APPLICATION D'UN RADIO-IMAGEUR (TRECAM) DANS LES CANCERS INVASIFS INFRA-CLINIQUES DU SEIN

Since its emergence in the middle of the twentieth century, nuclear medicine continues to evolve. At the same time diagnostic and therapeutic, it occupies an increasingly important place in the modern medical strategy. Nuclear imaging consists of injecting the patient with a radio-tracer to detect the radiation emitted. It provides quantitative access to the functionality of organs or the location of target structures such as tumor lesions. This imaging has been naturally integrated into surgical procedures, particularly in oncology (preoperatively and then intraoperatively). It is called radio-guided surgery. It makes possible to locate the radioactive target which will be removed during surgery.Technological advances in radiopharmaceutical instrumentation are driving new strategies that can target small structures. Gamma-ray imaging remains the most widespread and the most suitable. We are witnessing the development of miniaturized portable gamma imaging devices that allow visual control during surgery. These devices are promising but need to be evaluated.A short state-of-the-art of the various procedures in radioguided surgery and imagers used clinically is carried out in this thesis.For many years, the Imaging and Modeling in Neurobiology and Oncology Laboratory (UMR 8165) has been developing new miniaturized detection approaches for different types of radiation. Among them is the second-generation prototype called TReCam.This mini gamma camera has a field of view of 4.9 x 4.9 cm2 and integrates imaging technologies directly from particle physics. It consists of a collimator with parallel holes, a continuous scintillator LaBr3 (Ce) read by a multi-anode photomultiplier (PSPMT) and its electronics. The acquisition system gives the surgeon a real-time display of the radioactive image.This thesis work also consisted in evaluating the place of portable imagers in radioguided surgery, in particular mammary surgery, through the evaluation of the SNOLL procedure (identification of the tumor (T) and the sentinel lymph nodes (GS) by γ-labeling) with TreCam. It is based on three parts.The first part aimed at optimizing the performance of TReCam to improve the localization of lowradioactive structures with exposure times of around 10 seconds. To do this, different performance optimization strategies have been implemented in the collimator, electronics and processing algorithms (including neural networks) to improve the homogeneity of the detection. These performances were compared to those of a prototype developed at IMNC and integrating a new generation of photodetectors: the SiPM.The second part aimed to objectify the clinical performance of TReCam in the SNOLL procedure and to situate the limits of its exploitation. Using simulations conducted on the GATE platform and modeling the operating scene closer to clinical reality, we have shown that TreCam can detect GS up to 4.5 cm deep and located 4 cm from the T. Impact of the exposure time is not important. On the other hand, choosing the right energy window is essential.Finally, the third part concretizes the interdisciplinary ambition of this thesis. It is devoted to clinical evaluation of TReCam through the study of its contribution to the SNOLL breast procedure. This prospective interventional study included 47 patients (22 SNOLL procedures using TReCam at different times of the procedure and 25 standard SNOLL procedures). The results showed a qualitative interest in the use of TReCam by bringing a visual comfort during the procedure and must be used in addition to the monopixel probes.This work has shown the interest of such imagers in radioguided surgery but also set their current limits. Development efforts must be pursued at the level of both detectors and radiopharmaceuticals used for tracking.Depuis son émergence, la médecine