Publications by authors named "Frédéric Marchal"

89 Publications

[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients].

Gynecol Obstet Fertil Senol 2021 Sep 22. Epub 2021 Sep 22.

Université de Bordeaux, Bordeaux Population Health (U1219), Equipe Méthodes pour la Recherche Interventionnelle en Santé des Populations (MéRISP), France.

Introduction: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions "(ABL). Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process.

Methods: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care.

Results: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, p<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%).

Conclusion: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.
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http://dx.doi.org/10.1016/j.gofs.2021.09.010DOI Listing
September 2021

Response of Controlled Cell Load Biofilms to Cold Atmospheric Plasma Jet: Evidence of Extracellular Matrix Contribution.

Life (Basel) 2021 Jul 15;11(7). Epub 2021 Jul 15.

UPS, IUT "A", LBAE EA 4565 (Laboratoire de Biotechnologies Agroalimentaire et Environnementale), Université de Toulouse, IUT Site d'AUCH, 24 rue d'Embaquès, F-32000 Auch, France.

Aim: Study of the biocidal effect of a cold atmospheric-pressure plasma in ambient air on single-species bacterial biofilms with controlled cell density, characterized by different extracellular matrices.

Methods And Results: Two bacterial strains were chosen to present different Gram properties and contrasted extracellular matrices: ATCC 15442 (Gram-negative), and NRRL B-1299 (Gram-positive). biofilm exhibits a complex matrix, rich in proteins while presents the specificity to produce glucan-type exopolysaccharides when grown in the presence of sucrose. Plasma was applied on both surface-spread cells and 24-h grown biofilms with controlled cell loads over 5, 10, or 20 min. Surface-spread bacteria showed a time dependent response, with a maximal bacterial reduction of 2.5 log after 20 min of treatment. On the other hand, in our experimental conditions, no bactericidal effect could be observed when treating biofilms of and glucan-rich .

Conclusions: For biofilms presenting equivalent cell loads, the response to plasma treatment seemed to depend on the properties of the extracellular matrix characterized by infrared spectroscopy, scanning electron microscopy, or dry weight.

Significance And Impact Of Study: Both cell load standardization and biofilm characterization are paramount factors to consider the biocide effect of plasma treatments. The extracellular matrix could affect the plasma efficacy by physical and/or chemical protective effects.
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http://dx.doi.org/10.3390/life11070694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304013PMC
July 2021

Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database.

Gynecol Oncol 2021 Jul 19. Epub 2021 Jul 19.

Aix-Marseille Univ., CNRS, INSERM, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, Marseille, France. Electronic address:

Background: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes.

Methods: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features.

Results: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001).

Conclusions: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.019DOI Listing
July 2021

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

Clin Cancer Res 2021 Jun 9. Epub 2021 Jun 9.

Service de Biopathologie, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France.

Purpose: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas.

Experimental Design: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method.

Results: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA.

Conclusions: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers..
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0293DOI Listing
June 2021

Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial.

Lancet Oncol 2021 05 13;22(5):702-715. Epub 2021 Apr 13.

Hôpital Nord Franche-Comté, Montbéliard, France; University Hospital of Besançon, Besançon, France.

Background: Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences.

Methods: We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Eligible patients were adults aged 18-75 years and had newly diagnosed, biopsy-proven, rectal adenocarcinoma staged cT3 or cT4 M0, with a WHO performance status of 0-1. Patients were randomly assigned (1:1) to either the neoadjuvant chemotherapy group or standard-of-care group, using an independent web-based system by minimisation method stratified by centre, extramural extension of the tumour into perirectal fat according to MRI, tumour location, and stage. Investigators and participants were not masked to treatment allocation. The neoadjuvant chemotherapy group received neoadjuvant chemotherapy with FOLFIRINOX (oxaliplatin 85 mg/m, irinotecan 180 mg/m, leucovorin 400 mg/m, and fluorouracil 2400 mg/m intravenously every 14 days for 6 cycles), chemoradiotherapy (50 Gy during 5 weeks and 800 mg/m concurrent oral capecitabine twice daily for 5 days per week), total mesorectal excision, and adjuvant chemotherapy (3 months of modified FOLFOX6 [intravenous oxaliplatin 85 mg/m and leucovorin 400 mg/m, followed by intravenous 400 mg/m fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m over 46 h every 14 days for six cycles] or capecitabine [1250 mg/m orally twice daily on days 1-14 every 21 days]). The standard-of-care group received chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (for 6 months). The primary endpoint was disease-free survival assessed in the intention-to-treat population at 3 years. Safety analyses were done on treated patients. This trial was registered with EudraCT (2011-004406-25) and ClinicalTrials.gov (NCT01804790) and is now complete.

Findings: Between June 5, 2012, and June 26, 2017, 461 patients were randomly assigned to either the neoadjuvant chemotherapy group (n=231) or the standard-of-care group (n=230). At a median follow-up of 46·5 months (IQR 35·4-61·6), 3-year disease-free survival rates were 76% (95% CI 69-81) in the neoadjuvant chemotherapy group and 69% (62-74) in the standard-of-care group (stratified hazard ratio 0·69, 95% CI 0·49-0·97; p=0·034). During neoadjuvant chemotherapy, the most common grade 3-4 adverse events were neutropenia (38 [17%] of 225 patients) and diarrhoea (25 [11%] of 226). During chemoradiotherapy, the most common grade 3-4 adverse event was lymphopenia (59 [28%] of 212 in the neoadjuvant chemotherapy group vs 67 [30%] of 226 patients in the standard-of-care group). During adjuvant chemotherapy, the most common grade 3-4 adverse events were lymphopenia (18 [11%] of 161 in the neoadjuvant chemotherapy group vs 42 [27%] of 155 in the standard-of-care group), neutropenia (nine [6%] of 161 vs 28 [18%] of 155), and peripheral sensory neuropathy (19 [12%] of 162 vs 32 [21%] of 155). Serious adverse events occurred in 63 (27%) of 231 participants in the neoadjuvant chemotherapy group and 50 (22%) of 230 patients in the standard-of-care group (p=0·167), during the whole treatment period. During adjuvant therapy, serious adverse events occurred in 18 (11%) of 163 participants in the neoadjuvant chemotherapy group and 36 (23%) of 158 patients in the standard-of-care group (p=0·0049). Treatment-related deaths occurred in one (<1%) of 226 patients in the neoadjuvant chemotherapy group (sudden death) and two (1%) of 227 patients in the standard-of-care group (one sudden death and one myocardial infarction).

