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Decisions on market authorization (MA) and reimbursement have different durations across countries because of health technology assessment (HTA) procedures and negotiations between manufacturers and national authorities. To overcome this delay, France has implemented a Temporary Authorization for Use (ATU) program that allows early access to drugs before MA, in order to treat patients with unmet medical needs. The objectives of our study were to establish the added therapeutic benefit (ATB) of ATUs for solid tumors and to investigate the correlations between three tools evaluating ATB and survival outcomes and drug costs. Data on ATUs granted from January 2009 to December 2019 to treat solid tumors were analyzed. An assessment of their ATB was conducted using the American Society of Clinical Oncology-Value Framework (ASCO-VF), the European Society for Medical Oncology-Magnitude Clinical Benefit Scale (ESMO-MCBS) and the French HTA criterion, clinical added value (CAV). The latter score determines reimbursement and national market access. Thirty-five drugs in 39 indications were granted ATUs. All of them obtained MA and derived a clinical benefit to be reimbursed by the Social Security. Twenty-eight (71.8%) had CAV compared to preexisting therapies. 24/38 (63.2%) had a 4-5 ESMO-MCBS score and 19/33 (57.6%) had an ASCO-VF score over 45. No correlations were found between cost, PFS, OS, CAV and ASCO-VF score, while high ESMO-MCBS scores were correlated to OS. In conclusion, many patients were treated with innovations before MA thanks to ATU, although there are discrepancies between ATB scales, hence the importance of international collaboration in the evaluation of innovative therapies.
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Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , França , Humanos , OncologiaRESUMO
An elevated nitrogen concentration in water is one of the main problems affecting water quality in Mediterranean rivers. The objectives of this study were (1) to evaluate the contribution of the Tafna catchment to the nitrate load entering the Mediterranean Sea, (2) to quantify the impact of agriculture on the nitrate concentration in water bodies, (3) to evaluate nitrate loads entering groundwater, and (4) to quantify the role of reservoirs in nitrate retention. A SWAT model was applied during the period 2003 to 2011. The discharge calibration was based on a previous study by Zettam et al. (2017). NSE efficiencies ranged from 0.421 to 0.75, R2 ranged from 0.25 to 0.84, and PBIAS ranged from 3.68 to 39.42. The simulations of monthly nitrate loads were satisfactory in the upstream sampling stations, with NSE between 0.48 and 0.65 and R2 between 0.63 and 0.68. The PBIAS was satisfactory in all the sampling stations (- 36.30 to 10.42). In the downstream sampling stations, the calibration of the monthly nitrate loads was unsatisfactory (NSE ranged from - 0.26 to 0.21 and R2 ranged from 0.02 to 0.25). Fertilisation was the main N input in the catchment, while the main N output was plant uptake. The Tafna River carried an annual average of 37 to 85.5 t N year-1 into the Mediterranean Sea. The simulation also showed that reservoirs in the Tafna basin contain a large quantity of nitrates, i.e. 62% on average of the total amount of nitrates transported annually by the Tafna River.
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Nitratos/análise , Poluentes Químicos da Água/análise , África do Norte , África Ocidental , Agricultura , Monitoramento Ambiental , Mar MediterrâneoRESUMO
The investigation of ultrafast dynamics, taking place on the few to sub-picosecond time scale, is today a very active research area pursued in a variety of scientific domains. With the recent advent of X-ray free-electron lasers (XFELs), providing very intense X-ray pulses of duration as short as a few femtoseconds, this research field has gained further momentum. As a consequence, the demand for access strongly exceeds the capacity of the very few XFEL facilities existing worldwide. This situation motivates the development of alternative sub-picosecond pulsed X-ray sources among which femtoslicing facilities at synchrotron radiation storage rings are standing out due to their tunability over an extended photon energy range and their high stability. Following the success of the femtoslicing installations at ALS, BESSY-II, SLS and UVSOR, SOLEIL decided to implement a femtoslicing facility. Several challenges were faced, including operation at the highest electron beam energy ever, and achievement of slice separation exclusively with the natural dispersion function of the storage ring. SOLEIL's setup also enables, for the first time, delivering sub-picosecond pulses simultaneously to several beamlines. This last feature enlarges the experimental capabilities of the facility, which covers the soft and hard X-ray photon energy range. In this paper, the commissioning of this original femtoslicing facility is reported. Furthermore, it is shown that the slicing-induced THz signal can be used to derive a quantitative estimate for the degree of energy exchange between the femtosecond infrared laser pulse and the circulating electron bunch.
