Correlation between peritoneal cancer index and survival in advanced epithelial ovarian cancer with complete resection.

OBJECTIVE: The aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer. METHODS: Patients treated at the Gustave-Roussy Institute between December 2004 and November 2017 for advanced epithelial ovarian cancer in complete resection were included. The correlation between the peritoneal cancer index and survival was studied using statistical modeling. Multivariate analysis was performed with a logistic regression model. RESULTS: Of the 351 patients included, 94 (27%) had initial surgery and 257 (73%) had interval surgery. Median follow-up was 52.7 months (range 47.6-63.9). Median peritoneal cancer index was 10 (range 0-32). The linear model best represented the relationship between peritoneal cancer index and overall survival. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as the peritoneal cancer index increased. Overall survival and recurrence free survival were better in the initial surgery group (103.4 months (79.1-not reached (NR)) vs 66.5 months (59.1-95.3) and 31.8 months (23.7-48.7) vs 25.9 months (23.2-29), respectively). Risk factors for death were body mass index, peritoneal cancer index, and need for neoadjuvant chemotherapy. CONCLUSION: The peritoneal cancer index is a prognostic indicator, but its linear relationship with survival precluded setting a unique peritoneal cancer index cut-off. Moreover, the prognostic impact of peritoneal cancer index was stronger in the setting of neoadjuvant chemotherapy.

Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid.

BACKGROUND: Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing. METHODS: We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA. RESULTS: cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed. CONCLUSION: Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.

Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients.

Genomic testing is crucial for the management of ovarian cancer. DNA from biopsies at diagnostic laparoscopies or interval debulking surgery after neoadjuvant chemotherapy, has a high failure rate. At relapse, biopsies may not be feasible. The aim of our study was to evaluate the feasibility and usefulness of measuring genomic instability score (GIS) on cell-free DNA (cfDNA) from ascites.Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples. CfDNA was extracted from 1 to 4 ml of double-centrifuged fresh ascites. Targeted Next-generation sequencing (NGS) including TP53 mutation (TP53m) was performed on cfDNA to confirm the presence of tumor cfDNA. Single Nucleotide Polymorphism Array estimating somatic copy number alterations (SCNA) was performed to calculate GIS for Homologous-Recombination deficiency (HRD).Twenty nine ascites were collected from 20 patients with suspected or confirmed OC. 93% (27/29) samples had detectable cfDNA (median 1120 ng [24-5732]) even when obtained during chemotherapy. A deleterious mutation was identified in 100%, with high allelic frequencies (median 60% [3.3-87%]), confirming that cfDNA was tumoral. SCNA analyses on 17 patients showed 11 high GIS, and 6 low GIS. 4 patients with confirmed BRCA mutation had a high GIS on ascites. When available from the same patient, SCNA profiles on ascites and tumor were superimposable.Ascites is frequent at diagnosis and relapse and yields large amounts of tumoral cfDNA. SCNA analysis on ascitic cfDNA is feasible and can detect the same HRD scar as tumor testing. Ascites could provide an alternative to tumor sampling for HRD and BRCA testing.

The lymphatic system of the uterine cervix: towards a more precise definition of the drainage routes.

PURPOSE: Lymph node involvement in cancer of the uterine cervix is a major independent prognostic factor for overall survival. The aim of our study was to examine the lymphatic drainage regions of the different parts of the uterine cervix. METHODS: An anatomical study of fresh cadavers was conducted by injecting patent blue in the anterior or posterior lip of the uterine cervix and dissecting drainage regions. Furthermore, a retrospective radiological and pathological studies were conducted on patients who were treated for early-stage cancer of the uterine cervix with lymph node involvement. Radiological analysis of pre-therapeutic MRIs and/or pathological analysis of surgical specimens showed the precise location of the tumour. A correlation between the anatomy of the primary lesion site and the lymphatic area involved was established. RESULTS: We administered 15 cadaveric injections: 8 in the anterior lip of the uterine cervix and 7 in the posterior one. For 100% of the anterior lip injections, lymphatic drainage was bilateral ileo-obturator (n = 8/8) combined with bilateral parametrial drainage. For the posterior injections, there was never any ileo-obturator drainage, and 6 of the 7 (75%) posterior injections drained in the posterior uterine serosa. Concerning the clinical study, we included 21 patients. We observed a non-significant tendency towards bilateral lymph node involvement when the tumour of the anterior lip. CONCLUSION: Physiological lymphatic drainage of the uterine cervix presents anatomical specificities, depending on the structure studied, anterior or posterior lip of the cervix. Better knowledge of these specificities should allow personalized surgery for each patient.

Management of patients with advanced epithelial ovarian cancer: a European survey.

BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.

Surgical management of patients with advanced ovarian cancer: Results of a French National Survey.

INTRODUCTION: Desire to homogenize advanced stage ovarian cancer management has led to a debate on the need to centralize cares. The aim was to assess current practices to compare them with centralization motivation and to overview possible perspectives of evolution. METHODS: An anonymous questionnaire of 57 questions has been submitted from August 2021 to October 2021 to members of French gynecological oncological surgical societies. Questions encompassed all aspects of ovarian cancer surgical management, including institutions, technics, indications, and outcomes. RESULTS: Of the 40 responses, 77.5% managed less than 20 cases by themselves, but 67.5% practiced in institution managing more than 30 cases annually. Since the LION trial results' publication, 95% of practitioners have evolved their lymphadenectomy indications. More than 10% of surgery needed digestive resection for 90% of practitioners. Digestive resections rate was significantly higher for practitioners managing more than 20 cases (p<0.01), but it was not for institutions managing more than 30 cases annually (p=0,07). Surgeons performing more than 20 ovarian cancers annually reported less severe complications (p=0.04) compared to low-volume surgeons independently of institution volume. For more than a quarter of the practitioners, less than half of the patients can benefit from the enhanced recovery after surgery program despite benefits of such care. CONCLUSION: Our survey provides an overview of French practices in ovarian cancer management. This survey seems to confirm that minimum volume thresholds could lead to better outcomes. It also underlines that individual performances are as valuable as center volume.

Cervical Cancer and Fertility-Sparing Treatment.

Radical hysterectomy with pelvic node dissection is the standard treatment for early-stage cervical cancer. However, the latter can be diagnosed at a young age when patients have not yet achieved their pregnancy plans. Dargent first described the vaginal radical trachelectomy for patients with tumors <2 cm. It has since been described a population of low risk of recurrence: patients with tumors <2 cm, without deep stromal infiltration, without lymphovascular invasion (LVSI), and with negative lymph nodes. These patients can benefit from a less radical surgery such as conization or simple trachelectomy with the evaluation of the pelvic node status. Tumors larger than 2 cm have a higher risk of recurrence and their treatment is a challenge. There are currently two options for these patients: abdominal radical trachelectomy or neoadjuvant chemotherapy (NACT), followed by fertility-sparing surgery. All patients who wish to preserve their fertility must be referred to expert centers.

Results of a 2021 French National Survey on Management of Patients with Advanced Stage Epithelial Ovarian Cancer.

BACKGROUND: The aim of this study was to assess current French practices in the management of patients with advanced epithelial ovarian cancer. METHOD: a 58-question electronic survey was distributed anonymously to the members of the SFOG (French Society of Gynaecological Oncology), GINECO-ARCAGY (National Investigators Group for Ovarian and Breast Cancer Studies in France) and FRANCOGYN (French research group in oncological and gynaecological surgery). Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: a total of 107 participants responded to emailed surveys. Most of the respondents were obstetrician-gynaecologists (37.4%), surgical oncologists (34.6%) and medical oncologists (17.8%). According to most (76.8%) participants, less than 50% of patients were eligible for primary debulking surgery (PDS). The LION study criteria were applied in 69.5% of cases during PDS and 39% after chemotherapy. The timing of BRCA testing was very heterogeneous and ranged from 1 to 6 months. The use of bevacizumab as an adjuvant schedule was lower in cases of no residual disease (for 54.5% of respondents) compared to cases of residual disease (for 63.6% of respondents). In cases of BRCA1-2 mutations, olaparib was given by 75.8-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSION: this survey provides an extensive and a unique review of current French practices in the management of patients with advanced epithelial ovarian cancer in 2021.

[Surgical de-escalation in gynecologic oncology]. / Désescalade chirurgicale en oncologie gynécologique.

The evolution of knowledge in gynecologic oncology is leading to surgical de-escalation in several areas, particularly in lymph node staging. Sentinel lymph node biopsy that was initially used in low and intermediate risk endometrial cancer, has now been extended to high-intermediate and high-risk endometrial cancer. Sentinel lymph node biopsy plays also an important role in the nodal staging of early-stage cervical cancer. The radicality of hysterectomies in patients with early cervical cancer is under debate. Similarly, surgical staging with para-aortic lymphadenectomy in locally advanced cervical cancer should be performed only for few cases. Systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancers is not recommended anymore.

Robotic Prophylactic Nipple-Sparing Mastectomy with Immediate Prosthetic Breast Reconstruction: A prospective Study of 138 Procedures.

Bachground: Robotic breast surgery is an emergent procedure with encouraging preliminary results. The aim of this study is to assess the feasibility and the safety of robotic nipple sparing mastectomy (RNSM) with immediate prosthetic breast reconstruction (IPBR). Methods: This is a prospective study including from December 2015 to January 2020 all RNSM surgeries with IPBR, in patients with moderate ptosis and A B or C cup. The primary endpoint was the rate of major necrosis. Secondary endpoints were conversion rate, postoperative complications (infections, hematoma, implant exposure), aesthetic results and quality of life. Results: 79 patients underwent 138 RNSM with IPBR. The average follow-up was 28 months. 2 procedures required conversion. Two cases of major necrosis occurred (1.4%). 9 surgical site infections were observed (6.5%), 4 infections could be treated with implant replacement. Unfortunately, 5 others resulted in implant loss. 4 other implant losses occurred: 2 due to major necrosis, and 2 due to periprosthetic capsula. In total, 9 implants were lost (6.5%). Esthetical results were mostly very satisfying and quality of life was not affected by the mastectomy. Conclusions: RSNM with IPBR was associated with low rates of major necrosis. It is a safe and reproducible procedure that allows breast reconstruction without visible scar.

ROBOT-ASSISTED ABDOMINAL LAPAROSCOPIC RADICAL TRACHELECTOMY FOR EARLY STAGE CERVICAL CANCER :Case report with surgical intervention.

BACKGROUND: Vaginal radical trachelectomy to preserve fertility in women with early stage cervical cancer was first described by Dargent in 1994. Nowadays, robot-assisted abdominal laparoscopic radical is a new alternative. We want to share our first experience of robot-assisted radical trachelectomy. TECHNIQUE: We report the case of a 28 years-old women with an early stage cervical cancer (1B1) and has a wish for preserved fertility (no anterior pregnancy). She undergoes a robot-assisted laparoscopic radical trachelectomy. We divide the technique into 10 surgical steps. EXPERIENCE: The duration of the surgery was : 4H30 with a bleeding < 100cc. The post operative period was simple without complications. Since the intervention, we perform 3 more robot-assisted radical trachelectomy. None of them have a complication during the surgery and the post operative period was simple. CONCLUSION: Robot-assisted laparoscopic radical trachelectomy is a safe and acurate technique. We want to share our recent experience by sharing this video. The surgeon in our hospipal are used to pratic robot-assisted laparoscopic. However, it was our first robot-assisted laparoscopic radical trachelectomy. Thus we would like to demonstrate the feasibility and the reproducibility of this technique.