Efficacy, safety and pharmacokinetics of apatinib plus etoposide versus apatinib alone for platinum-resistant recurrent ovarian cancer: protocol of a multicenter, open-label, randomized phase 2 trial.

Background: Currently preferred single-agent nonplatinum chemotherapy or its combination with bevacizumab results in a low response rate and modest survival benefit for platinum-resistant recurrent ovarian cancer, and thus more effective regimens are needed. In our previous phase 2 trial, apatinib plus etoposide showed promising efficacy and an acceptable safety profile in platinum-resistant recurrent ovarian cancer patients. Due to the single-arm design, the role of apatinib still needs to be determined. Methods: In this phase 2 trial, 54 adult patients with platinum-resistant current ovarian cancer will be recruited at 17 sites in China. Patients with prior administration of small-molecule tyrosine kinase inhibitors or etoposide will be excluded. Patients will be randomized (1:1) to receive apatinib (375 mg, orally, once daily) alone or in combination with etoposide (50 mg, orally on days 1-14 of each 21-day cycle) until disease progression or intolerable toxicity. Randomization will be performed using a computerized central randomization system, stratified by platinum resistance for the first time (yes or no). Imaging examinations will be conducted every 6 weeks. The primary endpoint is the objective response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (version 1.1), which will be compared between groups using the Cochran-Mantel-Haenszel test. Discussion: This study will provide prospective data of 2 experimental regimens using a randomized design. It will help determine whether apatinib monotherapy can provide favorable clinical benefits or needs to be combined with chemotherapy to be effective. Trial Registration: ClinicalTrials.gov Identifier: NCT04383977. It was registered on May 12, 2020.

The clinicopathological characteristics and survival outcomes of primary expansile vs. infiltrative mucinous ovarian adenocarcinoma: a retrospective study sharing the experience of a tertiary centre.

Background: Mucinous ovarian carcinomas (MOCs) are rare ovarian tumours accounting for 3% of all epithelial ovarian carcinomas (EOCs). They are either expansile or infiltrative, based on the tumour's histological pattern of invasion. MOCs have a distinct molecular profile, natural history, chemo-sensitivity, and prognosis compared to other EOCs. The aim of this study was to describe patient and tumour characteristics, as well as survival outcomes of expansile and infiltrative primary MOCs. Methods: This was a retrospective cohort study conducted at a tertiary cancer centre. Patients had surgery for primary MOC between Jul 1, 2010 and Oct 28, 2022. All patients discussed at the Oxford multidisciplinary team (MDT) meeting with a diagnosis of MOC were included. We excluded patients with mucinous metastatic carcinoma (MMC), dual histological diagnoses, those who died before treatment was initiated, and patients with incomplete records. Results: A total of 47 patients were identified and 14 were excluded. Out of the remaining 33 MOCs, 23 (70.6%) were expansile and 10 (30.4%) were infiltrative. The median follow-up was 37 months (95% CI: 14.1-69.8). Patients with infiltrative tumours were older than those with expansile tumours (median age 62 vs. 55 years, P=0.049). Infiltrative tumours were diagnosed at a more advanced International Federation of Gynaecology and Obstetrics (FIGO) stage compared to expansile tumours: FIGO stage II/III 50% vs. 8.2% (P=0.002). We found paired-box gene 8 (PAX8) more frequently expressed in expansile tumours (75% vs. 37.5%, P=0.099). Adjuvant treatment was administered in 50% of patients with infiltrative disease, compared to only 13% of those with expansile disease (P=0.036). 80% of patients who have relapsed had received adjuvant chemotherapy, compared to 17.2% of patients without relapse (P=0.012). At 3 years, there was a statistically significant difference in progression-free survival (PFS) (94.7% vs. 65.6%, P=0.02) between the expansile and infiltrative groups, but no difference in overall survival (OS) (88.8% vs. 90%, P=0.875). Conclusions: Patients with infiltrative tumours were older, more likely to have bilateral tumours and more likely to have an advanced FIGO stage at diagnosis. Adjuvant treatment was more likely to be administered to patients with infiltrative tumours, however, this did not prevent relapse. PFS at 3 years was significantly higher in patients with expansile tumours. PAX8 was more frequently expressed by expansile tumours.

Synchronous ovarian and Bartholin gland carcinoma: Case report and review of literature.

