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Objective: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities., Methods: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens., Results: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients., Conclusion: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival., Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m 2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m 2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35., Findings: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group., Interpretation: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer., Funding: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre., Competing Interests: Declaration of interests GE reports consulting fees from MSD and Eisai; payment or honoraria from Eisai and GSK; support for attending meeting from MSD; and participation on Data Safety Monitoring Board or Advisory Board for GSK, MSD, and Eisai, outside the submitted work. JAL reports grants from AstraZeneca and Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/AbbVie, and Novocure; payment or honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, and GSK; participation on Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; and leadership role on the European Society for Medical Oncology's Clinical Practice Guidelines—Gynaecological Cancer—until December, 2023, past Vice President role for the European Society of Gynaecological Oncology, until 2021, and Chair for National Ovarian Cancer Audit Committee, outside the submitted work. MM reports payment or honoraria from MSD, Eisai, GSK, Roche, and Medscape; support for attending meetings or travel from Daiichi Sanko; and past role as a Chair of Cervical Cancer Research Network (until September 2021), outside the submitted work. AM reports participation on data safety monitoring board or advisory board for Cannariabio (on an ovarian cancer trial, since 2023) and executive committee member role with the Gynecologic Cancer Intergroup (since 2024), outside the submitted work. AH reports honoraria for educational activities from AbbVie, Almirall, Boehringer Ingelheim, Clovis Oncology, Ipsen, Takeda, AstraZeneca, Daiichi Sankyo, Merck Serono, MSD, UCB, Kyowa Kirin, Servier, Sobi, Pfizer, and Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study explored patients and providers' perspectives on therapeutic vaccines for cervical cancer and assessed barriers and facilitators., Methods: Qualitative semi-structured in-depth interviews were conducted with patients who had cervical dysplasia, or a past or current cervical cancer diagnosis and providers who provided care to patients with cervical abnormalities or cervical cancer. Data were analyzed using thematic analysis in NVivo., Results: A total of 28 in-depth interviews were conducted with patients (N = 15) and providers (N = 13). Participants in both groups expressed enthusiasm for the prospect of a therapeutic vaccine for cervical cancer and were encouraged by less invasive treatment opportunities. Perceived patient barriers included concerns about side effects, eligibility criteria, costs, transportation, and logistical obstacles. Providers echoed these concerns, highlighted additional structural barriers such as racism and limited availability of culturally sensitive educational aids, and underscored the need for provider training on this topic., Conclusion: Our results reinforce the need for future multi-level interventions discussing vaccine efficacy, durability, and safety, as well as addressing factors such as awareness, knowledge, and beliefs., Practice Implications: Our findings can contribute to the development of provider and patient-centered tools that promote therapeutic vaccine acceptance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Giuliano reports a relationship with Merck & Co Inc that includes: board membership and consulting or advisory. Dr. Giuliano’s institution has received funds to support HPV-related research. No other authors have conflicts of interest to report related to this paper. All authors attest that they meet the ICMJE criteria for authorship., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m 2 +triweekly cisplatin 40 mg/m 2 ), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m 2 ) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC., Competing Interests: Declaration of competing interest Dr. Peng-Hui Wang and Dr. Szu-Ting Yang, editorial board members at Taiwanese Journal of Obstetrics and Gynecology, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024. Published by Elsevier B.V.)

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls <15 years of age; (2) a high-performance screening procedure to 70% of women during the reproductive age (at the age of 35 and 45 years of age); and (3) an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Among the aforementioned three pillars, a full HPV vaccination has been introduced in our previous review, of which we have discussed the policy and strategy of HPV vaccination in the world and also reviewed the efficacy of HPV vaccination, with a successful reduction of over 90% of HPV-associated neoplasms. The aims of the current review will target another pillar-an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Since the early-stage cervical cancer has a favorable outcome and the treatment recommendation has been established, therefore, the current review focuses on women with persistent, recurrent and metastatic cervical cancers (advanced cervical cancers), which are still a biggest challenge based on its extremely worse outcomes before the introduction of immune checkpoint inhibitors (ICIs). Integration of ICIs into conventional chemotherapy (paclitaxel-cisplatin) has become the new standard therapy for those patients with advanced cervical cancers. The recent clinical trials, such as KENOTE 826 and KENOTE A18 showing a dramatical improvement of both progression free survival and overall survival have approved the therapeutic efficacy of this combination as ICI plus paclitaxel-platinum (cisplatin or carboplatin) with/without bevacizumab to women with persistent, recurrent and metastatic cervical cancers., Competing Interests: Declaration of competing interest Dr. Peng-Hui Wang and Dr. Szu-Ting Yang, editorial board members at Taiwanese Journal of Obstetrics and Gynecology, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To investigate the association between household income and overall survival (OS) of patients with cervical adenocarcinoma., Methods: We conducted a retrospective cohort study involving participants selected from the Surveillance, Epidemiology, and End Results (SEER) database. Data were collected on various variables, including demographic variables such as median household income and clinicopathological characteristics for all participants. Cox regression analysis was utilized to examine the association between household income and OS. Subgroup analysis, sensitivity analysis, and E-value were used to further confirm the association., Results: A total of 2217 patients were included in the study. Compared with low-income (<$35,000-$54,999), middle-income (55,000-$69,999) or high-income (≥$70,000) was significantly associated with a higher 5-year OS (70.8 %, 58.7 % vs 50 %) in patients with cervical adenocarcinoma. The HR was 0.49, 95 % CI 0.41-0.58, p < 0.001 and 0.66 (0.55-0.78), p < 0.001 respectively, in the unadjusted model. After adjustment for potential confounders, the results were similar (adjusted HR 0.54 (0.45-0.65), p < 0.001) and 0.79 (0.66-0.94), p = 0.01), respectively. This significant association was also present in the various adjusted models. Subgroup and sensitivity analyses suggested that the relationship remained robust and reliable. The E-value analysis indicated robustness to unmeasured confounding. There was evidence of an interaction between age at diagnosis, race, primary site, tumor grade, T, N, M, or Scope Reg LN Sur, and household income on increasing the 5-year OS of cervical adenocarcinoma., Conclusions: Our study found that middle or high household income was significantly associated with a better 5-year OS compared with low household income in patients with cervical adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Patients with cervical cancer undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected data on patient-reported outcomes to determine characteristics predictive of poor treatment experience., Methods and Materials: Between 2021 and 2023, we prospectively collected data on patient-reported outcomes from patients with cervical cancer undergoing definitive chemoradiation. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Question-Core 30 and the EORTC-Quality of Life Question-Cervical Cancer module were completed at baseline (BL) and at the end of treatment (EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, and disease-specific factors and BL financial toxicity, depression, social function, and emotional function. Receiver operating characteristic analysis provided appropriate predictive cutoff values. Univariable and multivariable (MVA) linear regression analyses were performed., Results: Forty-nine patients completed BL and EOT questionnaires. Median age was 43 years (range, 18-85 years). Most patients (59%) had stage III disease. BL financial toxicity ≥66.7, depression ≥66.7, social function ≤50, and emotional function ≤58 on the EORTC linear transformed scale of 0 to 100 were significant predictors for poor treatment experience (p ≤ .04) based on receiver operating characteristic analysis. On MVA, poor BL social function was associated with reduced EOT HRQOL (β, -9.3; 95% CI, -16.1 to -2.6; p < .008), decreased physical function (β, -24.4; 95% CI, -36.3 to -12.6; p < .001), and high symptom burden (β, 26.9; 95% CI, 17.5-36.3; p < .001). Earlier disease stage predicted decreased symptom burden (β, -6.7; 95% CI, -13.1 to -0.3; p = .039). BL financial toxicity was a significant predictor in univariable analysis (p = .001-.044) and showed a significant interaction term on MVA (p = .024-.041) for all 3 domains of poor treatment experience. Demographic and treatment-related factors were not predictive., Conclusions: Patients with cervical cancer with poor BL social function or high financial toxicity were at risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience., Competing Interests: Disclosures None., (Published by Elsevier Inc.)

