Personalized strategies for brachytherapy of cervix cancer.

Among most tailored approaches in radiation oncology, the development of brachytherapy for the treatment of cervical cancer patients has benefited from various technological innovations. The development of 3D image-guided treatments was the first step for treatment personalization. This breakthrough preceded practice homogenization and validation of predictive dose and volume parameters and prognostic factors. We review some of the most significant strategies that emerged from the ongoing research in order to increase personalization in uterovaginal brachytherapy. A better stratification based on patients and tumors characteristics may lead to better discriminate candidates for intensification or de-escalation strategies, in order to still improve patient outcome while minimizing the risk of treatment-related side effects.

[How do women in Réunion Island want to perform HPV test on vaginal sampling as part of cervical cancer screening?] / Modalités préférées des femmes à la Réunion pour le dépistage du cancer du col de l'utérus par prélèvement vaginal.

BACKGROUND: Since the introduction of HPV testing as a first-line screening method for women aged 30 and over, vaginal sampling (VS) by a healthcare professional or self-sampling (SS) is now possible for women who have not responded to the organized screening program using cervical uterine sampling. The aim of this study was to understand the choices made by a sample of women from La Reunion would like to perform their VS, and the content of the instructions they would like to receive. METHODS: We conducted a cross-sectional descriptive study using a single-answer questionnaire. Patients were either interviewed in doctors' office or offered the possibility to answer an online questionnaire. We included women aged 30 to 65 in La Reunion who were concerned by CC screening. We compared the answers of women who were up to date with their screening with those of women who were not. RESULTS: We included 202 women. The study showed that 64.9% of patients wished to collect the VS kit from a healthcare professional, 80.8% wished to perform SS and 52.5% wished to return it to the laboratory. The preferred language of the instruction was French, with pictures and drawings for 48.5% of patients. There was no significant difference between the answers of women who were up to date with their screening and those who were not. CONCLUSION: In a sample of women eligible for CC screening in La Reunion, the preferred methods for CC screening were to collect the PV kit from a healthcare professional, perform the SS at home and then return it to the laboratory. These responses differed from other studies. A feasibility study on a part of La Reunion's eligible population for CC screening would enable us to assess the feasibility and generalizability of a screening modality based on SS.

[High-grade lesions probability in ASCUS HPV positive patient according to HPV type]. / Probabilité diagnostique d'une lésion de haut grade chez les patientes ASCUS HPV positif en fonction du typage HPV.

OBJECTIVES: The aim of our study was to assess the proportion of high-grade histological lesions, according to HPV type, in patients referred for colposcopy involving a positive HPV-HR test and ASC-US cytology. METHODS: This is a retrospective descriptive study of asymptomatic patients aged 25 to 65 with a positive HPV-HR test and ASC-US cytology. Data were collected at the Nord Franche-Comté Hospital from September 2019 to February 2022. The primary outcome was the proportion of high-grade histological lesions in patients with ASC-US cytology combined to HPV 16 or 18 (associated or not with other HPV type), compared with HPV no 16 no 18. RESULTS: Among the 298 patients included, 67% were HPV no 16 no 18, 22% HPV 16 associated or not with others and 11% HPV 18 associated or not with others. We found significantly fewer high-grade lesions in patients with ASC-US cytology and HPV no 16 no 18 than in patients with HPV 16 or 18 (8.5% versus 22.7%, P<0.01). In patients presenting an ASC-US cytology with HPV no 16, no 18: 53% of the biopsies found no histological lesion compared with 30% for the other HPVs (P<0.01). CONCLUSIONS: We have highlighted the reality of colposcopists: a high ratio of normal coloscopy associated with normal or low-grade biopsies, in patients with a positive HPV-HR test no 16, no 18 and ASC-US cytology.

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network.

PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

[FRANCOGYN group: A brief history]. / Le groupe FRANCOGYN : bilan et avenir.

OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. METHODS: Literature review using PUBMed database with the keyword "FRANCOGYN". OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. RESULTS: The FRANCOGYN group was formed in December 2015, bringing together over the years more than 17 gynecological and oncological surgical department in France. The group carries out clinical research on gynecological pelvic cancers by constituting retrospective cohorts. Its legitimacy allows it to lead or co-lead the drafting of recommendations for clinical practice in the field of gynecological cancers. It now offers prospective randomized research funded by national grants. CONCLUSION: The FRANCOGYN network allows us to propose a national reflection on the surgical management of pelvic cancers in women, resulting in numerous international reference publications.

