Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

[High-intensity focused ultrasound for locally prostate cancer: An Afro-Caribbean single-center study]. / Ultrasons focalisés de haute intensité pour le traitement du cancer localisé de la prostate : étude mono-centrique caribéenne.

INTRODUCTION: High-intensity focused ultrasound (HIFU) has proved to be effective in the treatment of localized prostate cancer. The aim of this prospective study is to assess their first oncological and functional results in an Afro-Caribbean population. METHODS: From May 2018 to January 2020, 77 patients issued from French West Indies were included. Several treatments were carried out: whole-gland treatment hemi or focal ablation; in a primary setting (group I) or a salvage therapy (group II). PSA level was assessed at 2, 6, 9 and 12 months. MpMRI and post HIFU biopsy were performed between 6 and 9 months postoperatively. Continence, urinary end erectile functions were assessed by ICS, IPSS and IIEF scores. RESULTS: Groupe I included 71.2% patients, group II, 28.8%. The median age was 75.4 years [IQR 69.6-79.4]. The median follow-up was 8.3 months [IQR 3.5-12.25]. At inclusion, PSA was 7.7ng/ml [IQR 5.5-11.2] in group I, and 5.9ng/ml [IQR 4.4-7.9] in group II. In the whole population, there was 73.5% negative biopsies; 14.7% of the biopsies were positive in treated zone and 11.8% in non-treated zone. Regarding morbidities, urinary incontinence appeared in 7.5% and erectile dysfunction rate was 13.2%. CONCLUSION: Our study reveals the first experience of HIFU by Focal One® device in an Afro-Caribbean population. It seems to be a safe and reproducible treatment with acceptable oncological results and low genitourinary morbidity. Long term follow-up and a higher number of patients are necessary to validate these results.

Active surveillance in prostate cancer is possible for Afro-Caribbean population: Comparison of oncological outcomes with a Caucasian cohort.

BACKGROUND: Prostate cancer is supposedly more aggressive among Afro-Caribbean men. There is a lack of data in this population for active surveillance. Published series are retrospective or have small samples and results are discordant. The objective was to determinate whether actual active surveillance modalities can be applied for Afro-Caribbean men by comparing their oncological outcomes with Caucasian men. METHODS: A total of 449 consecutive patients who underwent active surveillance for favorable-risk prostate cancer in two French University-Medical-Centers between 2005 and 2018: 261 in Guadeloupe, French West Indies, and 188 in Bordeaux, metropolitan France. Median follow-up was 56 months, (95% CI [32-81]) and 52 months (95% CI [30-75]), respectively (P=0.07). Curative treatment was given in case of histological, biological, or imaging progression, or upon patient demand. Primary endpoints were treatment-free, overall and specific survival. Secondary outcomes were reasons of discontinuating active surveillance, histological poor prognosis factors after prostatectomy, CAPRA-S score, biochemical-recurrence-free after treatment and metastasis-free survival. Kaplan-Meier method was used. RESULTS: Median treatment free survival was 58.4 months (CI 95% [48.6-83.1]) for ACM and not reached at 120 months for CM (P=0.002). Overall survival (P=0.53), and specific survival (P=0.21) were similar in the two groups. CM were likely to have poor prognosis factor on prostatecomy piece (57 vs 30%, P=0.01). No difference for repartition of the CAPRA-S score (P=0.86), biochemical-recurrence-free (P=0.92) and metastasis-free (P=0.44) survival. CONCLUSIONS: Oncological outcomes for active surveillance of Afro-Caribbean and Caucasian men were similar in terms of mortality, recurrence and metastasis in our bicentric study, showing usability of current criteria for Afro-Caribbean. The higher rate of disease progression in the Afro-Caribbean population requires close monitoring. LEVEL OF EVIDENCE: 3.