Interpretation: Intensification of chemotherapy using FOLFIRINOX before preoperative chemoradiotherapy significantly improved outcomes compared with preoperative chemoradiotherapy in patients with cT3 or cT4 M0 rectal cancer. The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the decreased neurotoxicity indicates that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy. Therefore, the PRODIGE 23 results might change clinical practice.

Funding: Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer.
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http://dx.doi.org/10.1016/S1470-2045(21)00079-6DOI Listing
May 2021

Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort.

Ann Surg 2021 Feb 1. Epub 2021 Feb 1.

Department of Surgical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, 6 Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France Department of Surgical Oncology, Institut Godinot, 1 Rue du Général Koenig, 51100 Reims, France Department of Biostatistics, Institut Claudius Regaud - IUCT Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France Department of Medical Oncology, Institut de Cancérologie de l'Ouest Nantes & Angers, 15 rue André Boquel, 49055 Angers, France Department of Medical Oncology, Centre François Baclesse, 3 Avenue du Général Harris, 14000 Caen, France Department of Plastic and Reconstructive Surgery, Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France Medical Oncology Department, Centre Oscar Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France Department of Medical Oncology, Institut Bergonie, 229 Cours de l'Argonne, F-33000 Bordeaux, France Department of Surgical Oncology, Institut du Cancer de Montpellier, 208 Rue des Apothicaires, 34298 Montpellier, France Department of Medical Oncology, Centre Henri Becquerel, Rue d'Amiens, 76000 Rouen, France Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte-Marguerite, 13009 Marseille Department of Surgical Oncology, Centre Georges François Leclerc, 1 rue Professeur Marion, 21079 Dijon, France Department of Surgical Oncology, Centre Eugène Marquis, Avenue de la Bataille Flandres-Dunkerque, 35000 Rennes, France Department of Medical Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008 Lyon, France Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue de Valambrose, 06189 Nice, France Department of Medical Oncology, Institut Godinot, 1 Rue du Général Koenig, 51100 Reims, France Department of Medical Oncology, Centre Paul Strauss, 3 Rue de la Porte de l'Hôpital, 67000 Strasbourg, France Department of Medical Oncology, Institut Curie, 26 Rue d'Ulm, 75005 Paris & Saint-Cloud, France Department of Medical Oncology, Institut de Cancérologie de l'Ouest - René Gauducheau, Boulevard Professeur Jacques Monod, 44805 Nantes, France Department of Research and Development, R&D Unicancer, 101 Rue de Tolbiac, 75654 Paris, France Department of Medical Oncology, Institut Claudius Regaud - IUCT Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France.

Objective: The aim was to evaluate the impact of local surgery performed during the year following metastatic breast cancer (MBC) diagnosis on patients' outcomes from a large real-life cohort.

Summary Background Data: Locoregional treatment for patients with MBC at the time of diagnosis remains debated.

Methods: Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis.

Results: Out of 16,703 patients in the ESME database, 1,977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, p < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, p < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, p < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61 - 0.92] and 0.72 [0.63 - 0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype and age.

Conclusions: In the large ESME cohort, surgery within one year after de novo MBC diagnosis was associated with a significantly better OS and PFS.
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http://dx.doi.org/10.1097/SLA.0000000000004767DOI Listing
February 2021

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

Lancet Oncol 2021 02 18;22(2):256-266. Epub 2021 Jan 18.

Department of Digestive Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.

Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.

Methods: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m) or open (460 mg/m) abdomen techniques, and systemic chemotherapy (400 mg/m fluorouracil and 20 mg/m folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed.

Findings: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).

Interpretation: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.

Funding: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.
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http://dx.doi.org/10.1016/S1470-2045(20)30599-4DOI Listing
February 2021

NIR Imaging of the Integrin-Rich Head and Neck Squamous Cell Carcinoma Using Ternary Copper Indium Selenide/Zinc Sulfide-Based Quantum Dots.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 Dec 11.

Research Department, Institut de Cancérologie de Lorraine, Université de Lorraine, CNRS UMR7039 CRAN, 6 avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.

The efficient intraoperative identification of cancers requires the development of the bright, minimally-toxic, tumor-specific near-infrared (NIR) probes as contrast agents. Luminescent semiconductor quantum dots (QDs) offer several unique advantages for in vivo cellular imaging by providing bright and photostable fluorescent probes. Here, we present the synthesis of ZnCuInSe/ZnS core/shell QDs emitting in NIR (~750 nm) conjugated to NAVPNLRGDLQVLAQKVART (A20FMDV2) peptide for targeting integrin-rich head and neck squamous cell carcinoma (HNSCC). Integrin is usually not detectable in nonpathological tissues, but is highly upregulated in HNSCC. QD-A20 showed integrin-specific binding in two-dimension (2D) monolayer and three-dimension (3D) spheroid in vitro HNSCC models. QD-A20 exhibit limited penetration (ca. 50 µm) in stroma-rich 3D spheroids. Finally, we demonstrated the potential of these QDs by time-gated fluorescence imaging of stroma-rich 3D spheroids placed onto mm-thick tissue slices to mimic imaging conditions in tissues. Overall, QD-A20 could be considered as highly promising nanoprobes for NIR bioimaging and imaging-guided surgery.
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http://dx.doi.org/10.3390/cancers12123727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764319PMC
December 2020

Evaluation of Pre-Therapeutic Assessment in Endometrial Cancer Staging.

