Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Conservative management of abnormally invasive placenta complicated by local hyperfibrinolysis and beginning disseminated intravascular coagulation.

INTRODUCTION: Abnormally invasive placenta (AIP) is often associated with high maternal morbidity. In surgical treatment, caesarean hysterectomy or partial uterine resection may lead to high perioperative maternal blood loss. A conservative treatment by leaving the placenta in utero after caesarean delivery of the baby is an option to preserve fertility and to reduce peripartum hysterectomy-related morbidity. Nevertheless, due to increased placental coagulation activity as well as consumption of clotting factors, a disseminated intravascular coagulation (DIC)-like state with secondary late postpartum bleeding can occur. PURPOSE: Systematic review after the presentation of a case of conservative management of placenta percreta with secondary partial uterine wall resection due to vaginal bleeding, complicated by local hyperfibrinolysis and consecutive systemic decrease in fibrinogen levels. METHODS: Systematic PubMed database search was done until August 2019 without any restriction of publication date or journal RESULTS: Among 58 publications, a total of 11 reported on DIC-like symptoms in the conservative management of AIP, in the median on day 59 postpartum. In most cases, emergency hysterectomy was performed, which led to an almost immediate normalization of coagulation status but was accompanied with high maternal blood loss. In two cases, fertility-preserving conservative management could be continued after successful medical therapy. CONCLUSION: Based on these results, we suggest routinely monitoring of the coagulation parameters next to signs of infection in the postpartum check-ups during conservative management of AIP. Postpartum tranexamic acid oral dosage should be discussed when fibrinogen levels are decreasing and D-Dimers are increasing.

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer.

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and 111 (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE) and 147 (94%) did so systematically; 97 (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide, SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Laparoscopic radical hysterectomy in cervical cancer as total mesometrial resection (L-TMMR): a multicentric experience.

OBJECTIVE: To analyze the feasibility of total mesometrial resection by laparoscopy (L-TMMR) in a multicentric series of early stage cervical cancer. METHOD: We prospectively evaluated a consecutive series of cervical cancer patients with pre-operative FIGO stages IA2-IB1 at the Catholic University in Rome and in Campobasso and the Charitè University in Berlin. All cases were assessed at pre-operative MRI scan and clinically confirmed by investigation under anesthesia, adhering strictly to the FIGO criteria. The surgical and post-surgical data were collected. RESULTS: 104 women with cervical cancer were admitted between July 2013 and August 2014 and among them 71 patients with pre-operative FIGO stages IA2-IB1 were treated with L-TMMR. One laparotomic conversion was registered. The median operative time was 260min (120-670min), estimated blood loss was 100cm(3) (25-900cm(3)), and the median length of hospital stay was 6days (2-26days). We observed 8 intra-operative complications including a vascular injury of the left internal iliac vein that caused conversion, 6 vesical injuries and 1 ureteral injury managed laparoscopically. Two vescico-vaginal fistula and one hemoperitoneum were observed as major post-operative complications (4.2%). CONCLUSION: L-TMMR can be safely performed in selected cervical cancer patients. Further larger prospective trials are needed to evaluate the oncological outcome of patients undergoing this surgical procedure.