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1.
Emerg Infect Dis ; 30(3): 432-443, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325363

ABSTRACT

During 1979-2022, Cameroon recorded 32 laboratory-confirmed mpox cases among 137 suspected mpox cases identified by the national surveillance network. The highest positivity rate occurred in 2022, indicating potential mpox re-emergence in Cameroon. Both clade I (n = 12) and clade II (n = 18) monkeypox virus (MPXV) were reported, a unique feature of mpox in Cameroon. The overall case-fatality ratio of 2.2% was associated with clade II. We found mpox occurred only in the forested southern part of the country, and MPXV phylogeographic structure revealed a clear geographic separation among concurrent circulating clades. Clade I originated from eastern regions close to neighboring mpox-endemic countries in Central Africa; clade II was prevalent in western regions close to West Africa. Our findings suggest that MPXV re-emerged after a 30-year lapse and might arise from different viral reservoirs unique to ecosystems in eastern and western rainforests of Cameroon.


Subject(s)
Monkeypox virus , Mpox (monkeypox) , Humans , Cameroon/epidemiology , Monkeypox virus/genetics , Ecosystem , Mpox (monkeypox)/epidemiology , Africa, Western/epidemiology
2.
Ann Oncol ; 35(4): 351-363, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38246351

ABSTRACT

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Female , Middle Aged , Male , Sarcoma/pathology , Soft Tissue Neoplasms/therapy , Soft Tissue Neoplasms/pathology , Biopsy , France/epidemiology , Databases, Factual , Retrospective Studies
3.
Cancer Radiother ; 28(1): 93-102, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38212215

ABSTRACT

Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Sarcoma/radiotherapy , Sarcoma/pathology , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Soft Tissue Neoplasms/surgery
4.
Eur J Cancer ; 196: 113454, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38008029

ABSTRACT

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. RESULTS: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. CONCLUSIONS: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.


Subject(s)
Fibrosarcoma , Sarcoma , Soft Tissue Neoplasms , Humans , Female , Child , Male , Fibrosarcoma/surgery , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Gene Rearrangement , Recurrence
5.
Cancer Radiother ; 27(8): 689-697, 2023 Dec.
Article in French | MEDLINE | ID: mdl-37813717

ABSTRACT

PURPOSE: Conserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. PATIENTS AND METHODS: Clinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. RESULTS: From April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1-2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. CONCLUSIONS: Neoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Neoadjuvant Therapy , Retrospective Studies , Radiotherapy, Adjuvant/adverse effects , Sarcoma/diagnostic imaging , Sarcoma/radiotherapy , Sarcoma/surgery , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/radiotherapy , Edema
6.
Eur J Cancer ; 192: 113262, 2023 10.
Article in English | MEDLINE | ID: mdl-37625241

ABSTRACT

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.


Subject(s)
Hemangioendothelioma, Epithelioid , Neoplasms, Second Primary , Sarcoma , Humans , Female , Male , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Hemangioendothelioma, Epithelioid/therapy , Sarcoma/epidemiology , Sarcoma/therapy , Databases, Factual , France/epidemiology , Liver
7.
ESMO Open ; 8(3): 101569, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37285716

ABSTRACT

BACKGROUND: REGOBONE multicohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the cohort of patients with relapsed advanced or metastatic chordoma. METHODS: Patients with relapsed chordoma progressing despite 0-2 prior lines of systemic therapy, were randomised (2 : 1) to receive regorafenib (160 mg/day, 21/28 days) or placebo. Patients on placebo could cross over to receive regorafenib after centrally-confirmed progression. The primary endpoint was the progression-free rate at 6 months (PFR-6) (by RECIST 1.1). With one-sided α of 0.05, and 80% power, at least 10/24 progression-free patients at 6 months (PFR-6) were needed for success. RESULTS: From March 2016 to February 2020, 27 patients were enrolled. A total of 23 patients were assessable for efficacy: 7 on placebo, 16 on regorafenib, 16 were men, median age was 66 (32-85) years. At 6 months, in the regorafenib arm, 1 patient was not assessable, 6/14 were non-progressive (PFR-6: 42.9%; one-sided 95% CI = 20.6) 3/14 discontinued regorafenib due to toxicity; and in the placebo arm, 2/5 patients were non-progressive (PFR-6: 40.0%; one-sided 95% CI = 7.6), 2 were non-assessable. Median progression-free survival was 8.2 months (95% CI 4.5-12.9 months) on regorafenib and 10.1 months (95% CI 0.8 months-non evaluable [NE]) on placebo. Median overall survival rates were 28.3 months (95% CI 14.8 months-NE) on regorafenib but not reached in placebo arm. Four placebo patients crossed over to receive regorafenib after centrally-confirmed progression. The most common grade ≥3 regorafenib-related adverse events were hand-foot skin reaction (22%), hypertension (22%), pain (22%), and diarrhoea (17%), with no toxic death. CONCLUSION: This study failed to show any signal of benefit for regorafenib in patients with advanced/metastatic recurrent chordoma.


Subject(s)
Chordoma , Male , Humans , Aged , Female , Chordoma/drug therapy , Chordoma/chemically induced , Phenylurea Compounds/adverse effects , Pyridines/pharmacology , Pyridines/therapeutic use , Progression-Free Survival
8.
Nat Commun ; 13(1): 2012, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35440629

ABSTRACT

Transcriptionally active loci are particularly prone to breakage and mounting evidence suggests that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncover a function for the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in an R-loop dissolution-deficient background, we find that BLM promotes cell death. We report that upon excessive RNA:DNA hybrid accumulation, DNA synthesis is enhanced at DSBs, in a manner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.