Purposes: To investigate the value of machine learning-based radiomics for predicting disease-free survival (DFS) and overall survival (OS) undergoing concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC)., Materials and Methods: In this multicentre study, 700 patients with IB2-IVA cervical cancer who underwent CCRT with ongoing follow-up were retrospectively analyzed. Three-dimensional radiomics features of primary lesions and its surrounding 5 mm region in T2WI sequences were collected. Six machine learning methods were used to construct the optimal radiomics model for accurate prediction of DFS and OS after CCRT in LACC patients. Eventually, TCGA and GEO databases were used to explore the mechanisms of radiomics in predicting the progression and survival of cervical cancer. This study adhered CLEAR for reporting and its quality was assessed using RQS and METRICS., Results: In the prediction of DFS, the RSF model combined tumor and peritumor radiomics demonstrated the best predictive efficacy, with the AUC for predicting 1-year, 3-year, and 5-year DFS in the training, validation, and test sets of 0.986, 0.989, 0.990, and 0.884, 0.838, 0.823, and 0.829, 0.809, 0.841, respectively. In the prediction of OS, the GBM model best performer, with AUC of 0.999, 0.995, 0.978, and 0.981, 0.975, 0.837, and 0.904, 0.860, 0.905. Differential genes in TCGA and GEO suggest that the prediction of radiomics model may be associated with KDELR2 and HK2., Conclusion: Machine learning-based radiomics models help to predict DFS and OS after CCRT in LACC patients, and the combination of tumor and peritumor information has higher predictive efficacy, which can provide a reliable basis for therapeutic decision-making in cervical cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT., Materials and Methods: This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms., Results: Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT., Conclusion: Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners., Methods: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard.", Results: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists)., Conclusion: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers., Competing Interests: Declaration of competing interest None., (© 2024 Published by Elsevier Ltd.)

Objective: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer., Methods: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals., Results: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group., Conclusion: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy., (© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs)., Methods: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve., Results: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66., Conclusions: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital., Competing Interests: Conflict of interest The authors declare that they have no conflict of Interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer., Methods: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD)., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AAc, VSu, NC, AJPdSG, FCM, AR, AAy, J-YL, VSa, FZ, LG, JS, ET, KLin, RLaz, C-LC, RLam, HZ, AO, MC, SPo, TU, SPi, and LRD received funding to their institutions from MSD to support the study. DL reports consulting fees from AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis, and PharmaMar; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, ImmunoGen, GSK, Seagen, and Genmab; support for attending meetings or travel from AstraZeneca, Clovis Oncology, and GSK; participation on a data safety monitoring board or advisory board for Oncoinvest, Corcept, Sutro, AstraZeneca, ImmunoGen, GSK, Seagen, Genmab, Clovis Oncology, GSK, MSD, and PharmaMar; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Clovis Oncology, GSK, MSD, and PharmaMar; and other financial or non-financial interests in AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Incyte, MSD, Roche, Seagen, and Novartis. YX reports participation on a data safety monitoring board or advisory board for MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, and Sanofi; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, and Kaken; and support for attending meetings or travel from Regeneron. GS reports grants or contracts from MSD Italia; consulting fees from Tesaro and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Clovis Oncology Italy. ML reports grants or contracts from MSD, AstraZeneca, and Roche; speaker fees from AstraZeneca and Roche; and meeting support from Roche. PR-E reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from MSD, Asofarma, Novartis, Janssen, and AstraZeneca; support for attending meetings or travel from Roche, Novartis, Asofarma, and AstraZeneca; and participation on a data safety monitoring board or advisory board for Pfizer, Asofarma, Bristol Myers Squibb, and AstraZeneca. NC reports participation on a data safety monitoring board or advisory board for GSK, Toray, Tarveda Therapeutics, Umoja, Kartos, Zentalis, Profound, and Novita Pharmaceuticals. AJPdSG reports consulting fees, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and participation on a data safety monitoring board or advisory board for AstraZeneca, Astellas, Bayer, and Janssen; payment for expert testimony from Janssen; and support for attending meetings or travel from Janssen, MSD, and Bayer. FCM reports speaker fees from MSD, Bristol Myers Squibb, GSK, Eli Lilly, and BMS; payment for expert testimony from MSD, Janssen, GSK, Eli Lilly, and Bristol Myers Squibb; and meeting and travel support from MSD and Amgen. AR reports advisory board fees from MSD Israel. J-YL reports grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, Bristol Myers Squibb, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, OncoQuest, Ono, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and Ono. FZ reports grants or contracts, consulting fees, payment for expert testimony, support for attending meetings or travel, participation on a data safety monitoring board or advisory board, and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, from AstraZeneca, Eli Lilly, MSD, Pfizer, Roche, Daiichi Sankyo, Merck, Novartis, Genesis Pharma, and Gilead. LG reports institutional grants from GSK, Pfizer, MSD, Karyopharm, Tesaro, IMV, Alkermes, Clovis Oncology, ImmunoGen, Roche, Mersana, and AstraZeneca; consulting fees from GSK, Merck, Eisai, and Novocure; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from GSK, Merck, Eisai, Novocure, and Corcept; and support for attending meetings or travel from Corcept, GSK, AstraZeneca, and Merck. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, Eisai, and Novartis; support for attending meetings or travel from GSK, AstraZeneca, Roche, Novocure, ImmunoGen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO. KLin reports grants or contracts from GSK (paid to institution); payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Eisai; and participation on a data safety monitoring board or advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK. HZ reports contracted research and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events for MSD. AO reports grants or contracts from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Roche, ImmunoGen, MSD de España, Millennium Pharmaceuticals, PharmaMar, Regeneron, and Tesaro (paid to institution); consulting fees and participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, Roche, Genmab, GSK, ImmunoGen, iTeos, MSD de España, Mersana, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen, and Sutro; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiana de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; and support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche. SPo reports consulting fees from MSD, AstraZeneca, GSK, and Eisai; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, support for attending meetings or travel, and advisory board fees from MSD, AstraZeneca, and GSK; and leadership or fiduciary role in other board, society, committee, or advocacy group for the Austrian Association of Gynecologic Oncology (unpaid). SPi reports research funding from Roche, MSD, AZ, Pfizer, and GSK; and honoraria from AZ, Roche, MSD, GSK, and PharmaMar. LRD reports research funding (paid to institution) from and acting as an expert advisor (unpaid) for Merck & Co; writing fees for expert content for UpToDate; participation on a scientific advisory board for Aadi Bioscience; and serving on the Editorial Board of the British Journal of Obstetrics and Gynaecology. KLi, KY, ST, and SMK are full-time employees of MSD and hold stock or restricted stock units in the company., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200-284 J/cm 2 for cervical canal and the vaginal surfaces, 100-150 J/cm 2 for cervix surface. Vaginal giant CA and LSIL lesions got complete remission at 6-month follow-up. Mild tolerable adverse reactions were observed after STBF-PDT and relieved in 24 h. Thus, the combination of Ho: YAG laser and STBF-PDT may be a novel option for cervical and vaginal giant CA and LSIL, especially for special vaginal fornix areas., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare, (Copyright © 2024. Published by Elsevier B.V.)

This study provides an overview of the effectiveness and safety of PDT for the treatment of HPV-associated precancerous cervical conditions and contains recent findings from relevant research studies. A comprehensive literature search of MEDLINE/PubMed, Cochrane Central Library, and Google Scholar was conducted, including analytic epidemiological studies, and 11 papers were included. The narrative synthesis approach was used to summarize the results of the included studies. Studies were critically appraised using The Joanna Briggs Institute (JBI) tool for assessing the risk of bias. The results of the study demonstrate that CRR for HPV remission ranges from 66.7 % to 92.73 %, whereas for CIN1 it fluctuates from 57.1 % to 83.3 %. The frequency of recurrence of the disease ranged from 3.3 % to 8.9 % during the follow-up period of up to 2 years. Adverse events were observed in 8 (66 %) studies and the most common were cervical stenosis, abdominal pain, vaginal pain, and focal edema. Five types of topical and intravenous applications along with lasers of various wavelengths and intensities were mostly used. However, all studies demonstrated relatively similar results. According to the results, PDT has demonstrated favorable outcomes, but no impressive effect on the treatment of CIN. It should be emphasized, that the effectiveness of PDT for the treatment of HPV-associated CIN may vary depending on some variables, including the kind of PDT agent used, the dosage, duration and frequency of PDT administration, the severity and location of the lesions, and the host immunological response., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To characterize the real-world treatment patterns and outcomes of patients with high-risk locally advanced cervical cancer (HR-LACC)., Methods: This retrospective study identified and randomly selected adults diagnosed between 2010 and 2018 from the ConcertAI Oncology Dataset. For patients initially treated with concurrent chemoradiotherapy (CCRT), we estimated real-world progression-free survival (rwPFS) among those with persistent disease, real-world time on CCRT, and recurrence-free survival (rwRFS) using Kaplan-Meier methods., Results: The cohort included 300 patients. Median age at diagnosis was 51 years. 53.7 % were White and 30.0 % were Black; 52.0 % were premenopausal; 89.3 % had squamous cell histology; 75.3 % had stage III disease, and 92.7 % had no evidence of performance status impairment. Initial treatment included CCRT (N = 229), surgery (N = 28), antineoplastics only (N = 11), and radiation only (N = 5). Twenty-seven patients were untreated. Baseline characteristics for the CCRT-first patients were similar to the overall cohort; their median real-world time on treatment was 1.6 months; 78.2 % received cisplatin for a median of 1.2 months; 28.4 % received antineoplastics after CCRT, and 11.8 % initiated a second antineoplastic therapy. Of the CCRT-first patients, 27/143 with a complete response had subsequent recurrent disease (median rwRFS not reached). 