Real-life efficacy and safety of cemiplimab in advanced cervical cancer from a nominal use program in Italy: The MITO 44 study.

BACKGROUND: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy. METHODS: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data. RESULTS: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%. CONCLUSIONS: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

Dermatofibrosarcoma Protuberans of the Vulva: A Review of the MITO Rare Cancer Group.

BACKGROUND: Vulvar dermatofibrosarcoma protuberans is an extremely rare disease. Its rarity can hamper the quality of treatment; deeper knowledge is necessary to plan appropriate management. The purpose of this review is to analyse the data reported in the literature to obtain evidence regarding appropriate disease management. METHODS: We made a systematic search of the literature, including the terms "dermatofibrosarcoma protuberans", "vulva", and "vulvar", alone or in combination. We selected articles published in English from two electronic databases, PubMed and MEDLINE, and we analysed their reference lists to include other potentially relevant studies. RESULTS: We selected 39 articles, with a total of 68 cases reported; they were retrospective case reports and case series. Dermatofibrosarcoma protuberans of the vulva tends towards local recurrence; an early and timely pathological diagnosis, together with an appropriate surgical approach, are of utmost importance to ensure free margins and maximise the curative potential. CONCLUSIONS: Even if this is an indolent disease and it generally shows a good prognosis, appropriate management may help in reducing the rate of local recurrences that may hamper patients' quality of life. Management by a multidisciplinary team is highly recommended.

Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells.

Introduction: Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity. Methods: In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs). Results: Activated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature. Conclusion: These data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches.

Radiation Therapy for Gestational Trophoblastic Neoplasia: Forward-Looking Lessons Learnt.

Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.

Response to Controlled Ovarian Stimulation Is Not Impaired in Young Patients with a Sarcoma: Results from a Monocentric Case-Control Study.

Sarcomas are relatively common in the young and their treatment can impair fertility. Fertility preservation can be achieved via the cryopreservation of gametes after controlled ovarian stimulation before cancer treatment. A reduced response to hormonal stimulation in patients suffering from certain types of malignancy is reported. The purpose of this study was to assess the performance of oocyte cryopreservation in patients with sarcoma by comparing their outcomes with those of a population without cancer. Patients were matched by age with control women undergoing hormonal stimulation for isolated male factor infertility. The population included 84 women with a sarcoma and 355 controls. In the final analysis, 37 patients with sarcoma were matched in a 1:3 ratio with 109 healthy controls. Patients with sarcoma were generally younger and were stimulated with lower FSH doses. They did not perform worse than controls during stimulation, with an average retrieval of 10.6 oocytes vs. 8.1 in the controls. Linear regression on the number of retrieved mature oocytes confirmed that patients with sarcoma performed comparably to controls. In conclusion, patients with sarcoma can expect retrieval outcomes comparable to those of patients without cancer.

Identification of Psychological Profiles of Cancer Patients Undergoing Fertility Preservation Counseling.

Gonadotoxicity is one of the most distressing side effects of cancer treatment. Fertility preservation strategies should be included during the treatment pathway to prevent the risk of infertility, but the decision to preserve fertility often represents a challenging process that carries an emotional decision-making burden. The aim of this study is to characterize the psychological profiles of women undergoing fertility preservation counseling and to better understand their features. Eighty-two female cancer patients were included in the study. They were asked to complete a battery of self-administered tests which evaluated socio-demographic characteristics, defense mechanisms, depression, anxiety, and representations regarding the importance of parenthood. Based on the psychometric variables, cluster analysis identified four groups which showed significantly different combinations of these psychological characteristics. An additional analysis was performed to evaluate if sociodemographic variables were associated with the four groups, but the results did not show significant differences. These results suggest that very diverse psychological profiles may lead cancer patients to attend oncofertility counseling and choose fertility preservation. For this reason, all patients in childbearing age should have the opportunity to receive appropriate fertility preservation counseling in order to make an informed decision that could have an important impact on their long-term quality of life.

Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes.

