64 Can chemotherapy change tumor BRCA status and affect susceptibility to treatment?

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Contrast Agents during Pregnancy: Pros and Cons When Really Needed

Many clinical conditions require radiological diagnostic exams based on the emission of different kinds of energy and the use of contrast agents, such as computerized tomography (CT), positron emission tomography (PET), magnetic resonance (MR), ultrasound (US), and X-ray imaging. Pregnant patients who should be submitted for diagnostic examinations with contrast agents represent a group of patients with whom it is necessary to consider both maternal and fetal effects. Radiological examinations use different types of contrast media, the most used and studied are represented by iodinate contrast agents, gadolinium, fluorodeoxyglucose, gastrographin, bariumsulfate, and nanobubbles used in contrast-enhanced ultrasound (CEUS). The present paper reports the available data about each contrast agent and its effect related to the mother and fetus. This review aims to clarify the clinical practices to follow in cases where a radiodiagnostic examination with a contrast medium is indicated to be performed on a pregnant patient

Fertility sparing treatments in endometrial cancer patients: The potential role of the new molecular classification

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair

Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking surgery in advanced epithelial ovarian cancer: Is BRCA mutational status making the difference?

Introduction: The role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status. Methods: This is a retrospective, single center, case-control study. Data on AOC patients receiving HIPEC at the end of PDS as previously enrolled in a phase II monocentric trial (HIPEC group), were retrieved and matched for clinical and surgical characteristics with a group of cases who underwent PDS without receiving HIPEC between 01/2010 and 01/2015 (No HIPEC group). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥IIIB disease, aged between 18 and 70 years, with a laparoscopic Predictive Index value (PIV) ≤8 and residual disease ≤2.5 mm were included. Results: 70 patients were included. With the except of age (p = 0.012), the populations were balanced for the main characteristics. At a median follow-up of 48 months, no differences in Progression Free Survival (PFS) (p = 0.968) and Overall Survival (OS) (p = 0.789) were recorded. Survival analysis according to HIPEC administration and BRCA mutational status showed an improved PFS (p = 0.011) and OS (p = 0.003) in BRCA mutated compared to wild-type patients when HIPEC was not administered, whilst they were superimposable in case of HIPEC administration (p = 0.857 vs p = 0.372; respectively). No differences in terms of neither intra-operative (p = 1.0) nor early post-operative complications (p = 0.920) were detected. Conclusions: Our results show that HIPEC in AOC may be a promising treatment in BRCA wild-type patients, as it seems to balance their decreased chemosensitivity compared to mutation carriers

Minimally invasive salvage lymphadenectomy in gynecological cancer patients: A single institution series

Background: to assess the feasibility of minimally invasive surgery in the management of lymph-nodal recurrences of gynecological cancers, in terms of surgical and oncological outcomes. Methods: we retrospectively collected patients with isolated lymph-nodal recurrent disease of gynecological malignancies who underwent to minimally invasive lymphadenectomy at Catholic University of the Sacred Hearth in Rome (Italy), from January 2013 to November 2017. Results: Forty patients were considered eligible (31 LPS, 9 Robot); 24 (60.0%) with an ovarian cancer, 8 (20.0%) with a cervical cancer and 8 (20.0%) with an endometrial cancer recurrence. The most frequent site of lymph-nodal recurrence was represented by the aortic region (47.5%), while 18 patients (45.0%) experiencing pelvic lymph-nodal recurrence, 2 (5.0%) both pelvic and aortic relapse, and only 1 (2.5%) had an hepato-celiac lymph node recurrence. No patient required a laparotomic conversion. Median operative time was 220 min, median EBL was 80 mL, and median post-operative hospital stay was 2 days. There were 2 (5.0%) intra-operative and 4 (10.0%) post-operative complications, of which 2 were grade 3. The median follow-up was 22.5 months, and during this time 15 patients showed another relapse with a median time to progression of 12 months. Seven women died because of the disease. The 2-year post-relapse disease-free survival (PR-DFS) was 54.7%, and the 2-year post-relapse overall survival (PR-OS) was 79.3%. Conclusions: In our experience minimally invasive surgery is a valid therapeutic approach in very select patients with localized lymph-nodal recurrence of gynecological cancers, with benefits about peri and post-operative morbidities and without compromising their oncological outcome