[Follow-up of patients treated for an epithelial ovarian cancer, place of hormone replacement therapy and of contraception: Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Surveillance après traitement initial d'une tumeur épithéliale de l'ovaire, place du traitement hormonal de la ménopause et de la contraception. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

OBJECTIVES: To define follow-up modalities after an epithelial ovarian, tubal or primitive peritoneal cancer. To define possibilities of hormone replacement therapy (HRT) and contraceptive use after treatment. METHODS: Systematic review of the literature in French and English langage conducted on Pubmed/Medline and the Cochrane Library. RESULTS: After the treatment of an epithelial ovarian, tubal or primitive peritoneal cancer, symptoms evaluation for follow-up is recommended at 3 months, 6 months, 12 months, 18 months, 24 months, and then yearly (Grade B). Only patients with an initial complete surgery (CC0, without any macroscopic signs of disease), and with a good general condition (ECOG 0) should be followed with paraclinic tests, with a serum HE4 or CA125 concentration measurement, from 6 months after the end of treatments (GradeC). Systematic follow-up with CT of the chest, abdomen, and pelvis is not recommended (GradeC). Imaging test is recommended in case of an increased serum concentration of HE4 or CA125 (Grade B). An HRT should be proposed to women younger than 45 after a non-conservative treatment for a high grade serous (GradeC) or for a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma. HRT is not contra-indicated in women older than 45 presenting a climacteric syndrome after the treatment of a high grade serous (Grade B) or of a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma.

[Pelvimetrics measures as predictives factors of positives surgical margins after robot-assisted laparoscopic prostatectomy]. / Mesures pelvimétriques prédictives de marges chirurgicales au décours d'une prostatectomie totale robot-assitée pour cancer prostatique.

INTRODUCTION: Anthropometric data report that pelvic bone of African subjects are narrower and the pelvic cavity is deeper. The aim of the study was to evaluate the influence of pelvic dimensions (PD) on Positive surgical margins (PSM) rate in Afro-Caribbean population after robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: Preoperative pelvic MRI of all patients who have had RALP at the University Hospital Center of Guadeloupe between January 2013 and December 2015 was retrospectively analyzed. PD, including the Height of the upper edge of the prostate (HP), the Apical Depth (AD) and Ischial Spines Distance (ISD), and indexes (prostate volumetric index [ISD/VP], apical depth index [ISD/AD] and prostate depth index [ISD/(AD/HP)]) were compared according to the presence or absence of PSM with uni and multivariate analysis. RESULTS: One hundred and seventy-eight patients were included in the study, of whom 60 (33.7%) presented PSM. In univariate analysis, significant differences between the presence or absence of PSM were observed on the AD (30.3±8.7mm versus 24.8±8.0mm, P<0.001), the HP (9.5±8.5mm versus 16.8±11.9mm, P<0.001) and the ISD (89.6±8.8mm versus 96.1±8.4mm) as well as the indexes of apical depth and prostatic depth. In multivariate logistic regression, the ISD (P<0.001) and HP (P=0.02) were associated with increased likelihood of PSM, but not AD or indexes. CONCLUSION: This study suggests that interspinous distance is the best predictor of PSM during RALP in Afro-Caribbean patients. This measure may be useful to define the therapeutic pattern of patients with prostate cancer. A prospective study with a larger population, comparing RALP in Afro-Caribbean and in caucasians patients, would be needed.

[Epidemiology of urolithiasis in French West Indies: A retrospective study]. / Épidémiologie de la lithiase urinaire aux Antilles françaises : étude rétrospective monocentrique.

