Research Interests

DQDenis Querleu
Papers(12)
Comparison of SPECT-C…Robotic-assisted vers…Therapeutic role of p…ESGO/ESTRO/ESP guidel…Factors associated wi…Assessing minimally i…External beam radioth…Adherence to European…Effect of tumor burde…Response to: Correspo…ESGO/ISUOG/IOTA/ESGE …<scp>ESGO</scp>/<scp>…
Collaborators(10)
Nicolò BizzarriLuis ChivaGiovanni ScambiaChristina FotopoulouIgnacio ZapardielFrancesco FanfaniNicole ConcinDirk TimmermanDavid CibulaEnrique Chacon
Institutions(8)
Agostino Gemelli Univ…Clinica Universidad d…Imperial College Lond…Hospital Universitari…Medical University of…KU Leuven AssociationCharles University an…Universidad De Navarra

Papers

Robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese)

Nearly 65% of patients with endometrial cancer who undergo primary hysterectomy have concurrent obesity. Retrospective data show advantages in using robotic surgery in these patients compared with conventional laparoscopy, namely lower conversion rate, increased rate of same-day discharge, and reduced blood loss. Nevertheless, to date no prospective randomized controlled trials have compared laparoscopic surgery versus robotic-assisted surgery in morbidly obese patients. The robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese) trial aims to find the most appropriate minimally invasive surgical approach in morbidly obese patients with endometrial carcinoma. Robotic surgery will reduce conversions to laparotomy in endometrial cancer patients with obesity compared with those who undergo surgery with conventional laparoscopy. This phase III multi-institutional study will randomize consecutive obese women with apparent early-stage endometrial cancer to either laparoscopic or robot-assisted surgery. The RObese trial will include obese (BMI≥30 kg/m Conversion rate to laparotomy between laparoscopic surgery versus robot-assisted surgery. RObese is a superiority trial. The clinical superiority margin for this study is defined as a difference in conversion rate of -6%. Assuming a significance level of 0.05 and a power of 80%, the study plans to randomize 566 patients. Patient recruitment will be completed by 2026, and follow-up will be completed by 2029 with presentation of data shortly thereafter. Two interim analyses are planned: one after the first 188 and the second after 376 randomized patients. NCT05974995.

Therapeutic role of para-aortic lymphadenectomy in patients with intermediate- and high-risk endometrial cancer: a systematic review and meta-analysis

Lymph nodal involvement is a prognostic factor in endometrial cancer. The added value of para-aortic lymphadenectomy compared with pelvic nodal evaluation alone remains a matter of debate in the management of patients with intermediate- and high-risk endometrial cancer. A systematic review and meta-analysis was conducted to assess the prognostic value of para-aortic lymphadenectomy in terms of overall survival and disease-free survival in patients with intermediate- and high-risk endometrial cancer. The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched from January 2000 to April 2023. Studies on intermediate- and high-risk patients who underwent pelvic versus pelvic and para-aortic dissection were included in the analysis. The Methodological Index for Nonrandomized Studies (MINORS) and the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) were used for quality assessment of the selected articles. Fourteen studies were identified, encompassing 9415 patients with a median age of 62 years (IQR 56.5-66.5). The majority had International Federation of Gynecology and Obstetrics stage I-II disease (76%) and endometrioid histology (89%). The 72% of patients who underwent only pelvic nodal evaluation and the 87% who underwent pelvic and para-aortic lymphadenectomy received adjuvant treatment (p=0.44). Pelvic and para-aortic lymphadenectomy was associated with a significant improvement in 5-year overall survival (RR=0.71, 95% CI 0.57 to 0.88, p<0.01), translating to a 41% reduction in the risk of overall death. However, no significant differences were observed in the 5-year risk of recurrence (RR=1.12, 95% CI 0.94 to 1.34, p=0.15). Additionally, patients undergoing pelvic and para-aortic lymphadenectomy experienced a 26% increased risk of post-operative complications (RR=1.26, 95% CI 1.04 to 1.53, p=0.03) and prolonged operative times (MD=56.27, 95% CI 15.94 to 96.60, p<0.01). Pelvic and para-aortic lymphadenectomy appears to confer a prognostic benefit in patients with intermediate- and high-risk endometrial cancer. Robust prospective studies are needed to further validate these findings and elucidate the precise role of para-aortic lymphadenectomy in the optimal management of these patients.

Factors associated with bilateral sentinel lymph node mapping failure using indocyanine green in patients with apparent early-stage cervical cancer: An Italian retrospective multi-center study