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Transition to novel environments, such as groundwater colonization by surface organisms, provides an excellent research ground to study phenotypic evolution. However, interspecific comparative studies on evolution to groundwater life are few because of the challenge in assembling large ecological and molecular resources for species-rich taxa comprised of surface and subterranean species. Here, we make available to the scientific community an operational set of working tools and resources for the Asellidae, a family of freshwater isopods containing hundreds of surface and subterranean species. First, we release the World Asellidae database (WAD) and its web application, a sustainable and FAIR solution to producing and sharing data and biological material. WAD provides access to thousands of species occurrences, specimens, DNA extracts and DNA sequences with rich metadata ensuring full scientific traceability. Second, we perform a large-scale dated phylogenetic reconstruction of Asellidae to support phylogenetic comparative analyses. Of 424 terminal branches, we identify 34 pairs of surface and subterranean species representing independent replicates of the transition from surface water to groundwater. Third, we exemplify the usefulness of WAD for documenting phenotypic shifts associated with colonization of subterranean habitats. We provide the first phylogenetically controlled evidence that body size of males decreases relative to that of females upon groundwater colonization, suggesting competition for rare receptive females selects for smaller, more agile males in groundwater. By making these tools and resources widely accessible, we open up new opportunities for exploring how phenotypic traits evolve in response to changes in selective pressures and trade-offs during groundwater colonization.
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Isópodes , Animais , Filogenia , Isópodes/genética , Ecossistema , DNA , Sequência de BasesRESUMO
The aim of this study is to examine the trophic state of three reservoirs located in the northwest of Algeria based on the physicochemistry of water and the community of rotifers. The measurements of the physicochemical variables were carried out monthly over a 2-year period from December 2015 to November 2017. The rotifers were sampled simultaneously. Abiotic and biotic indices such as the Carlson index, QB/T, and TSIROT were determined in order to classify the three reservoirs according to their trophic state. Thus, the diversity indices of Shannon-Wiener (H'), Margalef richness index (D), Pielou evenness (J'), and the density were calculated in order to study the structure of the rotifers. The Kruskal-Wallis test confirmed the heterogeneity of the physicochemical quality (P value < 0.05) among the three reservoirs. A total of 71 species were identified during this study. The result of the various indices affirms this heterogeneity and indicates a trophic state hypereutrophic for the Hammam Boughrara reservoir, eutrophic for the Bakhadda reservoir and meso-oligotrophic for Sidi Yacoub. The use of canonical correspondence analysis (CCA) has shown that the structure of rotifers is influenced by local environmental factors. Some species such as the genus Brachionus species have shown their preference for extreme conditions. The use of biotic indices is highly recommended for the trophic state evaluation of reservoirs for a better water resources management.
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Biodiversidade , Rotíferos , Argélia , Animais , Estações do AnoRESUMO
Granulosa cell tumors is classified into juvenile and adult types and comprise less than 5% of ovarian tumors in women and are much rarer in men which only 45 have been previously reported. We report here a 40-year young man with a left testicular adult type granulosa cell tumor. The tumor measured 5.5X5X4cm; Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin. Post operative CT scans shows a lomboaortic lymphnodes treated by four cycles of chemotherapy type BEP (bleomycin, etoposide, cisplatin). The thoraco abdominal CT scans post chemotherapy shows the disappearance of the right testicular nodule and the lomboaortic lymphnodes. 2 years after treatment, the patient is alive and well with no signs of recurrence. Our report highlights one more case of this very rare tumor of the testis, which is quite problematic In terms of prognosis and management, and for this reason seems to have attracted the interest of many researchers recently.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumor de Células da Granulosa/patologia , Neoplasias Testiculares/patologia , Adulto , Bleomicina/uso terapêutico , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Seguimentos , Tumor de Células da Granulosa/diagnóstico por imagem , Tumor de Células da Granulosa/tratamento farmacológico , Humanos , Masculino , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
The most common primary sites for bone metastases in men are lung, prostate, kidney, thyroid or bladder. Colorectal origin is rare. Few studies have described this type of metastases; the axial skeleton or the pelvis are the most common metastasis locations. Craniofacial location is exceptional. We here report the case of a 38 years old man treated for metastatic rectal cancer metastasized to temporal bone. He initially had undergone surgical procedure for low anterior resection, tumor was classified as pT3N0M0; 24 months after the patient had left exophthalmos revealing a temporal tumoral process. Evolution and context favoured metastasis. In conclusion, this study reporting an exceptional case of craniofacial bone metastasis from multi-metastatic colorectal cancer will enrich the scarce data reported in the literature related to bone metastases from primary colorectal cancer.
