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Article: Cervical Cancer Associated with Pregnancy: Current Challenges and Future Strategies.

Le Guévelou, Jennifer / Selleret, Lise / Laas, Enora / Lecuru, Fabrice / Kissel, Manon

2024 Volume 16, Issue 7

Abstract: Cancer during pregnancy is defined as a tumor diagnosed in a pregnant woman or up to 1-year post-partum. While being a rare disease, cervical cancer is probably one of the most challenging medical conditions, with the dual stake of treating the cancer ... ...

Abstract	Cancer during pregnancy is defined as a tumor diagnosed in a pregnant woman or up to 1-year post-partum. While being a rare disease, cervical cancer is probably one of the most challenging medical conditions, with the dual stake of treating the cancer without compromising its chances for cure, while preserving the pregnancy and the health of the fetus and child. To date, guidelines for gynecological cancers are provided through international consensus meetings with expert panels, giving insights on both diagnosis, treatment, and obstetrical care. However, these expert guidelines do not discuss the various approaches than can be found within the literature, such as alternative staging modalities or innovative surgical approaches. Also, the obstetrical care of women diagnosed with cervical cancer during pregnancy requires specific considerations that are not provided within our current standard of care. This systematic review aims to fill the gap on current issues with regards to the management of cervical cancer during pregnancy and provide future directions within this evolving landscape.
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16071341
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Article ; Online: How to perform sentinel node detection in high-risk endometrial cancer: one step forward.

Balaya, Vincent / Lecuru, Fabrice / Laas, Enora

Journal of gynecologic oncology

2021 Volume 32, Issue 4, Page(s) e71

MeSH term(s)	Endometrial Neoplasms/surgery ; Female ; Humans ; Sentinel Lymph Node/diagnostic imaging ; Sentinel Lymph Node Biopsy
Language	English
Publishing date	2021-06-03
Publishing country	Korea (South)
Document type	Editorial ; Comment
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2021.32.e71
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Article ; Online: La recherche de ganglion sentinelle a-t-elle des indications dans les cancers digestifs ?

Faron, Matthieu / Laas, Enora

Bulletin du cancer

2019 Volume 107, Issue 6, Page(s) 660–665

Abstract: Despite being a standard of care in several cancers, sentinel lymph node (SLN) is not widespread in digestive cancers. European guidelines do not recommend its use for any digestive cancers. Particularity of the lymphatic vessel, intimately linked to ... ...

Title translation	Does sentinel lymph node identification has indication in digestive cancers?
Abstract	Despite being a standard of care in several cancers, sentinel lymph node (SLN) is not widespread in digestive cancers. European guidelines do not recommend its use for any digestive cancers. Particularity of the lymphatic vessel, intimately linked to blood vessel, may explain part of this phenomenon. Nevertheless, more indication could arise in the near future with the early diagnosis of tumor induced by cancer screening. Ruling out the lymphatic invasion could allow preserving the organ currently resected because of risk of lymph node positivity. This procedure is well studied in early gastric cancer in Korea and Japan. Several study have demonstrated that, a dual-tracer (isotopic and dye) allows to accurately identify the SLN. A randomized phase 3 trial is currently active in Korea to evaluate the oncological results of the procedure. Similar indication could arise for T1 tumor of the low-rectum, but currently available data are insufficient to recommend its use outside of a study. SLN may also be used to detect aberrant lymphatic drainage (rectum, ileum) but have been tested so far only in a few dozen of patients. Finally, SLN is disappointing in colon cancer, due to its low sensitivity and the absence of modification of the surgical procedure induced.
MeSH term(s)	Gastrointestinal Neoplasms/pathology ; Humans ; Lymphatic Metastasis/pathology ; Sentinel Lymph Node Biopsy
Language	French
Publishing date	2019-10-15
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	213270-9
ISSN	1769-6917 ; 0007-4551
ISSN (online)	1769-6917
ISSN	0007-4551
DOI	10.1016/j.bulcan.2019.06.013
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Article ; Online: Partial breast resection for multifocal lower quadrant breast tumour using virtual reality.

Laas, Enora / El Beheiry, Mohamed / Masson, Jean-Baptiste / Malhaire, Caroline

BMJ case reports

2021 Volume 14, Issue 3

Abstract: Oncoplastic surgery allows an increase in the number of indications for conservative breast cancer treatments. However, uncertainty as to whether it can be performed still exists in certain situations such as with multicentric or multifocal lesions, even ...

