.02 months (P = 0.025, HR: 0.218, 0.052-0.913). Continuous blood sampling of mice models also found that effective therapeutic intervention could increase ExoPD-L1 in the early stage. The combination of exosome inhibitor GW4869 and anti-PD-1 further inhibited tumor growth. Mice were injected with external ExoPD-L1OE and ExoPD-L1KO. The results showed that ExoPD-L1OE suppressed body immunity and promoted tumor growth. The results of flow cytometry showed that ExoPD-L1OE inhibited CD8+ T cells from releasing interferon-γand granzyme B. And ExoPD-L1OE also suppressed the CD8+ T cells proliferation in murine spleen. The coculture of CD8+ T cells and exosomes in vitro also confirmed the above conclusion. Conclusions: Compared with unstable and impressionable tumoral PD-L1, ExoPD-L1 seems to be better predictor for the efficacy of immunotherapy in CC, which was with easy accessibility and continuation. Exosome PD-L1 played an immunosuppressive role by inhibiting the proliferation and functional factor release of CD8+ T cell.
The safety and efficacy of cadonilimab in the treatment of advanced and metastatic cervical cancer: A retrospective, real-world study.
Authors: Fan Shi , Wang Tao , Zhang Qiying , Wang Juan , Su Jin , Zhang Jing , Wang Fei , Liu Zi 
Published: June 2023

e17515 Background: Recurrent/metastatic cervical cancer (r/m CC) patients have limited treatment options. Cadonilimab, a PD-1/CTLA-4 bi-specific antibody, was approved in China on 29 June 2022 for the treatment of patients with r/m CC who have progressed on or after platinum-based chemotherapy. As monotherapy provides encouraging safety and efficacy, it may be better combined with another therapy including chemotherapy, radiotherapy, targeted therapy, or immunotherapy. The objective of this retrospective study was to evaluate the safety and efficacy of Cadonilimab monotherapy/combination therapy in patients with advanced r/m CC. Methods: Patients with FIGO stage IIIc2r-IVb CC treated with Cadonilimab containing therapy were enrolled. All patients received at least one dose of Cadonilimab (10mg/kg, Q3W), among them, 5 patients received Cadonilimab monotherapy, 11 patients received concurrent radiotherapy, 19 patients received concurrent chemotherapy, 12 patients received targeted therapy, and 4 patients received local injection s of oncolytic virus. Treatment-related toxicity (TRAEs), objective response rate (ORR) and disease control rate (DCR) were evaluated. Results: 26 patients with a median age of 54 years (40-73 years) were evaluated up to 20 January 2023. As shown in the table, 21 patients were still on treatment, 5 patients were discontinued due to death. In the efficacy-evaluable population(n=24), the ORR was 70.8% (17/24,95% CI:51.2%-90.4%) with 3 (12.5%) CR,14 PR, 2 SD, and the DCR was 79.2%(19/24,95% CI:61.6%-96.7%). Immune-related AEs (irAEs) were all G1-2, and occurred in 4 (16.7%) patients. Main irAEs included hypothyroidism (n=3, 12.5%), fatigue (n=1, 4.2%), loss of appetite (n=1, 4.2%), hematologic toxicity (thrombocytopenia) (n=1, 4.2%), mucositis (n=1, 4.2%), and rash (n=1, 4.2%). Rashes and loss of appetite typically developed after the first cycle of Cadonilimab treatment, while hypothyroidism usually developed after the second or third cycle. 2 (8.3%) patients experienced G3-5 TRAEs, which were thought to be primarily related to chemotherapy. All the 5 deaths were heavily pretreated (≥3 lines) patients who received Cadonilimab monotherapy. Among the 24 patients, only 1 patient delayed treatment after the 1st cycle due to economic reasons. There were no toxic deaths reported. Conclusions: In the real world, Cadonilimab showed a manageable safety profile. Patients with advanced r/m CC tend to benefit from first-line/second-line Cadonilimab containing combination therapies due to the excellent response rates. [Table: see text]
Maintenance therapy for patients with recurrent or metastatic cervical cancer: A multicentre, cohort study.
Authors: Peng Chen , Guo Qiufen , Zhang Tingting , Chen Jinlong , Liu Naifu , Yan Peile , Lu Yuanyuan , Ma Anqun , Lv Pengzhong , Liu Jing , Xie Peng 
Published: June 2023