Diagnostics (Basel) 2020 Dec 4;10(12). Epub 2020 Dec 4.

Surgery Department, Institut de Cancérologie de Lorraine, 6, Avenue de Bourgogne, 54519 Vandoeuvre-les-Nancy, France.

Objective: The aim of this retrospective cohort study is to evaluate the concordance between the preoperative MRI and histology data with the final histopathological examination.

Method: This is a retrospective observational study of 183 patients operated for endometrioid cancer between January 2009 and December 2019 in the surgical oncology department of the Lorraine Cancer Institute (ICL) in Vandœuvre-lès-Nancy. The patients included are all women operated on for endometrioid-type endometrial cancer over this period. The exclusion criteria are patients for whom the pre-therapy check-up does not include pelvic MRI and those who have not had first-line surgery. The final anatomopathological results were compared with preoperative imaging data and with endometrial biopsy data.

Results: For the myometrial infiltration, the sensitivity of MRI was of 37% and the specificity of 54%. To detect nodal metastases, the sensitivity of MRI was of 21% and the specificity of 93%. We observed an under estimation of the FIGO classification ( = 0.001) with the MRI in 42.7% of cases (n = 76) and an overestimation in 24.2% of cases (n = 43). There was a concordance in 33.1% of cases (n = 59). We had a poor agreement between the MRI and final histopathological examination with an adjusted kappa (κ) of 0.12 [95% IC (0.02; 0.24)]. There was a moderate concordance on the grade between the pretherapeutic biopsy and the final histopathological examination on excised tissue with an adjusted kappa of 0.52 [95% IC 0.42-0.62)]. Endometrial biopsy underestimated the tumor grade in 28.9% of cases (n = 50) ( < 0.001), overestimated the tumor grade in 6.9% of cases (n = 12) and we observed a concordance in 64.2% of cases (n = 111).

Conclusion: The pre-operative assessment of endometrial cancer is inconsistent with the results obtained on final histopathological examination. A study with a systematic review should be done to assess the performance of MRI, only in expert centers, in order to consider a a specific care management for endometrial cancer patients: patients who have had an MRI in an outpatient center should have their imaging systematically reviewed, with the possibility of a new examination in case of incomplete sequences, by expert radiologists, and discussed in multidisciplinary concertation meeting in expert centers, before any therapeutic decision. The sentinel node biopsy must be used for low and intermediate risk endometrial cancer.
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http://dx.doi.org/10.3390/diagnostics10121045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761973PMC
December 2020

External Validation of the SERC Trial Population: Comparison with the Multicenter French Cohort, the Swedish and SENOMIC Trial Populations for Breast Cancer Patients with Sentinel Node Micro-Metastasis.

Cancers (Basel) 2020 10 11;12(10). Epub 2020 Oct 11.

Department of Surgical Oncology, Institut Paoli Calmettes & CRCM & Aix Marseille Univ, 232 Bd de Sainte Marguerite, 13009 Marseille, France.

Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively ( = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations.
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http://dx.doi.org/10.3390/cancers12102924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600229PMC
October 2020

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

Ann Surg Oncol 2021 Apr 12;28(4):2138-2145. Epub 2020 Sep 12.

Gustave Roussy, Villejuif, France.

Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.

- Methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.

Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.

Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.

Clinical Trial Registration: NCT02523612.
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http://dx.doi.org/10.1245/s10434-020-09107-zDOI Listing
April 2021

Pre-operative axillary ultrasound with fine-needle aspiration cytology performance and predictive factors of false negatives in axillary lymph node involvement in early breast cancer.

Breast Cancer Res Treat 2020 Oct 31;183(3):639-647. Epub 2020 Jul 31.

Institut de Cancérologie de Lorraine, Department of Surgical Oncology, Université de Lorraine, 54519, Vandoeuvre-lès-Nancy, France.

Purpose: Breast cancer is the most common cancer among females worldwide. Axillary lymph node involvement is an important prognostic factor in pre-operative evaluation. The aim of this study was to evaluate the sensitivity and accuracy of AUS during the initial breast cancer diagnosis and the contribution of ultrasound with guided FNAC (AUS + FNAC) in cases of suspicious node.

Methods: A retrospective study was conducted at the Lorraine Cancer Institute between 1 January and 31 December 2015. It included patients with early breast cancer, all of whom received AUS. If axillary node involvement was suspected, FNAC was performed. Sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) were performed depending on FNAC results.

Results: In total, 292 patients were included. 88 patients (30.1%) had a suspicious lymph node on ultrasound and had FNAC, of whom 53 tested positive for axillary node involvement (60.2%). Among the 35 patients who tested negative with FNAC, 15 had axillary metastatic involvement. Performance of AUS + FNAC was better than that of AUS alone, with sensitivity, specificity, positive predictive and negative predictive values of approximately 44.5%, 100%, 100% and 72.4%, respectively, and accuracy of approximately 77.4%. Luminal A subgroup, axillary involvement of less than two positive nodes or nodal tumor of less than 7 mm are independent factors of false negative rate.

Conclusions: AUS performance would seem to be improved by FNAC, with a false negative rate of approximately 26%. It may be possible to reduce the false negative rate of AUS if its contributing factors are taken into consideration, along with the impact of specific echographic signs as revealed by experienced radiologists.
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http://dx.doi.org/10.1007/s10549-020-05830-zDOI Listing
October 2020

Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.

Lancet Oncol 2020 09 24;21(9):1147-1154. Epub 2020 Jul 24.

