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.

Impact of COVID-19 on medical treatment patterns in gynecologic oncology: a MITO group survey.

OBJECTIVE: COVID-19 is a global public health emergency. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological tumors. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) performed a survey to evaluate the impact of the COVID-19 pandemic on medical treatment of gynecological cancer, with a focus on chemotherapy and oral treatment with poly(ADP)-ribose polymerase inhibitors (PARP-i). METHODS: The survey consisted of a self-administered online questionnaire, sent via email between November 2020 and January 2021 to all members of MITO group. RESULTS: Forty-nine centers completed the questionnaire. The majority of respondents (83%) use screening tests to determine COVID-19 status in patients who were to undergo chemotherapy or oral medications. All respondents to our survey continued cancer therapy in patients who tested negative for COVID-19 during the pandemic. Seventy-three percent of respondents declared they stopped treatment with chemotherapy or PARP-i only after a positive swab and resumed therapy when negative tests were confirmed. CONCLUSIONS: COVID-19 positivity impacted patterns of treatment in patients diagnosed with ovarian cancer within the MITO group. Further investigations are needed to evaluate whether these modifications influence oncological clinical outcomes.

Transvaginal ultrasound in evaluation and follow-up of ovarian granulosa cell tumors.

OBJECTIVE: Ultrasound features of granulosa cell tumors of the ovary are still poorly defined. The aim of this study is to widen current knowledge on the role of sonographic gray scale and pattern recognition in the characterization of these tumors and to compare the ultrasound characteristics of primary diagnosis and recurrences. METHODS: Transvaginal ultrasound images of primary diagnosis or recurrences of histologically-confirmed granulosa cell tumors of the ovary were retrospectively retrieved from a dedicated database designed for the collection of clinical and ultrasound data from January 2001 to January 2019. All patients included were treated at San Raffaele and Santa Chiara Hospitals. Women with a concomitant diagnosis of another malignancy other than endometrial carcinoma were excluded from the study. All ultrasound images were described according to International Ovarian Tumor Analysis terminology and examined by experienced ultrasound examiners. RESULTS: A total of 27 patients were included: 24 with adult and 3 with juvenile ovarian granulosa cell tumors. At primary diagnosis, mean ovarian mass size was 103.8 mm (range 30-200). On ultrasound evaluation at primary diagnosis, 12 patients presented with a multilocular solid lesion (48%), 9 with a solid lesion (36%), and 4 with a multilocular lesion(16%). The echogenicity of the cyst was low level or anechoic, mixed, or hemorrhagic in 56.3%, 31.2%, and 12.5% of cases, respectively. Most tumors (45.1%), including first diagnosis and relapses, had a moderate to high color score on doppler evaluation. CONCLUSIONS: Our study showed that sonographic features and pattern recognition of relapses were comparable to those of tumors at primary diagnosis. In order to highlight the importance of transvaginal ultrasound evaluation during follow-up, further studies based on a standardized ultrasound characterization of ovarian masses are recommended.

Management of recurrent ovarian cancer: when platinum-based regimens are not a therapeutic option.

Ovarian cancer relapses have been traditionally classified according to the platinum-free interval, leading to an arbitrary categorization of possible scenarios and treatment options. Its relevance in assessing treatment strategies has been revised in the last several years, as the panorama is constantly changing in the era of personalized medicine and targeted therapies. Factors to be considered while defining the best management of recurrent disease, and, consequently, the available treatment alternatives are increasing. Platinum remains one of the milestones of ovarian cancer treatment, but for some patients it might not be an ideal choice for several reasons other than limited platinum sensitivity. This review aims to analyze the scenarios in which platinum is not considered suitable in the management of patients with recurrent ovarian cancer, and the currently available alternatives.

Fibroblastic Malignant Peripheral Nerve Sheath Tumour of the Uterine Cervix: Report of a Case and Literature Review With Emphasis on Possible Differential Diagnosis.

Cervical sarcomas are rare neoplasms, accounting for <1% of all cervical malignancies and characterized by an aggressive course despite radical excision. We report the clinical and microscopic features of a spindle cell sarcoma arising as a polypoid endocervical mass in a 45-yr-old woman. The neoplasm was characterized by a monotonous, mildly atypical proliferation of spindle cells, displaying a fibrosarcoma-like parallel pattern of highly dense fascicles, growing under the cervical epithelium. Mitotic activity was conspicuous, with up to 40 mitoses per 10 HPF. On immunohistochemistry, tumor cells were patchy S-100 protein positive. Additional immunohistochemical markers performed to rule out smooth muscle, melanocytic, epithelial, and sarcomatous differentiation were negative. A possible monophasic synovial sarcoma was also excluded by negative fluorescence in situ hybridization t(X;18) analysis. Interestingly, the neoplasm showed a focal CD34 positivity, as reported in normal fibrocytic cells of the endocervical stroma. Giving the morphologic and immunohistochemical features, the neoplasm was eventually defined as malignant peripheral nerve sheath tumor. Histologic examination following radical surgery revealed the neoplasm was confined to the uterine cervix (FIGO stage IB1) and at 12 mo of follow-up, the patient is still free of disease. Malignant peripheral nerve sheath tumors are highly aggressive sarcomas that can rarely involve the uterine cervix. They have to be differentiated from melanoma, leiomyosarcoma, endometrial stromal sarcoma, synovial sarcoma, and other spindle cell neoplasms.