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Neoplasias Ósseas/secundário , Neoplasias Retais/patologia , Neoplasias Cranianas/secundário , Osso Temporal/patologia , Adenocarcinoma/patologia , Adulto , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Humanos , Masculino , Neoplasias Cranianas/diagnóstico , Neoplasias Cranianas/patologiaRESUMO
Bronchopulmonary cancer (CBP) in pregnant woman is a rare entity with a poor outcome. This situation is becoming increasingly common, due to the increase in smoking among women. Transplacental transmission of tumor associated with fetal damage is described especially among untreated women. Treatment is multidisciplinary and it is not well codified. We report the case of a 23 year old patient with small cell bronchial carcinoma diagnosed during pregnancy. She had received chemotherapy during pregnancy and it was well tolerated. Radiological evaluation objectified a stabilization of the pulmonary process. The treatment was completed with concomitant radiochemotherapy after delivery.
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Neoplasias Brônquicas/patologia , Complicações Neoplásicas na Gravidez/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Brônquicas/complicações , Neoplasias Brônquicas/terapia , Quimiorradioterapia/métodos , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/terapia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto JovemRESUMO
Granulosa Cell Tumors (GCT) of the ovary are rare tumors belonging to the group of sex cord stromal tumors. They represent 0.6 - 3% of all ovarian tumors and 5% of all malignant tumors. Two different types of GCT can be distinguished: juvenile granulosa cell tumor (JGT) which is characterized by its aggressive potential and adult granulosa cell tumor (AGT) which is the most common and the least aggressive type. GCT of the ovary usually develops recurrences within 5 years of initial diagnosis but they rarely develop local or peritoneal metastases. Although treatment options including surgery with or without chemotherapy or radiation have been reported in treating GCT relapses, there are no standardized protocols for the treatment of relapses. We here present our therapeutic strategy in the treatment of longterm relapses of GCT peritoneal carcinomatosis occurring in two patients 10 years after the initial diagnosis and a review of the literature.
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Tumor de Células da Granulosa/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Adulto , Feminino , Tumor de Células da Granulosa/diagnóstico , Tumor de Células da Granulosa/terapia , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Fatores de TempoRESUMO
INTRODUCTION: Imatinib, a tyrosine kinase inhibitor, is a major therapeutic option for the management of unresectable aggressive fibromatosis. Unfortunately, for most patients of low or very low average income countries, surgery often is the first treatment option. This is related to unavailability of chemotherapy or targeted therapy, and to a lack of financial resources or surgeons' lack of knowledge of other therapeutic options. CASE PRESENTATION: In 2010, a 26-year-old Moroccan man was referred to our oncology and radiotherapy center by his surgeon for the management of a recurrent tumor of his right subscapularis muscle. Before his assessment in our center, two resections were performed by his surgeon after performing an incision biopsy and magnetic resonance imaging. Postoperative magnetic resonance imaging was performed and showed a right axillary nodule size 2.1cm regarding a collection with a residual tumor. We decided to administer imatinib 400mg daily by mouth. Clinical and magnetic resonance imaging evaluation were performed regularly and reported a stable tumor. We reported no adverse side effects to imatinib regarding Common Terminology Criteria for Adverse Events grading. CONCLUSIONS: Recurrences are high during aggressive fibromatosis management. Systemic treatment with imatinib for unresectable or recurrent tumors with positive c-KIT could be the best therapeutic option. In our case report, the patient was stabilized with imatinib for 30 months and he had a very good quality of life.
