Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Cancers urologiques chez le transplanté rénal

But : Etudier les aspects épidémiologiques, cliniques, para-cliniques et pronostiques des cancers urologiques (cancer de la prostate, carcinomes urothéliaux et cancer du rein natif et transplanté) chez les transplantés rénaux de notre centre. Matériels et méthodes : De 1/1987 à 2/2006, 1050 patients consécutifs (384 femmes et 666 hommes) âgés de 44,7 +- 12,9 ans ont été transplantés et suivis dans notre centre. L immunosuppression utilisée dans notre centre était conventionnelle, quadruple et séquentielle. Le suivi a représenté 5434 personne-années. Un dosage du PSA et un toucher rectal ont été réalisés annuellement chez les hommes de 50 à 75 ans. Aucune surveillance spécifique des voies excrétrices urinaires et des reins natifs des transplantés n a été réalisée. Les cas de cancers urologiques chez les transplantés rénaux suivis dans notre centre ont été recensés de manière prospective. L incidence (I) et le risque relatif par rapport à la population générale (RR) ont été calculés. Résultats : Nous avons recensé 5 (I = 146/100 000/an RR = 1,95) cancers de prostate dont 2/5 étaient de haut risque de D Amico, 9 (I = 166/100 000/an RR = 2,58) tumeurs urothéliales de vessie dont 1/3 étaient d emblée infiltrantes, 2 (I = 37/100 000/an RR = 24,6) carcinomes urothéliaux des voies excrétrices supérieures et 12 (I = 221/100 000/an RR = 18,1) carcinomes à cellules rénales dont 46% de grade de Führman 3. Les âges moyens au diagnostic ont été de 58,7 +- 7,2 ans pour les cancers de prostate, 59,1 +- 7,9 ans pour les tumeurs urothéliales de vessie et 48,3 +- 9,8 ans pour les carcinomes à cellules rénales. Les survies globales et spécifiques ont été de 60% et 80% à 43 mois pour les cancers de prostate, 56% et 67% à 53 mois pour les tumeurs urothéliales de vessie et 83% et 92% à 48 mois pour les carcinomes à cellules rénales. Conclusion : Les cancers urologiques ont été plus fréquemment et plus précocement diagnostiqués et ont été histologiquement plus agressifs chez les patients transplantés que dans la population générale. L hypogonadisme lié à l insuffisance rénale chronique pourrait jouer un rôle dans le développement du cancer de la prostate. L immunosuppression a eu des conséquences thérapeutiques et pronostiques.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prognostic factors for cases with metastatic renal cell carcinoma in the era of targeted medicine.

International audiencePrognostic factors in the setting of treated metastatic renal cell carcinoma (mRCC) can theoretically predict drug response, progression-free survival or overall survival. These factors are potentially useful for informing patients and for tailoring medical treatment according to risk assessment. Prognostic factors were well defined in the era of immunotherapy. Since 2006, tyrosine kinase inhibitors and anti-angiogenic drugs have revolutionized the treatment of mRCC by improving progression-free survival and overall survival. Physicians now need new predictive tools adapted to targeted therapies. The aim of our study was to review the current knowledge about prognostic factors in mRCC by focusing on anatomical, clinical, biological, histological, radiological and molecular parameters. The most recent integrated prognostic models will be reviewed as well

Effet du carcinome in situ sur la survie de patients traités par chimiothérapie adjuvante après cystectomie

