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Introduction: Pelvic exenteration performed for recurrent/persistent gynecological malignancies has been associated with urological short- and long-term morbidity due to altered vascularization of tissues for previous radiotherapy. The aims of the present study were to describe the use of intravenous indocyanine green (ICG) to assess vascularity of urinary diversion (UD) after pelvic exenteration for gynecologic cancers, to evaluate the feasibility and safety of this technique, and to assess the postoperative complications. Methods: Prospective, observational, single-center, pilot study including consecutive patients undergoing anterior or total pelvic exenteration due to persistent/recurrent gynecologic cancers between August 2020 and March 2021 at Fondazione Policlinico Gemelli IRCCS, Rome, Italy. All patients underwent intravenous injection of 3–6 ml of ICG (1.25 mg/ml) once the UD was completed. A near-infrared camera was used to evaluate ICG perfusion of anastomoses (ileum–ileum, right and left ureter with small bowel, and colostomy or colorectal sides of anastomosis) a few seconds after ICG injection. Results: Fifteen patients were included in the study. No patient reported adverse reactions to ICG injection. Only 3/15 patients (20.0%) had an optimal ICG perfusion in all anastomoses. The remaining 12 (80.0%) patients had at least one ICG deficit; the most common ICG deficit was on the left ureter: 3 (20.0%) vs. 1 (6.7%) patient had no ICG perfusion on the left vs. right ureter, respectively (p = 0.598). 8/15 (53.3%) and 6/15 (40.0%) patients experienced grade ≥3 30-day early and late postoperative complications, respectively. Of these, two patients had early and one had late postoperative complications directly related to poor perfusion of anastomosis (UD leak, ileum–ileum leak, and benign ureteric stricture); all these cases had a suboptimal intraoperative ICG perfusion. Conclusion: The use of ICG to intraoperatively assess the anastomosis perfusion at time o

Improving single-agent chemoresistance risk identification in gestational trophoblastic neoplasia Gabriella Ferrandina 1, Giovanni Scambia 2 Affiliations expand PMID: 34181885 DOI: 10.1016/S1470-2045(21)00327-2 No abstract available

Objective: The aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging. Methods: MITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB-C dysgerminomas, IA-C G2-G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors). Results: A total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6-83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully. Conclusions: Our data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C dysgerminomas, IA-IC G2-G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component.

Objectives: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). Methods: A multi-institutional retrospective study was conducted within the MITO Group. Results: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. Conclusions: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.

Background: During the COVID-19 pandemic, cancer care had to be reorganized; national and international recommendations were published to manage anticancer treatments safely and to reduce the risk of SARS-CoV-2 infection for patients and health workers. Objective: To evaluate whether the adoption of recommendations for the management of patients with gynaecologic cancer receiving treatment during the pandemic resulted in containment of infections and continuing oncologic care. Methods: Based on the published recommendations, and according to the local Health Direction guidelines, we developed and drafted a security protocol to modify access of patients with gynaecologic cancer to the "Fondazione Policlinico Agostino Gemelli-IRCCS, Rome" between February 1 and April 30, 2020 and compared results with the corresponding 3 months of 2019. Results: Between February and April 2019, we registered 3254 admissions, including 2253 patients receiving intravenous chemotherapies, 298 receiving oral therapies, and 703 having hospital visits. Between February and April 2020, we registered 3213 admissions, including 2221 patients receiving intravenous chemotherapies, 401 receiving oral therapies, and 591 having hospital visits. Oral treatments and general visits were different in the two time periods (p<0.001). Despite the elevated patient flow, only one patient (0.1%) tested positive for COVID-19 and there were no cases among healthcare staff. Conclusions: Based on the adopted security protocol we provided continuity of care for all patients and limited the spread of the COVID-19 infection.

BACKGROUND: The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. METHODS: Patients with pathologic FIGO 2009 stage IA1–IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. RESULTS: 395 patients were included in the study. 93 (23.5%) patients had TFD ≤ 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD ≤ 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with lowrisk factors who did not receive adjuvant treatment (p = 0.002). Cohen’s kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. CONCLUSIONS: Pathologic TFD ≤ 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

OBJECTIVE: Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer).METHODS: Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse.RESULTS: Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered.CONCLUSIONS: Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance.