The primary aim of this study was to assess the factors associated with bilateral mapping failure in patients with apparent early-stage cervical cancer undergoing sentinel lymph node (SLN) biopsy using indocyanine green (ICG). Secondary aims were sensitivity, negative predictive value and lymph node recurrence. Retrospective multi-center study. Patients with cervical cancer apparent FIGO stage IA1 to IIA2, treated with primary surgery between 04/2015 and 12/2023 and undergoing SLN mapping attempt with ICG injection, were included. Appropriate statistical analysis was performed to assess study endpoints. Timeframe was divided in first period 04/2015-12/2019 and second period 01/2020-12/2023. 618 patients were included. Bilateral SLN mapping was achieved in 531 (85.9 %) women (36 of them, 5.8 %, underwent cervical re-injection of ICG). SLN unilateral mapping and mapping failure was observed in 71 (11.5 %) and 16 (2.6 %), respectively. The sensitivity, negative predictive value and accuracy were 85.9 %, 98.1 % and 98.3 %, respectively. False negative rate was 4/68 (5.9 %) in patients with unilateral mapping versus 6/316 (1.9 %) in those with bilateral mapping (p = 0.061). BMI>30 (p = 0.001) and pathologic tumor diameter >20 mm (p = 0.023) were the only factors independently associated with bilateral SLN mapping failure. ICG re-injection increased the rate of bilateral SLN detection from 81.3 % to 85.9 %. The rate of bilateral detection was 82.8 % versus 88.3 % in the first versus second study period, respectively (p = 0.061). 3-year DFS and OS in all patients were 89.7 % and 98.2 %, respectively. Seven patients (1.2 %) had lymph node recurrence in the group of any SLN mapping versus 1 (6.3 %) in no mapping group (p = 0.190). High BMI and larger tumors were associated with bilateral SLN mapping failure using ICG. The ICG cervical re-injection increased the rate of bilateral mapping. No lymph node recurrence difference was found in patients undergoing SLN mapping versus patients with mapping failure.

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis

We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.

Adherence to European ovarian cancer guidelines and impact on survival: a French multicenter study (FRANCOGYN)

The primary objective of the study was to validate the European Society for Medical Oncology (ESMO)-European Society of Gynecologic Oncology (ESGO) ovarian cancer guideline as a method of assessing quality of care, and to identify patient characteristics predictive of non-adherence to European guideline care. The secondary objectives were to analyze the evolution of practices over the years and to evaluate heterogeneity between centers. This retrospective multicenter cohort study of invasive epithelial ovarian cancer reported to the FRANCOGYN database included data from 12 French centers between January 2000 and February 2017. The main outcome was adherence to ESMO-ESGO guidelines, defined by recommended surgical procedures according to the International Federation of Gynecology and Obstetrics (FIGO) stage and appropriate chemotherapy. Mixed multivariable logistic regression analysis with a random center effect was performed to estimate the probability of adherence to the guidelines. Survival analysis was carried out using the Kaplan-Meier method and a mixed Cox proportional hazards model. 1463 patients were included in the study. Overall, 317 (30%) patients received complete guideline adherent care. Patients received appropriate surgical treatment in 69% of cases, while adequate chemotherapy was administered to 44% of patients. Both patient demographics and disease characteristics were significantly associated with the likelihood of receiving guideline adherent care, such as age, performance status, FIGO stage, and initial burden of disease. In univariate and multivariate survival analysis, adherence to the guidelines was a statistically significant and independent predictor of decreased overall survival. Patients receiving suboptimal care experienced an increased risk of death of more than 100% compared with those treated according to the guidelines (hazard ratio 2.14, 95% confidence interval 1.32 to 3.47, p<0.01). In both models, a significant random center effect was observed, confirming the heterogeneity between centers (p<0.001). Adherence to ESMO-ESGO guidelines in ovarian cancer was associated with a higher overall survival and may be a useful method of assessing quality of care.

Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer

We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC-IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3-4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors

ABSTRACTThe European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence‐based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models.ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence‐based, the current literature was reviewed and critically appraised.Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements.This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

SUCCOR cone study: conization before radical hysterectomy

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Radiomics systematic review in cervical cancer: gynecological oncologists’ perspective

Radiomics is the process of extracting quantitative features from radiological images, and represents a relatively new field in gynecological cancers. Cervical cancer has been the most studied gynecological tumor for what concerns radiomics analysis. The aim of this study was to report on the clinical applications of radiomics combined and/or compared with clinical-pathological variables in patients with cervical cancer. A systematic review of the literature from inception to February 2023 was performed, including studies on cervical cancer analysing a predictive/prognostic radiomics model, which was combined and/or compared with a radiological or a clinical-pathological model. A total of 57 of 334 (17.1%) screened studies met inclusion criteria. The majority of studies used magnetic resonance imaging (MRI), but positron emission tomography (PET)/computed tomography (CT) scan, CT scan, and ultrasound scan also underwent radiomics analysis. In apparent early-stage disease, the majority of studies (16/27, 59.3%) analysed the role of radiomics signature in predicting lymph node metastasis; six (22.2%) investigated the prediction of radiomics to detect lymphovascular space involvement, one (3.7%) investigated depth of stromal infiltration, and one investigated (3.7%) parametrial infiltration. Survival prediction was evaluated both in early-stage and locally advanced settings. No study focused on the application of radiomics in metastatic or recurrent disease. Radiomics signatures were predictive of pathological and oncological outcomes, particularly if combined with clinical variables. These may be integrated in a model using different clinical-pathological and translational characteristics, with the aim to tailor and personalize the treatment of each patient with cervical cancer.

Pelvic exenteration for vulvar cancer: contemporary outcomes from a multinational cohort study

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Clinical Trials (7)

18Papers
83Collaborators
7Trials
Uterine Cervical NeoplasmsOvarian NeoplasmsNeoplasm StagingNeoplasm Recurrence, LocalCarcinoma in SituPaget Disease, Extramammary