Micaela Petrone

Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and Endometrial Cancer: Safety and Efficacy

STUDY OBJECTIVES To evaluate the rate of intrauterine adhesions after hysteroscopic resection of hyperplastic and/or cancer areas and the efficacy of combined treatment. DESIGN Observational retrospective study. SETTING Patients affected by endometrial atypical hyperplasia of the endometrium or early stage endometrial carcinoma. PATIENTS Twenty-three patients, up to 45 years of age. INTERVENTION Conservative treatment based on hysteroscopic resection of hyperplastic and/or cancer areas and subsequent therapy with megestrol acetate 160 mg/day. METHODS AND MAIN RESULTS Approximately 5% of endometrial cancers (ECs) are diagnosed in women younger than 40 years old, usually with a good prognosis. From 2010 to 2014, 23 patients, up to age 45 years, who were affected by endometrial cancer (EC) grade 1 or atypical complex hyperplasia (ACH) and who wished to preserve fertility, underwent conservative treatment based on hysteroscopic resection of the hyperplastic and/or cancer areas and subsequent therapy with megestrol acetate 160 mg/day. Data with regard to age, body mass index, symptoms, history of infertility, and previous assisted reproductive technologies attempts, obstetrics history, previous diagnosis of intrauterine sinechiae, hysteroscopic findings, duration of therapy, follow-up reports, and reproductive outcomes were collected and analyzed. Of the 23 patients enrolled in the study, 3 patients (13%) presented with an endometrioid EC grade 1, and 20 patients (87%) had ACH. Twelve patients (52.2%) had complete remission after 3 months of progestin therapy, 9 patients (39.1%) had a complete remission after 6 months, and 2 (8.7%) patients had remission after 9 months. Six patients underwent a second hysteroscopic resection. The 3 patients with an initial diagnosis of EC had complete remission after a mean of 4 months of high-dose progestin therapy; in patients with ACH, remission occurred after a mean of 3 months. In all patients, intrauterine adhesions were not detected at any follow-up diagnostic hysteroscopy. After a median follow-up time of 25 months (range 8-37), we registered 1 (4.3%) relapse of disease. A total of 7 pregnancies in 6 patients were counted, after an average time of 7.4 months (range 3-13 months) after the end of progestin therapy. CONCLUSIONS Hysteroscopic resection of hyperplastic and/or cancer areas before high dosage progestin therapy seems to be a safe and effective approach in the management of ACH and in patients with early EC who wish to preserve fertility.

Surgery in advanced borderline tumors.

Our retrospective study evaluates the role of conservative surgery, performed in 10 of 22 patients affected by advanced stage serous borderline ovarian tumor. Although patients who underwent conservative surgery had a higher recurrence rate (60% after conservative surgery and 8% after radical surgery), all patients are alive without evidence of disease.

Folate receptor alpha antagonists in preclinical and early stage clinical development for the treatment of epithelial ovarian cancer

ABSTRACT Introduction: The prognosis of patients affected by ovarian cancer has not substantially changed in the last decades and improving survival still remains a challenge. In the promising era of ‘personalized therapy’ several new biologic therapies are currently being investigated: in this setting, targeting the folate receptor (FR) has been considered a new potential strategy for biologic therapy. Areas covered: The aim of the current review is to summarize, giving a critical overview,promising folate receptor alpha antagonists under preclinical or early clinical development for ovarian cancer. Expert opinion: Two categories of therapeutics are included in this class: FRα targeted mAbs and FRα-binding-ADC (Antibody drug conjugates); both share the interesting possibility of selecting patients via a biomarker which is already available. In the first class, farletuzumab has reached the most advanced stage in clinical evaluation and results of a Phase II randomized trial are awaited to assess its efficacy in a specific patients’ setting. MOv18 IgE represents a novel strategy to target FRα expressing cells, which has shown encouraging results in preclinical studies: further evaluation is needed in the clinical setting. IMGN 853 is an innovative FRα-binding ADC under development, with only preliminary results of a Phase I trial available.

Chemotherapy-Induced Nausea and Vomiting in Women With Gynecological Cancer: A Preliminary Single-Center Study Investigating Medical and Psychosocial Risk Factors.

Background: Chemotherapy is the treatment of choice for many gynecological tumors, but cytotoxic drugs lead to a wide range of stressful side effects; nausea and vomiting are 2 of the most common and distressing consequences of many chemotherapy regimens. Objective: The aim of this study is to investigate various risk factors that could influence the experience of nausea and vomiting after the first chemotherapeutic infusion. Methods: Women treated for various gynecological cancers (n = 94) took part in the study. Pharmacological and personal risk factors in the development of chemotherapy-induced nausea and vomiting (CINV) were assessed with the use of the State-Trait Anxiety Inventory and a self-report questionnaire. Regression analyses (both univariate and multiple) were performed to establish risk factors associated with CINV. Results: The study highlights the importance of working status (being involved in a working activity during treatment) as a protective factor for developing chemotherapy-induced nausea. Furthermore, younger age, levels of state anxiety, chemotherapy-induced nausea in previous treatments, and alcohol intake were found to have an effect on CINV, increasing its risk. Emetogenic potential was associated only with the presence of delayed vomiting. Conclusions: Although this is a preliminary study into the risk factors of CINV in gynecological tumors, these findings offer support that personal risk factors contribute to individual differences in the frequency and severity of CINV. Implications for Practice: Personal factors should be taken into consideration by the multidisciplinary treating team in gynecology.

