Oncological management of pregnancy-associated cancers: analysis from the French CALG (Cancer Associé à La Grossesse) network.

Background: Pregnancy-associated cancers constitute a major medical challenge. The objective of this study was to describe their epidemiological, oncological and obstetrical outcomes from the French CALG (Cancer Associé à La Grossesse) network.Material and methods: Retrospective analysis of patients diagnosed with a cancer associated with pregnancy between January 2015 and December 2018 after advice from the CALG network.Results: Of 218 patients, 197 (90%) were diagnosed with a cancer during pregnancy and 21 the year following delivery. Requests to the CALG network increased from 36 cases in 2015 to 77 cases in 2018. The disease was diagnosed at local and regional stages in 77% of cases. Breast cancer was the most frequent (56%), followed by ovarian (12%) and uterine cervical cancers (10%). Of the 218 patients, 157 (72%) underwent a treatment during pregnancy. Surgery and chemotherapy during pregnancy were performed in 83 patients (83/218, 38%) and 101 patients (46%) at a median term of 17 (IQR 11-24) and 25 (IQR 18-30) WG, respectively. Eighteen (8.5%) of the women had a pregnancy termination, two (1%) an abortion, one (0.5%) a miscarriage, one (0.5%) had a stillbirth and one (0.5%) patient died during pregnancy. The remaining 174 patients (88%) were allowed to continue the pregnancy. Eight recurrences and four deaths were observed with a median follow-up time of 2.6 years (IQR 2.2-3.8).Conclusions: Our data further describe the incidence and management of pregnancy-associated cancers in western Europe allowing comparisons with other regions.

Correlation between CA125 levels after sixth cycle of chemotherapy and clinical outcome in advanced ovarian carcinoma.

AIM: To correlate CA125 levels after platinum- and paclitaxel-based chemotherapy with progression-free survival (PFS) and overall survival (OS) in advanced ovarian carcinoma following primary cytoreduction. MATERIALS AND METHODS: The study was conducted on 247 patients. RESULTS: By log-rank test, PFS and OS were related to performance status (PS) (p=0.04 and p=0.00002), residual disease (p=0.00002 and p=0.001), ascites (p=0.00001 and p=0.0003) and post-chemotherapy CA125 using 10.8 U/ml as cut-off (p=0.0001 and p=0.01). PFS was related to post-chemotherapy CA125 assay (cut-off values of 7.1 U/ml (p=0.02), 18.5 U/ml (p<0.000001) and 35.0 U/ml (p=0.0001)). OS was related to FIGO stage (p=0.02). On multivariate analysis, residual disease, ascites and post-chemotherapy CA125 with any selected cut-off were independent prognostic variables for PFS, whereas residual disease, PS and post-chemotherapy CA125 (10.8 U/ml as cut-off) were independent prognostic variables for OS. CONCLUSION: Post-operative CA125 using 10.8 U/ml as cut-off was an independent prognostic variable for both PFS and OS.

Micro-RNAs and ovarian cancer: the state of art and perspectives of clinical research.

Dysregulation of microRNA (mi-RNA) expression plays a major role in the development and progression of most human malignancies. Members of the miR-200 family, miR-182, miR-214 and miR-221 are frequently up-regulated, whereas miR-100, let-7i, miR-199a, miR-125b, mir-145 and miR-335 are often down-regulated in ovarian cancer compared with normal ovarian tissue. Most mi-RNA signatures are overlapping in different tumor histotypes but some mi-RNAs seem to be histotype specific. For instance, the endometrioid type shares with the serous and clear cell types the up-regulation of miR-200 family members, but also presents over-expression of miR-21, miR-202 and miR-205. Clear cell carcinoma has a significantly higher expression of miR-30a and miR-30a*, whereas mucinous histotype has elevated levels of miR-192/194. In vitro and in vivo investigations have shown that several mi-RNAs can modulate the sensitivity of ovarian cancer to platinum and taxane, and clinical studies have suggested that mi-RNA profiling may predict the outcome of patients with this malignancy. Some mi-RNAs could be used as biomarkers to identify patients that might benefit from the addition of molecularly targeted agents (i.e. anti-angiogenic agents, MET inhibitors and poly(ADP-ribose) polymerase (PARP) inhibitors) to standard chemotherapy. Moreover, mi-RNAs could represent potential targets for the development of novel therapies.

Fertility outcome of breast cancer and Hodgkin's lymphoma female survivors: a growing clinical challenge for gynecologists and oncologists.

The issue of taking into consideration future fertility in young women with breast cancer and Hodgkin's lymphoma [HL] will become more and more common and represent a growing clinical challenge for gynecologists and oncologists. The present paper will review literature data on the attempts of preventing chemotherapy-induced ovarian damage in these women and on their fertility outcome. Gonadotropin-releasing hormone [Gn-RH] agonists have been widely investigated as agents able to prevent ovarian failure in animal models and in humans. The majority of the studies on women with breast cancer and HL have shown a protective effect of Gn-RH agonists. A recent meta-analysis of five randomized trials, including 528 premenopausal breast cancer patients, revealed that relative risk [RR] of developing premature ovarian failure within one year was 0.40 (95% confidence interval [CI] = 0.21-0.75) for the women who received Gn-RH agonists with chemotherapy compared to those who received chemotherapy alone. However, the concurrent administration of Gn-RH agonists during chemotherapy appeared to have no effect on spontaneous pregnancy rates. Limited information are available about pregnancies in breast cancer and HL survivors, but the current literature appears to show no apparent increase in pregnancy complications, spontaneous abortions, or congenital abnormalities compared to general obstetric population.

Antiangiogenic agents in advanced, persistent or recurrent endometrial cancer: a novel treatment option.

The limited efficacy of endocrine therapy and chemotherapy has stimulated several researches aimed to detect novel molecularly target therapies for advanced, persistent or recurrent endometrial cancer. Prior attempts to block vascular endothelial growth factor (VEGF) with sunitinib, sorafenib and thalidomide have obtained disappointing results. Bevacizumab has shown a promising activity in a phase II study. The percentages of patients with progression-free survival ≥6 months were similar for endometrioid (35%) and serous carcinoma (36%), but the number of cases was too small to assess the relevance of histological type for response to bevacizumab. In a phase II study, aflibercept was administered every 2 weeks to women with recurrent or persistent disease after chemotherapy. Forty-one percent of the patients were progression-free at 6 months, but 32% of the women had been removed from study because of toxicity. The detection of activating mutations of Fibroblast Growth Factor Receptor (FGFR)-2 in primary endometrial carcinoma has generated a new avenue for the development of molecularly target agents. Dovitinib, a tyrosine kinase inhibitor targeting both VEGF receptor (VEGFR) and FGFRs, is under clinical investigation in different malignancies including endometrial cancer.