Department of Surgical Oncology, University Hospital Gustave Roussy, Villejuif, France.

Background: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases.

Methods: We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m, or oxaliplatin 300 mg/m plus irinotecan 200 mg/m, plus intravenous fluorouracil 400 mg/m), or mitomycin-HIPEC (mitomycin 35 mg/m) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394.

Findings: Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0-54·8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61-1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients.

Interpretation: Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes.

Funding: French National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(20)30322-3DOI Listing
September 2020

Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial.

Gynecol Oncol 2020 08 25;158(2):382-389. Epub 2020 May 25.

Institut Paoli Calmettes Cancer Center, Marseille, France.

Objective: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence.

Methods: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery).

Results: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75-432) minutes and for CL was 145 (33-407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0-2500) and 50 (0-1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6-78.2), no significant differences in overall and disease-free survival were observed between the groups.

Conclusions: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.
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http://dx.doi.org/10.1016/j.ygyno.2020.05.010DOI Listing
August 2020

Quality of life, anxiety, and postoperative complications of patients undergoing breast cancer surgery as ambulatory surgery compared to non-ambulatory surgery: A prospective non-randomized study.

J Gynecol Obstet Hum Reprod 2021 Feb 11;50(2):101779. Epub 2020 May 11.

Département de Chirurgie, Institut de Cancérologie de Lorraine, Université de Lorraine Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France; CRAN, UMR 7039, Université de Lorraine, CNRS Vandœuvre-lès-Nancy, France.

Purpose: According to the latest recommendations a minimally invasive approach should be used to manage breast cancer and a global policy for minimizing costs encourages shorter periods of hospitalization. The aim of this study was to investigate the impact of length of hospitalization on quality of life, anxiety and depression and postoperative complications.

Methods: This is a prospective observational study of 412 female patients with breast cancer requiring a first mastectomy or lumpectomy to assess the impact of the length of hospitalization on quality of life (using the European Organization for Research and Treatment of Cancer Quality of Life QLQ30 and BR23 questionnaires) at postoperative day 14 (D+14), levels of anxiety at d-1 and D+1 (according to the Hospital Anxiety and Depression scale) and postoperative state at D+21.

Results: Our study included 244 patients that had ambulatory surgery and 124 that had non-ambulatory surgery. Global health status was significantly better for ambulatory surgery patients (adjusted p-value=0.014). There were no significant differences between the two groups for levels of anxiety, pain, lymphoceles and postoperative complications. No cases of nausea and vomiting requiring medical treatment were reported for either group.

Conclusions: Breast cancer surgery can be performed using ambulatory surgery with no significant differences compared to non-ambulatory surgery in terms of quality of life, perioperative anxiety, and postoperative complications. Indeed, our study suggests that ambulatory surgery improves patient outcome. It should be determined whether the mode of hospitalization has any long-term impact on the patient, as a shorter hospitalization period would allow decreasing waiting times.
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http://dx.doi.org/10.1016/j.jogoh.2020.101779DOI Listing
February 2021

Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial.

Lancet Gastroenterol Hepatol 2020 05 7;5(5):465-474. Epub 2020 Feb 7.

Department of Colorectal Surgery, Haut-Lévèque Hospital, CHU Bordeaux, France.

Background: GRECCAR 2 was the first multicentre, randomised trial to compare local excision with total mesorectal excision in downstaged low rectal cancer. Encouraging oncological results were noted at 3 years' follow-up but needed to be corroborated with longer follow-up. In this study, we aimed to report the 5-year oncological outcomes, including local recurrence, metastatic disease, and survival.

Methods: Patients age 18 years and older with T2T3 low rectal cancer, of maximum size 4 cm, who were clinically good responders after chemoradiotherapy (residual tumour ≤2 cm) were randomly assigned before surgery to either local excision or total mesorectal excision. Randomisation was centralised and not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was performed if pathological tumour stage was ypT2-3. The primary objective of this study was to assess the 5-year oncological outcomes of local recurrence, metastatic disease, disease-free survival, overall survival, and cancer-specific mortality, which were the secondary endpoints of GRECCAR 2. We used Kaplan-Meier estimates and Cox modelling to estimate and compare recurrence and survival in modified intention-to-treat and as-treated populations. This trial was registered with ClinicalTrials.gov, number NCT00427375.

Findings: Between March 1, 2007, and Sept 24, 2012, 148 patients who were good clinical responders were randomly assigned to treatment, three patients were excluded after randomisation (because they had metastatic disease, tumour >8 cm from anal verge, or withdrew consent), leaving 145 for analysis: 74 in the local excision group and 71 in the total mesorectal excision group. Median follow-up was 60 months (IQR 58-60) in the local excision group and 60 months (57-60) in the total mesorectal excision group. 23 patients died and five were lost to follow-up. In the local excision group, 26 had a completion total mesorectal excision for ypT2-3 tumour. In the modified intention-to-treat analysis, there was no difference between the local excision and total mesorectal excision groups in 5-year local recurrence (7% [95% CI 3-16] vs 7% [3-16]; adjusted hazard ratio [HR] 0·71 [95% CI 0·19-2·58]; p=0·60), metastatic disease (18% [CI 11-30] vs 19% [11-31]; 0·86 [0·36-2·06]; p=0·73), overall survival (84% [73-91] vs 82% [71-90]; 0·92 [0·38-2·22]; p=0·85), disease-free survival (70% [58-79] vs 72% [60-82]; 0·87 [0·44-1·72]; p=0·68), or cancer-specific mortality (7% [3-17] vs 10% [5-20]; 0·65 [0·17-2·49]; p=0·53).

Interpretation: The 5-year results of this multicentre randomised trial corroborate the 3-year results, providing no evidence of difference in oncological outcomes between local excision and total mesorectal excision. Local excision can be proposed in selected patients having a small T2T3 low rectal cancer with a good clinical response after chemoradiotherapy.

