Margherita Giorgini

Targeted drug delivery via folate receptors in recurrent ovarian cancer: A review

Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate–chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate–chemotherapy conjugates.

A prospective phase II study of topotecan (Hycamtin®) and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer

OBJECTIVES To evaluate the feasibility, toxicity and activity of neoadjuvant chemotherapy (NACT) using cisplatin and topotecan in patients affected by locally advanced cervical cancer (IB2-IIIB). METHODS Patients with histologically confirmed FIGO stage IB2-IIIB uterine cervical cancer were treated with topotecan 0.75 mg/m(2)/day (days 1-3) followed by cisplatin 75 mg/m(2) (day 1), every 21 days for three consecutive cycles. After the last cycle of chemotherapy, within 3 or 4 weeks, patients underwent radical surgery with lymph node dissection. RESULTS In the years 2007-2010, 46 women were enrolled into the study. Hematologic toxicity was the most relevant side effect. Thirty-eight patients (82.6%) underwent radical surgery after neoadjuvant chemotherapy (NACT) and were assessable for pathologic responses; surgery was not performed in 8 (17.4%) non-responder patients or with progression disease. Objective pathological response was recorded in 34 patients (89.5%); 6 patients (15.8%) achieved a complete response (CR), 28 (73.7%) patients achieved a partial response (PR); stable disease (SD) occurred in 2 patients (5.3%) with IIA initial disease and progression disease (PD) was registered in 2 patients (5.3%) with IIIB initial disease. The cumulative 2-year progression free survival (PFS) and overall survival (OS) of the 46 enrolled patients in the study were 70% and 81%, respectively; the 2-year PFS and OS of the 38 operated patients were respectively 79% and 95%. CONCLUSIONS The cisplatin-topotecan combination seems to be feasible and with an acceptable toxicity profile and a promising response rate for the treatment of locally advanced cervical cancer (LACC). Phase II and III studies are needed to compare this combination with other platinum-based chemotherapeutic associations.

Sexual Health and Quality of Life Assessment among Ovarian Cancer Patients during Chemotherapy

Background: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. Objective: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). Patients and Methods: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. Results: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). Conclusion: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.

CO2 Laser Treatment for Bartholin Gland Abscess: Ultrasound Evaluation of Risk Recurrence

STUDY OBJECTIVE To evaluate the efficacy of CO2 laser treatment and parameters correlated with recurrence in patients with Bartholin gland abscesses treated using this approach. DESIGN Prospective study (Canadian Task Force classification II-2). SETTING University hospital. PATIENTS One hundred forty-seven patients who met eligibility criteria. INTERVENTION Preoperative ultrasound evaluation of Bartholin gland lesions and CO2 laser treatment. MEASUREMENTS AND MAIN RESULTS All patients received CO2 laser therapy, with median operative time 15 minutes (range, 12-35 minutes). Median postoperative stay was 1 hours (range, 1-4 hours). Estimated 3-year relapse-free rate was 88.56%. Lesion wall thickness 0.5-1.5 mm, multilocular lesion, and hyperechogenic lesion were correlated with recurrence. CONCLUSION CO2 laser of Bartholin gland abscesses could be a valid option. Ultrasound characteristics of Bartholin gland lesions could predict lesion recurrence rate.

Multiple Bulky Lymph Nodal Metastasis in Microinvasive Cervical Cancer: A Case Report and Literature Review

Microinvasive squamous cell cervival carcinoma is characterized by an exceptional incidence of lymph nodal metastasis. We report the case of a 45-year-old woman affected by IA1 squamous cell carcinoma, found to have massive pelvic lymph nodal metastasis. After a systematic pelvic and aortic selective lymphadenectomy, at 16 months of follow-up, she is still disease-free. Patients suitable for conservative therapy should be carefully counselled about the established risks and benefits of nondestructive treatment options.

Unexpected Metastasis of High Grade Serous Ovarian Cancer to Breast:Case Report and Literature Review

Introduction: Metastasis of ovarian serous carcinoma to breast and/or axillary lymph nodes represents an unusual event. Nevertheless, their detection and distinction from mammary carcinoma are of huge clinical importance because the treatment and prognosis diverge significantly. Case presentation: We report a case of a 47 year-old Caucasian female patient with unforeseen metastasis to the breast and to axillary lymph nodes due to ovarian serous carcinoma. Conclusion: In patients with history of OSC who present with axillary or breast mass, an accurate histological diagnosis should be obtained since this has a great impact on treatment outcomes.