International audienceIntroduction: Factors predicting response to adjuvant chemotherapy (AC) are required to identify patients who will most benefit from it. The aim of this study was to evaluate the impact of carcinoma in situ (CIS) at radical cystectomy (RC) on recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS) of patients treated by AC. Materials and methods: A single-center retrospective study was performed on patients who received AC after RC without pre-RC chemotherapy or trimodal therapy. Results: Among the 150 patients analyzed, 52,7% had CIS on the RC specimens. Baseline characteristics were not significantly different between the CIS negative and positive groups. Most patients received a cisplatin-based AC (74%). The median follow-up of the cohort was 36,4 months. The presence of CIS was not significantly associated to disease-recurrence (OR = 0.67; 95%CI = 0.35–1.29; P = 0.23), cancer related death (OR = 0.70; 95%CI = 0.36–1.33; P = 0.27) or death by any cause (OR = 0.80; 95%CI = 0.42–1.52; P = 0.50). The presence of CIS had no significant impact on RFS (HR = 0.86; 95%CI = 0.56–1.33; P = 0.49), CSS (HR = 0.85; 95%CI = 0.53–1.36; P = 0.50) or OS (HR = 0.93; 95%CI = 0.60–1.45; P = 0.74). Conclusion: The presence of CIS on RC specimens did not have an impact on survival of patients treated by AC. CIS could be evaluated as a prognostic factor of response to novel adjuvant regimens such as immunotherapy.Il est nécessaire d’identifier les facteurs prédictifs de réponse à la chimiothérapie adjuvante (CA) pour mieux cibler les patients pouvant en bénéficier. L’objectif de cette étude était d’évaluer l’effet du carcinome in situ (CIS) sur la survie sans récidive (SSR), survie spécifique (SS) et survie globale (SG) de patients traités par CA après cystectomie.Matériel et méthodesUne étude monocentrique et rétrospective a été réalisée sur des patients traités par CA après cystectomie sans chimiothérapie ou traitement trimodal au préalable.RésultatsSur les 150 patients inclus, 52,7 % présentaient du CIS sur la pièce de cystectomie. Les caractéristiques des patients sans et avec CIS n’étaient pas significativement différentes. La plupart ont reçu une CA à base de cisplatine (74 %). Le suivi médian était de 36,4 mois. La présence de CIS n’était pas significativement associée à un risque de récidive (OR = 0,67 ; IC95 % = 0,35–1,29 ; p = 0,23), de décès par cancer (OR = 0,70 ; IC95 % = 0,36–1,33 ; p = 0,27) ou de décès toute cause (OR = 0,80 ; IC95 % = 0,42–1,52 ; p = 0,50). Elle n’avait pas d’influence significative sur la SSR (HR = 0,86 ; IC95 % 0,56–1,33 ; p = 0,49), SS (HR = 0,85 ; IC95 % = 0,53–1,36 ; p = 0,50) ou SG (HR = 0,93 ; IC95 % = 0,60–1,45 ; p = 0,74).ConclusionLa présence de CIS sur les pièces de cystectomies n’a pas d’impact significatif sur la survie après CA. Elle pourrait être évaluée pour les nouveaux traitements adjuvants telle que l’immunothérapie

[MTOR inhibitors: from transplantation to oncology. AFU 2006 Transplantation Committee Review of the literature]

International audienceThe use of mTOR inhibitors started about 30 years ago following the discovery of rapamycin, a macrolide derived from a soilborne microorganism Streptomyces hygroscopicus that exerts antibiotic, immunosuppressive and antiproliferative properties. Initially intended to be used as an antibiotic, a more detailed understanding of the mechanism of action of this class of drugs has rationalized and validated its use in the field of transplantation and oncology. Many clinical trials on mTOR inhibitors have been conducted in these two fields, in which urologists are actively involved. This review summarizes the current knowledge on the mechanism of action and clinical applications of mTOR inhibitors in renal transplantation and oncology

[MTOR inhibitors: from transplantation to oncology. AFU 2006 Transplantation Committee Review of the literature]

International audienceThe use of mTOR inhibitors started about 30 years ago following the discovery of rapamycin, a macrolide derived from a soilborne microorganism Streptomyces hygroscopicus that exerts antibiotic, immunosuppressive and antiproliferative properties. Initially intended to be used as an antibiotic, a more detailed understanding of the mechanism of action of this class of drugs has rationalized and validated its use in the field of transplantation and oncology. Many clinical trials on mTOR inhibitors have been conducted in these two fields, in which urologists are actively involved. This review summarizes the current knowledge on the mechanism of action and clinical applications of mTOR inhibitors in renal transplantation and oncology

Small intestinal submucosa xenograft to manage lower urinary tract prostheses perforation: a new path?