179 patients had persistent disease, among whom median (95 % confidence interval [CI]) rwPFS was 29.7 (16.9-59.3) months., Conclusion: In this study of United States-based clinical practices, most HR-LACC patients received CCRT as initial treatment. Many patients developed persistent disease after CCRT indicating a need for improved first treatment and maintenance options., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC and CD report research funding to their institution from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. MG was employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA at the time this research was conducted. MM and LC are employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. KY is employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, holds stock or stock options in Merck & Co., Inc., Rahway, NJ, USA, and reports travel, accommodations, or expenses from Merck & Co., Inc., Rahway, NJ, USA., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Patients with gynecologic malignancies have high psychosocial and symptom burden. We report data from a prospective trial evaluating patient-reported outcome (PRO) metrics in women undergoing definitive chemoradiation with brachytherapy (BT)., Methods and Materials: A single-institution prospective trial evaluating outcomes of gynecologic cancer patients undergoing BT. Questionnaires to assess PROs at baseline, post-BT, and 60-day follow-up were collected, using European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 and European Organization for Research and Treatment of Cancer-Quality of Life Question-Cervical Cancer Module validated metrics. Higher scores for functional scales/global health and lower scores for symptom items are favorable. European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 mean scores were compared with a reference population. When comparing the study population between time points, medians, interquartile range, and nonparametric testing were used., Results: Thirty-three patients were enrolled, and 29 (88%) completed baseline PRO metrics. Mean global health score was worse than the reference population of women with any cancer diagnosis at baseline (41 vs 59, P < .001) and decreased further at follow-up (42 vs 33, P = .005). Compared with the cervical cancer reference, our patients had significantly worse social function (62 vs 83, P = .03), financial toxicity (49 vs 10, P < .001), fatigue (49 vs 34, P = .04), nausea/vomiting (26 vs 9, P = .001), and appetite loss (36 vs 16, P = .004).The majority of patients described depression (53%), feeling less attractive (64%), life interference (66%), and/or worry (69%). At baseline, higher global health scores were associated with improved physical functioning (R 2 0.58, P < .001), social functioning (R 2 0.56, P < .001), and body image (R 2 0.40, P < .001); lower scores with more symptom burden (R 2 0.71, P < .001), financial toxicity (R 2 0.50, P < .001), and/or sexual worry (R 2 0.25, P = .001)., Conclusions: Patients with cervical cancer have significant symptom burden and psychosocial toxicity, contributing to decreased quality of life. These data highlight the need for improved support throughout treatment for this high-risk population., Competing Interests: Disclosures None., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Cervical cancer is the most common and deadly female cancer on the worldwide scale. Considering that the conventional surgery treatment and chemotherapy would cause certain side effects, photothermal therapy (PTT) possesses desired therapeutic efficiency and insignificant side effects against cervical cancer. However, the lack of efficient and safe photothermal agents that operate in the second near-infrared (NIR-II) window is a main obstacle hindering the clinical transformation of PTT. Titanium dioxide (TiO 2 )-based nanomaterials are commonly applied in the biomedicine field, but the weak absorption and low photothermal conversion efficiency (PCE) of TiO 2 in the NIR region limit their applications in PTT. Herein, we report the oxygen vacancy engineering that is a robust strategy to regulate the electronic structures of TiO 2 for photothermal conversion properties optimizing. The obtained oxygen vacancy-doped TiO 2-x nanosheets exhibit strong NIR-II absorption and high PCE owing to their decreased bandgap. Specifically, the PCE of TiO 2-x nanosheets is determined to be 69.5 % in the efficient NIR-II window, which is much higher than that of widely reported PTT agents. Complete tumor recession without recurrence or pulmonary metastasis is realized by enhanced NIR-II PTT via TiO 2-x nanosheets at an ultralow and safe laser exposure (0.6 W/cm 2 ). Our findings suggest that oxygen vacancy engineering of nanomaterials could regulate their photothermal conversion performances, promoting the further application of TiO 2 -based nanomaterials in the biomedical., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Vascular endothelial growth factor (VEGF) is a highly specific factor for tumors growth. However, the study on the mechanism of VEGF in cervical cancer, and the correlation between the expression level of VEGF and the therapeutic evaluation, prognosis of cervical cancer is not clear till now., Methods: In this study, RT-qPCR and IHC were used to evaluate the abnormal expression of VEGF in cervical cancer. The survival plots of the VEGF expression related to OS were observed by using the KM plotter. The mAbs against VEGF were screened and identified by ELISA addicted test, indirect ELISA, Western-blot, and dot-ELISA. We designed and prepared the overlapping truncations (V1, V2, V3) of VEGF to identify the B cell epitopes. Then, the epitopes recognized by anti-VEGF mAbs were mapped and displayed on a 3D structure of VEGF by using the PyMOL software. The highly specific and sensitive sandwich ELISA was established to detect the total VEGF quantification in 206 clinical sera samples, thus to evaluate the changes of VEGF before and after chemoradiotherapy in cervical cancer patients., Results: The VEGF was high expressed in cervical cancer tissues and cells, resulting a poor prognosis of cervical cancer. The mAbs 2E5 and 6D9 were selected with the titer of 1:256000 and 1:128000 respectively. The mAbs both had strong ability to combine with VEGF protein within 15 min and were identified as subclass IgG1 with κ-type light chains. 2E5 bound to V1 and V2, recognizing the N-terminal (1-121 aa) of VEGF, however 6D9 bound to V3, recognizing the C-terminal (116-174 aa) of VEGF. The 206 clinical samples were tested with the established VEGF-DAS-ELISA and calculated according to the equation (y = 0.0042088× + 0.105109, R 2  = 0.998). The results indicated that the expression levels of VEGF in cervical cancer samples were positively higher than those in normal samples. Importantly, we found the expression level of sera VEGF in cervical cancer patients decreased significantly after chemoradiotherapy. Therefore, the variable of VEGF levels in cervical cancer patients before and after treatment can be used as a new indicator of efficacy evaluation to guide the clinical treatment of cervical cancer., Conclusion: A sensitive DAS-ELISA was established successfully, using which we can track the VEGF to evaluate the efficacy and estimate prognosis of cervical cancer. It is helpful for the diagnosis, therapeutic evaluation and prognosis of cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2022. Published by Elsevier B.V.)

