Upregulation of bromodomain PHD finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival.

Bromodomain PHD finger transcription factor (BPTF) is a core subunit of the nucleosome-remodeling factor (NURF) complex, which plays an important role in the development of several cancers. However, it is unknown whether BPTF regulates the progression of ovarian cancer (OC). To investigate this, we measured the relative expression levels of BPTF in OC cell lines and tissues using Western blot and immunohistochemistry, respectively, and the results were analyzed using the χ2 test. We also examined the effects from BPTF knockdown on the proliferation, migration, invasiveness, and apoptosis of OC cell lines. Mechanistic studies revealed that these effects were achieved through simultaneous modulation of multiple signaling pathways. We found that BPTF was highly expressed in OC cell lines and tissues compared with a normal human ovarian epithelial cell line and non-cancerous tissues (P < 0.05). These results are also supported by the public RNA-seq data. BPTF overexpression was correlated with a poor prognosis for OC patient survival (P < 0.05). In vitro experiments revealed that the downregulation of BPTF inhibited OC cell proliferation, colony formation, migration, and invasiveness, and induced apoptosis. BPTF knockdown also affected the epithelial-mesenchymal transition (EMT) signaling pathways and induced the cleavage of apoptosis-related proteins. Consequently, BPTF plays a critical role in OC cell survival, and functions as a potential therapeutic target for OC.

Aberrant sphingomyelin 31P-NMR signatures in giant cell tumour of bone.

An understanding of the biochemistry of the giant cell tumour of bone (GCTB) provides an opportunity for the development of prognostic markers and identification of therapeutic targets. Based on metabolomic analysis, we proposed glycerophospholipid metabolism as the altered pathway in GCTB., The objective of this study was to identify these altered metabolites. Using phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR), sphingomyelin was determined to be the most dysregulated phospholipid in tissue samples from six patients with GCTB. Enzymes related to its biosynthesis and hydrolysis were examined using immunodetection techniques. High expression of sphingomyelin synthases 1 and 2, but low expression of neutral sphingomyelinase 2 (nSMase2) was found in GCTB tissues compared to non-neoplastic bone tissues. Sphingomyelin/ceramide biosynthesis is dysregulated in GCTB due to alterations in the expression of SMS1, SMS2, and nSMase2.

Should we perform subtotal hysterectomy associated with sacral colpopexy for genital prolapse to prevent the risk of endometrial cancer?

OBJECTIVE: In a menopausal woman scheduled for curative surgery for pelvic organ prolapse (POP) by sacral colpopexy (SC), the question of concomitant hysterectomy is frequently considered by the surgeon. The risk of endometrial cancer (EC) exists in this population, and increases with age and body mass index. The French college of gynecologists and obstetricians (CNGOF) decided to issue good practice guidelines on subtotal hysterectomy (SH) for postmenopausal women scheduled for SC for POP. METHODS: The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade, which depends on the quality of evidence (QE) (clinical practice guidelines). RESULTS: The prevalence of occult endometrial cancer (EC) found on pathological analysis after SH in this context (concomitant SH associated with SC) is low (<1%) (QE: high). Few studies have assessed the value of preoperative uterine exploration. Performing SH during SC is associated with its own risks, which may diminish the potential "carcinological prevention benefit". Uterine morcellation, performed by laparoscopy or a robot-assisted procedure, is associated with a low risk (<0.6%) of dissemination of an unknown sarcoma/EC (QE: moderate) A risk of dissemination of parasitic myomas (<0.5%) is also possible (QE: moderate). CONCLUSION: It is not recommended to perform a subtotal hysterectomy associated with sacral colpopexy for the sole purpose of reducing the occurrence of endometrial cancer (Recommendation: STRONG [GRADE 1-]; the level of evidence was considered to be low and the risk-benefit balance was considered not to be favorable).

Risk factors for anxiety and depression in Chinese patients undergoing surgery for endometrial cancer.

