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Résumé Introduction L'objectif de cette étude était de rappeler les pièges diagnostiques et les recommandations de prise en charge d'une masse rétropéritonéale. Méthodes Une revue de la littérature a été réalisée avec les mots clés : masse rétropéritonéale, réseau, diagnostic, recommandations, chirurgie. Résultats Un envahissement des organes de voisinage, des symptômes abdominaux ou un syndrome endocrinien peuvent évoquer une histologie extra-rénale. La tomodensitométrie thoraco-abdomino-pelvienne reste l'examen de référence. Des dosages hormonaux sont nécessaires en cas d'origine surrénalienne. La biopsie coaxiale par voie rétropéritonéale est recommandée avec congélation et relecture anatomopathologique. La résection chirurgicale en marges saines doit être planifiée en fonction du type histologique, en évitant une résection incomplète ou une effraction qui peut impacter sur la survie du patient. Conclusion Les tumeurs rétropéritonéales extra-rénales sont des tumeurs rares dont le pronostic est conditionné par la démarche diagnostique et la prise en charge initiale. Summary Introduction The aim of this study was to call back the diagnostic traps and the recommendations for treatment of a retroperitoneal mass. Methods A review of the literature was conducted using following keywords: retroperitoneal mass, network, diagnostic, recommendations, surgery. Results Invasion of contiguous organs, abdominal symptoms or endocrine syndrome can evoke an extra-renal histology. Thoraco-abdomino-pelvic computerized tomography (CT) is the standard imagery. Hormonal dosages are necessary in case of adrenal origin. Retroperitoneal coaxial biopsy is recommended with freezing and pathological verification. The surgical resection with negative margins should be planned according to pathology findings, with avoiding an incomplete resection or effraction, which could impact on patient's survival. Conclusion Retroperitoneal extra-renal tumors are rare tumors which prognosis is directly related to diagnostic procedure and initial management. [ABSTRACT FROM AUTHOR]

Background The role of percutaneous thermal ablation (PTA) in the multidisciplinary management of metastatic leiomyosarcoma (LMS) has not been thoroughly evaluated. Materials and methods Single institution retrospective review of all patients with LMS metastases treated with PTA from June 2004 to December 2014. Iterative PTAs were performed as a multifocal treatment for all recurrent or residual macroscopic metastases discovered on imaging after completion of systemic treatment, or alternatively as a targeted treatment of selective metastases found to be progressive on systemic treatment. The primary endpoint was the time to untreatable progression (TTUP), recorded as the time elapsed between the first PTA and the re-initiation of systemic chemotherapy to treat disease progression. Secondary endpoints were overall survival, the 1, 3 and 5-year survival rates, and local control rate. Results A total of 93 LMS metastases (average diameter 18.2 mm, range 3–45 mm) were successfully treated in 30 patients over 50 treatment sessions with a median follow-up of 34.6 months. The median TTUP was 14.2 months (range 2.4–122.8). The median overall survival after PTA was 48.3 months and the 1, 3 and 5-year overall survival rates were 96.7% (95%CI 84.3–100.0%), 62.0% (95%CI 45.8–84.0%), and 28.3% (95%CI 13.5–59.1%) respectively. Local control rate at 1 year was 95.2% and at 3 years was 89.4%. Conclusion Iterative PTA is an effective treatment line option for appropriately selected patients with metastatic LMS that can delay re-initiation of systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. Design: We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were 'hepatitis B reactivation', cross-referenced with 'chemotherapy', then 'hepatitis B' cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. Results: From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. Conclusion: Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigenpositive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption. [ABSTRACT FROM AUTHOR]