[Place of innovative therapies in the management of cervical cancer]. / Place des thérapies innovantes dans la prise en charge des cancers du col de l'utérus.

Despite optimized screening and prevention strategies, cervical cancer remains a major public health problem, even in developed countries. In France, the incidence is estimated at 3159 cases per year in 2023. While the management of early-stage cases is now highly standardized, few therapeutic advances were made in the treatment of metastatic stages before 2021, before the therapeutic arsenal that we know today took off. The aim of this review is to summarize these advances.

Place of radiotherapy for treatment of metastatic cervical, vaginal and endometrial uterine cancer.

Beyond classical palliative-intent irradiation schemes, there are increasing data suggesting a benefit for intensive locoregional treatments in metastatic gynecological cancers. Such approach aims at avoiding local symptoms related to tumor progression, but may also improve survival outcome by shrinking tumor burden to a microscopic state. This strategy is rarely considered upfront (in highly selected patients with very limited oligometastatic disease), but rather after systemic treatment. In case of tumor response (especially if complete response) of the metastatic sites, pelvic±para-aortic radiotherapy can be considered in combination with a brachytherapy boost to obtain long-term local control, in particular in cervical or vaginal cancer patients. Such approach seems particularly relevant when there is isolated persistence or progression of macroscopic disease within the pelvis. In parallel, there is also an increasing place for radiotherapy of oligo-metastatic sites. We review the literature on the place of radiotherapy in the management of cancers of the cervix and metastatic endometrial cancer.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022­2023 : Prise en charge du cancer du col de l'utérus avancé.

French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2022-2023: Management of advanced cervical cancer The prognosis of cervical cancer remained pejorative until recently, first-line treatment consisting of platinum-based chemotherapy, associated with bevacizumab whenever possible, without any other therapeutic innovation for several years. However in 2022, immunotherapy appeared in the therapeutic landscape. Pembrolizumab can now be prescribed, thanks to the early access status granted by the HAS in September 2022, in patients with PD-L1 positive tumors. In parallel, bevacizumab generic is now reimbursed, allowing its association with chemotherapy on top of pembrolizumab, if indicated. For patient relapsing after platinium salts, and who never received immunotherapy, cemiplimab could be delivered and reimboursed since spring 2023, whatever could be PD-L1 status. Pretherapeutic work-up includes imaging combining MRI and PET/CT or CT of the chest, abdomen and pelvis, as well as evaluation of PD-L1 status on tumor and immune cells to define the CPS score that will determine eligibility to pembrolizumab treatment (CPS > 1). Possibilities of locoregional treatment depend on individual situations and are discussed on a case-by-case basis in multidisciplinary meetings. Early supportive care is always recommended and inclusion in clinical trials must be systematically considered.

Development of a risk nomogram predicting urinary tract infection in patients with indwelling urinary catheter after radical surgery for cervical cancer.

BACKGROUND: Cervical cancer (CC) patients receiving indwelling catheterization after radical hysterectomy (RH) are vulnerable to urinary tract infection (UTI). However, no model or method is available to predict the risk of UTIs. Therefore, our aim was to develop and verify a risk model to predict UTI for patients receiving indwelling catheterization after radical cervical cancer surgery (ICa-RCCS). METHODS: We first collected clinical information of 380 patients receiving ICa-RCCS from January 2020 to December 2021 as a training cohort to develop the risk nomogram. UTI was then evaluated using 19 UTI predictor factors. The least absolute shrinkage and selection operator (LASSO) method was utilized for the extraction characteristics. Multivariable logistic regression analysis was then conducted to create the risk model for UTI prediction. The consistency coefficient and calibration curve were utilized to assess the model's fit accuracy. We performed bootstrapping with 1000 random samples for internal validation of the model, and decision curve analysis (DCA) for clinical application. RESULTS: Predictors in the risk nomogram included indwelling catheterization duration, whether it is secondary indwelling catheterization, history of UTIs, age, and history of chemotherapy before surgery. The risk nomogram presented good discrimination and calibration (C-index: 0.810, 95% CI: 0.759-0.861). During interval validation, the model reached a high C-index up to 0.7930. DCA revealed the clinical utility of predictive model for UTI. Clinical benefit was initiated at the decision threshold≥3%. CONCLUSION: We developed a novel UTI nomogram incorporating the age, history of chemotherapy before surgery, indwelling catheterization duration, whether it is secondary indwelling catheterization, and history of UTI to predict UTI risk for patients receiving ICa-RCCS. LEVEL OF EVIDENCE: B: 3a.