Multidisciplinary approach in the management of advanced ovarian cancer patients: A personalized approach. Results from a specialized ovarian cancer unit.

OBJECTIVE: The aim of the present study was to evaluate the impact of a multidisciplinary approach in patients' selection with advanced ovarian cancer (AOC) for different therapeutic strategies. METHODS: Patients referred at our institution between 2009 and 2012 for AOC were included. Primary multidisciplinary evaluation was performed in all patients. Different strategies included: 1. patients referred to primary neoadjuvant chemotherapy (NACT) and interval surgery (IDS) (group A); 2. patients considered for surgical exploration. After surgical exploration, patients were either considered for primary debulking (PDS; group B), or NACT (group C). RESULTS: A total of 363 patients were included. Of 38 patients (10.5%) in group A, 24 (63%) had sovradiaphragmatic/multiple liver metastases; 14 (37%) were excluded for PDS for anestehesiologic/medical reasons. Of 325 (89.5%) considered for surgical exploration, 295 (91%; group B) had primary surgery with debulking intent (N: 277) and were cytoreduced to no macroscopic disease (R0: N:200; 68%) o minimal RD<5mm (R1: N:77; 26%) or palliative intent (N:18; 6%); 30 (9%; group C) were referred for NACT. Of those, 27 (90%) underwent IDS, 3 had progressive disease. Overall survival (OS) and progression free survival (PFS) was different between the groups: OS: Group A: 34months; Group B: 59months; Group C: 29months; p<0.001. PFS: Group A: 10months; Group B; 21months; Group C: 12months; p<0.001. CONCLUSIONS: A multidisciplinary approach to patients referred to a tertiary center with AOC allows optimization of the treatment strategy, based on patients' characteristics (age, performance/nutritional status, comorbidities, functional status) and tumor diffusion (evaluated pre- and intraoperatively).

Feasibility of Transabdominal Cardiophrenic Lymphnode Dissection in Advanced Ovarian Cancer: Initial Experience at a Tertiary Center.

OBJECTIVES: The purpose of this retrospective report is to define the safety and feasibility, based on our preliminary experience, of surgical transdiaphragmatic resection of enlarged cardiophrenic lymph nodes (CPLNs), as a part of upfront debulking surgery. Supradiaphragmatic nodes located between the diaphragm and the heart are frequently a location for lymph node metastasis in advanced ovarian cancer, and their removal is aimed to obtain no gross residual disease at the primary cytoreductive surgery often requiring aggressive surgical procedures. PATIENTS AND METHODS: Between May 2012 and October 2016, a total of 22 patients among 443 with advanced high-grade serous ovarian cancer underwent cytoreductive procedures involving transdiaphragmatic resection of enlarged CPLNs at European Institute of Oncology in Milan. RESULTS: All patients who underwent CPLN resection had an extensive disease (median peritoneal cancer index, 18), and more than 77% required complex surgical procedures (complexity score, 3). No residual abdominal disease less than 5 mm at the end of surgery was described in 20 (90%) out of 22. All patients but one had confirmed CPLN positive nodes at histopathological study. The average operative time was 333 min (range, 244-455 min), and the average estimated blood loss was 1000 mL (range, 400-2000 mL). Blood transfusion was necessary in 13 out of 22 patients. Only 7 (33%) out of 21 patients required chest tube placement during the postoperative period. CONCLUSIONS: Transdiaphragmatic enlarged CPLN resection seems to be safe and feasible procedure when indicated to achieve no or minimal tumor residual disease. Nevertheless, its impact on survival of patients with stage IV ovarian cancer needs to be determined.

Robot-Assisted Vesico-Vaginal Fistula Repair: Our Technique and Review of the Literature.