This study analyzed risk factors for anxiety and depression in 714 patients who received surgery for endometrial cancer. Our data indicate that the incidence of postoperative anxiety and depression in 714 patients with endometrial cancer was 15.55% and 32.77%, respectively. Univariate and logistic regression analysis showed postoperative pain (odds ratio (OR) = 3.166, P = 0.000) and combined liver disease (OR = 2.318, P = 0.001) were independent risk factors for postoperative anxiety. Additionally, CD4+/CD8+ (OR = 0.513, P = 0.042) and natural killer (NK) cell ratios (OR = 0.692, P = 0.021) were independent protective factors for postoperative anxiety. As for depression, low literacy (OR = 1.943, P = 0.042), postoperative pain (OR = 2.671, P = 0.001), high clinical stage (OR = 3.469, P = 0.009), and combined liver disease (OR = 4.865, P = 0.000) were independent risk factors for postoperative depression. CD4+/CD8+ (OR = 0.628, P = 0.002) and NK cell ratio (OR = 0.710, P = 0.013) were independent protective factors for postoperative depression. In conclusion, patients with endometrial cancer have a higher incidence of postoperative anxiety and depression where postoperative pain, liver disease, and decreased immune function are risk factors for both anxiety and depression in these patients.

No 385 - Indications de l'examen pelvien.