Evidence indicates that different pathways of malignant degeneration underlie the development of endometriosis-associated ovarian tumors of endometrioid and clear cell histotypes. The aim of this study was to compare data from patients affected by these two histotypes to investigate the hypothesis of a dichotomy in the histogenesis of these tumors. Clinical data and tumor characteristics of 48 patients who were diagnosed with either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer arising from endometriosis (ECC, n = 22) or endometriosis-associated endometrioid ovarian cancer (EAEOC, n = 26) were compared. A previous diagnosis of endometriosis was detected more frequently in the ECC group (32% vs. 4%, p = 0.01). The incidence of bilaterality was significantly higher in the EAOEC group (35% vs. 5%, p = 0.01) as well as a solid/cystic rate at gross pathology (57.7 ± 7.9% vs. 30.9 ± 7.5%, p = 0.02). Patients with ECC had a more advanced disease stage (41% vs. 15%; p = 0.04). A synchronous endometrial carcinoma was detected in 38% of EAEOC patients. A comparison of the International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis showed a significantly decreasing trend for ECC compared to EAEOC (p = 0.02). These findings support the hypothesis that the origin, clinical behavior and relationship with endometriosis might be different for these histotypes. ECC, unlike EAEOC, seems to develop within an endometriotic cyst, thus representing a window of possibility for ultrasound-based early diagnosis.

The Experience of COVID-19 in a Sample of Gynecological Cancer Patients Undergoing Chemotherapy: A Focus on the Psychological Implications.

Cancer patients are at an increased risk of developing severe consequences due to the COVID-19 infection. However, psychological outcomes in this population have been overlooked in the literature. The present study aims to identify significant psychological differences between gynecological cancer patients undergoing chemotherapy before and during the pandemic. Additionally, we explore the correlations between COVID-19-related concerns and anxiety, depression, distress, and quality of life levels. Forty-two patients completed the STAI-Y, the EORTC QLQ-C30, the BDI II, the DT, and an ad-hoc questionnaire that investigated COVID-19-related concerns. The analyses did not show significant differences in the psychometric scales between the two groups, highlighting a considerable resilience against mental health and quality of life deterioration during the COVID-19 pandemic in gynecologic cancer patients. However, COVID-19-related concerns were positively associated with anxiety and inversely related to emotional functioning levels. These results emphasize the importance of a comprehensive patient care and the need to implement a multidisciplinary approach that includes psychological support in the treatment plan. Moreover, it is essential to encourage clear communication to convey comprehensive information about the impact of the pandemic on physical and psychological levels, as well as to offer psychoeducational tools to face the pandemic.

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness.

PURPOSE: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. METHODS: retrospective study, including 123 EC patients who underwent 18F-FDG PET (2009-2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80-20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. RESULTS: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. CONCLUSIONS: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients.

Experimental drugs for fallopian cancer: promising agents in the clinical trials and key stumbling blocks for researchers.

INTRODUCTION: Fallopian tube carcinoma (FC) as a single entity is a rare disease. Although its diagnosis is increasing thanks to the widespread use of prophylactic salpingectomy, there are no clinical trials exclusively designed for FC. AREAS COVERED: This review aims at identifying the most promising trials and future therapeutic pathways in the setting of FC. EXPERT OPINION: Hot topics in FC treatment include the consequences of using PARP inhibitors (PARPi) as first-line therapy, ways to overcome platinum resistance, and the role of immunotherapy. Patient selection is a key point for future development of target therapies. Next-generation sequencing (NGS) is one of the most investigated technologies both for drug discovery and identification of reverse mutations, involved in resistance to PARPi and platinum. New, promising molecular targets are emerging. Notwithstanding the disappointing outcomes when used by itself, immunotherapy in FC treatment could still have a role in combination with other agents, exploiting synergistic effects at the molecular level. The development of cancer vaccines is currently hampered by the high variability of tumor neoantigens in FC. Genomic profiling could be a solution, allowing the synthesis of individualized vaccines.

A prospective, observational study of chemotherapy-induced ovarian damage on follicular reserve and maturation.