Objective: To evaluate feasibility of neoadjuvant chemotherapy (NACT) followed by cold-knife conization (CKC) in patients with 2018 FIGO stage IB2–IIA1 cervical cancer who desired to maintain fertility. Design: Pilot study of conization after chemotherapy in stage IB2–IIA1 >2 cm cervical cancer. Setting: University hospital. Patient(s): From 2014 to 2018, 25 patients, <40 years of age, were enrolled. Interventions(s): After laparoscopic pelvic lymph-node assessment, NACT with cisplatin/paclitaxel q21 was administered to eligible patients. Responsive patients were treated with CKC. Main Outcome Measure(s): Obstetrical outcome: pregnancy rate. Oncologic outcome. Result(s): Thirteen out of 25 patients were eligible for fertility-sparing treatment. Oncologic outcome: The clinical overall response rate was 84.5% (11 out of 13 patients). One patient achieved stable disease, was managed by radical surgery, and is still alive; another one experienced progression of disease and died after 15 months. The optimal pathologic response was 69.1%. In the setting of fertility preservation patients, the median follow-up was 37 months (range 18–76). In this group we registered one distant recurrence, 12 months after CKC, in the liver; the patient is still alive and without evidence of disease. Obstetrical outcome: Among the nine patients amenable, three tried to conceive, and two spontaneous pregnancy occurred a few months after the end of treatment, for a pregnancy rate of 66.7%. Conclusion(s): This pilot study supports the feasibility of CKC after NACT as conservative treatment in stage IB2–IIA1 cervical cancer, with oncologic outcomes similar to those reported for trachelectomy in the same stage and with potential benefits in terms of obstetrical outcomes. Clinical Trial Registration Number: NCT02323841.

PURPOSE: Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery.METHODS: A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups.RESULTS: Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3days from surgery and they were susceptible to be discharged within 5days, compared, respectively, to 34.3% of Group 2 (n=15). Advantages were more evident in patients whose surgery took over 220min (OR 0.02, CI 95% 0.001-0.57; p<0.001) despite the type of surgical effort made.CONCLUSION: Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

PURPOSE: The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma.METHODS: This multicenter, retrospective observational cohort study included patients with FIGO 2009stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case-control matching was used to adjust the baseline characteristics.RESULTS: A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p=0.542 and p=0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p<0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively; p=0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively; p=0.114) or recurrence pattern (p=0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (p=0.011 and p=0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p=0.020).CONCLUSIONS: Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

Purpose: Segmental resection has been generally associated with increased peri-operative risk of major complications. While major complications are widely acknowledged, minor complications, such as slight, to moderate infections, peripheral sensory disturbances, bladder voiding dysfunction, postoperative urinary obstruction, and sexual disorders are less reported. The aim of this study is to investigate the surgery-related complications and functional disorders, as well as to evaluate their persistence after long-term follow-up in women undergone segmental resection for deep infiltrating endometriosis. Special attention is given to evaluating impairments of bowel, bladder, and sexual function. Methods: All clinical data obtained from medical records of women who underwent segmental resection for intestinal endometriosis between October 2005, and November 2017, in Catholic University Institutions. Perioperative morbidity was classified by Extended Clavien–Dindo classification. Postoperative intestinal, voiding, and sexual morbidity was estimated by the compilation of specific questionnaires. Results: Fifty women were included in the study. Forty-three high colorectal resections (86%), 6 low resections (12%), and 1 ultra-low resection (2%) were performed, while in 3 cases (6%) multiple resections were needed. The overall complication rate was 44%. Nineteen women (38%) experienced early complications and 3 women (6%) late complications. Long-term functional postoperative complications were composed of intestinal in 30%, urinary in 50%, and sexual in 64% of the study population. Median follow-up was 55.5 months. Conclusions: Segmental resection, when indicated, offers a radical and feasible approach for bowel deep infiltrating endometriosis, resulting in an improved general quality of life. The bowel and bladder complications appear to be acceptable and often reversible. Postoperative sexual dysfunctions, such as anorgasmia and insufficient vaginal lubrication, app

Objective: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. Methods: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. Results: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). Conclusions: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecogni

Purposes: The primary objective is to assess the long-term quality of life (QoL) and gastrointestinal well-being in patients with endometriosis (DIE) who underwent segmental resection (SR), through specific questionnaires focused on endometriosis and specific gastrointestinal evaluation. The secondary objectives are represented by the evaluation of peri-operative and post-operative outcomes of the procedure. Methods: This observational cohort study ENDO-RESECT (ClinicalTrials.gov ID: NCT03824054) reports all clinical data about women who underwent SR for DIE between October 2005 and November 2017. In the part of the study dedicated to the QoL assessment, the questionnaires adopted were the Endometriosis Health Profile (EHP30), the Psychological General Well-Being Index and the Hospital Anxiety and Depression Scale, the Gastrointestinal Well-being questionnaire and the Bristol Stool chart. Major post-surgical morbidity and obstetric outcomes were also collected. Results: 50 women (18% stage III and 82% stage IV rAFS) were considered for enrollment. EHP-30 interpretation demonstrated a significant improvement in all continuous variables, except for fertility concerns. The overall gastrointestinal QoL and most of the specific symptoms improved after surgery. Frequent bowel movements appeared in the 13% of the series not resulting in an impairment of general and gastrointestinal QoL. Constipation remained unchanged. Patients with depressive mood managed with laparoscopy, benefited the most from SR; moreover, patients with multinodular bowel localizations experienced a greater reduction in abdominal pain. Median FU after SR was 42.5 months (range 12–157 months). Only three (6%) cases of late major grade III complications were documented. The pregnancy rate was 50%. Conclusions: Improvement of general QoL and most of gastrointestinal symptoms was documented after SR.

Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting.

Purpose: Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role in locally advanced cervical cancer (LACC) patients with suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Our aim is to evaluate oncological and surgical outcomes of minimally invasive radical surgery (MI-RS) compared with open radical surgery (O-RS). Patients and methods: Data for stage IB2-IVA cervical cancer patients managed by CT/RT and RS were retrospectively analyzed. Results: Beginning with 686 patients, propensity score matching resulted in 462 cases (231 per group), balanced for FIGO stage, lymph node status, histotype, tumor grade, and clinical response to CT/RT. The 5-year disease-free survival (DFS) was 73.7% in the O-RS patients and 73.0% in the MI-RS patients (HR 1.034, 95% CI 0.708-1.512, p = 0.861). The 5-year locoregional recurrence rate was 12.5% (O-RS) versus 15.2% (MI-RS) (HR 1.174, 95% CI 0.656-2.104, p = 0.588). The 5-year disease-specific survival (DSS) was 80.4% in O-RS patients and 85.3% in the MI-RS group (HR 0.731, 95% CI 0.438-1.220, p = 0.228). Estimated blood loss was lower in the MI-RS group (p < 0.001), as was length of hospital stay (p < 0.001). Early postoperative complications occurred in 77 patients (33.3%) in the O-RS group versus 88 patients (38.1%) in the MI-RS group (p = 0.331). Fifty-six (24.2%) patients experienced late postoperative complications in the O-RS group, versus 61 patients (26.4%) in the MI-RS group (p = 0.668). Conclusion: MI-RS and O-RS are associated with similar rates of recurrence and death in LACC patients managed by surgery after CT/RT. No difference in early or late complications was reported.

Background: Uterine sarcomas are very rare tumours with different histotypes, molecular features and clinical outcomes; therefore, it is difficult to carry out prospective clinical trials, and this often results in heterogeneous management of patients in the clinical practice. Aim: We planned to set up an Italian consensus conference on these diseases in order to provide recommendations on treatments and quality of care in our country. Results: Early-stage uterine sarcomas are managed by hysterectomy + bilateral salpingo-oophorectomy according to menopausal status and histology; lymphadenectomy is not indicated in patients without bulky nodes, and morcellation must be avoided. The postoperative management is represented by observation, even though chemotherapy can be considered in some high-risk patients. In early-stage low-grade endometrial stromal sarcoma and adenosarcomas without sarcomatous overgrowth, hormonal adjuvant treatment can be offered based on hormone receptor expression. In selected cases, external beam radiotherapy ± brachytherapy can be considered to increase local control only. Patients with advanced disease involving the abdomen can be offered primary chemotherapy (or hormonal therapy in the case of low-grade endometrial stromal sarcoma and adenosarcoma without sarcomatous overgrowth), even if potentially resectable in the absence of residual disease in order to test the chemosensitivity (or hormonosensitivity); debulking surgery can be considered in patients with clinical and radiological response. Chemotherapy is based on anthracyclines ± ifosfamide or dacarbazine. Palliative radiotherapy can be offered for symptom control, and stereotactic radiotherapy can be used for up to five isolated metastatic lesions. Conclusions: Treatment of uterine sarcoma should be centralised at referral centres and managed in a multidisciplinary setting.

