Treatments for relapsed, BRCA-wild type, platinum-sensitive ovarian cancer: A systematic review and network meta-analysis.

INTRODUCTION: Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment for these patients. We compared the effectiveness of modern and older therapies in relapsed platinum-sensitive, BRCA-wild type, and ovarian cancers using a network meta-analysis (NMA). METHODS: A systematic search of PubMed, EMBASE, and Cochrane Library was performed up to October 31, 2022. Randomized controlled trials (RCT) that compared different second-line approaches were included. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: In total, 17 RCTs (n = 9405) comparing various strategies were included. The risk of death was significantly decreased with carboplatin + pegylated liposomal doxorubicin + bevacizumab compared to platinum-based doublet CT (hazard ratio [HR] = 0.59, 95%CI 0.35, 1). Various strategies, including secondary cytoreduction followed by platinum-based CT, carboplatin + pegylated liposomal doxorubicin + bevacizumab, and platinum-based CT with bevacizumab or cediranib, were better than platinum-based doublets alone for PFS. CONCLUSIONS: This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.

A uterine malformation diagnosed in the shock room: a case report which helps to identify how to avoid a potentially preventable life-threatening event.

An Indian wonen at her second pregnancy, with a previous preterm labour at 34.5 weeks, presented to the emergency room at 15.6 weeks, shocked due to massive hemoperitoneum. During the urgent surgery, a Mullerian malformation was detected, and a uterine rupture was diagnosed as the cause of the hemoperitoneum. Ultrasound and pelvic magnetic resonance results confirmed the malformation, determining that a unicornuate uterus with a rudimental horn within the pregnancy had taken place. We decided to report our case to underline that Mullerian malformation must be taken into consideration and evaluated at each routinary gynaecological visit or, at least, at the first pregnancy appointment, especially in the cases of women with previous adverse obstetric outcomes. The 2D abdominal ultrasound associated with trans-vaginal evaluation is an adequate procedure to test for suspected uterine malformations (if the operator keeps it in mind and is trained to check this kind of alteration), which is fundamental to reducing the risk of life-threatening events.

Chemotherapy for breast cancer during pregnancy induces vascular alterations and impaired development of placental villi: A preliminary histopathological study.

OBJECTIVE: To evaluate histological alterations in placentas of women affected by breast cancer and treated with chemotherapy during pregnancy. STUDY DESIGN: We retrospectively reviewed histological slides of 23 placentas of patients affected by breast cancer and treated with chemotherapy during pregnancy and 23 control placentas of women without breast cancer and with physiological pregnancies of the same gestational age. RESULTS: All the patients had breast ductal infiltrating carcinoma, 19 of 23 cases had a G3 cancer. All patients were treated with 2-6 cycles of chemotherapy starting after 16 weeks of gestation, with different protocols. No hypertensive complications and no pre-eclampsia episodes were observed; birth weight was consistent with gestational age in all babies in both group with no uneventful outcomes and no perinatal mortality or fetal malformations. Twenty out of 23 cases (86 %) showed hypoxia-induced villous alterations, including increased syncytial knotting (Tenney-Parker changes), perivillar fibrin deposits, distal villous hypoplasia or accelerated maturation and focal villous chorangiosis. These alterations were found in 19 out of 23 controls (83 %), with no statistically significant difference between the two groups. CONCLUSIONS: These results shows that chemotherapy in the second and third trimester of pregnancy may lead to non-specific alterations in placental vasculature and morphology.

Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study.

OBJECTIVE: Endometrioid and clear cell ovarian tumors have been referred to as "endometriosis associated ovarian cancers". However, very few studies have compared clinical and prognostic features of endometriosis-associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database. METHODS: Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n=27 and n=46, respectively). Clinical and pathological data have been compared. RESULTS: Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4±10.0 and 58.4±11.2years, p=0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p=0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates. CONCLUSIONS: Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading.

Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers.

OBJECTIVE: This study aimed to analyze long-term survival of clear cells (CCs) and endometrioid (E) ovarian cancer cases according to presence of endometriosis in the pathologic report. METHODS: This is a retrospective analysis of 47 CC and 66 E ovarian cancer cases observed consecutively at our center between 1990 and 2010.All cases had first surgery at our center or were referred to it for treatment and follow-up.Cases were identified according to the original diagnosis reported in clinical records.All pathologic reports were reviewed, and cases were classified with or without pathologic evidence of endometriosis on the basis of the pathologic report.Follow-up was updated in March 2011. The follow-up median was 147 months (range, 116-171). RESULTS: Endometriosis-associated ovarian cancer cases were more frequently diagnosed at stage I to II than cases without endometriosis: among the 36 endometriosis-associated ovarian cancer cases, 25 (69%) were at stage I or II, and the corresponding value was 35 (46%) of 77 among cases without endometriosis (P = 0.0173).The presence of endometriosis tended to be associated with a higher 10-year survival rate: after taking the potential confounding effect of stage into account, the finding was not statistically significant (hazards ratio, 0.7; 95% confidence interval, 0.3-1.5). CONCLUSIONS: This analysis shows that EA CCs and E ovarian cases are diagnosed at an earlier stage than cases without endometriosis. No clear association emerged between presence of endometriosis and survival.