Background: Hematologic toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer can lead to treatment breaks and compromise efficacy., Purpose: To evaluate the association between severe hematologic toxicity (HT) and clinical factors and pelvic apparent diffusion coefficient (ADC) during CCRT of cervical cancer patients., Methods: Data from 120 patients with cervical cancer who were treated with CCRT from January 2016 and December 2018 were retrospectively analyzed. The clinical data (age, menopausal status, clinical stage, body mass index, chemotherapy regimen and chemotherapy cycle) of the patients were collected, and the cohort were divided into two groups based on the HT grade: HT3+ group (HT grade ≥ 3; 66 patients) and HT3- group (HT grade<3; 54 patients). All patients performed MRI before CCRT, and pelvic (ilium, pubis, ischium) ADC value was measured on ADC map. The correlation between severe HT and clinical parameters and pelvic ADC value were analyzed by univariate analysis, and the diagnostic performance was further assessed by receiver operating characteristic (ROC) analysis., Results: In univariate analysis, the menopausal status (p = 0.012) and chemotherapy regimen (p = 0.011) were significantly correlated with severe HT in overall patients, and menopausal patients or patients receiving paclitaxel plus cisplatin (TP) regimen were more likely to develop severe HT. HT3+ group showed a significantly lower pelvic ADC value than HT3- group. The ADC value cut-offs derived from our study for predicting severe HT was 0.317 × 10 -3  mm 2 /s in overall patients. Neither clinical parameters nor pelvic ADCs were associated with severe HT in menopausal patients when analyzed separately (p > 0.05)., Conclusions: Severe HT was significantly associated with menopausal status and chemotherapy regimen in patients with cervical cancer treated with CCRT, and HT3+ group showed a lower pelvic ADC value., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Background: We evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients., Design: Patients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m 2 or cisplatin 40 mg/m 2 concurrently., Results: One hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness., Conclusions: Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Despite screening programs for early detection and the approval of human papillomavirus vaccines, around 6% of women with cervical cancer (CC) are discovered with primary metastatic disease. Moreover, one-third of the patients receiving chemoradiation followed by brachytherapy for locally advanced disease will have a recurrence. At the end, the vast majority of recurrent or metastatic CC not amenable to locoregional treatments are considered incurable disease with very poor prognosis. Historically, cisplatin monotherapy, then a combination of cisplatin and paclitaxel were considered the standard of care. Ten years ago, the addition of bevacizumab to chemotherapy demonstrated favorable data in terms of response rate and overall survival. Even with this improvement, novel therapies are needed for the treatment of recurrent CC in first as well as later lines. In the last decades, a better understanding of the interactions between human papillomavirus infection and the host immune system response has focused interest on the use of immunotherapeutic drugs in CC patients. Indeed, immune checkpoint inhibitors (pembrolizumab, cemiplimab, and others) have recently emerged as novel therapeutic pillars that could provide durable responses with impact on overall survival in patients in the primary (in addition to chemotherapy) or recurrent (monotherapy) settings. Tisotumab vedotin, an antibody-drug conjugate targeting the tissue factor, is another emerging drug. Several trials in monotherapy or in combination with immunotherapy, chemotherapy, or bevacizumab showed very promising results. There is a high need for more potent biomarkers to better accurately determine which patients would receive the greatest benefit from all these aforementioned drugs, but also to identify patients with specific molecular characteristics that could benefit from other targeted therapies. The Cancer Genome Atlas Research Network identified several genes significantly mutated, potentially targetable. These molecular data have highlighted the molecular heterogeneity of CC., Competing Interests: Disclosure CG grant/contracts: Astra-Zeneca; consulting fees: Ipsen, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD); honoraria for lectures, etc.: MSD, Bristol Myers Squibb (BMS), Ipsen, Pfizer, Pharmamar, AstraZeneca, GSK; support for meetings and/or travel: Ipsen, Pharmamar, Pfizer, MSD; participation on a data safety monitoring board or advisory board: MSD, BMS, Ipsen, AstraZeneca, GSK, Eisai. GJ grant/contracts: Novartis, Roche, Pfizer; consulting fees: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, Daiichi Sankyo, AbbVie; honoraria for lectures, etc.: Novartis, Roche, Amgen, Pfizer, BMS, Lilly, AstraZeneca, Seagen; support for meetings and/or travel: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca; participation on a data safety monitoring board or advisory board: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, Daiichi Sankyo, AbbVie; other financial or non-financial interests: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, MedImmune, Merck. FK grant/contracts: MSD, AstraZeneca, Pharmamar, Roche; consulting fees: MSD; honoraria for lectures, etc.: MSD, AstraZeneca, Pharmamar; support for meetings and/or travel: MSD, AstraZeneca, Roche; participation on a data safety monitoring board or advisory board: MSD, AstraZeneca. IR-C grant/contracts: BMS, MSD, GSK; consulting fees: GSK, AstraZeneca, Clovis, Pharmamar, Mersana, MSD, Novartis, Deciphera, Roche, Genentech; honoraria for lectures, etc.: GSK, AstraZeneca, Clovis, Pharmamar, Mersana, MSD, Novartis, Deciphera, Roche, Genentech; support for meetings and/or travel: GSK, Roche, AstraZeneca; participation on a data safety monitoring board or advisory board: Athena and Attend trials. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To provide a comprehensive assessment of women cancer in India utilizing the systematically collected data on all cancers by the National Cancer Registry Programme (NCRP)., Methods: The study examined 10,2287 cancer cases among women cancers providing cancer burden for major anatomical sites. Aggregated data of 28 PBCRs and 58 HBCRs under NCRP for 2012-16 was analysed for incidence rates, trends, cumulative risk of developing cancer, stage at detection and treatments offered., Results: Study results have found region -wide variation of women cancers by indicating highest proportions in western followed by southern region of India. North-Eastern region had lowest proportion. It was observed that breast is highest ranking cancer in most registry areas of urban agglomerations of country while cancer cervix was leading site in registries of rural areas like Barshi (15.3) and Osmanabad &Beed (13.1). States of Mizoram (23.2) and Tripura (9.5) along with Pasighat, Cachar and Nagaland. Median age of occurrence for women for these anatomical sites ranged from 45 to 60 years of age. For cancer breast, cervix and ovary -most cases were detected with regional spread. These findings were different for cancer corpus uteri where registries have reported higher proportions (49.3 %) of localized stage at detection. Loco regional cancers had higher proportions of multimodality treatments., Conclusion: Study provides a foundation for assessing the status of women cancers in the country. Variations between geographies would guide appropriate support for action to strengthen efforts to improve cancer prevention and control in underserved areas of the country. This would facilitate advocacy for better investments