Abstract	Oncoplastic surgery allows an increase in the number of indications for conservative breast cancer treatments. However, uncertainty as to whether it can be performed still exists in certain situations such as with multicentric or multifocal lesions, even when the breast volume can accommodate it. With the aid of a virtual reality software, DIVA, allowing the precise visualisation of tumours and breast volumes based entirely on the patient's MRI, we report the ability to rapidly confirm and secure an indication for partial surgery of multiple lesions in a 31-year-old patient. With the described approach, the patient did not have to suffer significant disfigurement from cancerous breast surgery without compromising safety.
MeSH term(s)	Adult ; Breast/diagnostic imaging ; Breast/surgery ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/surgery ; Humans ; Mammaplasty ; Mastectomy, Segmental ; Virtual Reality
Language	English
Publishing date	2021-03-16
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2021-241608
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Article: Sentinel Lymph Node Biopsy in Uterine Cancer: Time for a Modern Approach.

Laas, Enora / Fourchotte, Virginie / Gaillard, Thomas / Pauly, Léa / Reyal, Fabien / Feron, Jean-Guillaume / Lécuru, Fabrice

Cancers

2023 Volume 15, Issue 2

Abstract: Since the validation of the sentinel node technique (SLN) for vulvar cancer 20 years ago, this technique has been introduced in the management of operable cervical cancer and endometrial cancer. For cervical cancer a "one fits all" attitude has mainly ... ...

Abstract	Since the validation of the sentinel node technique (SLN) for vulvar cancer 20 years ago, this technique has been introduced in the management of operable cervical cancer and endometrial cancer. For cervical cancer a "one fits all" attitude has mainly been presented. However, this approach, consisting of a frozen section during the operation, can be discussed in some stages. We present and discuss the main option for each stage, as well as some secondary possibilities. For endometrial cancer, SLN is now the technique of choice for the nodal staging of low- and intermediate-risk groups. Some discussion exists for the high-risk group. We also discuss the impacts of using preoperatively the molecular classification of endometrial cancer. Patients with POLE or TP53 mutations could have different nodal staging. The story of SLN in uterine cancers is not finished. We propose a comprehensive algorithm of SLN in early cervical and endometrial cancers. However, several ongoing trials will give us important data in the coming years. They could substantially change these propositions.
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15020389
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Article ; Online: Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade-a worldwide perspective.

Gougis, Paul / Jochum, Floriane / Abbar, Baptiste / Dumas, Elise / Bihan, Kevin / Lebrun-Vignes, Bénédicte / Moslehi, Javid / Spano, Jean-Philippe / Laas, Enora / Hotton, Judicael / Reyal, Fabien / Hamy, Anne-Sophie / Salem, Joe-Elie

EClinicalMedicine

2024 Volume 70, Page(s) 102536

Abstract: Background: Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events (irAE) affecting every organ.: Methods: We extracted irAE from ... ...