The Enhanced Recovery After Surgery (ERAS) is a pathway designed to achieve early recovery for patients undergoing major surgery. The ERAS pathway included three important components preoperative, intraoperative, postoperative program. Pre-habilitation and re-habilitation are of paramount importance to improve patients' care. The ERAS is based on evidence-based medicine. Accumulating evidence highlighted that adopting ERAS resulted in lower complication rate, and shorter length of hospital stay in comparison to standard protocols of care. The adoption of the ERAS resulted in a significant improvement of patients' outcomes and a reduction of the overall cost of care. In the present review, we summarized current evidence on ERAS, focusing on the steps useful for its adoption into clinical practice.

Objective: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods: The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. Conclusions: National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

The aim of this study was to investigate the prevalence of peritoneal Human Papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between 03/2019 and 04/2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. 272 patients had cervical and peritoneal HPV-test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early-stage, 28.8% in locally-advanced (LACC), and 46.6% in the metastatic/persistent/recurrent setting (p=0.001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (p=0.003), presence of cervical HPV 16/18 genotypes (p<0.001), higher number of cervical high-risk (HR)-HPV per patient (p=0.018) and peritoneal carcinomatosis (p<0.001). Multivariate analysis demonstrated that lack of pre-operative cervical conization in early stages (p=0.030), while higher FIGO-stage (p=0.021) and presence of cervical HPV 16/18 (p=0.001) in LACC, were associated with PHP. This is a proof of concept study. A number of potential clinical implications, including prognosis, could be obtained by further studies.

Objective: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). Methods: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). Conclusions: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Objective: The aim of this retrospective study was to compare surgical and survival outcome in only patients with early-stage UCSs managed by laparotomic surgery (LPT) versus minimally invasive surgery (MIS). Methods: Data were retrospectively collected in four Italian different institutions. Inclusion criteria were UCS diagnosis confirmed by the definitive histological examination, and stage I or II according to the FIGO staging system. Results: Between August 2000 and March 2019, the data relative to 170 patients bearing UCSs were collected: of these, 95 were defined as early-stage disease (stage I-II) based on the histological report at the primary surgery, and thus were included in this study. Forty-four patients were managed by LPT, and 51 patients were managed by MIS. The operative time was lower in the MIS group versus the LPT group (p value 0.021); the median estimated blood loss was less in the MIS group compared to the median of LPT group (p value < 0.0001). The length of hospital stay days was shorter in the MIS patients (p value < 0.0001). Overall, there were eight (8.4%) post-operative complications; of these, seven were recorded in the LPT group versus one in the MIS group (p value 0.023). There was no difference in the disease-free survival (DFS) and overall survival (OS) between the two groups. Conclusion: There was no difference of oncologic outcome between the two approaches, in face of a more favourable peri-operative and post-operative profile in the MIS group.

In The Lancet Oncology, Michael Frumovitz and colleagues1 report quality-of-life outcomes of the randomised, phase 3, non-inferiority LACC trial.2 In the LACC trial, patients with early stage cervical cancer were randomly assigned (1:1) to receive open radical hysterectomy or minimally invasive surgery. At 3 years, compared with the open radical hysterectomy group, patients in the minimally invasive surgery group had worse disease-free survival (97·1% vs 91.2%; hazard ratio [HR] 3·74, 95% CI 1·63–8·58; p=0·002) and overall survival (99·0% vs 93·8%; HR 6·00, 1·77–20·30). On the basis of these results, in 2019, the National Comprehensive Cancer Network guidelines and the European Society of Gynaecological Oncology Scientific Committee recommended that the open approach should be considered the gold standard surgical approach for the treatment of early stage cervical cancer.

Large heterogeneity in therapeutic approaches to cervical cancer (CC) patients has been registered worldwide; a national survey exploring practice settings and equipments in CC treatment was distributed to radiation oncologists. Questionnaires were compiled in 90 of 194 Centers (compliance: 46.3 %). Most of respondents reported the presence of multidisciplinary tumor board, and modern equipments/techniques; 55.5 % of centers reported >1 brachytherapy (BT) equipment, thus implying the need to refer their patients outside for the remaining centers. Post-surgery radiotherapy was performed in 96.7 % of early CC (ECC) cases with pathological high risk factors. Exclusive chemoradiation with concomitant platinum schedules was referred to be used by 84.4 % of centers in locally advanced CC. Alternative options were reported with a range between 4.4 and 28.9 %. The present survey reports a broad spectrum of therapeutic options for CC in Italy. Availability and use of modern techniques is quite diffuse, but the distribution of BT resources and skills remains a challenge.