BACKGROUND: Chemotherapy negatively affects gonadal function, often resulting in premature ovarian failure (POF) due to ovarian reserve depletion. Mechanisms of gonadotoxicity, such as primordial follicle overactivation and "burnout", remain to be established. Ovarian tissue cryopreservation (OTC) before treatment plays an important role in safeguarding fertility. METHODS: This is a prospective observational study that aims to evaluate the feasibility of OTC after chemotherapeutic treatment initiation. Patients were divided into 2 groups depending on whether they received chemotherapy before the harvesting procedure (Group 1) or not (Group 2). The main outcomes of this study are serum anti-Mullerian hormone (AMH) levels and histological follicular counts on ovarian tissue biopsies. RESULTS: Between 2012 and 2020, 79 patients underwent OTC at our Hospital. Follicular counts from the ovarian biopsies of 30 post-pubertal patients and respective serum AMH levels were included in the analysis. AMH levels did not significantly differ between the 2 groups (P = 0.70) as well as the number of primordial follicles (P = 0.73). Ovarian biopsies of patients from Group 1 showed a higher number of primary follicles (P = 0.04) and atretic follicles (P = 0.05) with respect to Group 2. CONCLUSIONS: In conclusion, OTC appears to be feasible even after the start of chemotherapeutic treatment, since in treated patients, the main ovarian reserve indicators (number of primordial follicles and serum AMH levels) were not significantly reduced compared to untreated patients. The "burnout" theory of chemotherapeutic damage to the ovary seems to be supported by the higher number of primary follicles found in the ovaries of patients who received chemotherapy before OTC.

Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN).

BACKGROUND: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. METHODS: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. RESULTS: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. CONCLUSIONS: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

Socio-demographic and psychological factors associated with quality of life of women undergoing chemotherapy treatment for gynecological cancer.

PURPOSE: This research aimed to investigate the socio-demographic, clinical, and psychological variables predictive of a greater functioning and quality of life in patients with gynecological cancer after their first cycle of carboplatin and taxol-based chemotherapy. METHODS: The sample of the present research consisted of 104 patients. The European Organization on Research and Treatment of Cancer QLQ-C30, the State-Trait Anxiety Inventory-Form Y, and the Multidimensional Scale of Perceived Social Support were administered to each participant. RESULTS: The analyses showed that higher state anxiety levels predicted a lower role, emotional, and social functioning and a lower general quality of life. Higher trait anxiety levels and social support perceived from one's friends predicted a greater role functioning. Similarly, having a relationship predicted a greater physical, cognitive, and social functioning. On the contrary, the presence of relapsed cancer was negatively associated with these patients' quality of life. CONCLUSIONS: The present study highlighted the importance of identifying patients at higher risk of experiencing lower levels of functioning and worse general quality of life to implement tailored interventions from the beginning of treatment, thus improving the quality of life of these patients throughout the chemotherapy treatment.

Ovarian failure risk in post-pubertal patients with cancer: a prognostic model.

Aim: To develop a predictive model for ovarian failure (OF) after chemotherapy in young post-pubertal women with cancer. Methods: Retrospective, monocentric cohort study including 348 patients referring to the Oncofertility Unit of San Raffaele Hospital (Milan, Italy) from August 2011 to January 2020. A predictive model was constructed by multivariate logistic regression and receiver operating characteristic analysis. Results: Data about menstrual function resumption were available for 184 patients. The best predictive model for OF was identified by the combination of age; number of chemotherapy lines; vincristine, adriamycin, ifosphamide/adriamycin, ifosphamide; capecitabine; adriamycin, bleomycine, vinblastine, doxorubicin (area under the curve = 0.906; CI 95% 0.858-0.954; p = 0.0001). Conclusions: The model predicts the probability of loss of ovarian function at cancer diagnosis and with every change of treatment.

Chemotherapy can reduce fertility in young women surviving cancer. The effects of chemotherapy on ovarian function range from no damage to several degrees of reduced fertility. In some cases, premature menopause can occur. This variability depends on many different individual and treatment-related factors. In this study, we analyzed the outcomes in terms of menses regularity and fertility of 348 oncological patients receiving counseling on fertility at our unit from August 2011 to January 2020. We developed a predictive model to estimate the risk of premature menopause of each patient, to be used at diagnosis and every time a new treatment must be started. This model includes a combination of patient's age, number of lines of chemotherapeutic treatment, and three chemotherapy schedules commonly used in young patients with cancer. It allows an improved counseling on fertility, and it can aid decision making regarding fertility preservation strategies for each patient.

Fertility sparing surgery in sex-cord stromal tumors: oncological and reproductive outcomes.

Sex cord stromal tumors are rare neoplasms, frequently diagnosed in young women often as early-stage disease. In patients who desire to preserve fertility, when possible, unilateral salpingo-oophorectomy with peritoneal surgical staging is a safe alternative to radical treatment. In this review, we analyze the available literature on the obstetrical outcomes after fertility-sparing surgery in a total of 255 patients with sex cord stromal tumors. We found that the spontaneous conception rate in granulosa cells tumor is encouraging (88.5%). In particular, juvenile granulosa cell tumors are associated with a more successful pregnancy rate than adult granulosa cells tumors (11/26 (42.3%) in juvenile granulosa cells tumors compared with 28.5% in adult granulosa cell tumors, respectively.) On the other hand, the results of obstetrical outcomes in Sertoli-Leydig cells tumors are less promising (7/36 (19.4%)). Unfortunately, no evidence on this topic is available for sex cord tumor with annular tubules due to the low incidence. Regarding the oncological outcomes of 900 cases of sex cord stromal tumors treated conservatively, data are reassuring with comparable outcomes between patients treated with conservative and radical surgery. Given the limited available data on this rare tumor, further studies are needed to evaluate the safety of conservative approaches and to define the obstetrical outcomes in this patient population.

18F-FDG PET/CT May Predict Tumor Type and Risk Score in Gestational Trophoblastic Disease.

PURPOSE: The aim of this study was to investigate the role of 18F-FDG PET/CT in predicting pathological prognostic factors, including tumor type and International Federation of Gynecology and Obstetrics (FIGO) score, in gestational trophoblastic disease (GTD). METHODS: Retrospective monocentric study including 24 consecutive patients who underwent to 18F-FDG PET/CT from May 2005 to March 2021 for GTD staging purpose. The following semiquantitative PET parameters were measured from the primary tumor and used for the analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolisis (TLG). Statistical analysis included Spearman correlation coefficient to evaluate the correlations between imaging parameters and tumor type (nonmolar trophoblastic vs postmolar trophoblastic tumors) and risk groups (high vs low, defined according to the FIGO score), whereas area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive value of the PET parameters. Mann-Whitney U test was used to further describe the parameter's potential in differentiating the populations. RESULTS: SUVmax and SUVmean resulted fair (AUC, 0.783; 95% confidence interval [CI], 0.56-0.95) and good (AUC, 0.811; 95% CI, 0.59-0.97) predictors of tumor type, respectively, showing a low (ρ = 0.489, adjusted P = 0.030) and moderate (ρ = 0.538, adjusted P = 0.027) correlation. According to FIGO score, TLG was instead a fair predictor (AUC, 0.770; 95% CI, 0.50-0.99) for patient risk stratification. CONCLUSIONS: 18F-FDG PET parameters have a role in predicting GTD pathological prognostic factors, with SUVmax and SUVmean being predictive for tumor type and TLG for risk stratification.

Weekly Paclitaxel Administered During a Twin Pregnancy for Recurrent Breast Cancer: Case Report and Review of the Literature.

Although cancer treatment during single pregnancy has been standardized, how to manage cancer diagnosed during a multiple gestation is still unclear. Chemotherapy during pregnancy has shown to be safe, however, there are reports of increased risks of fetal complications such as intrauterine growth restriction and preterm birth. Also, how to best adjust this to the pharmacokinetic characteristics of a twin gestation has yet to be fully investigated. We report the case of an IVF twin pregnancy with a diagnosis of breast cancer recurrence shortly after conception, and how the pregnancy was managed to obtain optimal obstetric, maternal/oncological, and fetal outcomes.

The neglected members of the family: non-BRCA mutations in the Fanconi anemia/BRCA pathway and reproduction.

BACKGROUND: BReast CAncer (BRCA) genes are extensively studied in the context of fertility and reproductive aging. BRCA proteins are part of the DNA repair Fanconi anemia (FA)/BRCA pathway, in which more than 20 proteins are implicated. According to which gene is mutated and which interactions are lost owing to the mutation, carriers and patients with monoallelic or biallelic FA/BRCA mutations exhibit very different phenotypes, from overt FA to cancer predisposition or no pathological implications. The effect of the so far neglected non-BRCA FA mutations on fertility also deserves consideration. OBJECTIVE AND RATIONALE: As improved treatments allow a longer life expectancy in patients with biallelic FA mutations and overt FA, infertility is emerging as a predominant feature. We thus reviewed the mechanisms for such a manifestation, as well as whether they also occur in monoallelic carriers of FA non-BRCA mutations. SEARCH METHODS: Electronic databases PUBMED, EMBASE and CENTRAL were searched using the following term: 'fanconi' OR 'FANC' OR 'AND' 'fertility' OR 'pregnancy' OR 'ovarian reserve' OR 'spermatogenesis' OR 'hypogonadism'. All pertinent reports in the English-language literature were retrieved until May 2021 and the reference lists were systematically searched in order to identify any potential additional studies. OUTCOMES: Biallelic FA mutations causing overt FA disease are associated with premature ovarian insufficiency (POI) occurring in the fourth decade in women and with primary non-obstructive azoospermia (NOA) in men. Hypogonadism in FA patients seems mainly associated with a defect in primordial germ cell proliferation in fetal life. In recent small, exploratory whole-exome sequencing studies, biallelic clinically occult mutations in the FA complementation group A (Fanca) and M (Fancm) genes were found in otherwise healthy patients with isolated NOA or POI, and also monoallelic carrier status for a loss-of-function mutation in Fanca has been implicated as a possible cause for POI. In those patients with known monoallelic FA mutations undergoing pre-implantation genetic testing, poor assisted reproduction outcomes are reported. However, the mechanisms underlying the repeated failures and the high miscarriage rates observed are not fully known. WIDER IMPLICATIONS: The so far 'neglected' members of the FA/BRCA family will likely emerge as a relevant focus of investigation in the genetics of reproduction. Several (rather than a single) non-BRCA genes might be implicated. State-of-the-art methods, such as whole-genome/exome sequencing, and further exploratory studies are required to understand the prevalence and mechanisms for occult FA mutations in infertility and recurrent miscarriage.

[Anti-angiogenic drugs and hypertension: from multidisciplinary collaboration to greater care].

Anti-angiogenic drugs are widely used in cancer therapy. Their main targets of action are the vascular endothelial growth factor (VEGF) and its receptors (VEGF-R). Anti-angiogenic drugs are used to reduce the growth of the tumor and its metastases by acting on the phenomenon of tumor neo-angiogenesis. However, they are known for their side effects such as hypertension, acute kidney injury (AKI), and congestive heart failure. Methods: retrospective study conducted on 57 consecutive patients known for ovarian cancer. Patients treated with Bevacizumab, as first-line, relapse, or maintenance treatment (2015-2022). Results: according to FIGO staging, 98.2% (56 out of 57) of the patients in the study had third degree disease (G3). 49% of patients developed hypertension after starting Bevacizumab therapy (82% grade 2 according to CTCAE v.5). 89% of hypertensive patients started treatment and its management was multidisciplinary with nephrological consultation in 68% of cases. Only 3 out of 57 women discontinued treatment due to hypertension, and in only one of them it was not possible to restart it. Conclusions: the evaluation of the patient by a multidisciplinary team (gynecologist and nephrologist) is essential to minimize the morbidity and mortality of patients, and to avoid the interruption of antineoplastic treatment.