Publications by authors named "E Lambaudie"

171 Publications

[Muscle Relaxant And Reversal Practices And Impact Of Reversal Modalities On Operating Room And Postoperative Room Duration - Results Of A Delphi Study].

Ann Pharm Fr 2021 Jul 24. Epub 2021 Jul 24.

Department of Anesthesia, Hospital Paris Saint Joseph, 185 Rue Raymond Losserand, 75014 Paris, France.

Objective: The objectives of this Delphi study are to describe muscle relaxant and reversal practices in France and to seek a consensus on the impact of the reversal method on the time spent in the OR and PACU.

Method: A two-round Delphi survey was conducted on a panel of French anesthetists involved in colectomies, hysterectomies or bariatric surgery. The questionnaire was designed in collaboration with a scientific committee and was intended to assess neuromuscular blockade reversal techniques and their impact on time spent in the OR and PACU. The first round gathered data on practices and the second round sought a consensus for the time aspect.

Results: Overall, all participants (99%) monitored neuromuscular blockade, with a majority (82%) doing so continuously. Of the participants, 22% routinely used a reversal drug. The time saved in the OR or PACU with sugammadex varied between 1 and 43 minutes depending on the surgery and the neuromuscular blockade reversal method it was compared to.

Conclusion: Although SFAR recommendations (French Society of Anesthesia & Intensive Care Medicine) were generally well followed, the use of neuromuscular blockade reversal drugs was observed to be not fully integrated into regular practice, despite the fact that more than half of patients were reported to have residual neuromuscular blockade post-surgery and that sugammadex is known to reduce time spent in the OR and PACU compared to other neuromuscular blockade reversal methods.
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http://dx.doi.org/10.1016/j.pharma.2021.07.003DOI Listing
July 2021

Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology.

Biomedicines 2021 Jun 2;9(6). Epub 2021 Jun 2.

Immunomonitoring Department, Institut Paoli-Calmettes, 13009 Marseille, France.

Endometrial cancer (EC) can easily be cured when diagnosed at an early stage. However, advanced and metastatic EC is a common disease, affecting more than 15,000 patients per year in the United Sates. Only limited treatment options were available until recently, with a taxane-platinum combination as the gold standard in first-line setting and no efficient second-line chemotherapy or hormone therapy. EC can be split into four molecular subtypes, including hypermutated cases with POLE mutations and 25-30% harboring a microsatellite instability (MSI) phenotype with mismatch repair deficiency (dMMR). These tumors display a high load of frameshift mutations, leading to increased expression of neoantigens that can be targeted by the immune system, including (but not limited) to T-cell response. Recent data have demonstrated this impact of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors on chemo-resistant metastatic EC. The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors. Most responders experiment long responses that last more than one year. Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib. Approvals have, thus, been obtained or are underway for EC with immune checkpoint inhibitors (ICI) used as monotherapy, and in combination with antiangiogenic agents. Combinations with other targeted therapies are under evaluation and randomized studies are ongoing to explore the impact of ICI-chemotherapy triplets in first-line setting. We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy.
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http://dx.doi.org/10.3390/biomedicines9060632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228955PMC
June 2021

Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial.

Genome Med 2021 May 18;13(1):87. Epub 2021 May 18.

Department of Medical Oncology, Gustave Roussy Cancer Campus, UMR981 Inserm, Villejuif, France.

Background: The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores.

Methods: Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 "candidate cancer" genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a "matched therapy" and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES).

Results: Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68-75%). Only 94/550 patients (17%, 95%CI 14-21) received an "AGA-matched therapy" on progression. The most frequent AGAs leading to "matched therapy" included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such "matched therapy" improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of "matched therapy" was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with "matched therapy," and 6-month overall survival (OS) was 62% (95%CI 52-73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH.

Conclusions: Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a "matched therapy" in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results.

Trial Registration: ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158 .
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http://dx.doi.org/10.1186/s13073-021-00897-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132379PMC
May 2021

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort.

ESMO Open 2021 Jun 10;6(3):100151. Epub 2021 May 10.

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

Background: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm.

Patients And Methods: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status.

Results: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS.

Conclusion: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.
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http://dx.doi.org/10.1016/j.esmoop.2021.100151DOI Listing
June 2021

Care as Usual: An Acceptable Strategy to Apply During the COVID-19 Pandemic in a French Tertiary Gynecologic Oncology Department.

Front Oncol 2021 21;11:653009. Epub 2021 Apr 21.

Department of surgical oncology, Institut Paoli-Calmettes and CRCM, CNRS, INSERM, Aix Marseille Université, Marseille, France.

We describe and analyze a "care as usual" strategy of a French Comprehensive Cancer Center during the COVID-19 pandemic to manage surgical patients with gynecological cancer. We conducted a retrospective analysis evaluating the surgical activity in our gynecologic oncology department between January 21 and May 12, 2020. We compared the surgical activity and surgical and oncologic outcomes during the pre-lockdown period and the pandemic period. The main objective was to evaluate the impact of the COVID-19 pandemic on surgical activity. The secondary objectives were to analyze the surgical and the oncologic outcomes. We compared the surgical activity during the 8 weeks after the national lockdown (85 procedures) to the surgical activity in the 8 weeks preceding the lockdown (127 procedures). We observed a 33% decrease in activity between the two periods. The clinical and epidemiologic characteristics were similar between the two periods. There were no differences between the surgical approaches ( = 0.592), the surgical complexity ( = 0.323), the length of stay ( = 0.85), and even for the complex procedure ( = 0.96) and the perioperative ( = 0.791) and postoperative complication rates ( = 0.102). We observed a significant decrease in the time of return to intended oncological treatment (RIOT) during the lockdown period with an average of 31.9 days compared to 46.9 days in the pre-lockdown period ( = 0.003). During the COVID-19 pandemic, "care as usual" represents an acceptable strategy without impairing the oncologic outcome in a Comprehensive Cancer Center with a patient-centered clinical pathway for gynecologic oncologic surgical patients.
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http://dx.doi.org/10.3389/fonc.2021.653009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097084PMC
April 2021
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