OBJECTIF: L'objectif principal du présent document est de clarifier les indications de l'examen pelvien. UTILISATEURS CONCERNéS: Médecins, y compris les gynécologues, obstétriciens, médecins de famille, urgentologues; infirmières, y compris les infirmières autorisées et les infirmières praticiennes; sages-femmes, y compris les sages-femmes en pratique clinique et les apprenties sages-femmes et les apprentis en médecine, y compris les étudiants de médecine, résidents, stagiaires (fellows); et tous les autres fournisseurs de soins de santé qui prodiguent des soins aux femmes. POPULATION CIBLE: La présente publication fournit des données probantes et des recommandations fondées sur des avis d'experts sur l'examen pelvien chez les femmes adultes (18 ans et plus) avec et sans symptômes gynécologiques. ISSUES: La présente publication clarifie les indications de l'examen pelvien dans le contexte des déclarations de groupes d'étude nationaux récemment publiées sur l'utilité de l'examen pelvien. L'objectif est de veiller à ce que les femmes qui présentent des indications cliniques d'examen fassent rapidement l'objet d'une évaluation clinique adéquate pour diagnostiquer les maladies traitables. DONNéES PROBANTES: Pour la présente opinion de comité, les études pertinentes ont été repérées dans PubMed et Medline à l'aide des termes suivants, seuls ou combinés, et les recherches ont été limitées aux publications en anglais portant sur des humains sans date limite de publication : pelvic examination, bimanual examination, speculum examination, rectovaginal examination, ovarian cancer screening, asymptomatic women, periodic health examination. La recherche a été effectuée en mai et en juin 2018. Les données probantes pertinentes ont été retenues dans l'ordre suivant : méta-analyses, revues systématiques, lignes directrices et déclarations des groupes d'étude nationaux, essais cliniques randomisés, études de cohorte prospective, études observationnelles, revues non systématiques, études de série de cas et rapports. Des articles supplémentaires ont été repérés en consultant les notices bibliographiques des publications sélectionnées. Une revue systématique officielle n'a pas été menée pour tous les sujets discutés en raison du manque de données probantes et du nombre de différents sous-thèmes abordés. Le nombre total de publications examinées dans le cadre de cette revue était de 66. MéTHODES DE VALIDATION: Les auteurs principaux ont rédigé le contenu et les recommandations et ils se sont entendus sur ces derniers. Les conseils d'administration de la Society of Gynecologic Oncology of Canada (GOC), de Collège des médecins de famille du Canada (CMFC) et de la Société des obstétriciens et gynécologues du Canada (SOGC) ont approuvé la version définitive aux fins de publication après que leurs comités représentatifs respectifs l'aient passée en revue. La qualité des données probantes utilisées dans le présent document a été évaluée au moyen des critères du cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). (Tableaux 1 et 2) Le résumé des conclusions est disponible sur demande. AVANTAGES, PRéJUDICE ET COûTS: La présente opinion de comité devrait aider toutes les femmes qui souffrent ou non de symptômes gynécologiques qui se présentent chez le gynécologue et un fournisseur de soins primaires. Elle aidera les praticiens à déterminer les indications d'examen pelvien afin de réduire le nombre d'examens inutiles et susceptibles de porter préjudice tout en augmentant le nombre d'examens indiqués afin de réduire les retards de diagnostic des affections gynécologiques traitables. MISE à JOUR DE LA DIRECTIVE CLINIQUE: La présente opinion de comité de la SOGC sera automatiquement passée en revue cinq ans après sa publication pour déterminer si une partie ou l'ensemble de l'opinion de comité devrait être mis à jour. Cependant, cette revue peut être effectuée plus tôt si de nouvelles recherches révolutionnaires sont publiées entre-temps. DÉCLARATIONS SOMMAIRES: 1) Les déclarations et les directives nationales et internationales sur l'examen pelvien ne devraient pas être interprétées comme si l'examen pelvien est superflu, qu'il ne contribue pas à l'évaluation physique ou que l'examen pelvien chez les femmes symptomatiques devrait être omis. 2) L'examen pelvien peut comprendre les examens visuels, au spéculum, bimanuel, à un doigt ou rectovaginal selon l'indication d'examen. 3) Aucune étude publiée à ce jour n'a évalué adéquatement quelque composante que ce soit de l'examen pelvien comme méthode de dépistage pour quelconque type de maladie gynécologique maligne, à l'exception de l'examen au spéculum pour le dépistage cytologique du cancer du col de l'utérus. Ainsi, toute recommandation universelle, pour ou contre les examens pelviens pour d'autres indications ne peut qu'être faite selon l'opinion des spécialistes et des données probantes de faible qualité. 