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.
The perception of cervical cancer screening and prevention among Saudi women.
Authors: Abusanad Atlal M. , Alharbi Lama , Alsalamah Seham , Almasary Manal , Alharthi Amnah , Al-hajeili Marwan R. 
Published: June 2023

e17519 Background: Cervical cancer (CC) is the fourth cause of malignancy-related deaths among women globally. In Saudi Arabia, it is the 8th most prevalent cancer and the 7th cause of cancer mortality among women between the ages of 15–44. There is a limited national data on the awareness of CC, human papilloma virus (HPV), and knowledge of screening and prevention. We present the largest national study to date investigating knowledge of Saudi women toward CC, the HPV vaccine, Pap smear, and influencing factors of their application. Methods: A structured questionnaire of 22 questions included demographic data, CC awareness and associated risk factors, evaluation of Pap-smear and HPV vaccine knowledge and their application was constructed and validated. Participants were exclusively female. It was distributed across the country and scored according to a pre-defined scoring system. Influencing factors of CC, Pap-smear and HPV vaccine knowledge and awareness were examined. A regression model to predict the possibility of performing Pap-smear was generated. P-value of 0.05 and less indicated statistical significance in all tests. Results: 2539 female participants completed the questionnaire with (41%) aged 18 - 25 years old. A sizable portion were from the central region (30.4%) and a majority had a university degree (73.1%). 65% of the participants were sexually active. Two thirds of the participants have heard about Pap-smear and its role in detecting CC but only 20% took the test. Although one third knew that the HPV vaccine can prevent CC, only 2% received the vaccination. Poor knowledge on locating the Pap-smear and HPV vaccine were reported among participants. 12% reported that health campaigns were their source of information. Factors associated with adequate knowledge are listed in table. Age predicted the possibility of performing Pap-smear with participants of 18 - 25 years old are more likely to take the test (P=0.00). Conclusions: This large study evaluated the knowledge and awareness of CC, Pap-smear, and the HPV vaccine across the country. It demonstrated the need for better advocacy and for a nation-wide campaigning to further utilize early detection and preventive procedures. [Table: see text]
Ribosomal protein S26 (RPS26) expression of advanced cervical cancer (CC) to predict response to programmed death-1 inhibitor combination therapy: A secondary analysis of the CIBI308ALTER-C201 trial.
Authors: Liu Jing , Li Li , Chen Ying , Song Yanwen , Luo Lan , Zhu Shitao , Xu Qin 
Published: June 2023

e17520 Background: PD-1 inhibitor combination therapy is widely used in cervical cancer, and improves prognosis. However, there is still a lack of effective predictive markers. The results of previous single-cell analysis of cervical cancer in our research group suggested that RPS26 is related to changes in the immune microenvironment. The purpose of this study is to evaluate whether RPS26 can be used as a prognostic marker for cervical cancer PD-1 inhibitor combination therapy. Methods: A total of 36 patients with CC were recruited. 18 patients were from CIBI308ALTER-C201 trail，and the other 18 were not. All patients underwent next-generation sequencing (NGS). Tumor RPS26 expression was assigned by immunohistochemistry as follows: 0, 1+, 2+, 3+. Significant difference was tested by Fisher's exact test. Kaplan-Meier analysis were applied for survival analysis. Results: The PFS of patients from CIBI308ALTER-C201 trail was significantly longer among patients with RPS26 expression for 2+/3+ than 0/1+ (not reached v 9.877 months, p= 0.0497). There were 11, 14, 9 and 2 patients with RPS26 expression of 0, 1+, 2+, and 3+, respectively. There were 12 and 24 for PIK3CA mutant patients and wild-type, respectively. There was no patient with RPS26 expression for 0 in the PIK3CA mutant group, and 9 patients with RPS26 expression for 0 in the PIK3CA wild group. The expression of RPS26 was significantly different between the two groups ( p= 0.0163). Conclusions: Our study suggested that RPS26 could be novel predictive biomarkers in patients with CC treated with PD-1 inhibitor combination therapy, and PIK3CA mutation enhances RPS26 expression in CC.
Tertiary lymphoid structure prevalence and prognostic value in cervical cancer.
Authors: Gorecki Grace , Coffman Lan Gardner , Taylor Sarah E. , Bruno Tullia C. 
Published: June 2023

e17521 Background: Recurrent or progressive cervical cancer have limited second-line treatment options. Response rates are often poor to second-line therapy (average response rate of 15%). Identification of factors which predict response to immunotherapy and targets to enhance the immune response are critically needed in cervical cancer. Chronic inflammation can initiate an immune response in non-secondary lymphoid organs (SLO) and form a Tertiary Lymphoid Structure (TLS). TLS is composed of immune cells clustered and organized and responsible for immune cell chemotaxis, which impacts cancer therapeutic response. Chemokine ligand 13 (CXCL13) is related to B cell attraction and TLS formation. Recent work from our group demonstrated human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) exhibited greater tumor infiltrating B cells (TIL-Bs) and TLS vs HPV negative disease indicating a role for viral infection in immune infiltration. Most cervical cancer is caused by HPV infection, therefore we investigated prognostic significance of immune infiltration in cervix cancer. Methods: A cohort analysis was conducted on 43 patients diagnosed with early stage cervical cancer. The presence of B cells, CD8 T cells, and CXCL13 was analyzed using singleplex immunohistochemistry staining. We separated infiltration into high infiltration and low infiltration, defined by their median value. TLS was identified using a multiplex immunofluorescence for TLS maturity panel. Histological findings were associated with cohort data. Results: High intratumoral infiltration of CD8 T cells was associated with longer overall survival in cancer patients. Median survival was 45 months for low infiltration group, whereas it was not reached by higher T cell infiltration (p < 0.05). The prognostic value of T cell infiltration was stronger in adenocarcinoma, typically associated with worse outcomes, than in squamous cell carcinoma. In adenocarcinoma, median survival was 58 months for low T cell infiltration, it was not reached by high infiltration group. CXCL13 levels were prognostic for recurrence-free survival, with median survival of 53 months in low expression group and not reached in high CXCL13 presence group (p < 0.05). The presence of TLS compared to low B cell infiltration was associated to higher survival, with 0% of deaths in the TLS group vs 40% in low B cell infiltration. While there was no correlation between TIL-B and patient outcomes, the presence of B cells in the aggregation process and higher CXCL13 levels were associated with improved survival, with 9% deaths vs 36% in low B cell group, possibly due to the support of TLS formation by B cell aggregation surrounded by CXCL13. Conclusions: Our study suggests that the presence of TLS, whether forming or established, is linked to improved clinical outcomes in cervical cancer. Further research is necessary to investigate the response of this cancer type to immunotherapy.
Association between cervical immune markers and cervical high-risk HPV infections.
Authors: Adebamowo Sally Nneoma , Famooto Oluranti Ayotunde , Adebamowo Clement Adebayo ,   for the H3Africa ACCME Research Group
Published: June 2023

e17522 Background: Evidence suggests that human papillomavirus (HPV) infection of the cervix, alters local immune markers. The aim of this study was to comprehensively evaluate the types and concentration of cervical cytokines and chemokines in HPV-negative compared to HPV-positive women in sub-Saharan African. Methods: The study population was 275 women enrolled in the African Collaborative Center for Microbiome and Genomics (ACCME) HPV cohort study. The concentration of 27 chemokines, cytokines and growth factors was quantified from cervical samples, using multiplexed bead-based immunoassays. HPV types were characterized using SPF25/LiPA10. Regression models were used to estimate the association between each immune marker and HPV infection. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for fold-change in immune marker levels divided into quartiles, using the lowest quantile as a reference category. Results: The mean (±SD) age of the women was 41 (±8) years. Some, 49% (134/275) were HPV negative and 51% (141/275) were HPV positive. Of the HPV positive women, 39% (55/141) had low-risk HPV (lrHPV) types and 93% (131/141) had high-risk HPV (hrHPV) types. Compared to HPV negative women, lrHPV-positive women had significantly higher median concentration of IFN-g, IL-2, IL-4, IL-7, IL-10 and IL-13. While hrHPV-positive women had significantly lower median concentration of GMCSF, interleukin (IL)-1RA and MCP-1; and higher median concentration of interferon-g (IFN-g), IL-b, IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15 and MCP-1b, compared to HPV negative women. Women had significantly higher odds of lrHPV infection if they were in the highest quartile for IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70 and IL-13. While women had significantly lower odds of hrHPV infection if they were in the highest quartile for IL-IRA (OR 0.16, 95% CI: 0.07, 0.34) or MCP-1 (OR 0.39, 95% CI: 0.18, 0.83), and significantly higher odds of hrHPV infections if they were in the highest quartile for eotaxin, IFN-g, IL-1b, IL-4, IL-5, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1a, MIP-1b or TNFa. Conclusions: Consistent with findings from other populations, higher concentration of pro-inflammatory immune markers in the cervix were associated with higher odds of high-risk HPV infections among African women.