Switching from standard to dose-dense chemotherapy in front-line treatment of advanced ovarian cancer: a retrospective study of feasibility and efficacy

BACKGROUND: Current standard neoadjuvant treatment for advanced ovarian cancer is 3-weekly platinum-based chemotherapy (CP3w). Patients unable to have interval debulking surgery (IDS) or with significant residual disease have a poor outcome to CP3w treatment. We investigated the outcome in patients who were switched to dose-dense chemotherapy. METHODS: We retrospectively analysed 30 patients treated at UCLH in 2009–2013, who switched to dose-dense chemotherapy after neoadjuvant CP3w, having achieved a poor response/progressed and unable to proceed to IDS (n=21), or had >1 cm residual disease after IDS (n=9). Treatment was 3-weekly carboplatin and weekly paclitaxel (n=23), or both drugs weekly (n=7). For comparison, we included 30 matched patients treated with CP3w followed by IDS (n=24, without or ≤1 cm residual disease; n=6, with >1 cm residual disease). Time to progression (TTP) and overall survival (OS) were measured from the date of diagnosis until progression (CT scan or CA-125) and death from any cause, respectively. RESULTS: Baseline characteristics were similar in both groups. The response rate to dose-dense chemotherapy was 70% (Gynecological Cancer Intergroup criteria). In the dose-dense group, 24 patients had tumour progression and 16 died; the corresponding numbers in the control group were 24 and 11. Median TTP was 15.8 months with dose-dense therapy, higher than expected for this patient group, and the same as in the control group (15.7 months) undergoing IDS, p=0.27. Median TTP in patients with residual disease postsurgery was 16.5 months (dose-dense) and 10.8 months (controls), p=0.02. TTP in dose-dense patients who did not have surgery was 10.4 months. Median OS was 31.3 (dose-dense) and 59.6 months (controls), p=0.06. Dose-dense chemotherapy was well tolerated: only three patients interrupted treatment due to toxicity. CONCLUSION: Switching to dose-dense chemotherapy in patients who failed to respond to CT3w neoadjuvant chemotherapy appears to be an effective strategy and requires further investigation

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Effectiveness of CO2 laser on urogenital syndrome in women with a previous gynecological neoplasia: A multicentric study

Background: Many women diagnosed with gynecological cancers undergo adjuvant therapy, which may lead to transient or permanent menopause that ultimately leads to urogenital syndrome and vulvovaginal atrophy. Studies advise against the use of estrogen in women with a history of hormone-dependent cancer. One alternative is vaginal microablative fractional CO2 laser, which promotes tissue regeneration through the production of collagen and elastic fibers. Objective: To evaluate the effectiveness of CO2 laser in the treatment of urogenital syndrome - in particular, symptomatic vulvovaginal atrophy in women who have survived gynecological cancers. Methods: A retrospective study was carried out, including all patients with a history of gynecological cancers and vulvovaginal atrophy who underwent CO2 laser treatment between November 2012 and February 2018 in four Italian centers. The study was approved by the local ethics committee of each participating institution. The inclusion criteria were women aged between 18 and 75; Eastern Cooperative Oncology Group performance status &lt;2; and history of breast, ovarian, cervical, or uterus cancer. Patients had to have vulvovaginal atrophy and at least one of the following symptoms of urogenital syndrome: vaginal dryness, dyspareunia, vaginal introitus pain, burning, or itching. Three applications were administered at baseline, 30 days, and 60 days. All patients were evaluated before the first laser session, at each session, and 4 weeks after the last session. In particular, patients were asked to indicate the intensity of symptoms before the first session and 4 weeks after the last session, using Visual Analog Scale (VAS) scoring from 0 ('no discomfort') to 10 ('maximum discomfort'). Results: A total of 1213 patients underwent CO2 laser treatment and of these, 1048 were excluded because they did not meet the inclusion criteria in the analysis. Finally, a total of 165 patients were included in the study. The mean age at the time of treatment was 53 years (range 31-73). Dryness improved by 66%, dyspareunia improved by 59%, burning improved by 66%, pain at introitus improved by 54%, and itching improved by 54%. The side effects were evaluated as pain greater than VAS score 6 during and after the treatment period. No side effects were seen in any sessions. Conclusions: Fractional microablative CO2 laser therapy offers an effective strategy in the management of the symptoms of genitourinary syndrome in post-menopausal women and in survivors of gynecological cancer

Role of human epididymis protein 4 (HE4) as predictor of response to platinum based chemotherapy: A systematic review of literature

