Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.

Adnexal Torsion in Pediatric Age: Does Bolli's Score Work? Report of Two Cases.

Adnexal torsion is a surgical emergency requiring early diagnosis in order to avoid demolitive surgery. Adnexal torsion's diagnosis could be very difficult in pediatric patients because children cannot explain symptoms accurately. Furthermore reproductive organs lie high in abdomen, causing unclear examinations findings. For reducing diagnostic mistakes or delay clinical and hematological criteria could be useful. No radiological criteria (CT or MRI) should be taken in count because of the costs and the required time. By combining clinical presentation in patients with OT three useful diagnostic variables have been identified: age, duration of pain, vomiting. Presence of vomiting, short duration of abdominal pain and high CRP levels have great predictive value for the diagnosis of adnexal torsion. In those patients an exploratory laparoscopy should be performed without any doubt and/or delay. These data may aid physicians in the evaluation of abdominal pain in premenarchal girls.

The role of staging and adjuvant chemotherapy in stage I malignant ovarian germ cell tumors (MOGTs): the MITO-9 study.

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.

Is surgical restaging indicated in apparent stage IA pure ovarian dysgerminoma? The MITO group retrospective experience.

OBJECTIVE: Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for pure ovarian dysgerminoma (POD), except for correctly staged IA patients. The aim of study was to evaluate the outcome of IA POD patients with incomplete surgical staging in order to define the proper management. METHODS: Data concerning primary treatment and recurrence were reviewed for 26 patients with stage IA POD treated in MITO (Multicenter Italian Trials in Ovarian Cancer) centers. RESULTS: Median age was 22.5years. Primary surgery was fertility sparing for 17 patients (65.4%) and radical surgery was performed in 9 patients due to older age or gonadal dysgenesis. Only five patients (19.2%) had complete surgical staging; 38.5% had lymph node dissection, 46.2% had peritoneal biopsies and/or omentectomy and 65.4% had peritoneal washing. Seven patients received adjuvant chemotherapy. Overall recurrence rate was 11.5%: all recurrences occurred in the group submitted to incomplete staging procedure. No patients treated with adjuvant chemotherapy relapsed. One patient had pelvic recurrence, one patient relapsed in the abdomino-pelvic peritoneum and lymph nodes and the third patient showed a peritoneum, lymph nodal and residual ovary relapse. All patients with recurrence were cured by salvage therapy: 2 patients were treated with surgery plus chemotherapy and one only with chemotherapy. After a median follow-up of 100months all patients are alive without evidence of disease. Six patients opted for conception and delivered healthy infants, two with IVF with donor oocyte. CONCLUSIONS: IA POD prognosis is excellent. Conservative surgery with a complete surgical staging is the gold standard. Patients with incomplete staging could undergo surgical restaging or surveillance. Chemotherapy should be reserved to relapse with excellent chances of therapeutic success.

Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group.

BACKGROUND: The objective of the study was to estimate the antitumor activity of pemetrexed in patients with advanced/recurrent carcinoma of the cervix and to determine the nature and degree of toxicity. METHODS: A multicenter phase II trial was conducted by the Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) Group. Patients with advanced/recurrent measurable carcinoma of the cervix that had failed one prior chemotherapy regimen in association or not with radiotherapy were treated with pemetrexed at a dose of 500 mg/m(2) every 21 days. All the patients had a measurable lesion according to RECIST criteria in a not previously irradiated field. RESULTS: From November 2006 to September 2008, 43 patients were entered by seven member institutions of the MITO-Group. A total of 164 cycles (median 2, range 1-9) were administered. The treatment was well tolerated. More serious toxic effects (grades 3 and 4) included leukopenia in 27.9% and neutropenia in 30.2% of patients. No treatment-related deaths were reported. Six patients (13.9%) had partial responses (at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) with a median response of 7 weeks (range 3-27). Twenty-three patients (53.4%) had stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) and fourteen (32.5%) patients had progressive disease. Median progression-free survival was 10 weeks and overall survival was 35 weeks. CONCLUSION: Pemetrexed showed moderate activity against advanced/recurrent cervical cancer that had failed prior chemotherapy.

Carboplatin and pegylated liposomal doxorubicin for advanced ovarian cancer: preliminary activity results of the MITO-2 phase III trial.

BACKGROUND: Based on the efficacy of pegylated liposomal doxorubicin (PLD) in relapsed ovarian cancer, we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer. Because of limited phase I and II data on PLD plus carboplatin in this setting, we conducted an interim activity analysis. PATIENTS AND METHODS: Patients with stage 1c-IV epithelial ovarian cancer were randomized to carboplatin AUC 5 plus either paclitaxel 175 mg/m(2) or PLD 30 mg/m(2) every 3 weeks for 6 cycles. The interim activity analysis was planned according to a single-stage phase II design with an auspicated 50% response rate; 50 patients eligible for response assessment were required. Response was defined according to RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: A complete response was achieved in 14 patients (28%) and a partial response in 20 (40%), which produced an overall response rate of 68%. The activity exceeded the minimum required for study continuation. Stable disease was reported in an additional 10 patients (20%). CONCLUSIONS: The adopted schedule of PLD plus carboplatin demonstrates activity as a first-line treatment for advanced ovarian cancer.

Ovarian cystic teratoma with primary epithelial cell melanoma.