OBJECTIVE: Our first objective was to report our experience on robot-assisted vesico-vaginal fistula (VVF) repair after radical surgery for gynecologic malignancies without omental flap interposition using a da Vinci robotic system. The second objective was to critically review the literature in order to analyze surgical solutions used to avoid repair failure. MATERIALS AND METHODS: Five patients with VVF diagnosed after previous open surgery for gynecologic malignancies referred to our tertiary institutions were selected. After an adequate oncologic follow-up, based on the fistula diameter and conservative management failure, robotic surgery repair was proposed. A bivalve 2-layer suturing technique was carried out without tissue interpositions; omentum was not available secondary to previous surgery including hysterectomy, ovaryectomy, and omentectomy and citoreductive peritoneomectomy. A systematic review of the literature was performed in December 2016 using the PubMed database with the following keywords: robotic, robot-assisted, vesico-vaginal, fistula repair. RESULTS: Median age was 62 years (range 55-71) bearing long-lasting VVF were referred to our divisions. Median fistula diameter was 5 mm (range 3-8 mm). Fistula site was the trigone and identified during cystoscopy near the mid-line, left, and right urether meatus, respectively. The median overall and console operatory time were 250 and 120 min, respectively. Blood loss was insignificant (median 40 mL) and the median length of stay was 7 days without any complication. Ten papers were found fulfilling the mentioned criteria, from which 6 were case reports, single or multiple, accounting for the overall 41 robotic-approach-operated patients. CONCLUSION: The quality of the dissection and suture associated with efficient urine drainage are in our opinion the key elements of the success of our technique, which can be performed even without omentum or other tissue flap or graft interposition.

Clinical and Oncologic Outcomes of Robotic Versus Abdominal Radical Hysterectomy for Women With Cervical Cancer: Experience at a Referral Cancer Center.

OBJECTIVES: To compare the clinical and oncologic outcomes of robotic radical hysterectomy (RRH) vs abdominal radical hysterectomy (ARH) in patients with cervical carcinoma. METHODS: A retrospective analysis of women who underwent radical hysterectomy for cervical cancer from December 2006 to December 2014 at European Institute of Oncology was performed. Patients who underwent RRH were compared with women operated on by ARH. The groups were matched by age, body mass index, tumor size, International Federation of Gynecology and Obstetrics stage, comorbidity, previous neoadjuvant chemotherapy, histology type, and tumor grade. RESULTS: A total of 203 and 104 women who underwent RRH and ARH, respectively, were analyzed. Baseline characteristics, stage of disease, histology type, and grade of differentiation were similar between groups. Surgical time was significantly shorter in the ARH group (208 vs 282 minutes, P ≤ 0.001). Robotic radical hysterectomy was associated with significantly less estimated blood loss (219 vs 104 mL, P = 0.001) and with significantly shorter hospital stay (5.2 vs 3.9 days, P ≤ 0.001). Abdominal radical hysterectomy was correlated with a significantly higher number of lymph nodes removed (25.8 vs 22, P = 0.003). None of the robotic procedures required conversion to laparotomy. A significantly higher number of patients in ARH required postoperative transfusion (11 [10.5%] vs 6 [2.9%], P = 0.006). Lower extremity lymphedema was significantly higher in ARH (28 [27.5%] vs 17 [8.3%], P = 0.001). Recurrence rates as well as progression-free survival and overall survival were similar between groups at a median follow-up of 41.64 months. CONCLUSIONS: Robotic radical hysterectomy is safe and feasible and is associated with improved clinical outcomes. Although longer follow-up is needed, early data show equivalent oncologic outcomes compared with other surgical modalities.

Platinum-based neoadjuvant chemotherapy followed by radical surgery for cervical carcinoma international federation of gynecology and obstetrics stage IB2-IIB.

OBJECTIVE: The objective of this study was to determine the response rate to chemotherapy, as well as the progression-free survival (PFS), the overall survival (OS), and the main prognostic factors in patients treated at the European Institute of Oncology in Milan, Italy. METHODS: Retrospective data were collected on patients with uterine cervical carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB, who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy. RESULTS: A total of 121 patients were studied. The median (range) age was 45 years old (23-69 years). The distribution of patients by International Federation of Gynecology and Obstetrics stage was as follows: n = 88 (73%) with stage IB2, n = 7 (6%) with stage IIA, and n = 26 (21%) with stage IIB. The median (range) tumor size was 50 mm (20-90 mm). Neoadjuvant chemotherapy involved a combination of cisplatin, paclitaxel, and ifosfamide in 80 patients (65%). Using this treatment, 112 patients (93%) received 3 cycles of NACT, whereas 6 (5%) received 4 cycles. Complete and partial pathology response was observed in 9 patients (7%) and 79 patients (66%), respectively. Adjuvant radiotherapy was not necessary in 65% of patients. A 5-year PFS and OS of 58% and 71%, respectively, were observed. Independent prognostic factors for PFS and OS were identified, including response to NACT, persistent lymph node metastases, and parametrial involvement. CONCLUSIONS: Neoadjuvant chemotherapy in this group of tumors is a promising treatment strategy and should be discussed with patients. Although these results are comparable to those obtained by standard chemoradiation treatment, one strategy should not be recommended over the other until the results of the ongoing phase 3 trial for NACT are released.

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.

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.

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

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.