Funding: National Cancer Institute of France.
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http://dx.doi.org/10.1016/S2468-1253(19)30410-8DOI Listing
May 2020

[Tolerance of Tamoxifen as an adjuvant therapy and long-term follow up of 55 premenopausal breast cancer women, cared for at the Institut de cancérologie de Lorraine, treated with Tamoxifen].

Bull Cancer 2019 Dec;106(12S1):S75-S100

Département du Parcours Sein, Institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.

Introduction: Objectives: the purpose of this study is to assess TAM safety in terms of side effects and hormonal status, the persistence of the treatment over a five years time-frame and to report the remote follow-up data.

Methods: Fifty five patients were included patients between January 2001 and November 2002 at the Institut de cancérologie de Lorraine. The subjects were aged 50 years or less, premenopausal at diagnosis and treated with adjuvant TAM therapy at a daily dose of 20 mg, for an expected duration of 5 years, at a daily. After 2 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in the institution (1x/year). All data were retrospectively evaluated in 2019.

Results: In these 55 patients, the cumulative incidences of cysts and hot flushes 5 years after treatment were 68.5 % and 77.6 %, respectively. Of the 33 patients with chemoreactive amenorrhea, half had cycles which resumed within a median of 9 months. In the 10 patients without chemotherapy-induced amenorrhea, 4 had a cycle stop. Of these, 3 patients had cycles that, resumed within 1, 4 and 8 months. 34 patients (61.3 %) had taken Tamoxifen for at least 5 years. After 15 years of treatment, overall and progression-free survival was 90.7 % and 67.4 %, respectively.

Conclusion: The observation of the tolerance to the treatment for 5 years and beyond, contributes to the quality of information delivered to future patients starting the treatment, allowing a better understanding and in the long term a better observance.
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http://dx.doi.org/10.1016/S0007-4551(20)30050-3DOI Listing
December 2019

Identification of Specific Tumor Markers in Vulvar Carcinoma Through Extensive Human Papillomavirus DNA Characterization Using Next Generation Sequencing Method.

J Low Genit Tract Dis 2020 Jan;24(1):53-60

Service de Biopathologie, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France.

Objectives: A subset of vulvar carcinomas (VC) are associated with human papillomavirus (HPV) DNA. This trait can be used to identify tumor markers for patient's follow-up. A large diversity of HPV prevalence in VC has been reported, but no data are available concerning the insertional HPV status in this tumor type. Therefore, we have used an innovative next generation sequencing (NGS)-based CaptHPV method able to provide an extensive characterization of HPV DNA in tumors.

Material And Methods: Tumor tissue specimens from 55 patients with VC were analyzed using p16 immunohistochemistry, in situ hybridization, polymerase chain reaction, and CaptHPV-NGS assays.

Results: Our analyses showed that 8 (14.5%) of 55 cases were associated with HPV 16 DNA. No other HPV genotypes were identified. The HPV genome was in a free episomal state only in one case and both episomal and integrated into the tumor cell genome in 7. There was a single insertion in 5 cases and multiple sites, scattered at different chromosomal loci in two. ISH data suggest that some of these might reflect tumor heterogeneity. Viral integration targeted cellular genes among which were TP63, CCDC148, LOC100133091, PKP1, and POLA2. Viral integration at the PKP1 locus was associated with partial gene deletion, and no PKP1 protein was detected in tumor tissue.

Conclusions: Using the NGS-based innovative capture-HPV approach, we established a cartography of HPV 16 DNA in 8 VC cases and identified novel genes targeted by integration that may be used as specific tumor markers. In addition, we established a rationale strategy for optimal characterization of HPV status in VC.
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http://dx.doi.org/10.1097/LGT.0000000000000498DOI Listing
January 2020

Short-term and Long-term Outcome of Endoluminal Vacuum Therapy for Colorectal or Coloanal Anastomotic Leakage: Results of a Nationwide Multicenter Cohort Study From the French GRECCAR Group.

Dis Colon Rectum 2020 03;63(3):371-380

Department of Digestive and Surgical Oncology, Assistance Publique-Hôpitaux de Paris, University Paris-Sud, Le Kremlin Bicêtre, France.

Background: The indications and efficacy of endoluminal vacuum therapy for the management of colorectal/coloanal anastomotic leakage are not well defined.

Objective: This study aimed to evaluate the efficacy and to define adequate indications of endoluminal vacuum therapy to treat colorectal/coloanal anastomotic leakage.

Design: The retrospective cohort evaluated in this study is based on a prospectively maintained database.

Settings: This study was conducted in 8 centers from the French GRECCAR study group.

Patients: Patients with colorectal/coloanal anastomotic leakage treated with endoluminal vacuum therapy were included.

Main Outcome Measures: The primary outcome measured was the success rate of endoluminal vacuum therapy defined by the complete healing of the perianastomotic sepsis and a functional anastomosis. The predictive factors of success of endoluminal vacuum therapy and long-term functional result (low anterior resection syndrome score) were also analyzed.

Results: Among 62 patients treated for an anastomotic leakage of colorectal/coloanal anastomosis from 2012 to 2017, 47 fulfilled the inclusion criteria. The patients had a mean of 6.6 (±5.8) replacements for a total of 27 (±34) days treatment duration, associated with diverting stoma in 81%. After 37 months median follow-up, a successful treatment of anastomotic leakage using endoluminal vacuum therapy could be achieved in 26 patients (55%). The success rate was improved in patients undergoing primary endoluminal vacuum therapy compared to salvage endoluminal vacuum therapy (73% vs 33%, p = 0.006) and when endoluminal vacuum therapy was initiated within 15 days compared to more than 15 days after the diagnosis of anastomotic leakage (72.4% vs 27.8%, p = 0.003). At 12 months, 53% of patients who responded had minor low anterior resection syndrome and only 3 necessitated anastomotic stricture dilation.