INTRODUCTION: The incidence of urolithiasis is increasing with dietary changes especially in developed countries. Guadeloupe is a French department overseas where western diet meets traditional local food. The objective was to describe and analyze the epidemiology of urolithiasis in Guadeloupe. MATERIAL AND METHODS: We conducted a retrospective single-center study throughout the year 2015 on patients hospitalized for urolithiasis at University Hospital of Pointe-à-Pitre. Data of the patients, treatments performed and the types of stones were recorded. According to their mineral content, groups were composed. RESULTS: In total, 165 patients were included. The sex ratio was 1.61. The median body mass index (BMI) was 26.5kg/m2. The most common stone was oxalocalcic (64.7%). Mixed stones (24.7%) were in second place. There were only 3.5% of uric acid urolithiasis. Calcium oxalate stones were predominantly monohydrate. The oxalocalcic stones were significantly more frequent in men (80% versus 47.5%, P=0.01) and in the age group over 50 years old (72.2% versus 51.6%, P=0.04). There was no association between the type of stone and the BMI. CONCLUSION: Epidemiology of urolithiasis in our French Caribbean island is, therefore, similar to continental France. However, our population is distinguished by the proportion of women affected and by the different proportions among each type of stone. Other studies on larger samples are needed to study these specificities. LEVEL OF EVIDENCE: 4.

[Impact of Gleason score on biochemical recurrence free survival after radical prostatectomy with positive surgical margins]. / Impact du score de Gleason sur la survie sans récidive biologique après prostatectomie totale pour cancer avec marges chirurgicales positives.

PURPOSE: Research of predictive factors of biochemical recurrence to guide the establishment of an adjuvant treatment after radical prostatectomy for cancer with positive surgical margins. METHODOLOGY: A retrospective cohort of 1577 afro-caribbean patients undergoing radical prostatectomy operated between 1st January 2000 and 1st July 2013 was analyzed. In this cohort, 406 patients had positive surgical margin, we excluded 11 patients who received adjuvant therapy (radiotherapy, hormonotherapy, radio-hormonotherapy) and 2 patients for whom histological analysis of the surgical specimen was for a pT4 pathological stage. After a descriptive analysis, we used a Cox model to look for predictors of survival without biochemical recurrence then, depending on the significant variables, we separated our population into six groups: stage pT2 with Gleason score≤3+4 (group 1), stage pT2 with a score of Gleason≥4+3 (group 2), stage pT3a with a Gleason core≤3+4 (group 3), pT3a stage with a score of Gleason≥4+3 (group 4), stage pT3b with a Gleason score≤3+4 (group 5) and stage pT3b Gleason≥with a score of 4+3 (group 6) and compared survival without biochemical recurrence using a log rank test. After radical prostatectomy with surgical margins with an anatomopathological stage≤pT3b, a Gleason score≥4+3 had a pejorative survival without biochemical recurrence than pathological stage (P<0.001). RESULTS: In multivariate analysis, predictors of survival without biochemical recurrence after radical prostatectomy with positive surgical margins were the majority Gleason postoperative (P<0.0001), pathological stage (P=0.049) adjusted preoperative PSA (P=0.826), with the body mass index (BMI) (P=0.59) and tumor volume (P=0.95). CONCLUSION: A high postoperatively Gleason score (≥4+3) has a better predictive value of biochemical recurrence than pathological stage pT2 or pT3 at the patients having been treated for prostate cancer by radical prostatectomy with positive surgical margins. LEVEL OF EVIDENCE: 4.

[Should a systematic fertility preservation be proposed to healthy women carrying a BRCA1/2 mutation?]. / Faut-il proposer systématiquement une préservation de la fertilité aux femmes porteuses de mutation BRCA1/2 indemnes ?