nucléaire ne cesse d’évoluer. A la fois diagnostique et thérapeutique, elle occupe une place importante dans la stratégie médicale moderne. L’imagerie nucléaire consiste après injection au patient d’un radiotraceur, à détecter le rayonnement émis. Elle donne accès quantitativement à la fonctionnalité des organes ou à la localisation de structures cibles telles que des lésions tumorales. Cette imagerie a naturellement intégré les procédures chirurgicales en particulier en cancérologie (en pré et per opératoire). On parle de chirurgie radioguidée. Cette dernière permet de localiser lors du geste chirurgical les structures radiomarquées devant être retirées.Les avancées technologiques au niveau des radiopharmaceutiques et en instrumentation sont à l’origine de nouvelles stratégies de radioguidages pouvant cibler de petites structures. L’imagerie par rayonnement gamma reste la plus répandue et la mieux adaptée. On assiste au développement de dispositifs d’imagerie gamma portables miniaturisés permettant un contrôle visuel en per opératoire. Ces dispositifs sont prometteurs mais doivent être évalués.Un état des lieux des différentes procédures en chirurgie radioguidée et des imageurs utilisés en clinique est réalisé dans cette thèse.Le laboratoire Imagerie et Modélisation en Neurobiologie et Cancérologie (UMR 8165) développe de longue date de nouvelles approches de détection miniaturisée pour les différents types de rayonnement. Parmi celles-ci le prototype de deuxième génération appelé TReCam.Cette mini gamma caméra présente un champ de vue de 4,9 x 4,9 cm2 et intègre des technologies d’imagerie directement issues de la physique des particules. Elle est formée d’un collimateur à trous parallèles, d’un scintillateur continu LaBr3 (Ce) lu par un photomultiplicateur multi-anode et son électronique. Le système d’acquisition donne au chirurgien un affichage en temps réel de l’image radioactive.Ce travail de thèse a consisté également à évaluer la place des imageurs portables en chirurgie radioguidée, en particulier mammaire, à travers l’évaluation de la procédure SNOLL (repérage par marquage ɣ de la tumeur (T) et des ganglions sentinelles (GS)) avec TreCam. Il a reposé sur trois parties.Un premier volet a visé l’optimisation des performances de TReCam pour favoriser la localisation de structures peu radioactives dans des temps d’exposition de l’ordre de la dizaine de secondes. Pour ce faire, différentes stratégies d’optimisation des performances ont été mises en place au niveau du collimateur, de l’électronique et des algorithmes de traitement (dont réseaux de neurones) pour améliorer l’homogénéité de la détection.Le deuxième volet visait à objectiver les performances cliniques de TReCam pour la procédure SNOLL et situer les limites de son exploitation. A l’aide de simulations menées sur la plateforme GATE et modélisant la scène opératoire au plus près de la réalité clinique, nous avons montré que TreCam peut détecter des GS jusqu’à 4,5 cm de profondeur et situé à 4 cm de la T. L’impact du temps de pose n’est pas important. Par contre, le choix de la bonne fenêtre en énergie est primordial.Enfin, le troisième volet concrétise l’ambition interdisciplinaire de cette thèse. Il est consacré à l’évaluation clinique de TReCam à travers l’étude de son apport à la procédure SNOLL mammaire. Cette étude prospective interventionnelle incluant de 47 patientes (22 procédures SNOLL utilisant TReCam aux différents temps de la procédure et 25 procédures SNOLL standard). Les résultats ont montré un intérêt qualitatif à l’utilisation de TReCam en apportant un confort visuel lors de la procédure en complément de la sonde monopixel.Ce travail a montré l’intérêt de tels imageurs en chirurgie radioguidée mais aussi situé leurs limites actuelles. Des efforts de développement doivent être poursuivis tant au niveau des détecteurs qu’au niveau des radiopharmaceutiques utilisés pour le repérage