Limitations: This was a noncomparative cohort study.

Conclusion: Endoluminal vacuum therapy appears to be effective to treat colorectal anastomotic leakage especially when it is used as primary treatment of the fistula. Long-term functional outcome of patients undergoing conservative management of anastomotic leakage may be improved with endoluminal vacuum therapy. See Video Abstract at http://links.lww.com/DCR/B103. RESULTADOS A CORTO Y LARGO PLAZO DE LA TERAPIA DE VACÍO ENDOLUMINAL PARA LA FUGA ANASTOMÓTICA COLORRECTAL O COLOANAL: RESULTADOS DE UN ESTUDIO DE COHORTE MULTICÉNTRICO A NIVEL NACIONAL DEL GRUPO FRANCÉS GRECCAR: Las indicaciones y la eficacia de la terapia de vacío endoluminal para el tratamiento de la fuga anastomótica colorrectal / coloanal no están bien definidas.Evaluar la eficacia y definir indicaciones adecuadas de la terapia de vacío endoluminal para tratar la fuga anastomótica colorrectal / coloanal.Cohorte retrospectivo basada en una base de datos mantenida prospectivamente.Este estudio se realizó en 8 centros del grupo de estudio Francés GRECCAR.Se incluyeron pacientes con fuga anastomótica colorrectal / coloanal tratados con terapia de vacío endoluminal.Tasa de éxito de la terapia de vacío endoluminal definida por la curación completa de la sepsis perianastomótica y una anastomosis funcional. También se analizaron los factores predictivos del éxito de la terapia de vacío endoluminal y el resultado funcional a largo plazo (puntaje bajo del síndrome de resección anterior).Entre 62 pacientes tratados por una fuga anastomótica de anastomosis colorrectal / coloanal de 2012 a 2017, 47 cumplieron los criterios de inclusión. Los pacientes tuvieron una media de 6.6 (±5.8) reemplazos para un total de 27 (±34) días de duración del tratamiento, asociado con estoma de desvio en el 81%. Después de una mediana de seguimiento de 37 meses, se pudo lograr un tratamiento exitoso de la fuga anastomótica usando terapia de vacío endoluminal en 26 pacientes (55%). La tasa de éxito mejoró en pacientes sometidos a terapia de vacío endoluminal primaria en comparación con la terapia de vacío endoluminal de rescate (73% frente a 33%, p = 0.006) y cuando la terapia de vacío endoluminal se inició dentro de los 15 días en comparación con más de 15 días después del diagnóstico de fuga anastomótica (72.4% vs 27.8%, p = 0.003). A los 12 meses, el 53% de los pacientes que respondieron tenían síndrome de resección anterior baja leve y solo 3 necesitaban dilatación de estenosis anastomótica.Estudio de cohorte no comparativo.La terapia de vacío endoluminal parece ser efectiva para tratar la fuga anastomótica colorrectal, especialmente cuando se usa como tratamiento primario de la fístula. El resultado funcional a largo plazo de los pacientes sometidos a un tratamiento conservador de la fuga anastomótica puede mejorarse con la terapia de vacío endoluminal. Consulte Video Resumen en http://links.lww.com/DCR/B103.
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http://dx.doi.org/10.1097/DCR.0000000000001560DOI Listing
March 2020

Comparison of postoperative complications and quality of life between patients undergoing continent versus non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.

Int J Gynecol Cancer 2020 02 2;30(2):233-240. Epub 2019 Dec 2.

Institut Claudius Regaud, Toulouse, Occitanie, France

Background: Pelvic exenteration and its reconstructive techniques have been associated with high postoperative morbidity and a negative impact on patient quality of life. The aim of our study was to compare postoperative complications and quality of life in patients undergoing continent compared with non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.

Methods: We designed a multicenter study of patients from 10 centers who underwent an anterior or total pelvic exenteration with urinary reconstruction for histologically confirmed persistent or recurrent gynecologic malignancy after previous treatment with radiotherapy. From January 2005 to September 2008, we included patients retrospectively, and from September 2008 to May 2009, patients were included prospectively which allowed collection of quality of life data. Demographic, surgical, and follow-up data were analyzed. Postoperative complications were classified according to the Clavien-Dindo classification. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 (V.3.0) and EORTC-QLQ-OV28 quality of life questionnaires. We compared patients who underwent a continent urinary diversion with those who underwent a non-continent reconstruction.

Results: We included 148 patients, 92 retrospectively and 56 prospectively. Among them, 77.4% had recurrent disease and 22.6% persistent disease after the primary treatment. In 70 patients, a urinary continent diversion was performed, and 78 patients underwent a non-continent diversion. Median age of the continent and incontinent groups was 53.5 (range 33-78) years and 57 (26-79) years, respectively. There were no significant differences between the continent and non-continent groups in median length of hospitalization (28.5 vs 26 days, P=0.19), postoperative grade III-IV complications (42.9% vs 42.3%, P=0.95), complications needing surgical (27.9% vs 34.6%, P=0.39) or radiological (14.7% vs 12.8%, P=0.74) intervention, and complication type (digestive (23.2% vs 16.7%, P=0.32) and urinary (15.9% vs 16.7%, P=0.91)). There were no significant differences between the groups in global health, global quality of life, and body image perception scores 1 year after surgery.

Conclusion: Continent and incontinent urinary reconstructions are equivalent in terms of postoperative complications and quality of life scores.
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http://dx.doi.org/10.1136/ijgc-2019-000863DOI Listing
February 2020

[Factors limiting outpatient management in breast surgery].

Bull Cancer 2019 Dec 15;106(12):1115-1123. Epub 2019 Oct 15.