High-resolution melting analysis coupled with next-generation sequencing as a simple tool for the identification of a novel somatic BRCA2 variant: A case report

In a 72-year-old woman with no associated personal or family history of breast and/or ovarian cancers, we identified a novel somatic pathogenic BRCA2 variant (c.18_28delAGAGAGGCCAA, p.Lys6Asnfs*4) using next-generation sequencing (NGS). The variant allele frequency (VAF) was 16%, and Sanger sequencing was unable to identify this variant. Adopting a high-resolution melting analysis strategy coupled with NGS, we successfully highlighted the presence of the c.18_28delAGAGAGGCCAA allele

Minimal residual disease at primary debulking surgery versus complete tumor resection at interval debulking surgery in advanced epithelial ovarian cancer: A survival analysis

Objectives: To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1\u201310 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no gross residual disease (NGR) at interval debulking surgery (IDS). Methods: Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1\u201310 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed. Results: 207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p < 0.0001 respectively). After a median follow up of 56.4 months (range 59.2\u201365.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022). Conclusions: IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications

Robotic versus laparoscopic radical hysterectomy in early cervical cancer: A case matched control study

Background: This study aims at evaluating the feasibility, surgical outcome and oncological results observed after robotic radical hysterectomy (RH) compared to laparoscopy for patients with early stage cervical cancer (ECC) patients. Methods: Between January 2010 and October 2016, 210 patients underwent RH for treatment of ECC: 70 underwent robotic approach (Cases), and 140 underwent laparoscopic approach (Controls). Results: There was no statistically significant difference between the two approaches with regard to clinical patient characteristics and in terms of extent of RH and rate of pelvic and aortic lymphadenectomy. Operative time was significantly longer in the robotic versus laparoscopic group (median = 243 min, range 90–612 versus median = 210 min, range 80–660; p value = 0.008). Conversion to laparotomy was necessary in 4 patients (1.9%) in the whole series. No difference was found in terms of intraoperative and postoperative complications between the two groups. Overall, during the observation period, 34 (16.2%) patients experienced any grade postoperative complications, and 21 (10.0%) had >G2 complications. The 3-yr DFS was 88.0% versus 84.0% in robotic and laparoscopic group, respectively (p value = 0.866). Central and/or lateral pelvic disease represented the most common site of relapse. The 3-yr OS was 90.8% in patients underwent robotic RH versus 94.0% in patients underwent laparoscopic RH (p value = 0.924). Conclusions: The present study shows the equivalence of robotic and laparoscopic approaches to radical surgery of ECC patients, in terms of perioperative and postoperative outcomes with equivalent survival figures, and thus the choice of approach can be tailored to the choice of patient and surgeon

Feasibility of tumor testing for BRCA status in high-grade serous ovarian cancer using fresh-frozen tissue based approach

Objective: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center. Methods: We consecutively enrolled a series of 456 newly diagnosed FIGO-Stage IIIC-IV, high grade serous-ovarian cancer patients. All patients receiving tumor-biopsy underwent tBRCA-testing. Results: Clinically relevant tissue-BRCA (tBRCA) variants were observed in 145 women (31.8%), particularly we recognized 89 (61.4%) patients with BRCA1-pathogenetic variants (PVs) and 56 women (38.6%) with BRCA2-PVs. Among 292 tBRCA wild-type (wt) patients, 88 cases were germline BRCA tested (gBRCA) and 86 (97.8%) were confirmed as gBRCAwt, while 1 (1.1%) had gBRCA variant of uncertain significance and 1 had gBRCA mutation (1.1%). The concordance of tumor test versus germline BRCA test was 86.3% (209/242). Large genomic rearrangements (LGRs) were suspected in 13/292 tBRCAwt patients (4.5%) by using bioinformatic algorithm and multiplex ligation-dependent probe amplification (MLPA) was performed, with evidence of PVs in only 1 case. Conclusions: Fresh-frozen tissue-based BRCA screening workflow is feasible and reliable. It allows to enlarge the BRCA mutated population that might receive PARPi with the greatest benefit, without missing cascade testing for family members and therefore, maintaining its preventive role