and research on women cancers., Competing Interests: Declarations of interest There are no potential conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To identify the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and magnetic resonance imaging (MRI)-based radiomics combined with clinical prognostic factors (CPF) in predicting concurrent chemoradiotherapy (CCRT) sensitivity of locally advanced cervical cancer (LACC)., Methods: A retrospective analysis of 163 patients (assigned to training or test groups) who underwent conventional MRI and IVIM-DWI before CCRT were divided into sensitive and resistant groups according to their efficacy at 6 months after CCRT. Per-treatment IVIM-DWI parameters (ADC, D, D ⁎ and f value), 3D texture features (from axial T 2 WI) and CPF were measured, analyzed and screened. The prediction model and its nomogram were developed by combining screened parameters and then validated internally and externally., Results: Clinical stage, f value, D value, InverseVariance, SizeZoneNonUniformity, and Minimum were selected to construct prediction model. All parameters except D value showed independent diagnostic value in multivariate Logistic regression analysis and composed prediction model, with AUCs of 0.987 and 0.984 for training and test groups, respectively. The calibration curve (Brier score of 0.042, C-index of 0.987), decision curve and clinical impact curve further demonstrated the reliability and clinical value of prediction model., Conclusion: IVIM-DWI, MRI-based radiomics and CPF showed high clinical value in predicting CCRT sensitivity for LACC with better predictive performance when combined., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To build radiomics based OS prediction tools for local advanced cervical cancer (LACC) patients treated by concurrent chemoradiotherapy (CCRT) alone or followed by adjuvant chemotherapy (ACT). And, to construct adjuvant chemotherapy decision aid., Methods: 83 patients treated by ACT following CCRT and 47 patients treated by CCRT were included in the ACT cohort and non-ACT cohort. Radiomics features extracted from primary tumor area of T2-weighted MRI. Two radiomics models were built for ACT and non-ACT cohort in prediction of 3 years overall survival (OS). Elastic Net Regression was applied to the the ACT cohort, meanwhile least absolute shrinkage and selection operator plus support vector machine was applied to the non-ACT cohort. Cox regression models was used in clinical features selection and OS predicting nomograms building., Result: The two radiomics models predicted the 3 years OS of two cohorts. The receiver operator characteristics analysis was used to evaluate the 3 years OS prediction performance of the two radiomics models. The area under the curve of ACT and non-ACT cohort model were 0.832 and 0.879, respectively. Patients were stratified into low-risk group and high-risk group determined by radiomics models and nomograms, respectively. And, the low-risk group patients present significantly increased OS, progression-free survival, local regional control, and metastasis free survival compare with high-risk group (P < 0.05). Meanwhile the prognosis prediction performance of radiomics model and nomogram is superior to the prognosis prediction performance of Figo stage., Conclusion: The two radiomics model and the two nomograms is a prognosis predictor of LACC patients treated by CCRT alone or followed by ACT., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Treatment for cervical cancer can cause cessation of ovarian function in young patients. Physician counselling practices related to premature menopause and hormonal therapy (HT) for young cervical cancer patients is not well known. The primary objective of this study was to assess the frequency of HT counselling and usage among young cervical cancer patients. The secondary objective was to assess clinical and demographic factors associated with HT use., Methods: This retrospective review included adult women younger than age 50 years who received treatment for cervical cancer between 2007 and 2017. Patient and disease characteristics, disease outcome, and documentation of HT and bone health counselling were collected from electronic records. Descriptive statistical analysis was performed for the primary objective, and independent t tests and χ 2 tests were used for secondary objective data analysis., Results: In this study, 67 premenopausal women with cervical cancer (stages I-III) lost ovarian function from cancer treatment, of whom 52% had received counselling on HT from their oncologists. Thirty-nine percent of patients were using HT at the time of their last review. Younger women were more likely than older women to receive HT counselling (mean age 37.3 ± 6.6 y vs. 42.4 ± 6.0 y; P = 0.001). Counselling frequency and usage of HT were not affected by cancer stage, body mass index, or smoking status., Conclusion: Young asymptomatic patients should receive HT if not contraindicated, yet half of qualified cervical cancer patients in this study received counselling on premature menopause and HT. Structured counselling on HT should be implemented as an integral part of cervical cancer care., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: Radiotherapy remains an essential part of the management of locally advanced cervical cancer. Post-treatment surveillance allows for tumor response assessment and early detection of progressive prosecutions or local recurrences that may benefit from salvage treatment. The objective of this work is to assess the effectiveness of this therapeutic modality., Materials Methods: This is a retrospective study of 69 patients treated with concomitant radiation chemotherapy followed by high dose rate intracavitary brachytherapy. The tumor response was assessed by gynecologic physical examination at three months after the end of treatment., Results: Median age of patients is 54.9 years (33-78 years). The most common histological type is squamous cell carcinoma (89.9%). The average dose received during external radiotherapy is 52.2Gy (46-60Gy). The average dose received during brachytherapy is 27.5Gy (18-28Gy). Three months after completion of treatment, 95.6% of patients had complete tumor remission, and only 4.4% had a tumor residue of 1cm., Conclusion: Radiation chemotherapy with brachytherapy allows for improved short-term local control in cervical cancer., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The aim of this article is a retrospective analysis of PDT effectiveness in the treatment in early-stage cervical cancer and also analysis of HPV elimination via PDT MATERIAL AND METHODS: A total of 28 patients were analyzed retrospectively, all with PDT treatment for early-stage cervical cancer. Patients underwent one PDT session or a multi-course PDT approach. This depended on individual reaction and response to therapy after the first session. A multi-course approach was performed over two months. Treatments were performed from 2015 to 2020. Relapse-free probability was assessed for these patients by Kaplan Meier estimator at 60 months and HPV elimiantion was also examined.., Results: HPV elimination was in 82% of cases in three-month period after PDT (R 2  = 0.71). Among the analyzed cases, full HPV elimination was detected in more than 90% of cases. Relapse-free probability from cervical cancer is 0,8 (CI95%: 0,53-1) at 60 months. Patients had mild (35.7%) and severe (28.6%) leucocyte reactions after PDT in three months., Conclusion: The article demonstrates treatment results for CC and detected a five-year period relapse-free probability after PDT. Patients completing a multi-treatment PDT protocol for invasive cervical cancer can achieve both high response rate and relapse-free survival., (Copyright © 2021. Published by Elsevier B.V.)