Isolated contralateral groin relapse in vulvar cancer

Surgical therapy of vulvar carcinoma consists of vulvectomy/hemivulvectomy plus inguinofemoral lymphadenectomy [1, 2]. Patients affected by small well-lateralized lesions can be treated by omolateral groin lymphadenectomy; in case of positive omolateral inguinal nodes, median lesions and/or carcinomas C2 cm, bilateral groin lymphadenectomy should be performed [1, 2]. Also in patients affected by vulvar cancer with multiple lymph node metastases, radical surgery followed by chemotherapy is a feasible strategy, with an acceptable short and long term complication rate and result in terms of overall survival and disease-free survival is promising [3]. However, radical surgery may compromise anatomical structure causing severe mutilation. That’s why chemotherapy, with or without concomitant radiotherapy starts to be strongly recommended either as neoadjuvant strategy or adjuvant treatment [4]. On the other hand, treatment of recurrent disease is not well standardized and no clear indications for lymphadenectomy are proposed. A 70-year-old patient presented at our Institution with vulvar cancer sited in the right labium major. Abdominopelvic computed tomography (CT) scan and chest X-ray were negative for disease. She underwent right modified hemivulvectomy plus omolateral groin lymphadenectomy, with a skin incision parallel to the inguinal ligament above the inguinal cutaneous fold [5]. Histology showed a moderately differentiated squamous vulvar carcinoma of 1.7 cm, and 5 mm depth of invasion, fully excised, with negative margin, measured in microscopic view 2 cm [6] and negative nodes. No adjuvant treatment was proposed. After 6 years of negative follow up, the patient presented recurrent cancer measuring about 1 cm sited again in the right hemivulva. Total body CT scan was negative for distant metastasis. Patient underwent surgical removal of recurrence. Histology showed a moderately differentiated squamous carcinoma of 0.8 cm with negative margins. No further treatment was proposed. One year later patient was admitted with fever and an abscess sited at the level of the left groin. CT scan revealed left inguinal confluent abscessed lymphadenopathy, strictly adherent to femoral vessels and nerves. Biopsy of the mass confirmed abscessed groin nodal relapse from vulvar carcinoma and culture results were positive for Pseudomonas aeruginosa. No vulvar lesions were detected (Fig. 1). In few days, the patient died of sepsis and bleeding. The management of local relapse of vulvar carcinomas should be individualized. Many authors have reported good results when a local excision with adequate resection margins is performed [7]. However, no clear indications for lymphadenectomy are reported. The present case suggests that, in recurrent disease, even in case of good lateralized lesions, contralateral lymphadenectomy should be considered. Iversen et al. [8] reported the presence of contralateral lymphatic drainage in 67 % of patients after injection with 99mTc-colloid in different areas of the vulva. Indeed, in selected cases of recurrent disease, such as the above discussed, the sentinel lymph node procedure can be helpful to better plan the surgical approach. Moreover, Bellati et al. demonstrated the frequent expression of cancer testis tumour associated antigens I. Palaia (&) M. Giorgini M. Graziano V. Di Donato C. Marchetti A. Musella P. Benedetti Panici Department of Obstetrics and Gynecology, ‘‘La Sapienza’’ University, Rome, viale del Policlinico 155, 00155 Rome, Italy e-mail: innocenza.palaia@uniroma1.it

Limits of 18F-Fluorodeoxyglucose positron emission tomography in recurrence diagnosis of borderline ovarian tumor

Most borderline ovarian tumors (BOT) occur in young women and exhibit a low malignant behavior. Nevertheless, an accurate long-term follow-up is required because, frequently, recurrence arises after many years from primary treatment, especially in patients affected by BOT with invasive peritoneal implants, which have a worse prognosis. We report the case of a pelvic recurrence of serous BOT firstly suspected by physical examination but misdiagnosed by 18F-fluorodeoxyglucose positron emission tomography and computed tomography and identified only by magnetic resonance imaging, 7 years after primary treatment. We also reviewed the literature concerning the role of 18F-fluorodeoxyglucose positron emission tomography in the management and follow-up of BOT.