Role of Surgery in the Management of Hydatidiform Mole in Elderly Patients: A Single-Center Clinical Experience.

Objective Women older than 40 years develop gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) more often than do younger women. Therefore, in elderly women, primary hysterectomy has been advocated as first-line treatment. The aim of the present study was to evaluate whether hysterectomy could reduce the incidence of GTN after a diagnosis of HM. Methods Seventy-six of 442 patients referred to our unit for an HM between 1994 and 2015 were older than 40 years old. Among these, 12 patients were treated by primary hysterectomy. We compared clinical features, serum human chorionic gonadotrophin (hCG), incidence of GTN, and further treatments in these patients and in those who underwent evacuation and serum hCG monitoring, using univariate and multivariate analyses. Results Patients treated by primary hysterectomy all had a diagnosis of a complete or invasive HM, had more hyperemesis than did control subjects (82% vs 37%, P = 0.008), and had an increased uterine volume (100% vs 41%, P = 0.001). Seven of them developed a subsequent GTN, whereas 5 patients achieved complete remission of disease after surgery (58% vs 30%, P = 0.094). All the patients who developed a GTN after surgery showed lower hCG levels than did control subjects (mean, 671.4 [SD, 1178.4] IU/L vs 23,919.4 [SD, 34,284.9] IU/L; P = 0.005), but there were no significant differences in the amount and type of chemotherapy needed to achieve remission. Conclusions Primary hysterectomy after 40 years old in women affected by HM does not reduce the incidence of GTN and amount of chemotherapy. Although further studies are needed to confirm these results, a careful hCG monitoring should be recommended in these high-risk patients.

Investigational therapies currently in Phase II clinical trials for the treatment of pelvic serous carcinomas

Introduction: Pelvic serous carcinomas (PSCs) are a controversial entity, which mostly comprise fallopian tube carcinoma (FTC), primary peritoneal carcinoma (PPC) and serous ovarian carcinoma (OC). Despite incremental attention towards understanding pelvic serous carcinogenesis, the gold standard treatment and survival rates have not substantially changed in these last decades. Areas covered: This review summarizes and gives a critical overview of the ongoing Phase II trials investigating therapies for PSC. Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of PSC, including FTC, PPC and serous OC. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for PSC, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each woman with a molecularly defined disease, a deeper knowledge of the molecular biology and genetics underlying FTC and its relation as a precursor of PSC is needed.

Neoadjuvant chemotherapy in high-risk ovarian cancer patients: Role of age

Objective: To review a single-center clinical experience with neoadjuvant chemotherapy (NACT) in a population of frail epithelial ovarian cancer (EOC) patients and investigate the prognostic role of advanced age. Methods: We retrospectively reviewed clinical data from 102 advanced EOC patients treated with NACT and presenting high perioperative risk. Patients were divided into 2 groups: group A, including patients aged 70 years or older; and group B, including patients below 70 years old. Univariate and multivariate analyses were performed to compare survival and prognostic factors for survival between the two groups. Results: Forty-two patients (41.2%) were older than 70 years. Elderly patients were more likely to present comorbidities (p = 0.0001), poor performance status (p = 0.04), and multiple indications for NACT (p = 0.03). They showed a reduced response to NACT, since only 64% of elderly patients underwent surgical debulking (98.3% vs 64.3%, p = 0.001) and, among these, half of them were optimally debulked (79.3% vs 50%, p = 0.01). Median progression-free survival (PFS) and overall survival (OS) were significantly lower in group A (respectively, 9 vs 13 months, p = 0.005, and 21 vs 29 months, p = 0.01). Advanced age, IV stage, presence of ascites, and residual disease >1 cm were significantly associated with a lower PFS. However, when analyzing factors associated with OS, the only significant ones were higher American Society of Anesthesiologists score and residual disease >1 cm. Conclusions: Age was not found to be a prognostic factor for survival. This highlights the necessity of validated geriatric assessment tools predicting functional age and treatment tolerability to avoid undertreatment of elderly patients.

Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24)

BackgroundThe variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking.ObjectiveThe MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III–IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab.Patients and MethodsOf the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms.ResultsIn the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p < 0.0001). In multivariate analyses, the NLR was significantly associated with OS (p = 0.016), and the PLR was significantly associated with PFS (p = 0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p < 0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p = 0.026 and p = 0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p = 0.024 and p = 0.017, respectively).ConclusionOur results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.

Fertility sparing surgery in epithelial ovarian cancer in Italy: perceptions, practice, and main issues.

Abstract About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stage I disease. For this subset of women, the issue of fertility sparing surgery (FSS) has become critical. The aim of this survey was to investigate the management of EOC patients desiring to preserve fertility in Italy. A questionnaire consisting of 30 items was developed to evaluate: patient-selection criteria, rate of FSS, patient’s counseling- and pregnancy-timing, fertility preservation, obstetrics, and oncologic outcomes. One expert clinician for each of 50 major gynecologic oncology centers was invited to participate. Data were entered into a database and statistically analyzed. 74% of questionnaires were complete. The proportion of EOC patients treated with FSS was <10%, 10%–20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age, fertility preservation desire, histotype, and stage were considered relevant to select patients for a conservative treatment for 64.8%, 72.9%, and 78.3% of responders, respectively. Only 17 centers (45.9%) resulted to have an assisted reproductive technique service and Obstetrics Department. Our survey highlights discrepancies among oncologists in the management of patients with early EOC undergoing FSS. More efforts should be made to define and broadcast the best management before and after surgery.