Clear cell and papillary serous endometrial carcinomas: survival in a series of 128 cases.

PURPOSE: Clear cell (CC) and papillary serous carcinoma (PS) are histotypes at high risk of recurrence. We analyse patients' survival in a retrospective series of 128 CC and PS endometrial cancer cases. METHODS: All women with a histologically confirmed CC and PS endometrial cancer who underwent primary surgery in five institutions in Lombardy, Italy, were eligible for this study. A total of 77 (60.2 %) were PS endometrial cancer cases, 45 (35.2 %) CC cases and 6 (4.6 %) cases had mixed CC and PS histotype. RESULTS: 54 (42 %) cases were diagnosed at stage I, 10 (8 %) at stage II, 47 (37 %) at stage III and 17 (13 %) at stage IV. Recurrence was observed in 49 cases (38.3 %). The median time at recurrence was 12 months (interquartile range 7-18). The rate of recurrence was 20.3 % in cases at stage I-lI and 56.2 % in cases at stage III-IV (p < 0.0001). With regard to the site of recurrence 24 recurrences were in and 52 outside the pelvis. Finally, the rate of recurrence was 32.6 % (14 cases) in CC cases, 43.1 % (31 cases) in PS cases and 66.7 % (4 cases) in cases with mixed histotype. The 5-year progression-free survival was 59.5 % (67.4 % for CC cases, 55.1 % for PS and mixed cases). CONCLUSION: In this study including CC and PS endometrial cancers, the 5-year survival from surgery was 72.7 % and the 5-year progression-free survival was 59.5 %.

Paclitaxel/carboplatin versus topotecan/paclitaxel/carboplatin in patients with FIGO suboptimally resected stage III-IV epithelial ovarian cancer a multicenter, randomized study.

OBJECTIVE: The objective of this prospective randomized phase III trial was to compare paclitaxel plus carboplatin (PC) versus topotecan plus carboplatin and paclitaxel (TPC) in women with suboptimal stage III (residual tumour >1cm) or stage IV ovarian cancer to evaluate the survival rate and toxicities. METHODS: Eligible for the study were patients aged at least 18 years old with histological/cytological diagnosis of FIGO stages III (residual tumour ≥1 cm after primary surgery)--IV epithelial ovarian cancer. Patients were randomized to iv PC on day 1, every 21 days or iv topotecan daily for three days and PC on day 3, every 21 days. RESULTS: The intention to treat population was made of 326 patients in total, 170 in the PC group and 156 in the TPC group. The life table estimates of survival probabilities at one, three and five years were, respectively, 0.94 (95% CI: 0.88-0.97), 0.53 (95% CI: 0.44-0.62) and 0.32 (95%CI: 0.23-0.42) in the PC group, and 0.92 (95% CI: 0.86-0.95), 0.52 (95% CI: 0.42-0.61), and 0.32(95%CI: 0.22-0.43) in the TPC group (log-rank test at 5 years: ns). The results of the survival analysis based on Cox regression model showed no statistically significant differences between groups (p-value: ns). The number of subjects with at least one event with possible relationship to study medication was 151 (88.8%) in the PC group and 139 (89.1%) in the TPC group (p=ns). In the PC group, 79 patients (23.6%) experienced at least one Adverse Event (AE) graded as severe and 16 patients (4.8%) at least one life-threatening AE, whilst in the TPC group, the number of patients who presented at least one severe or life-threatening AE was 86 (24%) and 37 (10.3%), respectively. CONCLUSION: The results of the present study show that the addition of topotecan to a standard paclitaxel/carboplatin regimen in the treatment of advanced epithelial ovarian cancer did not result in significant advantages in terms of survival rate. A slightly worse toxicity profile for TPC was observed.

Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study.

BACKGROUND: Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. METHODS: The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. RESULTS: Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). CONCLUSION: This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

Selective uterine artery embolization: a new therapeutic approach in a patient with low-risk gestational trophoblastic disease.

We report a case of persistent gestational trophoblastic disease (GTD) in which a selective uterine artery embolization instead of invasive surgery achieved both the control of pelvic hemorrhage and of disease.

Paclitaxel 175 or 225 mg per meters squared with carboplatin in advanced ovarian cancer: a randomized trial.

PURPOSE: To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study. RESULTS: Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. CONCLUSION: This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.