Université de Lorraine, institut de cancérologie de Lorraine, département de chirurgie, 6, avenue de Bourgogne, 54511 Vandoeuvre-les-Nancy, France; Université de Lorraine, CNRS Vandoeuvre-les-Nancy, CRAN, UMR 7039, Vandoeuvre-les-Nancy, France.

Introduction: Breast cancer surgery associates interventions of short duration and low morbidity, mostly accessible for outpatient management.

Methods: We performed a descriptive, retrospective, monocentric study involving 1735 patients operated between 1st of July 2015 and the 31st of December 2017 of a mammary or axillary lymph node procedure. A comparative study was carried out, involving 2 groups of patients treated either on an outpatient or conventional hospitalization mode, in order to find the main medico-social factors that could constitute barriers to this ambulatory modality.

Results: In total, 992 patients were treated in outpatient surgery and 743 in conventional surgery. The mean age of the ambulatory group was 56.9 years (±11.2), versus 65.9 years (±13.5) in the conventional hospitalization group. Thirteen stays (1.3%) had to be converted into conventional hospitalization. The main factors limiting outpatient management are age≥70 years, BMI≥25, isolation of the patient, total mastectomy, and drainage.

Conclusion: Because of social, medical or psychological constraints, the rate of outpatient breast surgery remains in our practice, stable in recent years at 56%. Some ways of improvement can be envisaged, but it is likely that this rate will only increase in a very gradual manner in the years to come.
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http://dx.doi.org/10.1016/j.bulcan.2019.08.018DOI Listing
December 2019

Predictive factors of axillary positive sentinel lymph node biopsy in extended ductal carcinoma in situ treated by simple mastectomy at once.

J Gynecol Obstet Hum Reprod 2020 Mar 25;49(3):101641. Epub 2019 Sep 25.

Institut de Cancérologie de Lorraine, Department of Surgical Oncology, Université de Lorraine, F-54519 Vandoeuvre-lès-Nancy, France; Université de Lorraine, CNRS UMR7039, CRAN, F-54000 Nancy, France.

Background: The incidence of positive sentinel lymph node biopsy (SLNB) in ductal carcinoma in situ (DCIS) ranged from 0 to 14%. The main hypothesis would be the presence of an invasive contingent on the final histology. The objective was to identify predictive factors of sentinel lymph node positivity in the management of extended ductal carcinoma in situ treated by simple mastectomy.

Methods: This was a retrospective study carried out at the Lorraine Cancer Institute from January 2003 to December 2017. Women with DCIS on core-needle biopsy whose management consisted of simple mastectomy and SLNB procedure were included.

Results: 188 patients were analyzed. Preoperatively, 18 patients (9.6%) had DCIS with microinvasion, while the others had pure DCIS. Eight patients (4.2%) had positive sentinel lymph node biopsy, the majority of which were single micrometastases. Predictive factor of node invasion was microinvasion on biopsy (p<0.01). Only in cases of pure DCIS, the percentage of positive SLNB was reduced to 2.9%. Invasive carcinoma was found in the majority of patients with positive axillary SLNB procedure (75%, n=6), compared to 16.7% (n=30) without SLNB involvement (p<0.01).

Conclusions: The low rate of positive sentinel node biopsy in pure ductal carcinoma in situ suggests that in the absence of microinvasion, the sentinel procedure would seem less appropriate. New techniques for identifying sentinel lymph node biopsy could report axillary staging after definitive histologic results.
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http://dx.doi.org/10.1016/j.jogoh.2019.101641DOI Listing
March 2020

[Understanding lower gynaecological cancer consultation delay and help-seeking behavior in patients over 65].

Bull Cancer 2019 Sep 8;106(9):747-758. Epub 2019 Jun 8.

Université de Lorraine, CNRS, institut de cancérologie de Lorraine, département de chirurgie, CRAN, UMR 7039, 6, avenue de Bourgogne, CS 30519, 54519 Vandœuvre-lès-Nancy cedex, France.

Introduction: Delays for consultation of more than six months exist for uterine cancer. Delays in diagnosis of more than five years exist for vulvar cancer. The peak incidence of these neoplasms appear after the age of 65 years. Patient's symptoms are characteristically swelling, vaginal bleeding or itching. This study aims to understand what is happening during this period for women over 65 years old. It also tries to identify triggers during the help-seeking period.

Methods: Qualitative studies using semi-structured interviews with dual analyses (semio-pragmatic and psychodynamic) have been conducted on a population of older (65+) gynaecologic cancer patients, recruited from a French oncology centre.

Results: Twelve patients were interviewed. Patients' courses of action were determined by the characteristics of their symptoms, their feelings and their emotions. Representations, subjective beliefs and past experiences were employed to make sense of their symptoms. The patient's friend and family circle had an important role in incentivizing the patient to seek consultation. Multiple factors affected the path towards consulting the doctor. The initial medical contact included several challenges. The patient would consult a doctor earlier if he had more information about his illness and if his relationship with the doctor was better.

Conclusion: Our findings are similar to those of other cancers. The peculiarity for this population appears to be the different representations of age-related changes in the reproductive system, and the taboo associated with this issue when facing friends and family.
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http://dx.doi.org/10.1016/j.bulcan.2019.04.007DOI Listing
September 2019

Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis.

J Clin Oncol 2019 08 14;37(23):2028-2040. Epub 2019 May 14.

1Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France.

Purpose: Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC.

Patients And Methods: From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors.

Results: After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 2; = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% ( = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% 10.1%, respectively; = .820) or major complication rate (53.7% 55.3%, respectively; = .496).

Conclusion: Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.
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http://dx.doi.org/10.1200/JCO.18.01688DOI Listing
August 2019

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

EBioMedicine 2019 May 2;43:253-260. Epub 2019 Apr 2.

Institut de cancérologie de l'Ouest - site Paul Papin (ICO) 15, Rue André Boquel, 49055 Angers, France.