Aim To report initial results of observation as well as surgery in patients with desmoid tumors (DTs) of the breast, a rare tumor for which data are scarce. Patients and methods The initial approaches were categorized as either front-line loco-regional treatment [(surgery or radiotherapy group, SRG) n = 20] or initial observation [(no surgery/no radiotherapy group, NSRG) n = 11]. Results A total of 27 women and 4 men were assessed between 1992 and 2013 and included in this study. Patient characteristics were adequately balanced in the 2 groups. Fifteen patients (48.4%) had a past history of breast surgery in the previous 24 months. The median initial DT size on MRI was 50 mm. The median follow-up was 36 months. In the SRG, 8/20 patients (40%) experienced recurrence. The median time to recurrence was 29 months. During the study period, 6 patients in the SRG (30%) received a mastectomy at the time of diagnosis (n = 3) or at relapse (n = 3), 7 patients (35%) received a thoracic wall resection and 8 patients (40%) received radiotherapy at the time of diagnosis (n = 2) or at recurrence (n = 5). In the NSRG, the median tumor size change was −4 mm (range −13 to +20). Three patients changed treatment strategies during the observation period; one received surgery, and 2 were administered anti-hormonal treatment. Conclusions Loco-regional treatments of breast DTs resulted in undesired disfigurement. Front-line observation yielded encouraging results and could enable the identification of patients who require loco-regional treatment. This strategy needs further evaluation. [ABSTRACT FROM AUTHOR]

Aim To evaluate the indications and results of preoperative radiotherapy (RT) on a series of selected patients treated at our institution with curative intent for a limb sarcoma (STS). Patients and methods From 05/1993 to 12/2011, 64 STS patients received preoperative RT. Results RT was delivered as a “limb salvage treatment” prior to surgery for the following reasons: as the preferential induction treatment in 53 patients (83%) or as a second intent (17%) after the failure of neoadjuvant systemic chemotherapy/isolated limb perfusion. Surgery was performed after RT in 54 (84%) patients and final limb salvage was performed in 98%. Musculo-cutaneous flap reconstruction was planned upfront in 44% patients, and 19% had a skin graft. Seven patients (13%) had a postoperative RT boost. Thirteen (20%) patients had grade (G) 3/4 adverse events, one after RT and 12 after surgery. At a median follow-up of 3.5 years, the 3-year actuarial overall survival (OS) and distant relapse (DR) rates were 83% and 31%, respectively. Two patients developed a local relapse and two a local progression (non-operated patients). In the multivariate analysis (MVA), histological subtype (leiomyosarcoma) and grade 3 were predictive of poorer survival. Patients with >3 month delay between the start of RT and surgery at our institution had an increased risk of DR in the MVA. Conclusion Induction RT should be personalised according to histological subtype, tumour site and risks-benefit ratio of preoperative radiotherapy and is best managed by a multidisciplinary surgical and oncology team in a specialist sarcoma centre. [ABSTRACT FROM AUTHOR]

Background There are limited data about the role of chemotherapy in patients with Methods The medical charts of 180 patients with advanced chondrosarcomas having received chemotherapy in 15 participating institutions between 1988 and 2011 were reviewed. Results Median age was 52 years. Sixty-three percent of patients had conventional chondrosarcoma and 88% had metastatic disease. Combination chemotherapy was delivered in 98 cases (54.5%). One hundred and thirty-one patients (73%) received an anthracycline-containing regimen. Using RECIST, the objective response rate was significantly different according to histological subtype, being 31% for mesenchymal chondrosarcoma, 20.5% for dedifferentiated chondrosarcoma, 11.5% for conventional chondrosarcoma and 0% for clear-cell chondrosarcoma (P = 0.04). Median progression-free survival (PFS) was 4.7 months [95% confidence interval (CI) 3–6.5]. Performance status (PS) ≥2, number of metastatic sites ≥1 and single-agent regimen were independently associated with poor PFS. Median overall survival (OS) was 18 months (95% CI 14.5–21.6). PS, number of metastatic sites and palliative surgery were independently associated with OS. Conclusions Conventional chemotherapy have very limited efficacy in patients with advanced chondrosarcoma, the highest benefit being observed in mesenchymal and dedifferentiated chondrosarcoma. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma. [ABSTRACT FROM AUTHOR]