PURPOSES: The primary objective is to assess the long-term quality of life (QoL) and gastrointestinal well-being in patients with endometriosis (DIE) who underwent segmental resection (SR), through specific questionnaires focused on endometriosis and specific gastrointestinal evaluation. The secondary objectives are represented by the evaluation of peri-operative and post-operative outcomes of the procedure. METHODS: This observational cohort study ENDO-RESECT (ClinicalTrials.gov ID: NCT03824054) reports all clinical data about women who underwent SR for DIE between October 2005 and November 2017. In the part of the study dedicated to the QoL assessment, the questionnaires adopted were the Endometriosis Health Profile (EHP30), the Psychological General Well-Being Index and the Hospital Anxiety and Depression Scale, the Gastrointestinal Well-being questionnaire and the Bristol Stool chart. Major post-surgical morbidity and obstetric outcomes were also collected. RESULTS: 50 women (18% stage III and 82% stage IV rAFS) were considered for enrollment. EHP-30 interpretation demonstrated a significant improvement in all continuous variables, except for fertility concerns. The overall gastrointestinal QoL and most of the specific symptoms improved after surgery. Frequent bowel movements appeared in the 13% of the series not resulting in an impairment of general and gastrointestinal QoL. Constipation remained unchanged. Patients with depressive mood managed with laparoscopy, benefited the most from SR; moreover, patients with multinodular bowel localizations experienced a greater reduction in abdominal pain. Median FU after SR was 42.5 months (range 12-157 months). Only three (6%) cases of late major grade III complications were documented. The pregnancy rate was 50%. CONCLUSIONS: Improvement of general QoL and most of gastrointestinal symptoms was documented after SR.

BJECTIVE: This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. METHODS: This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). RESULTS: As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. CONCLUSIONS: In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Background: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. Methods: Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. Findings: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4–18.6) for CP (p = 0.0027, HR 0.46, CI 0.28–0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16–0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. Interpretation: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.

BACKGROUND: Recently, it was reported that minimally invasive surgery (MIS) has a negative impact on early-stage cervical cancer (ECC) patient survival. At the same time, advantages of MIS regarding quality of life and low rate of intra- and postoperative complications are well known. Therefore, it is essential to select patients who may benefit from MIS without worsening their oncologic outcomes. The aim of this study is to investigate which pathological factors could guide surgeons' choice about the best approach in ECC. PATIENTS AND METHODS: Patients with 2009 FIGO stage from IA1 with lymphovascular space invasion (LVSI) to IB1/IIA1 treated by open or laparoscopic surgery were judged eligible for the study. Disease-free survivals (DFS) of both approaches were tested in subgroups, defined according to histology, tumor size, grading, LVSI, parametrial involvement, and nodal status. RESULTS: A total of 423 patients were enrolled (217 in the open and 206 in the laparoscopic group). No difference between open surgery and laparoscopy was found among subgroups defined according to histology, grading, LVSI, parametrial involvement, or nodal status. Among patients with tumor > 20 mm, laparoscopy showed a significantly higher relapse risk [hazard ratio (HR): 2.103, p = 0.030]. Among patients with tumor < 20 mm, laparoscopy showed DFS superimposable to open surgery (HR: 0.560, p = 0.128). CONCLUSIONS: Tumor size of 20 mm appeared as the only independent discrimination criterion in patients whose prognosis is affected by surgical approaches.

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC.