Should all women with BRCA1 or BRCA2 genes mutations be considered at risk of prematurely impaired fertility, and thus should a fertility preservation systematically be proposed? Women carrying mutations of BRCA1 or BRCA2 are at high risk for breast and tubo-ovarian cancer. The treatment of a breast cancer at a young age, unrare in this population, is associated with a risk of infertility, due to the ovarian toxicity of chemotherapy, to the recommended duration of hormonotherapy when indicated, and to the time advised before starting a pregnancy. Furthermore, some data in the literature suggest a higher risk of premature ovarian failure among women with BRCA1/2 mutation: advance of the age at menopause and poorer response to ovarian stimulation have been observed. Several pathophysiological hypotheses support this finding, as the involvement of the BRCA genes in maintaining telomere length, the DNA repair anomalies promoting oocyte apoptosis, differences in FMR1 genotype. Current fertility preservation techniques have limitations, some of them being specific to BRCA1/2 women: absence of oncological risk due to stimulation in BRCA1/2 women not clearly demonstrated, oocyte vitrification techniques limited rentability, graft of ovarian cortex not suitable in these women at high risk. Thus, data on the increased risk of premature ovarian failure remaining weak, such a systematic proposal seems questionable.

Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. METHODS: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. RESULTS: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. CONCLUSION: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

Nephron sparing surgery for De Novo kidney graft tumor: results from a multicenter national study.

Nephron sparing surgery (NSS) results in the transplanted population remain unknown because they are only presented in small series or case reports. Our objective was to study renal sparing surgery for kidney graft renal cell carcinomas (RCC) in a multicenter cohort. Data were collected from 32 French transplantation centers. Cases of renal graft de novo tumors treated as RCC since the beginning of their transplantation activity were included. Seventy-nine allograft kidney de novo tumors were diagnosed. Forty-three patients (54.4%) underwent renal sparing surgery. Mean age of grafted kidneys at the time of diagnosis was 47.5 years old (26.1-72.6). The mean time between transplantation and tumor diagnosis was 142.6 months (12.2-300). Fifteen tumors were clear cell carcinomas (34.9%), and 25 (58.1%) were papillary carcinomas. Respectively, 10 (24.4%), 24 (58.3%) and 8 (19.5%) tumors were Fuhrman grade 1, 2 and 3. Nine patients had postoperative complications (20.9%) including four requiring surgery (Clavien IIIb). At the last follow-up, 41 patients had a functional kidney graft, without dialysis and no long-term complications. NSS is safe and appropriate for all small tumors of transplanted kidneys with good long-term functional and oncological outcomes, which prevent patients from returning to dialysis.

[The significance of PSA density as predictive factor in Afro-Caribbean patients eligible for active surveillance by the French protocol criteria]. / Intérêt de la densité du PSA comme facteur prédictif chez les patients afro-caribéens éligibles à la surveillance active du cancer de prostate selon les critères du protocole français.

OBJECTIVES: Study the interest of addition of PSA density (PSAD), to the selection criteria of the French protocol for inclusion patients Afro-Caribbean on active surveillance prostate cancer. METHODS: A retrospective analysis of 1505 patients who had, in turn, a radical prostatectomy for cancer between 2000 and 2012, in a single reference center. One hundred and forty-one patients was eligible, at the time of their diagnosis, for active surveillance by the criteria of the French protocol. This population was divided into 2 groups according to the histological analysis of the prostatectomy specimen confirmed indolent cancer or overturned. The median PSAD of each group was calculated to be compared. Secondarily, the most discriminating PSAD was investigated by the method of ROC after constitution tables intrinsic validity in this population. This threshold has secondary conducting a comparative analysis of the underestimation of cancer in terms of aggressiveness and/or extension between patients selected according to the criteria of the French protocol and "on-selected" patients according to these criteria and their PSAD. RESULTS: Of the 141 patients identified for analysis, histological examination of the prostatectomy specimen has to show that 42 patients (29.7 %) were actually more aggressive cancer (20.6 % of Gleason ≥ 7), wider (4.2 % ≥ pT3) or larger and more aggressive (4.9 %) than foreshadowed criteria French protocol. The median PSAD these 42 patients were significantly higher than the median PSAD patients correctly estimated (0.18 vs. 0.14, p-value=0.046). The application of the most discriminating threshold: 0.15 ng/ml/cm(3) in this population allowed to significantly improve the selection of candidates of the 79 "on-selected" patients, six (20.2 %) were actually more aggressive cancer (13.9 % of Gleason ≥ 7), wider (2.5 % ≥ pT3) or larger and more aggressive (3.8 %). CONCLUSION: The criteria for the French protocol for active surveillance, applied to the Caribbean population underestimate 29 % of non-latent cancers. Adjuvants criteria that must be inexpensive, sensitive and specific seem necessary in this population. A PSAD<0.15 ng/ml/cm(3) could be one of these criteria.