Background: Glutathione-S-transferases (GST) regulate the cellular response to oxidative stress. We previously highlighted the importance of oxidative stress in taxane toxicity and therefore investigated the relationship between the GST isoforms M1, T1 and P1 gene polymorphisms and docetaxel (Taxotere)-induced peripheral neuropathy (DIPN). [ABSTRACT FROM PUBLISHER]

Clin Microbiol Infect 2012; 18: E137-E139 Abstract Medical residents are particularly exposed to the risk of occupational infection. We aimed to determine the vaccination coverage in residents with an anonymous self-reporting electronic questionnaire. A total of 250 residents took part in this survey. Vaccination rates were particularly high for mandatory vaccinations (diphtheria, tetanus, poliomyelitis, hepatitis B virus and tuberculosis). Regarding recommended vaccinations (influenza, 45.6%; pertussis, 65.2%; measles, 62.8%; varicella, 62.8%), rates were insufficient to prevent hospital epidemics, but higher than those reported in other healthcare workers. Further immunization programmes should target residents, and not only senior healthcare workers, with a critical role for occupational medicine departments. [ABSTRACT FROM AUTHOR]

Accidental blood exposure (ABE) exposes healthcare workers, including medical residents, to the risk of occupational infection. We aimed to determine the characteristics of ABEs in residents with an anonymous self-reporting electronic questionnaire. A total of 350 residents (33% from surgical disciplines) entered this survey. One hundred and eighty-five residents (52%) reported at least one ABE during their residency (median, 2; range, 1-25), 53% of which occurred in operating theatres. Sixty-nine per cent of residents followed the current procedures for local disinfection. ABEs were notified to the hospital administration by 62% of residents, but only 51% of residents were referred to the occupational medicine department. The most frequently reported concerns following ABEs were human immunodeficiency virus (52%) and hepatitis C virus infection (39%). In 74% of cases, the serological status of the index patient was investigated. Only 54% of residents were aware of their hepatitis B surface antibody titres. Medical residents behaved inappropriately in 33% of cases in this survey. Further educational programmes should include residents, and not only senior healthcare workers, in order to improve individual behaviours. [ABSTRACT FROM AUTHOR]

Fenofibrate, a lipid-lowering drug frequently prescribed for everolimus-induced hypertriglyceridemia, was found to lower by >50% everolimus exposure in a breast cancer patient, probably due to CYP3A4 induction. Since everolimus plasma concentrations correlate with its anti-tumour activity, clinicians should probably avoid the use of fenofibrate in patients treated with everolimus. [ABSTRACT FROM PUBLISHER]