4) Chez les femmes asymptomatiques dont le risque de cancer du col de l'utérus est moyen, le dépistage cytologique du cancer du col de l'utérus réduit à la fois son incidence et son taux de mortalité en détectant les lésions préinvasives traitables. 5) Chez les femmes asymptomatiques dont le risque de tumeur ou affection maligne est moyen, un examen visuel et bimanuel au moment d'obtenir des échantillons cytologiques cervicaux peut apporter une valeur ajoutée à cette méthode de dépistage. Les femmes peuvent ne pas soulever certaines inquiétudes sur le plan gynécologique jusqu'au moment de l'examen pelvien; l'examen offre une occasion de sensibiliser les patientes et de maintenir les compétences du praticien; de plus, même si le sujet n'a pas encore été étudié adéquatement, il pourrait comporter des effets positifs sur les tumeurs ou affections malignes ovariennes et vulvaires qui nécessiteraient des analyses plus poussées. Ces avantages potentiels devraient être soupesés par rapport aux préjudices potentiels comme l'inconfort de la patiente et les faux positifs ou négatifs qui pourraient la rassurer à tort ou entraîner des analyses et des interventions non justifiées. RECOMMANDATIONS: Femmes symptomatiques 1) Toute femme qui exprime des plaintes de nature gynécologique, y compris, mais sans s'y limiter, des plaintes concernant la vulve, des pertes vaginales, des saignements préménopausiques anormaux, des saignements postménopausiques, l'infertilité, des symptômes de prolapsus des organes pelviens, l'incontinence urinaire, de nouveaux symptômes gastro-intestinaux inexpliqués (douleur abdominale, distension abdominale ou ballonnement et difficulté à manger ou satiété précoce), la douleur pelvienne ou la dyspareunie, devrait subir des composantes pertinentes de l'examen pelvien afin de détecter les maladies bénignes ou malignes (forte, basse). 2) Les fournisseurs de soins de santé peuvent envisager de discuter des risques et avantages de l'exécution d'un examen pelvien de base qui comprend un examen visuel et un examen bimanuel avant de prescrire une hormonothérapie substitutive ou un traitement hormonal de la ménopause (faible, très basse). Femmes asymptomatiques 3) Les professionnels de la santé devraient faire le dépistage cytologique du cancer du col de l'utérus conformément aux lignes directrices provinciales ou territoriales (forte, forte). 4) Les données sont insuffisantes pour orienter les recommandations sur l'examen pelvien aux fins de dépistage de tumeurs ou affections malignes de nature gynécologique non cervicales ou de toute maladie gynécologique bénigne chez les femmes asymptomatiques en santé dont le risque de tumeur ou affection maligne est moyen. Cependant, les professionnels de la santé peuvent envisager d'effectuer un examen pelvien aux fins de dépistage comprenant les examens visuel, bimanuel et au spéculum conjointement avec le prélèvement d'échantillons cytologiques cervicaux selon les intervalles recommandés dans les lignes directrices provinciales ou territoriales. Cette pratique pourrait permettre de détecter d'importantes maladies bénignes ou malignes non reconnues ou signalées par la patiente (faible, très basse). 5) Chez les femmes âgées de plus de 70 ans qui n'ont plus à subir de dépistage cytologique cervical, les professionnels de la santé devraient envisager de continuer chez les femmes asymptomatiques le dépistage périodique des maladies vulvaires en examinant la vulve, le périnée et l'anus afin de détecter les maladies bénignes ou malignes méconnues de cette population. Les données sont insuffisantes pour déterminer des recommandations sur la fréquence de cet examen (faible, basse). 6) Des examens pelviens de dépistage plus fréquents pour déceler les signes précoces de tumeurs ou affections malignes primitives, récidivantes ou métastatiques en l'absence de symptômes pourraient s'avérer bénéfiques pour les femmes qui ont des antécédents personnels de tumeurs malignes de nature gynécologique, un diagnostic génétique qui augmente le risque de tumeurs ou affections malignes gynécologiques ou des antécédents d'exposition in utero au diéthylstilbestrol. Puisque les données pour déterminer ces intervalles de dépistage sont inadéquates, on devrait les déterminer en fonction des lignes directrices provinciales ou territoriales et de l'opinion des spécialistes (faible, très basse). 7) Les options non effractives et par auto-prélèvement de dépistage de la chlamydia et de la gonorrhée sont acceptables chez les femmes asymptomatiques, mais l'examen pelvien, qui comprend les examens visuel, bimanuel et au spéculum, est requis en présence de symptômes pour écarter la possibilité d'une maladie inflammatoire pelvienne ou d'un abcès tubo-ovarien (forte, basse). 8) Aucun examen pelvien n'est requis avant la prescription de contraception hormonale chez une femme en santé qui ne présente aucun symptôme gynécologique (forte, basse).

Thoracotomy and esophageal surgery: Key points to preserve the possibilities of flaps.

Anastomotic leakage frequently complicates esophagectomy and can trigger a rare life- threatening complication, a tracheoesophageal fistula. No guideline has yet addressed this complication. Plastic surgeons play a crucial role for salvage surgery. When a re-operation is chosen the possibilities of flap interposition depend on how the thoracotomy was initially performed. This study tried to identify key techniques in order help thoracic or general surgeons to preserve all the local flaps available for TEF if it occurs. These techniques improve flap conservation, helping plastic surgeons when a later transposition flap is required.

No 366 - Prise en charge gynécologique du cancer du sein et de l'ovaire héréditaire.

OBJECTIF: La présente opinion de comité énumère les recommandations pour la prise en charge gynécologique des femmes ayant reçu un diagnostic de syndrome du cancer du sein et de l'ovaire héréditaire (CSOH) en ce qui a trait au dépistage, à la contraception, à la chimioprophylaxie, aux facteurs à considérer pour la fertilité, à la chirurgie de réduction du risque et aux soins post-ovariectomie. UTILISATEURS CIBLES: La présente opinion de comité s'adresse aux gynécologues oncologues, aux gynécologues généralistes, aux médecins de famille, aux conseillers en génétique, aux infirmières autorisées, infirmières praticiennes, aux résidents et aux autres fournisseurs de soins. POPULATION CIBLE: Les femmes adultes (18 ans et plus) présentant une mutation des gènes BRCA1 ou BRCA2 ou d'autres gènes associés au cancer de l'ovaire. DONNéES: Pour la revue de la littérature, les bases de données Medline, Cochrane et PubMed ont entre autres été interrogées. Les termes de recherche des Medical Subject Headings utilisés ont été BRCA ET gynaecology management [prise en charge gynécologique], hormone replacement therapy [hormonothérapie substitutive], risk reduction [réduction des risques], chemoprophylaxis [chimioprophylaxie] et fertility [fertilité], et les recherches ont ciblé les articles publiés entre janvier 2010 et octobre 2017. La recherche de publications s'est déroulée de juillet à octobre 2017. Au total, 183 études ont été sélectionnées, et 101 ont été utilisées. VALEURS: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs principaux. Le Conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version finale avant publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interprétation des recommandations fortes et conditionnelles (faibles) est décrite dans le tableau 2. Le résumé des conclusions peut être fourni sur demande. AVANTAGES DéSAVANTAGES, ET COûTS: Nous pouvons nous attendre à une diminution des risques allant jusqu'à 90 % chez les femmes prédisposées au CSOH qui subissent une salpingo-ovariectomie bilatérale de réduction du risque. Les méfaits associés à la ménopause précoce iatrogène sont compensés par les avantages découlant de la réduction du risque. En réduisant l'occurrence de cancers des trompes, de l'ovaire et du péritoine, nous pouvons nous attendre à des économies dans le système de santé. MIS à JOUR: Une revue des données probantes sera menée cinq ans après la publication de la présente opinion afin de déterminer si une mise à jour complète ou partielle s'impose. Cependant, si de nouvelles données probantes importantes sont publiées avant la fin du cycle de cinq ans, le processus pourrait être accéléré afin que certaines recommandations soient mises à jour rapidement. COMMANDITAIRE: Cette directive clinique a été élaborée à l'aide de ressources financées par la Société des obstétriciens et gynécologues du Canada.

[FREGAT: French clinico-biological database dedicated to esogastric cancers]. / FREGAT : base clinicobiologique nationale française dédiée à la recherche sur les cancers œsogastriques.

Even though esogastric cancers are estimated at 1.5 million new cases worldwide with an expected 2.11 million new cases by 2025, prognosis remains poor and research is unsatisfactory compared to other cancers. There is an urgent need to intensify research via innovative and ambitious programs to improve patient's survival and quality of life. Incidence of esogastric cancers is particularly high in France, and the creation of a national clinicobiological database prospectively collecting epidemiological, human and social, clinical, pathological, biological data, sustained by biobanks of blood and tissues, is a critical point to improve research and care for these cancers considering all determinants of the disease with a more integrated approach. FREGAT clinicobiological database, funded and labeled by the French NCI in 2012, gathers the vast majority of university hospitals and cancer centers in France. This research relies on preexisting networks ensuring its efficacy and quality. Beyond significant increase of inclusions opened since January 2015, the establishment of public multiprivate industrial partnerships and creation of numerous French and European scientific projects, make FREGAT a decisive tool for research on esogastric cancers.

[HIPEC morbidity and implications for post-surgical treatment. A medical oncologist advice]. / Effets secondaires des CHIP et implications sur les traitements post-chirurgicaux. L'avis d'une oncologue médicale.

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities.

[Current post-surgical treatment strategies in first-line ovarian cancer]. / Stratégies thérapeutiques post-chirurgicales actuelles dans les cancers de l'ovaire en première ligne de traitement.

Although the management of epithelial ovarian cancer has evolved significantly over the past few years, it remains a public health issue, as most patients are diagnosed at an advanced stage and relapse after first line treatment. Chemotherapy remains the standard adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) stage I and II tumors, with some exceptions. For FIGO stage III/IV tumors, carboplatin- and paclitaxel-based chemotherapy are the standard of care, in combination with targeted therapies, especially bevacizumab and/or poly-(ADP-ribose) polymerase inhibitors, that have become a key milestone of first-line treatment. Our decision making for the maintenance therapy is based on the FIGO stage, tumor histology, timing of surgery (i.e. primary or interval debulking surgery), residual tumor, response to chemotherapy, BRCA mutation and homologous recombination (HR) status.

The association between oral contraceptive pills and ovarian cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Previous study results have been inconclusive, so this meta-analysis aims to evaluate the association between ovarian cancer and oral contraceptive pills (OCPs). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched to identify studies on the association between OCPs and ovarian cancer from January 1, 2000 through February 5, 2023. The pooled relative risk (RR) and odds ratio (OR) were used to measure this relationship. RESULTS: A total of 67 studies were included. In the association between ever-use compared with never-use of OCPs and ovarian cancer risk, the pooled RR in cohort studies was 0.69 [95% CI: 0.61, 0.78]. For the relationship between duration of OCPs use and ovarian cancer in the cohort studies, no association between duration of use1-12 months 0.92 [95% CI: 0.82, 1.03] and duration of use 13-60 months 0.87 [95% CI: 0.73, 1.04], but there is a statistically significant inverse relationship between duration of use 61-120 months 0.62 [95% CI: 0.48, 0.81] and more than 120 months 0.51 [95% CI: 0.32, 0.80] and ovarian cancer. For the relationship between OCPs and histological subtype of epithelial ovarian cancer in the cohort studies, the pooled RR for invasive was 0.70 [95% CI: 0.56, 0.87], but no association between OCPs and borderline ovarian cancer 0.64 [95% CI: 0.31, 1.31]. CONCLUSION: Our analysis shows a statistically significant inverse relationship between ever-use compared to never-use of OCPs and ovarian cancer risk,and also between invasive cancer and OCPs. By increasing the duration of OCPs use, the risk of ovarian cancer decreased.

[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.

[Arguments for centralization of surgical treatment of ovarian cancer in France based on morbidity and mortality data]. / Intérêts de la centralisation de la chirurgie du cancer de l'ovaire en France.

OBJECTIVE: To examine the current state for ovarian cancer surgery in France from 2009 to 2016 and to examine the impact of the volume of activity on morbidity and mortality by institution. MATERIAL AND METHOD: National retrospective study analyzing surgical sessions for ovarian cancer from the program of medicalization of information systems (PMSI), from January 2009 to December 2016. Institutions were divided according to the number of annual curative procedures into 3 groups: A<10; B: 10-19; C≥20. A propensity score (PS) and the Kaplan-Meier method were employed for statistical analyses. RESULTS: In total, 27,105 patients were included. The 1-month mortality rate in group A, B and C was 1.6; 1 and 0.7 %, respectively (P<0.001). Compared to group C, the Relative Risk (RR) of death within the first month was 2.22 for group A and 1.32 for group B (P<0.01). After MS, the 3- and 5-year survival in group A+B and group C were 71.4 and 60.3% (P<0.05) and 56.6, and 60.3% (P<0.05), respectively. The 1-year recurrence rate was significantly lower in group C (P<0.0001). CONCLUSION: An annual volume of activity>20 advanced stage ovarian cancers is associated with a decrease in morbidity, mortality, recurrence rate and improved survival.

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.

Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer.

PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.

[State of results of HIPEC for epithelial ovarian cancer in the primary treatment or for relapse]. / État des lieux des résultats en termes de survie de la CHIP en primo-traitement et en récidive dans le cancer épithélial de l'ovaire.