Application of gamma camera (TreCam) in non palpable invasive breast cancer

Depuis son émergence, la médecine nucléaire ne cesse d’évoluer. A la fois diagnostique et thérapeutique, elle occupe une place importante dans la stratégie médicale moderne. L’imagerie nucléaire consiste après injection au patient d’un radiotraceur, à détecter le rayonnement émis. Elle donne accès quantitativement à la fonctionnalité des organes ou à la localisation de structures cibles telles que des lésions tumorales. Cette imagerie a naturellement intégré les procédures chirurgicales en particulier en cancérologie (en pré et per opératoire). On parle de chirurgie radioguidée. Cette dernière permet de localiser lors du geste chirurgical les structures radiomarquées devant être retirées.Les avancées technologiques au niveau des radiopharmaceutiques et en instrumentation sont à l’origine de nouvelles stratégies de radioguidages pouvant cibler de petites structures. L’imagerie par rayonnement gamma reste la plus répandue et la mieux adaptée. On assiste au développement de dispositifs d’imagerie gamma portables miniaturisés permettant un contrôle visuel en per opératoire. Ces dispositifs sont prometteurs mais doivent être évalués.Un état des lieux des différentes procédures en chirurgie radioguidée et des imageurs utilisés en clinique est réalisé dans cette thèse.Le laboratoire Imagerie et Modélisation en Neurobiologie et Cancérologie (UMR 8165) développe de longue date de nouvelles approches de détection miniaturisée pour les différents types de rayonnement. Parmi celles-ci le prototype de deuxième génération appelé TReCam.Cette mini gamma caméra présente un champ de vue de 4,9 x 4,9 cm2 et intègre des technologies d’imagerie directement issues de la physique des particules. Elle est formée d’un collimateur à trous parallèles, d’un scintillateur continu LaBr3 (Ce) lu par un photomultiplicateur multi-anode et son électronique. Le système d’acquisition donne au chirurgien un affichage en temps réel de l’image radioactive.Ce travail de thèse a consisté également à évaluer la place des imageurs portables en chirurgie radioguidée, en particulier mammaire, à travers l’évaluation de la procédure SNOLL (repérage par marquage ɣ de la tumeur (T) et des ganglions sentinelles (GS)) avec TreCam. Il a reposé sur trois parties.Un premier volet a visé l’optimisation des performances de TReCam pour favoriser la localisation de structures peu radioactives dans des temps d’exposition de l’ordre de la dizaine de secondes. Pour ce faire, différentes stratégies d’optimisation des performances ont été mises en place au niveau du collimateur, de l’électronique et des algorithmes de traitement (dont réseaux de neurones) pour améliorer l’homogénéité de la détection.Le deuxième volet visait à objectiver les performances cliniques de TReCam pour la procédure SNOLL et situer les limites de son exploitation. A l’aide de simulations menées sur la plateforme GATE et modélisant la scène opératoire au plus près de la réalité clinique, nous avons montré que TreCam peut détecter des GS jusqu’à 4,5 cm de profondeur et situé à 4 cm de la T. L’impact du temps de pose n’est pas important. Par contre, le choix de la bonne fenêtre en énergie est primordial.Enfin, le troisième volet concrétise l’ambition interdisciplinaire de cette thèse. Il est consacré à l’évaluation clinique de TReCam à travers l’étude de son apport à la procédure SNOLL mammaire. Cette étude prospective interventionnelle incluant de 47 patientes (22 procédures SNOLL utilisant TReCam aux différents temps de la procédure et 25 procédures SNOLL standard). Les résultats ont montré un intérêt qualitatif à l’utilisation de TReCam en apportant un confort visuel lors de la procédure en complément de la sonde monopixel.Ce travail a montré l’intérêt de tels imageurs en chirurgie radioguidée mais aussi situé leurs limites actuelles. Des efforts de développement doivent être poursuivis tant au niveau des détecteurs qu’au niveau des radiopharmaceutiques utilisés pour le repérage.Since its emergence in the middle of the twentieth century, nuclear medicine continues to evolve. At the same time diagnostic and therapeutic, it occupies an increasingly important place in the modern medical strategy. Nuclear imaging consists of injecting the patient with a radio-tracer to detect the radiation emitted. It provides quantitative access to the functionality of organs or the location of target structures such as tumor lesions. This imaging has been naturally integrated into surgical procedures, particularly in oncology (preoperatively and then intraoperatively). It is called radio-guided surgery. It makes possible to locate the radioactive target which will be removed during surgery.Technological advances in radiopharmaceutical instrumentation are driving new strategies that can target small structures. Gamma-ray imaging remains the most widespread and the most suitable. We are witnessing the development of miniaturized portable gamma imaging devices that allow visual control during surgery. These devices are promising but need to be evaluated.A short state-of-the-art of the various procedures in radioguided surgery and imagers used clinically is carried out in this thesis.For many years, the Imaging and Modeling in Neurobiology and Oncology Laboratory (UMR 8165) has been developing new miniaturized detection approaches for different types of radiation. Among them is the second-generation prototype called TReCam.This mini gamma camera has a field of view of 4.9 x 4.9 cm2 and integrates imaging technologies directly from particle physics. It consists of a collimator with parallel holes, a continuous scintillator LaBr3 (Ce) read by a multi-anode photomultiplier (PSPMT) and its electronics. The acquisition system gives the surgeon a real-time display of the radioactive image.This thesis work also consisted in evaluating the place of portable imagers in radioguided surgery, in particular mammary surgery, through the evaluation of the SNOLL procedure (identification of the tumor (T) and the sentinel lymph nodes (GS) by γ-labeling) with TreCam. It is based on three parts.The first part aimed at optimizing the performance of TReCam to improve the localization of lowradioactive structures with exposure times of around 10 seconds. To do this, different performance optimization strategies have been implemented in the collimator, electronics and processing algorithms (including neural networks) to improve the homogeneity of the detection. These performances were compared to those of a prototype developed at IMNC and integrating a new generation of photodetectors: the SiPM.The second part aimed to objectify the clinical performance of TReCam in the SNOLL procedure and to situate the limits of its exploitation. Using simulations conducted on the GATE platform and modeling the operating scene closer to clinical reality, we have shown that TreCam can detect GS up to 4.5 cm deep and located 4 cm from the T. Impact of the exposure time is not important. On the other hand, choosing the right energy window is essential.Finally, the third part concretizes the interdisciplinary ambition of this thesis. It is devoted to clinical evaluation of TReCam through the study of its contribution to the SNOLL breast procedure. This prospective interventional study included 47 patients (22 SNOLL procedures using TReCam at different times of the procedure and 25 standard SNOLL procedures). The results showed a qualitative interest in the use of TReCam by bringing a visual comfort during the procedure and must be used in addition to the monopixel probes.This work has shown the interest of such imagers in radioguided surgery but also set their current limits. Development efforts must be pursued at the level of both detectors and radiopharmaceuticals used for tracking

