[Fertility preservation in cervical cancer, analysis of 30 years of practice and immersion in future developments]. / La préservation de fertilité en cas de cancer du col, analyse de 30 ans de pratique et immersion dans les évolutions à venir.

OBJECTIVES: The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP. METHODS: This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices. RESULTS: 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term. CONCLUSION: Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.

Artificial intelligence and breast screening: French Radiology Community position paper.

The objective of this article was to evaluate the evidence currently available about the clinical value of artificial intelligence (AI) in breast imaging. Nine experts from the disciplines involved in breast disease management - including physicists and radiologists - convened a meeting on June 3, 2019 to discuss the evidence for the use of this technology in plenary and focused sessions. Prior to the meeting, the group performed a literature review on predefined topics. This paper presents the consensus reached by this working group on recommendations for the future use of AI in breast screening and related research topics.

Detection and characterization of MRI breast lesions using deep learning.

PURPOSE: The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions. MATERIALS AND METHODS: We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores. RESULTS: We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set. CONCLUSION: This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort.

Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI.

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.

Modulation of Rb phosphorylation and antiproliferative response to palbociclib: the preoperative-palbociclib (POP) randomized clinical trial.

Background: The cyclin-dependent kinase 4 (CDK4)/6 inhibitor Palbociclib is a new standard treatment in hormone-receptor positive breast cancer patients. No predictive biomarkers have been identified and no pharmacodynamics has properly been described so far. Patients and methods: Patients with early-breast cancer were randomized 3 : 1 to oral palbociclib 125 mg daily for 14 days until the day before the surgery versus no treatment. Primary objective was antiproliferative response defined as a natural logarithm of Ki67 expression at day 15 below 1. Secondary end points were subgroups analyses and safety. Exploratory analyses included search for predictive biomarkers. Immunostainings (Ki67, RB, pRB, p16, pAKT, pER, pCDK2, CyclinD1), FISH (CCND1) and gene expression (GE) arrays were carried out at baseline and at surgery. In addition, activating PIK3CA and AKT1 mutations were assessed at baseline. Results: 74 patients were allocated to palbociclib and 26 to control. Most patients (93%) were hormone-receptor (HR)-positive, whereas 8% were HER2-positive. Palbociclib led to significantly more antiproliferative responses when compared with control (58% versus 12%, P < 0.001), and to a significantly higher Ki67 decrease (P < 0.001). In the HR-positive/HER2-negative subgroup, this antiproliferative effect was even more marked in the palbociclib arm when compared with control (70% versus 9%, P < 0.001). Palbociclib treatment led also to a significantly higher decrease from baseline in phospho-Rb when compared with control (P < 0.001). Among treated patients, changes in Ki67 correlated with changes in phospho-Rb (Spearman rank r = 0.41, P < 0.0001). GE analyses confirmed a major effect on proliferation and cell cycle genes. Among treated patients, CCNE2 expression was significantly more decreased in antiproliferative responders versus nonresponders (P = 0.006). Conclusion: Short-term preoperative palbociclib decreases Ki67 in early-breast cancer patients. Early decrease of Rb phosphorylation correlates with drug's effect on cell proliferation and could potentially identify patients with primary resistance. Clinical trial registration: NCT02008734.

Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria.

BACKGROUND: Immune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non-small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population. PATIENTS AND METHODS: We conducted a monocentric retrospective analysis of consecutive advanced NSCLC patients treated with an anti-programmed cell death-1 or anti-program death-ligand 1. Response patterns and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were described, and associations of response patterns and clinical outcome were explored. RESULTS: Overall, 160 patients treated between February 2013 and October 2016 were included. Atypical responses were observed in 20 patients (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease, and 123 patients (77%) exhibited progression. Eighty progressive patients were assessable for irRECIST and iRECIST: 15 patients were assessed differently; however, only three (3.8%) mismatches with a theoretical impact on the therapeutic decision were identified. Patients with PsPD or dissociated response had higher overall survival than patients with true progression. CONCLUSION: Atypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1 evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of the progressive patients. Immune-related RECIST and iRECIST identified these unconventional responses, with a 3.8% discrepancy rate.