Objective: Although epithelial ovarian cancer (EOC) treatment has greatly improved over the last three decades, a fraction of patients (40-60%) with advanced-stage disease fail to completely respond to standard therapy, because of chemo-resistance to platinum. For this reason, new predictive and monitoring tools were studied to identify platinum resistant EOC patients, with the purpose of improving and personalizing the treatment. In this review, we aim to discuss the latest evidence reported in the literature about the use of Human Epididymis 4 (HE4) to predict platinum resistance among EOC patients. Methods: A comprehensive search of the literature was conducted using the terms “HE4 epithelial ovarian cancer” and “human epididymis protein 4 epithelial ovarian cancer” and they were combined with the terms “chemotherapy”, “platinum” and “response”. Results: The search identified twelve papers, from January 1952 to December 2019, in line with eligibility criteria for this systematic review, all of which demonstrated good performance of HE4 in predicting platinum sensitivity or resistance. Conclusions: All the available studies present limited and non-homogeneous data, therefore more studies are needed to validate and reinforce the role of HE4 in predicting the response to platinum based chemotherapy among ovarian cancer patients

The effects of giving patients verbal or written pre-operative information in gynecologic oncology surgery: A randomized study and the medical-legal point of view

Objectives: To evaluate the verbal and written preoperative information in patients undergoing surgery for malignant gynaecologic disease, in terms of satisfaction about preoperative received informations, hospitalization days, postoperative pain experienced using visual analogue scale (VAS) and number of pain drugs used daily.Study design: From January 2008 to December 2012, Consecutive patients with diagnosis of endometrial cancer, referred to the Division of Gynecology of University Campus Bio-Medico of Rome, were enrolled. Eligible subjects were randomized into two groups: Group V (Verbal information ward) consisted of patients who had verbal preoperative information about surgical procedure and postoperative management and Group W (Written Information ward) consisted of patients who had written preoperative information. All preoperative and postoperative data were recorded. Concerning satisfaction about preoperative received informations, patients were asked to complete the QLQ-C30 and the EORTC INFO25.Results: 190 patients were considered in this study. Group W (n = 92) has a better info satisfaction (p = 0.0008, statistically significant), a mean VAS value lower (p = 0.02, statistically significant) and also a lower number of hospitalization days (p = 0.0265, statistically significant) and pain medications used daily, (p = 0.0120, statistically significant), comparing with group V (n = 98).Conclusions: We support the use of preoperative information leaflet to better prepare patients for a surgical procedure, showing a faster recovery, low medications use and a better quality of life outcome. (C) 2014 Elsevier Ireland Ltd. All rights reserved

The effects of giving patients verbal or written pre-operative information in gynecologic oncology surgery: a randomized study and the medical-legal point of view.

Objectives To evaluate the verbal and written preoperative information in patients undergoing surgery for malignant gynaecologic disease, in terms of satisfaction about preoperative received informations, hospitalization days, postoperative pain experienced using visual analogue scale (VAS) and number of pain drugs used daily. Study design From January 2008 to December 2012, consecutive patients with diagnosis of endometrial cancer, referred to the Division of Gynecology of University Campus Bio-Medico of Rome, were enrolled. Eligible subjects were randomized into two groups: Group V (Verbal information ward) consisted of patients who had verbal preoperative information about surgical procedure and postoperative management and Group W (Written Information ward) consisted of patients who had written preoperative information. All preoperative and postoperative data were recorded. Concerning satisfaction about preoperative received informations, patients were asked to complete the QLQ-C

Total rectosigmoidectomy versus partial rectal resection in primary debulking surgery for advanced ovarian cancer

Purpose: To compare in a sample of Italian patients intraoperative, perioperative complications, Quality of Life (QoL), recurrence rate and overall survival of advanced ovarian cancer (AOC) patients according to the type of surgery performed on sigma-rectum, total rectosigmoid resection (TRR) versus partial rectosigmoid resection (PRR). Methods: From May 2004 to May 2010, consecutive patients affected by epithelial AOC (FIGO Stage IIIeIV) were assessed for this prospective caseecontrol study, According to the type of colorectal surgery performed to approach rectosigmoid involvement, patients were allocated into Group A (TRR) and Group B (PRR). PRR was performed when the complete removal of disease led to a laceration &lt;30e40% of intestinal wall circumference. Results: 82 and 72 patients were included in Group A and Group B respectively. Surgical outcomes were statistically similar except hospital stay which was significantly lower in the PRR group. There was not a statistically significant difference as regarding intra-operative, perioperative and postoperative complications, even if a higher rate of major complications were recorded in TRR. An improvement in QoL’s scores has been recorded in PRR’s group. There was not a statistically difference concerning the optimal debulking rate (92% and 96% respectively) and 5-year Overall Survival (48% and 52% respectively). Conclusions: PRR seems to be feasible in over 40% of patients with advanced ovarian cancer and recto-sigmoid colon involvement. It is related to higher QoL and can be easily performed, without jeopardizing surgical radicality, in those cases in which conservative surgery at intestinal tract does not compromise residual tumor