The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT / PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT / PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility. VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes. A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib. ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment. • This study comprehensively documents the landscape of KIT and PDGFRA mutations in metastatic, imatinib-resistant GIST. • Selective pressure exerted with prior lines promotes a shift toward increased resistant subpopulations in the KIT A-loop. • Individual mutations in KIT / PDGFRA determine TKI sensitivity and resistance in metastatic GIST. • ctDNA-detected KIT/PDGFRA mutations in imatinib-resistant GIST prognosticate third- or fourth-line TKI treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: The use of tyrosine kinase inhibitors (TKis) during pregnancy in humans remains rare, and little data are available on their transplacental passage. Erlotinib and gefitinib are the first-line targeted therapy in case of stage IV nonsmall- cell lung cancer with an EGFR-activating mutation. There are no data available regarding the comparative use of these TKis in pregnant patients. We aimed to compare the transplacental transfer of gefitinib, imatinib and erlotinib, using the ex vivo method of human perfused cotyledon, and to determine the placental accumulation of TKis. Materials and methods: Term placentas were perfused after delivery with gefitinib, imatinib and erlotinib at targeted maternal concentrations around the steady-state plasma trough concentration (i.e. 500, 1000 and 1500 ng/ml, respectively). Samples from fetal and maternal circulations were collected in order to monitor TKis concentrations. Main transfer parameters such as fetal transfer rate (FTR), clearance index (CI) and placental uptake were assessed. Results: Mean FTR of gefitinib, imatinib and erlotinib were 16.8%, 10.6% and 31.4%, respectively. Mean CI of gefitinib, imatinib and erlotinib were 0.59, 0.48 and 0.93, respectively. Placental uptake in cotyledon was 0.030% %, 0.010% and 0.003% for gefitinib, imatinib and erlotinib, respectively, corresponding to a mean mass of 27.7 μg for gefitinib, 15.7 μg for imatinib and 6.8 μg for erlotinib. Conclusion: The results suggest that TKis cross the placenta at therapeutic level. Particularly, erlotinib crosses the placenta at a higher rate than gefitinib or imatinib. All of them have a very low placental uptake. These data may suggest that gefitinib should be preferred to erlotinib for the treatment of pregnant woman with lung cancer harboring an EGFRactivating mutation, during the second and third trimesters of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Influenza vaccination is recommended to cancer patients undergoing chemotherapy, but vaccine coverage remains low. During the 2009 influenza pandemic, French recommendations were to vaccinate immunocompromised patients with two doses of adjuvanted vaccine. This study aimed to evaluate vaccine immunogenicity in cancer patients receiving chemotherapy. Patients and methods: VACANCE is a prospective open-label study that evaluated the immunogenicity and safety of two doses of AS03A-adjuvanted H1N1v vaccine in cancer patients receiving cytotoxic and/or targeted therapies. Serum haemagglutination-inhibited antibody titres against influenza A H1N1v were measured at days 1, 21, and 42, to estimate the proportion of participants with antibody titres ≥1 : 40 [seroprotection rate (SPR)], the efficacy of seroconversion, and factors that increased the geometric mean titre. Results: Sixty-five patients were included. At baseline, 5% of patients had vaccine strain titres of specific haemagglutination inhibition antibodies that were ≥1 : 40. After one and two doses of vaccine, SPRs were48% and 73%, respectively, and seroconversion rates were 44% and 73%, respectively. Vaccine-related adverse events were mild to moderate. Conclusions: A single dose of AS03-adjuvanted A/H1N1 vaccine triggered a low immune response in cancer patients on chemotherapy depending on their treatment type and frequency. Two doses are needed for these cancer patients. [ABSTRACT FROM PUBLISHER]

Background The development of immune checkpoint blocker development brings new hope in older patients (OPs) because of clinical efficacy and low toxicity. Clinical indications are rising steadily, but very few data are available in the geriatric population where comorbidities, reduced functional reserve and immunosenescence may affect efficacy and tolerance. Methods All cases of patients enrolled in immunotherapy phase I trials between January 2012 and December 2016 in the Drug Development Department (DITEP) at Gustave Roussy were retrospectively reviewed. Case–control analysis was performed in OPs (patients ≥ 70 years) matched to younger patients (YPs) (patients < 70 years) by trial and treatment dose. We compared cumulative incidence, grade and type of immune-related adverse events (IrAEs) and survival outcomes. Results Among the 46 OPs and the 174 YPs enrolled in 14 phase I/II trials, 10 (22%) and 23 (13%) patients experienced grade III–IV IrAEs. Cumulative incidence of grade I–II IrAEs was significantly higher in OPs than YPs (p < 0.05). No significant difference was observed between the two groups for grade III–IV IrAEs (p = 0.50). Older age was not associated with lower dose intensity of treatment (p = 0.14). No significant difference was observed between OPs and YPs in median progression-free survival (hazards ratio 1.41, 95% confidence interval [CI] [0.94–2.11] p = 0.09) or median overall survival (HR 0.92, 95% CI [0.61–1.39] p = 0.77). Conclusion Immune checkpoint blockade appears to be an acceptable treatment option for OPs in the setting of phase I trials. [ABSTRACT FROM AUTHOR]

Background: Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. Patients and methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Results: Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P<0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis. Conclusion: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB. [ABSTRACT FROM AUTHOR]