Limited applicability and implementation of the international oncology treatments guidelines in low- and middle-income countries, an example from the Mediterranean area borders.

The quality of cancer care in the modern era is based on a precise diagnosis and personalized therapy according to patients and their disease based on validated guidelines with a high level of evidence. During cancer patients' management, the objective is first to make an accurate diagnosis and then offer the best treatment, validated beforehand in a multidisciplinary board meeting, with the best benefit/risk ratio. In the context of many low- and middle-income countries, the limited available means do not allow an adequate offer, resulting in non-optimal patients' care. In addition, in many low- and middle-income countries, priority can be given to other types of disease than cancer, which may considerably reduce allocation of specific resources to cancer care. Thus, the limited availability of systemic therapy, radiotherapy machines, brachytherapy and technological development may come up against another difficulty, that of geographical distribution of the means in the countries or a lack of expertise due to insufficient training programs. For all these reasons, the implementation of the guidelines established in Western countries could be impossible for many low- and middle-income countries which, moreover, have to face a completely different epidemiology of cancers compared to developed countries. In this work, we will discuss through a few examples of common cancers on both borders of the Mediterranean area, the applicability of the guidelines and the limits of their implementation for optimal cancer care.

Low attendance in cervical cancer screening, geographical disparities and sociodemographic determinants of screening uptake among adult women in Burkina Faso : results from the first nationwide population-based survey.

OBJECTIVE: To explore the level, geographical disparities and sociodemographic determinants of cervical cancer screening uptake among adult women in Burkina Faso by using data from the first national population-based survey. METHODS: This was a cross-sectional secondary analysis of primary data obtained by the 2013 World Health Organization (WHO) Stepwise Approach to Surveillance survey conducted in Burkina Faso. All 13 Burkinabè regions, with their different rates of urbanization, were surveyed. Lifetime cervical cancer screening uptake was explored. We included 2293 adult women for analyses and performed Student's t, chi-square and Fisher's exact tests, and logistic regression. RESULTS: Only 6.2% (95% CI: 5.3-7.3) of women had ever been screened for cervical cancer. For two regions ("Centre" and "Hauts-Bassins"), the pooled frequency was 16.6% (95% CI: 13.5-20.1) while in the other eleven regions it was significantly lower, 3.3% (95% CI: 2.5-4.2). In urban and rural areas, the respective frequencies for the screening uptake were 18.5% and 2.8% (p < 0.001), and in educated and un-educated women, frequencies were 27.7% and 3.3% (p < 0.001) respectively. The sociodemographic factors associated with screening uptake were being educated (adjusted odd-ratio [aOR] = 4.3; 95% CI: 2.8-6.7), urban residence (aOR = 3.8, 95% CI: 2.5-5.8) and having an occupation providing income (aOR = 3.1, 95% CI: 1.8-5.4). CONCLUSION: There was a significantly wide range in screening uptake between Burkina Faso regions, and the overall national as well as the region-specific levels were far below the WHO's target for cervical cancer elimination. Cervical cancer interventions should be tailored specifically for Burkinabè women with different educational levels, and prevention strategies based on community engagement integrating psychosocial considerations could be helpful.

[Budget impact of self-testing in the national cervical cancer screening program]. / Impact budgétaire de l'utilisation de l'autotest dans le cadre du programme national de dépistage du cancer du col de l'utérus.