International audienceIntroduction and hypothesis: Tapes for stress urinary incontinence (SUI) and meshes for pelvic organ prolapse can result in postoperative complications, such as urethral (UP) or bladder (BP) perforations. Martius fat pad (MFP) is an historic procedure, widely used to treat lower urinary tract (LUT) fistulae. We report our experience with the insertion of the biological small intestinal submucosa (SIS) xenograft as an alternative to MFP in these prosthetic complications. Methods: We conducted a retrospective, monocentric study which included all patients who underwent SIS insertion during surgical removal of tape/vaginal mesh for UP or BP from 2011 to 2019. Preoperative assessment was based on history, symptoms, physical examination and urethrocystoscopy. Primary outcome was successful repair defined as absence of any LUT defect. Secondary outcomes were complications, LUT symptoms, pain and additional SUI surgical procedures. Results: Thirty-eight patients were included. Twenty-six had a UP and eight a BP. In four cases, perforation involved both the bladder neck and urethra. All LUT defects were cured. Six postoperative complications were reported (five of grade ≤ 2 and one of grade 3b according to the Clavien-Dindo classification). At the mean follow-up of 37.2 (range 6–98) months, 14 patients (36.8%) presenting a postoperative SUI underwent a SUI surgical procedure and 1 patient had a laparoscopic sacrocolpopexy for cystocele recurrence. Conclusion: Absorbable SIS xenograft is an effective and safe graft for the management of lower urinary tract tape and mesh perforations. The cost has to be balanced with the good results, short operative time and no fat pad complications as in MFP

Morbidity of retropubic radical prostatectomy for prostate cancer in renal transplant recipients: multicenter study from Renal Transplantation Committee of French Urological Association.

International audienceOBJECTIVES: To evaluate the morbidity and surgical complications of retropubic radical prostatectomy (RRP) in renal transplant recipients (RTRs) and compare these results with the observed morbidity in a control group of nontransplanted patients. METHODS: We conducted a multicenter retrospective study and reviewed the charts and records of 20 RTRs who had undergone RRP for localized prostate cancer at four French renal transplant centers belonging to the Renal Transplantation Committee of the French Urological Association from April 1996 to April 2007. A total of 40 patients who had undergone RRP at the same centers, by the same surgeons, were analyzed as the case-control population. RESULTS: The mean operating time (163 +/- 41 vs 160 +/- 66 minutes), blood loss (516 +/- 279 vs 566 +/- 449 mL), transfusion rate (20% vs 22.5%), and hospital stay (11.9 +/- 5.44 vs 9.45 +/- 2.8 days) were similar in the RTR and case-control populations. No graft loss or graft injury was reported in the RTRs, except for two ureteral injuries that were immediately repaired during RRP. No decrease in the kidney graft function was observed after RRP. The rate of medical complication (deep venous thrombosis, pulmonary embolism, urinary tract infection) was similar in both groups, except for the rate of bacterial systemic infection, which was significantly greater in the RTRs than in the controls (15% vs 2.5%, P = .01). CONCLUSIONS: In our study, RRP was a safe procedure to treat localized prostate cancer in RTRs. RRP resulted in the same morbidity in RTRs as in the case-control population

Concentration and chain length of polyethylene glycol in islet isolation solution: evaluation in a pancreatic islet transplantation model.

International audienceTo improve graft preservation and consequently reduce conservation injuries, the composition of preservation solution is of outmost importance. It was demonstrated that the colloid polyethylene glycol (PEG), used in SCOT solution, has protective effects on cell membranes and immunocamouflage properties. The aim of this study was to optimize the concentration and chain length of PEG to improve pancreatic islet preservation and outcome. In a model of murine islet allotransplantation, islets were isolated with SCOT containing various concentrations of PEG 20 kDa or 35 kDa. Better islet yield (IEQ) was obtained with SCO +PEG at 15-30 g/L versus other PEG concentrations and control CMRL-1066 + 1% BSA solution (p < 0.05). Allograft survival was better prolonged (up to 20 days) in the groups SCOT + PEG 20 kDa 10-30 g/L compared to PEG 35 kDa (less than 17.8 days) and to control solutions (less than 17.5 days). In terms of graft function recovery, the use of PEG 20 kDa 15-30 g/L induced no primary nonfunction and delayed graft function contrary to CMRL-1066 and other PEG solutions. The use of the extracellular-type solution SCOT containing PEG 20 kDa 15 g/L as colloid could be a new way to optimize graft integrity preservation and allograft outcome