Endométriose abdominopelvienne profonde (distribution lésionnelle et implications physiopathologiques)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Accuracy of peritoneal carcinomatosis extent diagnosis by initial FDG PET CT in epithelial ovarian cancer: A multicentre study of the FRANCOGYN research group

International audienceIntroduction - Peritoneal carcinomatosis extent in ovarian cancer is difficult to evaluate by imaging techniques even though it determines the surgical complexity and survival. The aim of this study was to estimate the accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET CT (Positron-emission tomography coupled with Computerised Tomography) performed before any treatment, in the diagnosis of the extent of peritoneal carcinomatosis. We compared these results to per-operative observations/ histology samples obtained during surgery (laparotomy/ laparoscopy). Material and methods - All women managed for an epithelial ovarian cancer between 1st January 2000 and 30th June 2016 were included if they had a FDG PET CT, before initiation of any treatment (neoadjuvant chemotherapy or frontline cytoreductive surgery). The extent of disease on histology samples from cytoreductive surgery/observations during exploratory laparoscopy were compared with the PET CT results. Results - Over the study period, 980 women were managed for epithelial ovarian cancer, among them 90 (9.2 %) had a PET CT before any treatment. The diagnostic reliability of an ovarian lesion was 67.8 %, a colon lesion was 61.25 %, a small intestine lesion was 50.6 %, an epiploic lesion was 41.7 %, a pelvic ganglionic invasion was 62.9 % and a paraortic lymph node invasion was 61.5 %. PET CT was less effective than a standard CT examination. Conclusion - PET CT is not the most effective imaging examination to estimate the extent of peritoneal carcinomatosis during the initial management of an epithelial ovarian cancer

Is there a role for a handheld gamma camera (TReCam) in the SNOLL breast cancer procedure?

International audienceACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) and radio-guided occult lesion localization (ROLL). The safety and benefits of radio-guided localization in the surgical treatment of non-palpable breast cancer have been confirmed. The aim of this study was to evaluate the potential role for an intra-operative handheld tumor resection gamma camera (TReCam) in SNOLL procedures.METHODS: Fifteen patients were enrolled. The SNOLL procedure was performed in all patients with conventional lymphoscintigraphy (LS). TReCam was used to obtain nuclear imaging in the operating theater. Concordance between LS and TReCam images, duration of use and assessment of difficulties in data acquisition with TReCam were reported.RESULTS: Concordance for tumor localization between single-detector gamma probe and TReCam was excellent (15/15). The number of radioactive SLNs visualized between LS and TReCam was equivalent in 53.3% of cases (8/15). TReCam was considered to be very easy-to-use (12/15) or easy-to-use (3/15). Average duration of acquisition with TReCam was 4 minutes and 45 seconds for the SLN procedure, and 2 minutes and 10 seconds for lumpectomy.CONCLUSIONS: This study suggests that TReCam is easy-to-use and does not increase operative time. Its exact role in radio-guided surgery needs to be clearly defined in a larger study. However, its usefulness and benefits in radio-guided breast surgery seem to be promising

Risk Factors for Recurrence of Borderline Ovarian Tumours after Conservative Surgery and Impact on Fertility: A Multicentre Study by the Francogyn Group