OBJECTIVES: A nationwide screening program for cervical cancer (CC) was organized in 2018 as part of the 2014-2019 French cancer plan, with the objective of reducing CC incidence and mortality in France by reaching an 80 % coverage rate. As an alternative to pap smear, vaginal self-sampling (VSS) aimed at identifying high-risk HPV carriage could help to achieve this goal. The objective of the present study is to compare the respective budgetary impacts of several self-sampling strategies. METHOD: A budget impact model was developed to compare non-use of self-sampling in CC screening to the 5-year costs of 5 VSS strategies viewed from an all-payer perspective. While the first strategy was based on mailing the VSS kit with a reminder to participate in the screening program, the second was based on accompanying the mailed kit with an invitation to participate. The third and fourth strategies were based on providing health professionals with the kit, and thereby offering self-sampling as an alternative to pap smears for women undergoing CC screening and having previously received the kits. Finally, the fifth strategy was based on self-sampling as the one and only CC screening modality. The parameters of the model were based on past screening participation data and experiments in France on organized screening and VSS use. The costs included those of procedures associated with screening and program organization. RESULTS: All in all, the costs associated with cervical cancer screening would represent approximately 1 billion euros over 5 years. All strategies would be associated with participation ranging from 81% to 84%, which would represent an increase of 4.7% to 5.2% of lesions diagnosed by screening and a cost reduction between €30M and €87M over 5 years, with the exception of the strategy based on sending the kit (with the reminder associated or not) to the health professionals offering this option (+€23M and +€6M). CONCLUSIONS: In conclusion, the use of self-sampling as an alternative to pap smears for non-participating women would increase participation, with only a moderate budgetary impact and could, in some cases, even induce savings.

[Revision of the French colposcopic terminology]. / Nouvelle classification française des images colposcopiques.

OBJECTIVES: To revise the 1983 colposcopic terminology form the French Society of Colposcopy and cervicovaginal pathology (SFCPCV). METHODS: All the three following steps of colposcopic examination were considered for the description of various colposcopic features: inspection without coloration, followed by the application of acetic acid and iodine staining. This revised terminology now includes the different possible colposcopic aspects of the normal cervix, including the ectropion and the normal transformation zone. It also includes colposcopic appearance of abnormal glandular cervical epithelium and of vaginal epithelium. The revised nomenclature was reviewed by all the board of the SFCPCV and was finally approved during the 45th annual conference of the SFCPCV. RESULTS: Abnormal transformation zone grade (TAG) 1a and 1b have been brought together under the sole TAG1 designation. TAG2a and TAG2b now correspond to TAG2, whereas TAG2c corresponds to TAG3. Colposcopic report should mention the interpretability of the colposcopic examination, with the precise type of the squamocolumnar junction (1, 2 or 3), the colposcopic impression, the size of any TAG and finally mention whether one or multiple biopsies were taken and their precise location. Colposcopic impression must give priority to the most pejorative colposcopic aspect which takes precedence over others. CONCLUSION: When performing colposcopy, one should keep in mind that this examination only relies on the interpretation of various colposcopic signs and images with this not guaranteeing for diagnosis. Only histological analysis of a possible guided cervical biopsy provides for a precise diagnosis.

[Immunotherapy in oncogynaecology]. / Immunothérapies validées en oncogynécologie.

Immune checkpoint inhibitors have deeply changed treatment paradigm of many tumor types, notably by providing long-term remissions, even in the metastatic setting. These immunotherapies aim to restore T-cells activity against tumour cells, in particular via the inhibition of PD1/PD-L1 interaction. As for lung or renal carcinomas, and melanomas, the management of endometrial and uterine cervical cancers has been disrupted by PD1/PD-L1 inhibitors efficacy. In locally advanced or metastatic cervical carcinomas, the combination of platinum-based chemotherapy with pembrolizumab demonstrated improved overall and progression-free survival in all subgroups of patients, and became the new standard of care. Regarding endometrial cancers, while single-agent immunotherapies have shown very limited activity in an unselected population, dostarlimab and pembrolizumab have been associated with remarkable antitumor activity in case of microsatellite instability (dMMR/MSI), detected in around 30% of patients. Finally, in endometrial cancer that has progressed after first-line chemotherapy, the association of pembrolizumab with an oral antiangiogenic kinase inhibitor (lenvatinib) has demonstrated its superiority over second-line chemotherapy regimens, regardless molecular subgroups, and has become the new standard of care in this indication.

Cervical cancer in Morocco: A systematic review.