Background: Surgery followed by platinum-based chemotherapy is the standard of care for MOGCTs, except for stage IA dysgerminoma and stage IA grade 1 immature teratoma where surveillance only is recommended. The role of adjuvant chemotherapy and surgical staging is debated. Patients and methods: Data from 144 patients with stage I MOGTs were collected among MITO centers (Multicenter Italian Trials in Ovarian Cancer) and analyzed. Results: Fifty-five (38.2%) patients were affected by dysgerminomas, 49 (34%) by immature teratomas, 26 (18.1%) by yolk sac tumors and 14 (9.7%) by mixed tumors. Seventy-three (50.7%) patients receive surgery plus chemotherapy, while 71 (49.3%) patients underwent surgery alone. The latter group included 32 dysgerminomas (14 IA-13 Ix, 3 IB, and 2 IC), 34 immature teratomas (20 1A-13 IA grade 1, 6 Ix, 1 IB, and 7 IC), 4 mixed tumors and 1 yolk sac tumor. Forty-four patients did not received chemotherapy, even if it would have been indicated by recommended approach. 94 (65.3%) patients received peritoneal surgical staging. Twenty-three (15.9%) developed a recurrence. Incomplete surgical staging was associated with recurrence (P < 0.05; OR 2.37) at Cox regression analysis. Seven patients died. Four patients were affected by yolk sac tumors, two by mixed tumors and one by immature teratoma. Five patients died for disease, one for acute leukemia and one for suicide. Prognostic parameter analyses showed that yolk sac component is a predictor for survival (P < 0.05). Five-years OS rates were 96.8% and 88.7% in the surgically staged and the incomplete staged group, respectively, while 93.8% and 94.1% in the standard treatment and in the surveillance group, respectively. Conclusions: This study shows that surveillance seems not to affect survival; chemotherapy should be reserved for relapse resulting in high cure rate. Incomplete peritoneal surgical staging is associated with recurrence. Yolk sac histology worsens the prognosis.

Timely access to cancer therapies with significant added value is an important expectation for patients and a primary responsibility for every public health service. Over time, collaboration between the pharmaceutical industry and regulatory agencies has made it possible to agree to implement tools in order to accelerate the development and approval of potentially innovative drugs. In Italy, too, several early access tools have been introduced. In June 2018 a panel of experts agreed on the need to simplify and streamline early access assessment criteria and processes. The panel developed a proposal to categorize cancer drugs eligible for early access. In the curative setting, the evaluation of the medical need should take into account both the relapse rate, attributed on the basis of the disease free survival (DFS), and the strength of the recommendations of the Italian Association of Medical Oncology (AIOM) for any therapeutic alternatives already available. The panel then found it appropriate to use the European Society for Medical Oncology (ESMO) criteria for the evaluation of the clinical benefit. The sum of the scores assigned to the three parameters should allow the clinical value of the drug to be defined and, consequently, the priorities for early access to be established. This multiparameter approach can also be adapted to the non-curative setting. The early access process should be reserved for first-in-class drugs and should provide for the recognition of a conditional reimbursement within 60 days, financed by a special fund. The proposal developed by the panel has the objective of starting a proactive discussion with the Italian health authority.

Objective: Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy. Methods: In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were randomized to receive Carboplatin-Paclitaxel standard dose for 6–8 cycles vs Carboplatin-Paclitaxel and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). Results: 108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months, HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients. The PFS increase became significant when an exploratory analysis with the Breslow test was used. Moreover, patients treated with Bevacizumab experienced a significant increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were more frequent in the experimental arm (“de novo” grade ≥2 hypertension 21% vs 0% and grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment arm, respectively). Conclusions: Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless, these preliminary data suggests some effectiveness of the antiangiogenic agent which merits further exploration in a larger population with a better molecular characterization.

Purpose: This prospective study aimed to evaluate whether 18F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery. Methods: Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard. Results: At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVmax and SUVmean were significantly higher in pR0 than in pR1–pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1–pR2 than in pR0 patients. At final evaluation, SUVmax, SUVmean and TLG were significantly higher in pR1–pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUVmean, early delta TLG, and final delta SUVmax better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18F-FDG-PET/CT (93.5% and 92.3%, respectively). Conclusion: In LACC patients treated with CRT followed by surgery, early variations in metab

AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary end point) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2 ) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2-21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with >1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83-1.17, p = 0.86; median 62.0 months with nintedanib versus 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the non-high-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75-0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports.

A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer. BACKGROUND: A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor. METHODS: To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer. RESULTS: We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1 (NDRG1) and signal transducer and activator of transcription 1 (STAT1) as biomarkers of LACC patients' responsiveness to CRT. The dataset collected through qPCR on these genes was used as training dataset to implement a Random Forest algorithm able to predict the response of new patients to this treatment. Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. CONCLUSIONS: Our results define a predictive gene signature that can help in cervical cancer patient stratification, thus providing a useful tool towards more personalized treatment modalities.