Rectosigmoid resection at the time of primary cytoreduction for advanced ovarian cancer. A multi-center analysis of surgical and oncological outcomes.

OBJECTIVE: The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer. METHODS: We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected. RESULTS: A total of 238 patients were identified; 180 (75%) had stages IIC-IIIC and 58 (25%) had stage IV. Complete cytoreduction was achieved in 41% of the cases. Stapled coloproctostomy was performed in 98% while hand sewn in only 2%; a protective ileostomy and colostomy were necessary (constructed) in 2 (0.8%) and 5 (2%) cases respectively. The complications associated to rectosigmoid resection were anastomotic leakage in 7 (3%) patients and pelvic abscess in 9 (3.7%). Fifty percent of patients recurred during the study period, but only 5% of them showed a relapse at the level of the pelvis whereas 8% presented with abdominal recurrence associated with pelvic disease as well. The median overall survival time among patients with complete cytoreduction was 72 months compared with 42 months among the rest of patients (p=0.002). CONCLUSIONS: Rectosigmoid colectomy may significantly contribute to achieve a complete primary cytoreduction for advanced stage ovarian, tubal and peritoneal cancers. Pelvic complete debulking accomplished by rectosigmoid resection could be associated with a lower rate of pelvic recurrence as well.

Splenectomy as part of primary cytoreductive surgery for advanced ovarian cancer: a retrospective cohort study.

BACKGROUND: The aim of surgical approach in advanced ovarian cancer should be the complete removal of all visible disease. Our purpose was to compare perioperative features and postoperative complications, and secondarily oncological outcomes, between patients who underwent splenectomy and those who did not at the time of surgery. MATERIALS AND METHODS: Thirty-three subjects underwent splenectomy, and we selected 99 controls with similar surgical characteristics but who did not undergo splenectomy. Data collected included perioperative details and follow-up data. RESULTS: Longer operating time (33 minutes longer; P = 0.02), larger estimated blood loss (812 mL more; P = 0.03), higher rate of intraoperative blood transfusions (78.8% vs 42.4%; P < 0.01), and intensive care unit stay (1.4 vs 0.5 days; P < 0.01) as well as higher pneumonia rate (2% vs 0%; P = 0.01) were observed in the splenectomy group. Disease-free and overall survival rates were 30.3% and 66.6%, respectively, in the splenectomy group, and 33.3% and 59.6%, respectively, in the control group. CONCLUSIONS: Splenectomy at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to achieve complete cytoreduction with low perioperative complication rate. This procedure seems to be an acceptable and rational intervention to increase the survival rates of those 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.

Hybrid PET/MRI in Staging Endometrial Cancer: Diagnostic and Predictive Value in a Prospective Cohort.

AIM: The assessment of deep myometrial invasion (MI) and lymph node involvement is of utmost importance in the preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. The main aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and lymphnodal involvement detection. PATIENTS AND METHODS: Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI (December 2018-March 2021) for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean with a threshold of 40% of SUVmax-SUVmean40, metabolic tumor volume, total lesion glycolysis) and MRI (volume index [VI], total tumor volume, tumor volume ratio [TVR], mean apparent diffusion coefficient, minimum apparent diffusion coefficient) parameters were calculated on the primary tumor, and their role in predicting EC risk group, the presence of lymphovascular space invasion (LVSI), and MI was assessed. Receiver operating characteristics analysis was used to assess the predictive value of PET and MRI parameters on EC characteristics. RESULTS: Patients' median age was 66.57 years (SD, 10.21 years). 18F-FDG PET/MRI identified the primary tumor in all patients. Twenty-two of 35 patients had high-risk EC and 13/35 low-risk disease; 13/35 presented LVSI, 22/35 had deep MI at histological examination, and 13/35 had p53 hyperexpression.PET/MRI was able to detect lymphnodal involvement with high accuracy and high specificity (sensitivity of 0.8571, specificity of 0.9286, accuracy of 0.9143), also showing a high negative predictive value (NPV) for lymphnodal involvement (NPV of 0.9630, positive predictive value [PPV] of 0.7500).The assessment of deep MI using PET/MRI correctly staged 27 patients (77.1%; sensitivity of 0.7273, specificity of 0.8462, accuracy of 0.7714), with also a good PPV (PPV of 0.8889, NPV of 0.647).MRI-derived total tumor volume, VI, and TVR were significant in predicting EC groups (high-risk vs low-risk patients) (P = 0.0059, 0.0235, 0.0181, respectively). MRI-derived volume, VI, TVR, and PET-derived metabolic tumor volume and total lesion glycolysis were able to predict LVSI (P = 0.0023, 0.0068, 0.0068, 0.0027, 0.01394, respectively). Imaging was not able to predict grading, presence of deep MI, nor hyperexpression of p53. CONCLUSIONS: 18F-FDG PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk group.