Abstract	Background: Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events (irAE) affecting every organ. Methods: We extracted irAE from VigiBase, the international pharmacovigilance database, first reported in 2008 until 01/2023 to characterize irAE reporting trends, clinical features, risk factors and outcomes. Findings: We distinguished 25 types of irAE (n = 50,347cases, single irAE/case in 84.9%). Cases mainly involved anti-PD1 (programmed-death-1) monotherapy (62.4%) in male (61.7%) aged 64.3 ± 12.6 years. After 2020 vs. prior to 2016, proportion of anti-CTLA4 (Cytotoxic-T-Lymphocyte-Antigen-4) monotherapy prescription almost vanished (1.6% vs. 47%, respectively) contrasting with increased use of anti-PDL1 (PD1-ligand) monotherapy (18% vs. 0.9%) and anti-CTLA4+anti-PD(L)1 combination (20% vs. 8.9%). Anti-LAG3 (Lymphocyte-Activation-Gene-3) prescription was limited (<1%) in the studied timeframe. After 2020, over 14 different cancer types were treated vs. almost exclusively melanoma and lung cancers before 2016. Overall, the most reported irAE were skin reactions (22.9%), pneumonitis (18.5%), enterocolitis (14.4%) and thyroiditis (12.1%). ICI-myotoxicities (6.6%) included myositis, myocarditis and myasthenia-gravis like syndrome and were the most overlapping irAE (up to 30% overlap, vs. <3% in general for other inter-irAE overlap). The top factors associated with specific irAE (odds-ratio>5) were presence of thymic cancer for ICI-myotoxicities or hepatitis; presence of melanoma for vitiligo, uveitis or sarcoidosis; specific types of ICI regimen (anti-LAG3 for meningitis, anti-CTLA4 for hypophysitis); and specific reporting regions (eastern Asia for cholangitis). Median time-to-onset ranged from 31 to 273 days, being shortest for myotoxicities and most delayed for skin-bullous auto-immune reactions. Overall fatality was highest for myocarditis = 27.6%, myasthenia = 23.1%, severe cutaneous adverse reactions (SCAR) = 22.1%, myositis = 21.9%, pneumonitis = 21%, and encephalomyelitis = 18%; generally decreasing after 2020, except for myasthenia and SCAR. When reported, irAE recurrence rate after rechallenge was 28.9% (n = 275/951). Interpretation: This up-to-date comprehensive worldwide pharmacovigilance study defines the spectrum, characteristics, and evolution of irAE reporting summarizing over a decade of use. Multiple risk factors and clinical peculiarities for specific irAE have been identified as signals to guide clinical practice and future research. Funding: Paul Gougis was supported by the academic program: "Contrats ED: Programme blanc Institut Curie PSL" for the conduct of his PhD. Baptiste Abbar was supported by "the Fondation ARC Pour le Rechercher Sur le Cancer". The RT2L research group (Institut Curie) was supported by the academic program "SHS INCa", Sanofi iTech award, and by Monoprix∗.
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2024.102536
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Article ; Online: Rethinking surgical revisions: impact of the MonarchE trial on axillary dissection in hormone-positive HER2-negative early breast cancer patients potentially eligible for abemaciclib.

Gaillard, Thomas / Piketty, Jeanne / Feron, Jean-Guillaume / Girard, Noemie / Pauly, Lea / Gauroy, Elodie / Darrigues, Lauren / Grandal, Beatriz / Pierga, Jean-Yves / Hamy-Petit, Anne-Sophie / Reyal, Fabien / Laas, Enora

British journal of cancer

2024 Volume 130, Issue 7, Page(s) 1141–1148

Abstract: Introduction: The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 status, may require revisiting surgical ...

Abstract	Introduction: The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 status, may require revisiting surgical interventions, including invasive axillary lymph node dissection (ALND)-a procedure that current guidelines generally do not recommend. Methods: We conducted a single-centre, retrospective, observational cohort study on non-metastatic breast cancer patients managed from 2002 to 2011, at the Institut Curie. Data collection involved clinical and histological characteristics plus treatment follow-up. Results: Out of 8715 treated patients, 721 met the inclusion criteria. Overall, 12% (87) were classified as N2 ( ≥ 4 positive lymph nodes), thus eligible for abemaciclib per "node criterion." Tumour size, positive sentinel lymph nodes, and lobular histology showed a significant correlation with N2 status. Approximately 1000 ALNDs would be required to identify 120 N2 cases and prevent four recurrences. Conclusion: The MonarchE trial may significantly affect surgical practices due to the need for invasive procedures to identify high-risk patients for adjuvant abemaciclib treatment. The prospect of unnecessary morbidity demands less invasive N2 status determination methods. Surgical decisions must consider patient health and potential treatment benefits.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/drug therapy ; Breast Neoplasms/surgery ; Breast Neoplasms/pathology ; Sentinel Lymph Node Biopsy ; Retrospective Studies ; Reoperation ; Lymphatic Metastasis/pathology ; Lymph Node Excision/adverse effects ; Axilla/pathology ; Lymph Nodes/pathology ; Aminopyridines ; Benzimidazoles
Chemical Substances	abemaciclib (60UAB198HK) ; Aminopyridines ; Benzimidazoles
Language	English
Publishing date	2024-01-27
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-024-02580-3
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Article ; Online: Comment améliorer la qualité méthodologique et l’adoption en routine des résultats des essais chirurgicaux ?

Laas, Enora / Feron, Jean Guillaume / Laki, Fatima / Fourchotte, Virginie / Osdoit, Marie / Asselain, Bernard / Reyal, Fabien / Lecuru, Fabrice

Bulletin du cancer

2022 Volume 109, Issue 10, Page(s) 1059–1065

Abstract: Surgical studies have specific issues, such as quality assurance on procedures, standardization of techniques, surgeon effect, timing of randomization, blinding respect or choice of the reference arm. All these difficulties conducted to criticism many ... ...

Title translation	How to improve the surgical trials quality in daily practice.
Abstract	Surgical studies have specific issues, such as quality assurance on procedures, standardization of techniques, surgeon effect, timing of randomization, blinding respect or choice of the reference arm. All these difficulties conducted to criticism many trials, and lack of results implementation. Indeed, adherence to methodological guidelines is often poor. Twelve recommendations were recently issued by the JAMA surgery revue for good practice in surgical studies to improve the quality of surgical trials in general and surgical oncology. We detail here the main issues of surgical trials in gynaecological oncology surgery, as well as possibilities of improvement for future studies.
MeSH term(s)	Humans ; Medical Oncology ; Surgical Oncology
Language	French
Publishing date	2022-08-19
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	213270-9
ISSN	1769-6917 ; 0007-4551
ISSN (online)	1769-6917
ISSN	0007-4551
DOI	10.1016/j.bulcan.2022.04.013
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Article ; Online: Percutaneous Uterine Needle Biopsy with Microscopic and Array-CGH Analyses for Preoperative Sarcoma Diagnosis in Patients with Suspicious Myometrial Tumors on MRI: A Prospective Pilot Study (SARCGYN).

Smadja, Jeremy / El Zein, Sophie / Pierron, Gaelle / Watson, Sarah / Laas, Enora / Ramtohul, Toulsie / Tzanis, Dimitri / Servois, Vincent / Bonvalot, Sylvie

Annals of surgical oncology

2022

Abstract: Background: Unlike for soft tissue sarcomas, percutaneous biopsy is not validated for uterine myometrial tumors, leading to leiomyosarcoma inadvertent morcellation and overtreatment in childbearing patients. This study aimed to evaluate preoperative ... ...

Abstract	Background: Unlike for soft tissue sarcomas, percutaneous biopsy is not validated for uterine myometrial tumors, leading to leiomyosarcoma inadvertent morcellation and overtreatment in childbearing patients. This study aimed to evaluate preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-comparative genomic hybridization (MCGH-PUB). Methods: This was a prospective single-center cohort study including all consecutive patients who were candidates for hysterectomy because of suspected uterine leiomyosarcoma on magnetic resonance imaging (MRI) who received PUB. Microscopic and array-CGH analyses with genomic index (GI) counts were performed to guide the therapeutic strategy. Smooth-muscle tumors with suspect features with a GI above 15 were deemed malignant, as were tumors without microscopic malignant features with a complex genomic profile (GI above 30 or malignant profile). Preoperative diagnoses based on M-PUB and MCGH-PUB were compared with the postsurgical pathological specimen or follow-up. Results: From November 2016 to February 2022, 34 patients were included. Based on the surgical specimen (N = 23) or follow-up (N = 11), final diagnoses were 11 sarcomas and 23 non-sarcomas. The median follow-up was 12 months (IQR 6-37). The diagnostic accuracies of M-PUB and MCGH-PUB were 94% and 100%, respectively. The sensitivity, specificity, and negative predictive value of MCGH-PUB were 100%, 100%, and 100%, respectively. A high GI was significantly associated with malignancy (P < 0.001). Genomic analyses allowed malignancy upgrades for four tumors. There were no complications and no dissemination along the biopsy track. Conclusion: MCGH-PUB is safe and accurate for preoperatively diagnosing uterine sarcomas and should be used routinely after suspicious MRI to tailor surgery.
Language	English
Publishing date	2022-10-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-022-12697-5
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Article ; Online: Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns.

Gougis, Paul / Hamy, Anne-Sophie / Jochum, Floriane / Bihan, Kevin / Carbonnel, Marie / Salem, Joe-Elie / Dumas, Elise / Kabirian, Rayan / Grandal, Beatriz / Barraud, Solenn / Coussy, Florence / Hotton, Judicael / Savarino, Raphaelle / Marabelle, Aurélien / Cadranel, Jacques / Spano, Jean-Philippe / Laas, Enora / Reyal, Fabien / Abbar, Baptiste

JAMA network open

2024 Volume 7, Issue 4, Page(s) e245625

Abstract: Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking.: Objective: To assess the risk of pregnancy-, fetal- ...

Abstract	Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. Objective: To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. Design, setting, and participants: In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Exposure: Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Main outcomes and measures: The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. Results: A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. Conclusions and relevance: In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Humans ; Female ; Adult ; Cohort Studies ; Immune Checkpoint Inhibitors/adverse effects ; Premature Birth ; Abortion, Spontaneous ; Hypothyroidism ; Neoplasms
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2024.5625
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