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Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Fibromatose Agressiva/terapia , Neoplasias Musculares/terapia , Recidiva Local de Neoplasia/terapia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Manguito Rotador/cirurgia , Adulto , Humanos , Mesilato de Imatinib , Estudos Longitudinais , MasculinoRESUMO
Objective. To determine the current shortfall of medical oncologists (MOs) and the projected supply. Background. Morocco, the medical oncology (MO) is a relatively new specialty. Medical oncology was recognized as a separate specialty in 1994 but the real taking-off was done only since the 2000s after the creation of the chair of medical oncology in the University of Rabat. The GRIOMM (Moroccan group of trialist in medical oncology) was created in 2011 and conducted its first study, EVA-onco, concerning the practice of medical oncology in Morocco in 2011. Design. EVA-onco is a prospective study concerning the practice of medical oncology in Morocco in 2011. Results. The entire public cancer centers completed the survey. There were no missing data. The number of medical oncologist per 100000/habitants in Morocco was 0.09. The average number of new patients seen per medical oncologist was 718 patients (ranging by state from 97 to 1875). The shortfall of MOs was estimated at 26 at least in 2011 according to the national recommendations. Conclusions. Since 2010, a national strategy to increase the capacity of MO workforce existed. The current shortfall of MO is expected to disappear in the future.
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INTRODUCTION: Primary lymphoma of the prostate is very rare. In this paper we present a case of early stage non-Hodgkin lymphoma of the prostate managed with six cycles of rituximab-based chemotherapy, and review the related literature. CASE PRESENTATION: An 84-year-old man was admitted to our hospital having signs and symptoms suggestive of prostatic disease for 3 years. Histological and immunocytochemical studies of trans-urethral biopsy of the prostate showed diffuse large B-cell lymphoma. Radiological assessment of disease confirmed the diagnosis of early stage lymphoma of the prostate. The patient was managed by 6 of rituximab 375 mg/m2 on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and prednisone 50 mg/m2 on days 1 to 5 with complete clinical and radiological response. He remained disease free, until now, 30 months after the end of chemotherapy. CONCLUSION: According to the literature, the treatment and prognosis of primary lymphoma of the prostate is the same as that of other nodal lymphomas. Rituximab-based regimen should be considered in the management of prostatic diffuse large B-cell lymphoma.
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OBJECTIVE: A multicenter, open-label, phase 2 study evaluated the efficacy and safety of intravenous vinflunine as third-line treatment in patients with progressing metastatic breast cancer (MBC) after failure of anthracycline- and taxane-based chemotherapy. PATIENTS AND METHODS: Fifty-six patients with MBC, relapsing after receiving 2 previous treatments for advanced disease, including both anthracyclines and taxanes, received 320 mg/m(2) of vinflunine once every 3 weeks (median number of 2.5 cycles, range: 1-13). RESULTS: According to an independent radiologist, the response rate was 12.5% (95% CI: 5.2-24.1) and 14% (95% CI: 5.3-27.9) (6 partial responses) in the treated and evaluable populations, respectively. Disease control was achieved in 42.9% and 51.2% of the patients, respectively. Median progression-free survival was 2.6 months (95% CI: 1.6-4.0 months) with a median overall survival of 11.4 months (95% CI: 7.4-14.2 months). Duration of response was 6.8 months (95% CI: 5.6 months, upper limit not reached). Leukopenia was the most frequent hematologic toxicity, with grade 3/4 severity in 49.1% of the patients. Grade 3 neutropenia in 30.9%, grade 4 in 40.0% of patients, febrile neutropenia (5.4%), and 1 case of neutropenia infection (1.8%) were reported. Other grade 3 toxicities included anemia (5.5%), fatigue (14.3%), and constipation (7.1%), which were noncumulative. The adverse events associated with vinflunine were predictable and manageable. CONCLUSIONS: Vinflunine is an active and well-tolerated agent as third-line treatment of patients with MBC after failure of anthracycline- and taxane-based therapy. These results warrant further investigation of vinflunine monotherapy or in combination for the treatment of MBC.