Breast pain and imaging.

Breast pain is a common reason for consultation and a source of anxiety for patients. Cyclical breast pain can be distinguished from non-cyclical pain and breast pain with other symptoms. Many causes, usually benign are possible and the clinical enquiry and physical examination are essential to establish predisposing factors. Although imaging is not always needed for isolated breast pain, it is still useful for the diagnosis of specific causes such as tension cysts, giant adenofibromas or Mondor's thrombophlebitis. Ultrasound is the first line investigation before mammography, MRI or biopsy, which may be indicated for suspicious abnormalities. Some cancers may be associated with pain, which implies that radiologists and physicians should always take breast pain seriously.

Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia.

BACKGROUND: Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide). PATIENTS AND METHODS: The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded. RESULTS: Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾ 2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91-99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth. CONCLUSION: With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.

Whole body MRI in paediatric oncology.

Whole body MRI provides excellent contrast resolution imaging and is an interesting alternative to nuclear medicine examinations in paediatric oncology because it does not involve exposure to radiation. This technique, now feasible in clinical practice, helps to evaluate metastatic spread and response to treatment, which are of great prognostic interest. Numerous studies have demonstrated the non-inferiority of this technique when compared to nuclear medicine examinations. However, there is still a need to standardize indications in each type of cancer and at every stage of it. This article first discusses the technical principles of whole body MRI, then reviews current clinical applications for the modality in children, and finally, discusses future useful developments for paediatric oncology.

Preoperative imaging prior to breast reconstruction surgery: benchmarking bringing together radiologists and plastic surgeons. Proposed guidelines.

BACKGROUND: Prescription of preoperatory imaging assessment prior to planned breast reconstruction surgery (reduction or augmentation mastoplasty, correction of congenital breast asymmetry) is poorly codified. The objective of this study was to analyze the attitudes of French radiologists and plastic surgeons with regard to prescription of preoperative imaging in the framework of non-oncologic breast surgery. MATERIAL AND METHODS: This is a descriptive and comparative observational study involving two groups, one consisting of 50 plastic surgeons (P) and the other of 50 radiologists (R) specialized in breast imaging. A questionnaire was handed out to radiologists during a conference on breast imaging at the Institut Gustave-Roussy in Paris (France) held on 17th December 2012. The same questionnaire was handed out to plastic surgeons at the National Congress of the French Society of Plastic and Reconstructive Surgery (SOFCPRE) held on 19th, 20th and 21st November 2012, also in Paris (France). The questionnaire focused on prescription of preoperative and postoperative imaging evaluation for non-oncologic breast surgery in patients with no risk factors for breast cancer or clinically identified indications. RESULTS: Forty-six percent of the plastic surgeons considered an imaging exam to be recent when it had been carried out over the previous 6 months, while 40% of the radiologists set the figure at 1 year. Clinical breast density exerted no influence on 92% of the plastic surgeons and 98% of the radiologists. A majority of the plastic surgeons would prescribe a preoperative exam regardless of age (57% for breast reduction, 61% for breast implant placement and 61% for surgical correction of asymmetry) while the radiologists would prescribe exams mainly for patients over 40 years (50% for reduction, 44% for augmentation, 49% for asymmetry correction). The plastic surgeons would prescribe either ultrasound or mammograms (59% for reduction, 72% for augmentation, 66% for asymmetry correction) while radiologists would usually prescribe mammograms (64%, 57%, 64%). Most of the radiologists, along with the plastic surgeons, did not think that postoperative examination is justified (58% of P and 62% of R for reduction, 56% P and 68% of R for augmentation, 52% of P and 64% of R for asymmetry correction). CONCLUSION: In 2012, there existed no French consensus on prescription of a preoperative imaging assessment in the framework of non-oncologic breast surgery in patients without risk factors for breast cancer. Active cooperation bringing together radiologists and plastic surgeons is likely to facilitate the harmonizing of their respective practices. In this paper, we propose guidelines that could help them to synchronize their efforts.

Breast elastography: the technical process and its applications.

Breast elastography is being increasingly used to better characterize breast lesions. Published studies have shown that it improved specificity of B mode ultrasound. Two elastography modes are available: free-hand elastography and shear wave elastography. Free-hand elastography is obtained by a mechanic wave induced by the ultrasound probe, deforming the target, either by small movements induced by breathe. An elastogram is obtained and displayed either as a colour map or a size ratio or elasticity ratio measurement. The second mode is shear wave elastography; two methods are available: Shear Wave Elastography (SWE) and ARFI mode (Acoustic Radiation Force Impulse). Shear wave elastography is less operator-dependent than free-hand elastography mode and provides a quantitative approach. A value of over 80kPa (SWE) or velocity results of over 2m/s (ARFI) are considered as suspicious. False negatives may occur in soft breast cancers (mucinous carcinoma, carcinoma with an inflammatory stroma, etc.) and false positives may be seen with poorly deformable benign lesions such as old fibrous adenomas. In practical use, elastography is a useful complementary tool for undetermined breast lesions categorized as BI-RADS 4a or BI-RADS 3, or for cystic lesions but cannot avoid fine needle aspiration or core biopsy if ultrasound features are clearly suspicious.

Computed-aided diagnosis (CAD) in the detection of breast cancer.

Computer-aided detection (CAD) systems have been developed for interpretation to improve mammographic detection of breast cancer at screening by reducing the number of false-negative interpretation that can be caused by subtle findings, radiologist distraction and complex architecture. They use a digitized mammographic image that can be obtained from both screen-film mammography and full field digital mammography. Its performance in breast cancer detection is dependent on the performance of the CAD itself, the population to which it is applied and the radiologists who use it. There is a clear benefit to the use of CAD in less experienced radiologist and in detecting breast carcinomas presenting as microcalcifications. This review gives a detailed description CAD systems used in mammography and their performance in assistance of reading in screening mammography and as an alternative to double reading. Other CAD systems developed for MRI and ultrasound are also presented and discussed.

Pure and mixed mucinous carcinoma of the breast: fine needle aspiration cytology findings and review of the literature.

OBJECTIVE: Mucinous (colloid) breast carcinoma accounts for 1-6% of all breast cancer. It comprises pure mucinous tumours and mixed infiltrating ductal carcinomas with a mucinous component. As this latter mixed form has a worse prognosis than pure colloid carcinoma, making this diagnosis on fine needle aspiration cytology (FNAC) might influence the choice of treatment. METHODS: We report a consecutive series of 22 cases consisting of 17 mixed and five pure mucinous carcinomas diagnosed by cytology and verified on histopathology. Patients underwent FNAC at the one-stop clinic of our institution during a 7-year period of time. Cytological findings were evaluated by a semi-quantitative method and included percentage of smear surface occupied by mucin, shape of cell groupings, size and outline of tumour nuclei as well as presence or absence of nucleolus. RESULTS: Three of five pure mucinous carcinomas displayed at least two of the following features: abundant mucin, small nuclei and/or regular nuclear outlines. Sparse mucin, large nuclei, irregular nuclear outlines or the presence of nucleoli were found in 7 out of 17 mixed mucinous carcinomas but not in pure tumours. CONCLUSION: Cytopathological identification of patients with pure mucinous carcinomas may be performed in a limited number of cases.

Breast elasticity: principles, technique, results: an update and overview of commercially available software.

Breast ultrasound elasticity evaluation has become a routine tool in addition to diagnostic ultrasound during the last five years. Two elasticity evaluation modes are currently available: free-hand elastography and shear-wave elastography (SWE). Most of the commercially available elastography scanners have specific procedures which must be understood by the users. Free-hand elastography usually displays qualitative imaging such as an elastogram, but most of the companies now use it to quantify the relative stiffness between a lesion and the surrounding breast tissue. SWE is a new mode theoretically independent of the sonographer which displays more quantitative information, and can be useful for characterizing breast lesions. Recent studies on elastography suggest that elasticity imaging can increase B-mode accuracy and specificity in differentiating benign and malignant breast lesions. This functional imaging mode could help reduce the number of biopsies performed for benign breast lesions. This review gives a detailed description of the main commercially available systems and the results of current applications in the evaluation of breast elasticity.

[Conformal accelerated partial breast irradiation: state of the art]. / Irradiation partielle accélérée conformationnelle du sein : état des lieux.

Breast conserving treatment (breast conserving surgery followed by whole breast irradiation) has commonly been used in early breast cancer since many years. New radiation modalities have been recently developed in early breast cancers, particularly accelerated partial breast irradiation. Three-dimensional conformal accelerated partial breast irradiation is the most commonly used modality of radiotherapy. Other techniques are currently being developed, such as intensity-modulated radiotherapy, arctherapy, and tomotherapy. The present article reviews the indications, treatment modalities and side effects of accelerated partial breast irradiation.

[MR imaging patterns of bone marrow]. / Approche didactique de la moelle osseuse en IRM.

The marrow contains a variable amount of yellow or fatty marrow and red or cellular marrow creating the signal intensity observed on MRI. Marrow replacement (by cells not normally present in bone marrow) typically is T1W hypointense. Marrow proliferation (by cells normally present in bone marrow) may be T1W hypointense (pseudo marrow replacement) or show intermediate T1W signal intensity due to red marrow redistribution. Marrow edema (reaction to an external process) show intermediate T1W hypointensity (mixture of water and marrow). Location will allow correct diagnosis. Bone marrow ischemia usually results in a necrotic fragment surrounded by a thin T1W hypointense rim.

[Accelerated partial breast irradiation: bifractionated 40Gy in one week. A French pilot phase II study]. / Étude pilote française de phase II d'irradiation partielle accélérée du sein conformationnelle tridimensionnelle bi-fractionnée hebdomadaire de 40Gy.

PURPOSE: Since 2009, accelerated partial breast irradiation (APBI) in North America has been allowed to be used for selected group of patients outside a clinical trial according to the ASTRO consensus statement. In France, accelerated partial breast irradiation is still considered investigational, several clinical trials have been conducted using either intraoperative (Montpellier) or Mammosite(®) (Lille) or brachytherapy modality (PAC GERICO/FNCLCC). Here, we report the original dosimetric results of this technique. PATIENTS AND METHODS: Since October 2007, Institut Gustave-Roussy has initiated a phase II trial using 3D-conformal accelerated partial breast irradiation (40 Gy in 10 fractions BID in 1 week). Twenty-five patients with pT1N0 breast cancer were enrolled and were treated by two minitangent photons beams (6MV) and an "en face" electron beam (6-22 MeV). RESULTS: The mean clinical target volume and planning target volume were respectively 15.1cm(3) (range: 5.2-28.7 cm(3)) and 117 cm(3) (range: 52-185 cm(3)). The planning target volume coverage was adequate with at least a mean of 99% of the volume encompassed by the isodose 40 Gy. The mean dose to the planning target volume was 41.8 Gy (range: 41-42.4 Gy). Dose inhomogeneity did not exceed 5%. Mean doses to the ipsilateral lung and heart were 1.6 Gy (range: 1.0-2.3 Gy) and 1.2 Gy (range: 1.0-1.6 Gy), respectively. CONCLUSION: The 3D conformal accelerated partial breast irradiation using two minitangent and "en face" electron beams using a total dose of 40 Gy in 10 fractions BID over 5 days achieves appropriate planning target volume coverage and offers significant normal-tissue sparing (heart, lung). Longer follow-up is needed to evaluate the tissue tolerance to this radiation dose.

Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma.

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.