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.

Methods: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.

Findings: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.

Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.
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http://dx.doi.org/10.1016/j.ebiom.2019.03.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562019PMC
May 2019

The targeting ability of fluorescent quantum dots to the folate receptor rich tumors.

Photodiagnosis Photodyn Ther 2019 Jun 15;26:150-156. Epub 2019 Mar 15.

Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, Campus Sciences, Boulevard des Aiguillette, 54506 Vandoeuvre-lès-Nancy, France; Surgical Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519 Vandoeuvre-lès-Nancy, France. Electronic address:

Background: Quantum dots (QDs) bring new insights in cancer theranostics. Exceptional brightness together with the simple possibility to modify surface with targeting molecules make QDs attractive agents in fluorescence guided surgery and photodynamic therapy. Currently, many targeted QDs have been developed for theranostic purpose. However, their targeting ability was tested mainly in two dimensional monolayer tumor cell models, while our study includes 3D tumor model reflecting the specificity of in vivo tumor environment.

Methods: Core/multilayer shell CdSe/CdS/ZnS QDs were conjugated with folic acid (FA) and characterized spectroscopically. Cytotoxicity of QDs on KB and A549 cells lines were evaluated using the MTT assay. Cellular uptake of QDs was assessed by epifluorescent microscopy. To study the distribution of QDs in tumor tissue, KB spheroids were prepared by means of the liquid overlay technique and then frozen cut of spheroids treated with QDs were imaged by epifluorescence microscopy.

Results: We confirmed the specificity of QD-FA for the folic acid receptor positive KB cells. In 3D tumor spheroid model we demonstrated uptake enhancement of QD-FA compared with non-targeted QD. It was demonstrated that penetration profiles were similar for both QDs with penetration depth never exceeding 100 μm.

Conclusions: We have demonstrated the effectiveness of FA conjugated QDs to target tumor spheroids thus confirming the crucial role of FRα receptor as a target. Further improvement of QD-FA targeting ability could be performed using dual targeting different targeting agents, such as FA and cyclic RGD.
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http://dx.doi.org/10.1016/j.pdpdt.2019.03.010DOI Listing
June 2019

Experience implication in subjective surgical ergonomics comparison between laparoscopic and robot-assisted surgeries.

J Robot Surg 2020 Feb 12;14(1):115-121. Epub 2019 Mar 12.

Service d'Obstétrique, de Gynécologie et de Médecine Fœtale, Centre Hospitalier Régional de Tours, 2 boulevard Tonnellé, 37044, Tours Cedex 9, France.

Introduction: Laparoscopic surgery (LS) may lead to musculoskeletal disorders (MSDs) and an increase in physical and mental workloads to the surgeon. Robot-assisted surgery (RAS) should improve the ergonomy of the surgeon. This study assesses the experience influence in surgical ergonomics between LS and RAS.

Methods: LS and RAS lasting more than 60 min of effective operative time were compared. During the surgical procedure, the physical discomfort was evaluated using the Borg scale. At the end, the mental workload was evaluated using the NASA-TLX index. After global analysis, the experienced and young surgeons were assessed.

Results: 88 RAS and 82 LS were evaluated. During LS, the physical discomfort was significantly higher in all segments, and the pain increased significantly during the procedure in all segments compared to that evaluated in the RAS (p < 0.05). Forearms and the back were the most painful. The young surgeons did not display any improvement in the physical ergonomics of the RAS compared to the LS. Concerning the mental ergonomics, the overall workload and performance were significantly greater during the LS compared to the RAS (p < 0.05). For the young surgeons, the overall workload, the effort, the mental and the physical demands were greater during LS (p < 0.05). For the experienced surgeons, the physical demand was lower during the RAS compared to the LS (p < 0.05). However, the experienced surgeons expressed a feeling of greater performance after the LS (p < 0.01). RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons.

Conclusion: RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons.
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http://dx.doi.org/10.1007/s11701-019-00933-2DOI Listing
February 2020

Well-Differentiated Papillary Mesothelioma of the Peritoneum: A Retrospective Study from the RENAPE Observational Registry.

Ann Surg Oncol 2019 Mar 11;26(3):852-860. Epub 2019 Jan 11.

Department of Surgery, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.

Background: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare entity. Questions regarding management are still being debated as no more than 50 cases have been reported in the literature.

Objective: We aimed to analyze the clinical, therapeutic, and prognostic data of patients with WDPMP from the RENAPE observational registry.

Patients And Methods: All patients diagnosed with WDPMP and prospectively included in the RENAPE national registry between 2010 and 2018 were also included in our study. Expert pathologists from the RENA-PATH group confirmed all cases. All clinical, therapeutic, postoperative, and prognostic data were extracted and analyzed.

Results: We report on 56 patients with a mean age of 52 years (range 21-74). WDPMP was incidentally diagnosed during imaging or surgery in 16% and 36% of patients, respectively, and an association with synchronous malignancy was found in 18% of patients. Nine lesions showed discrete signs of fatty invasion. The median Peritoneal Cancer Index was 11 (range 0-33). Eleven patients were treated with definitive excision, 4 were treated with cytoreductive surgery (CRS) only, 37 were treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), and 2 were treated with CRS plus HIPEC plus early postoperative intraperitoneal chemotherapy. CRS was considered to be complete in 90% of cases. One patient died postoperatively and 16 patients (31%) faced postoperative complications. The median disease-free survival was 144 months; Four patients relapsed, with a median period of 27 months. No prognostic factors could be identified.

Conclusions: Our analysis confirms the favorable prognosis of WDPMP. CRS and HIPEC could be a therapeutic option for diffuse, symptomatic, and/or recurrent disease.
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http://dx.doi.org/10.1245/s10434-018-07153-2DOI Listing
March 2019
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