BACKGROUND: This systematic review aims to determine the epidemiological profile, etiology and risk factors, prevention, diagnosis, treatment, cost-effectiveness, survival, and quality of life related to cervical cancer in Morocco. METHODS: This study was conducted according to the recommendations of the "preferred reporting items for systematic reviews and meta-analysis." The PubMed, ScienceDirect, Springer, Web of Science data bases were used, as was Google Scholar for the grey literature. The review protocol was registered in the PROSPERO register (CRD42021235241). RESULTS: Fifty studies were selected. The mean age was 49.31 ±6.3 years. HPV infection prevalence ranged from 13.30% to 76%, with a peak in HIV-positive women. Acceptability of the HPV vaccine was higher among parents (35% and 82%) than among adolescents (16.9% to 46.6%). Knowledge of the vaccine and its price are two key factors related to vaccine acceptability among parents. This systematic review highlights that the fact that few eligible women (not more than 11%) were participating in the cervical cancer screening program. Moroccan women's level of knowledge and awareness regarding cervical cancer screening was low, negatively impacting their use of such screening tools, as illustrated by the high percentage (mean 76.32% ± 17.21) of women who had never been screened for cervical cancer. Treatment was the most significant component of the global care budget (95.87%), with an annual cost of $13,027,609. Five-year overall survival ranged from 41.3% to 73.6%, with higher survival rates for patients diagnosed at an earlier stage (77.3-85% for stage I). Lastly, low quality of life was observed in women with tumors at an advanced stage who had received brachytherapy and lacked social support. CONCLUSIONS: Subjects that require further investigation include Moroccan women's knowledge, attitudes, and awareness, especially among those at high risk of developing cervical cancer, and its impact on their quality of life and survival.

[Database's development for prospective national collection of clinical data on cervical cancer: A Delphi survey identifying consensual variables]. / Élaboration d'une base de recueil nationale prospective des données cliniques sur le cancer du col utérin: utilisation de la méthode Delphi pour l'identification de variables consensuelles.

INTRODUCTION: Cervical cancer (CC) is associated with poor prognosis and therapeutic morbidity in young women. The impact of European recommendations for treatments and follow-up of these patients must be assessed. There is no real-time CCU tracking basis. Main objective of our study was to identify the items of the clinical and therapeutic data necessary for the constitution of a national, dynamic and prospective clinical database allowing to characterize treatments and follow-up of patients with CC in France. METHODS: An exhaustive bibliographic research was lead with the help of the ESGO recommendations. A list of qualitative and quantitative variables characterizing CC was established. These variables were assessed by a panel of national experts from the Francogyn group, using the Delphi survey. The rate of agreement was calculated for each variable. RESULTS: 345 variables divided into 6 sections were identified and submitted to 26 experts. 17 experts responded to the three rounds of the Delphi method. A total of 273 items were validated. The majority of experts (90 %) also gave a favorable opinion on the addition of a quality of life section in the database. CONCLUSION: This is the first study identifying 273 items chosen by consensus. The items are collected in a future national gynecological database "Epigyn".

Cholecalciferol induces apoptosis via autocrine metabolism in epidermoid cervical cancer cells.

The anti-cancer effects of vitamin D are of fundamental interest. Cholecalciferol is sequentially hydroxylated endogenously to calcidiol and calcitriol. Here, SiHa epidermoid cervical cancer cells were treated with cholecalciferol (10-2600 nmol/L). Cell count and viability were assayed using Crystal Violet and Trypan Blue, respectively. Apoptosis was assessed using flow cytometry for early and late biomarkers along with brightfield microscopy and transmission electron microscopy. Autocrine vitamin D metabolism was analysed by reverse transcription-quantitative PCR and immunoblotting for activating enzymes: 25-hydroxylases (CYP2R1 and CYP27A1) and 1α-hydroxylase (CYP27B1), the catabolic 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR). Data were analysed using one-way ANOVA and Bonferroni post-hoc test, and p < 0.05 was considered significant. After cholecalciferol, cell count (p = 0.011) and viability (p < 0.0001) decreased, apoptotic biomarkers were positive, mitochondrial membrane potential decreased (p = 0.0145), and phosphatidylserine externalisation (p = 0.0439), terminal caspase activity (p = 0.0025), and nuclear damage (p = 0.004) increased. Microscopy showed classical features of apoptosis. Gene and protein expression were concordant. Immunoblots revealed increased CYP2R1 (p = 0.021), VDR (p = 0.04), and CYP24A1 (p = 0.0274) and decreased CYP27B1 (p = 0.031). The authors conclude that autocrine activation of cholecalciferol to calcidiol may mediate VDR signalling of growth inhibition and apoptosis in SiHa cells.

Health, illness and cancer in Mayotte: Multicultural experiences in a medically underserved French Territory.

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.

[Place of PARP inhibitors in the treatment of endometrial and cervical cancers]. / Place des inhibiteurs de PARP dans le traitement des cancers de l'endomètre et du col de l'utérus.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.