International audienceIntroduction: Borderline ovarian tumours (BOT) represent 10–20% of epithelial tumours of the ovary. Although their prognosis is excellent, the recurrence rate can be as high as 30%, and recurrence in the infiltrative form accounts for 3% to 5% of recurrences. Affecting, in one third of cases, women of childbearing age, the surgical strategy with ovarian conservation is now recommended despite a significant risk of recurrence. Few studies have focused exclusively on patients who have received ovarian conservative treatment in an attempt to identify factors predictive of recurrence and the impact on fertility. The objective of this study was to identify the risk factors for recurrence of BOT after conservative treatment and the impact on fertility. Material and methods: This was a retrospective, multicentre study of women who received conservative surgery for BOT between February 1997 and September 2020. We divided the patients into two groups, the “R group” with recurrence and the “NR group” without recurrence. Results: Of 175 patients included, 35 had a recurrence (R group, 20%) and 140 had no recurrence (NR group, 80%). With a mean follow‐up of 30 months (IQ 8–62.5), the overall recurrence rate was 20%. Recurrence was BOT in 17.7% (31/175) and invasive in 2.3% (4/175). The mean time to recurrence was 29.5 months (IQ 16.5–52.5). Initial complete peritoneal staging (ICPS) was performed in 42.5% of patients (n = 75). In multivariate analysis, age at diagnosis, nulliparity, advanced FIGO stage, the presence of peritoneal implants, and the presence of a micropapillary component for serous tumours were factors influencing the occurrence of recurrence. The post‐surgery fertility rate was 67%. Conclusion: This multicentre study is to date one of the largest studies analysing the risk factors for recurrence of BOT after conservative surgery. Five risk factors were found: age at diagnosis, nulliparity, advanced FIGO stage, the presence of implants, and a micropapillary component. Only 25% of the patients with recurrence underwent ICPS. These results reinforce the interest of initial peritoneal staging to avoid ignoring an advanced tumour stage

Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer using a propensity score matching analysis: Results from the FRANCOGYN study group

International audienceINTRODUCTION:Pre-treatment evaluation of nodal status is crucial in women presenting with locally advanced cervical cancer (LACC). However, the prognostic impact of surgical staging remains to be proved, as published results comparing surgical versus radiological staging are contradictory. The aim of this study was to compare the prognosis of women with FIGO stage IB2-IIB CC who underwent surgical nodal staging including either exclusive para-aortic lymphadenectomy (PAL) or comprehensive pelvic + para-aortic lymphadenectomy (P-PAL).MATERIALS AND METHODS:Data of 314 women with FIGO stage IB2 to IIB CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. The prognosis and outcomes were compared by Propensity score (PS) matching (PSM) analysis.RESULTS:The median follow-up was 33 months (2-114). When comparing women who underwent PAL vs P-PAL, the recurrence rates were 26% (37/144) and 28% (41/144), respectively (p = 0.595). The respective 3-year recurrence free survival (RFS) for P-PAL and PAL were 72.9% (95% CI, 65.7-81.0) and 70.7% (95% CI, 62.4-80.2), (p = 0.394). The respective 3-year overall survival (OS) rates for P-PAL and PAL were 86.8% (95% CI, 81.1-92.9) and 78.6% (95% CI, 70.4-87.7) (p = 0.592). In the sub-group of women with lymph node metastases, RFS was improved for women who underwent P-PAL compared to those with exclusive PAL (p = 0.027), with no difference in OS (p = 0.187).CONCLUSIONS:Comprehensive P-PAL does not seem to be of significant therapeutic benefit compared to exclusive PAL

Lymphovascular space invasion and Estrogen Receptor status in high-grade serous ovarian cancer-a multicenter study by the FRANCOGYN group

International audienceBACKGROUND: The aim of this study was to evaluate the impact of Lymphovascular Space Invasion (LVSI) on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for high-grade serous epithelial ovarian cancer (HGSOC). MATERIALS AND METHODS: Retrospective multicenter study by the FRANCOGYN research group between January 2001 and December 2018. All patients managed for HGSOC and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A Cox analysis for OS and RFS analysis was performed in all populations. RESULTS: Over the study period, 410 patients were included in the thirteen institutions. Among them, 289 patients had LVSI (33.9%). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p<0.001) and RFS (p<0.001), Association of LVSI status and estrogen receptor status (ER) also affected OS and RFS (p=0.04; p=0.04 respectively). CONCLUSION: The presence of LVSI in HGSOC has an impact on OS and RFS and should be routinely included in the pathology examination along with ER status