Peritoneal carcinomatosis is an unavoidable development of ovarian cancer, from the first treatment to relapses, and is the main cause of patients death. Hyperthermic intraperitoneal chemotherapy (HIPEC), is a hope for cure for patients with ovarian cancer. HIPEC is based on direct application of chemotherapy on the perioneum with high concentration of chemotherapy enhanced with specific effects of hyperthermia. Theoretically, HIPEC could be proposed at different steps of ovarian cancer development. But the hypothesis of efficiency of a new treatment must be assessed before being routinely applied. Numerous clinical series are already published about HIPEC used in primary treatment of ovarian cancer or for relapses. These series are mostly retrospectives and based on heterogeneous parameters as inclusion criteria of patients, intra peritoneal chemotherapy, concentration, temperature, duration of HIPEC. Taking into account this heterogeneity it is not possible to draw strong scientific conclusions about HIPEC efficiency to treat ovarian cancer patients. We proposed a review allowing a better understanding of current recommendations of the use of HIPEC in ovarian cancer patients.

[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.

[Impact of HPV status on nutritional status during radio chemotherapy for oropharyngeal cancer]. / Impact du statut HPV sur l'évolution nutritionnelle au cours de la chimioradiothérapie des patients atteints d'un cancer de l'oropharynx.

PURPOSE: Patients with oropharyngeal cancer are at high nutritional risk before and during treatment. Little is known about the influence of human papillomavirus (HPV) infection on nutritional status and its evolution during treatment. MATERIALS AND METHODS: A single-center retrospective study was conducted between August 2017 and December 2020 including 48 patients (14 HPV-induced: HPV+ and 34 non-HPV-induced: HPV-) with oropharyngeal squamous cell carcinoma treated by radiotherapy±chemotherapy (RT/CT). Nutritional risk at the time of tumor assessment (TA) was assessed by weight loss, swallowing ability, and the presence of digestive disorders in 4 stages of increasing severity. Nutritional status was assessed by weight and nutrition risk index (NRI) at the time of TA, before the start and at 3 months from the end of RT±CT. During RT±CT, the NRI and the systemic inflammatory response index (SIRI=neutrophils * monocytes/lymphocytes) were assessed weekly. RESULTS: HPV+patients were at lower nutritional risk at TA (50% grade ≥2 vs 85%, P=0.02), lost more weight (6% of their body weight vs 3%, P=0.05), and increased their SIRI by 7.5 points more than HPV- patients (P=0.04) during RT/CT. CONCLUSION: HPV+ oropharyngeal cancer patients are at high nutritional risk even in the absence of undernutrition at the outset of management.

Practice-changing clinical trials in radiation oncology for gastrointestinal malignancies in 2021-2023.

Gastrointestinal cancers are one of the most frequent cancers and a leading cause of cancer deaths worldwide. We provide an overview of the most important practice-changing trials that were either published or presented at the international scientific meetings in 2021-2023. Highlights included reports on three phase III trials (CONCORDE/PRODIGE 26, ARTDECO, and a study by Xu et al.) that evaluated dose escalation in the definitive setting for locally advanced oesophageal cancers, as well as two phase III trials that evaluated the role of chemotherapy (neo-AEGIS) and targeted therapy (NRG/RTOG 1010) in the neoadjuvant setting for adenocarcinoma oesophageal cancers or gastroesophageal junction cancer. CheckMate 577 evaluated nivolumab in patients who had residual pathological disease after neoadjuvant chemoradiation followed by complete resection. The use of radiation therapy for borderline and locally advanced pancreatic cancer is also discussed (SMART and CONKO-007 trials). Stereotactic body radiation therapy followed by sorafenib was compared to sorafenib alone in patients with hepatocellular carcinoma in the NRG/RTOG 1112 study. New options in the management of rectal cancer are emerging such as total neoadjuvant treatment (PRODIGE 23, RAPIDO, PROSPECT), organ preservation (OPRA, OPERA), and the role of immunotherapy in patients with DNA mismatch-repair deficient/microsatellite instability. Finally, preliminary results of the ACT 4 trial that evaluated de-escalation in anal cancer are presented.