We report a rare case of malignant melanoma arising in a cystic teratoma of the ovary occurring in a 60-year-old woman who died in four months despite the combined treatment administrated (surgery and chemotherapy). Diagnosis of ovarian melanoma was confirmed by immunohistochemical positivity to S-100 protein and HMB 45. There was no evidence of extra-ovarian primary melanoma on clinical examination; therefore the diagnosis was primary ovarian melanoma. Melanoma metastases were detected on the uterus, the right ovary, the omentum and in one of the three excised left external iliac lymph nodes. A review of the literature is analyzed and discussed.

[Peritonectomy and hyperthermic chemoperfusion in peritoneal carcinomatosis. Preliminary results]. / Peritonectomia e chemioperfusione ipertermica nella carcinomatosi peritoneale. Risultati preliminari.

BACKGROUND: Peritoneal carcinomatosis can be actually treated by new surgical and oncological techniques. Aim of this work is to report preliminary results of a group of patients with peritoneal carcinomatosis, submitted to peritonectomy and intraperitoneal hypertermic chemoperfusion (IPHC). METHODS: Age, sex, type of neoplasm, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CC), operative time, morbidity and mortality of patients submitted to IPHC have been considered. RESULTS: From May 2001 to December 2004, 10 patients were submitted to peritonectomy and IPHC: 9 (90%) females and 1 (10%) male, aged from 49 to 72 years. Seven patients (70%) were affected of peritoneal carcinomatosis from ovarian tumor, three patients (30%) from colon cancer. The PCI was ranged from 8 to 25. The operative time was ranged from 6 to 14 hours. Two patients with a CC of 2 developed relaps and died respectively after 2 and 4 months. The remaining patients had a CC between 0 and 1. Of these last patients, 1 affected by ovarian cancer died 24 months after, 1 patient died 3 days after surgery for septic shock; the other patients are still alive with a period ranged from 1 to 30 months. CONCLUSIONS: Our preliminary results suggest that the peritonectomy and IPHC can be effective only in patients with CC of 0 or 1, in the remaining cases these therapeutical methods should be avoided.

Piver's radical hysterectomy (type III): Endo-Gia 30 stapler versus traditional forcipressure for resection of the cardinal ligament.

OBJECTIVE: Morbidity and costs associated with Piver's radical hysterectomy (type III) are noteworthy. The Endo-Gia stapler method for resection of cardinal ligaments can reduce duration of surgery and hospitalization, blood loss, costs and postoperative infection rates. METHOD: Two groups of patients (homogeneous for age, weight and medical condition) were studied: one group was operated on using the Endo-Gia stapler method (n=52) and the other with the traditional forcipressure (n=13). The size of parametrial tissue removed, blood loss, duration of surgery, duration of hospitalization, cost of materials and postoperative fever were compared in the two groups. RESULT: Mean operative times were lower in the Endo-Stapler group than in the controls (mean 180 min versus 220 min). Mean blood loss was 300 cc in the stapler group versus 450 cc in the forcipressure group. Mean cost of surgery (considering costs of materials, hospital stay. duration of surgery), was lower in the stapler group (3,095 euros) than in the group who underwent traditional surgery (3,434 euros). CONCLUSION: Our data suggest the Endo-Gia stapler method significantly reduces blood loss, operative time and cost.

Goserelin acetate to avoid hysterectomy in pre-menopausal women with fibroids requiring surgery.

OBJECTIVE: To obtain information on the efficacy of repeated short cycles of GNRH agonist treatment in order to avoid hysterectomy in near-menopausal women with symptomatic fibroids. STUDY DESIGN: 72 pre-menopausal women (mean age 50 years) with one or more uterine fibroids >10 cm in diameter, symptomatic menorrhagia lasting three months or more and haemoglobin=9 g/dl entered the study. The patients were randomized with ratio of approximately 1:4 to: (a) immediate surgery; or (b) treatment with goserelin acetate. Patients randomized to goserelin acetate received a first cycle of 3.6 mg depot once every 28 days for four months. They were followed-up for three years. If menorrhagia was observed during the follow-up the woman was given goserelin acetate 3.6 mg depot for another three months. In case of further menorrhagia, a third cycle of goserelin acetate 3.6 mg depot for three months was given. After the third cycle of therapy if there was still menorrhagia, the patient underwent hysterectomy plus bilateral oophorectomy. RESULTS: A total of 13 women were assigned to the immediate surgery group and 59 to goserelin. Three years after trial entry a total of 23 women allocated to goserelin acetate treatment had undergone hysterectomy. CONCLUSION: This study suggests that GNRH agonists are efficacious for avoiding hysterectomy in women near menopause with uterine fibroids.

Borderline ovarian tumors. Case reports and review of literature.

A borderline ovarian tumor or carcinoma of low malignant potential (LMP) may be defined as a tumor which possesses some, but not all, of the morphologic criteria of malignancy. The incidence ranges from 9% to 16.3% of the epithelial neoplasm and they are mainly at Stage I. Four cases of borderline ovarian tumor are described. Two (case 1 and case 2) given the patients' ages and the extent of the disease were treated with conservative therapy (monolateral ovariosalpingectomy), the other two, on the contrary, (case 3 and case 4) were treated with radical surgery. Given that, from current knowledge, non-invasive foci of a borderline type do not react to chemotherapy, no adjuvant chemotherapy was carried out. Antiblastic therapy is indicated only in sporadic cases of clearly invasive growth of the peritoneal foci. The follow-up, carried out every six months, was negative for partial or total recurrence of the disease, in all the patients.