External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The island of Mayotte is part of the French territory and one of the European Union's Outermost Regions but there is a significant lack of data and research on health and cancers in Mayotte. This article reviews the literature on health, disease and cancer in Mayotte, from the perspectives of social science and epidemiology. It starts by shedding light on the specificities of Mahoran demography and society, and shows the healthcare infrastructure is insufficient to meet the population's needs. It then reviews social science studies on health and illness in Mayotte and shows that the political issue of migration permeates the management and the experiences of health on the island. It ends with a focus on the epidemiology of cervical cancer and a review of the available data on screening, treatment and prevention. The article concludes with a quick review of ongoing research and urgently calls for more data and research on this critical public health issue., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Various articles have addressed the impact of hysterectomy on survival outcomes of patients with locally advanced cervical cancer (LACC). This study was designed to evaluate whether treatment modalities that include hysterectomy as an option for the treatment of LACC patients are superior to standard chemo-radiotherapy., Methods: Literature search was performed using the Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Clinicaltrials.gov databases. Observational (prospective and retrospective) and randomized trials that included adjuvant hysterectomy in at least one treatment group. A network meta-analysis was carried out in R 3.4.3 using the pcnetmeta package, which uses a Bayesian hierarchical model. The credibility of evidence was appraised with the Confidence In Network Meta-Analysis (CINeMA) tool., Results: Overall, 14 studies were included in the present systematic review that involved 2302 patients with LACC. Every potential combination of external beam radiotherapy, intracavitary brachytherapy, chemotherapy and surgery was considered to be eligible for inclusion. The results of the network meta-analysis suggested that the various treatment alternatives did not differ in terms of survival outcomes. Furthermore, the qualitative analysis revealed that hysterectomy was accompanied by considerable perioperative morbidity; therefore, rendering its addition to the treatment scheme of LACC patients inappropriate., Conclusions: Patients with LACC do not seem to benefit substantially by the addition of hysterectomy to standard chemo-radiotherapy. Moreover, the operation is accompanied by substantial perioperative morbidity, thus, its implementation in clinical practice should be avoided., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To explore the relationships of health literacy, preferred involvement, and patient activation with perceived involvement in care among patients with breast and cervical cancer., Methods: A cross-sectional survey was conducted with patients aged 20 years or older, aware of their cancer diagnosis, and currently receiving care at the National Cancer Center, Mongolia. Descriptive statistics and multivariate regression analysis were used to identify the relationships among study variables., Results: Two hundred twenty-five patients were included in the final analysis. Patients' perceived involvement was examined as two subdomains: patient information seeking (PIS) and patient decision-making (PDM). Patient health literacy was found to only significantly influence PIS, and patient preferred involvement demonstrated a significant influence only on PDM. However, patient activation predictor was found to significantly influence both PIS and PDM (PIS [β = 0.22, p = 0.00] and PDM [β = 0.14, p = 0.00])., Conclusion: Health literacy, preferred involvement, and patient activation each demonstrated distinct influences on patients' perceived involvement subdomains, with patient activation being the most important predictor., Practice Implications: Comprehensive strategies at the healthcare organization, professional, and patient levels may help to facilitate and advance patient involvement in care, and ultimately improve the quality of healthcare services respective to domain of patient-centeredness., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The sub-committee constituted by the Indian Council of Medical Research (ICMR) for the management of cervical cancer (CC) detailed in the consensus document (2016) reported CC as a significant cause of morbidity and mortality in women. The incidence of an increase in CC and associated mortality in women is a major cause of cancer. To date, human papilloma viral (HPV) infection accounts for more than 99% of CC. However, there are individuals infected with HPV do not develop CC. There is a greater correlation between HPV infection and upregulation of the epidermal growth factor receptor (EGFR) signaling cascade during the initiation, sustenance, and progression of CC. Therefore, EGFR is often targeted to treat CC using tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAB). The current review analyzed the existing clinical/pre-clinical studies and the significance of EGFR abundance using the Kaplan-Meier (KM) survival plot analysis for disease-free survival (DFS) and overall survival (OS). We performed a series of bioinformatics analyses to screen the crucial role of the EGFR gene in CC. Further, different transcription factors that are dysregulated due to EGFR abundance and their relevance were determined using computational tools in this review. Endogenous microRNAs (miRNA) that undergo changes due to alterations in EGFR during CC were identified using computational database and consolidated the information obtained with the published in the area of miRNA and EGFR with special reference to the initiation, sustenance and progression of CC. The current review aims to consolidate contemporary approaches for targeting CC using EGFR and highlight the current role of miRNA and genes that are differently regulated during CC involving EGFR mutations. Potential resistance to the available EGFR therapies such as TKIs and mABs and the need for better therapies are also extensively reviewed for the development of newer therapeutic molecules with better efficacy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Upon discovery of lymph node metastasis during radical hysterectomy with pelvic lymphadenectomy in early-stage cervical cancer, the gynaecologist may pursue one of two treatment strategies: abandonment of surgery followed by primary (chemo)radiotherapy (PRT) or completion of radical hysterectomy, followed by adjuvant (chemo)radiotherapy (RHRT). Current guidelines recommend PRT over RHRT, as combined treatment is presumably associated with increased morbidity. However, this review of literature suggests there are no significant differences in survival and recurrence and total proportions of adverse events between treatment strategies. Additionally, both strategies are associated with varying types of adverse events, and affect quality of life and sexual functioning differently, both in the short and long term. Although total proportions of adverse events were comparable between treatment strategies, lower extremity lymphoedema was reported more often after RHRT and symptom experience (e.g. distress from bladder or bowel problems) and sexual dysfunction more often after PRT. As reporting of adverse events, quality of life and sexual functioning were not standardised across the articles included, and covariate adjustment was not conducted in most of the analyses, comparability of studies is hampered. Accumulating retrospective evidence suggests no major differences on oncological outcome and morbidity after PRT and RHRT for intraoperatively discovered lymph node metastasis in cervical cancer. However, conclusions should be considered cautiously, as all studies were of retrospective design with small sample sizes. Still, treatment strategies seem to affect adverse events, quality of life and sexual functioning in different ways, allowing room for shared decision-making and personalised treatment., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Once again this year, the Editorial Board presents here a summary of the most important advances in treatment and patient care in oncology over the past year. Some of the most important results in breast and gynecological cancers (endometrium and cervix), lung, brain, urologic and digestive cancers. Are also presented progresses in hematological malignancies, pediatric oncology, and of course supportive care essential for our patients., (Copyright © 2021. Published by Elsevier Masson SAS.)

Aims: Human papillomavirus (HPV) L1, L2 and E7 proteins were used as target antigens for development of preventive and therapeutic vaccines. Moreover, linkage of antigens to heat shock proteins (HSPs) could enhance the potency of vaccines. Curcumin and nanocurcumin compounds were suggested as the chemopreventive and chemotherapeutic agents against cancer. In this study, two multiepitope DNA and peptide-based vaccine constructs (L1-L2-E7 and HSP70-L1-L2-E7) were used along with curcumin and nanocurcumin to evaluate immune responses, and protective/therapeutic effects in tumor mouse model., Main Methods: At first, the multiepitope L1-L2-E7 and HSP70-L1-L2-E7 fusion genes were subcloned in eukaryotic and prokaryotic expression vectors. The recombinant multiepitope peptides were generated in E. coli strain. Then, the cytotoxic effects of curcumin and nanocurcumin were evaluated on HEK-293 T non-cancerous and C3 cancerous cells. Finally, mice vaccination was performed using different regimens. Curcumin and nanocurcumin compounds were administered alone or along with different vaccine constructs., Key Findings: Our data indicated that the use of nanocurcumin along with the multiepitope HSP70-L1-L2-E7 vaccine construct could completely protect mice against HPV-related C3 tumor cells, and eradicate tumors in a therapeutic test. Furthermore, nanocurcumin showed higher protection than curcumin alone. Generally, curcumin and nanocurcumin compounds could reduce tumor growth synergistically with the multiepitope vaccine constructs, but they did not influence the immune responses in different regimens., Significance: These data demonstrated that the designed multiepitope vaccine constructs along with curcumin and nanocurcumin can be used as a promising method for HPV vaccine development., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Node involvement is one of the main prognostic factors for cervical cancer. Para-aortic lymph node (PALN) assessment is crucial for treating advanced cervical cancer, to define irradiation fields. Objective of this study was to develop a score predicting para-aortic lymph node involvement in patients with advanced cervical cancer., Patients and Method: We performed a multicenter, retrospective, study on 9 French centers from 2000 to 2015, including patients with advanced squamous cell cervix carcinoma who had PALN status assessed by imaging and/or by surgery. Factors associated with a risk of PALN involvement were determined by univariate and multivariate analysis using a logistic regression model. A score was then developed and validated., Results: A total of 1446 patients treated for cervical cancer were included. Of these, 498 had an advanced squamous cell cervical cancer. Ninety-one patients (18.3%) had positive PALN. After univariate and multivariate analysis, tumor size on pelvic MRI, initial SCC, and suspected pelvic node involvement on PET-CT were included in our score. This model allowed the population to be divided into 3 risk groups. Area under the ROC curve of the score was 0.81 (95%CI = 0.72-0.90). In the low-risk group, 9% (28/287) had PALN involvement, whereas in the high-risk group, 43% (22/51) had PALN involvement., Conclusion: We developed a simple score predicting PALN involvement in advanced cervical cancers. Three risk groups can be defined, and patients considered to be at low risk may avoid para-aortic staging as well as extensive field irradiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The aim of the present study was to compare the effects (assessed by clonogenic survival and γH2AX foci assays) of low-dose fractionated radiation LDFR (4 × 0.125 Gy, 4 × 0.25 Gy and 4 × 0.5 Gy) versus single radiation doses (0.5 Gy, 1 Gy and 2 Gy) on cisplatin and paclitaxel in HRS-negative cervix cancer cell lines SiHa and CaSki to see if the effects of LDFR can emerge in cells that not present low-dose hyper-radiosensitivity (HRS) phenomenon. Additionally, we report the effects in normal fibroblasts (HRS-negative and HRS-positive) from two patients with cervix cancer to see if the chemopotentiating effects of LDFR also apply to normal cells. LDFR (4 × 0.125 Gy, 4 × 0.25 Gy and 4 × 0.5 Gy) as well as single doses (0.5 Gy, 1 Gy and 2 Gy) enhanced cytotoxicity of cisplatin and paclitaxel in all the cell lines. Cisplatin-potentiating effects were maximum with LDFR 4 × 0.5 Gy, and were two-fold greater than those with a single dose of 2 Gy in SiHa, CaSki and HFIB2 cells. Paclitaxel-enhancing effects were also maximum with LDFR 4 × 0.5 Gy, however only in HRS-positive HFIB2 fibroblasts were significantly greater than those with a single dose of 2 Gy. The results demonstrate that LDFR may enhance the effects of cisplatin and paclitaxel in SiHa and CaSki cells, although they lack HRS phenomenon, and show that the magnitude of the potentiating effects of LDFR depends on cytostatic type and the size of low doses. In normal fibroblasts the chemopotentiating effects of LDFR seem to depend on HRS status. In conclusion, the unique enhancing effects of LDFR on cisplatin in cervical cancer cell lines, even when HRS negative, suggest that all patients with cervical cancer may benefit from the addition of LDFR to adjuvant cisplatin-based chemotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: The 5-fraction scheme (5×5-5.5Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy., Materials and Methods: The medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed., Results: Thirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose=25Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29-87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTV HR reached 79.5Gy (EQD2). Median D90% to CTV IR reached 59.5Gy (EQD2). Median Bladder D2cc was 69.8Gy (EQD2). Median Rectum D2cc was 58.3Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4-5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n=7, 18.4%), nodal (n=6, 15.7%) and/or distant (n=7, 18.4%) relapse. Three-year overall survival rate was of 81.6%., Conclusion: The 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients' characteristics (age, comorbidities) may explain such results., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC., Methods: We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR., Results: HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013)., Conclusion: This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing The data that support the findings of this study are available from Institut Curie but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Institut Curie., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the performances of systematic posttreatment pelvic magnetic resonance imaging (PPMRI) in predicting prognosis of patients treated with chemoradiation therapy (CRT) for locally advanced cervical cancer (LACC)., Materials and Methods: Multi-institutional data from 216 patients presenting FIGO IB2-IIB cervical cancer for which PPMRI was performed following CRT were retrospectively reviewed. Incomplete response was defined as the identification of persistent lesion on PPMRI. Primary endpoints were patients' 5-year recurrence free (RFS) and overall (OS) survivals. Secondary endpoint was the identification of residual histologic disease on hysterectomy specimens when completion surgery was performed., Results: PPMRI identified an incomplete response in 102 (47.2%) cases. A 70% or more reduction in tumor size on PPMRI was identified as the best predictive cut-off for recurrence (37.7% sensitivity and 78.7% specificity) and death (50% sensitivity and 77.9% specificity) with significant impact on those risks (HRa: 0.42; 95%CI: 0.23-0.77 and HRa: 0.18; 95%CI: 0.06-0.50, respectively). Completion hysterectomy was performed in 117 (54.4%) cases, with histologic residual disease in 55 (47.4%). PPMRI demonstrated 74.5% sensitivity and 50.8% specificity in predicting residual disease. Although survival of patients with complete response at PPMRI was not impacted by completion hysterectomy, it significantly increased 5-year RFS and OS of those with incomplete response: 38.7% vs. 65.3% (p < 0.001) and 63% vs. 82.9% (p = 0.038), respectively., Conclusion: A 70% or more reduction of in tumor size on PPMRI following CRT in patients with LACC is predictive of RFS and OS. PPMRI could help triaging patients who could benefit from completion hysterectomy., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)