[Stage IV prostate cancer in Guadeloupe, a French Caribbean archipelago]. / Cancer de prostate non localisé au diagnostic en Guadeloupe.

OBJECTIVES: To study clinical characteristics, in terms of survival and response to treatment, of patients with non-localized prostate cancer at diagnosis in an Afro-Caribbean population from Guadeloupe. METHODS: Cases of stage IV prostate cancer (T4N0M0, TxN1M0 and TxNxM1) at diagnosis in the Pointe à Pitre Hospital were selected from 1995 to 2012 and studied. RESULTS: One hundred and eighty-three patients were included. Median age at diagnosis was 70.3 years old (79.2% were more than 65 years). A total of 81.5% of them was TxNxM1 and 11.5% was TxN1M0. Median disease free survival was 18.5 months. Median overall survival was 49.0 months. CONCLUSION: This study about non-localized prostate cancer at diagnosis in an Afro-Caribbean population from a French Caribbean archipelago seemed to show no difference with general population suffering from the same disease, although prostate cancer incidence in this area is one of the highest in the world.

Cation exchange versus multimodal cation exchange resins for antibody capture from CHO supernatants: identification of contaminating host cell proteins by mass spectrometry.

We compared classical and multimodal cation exchange resins for the capture of recombinant antibodies from Chinese hamster ovary (CHO) cell culture supernatant. Both Capto S and Capto MMC resins present anionic groups while the multimodal Capto MMC also features a hydrophobic moiety. First we screened optimal binding and elution conditions in microplates with a pure antibody. We validated the results on the lab-scale with columns with a pure antibody and a CHO cell culture supernatant. Both resins achieved good yield and purity for the capture step of an antibody. However, the multimodal resin appeared more efficient and selective. Then we identified proteins in the antibody fraction by mass spectrometry in order to highlight the behavior of host cell proteins (HCPs).

[Radiotherapy with androgen deprivation in high-risk prostate cancer: what outcomes on a Caribbean population?]. / Radiohormonothérapie dans le cancer de la prostate à haut risque : quels résultats sur une population Antillaise ?

OBJECTIVE: To analyze in a Caribbean population at 90% of African descent, the results of radiotherapy with androgen deprivation (AD) in high-risk prostate cancer (PCa). PATIENTS AND METHODS: Fifty-nine consecutive patients with a high-risk PCa as defined by the D'AMICO classification and treated by radiotherapy with AD between January 2003 and April 2009 in our center were analyzed. The median dose of radiation and the median duration of AD were 70Gy and 37months respectively. Biochemical recurrence (BF), as primary outcome was defined according to the PHOENIX criteria (nadir PSA+2ng/mL). Multivariate analysis was performed to identify predictive factors of BF. The median follow-up was 47months. RESULTS: Eight (13.6%) patients had BF and four (6.8%) developed metastases. Six (10.2%) died during the follow-up. The 5years acturial biochemical disease-free survival was 79.7%. Multivariate analyses have shown that Gleason sum (GS) superior to 7 (P=0.029), AD duration less than 24months (P=0.004) and the rate of Nadir PSA greater or equal to 0.5ng/mL (P=0.011) were independent predictive factors of BF. CONCLUSION: This study was the first to our knowledge, to provide that radiotherapy associate with AD for HRPC among Caribbean men is effective as observed in other populations. Patients with GS superior to 7 could be considered for more aggressive treatments in clinical trials.

De novo kidney graft tumors: results from a multicentric retrospective national study.

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis.