Long-term clinical outcomes of preoperative brachytherapy in early-stage cervical cancer.

OBJECTIVE: The treatment of early-stage cervical cancer (CC) is primarily based on surgery. Adjuvant (chemo)radiotherapy can be necessary in presence of risk factors for relapse (tumor size, deep stromal invasion, lymphovascular space invasion (LVSI), positive margins, parametrial or lymph node involvement), increasing the risk of treatment toxicity. Preoperative brachytherapy can reduce tumor extension before surgery, potentially limiting the need for adjuvant radiotherapy. This study reports long-term clinical outcomes on efficacy and toxicity of preoperative pulse-dose-rate (PDR) brachytherapy in early-stage CC. METHODS: All patients treated at Institut Curie between 2007 and 2022 for early-stage CC by preoperative brachytherapy were included. A PDR technique was used. Patients underwent hysterectomy associated with nodal staging following brachytherapy. RESULTS: 73 patients were included. The median time from brachytherapy to surgery was 45 days [range: 25-78 days]. With a median follow-up of 51 months [range: 4-185], we reported 3 local (4 %), 1 locoregional (1 %) and 8 metastatic (11 %) relapses. At 10 years, OS was 84.1 % [95 % CI: 70.0-100], DFS 84.3 % [95 % CI:74.6-95.3] and LRFS 92.8 % [95 % CI:84.8-100]. Persistence of a tumor residue, observed in 32 patients (44 %), was a significant risk factor for metastatic relapse (p = 0.02) and was associated with the largest tumor size before brachytherapy (p = 0.04). Five patients (7 %) experienced grade 3 toxicity. One patient (1 %) developed grade 4 toxicity. Ten patients (14 %) received adjuvant radiotherapy, increasing the risk of lymphedema (HR 1.31, 95 % CI [1.11-1.54]; p = 0.002). CONCLUSIONS: PDR preoperative brachytherapy for early-stage cervical cancer provides high long-term tumor control rates with low toxicity.

Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer.

BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis. MATERIALS AND METHODS: We identified 175 patients with primary HER2-positive breast cancers receiving NAC+/- trastuzumab between 2002 and 2011. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Univariate and multivariate analyses were carried out to assess the association of clinical and pathological factors with pathological complete response (pCR) and disease-free survival. RESULTS: Baseline TIL levels were not significantly associated with pCR. TIL levels decreased during treatment in 78% of the patients. The magnitude of the decrease was strongly associated with pCR. After chemotherapy, TIL levels were high in tumors displaying aggressive patterns (high residual cancer burden score, mitotic index >22, tumor cellularity >5%). In the population with residual disease, TIL levels >25% at the end of NAC were significantly associated with an adverse outcome (TILs >25%, HR = 7.98, P = 0.009) after multivariate analyses including BMI, post-NAC mitotic index and tumor grade. CONCLUSION: A decrease in TIL levels during chemotherapy was positively associated with response to treatment. In tumor failing to achieve pCR, post-NAC lymphocytic infiltration was associated with higher residual tumor burden and adverse clinical outcome. Further studies are required to characterize immune infiltration in residual disease to identify candidates who could benefit from second-line therapy trials including immune checkpoint inhibitors.

[Exploration of breast inflammation excluding pregnancy and breastfeeding: Guidelines]. / Exploration d'une inflammation du sein en dehors de la grossesse et de la période d'allaitement: recommandations.

Breast inflammation, excluding breast-feeding and pregnancy, is a rare breast pathology. We conducted a PubMed database search of all studies focusing on mastitis or breast inflammation exploration. While the most frequent aetiologies are infectious and inflammatory, inflammatory breast cancer can be diagnosed (LE2). Aetiologic diagnostic is difficult due to the absence of any clinical and imaging specific signs (LE3). The presence of mass, suspect lymph nodes or skin thickening in a woman older than 40 years old should orient toward inflammatory breast cancer (LE3). A suspect lesion must lead to perform a biopsy under sonography (grade A). In the absence of evidence for a malignant pathology after initial evaluation, we recommend starting an antibiotic treatment (grade C) with a clinical follow-up at the end of the treatment (grade B). If the symptoms persist, we recommend a new imaging (± MRI) (grade C) and a biopsy (grade C). Benign inflammatory pathologies may require a biopsy to exclude an inflammatory breast cancer and precise the diagnosis. Their specific management and treatment are presented in detail in the following chapters and may involve steroids.

[Clinical practice guidelines: Benign breast tumor--Aims, methods and organization]. / Recommandations pour la pratique clinique: tumeurs bénignes du sein--Objectifs, méthodes et organisation.

Conversely to breast cancer, few data and guidelines are available to explore and manage benign breast disorders. Therefore, the Collège national des gynécologues et obstétriciens français (CNGOF - French College of Gynaecologists and Obstetricians) decided to establish clinical practice guidelines for benign breast tumour (BBT). CNGOF appointed a committee with responsibility for selecting experts, compiling questions and summarizing the recommendations. The summary of valid scientific data for each question analyzed by the experts included a level of evidence, based on the quality of the data available and defined accordingly rating scheme developed by the Haute Autorité de santé (French National Authority for Health).

[Inflammatory and infectious breast mastitis outside of pregnancy and lactation: Guidelines]. / Mastites inflammatoires et infectieuses du sein en dehors de la grossesse et de la période d'allaitement : recommandations.

OBJECTIVES: This work's objective was to define the various non-cancerous inflammatory and infectious mastitis, which may occur outside of pregnancy and lactation, and to identify recommendations for their care based on an exhaustive literature review. MATERIALS AND METHODS: A literature review was conducted by consulting Medline, Cochrane Library, Google scholar and international recommendations in French and English until 31st August 2014. RESULTS AND CONCLUSION: Infectious mastitis (periareolar abscess) is the most common form of non-puerperal abscesses and it is recommended that a suction/drainage needle for abscesses under 5 cm, involving antibiotic therapy (grade C). For abscesses over 5 cm, there is no evidence to recommend a first surgery or suction/drainage. Inflammatory mastitis can be primary or secondary to a systemic disease (diabetes, collagen…; LE4). In case of idiopathic granulomatous mastitis, a steroid therapy or surgery may be indicated, without one or the other of these methods can be recommended. In case of plasma cell mastitis or ductal ectasia, no treatment is recommended.

[Benign breast tumors: Recommendations of Collège National des Gynécologues Obstétriciens Français (CNGOF)--Short text]. / Tumeurs bénignes du sein: recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF)--Texte court.

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C).

Prognostic impact of discrepant Ki67 and mitotic index on hormone receptor-positive, HER2-negative breast carcinoma.

BACKGROUND: Inconsistencies between mitotic index (MI) and Ki67 measures have been identified in many breast tumour samples. The aim of this study was to describe the prognosis of hormone receptor-positive (HR+) HER2- tumours having discrepant MI and Ki67. METHODS: We included a cohort of breast cancer patients initially treated by surgery between 2001 and 2005 in the Institut Curie. Breast cancer-specific survival (BCSS) and disease-free survival (DFS) were analysed according to three proliferation groups: high MI/high Ki67 (MI=3, Ki67>20%), low MI/low Ki67 (MI<3, Ki67⩽20%) and discrepant (high MI/low Ki67 or low MI/high Ki67). RESULTS: Among the 1430 patients, 19.6% had discrepant Ki67 and MI, 11.6% had high markers and 68.8% had low markers. The 5-year BCSS was 95.8%, 95% CI (0.93-0.98) in the discrepant group, 99.3%, 95% CI (0.993-0.999) in the low-proliferation group and 91.8%, 95% CI (0.88-0.96) in the high-proliferation group. In multivariate analysis, the survival of the discrepant group was lower than that of the low-proliferation group: BCSS hazard ratio (HR)=3.01 (1.32-6.84; P=0.008) and DFS HR=2.07, 95% CI (1.31-3.26; P=0.002). Among grade 2 tumours in multivariate analysis, DFS of the discrepant group was lower than that of the low MI/low Ki67 group: HR=1.98, 95% CI (1.14-3.46), P=0.02. Regarding BCSS, the obtained results were similar. CONCLUSION: The prognosis of patients with discrepant MI and Ki67 appears intermediate between that of low MI/low Ki67 and high MI/high Ki67 groups. These markers should be jointly analysed to clarify prognosis.

Are we able to predict survival in ER-positive HER2-negative breast cancer? A comparison of web-based models.

BACKGROUND: Several prognostic models have been proposed and demonstrated to be predictive of survival outcomes in breast cancer. In the present article, we assessed whether three of these models are comparable at an individual level. METHODS: We used a large data set (n=965) of women with hormone receptor-positive and HER2-negative early breast cancer from the public data set of the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study. We compared the overall performance of three validated web-based models: Adjuvant!, CancerMath.net and PREDICT, and we assessed concordance of these models in 10-year survival prediction. RESULTS: Discrimination performances of the three calculators to predict 10-year survival were similar for the Adjuvant! Model, 0.74 (95% CI 0.71-0.77) for the Cancermath.net model and 0.72 (95% CI 0.69-0.75) for the PREDICT model). Calibration performances, assessed graphically, were satisfactory. Predictions were concordant and stable in the subgroup, with a predicted survival higher than 90% with a median score dispersion at 0.08 (range 0.06-0.10). Dispersion, however, reached 30% for the subgroups with a predicted survival between 10 and 50%. CONCLUSION: This study revealed that the three web-based predictors equally perform well at the population level, but exhibit a high degree of discordance in the intermediate and poor prognosis groups.

Fertility before and after surgery for deep infiltrating endometriosis with and without bowel involvement: a literature review.

AIM: Endometriosis affects from 10% to 15% of women of childbearing age and 20% of these women have deep infiltrating endometriosis (DIE). The goal of this review was to assess the impact of various locations of DIE on spontaneous fertility and the benefit of surgery and Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) on fertility outcomes. METHODS: MEDLINE search for articles on fertility in women with DIE published between 1990 and April 2013 using the following terms: "deep infiltrative endometriosis", "colorectal", "bowel", "rectovaginal", "uterosacral", "vaginal", "bladder" and "fertility" or "infertility". Twenty-nine articles reporting fertility outcomes in 2730 women with DIE were analysed. RESULTS: Among the women with DIE and no bowel involvement (N.=1295), no preoperative data on spontaneous pregnancy rate (PR) were available. The postoperative spontaneous PR rate in these women was 50.5% (95% Confidence Interval [CI] =46.8-54.1) and overall PR (spontaneous pregnancies and after MAR) was 68.3% (95% CI=64.9-71.7). No evaluation of fertility outcome according to locations of DIE was feasible. For women with DIE with bowel involvement without surgical management (N.=115), PR after MAR was 29%; 95% CI=20.7-37.4). For those with bowel involvement who were surgically managed (N.=1320), postoperative spontaneous PR was 28.6% (95% CI=25-32.3) and overall postoperative PR was 46.9% (95% CI=42.9-50.9). CONCLUSION: For women with DIE without bowel involvement, surgery alone offers a high spontaneous PR. For those with bowel involvement, the low spontaneous and relatively high overall PR suggests the potential benefit of combining surgery and MAR.

[Delays in treatment of breast cancer: experience of an expert center of the Assistance Publique-Hôpitaux de Paris (AP-HP)]. / Délais au traitement du cancer du sein : expérience d'un centre expert (CEX) de l'Assistance Publique des Hôpitaux de Paris (AP-HP).

OBJECTIVES: The National Institute of the Cancer (INCA) recently published a study over the deadlines of medical care of breast cancers. We compared our delay within the framework of our expert center with their results. PATIENTS AND METHODS: Our work is a retrospective unicentric non-interventional study. We included all the patients taken care for a breast cancer to the hospital Tenon in Paris. The criteria of inclusion were a primitive breast cancer, having accepted a care for a first cancer operated over a period of three months. We recovered 9 key deadlines to study the care of our patients. RESULTS: Sixty-six patients were included. The mean age was of 55.6 years. The deadline of access to the hospital Tenon was 8.7 ± 7.7 days for the meetings of gynecology and 4.3 ± 4 days for those of radiology. The deadline of access to the diagnosis was 31.8 ± 26 days. The deadlines of access to the meeting of multidisciplinary dialogue pre-therapeutic was 13 ± 11 days. The access to the first management time was 18.5 days for the neoadjuvant chemotherapy and 13.5 days for surgery. The deadline of access to the postoperative therapeutic proposal was on average 20 ± 8 days. The deadline of access to the postoperative radiotherapy was of 197 days in case of postoperative chemotherapy vs 47.5 days without chemotherapy. The global deadline mammography-radiotherapy was of 188 days. DISCUSSION AND CONCLUSION: The deadline of access to the diagnosis, to the postoperative therapeutic proposal and the global deadline mammography-radiotherapy with adjuvant chemotherapy or neoadjuvant were longer in our center compared with the results of the INCA. The deadlines of access to the surgery and access to the radiotherapy without postoperative chemotherapy were shorter on the other hand. The contribution of the diagnosis in one day for breast cancer is probably going to allow us to improve the deadlines of care in our structure.

[Obstetric and neonatal outcomes of adolescent pregnancies: a cohort study in a hospital in Seine-Saint-Denis France]. / Devenir obstétrical et néonatal des grossesses chez les adolescentes : cohorte de patientes en Seine-Saint-Denis.

OBJECTIVES: The aim of this study was to describe the characteristics, monitoring, obstetrical complications, childbirth and neonatal outcomes of pregnancies among minors in a cohort of adolescents from Seine-Saint-Denis (France). PATIENTS AND METHODS: This is a retrospective, cohort, comparative study, conducted from January 1, 1996 to July 31, 2011, made from the database of Jean-Verdier hospital in Seine-Saint-Denis. Three groups were established: patients aged less than 16 years old, patients aged over 16 years old and under 18 years old compared to a group consisting of older primiparas from 18 to 25 years old. The criteria considered were the characteristics of pregnancy, terms of delivery, neonatal outcome and conduct of post-partum. RESULTS: Minor patients were statistically more likely to be single, student, smoking and anemia compared to young adults. The obstetrical care was lower for minor compared to the control group with a number of consultations and ultrasounds lower (P < 0.001). Obstetrical complications were similar in the three groups outside of preterm labor. Adolescentes under 16 years old had a higher preterm delivery risk in multivariate analysis (RR = 0.33 CI 95% [0.12; 0.90] P = 0.03). Adolescents had fewer cesarean and instrumental deliveries (P < 0.05). DISCUSSION AND CONCLUSION: Teenage pregnancy remains an important managing issue for maternities, particularly from a social standpoint. On the medical side, one preterm delivery appears to be more common among these adolescents.

[Comparison of the rate of maternal complications of nifedipine and nicardipine in cases of preterm labor: historical study on two consecutive periods]. / Comparaison de la fréquence des complications maternelles de la nifédipine et de la nicardipine en cas de menace d'accouchement prématuré à membranes intactes : étude historique portant sur deux périodes consécutives.

OBJECTIVES: Calcium channel blockers are the most frequently used tocolytics as first-line in France, frequently intravenously (nicardipine [Loxen(®)]). We would like to compare the side effects of intravenous nicardipine and oral nifedipine. MATERIALS AND METHODS: We performed a restrospective study on two consecutive periods. On the first period (March 2007-September 2008), 110 patients received intravenous nicardipine for preterm labor, and 67 patients received oral nifedipine on the second period (October 2008-January 2010). Side effects were recorded. RESULTS: Patients in the nicardipine-treated group had significantly more side effects (31% versus 16% for nifedipine group, P=0.03). No-administration way related adverse events did not differ between the two groups (P=0.1). There was more low blood pressure in patients treated with nifedipine (P=0.03), but shorter hospital stay (5.4 days versus 7.9 days with nicardipine, P=0.05). CONCLUSION: Using nifedipine simplifies tocolysis administration, and decreases hospital stays without increasing the risk of prematurity.