Objective: To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. Methods: Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. Results: Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). Conclusions: Our clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.

n 6.2% of gynaecologic malignancies, vascular involvement is reported. Cytoreductive surgery presents in those cases a higher rate of major complications. Arterial-enteric fistula is a very rare post-surgical complication with serious repercussions on the patient's life due to intestinal haemorrhage and the overlapping sepsis. This is the first case report about iliac-colonic fistula formation in recurrent ovarian cancer with lymph-node metastasis after laparoscopic secondary cytoreductive surgery in a 75-year-old woman and its successful surgical management. A literature review about arterial-enteric fistula formation in gynaecologic cancer treatment, specifically ovarian cancer, is also reported, hypothesising the risk factors of this severe postoperative complication and possible surgical solutions.

Objective. About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). Methods. Survival curves were calculated using the Kaplan-Meiermethod and comparedwith log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. Results. Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5). Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p b 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p=0.05). Between FSS and RS, no difference in OS was detected. Atmultivariate analysis,FIGO stage IC and cystectomy retained significant predictive value for worse survival. Conclusions. This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach

Background: Chemotherapy-induced neutropenia (CIN) has been associated with improved prognosis in several cancer conditions. Contrasting data have been produced in ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynaecologic malignancy. Most women with advanced epithelial ovarian cancer will experience many episodes of recurrent disease with progressively shorter disease-free intervals. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Enormous progress has been made in the management of this disease, and new targeted treatments such as antiangiogenic drugs, poly(adenosine diphosphate-ribose) polymerase inhibitors, and immune checkpoint inhibitors offer potential for improved survival. A variety of combination strategies are being evaluated to leverage these agents. The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of ovarian cancer with particular attention to Phase III and ongoing trials.

Background and Objective: This study aims to investigate the surgical outcomes observed in robotic transperitoneal aortic lymphadenectomy (AL) in gynecological cancer patients. Methods: Retrospective data were collected and analyzed on 71 patients undergoing robotic surgical procedures for gynecological cancers, including transperitoneal AL, between December 2014 and February 2018 at the Catholic University of the Sacred Heart, Rome, Italy. Results: Median age of the sample population was 50 years (range, 26-76 years). The median operative time was 210 minutes (range, 75-480 minutes), the median estimated blood loss was 50 ml (range, 20-300 ml). The number of para-aortic nodes removed was 12 (range, 7-43). In the whole series, 13 patients (18.3%) had at least one metastatic node. Overall, 10 patients (14.1%) experienced any grade early postoperative complications. Three patients experienced more than one complication. Three intraoperative complications occurred with two cases of vascular injury. Conversion to laparotomy was necessary for one patient (1.4%). Conclusions: The present study shows the safety and adequacy of robotic transperitoneal AL as surgical staging step for gynecological cancers in terms of perioperative and postoperative outcomes.

Objective Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. Patients and methods A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan–Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. Results A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96 months (range 7–300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. Conclusions This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity.

Background To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. Methods Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). Results The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). Conclusions This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.

STUDY OBJECTIVE: This study aims to evaluate the feasibility, surgical outcome and oncological results observed after robotic staging compared to conventional laparoscopic staging for patients with early-stage ovarian cancer (EOC) patients. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Catholic University of the Sacred Hearth, Rome, Italy. PATIENTS: 96 patients underwent minimally invasive staging for presumed stage I ovarian cancer: 32 underwent robotic approach (Cases), and 64 underwent laparoscopic approach (Controls). MEASURE: ments and Results: There was no statistically significant difference between the two approaches with regard to final FIGO stage, histology and grade of tumors. In the whole series 15 patients (15.6%) were upstaged, with no statistically significant difference between the two groups. Median number of pelvic lymph nodes removed was 14 (range 3-42) and 11 (range 2-29) in the robotic and laparoscopic group (p value= 0.235), respectively. Median number of aortic lymph nodes removed was 11 (range 3-26) and 12 (range 1-39) in the robotic and laparoscopic group (p value= 0.263), respectively. Operative time was significantly shorter in the robotic group compared to the laparoscopic group (p value= 0.043), while the amount of estimated blood loss was similar (p value= 0.691). No difference was found in terms of early and postoperative complications. Overall, 72 patients were considered as requiring adjuvant treatment. Two patients experienced peritoneal recurrence. CONCLUSIONS: The present study suggests that there is no relevant difference between robotic and laparoscopic approach in staging EOC. Further prospective trials are needed to confirm our results.

OBJECTIVE: To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL). MATERIAL AND METHODS: This is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI≥8 or≤12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS. RESULTS: Between October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III-IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two

BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum.