Enrica Bentivegna

Prospective Multicenter Study Evaluating the Survival of Patients With Locally Advanced Cervical Cancer Undergoing Laparoscopic Para-Aortic Lymphadenectomy Before Chemoradiotherapy in the Era of Positron Emission Tomography Imaging

PURPOSE The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. RESULTS Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). CONCLUSION To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.

Oncological outcomes after fertility-sparing surgery for cervical cancer: a systematic review

Fertility preservation in young patients with cervical cancer is suitable only for patients with good prognostic factors and disease amenable to surgery without adjuvant therapy. Consequently, it is only offered to patients with early-stage disease (stage IB tumours <4 cm), negative nodes, and non-aggressive histological subtypes. To determine whether fertility preservation is suitable, the first step is pelvic-node dissection to establish nodal spread. Tumour size (≤2 cm vs >2 cm) and lymphovascular space invasion status are two main factors to determine the best fertility-sparing surgical technique. In this systematic Review, we assess six different techniques that are available to preserve fertility (Dargents procedure, simple trachelectomy or cone resection, neoadjuvant chemotherapy with conservative surgery, and laparotomic, laparoscopic and robot-assisted abdominal radical trachelectomy). The choice between the six different fertility preservation techniques should be based on the experience of the team, discussion with the patient or couple, and, above all, objective oncological data to balance the best chance for cure with optimum fertility results for each procedure.

Neutrophilia in locally advanced cervical cancer: A novel biomarker for image-guided adaptive brachytherapy?

Objective To study the prognostic value of leucocyte disorders in a prospective cohort of cervical cancer patients receiving definitive chemoradiation plus image—guided adaptive brachytherapy (IGABT). Results 113 patients were identified. All patients received a pelvic irradiation concomitant with chemotherapy, extended to the para-aortic area in 13 patients with IVB disease. Neutrophilia and leukocytosis were significant univariate prognostic factors for poorer local failure-free survival (p = 0.000 and p = 0.002, respectively), associated with tumor size, high-risk clinical target volume (HR-CTV) and anemia. No effect was shown for distant metastases but leukocytosis and neutrophila were both poor prognostic factors for in-field relapses (p = 0.003 and p < 0.001). In multivariate analysis, HR-CTV volume (p = 0.026) and neutrophils count > 7,500/μl (p = 0.018) were independent factors for poorer survival without local failure, with hazard ratio (HR) of 3.1. Materials and methods We examined patients treated in our Institution between April 2009 and July 2015 by concurrent chemoradiation (45 Gy in 25 fractions +/− lymph node boosts) followed by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate brachytherapy (15 Gy to the intermediate-risk clinical target volume). The prognostic value of pretreatment leucocyte disorders was examined. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10,000 and 7,500/μl, respectively. Conclusions Neutrophilia is a significant prognostic factor for local relapse in locally advanced cervical cancer treated with MRI-based IGABT. This biomarker could help identifying patients with higher risk of local relapse and requiring dose escalation.

Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients

OBJECTIVE To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. DESIGN Retrospective multicenter study. SETTING Teams having reported recurrence after FSS for EOC. PATIENT(S) Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. INTERVENTION(S) FSS (salpingo-oophorectomy for a majority of cases) for EOC. MAIN OUTCOMES MEASURE(S) Recurrences rates and characteristics of recurrent disease. RESULT(S) Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). CONCLUSION(S) The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences.

A New Single-Port Approach to Perform a Transperitoneal Step and an Extraperitoneal Para-Aortic Lymphadenectomy with a Single Incision

Chemoradiation therapy (CRT), a combination of external beam irradiation and brachytherapy with concurrent chemotherapy, is considered the standard treatment for bulky cervical cancer ( stage IB2 according to the International Federation of Gynecology and Obstetrics [FIGO] classification) by many North American and Western European teams. The incidence of para-aortic (PA) nodal metastasis n these tumors ranges from 10% to 25%. Positron emission tomography (PET) with or without CT imaging is the most accurate imaging modality for evaluating extrapelvic disease in locally advanced cervical cancer (LACC), When PA nodes are known to be metastatic, the radiation field is extended from the pelvis to include the PA area. However, the rate of false negatives at PET-CT assessment of PA metastasis in LACC is 12%, increasing to 22% if PET-CT reveals pelvic lymph nodes with suspicious metastases. The concept of surgical staging has gained momenum with the development of laparoscopy, which reduces urgical complications. Since January 2011, this surgical taging procedure has been performed more often in our nstitution using a single-port extraperitoneal approach, hich was previously described by our team. We have efined this procedure and developed a “real” single-port pproach avoiding a second transumbilical port (to explore he peritoneum), which was used in the first procedure. We eport in this series a new procedure for performing these wo steps via a single access with only one incision.

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.

Gliomatosis peritonei: a particular entity with specific outcomes within the growing teratoma syndrome.

Objectives Ovarian immature teratoma may be associated with peritoneal spread that could, after adjuvant chemotherapy, develop into disease exclusively composed of mature implants (growing teratoma syndrome) and/or gliomatosis peritonei (GP), defined as the presence of pure mature glial tissue. However, very few specific series are devoted to the outcomes of pure GP. This was the aim of the present study. Patients From 1997 to 2013, data concerning patients treated for stage II/III immature teratoma were reviewed. All slides were reviewed by an expert pathologist. Patients with ovarian cancer associated with peritoneal spread in the form of pure GP (initially if patients were treated without adjuvant treatment or after adjuvant chemotherapy if done) were analyzed. Results Ten patients fulfilled the inclusion criteria. The median age of patients at diagnosis was 36 years (range, 14–41 years). Six patients had undergone a conservative treatment. Five patients had macroscopic residual disease at the end of surgery. The median duration of follow-up from the diagnosis of GP was 39 months (range, 6–114 months). Six patients had undergone secondary surgery. Among them, 5 had incompletely resected macroscopic GP. No patients had died of their disease. All patients were asymptomatic at the time of the last consultation (1 of them with abnormal radiologic imaging). Conclusions Gliomatosis peritonei is a particular entity of the condition described as growing teratoma syndrome because residual peritoneal disease can be asymptomatic totally stable over a long period which raises the question of a more conservative surgical approach in patients with massive peritoneal spread.

Fertility-sparing surgery in epithelial ovarian cancer

Since the last two decades, the feasibility of fertility-sparing surgery in early-stage epithelial ovarian cancer has been explored by several teams. Despite the impossibility of conducting a randomized trial to validate this management, evidence-based data suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. Conservative surgery maintains organ function, enables patients of childbearing age to preserve their fertility and improves their quality of life. In this review, we analyze the main series in the literature on this topic in order to highlight the selected criteria for conservative management and to summarize oncological and fertility outcomes.

Outcome of patients with advanced-stage borderline ovarian tumors after a first peritoneal noninvasive recurrence: impact on further management.

Objectives The aims of this study were to report the outcome of patients with advanced-stage serous borderline ovarian tumors (SBOT) after a first noninvasive recurrence and the impact of conservative treatment in that context and to define the best management for those patients. Study Design From 1973 to 2006, 168 patients were treated at or referred to our institution for an SBOT with peritoneal implants. Their slides were reviewed by the same expert pathologist. Selection criteria were as follows: advanced stage (International Federation of Gynecology and Obstetrics ≥II), with at least 1 recurrence (only noninvasive ones) and more than 5 years of follow-up. Results Twenty patients met the inclusion criteria. The median duration of follow-up was 12 years (range, 6–23 years). Median age was 26 years (14–61 years). Initial surgical management was conservative for 14 patients and radical for 6. In the study population, 4 patients recurred, all with invasive disease. Time to invasive recurrence was at least 3 years for 3 of 4 patients. None of those 4 patients had a second-look surgery initially or after the first recurrence. Two patients had small-sized residual disease after initial management; only 1 of these 4 patients is currently alive and disease-free. There was no significant difference between conservative and radical treatment of the risk of second recurrence. Conclusions This study emphasizes the need for a long follow-up after recurrence of advanced-stage SBOT and the risk of a new invasive recurrence after a first noninvasive peritoneal recurrence. Conservative treatment does not seem as a risk factor and is still justified after a first noninvasive recurrence for young patients who desire to preserve fertility.

Preoperative image-guided brachytherapy in early stage cervical cancers

OBJECTIVE To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. MATERIALS/METHODS We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6-8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/- para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. RESULTS 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity (p=0.02). CONCLUSIONS A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.