To our knowledge, this is the first reported case of synchronous ovarian and vulva (Bartholin gland) cancer. A postmenopausal woman presented with a complex multiloculated left adnexal mass and 2-cm right Bartholin gland mass. CA 125 was 59 IU/mL. Computed tomography of chest, abdomen, and pelvis showed a very large (32 × 13.5 × 22.5 cm) complex mass arising from the pelvis and extending to the level of the T12/L1 disk space. A right Bartholin mass with suspicious right inguinal nodes was seen. Midline laparotomy, total abdominal hysterectomy, bilateral salpingo-oophrectomy, infracolic omentectomy, pelvic peritoneal biopsies, and peritoneal washings were carried out. Wide local excision of the right Bartholin gland mass was carried out in the same setting. Histopathology came back as Stage 2B left ovarian clear-cell carcinoma and synchronous right Bartholin gland adenoid cystic carcinoma with lymphovascular invasion, incompletely excised, staged at least FIGO Stage 1B. Following local multidisciplinary team discussion and positron emission tomography scan review, the local committee agreed to start three cycles of adjuvant chemotherapy then proceed with Bartholin gland scar re-excision and bilateral groin lymph node dissection. After the three cycles, the groin lymph nodes came back as metastatic adenocarcinoma with overall morphologic and immunohistochemical features consistent with metastatic ovarian clear-cell carcinoma. Postoperative adjuvant chemotherapy was given. Initial follow-up period over 9 months was uneventful.

Cervical cancer during the covid pandemic: Are patients presenting with more advanced or larger tumours?

OBJECTIVES: Concerns were raised by clinicians at the Oxford Gynaecological Cancer MDT that there was an increasing number of women presenting with large cervical tumours requiring chemo-radiotherapy, possibly due to delays associated with the COVID pandemic. This audit was undertaken to assess whether this was a real event. STUDY DESIGN: This retrospective cohort study collated the data from the central pathology service covering Oxfordshire, in the Oxford Gynaecological cancer centre. The control population consisted of patients treated during the 2 years pre-pandemic (1st Jan 2018-31 Dec 2019) and the study group the 2-year pandemic period (1st Jan 2020 until 31st December 2021). A total of 153 patients (74 control and 79 study) were diagnosed of cervical cancer during the study period. Variables included in the analysis were age, pathway of referral and diagnosis (cytology or clinical), FIGO stage, tumour histology, tumour size (using maximum diameter on MRI) and treatment. Student's t-test was used for continuous and discrete variables, respectively. The X2 test was used for the statistical analysis of proportions. RESULTS: There was no statistically significant differences was noted in the referral pathways during both periods. Statistically significant stage migration from FIGO stage II to III was detected (p < 0.05), though no statistically significant change in tumour size. However, the pattern of tumour volume on case-to-case comparison elicited more cases with larger volumes during the pandemic periods. CONCLUSIONS: Referral pathways of diagnosed cancer cervix was not affected during the pandemic in Oxfordshire. Therapeutic treatment numbers were unchanged - but some changes in tumour volume were likely the reason for the impression more such cases. Whether the stage shift noted here is representative of the wider population requires further studies.

The Prevalence Of Specific Gene Polymorphisms Related To Thrombophilia In Egyptian Women With Recurrent Pregnancy Loss.

BACKGROUND: Despite the enhanced progress in identifying a number of leading causes to fetal miscarriage, still some women suffer from recurrent pregnancy loss (RPL) for unknown cause. A hidden genetic influence of coexisting hereditary thrombophilia was assumed to have a role. AIM: The aim was to investigate the association between unexplained RPL and thrombophilic gene variants of angiotensin I-converting enzyme (ACE) (rs4646994) and ß-fibrinogen (rs1800790) genes. SETTINGS AND DESIGN: The present case-control study was conducted on unexplained RPL in eighty women and eighty matched controls with no history of previous pregnancy loss. MATERIALS AND METHODS: Analysis of extracted DNA was performed using polymerase chain reaction-restriction fragment length polymorphism method. STATISTICAL ANALYSIS: The frequency of genotypes and alleles was compared between groups using Chi-square test or Fisher's exact test. Risk assessment was made by odds ratio (OR) at a 95% confidence interval (CI). RESULTS: Women with RPL group had higher frequency of DD than controls (47.5%, 31.25%, respectively, P = 0.086). D allele frequency was 0.67 and 0.54 in the control (P = 0.022). D allele carriers were at higher risk of RPL than the control as OR was 1.694 at 95% CI from 1.08 to 2.67. There was no association between the rs1800790 variant of ß-fibrinogen gene and RPL. CONCLUSION: Females who are carriers for D allele of ACE I/D gene polymorphism are more liable to suffer from RPL. Screening for hereditary thrombophilia in females who are planning to conceive and have a history of RPL of unidentified cause is of great value to provide proper management and genetic counseling to high-risk couples.