Subject(s)
Chromatin , DNA Breaks, Double-Stranded , Chromatin/genetics , DNA/genetics , DNA/metabolism , DNA Repair , Humans , RNA/genetics , RecQ Helicases/genetics , RecQ Helicases/metabolism , Recombinational DNA Repair
9.
ESMO Open ; 7(2): 100402, 2022 04.
Article in English | MEDLINE | ID: mdl-35202953

ABSTRACT

BACKGROUND: Synovial sarcoma (SS) occurs in both adult and pediatric patients. The primary aim of this study is to describe the outcomes, prognostic factors, and treatment of patients with metastatic SS within a nationwide cohort. PATIENTS AND METHODS: All pediatric and adult patients with metastatic SS are registered in the French Sarcoma Group database. Data were collected from the national database https://conticabase.sarcomabcb.org/ up to March 2020. Descriptive and comparative analyses were conducted using SAS 9.4 and Stata Special Edition 16.1 software. RESULTS: Between January 1981 and December 2019, 417 patients with metastatic SS from 17 French sarcoma centers were included, including 64 (15.3%) under the age of 26 years. Median age was 42.5 years (range 9-87 years). The metastases were synchronous (cohort 1) or metachronous (cohort 2) in 18.9% (N = 79) and 81.1% (N = 338) patients, respectively. Median overall survival (OS) from the date of metastasis was 22.3 months (95% confidence interval 19.7-24.1 months). First-line chemotherapy without ifosfamide and/or doxorubicin was unfavorable for progression-free survival and OS (P < 0.001). Concerning cohort 1, young age, surgery of the primary tumor, and single metastatic site were independent favorable prognostic factors for OS. In cohort 2, surgery within an expert French Sarcoma Group center, absence of chemotherapy in the perioperative setting, the lungs as a single metastatic site, time to first metastasis >12 months, local therapy, and ifosfamide in the first metastatic line were independent favorable prognostic factors. CONCLUSIONS: The outcome of patients with metastatic SS is influenced by local treatment, management in reference centers, and cytotoxic treatments given in the perioperative and metastatic setting.


Subject(s)
Antineoplastic Agents , Sarcoma, Synovial , Sarcoma , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Child , Doxorubicin/therapeutic use , Humans , Ifosfamide/therapeutic use , Middle Aged , Sarcoma/drug therapy , Sarcoma, Synovial/drug therapy , Sarcoma, Synovial/pathology , Young Adult
11.
Ann Oncol ; 30(7): 1143-1153, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31081028

ABSTRACT

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.


Subject(s)
Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Sarcoma/mortality , Sarcoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , France/epidemiology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Prospective Studies , Referral and Consultation/statistics & numerical data , Registries , Sarcoma/pathology , Surgical Procedures, Operative/standards , Surgical Procedures, Operative/statistics & numerical data , Survival Rate , Young Adult
12.
Prog Urol ; 29(1): 12-17, 2019 Jan.
Article in French | MEDLINE | ID: mdl-30340845

ABSTRACT

Spermatic cord sarcomas are rare tumors for which the most important is the initial diagnostic procedure. They are frequently misdiagnosed after surgery for inguinal hernia, inguinal lymphadenectomy or testicular malignancy. Any clinical suspicion has to lead to perform imaging with MRI and a core needle biopsy in order to obtain an accurate preoperative diagnosis. Liposarcoma and leiomyosarcoma are the most common histological subtypes in elderly adults, rhabdomyosarcoma in children or in young adults. A CT scan will precede the treatment in order to look for distant metastasis and abdominal involvement. The therapeutic strategy as well as the surgical planning are then adapted to the histological, morphological and prognostic factors. Surgery is the cornerstone for the treatment of spermatic cord sarcoma. The minimum requirements for the surgical procedure are a wide excision of the tumor en bloc with radical orchidectomy, excision of the ipsilateral scrotum and high spermatic cord ligation. It could be enlarged to the anterior abdominal wall and adjacent organs some required a soft tissue flap. Spermatic cord sarcoma and trunk wall sarcoma have the same prognosis for which local recurrence could significantly decrease survival. Consequently, surgeon in charge with these tumors has to be familiar with soft tissue sarcoma and the management of these patients must be carried out under the supervision of a multidisciplinary team within the Netsarc network.


Subject(s)
Genital Neoplasms, Male/therapy , Sarcoma/therapy , Spermatic Cord/pathology , Adult , Aged , Child , Diagnosis, Differential , Genital Neoplasms, Male/diagnosis , Genital Neoplasms, Male/pathology , Humans , Male , Prognosis , Sarcoma/diagnosis , Sarcoma/pathology , Urologic Surgical Procedures, Male , Young Adult
13.
AIDS Care ; 30(12): 1502-1506, 2018 12.
Article in English | MEDLINE | ID: mdl-29991274

ABSTRACT

In sub-Saharan Africa, where people living with HIV are frequently stigmatized, the intake of antiretroviral treatment (ART) remains a critical issue for many patients. Although the secret intake of ART may hinder the adherence to treatment, data on its specific impact on therapeutic effectiveness are lacking. We therefore assessed the association between secret intake of ART (i.e., hidden from family) and HIV-1 viremia among patients treated in a public routine clinic in Burkina Faso. We performed a cross-sectional study from December 2012 to September 2013 among patients on ART at the Day Care Unit in Bobo Dioulasso. Patients were eligible for the study if they were 15 years old or over, infected with HIV-1 or HIV-1 + 2, and on ART for at least six months. HIV-1 viral load was measured using Biocentric or Abbott Real Time assay. Study-specific data were collected by social workers using face-to-face interviews, and medical data using the routine electronic database. The association between secret intake of ART and viral load >300 copies/mL was assessed using a multivariate logistic regression. Of 771 patients (women 81.4%; median age 41 years; median time on ART 51 months), 408 reported secret intake of ART and 363 declared open intake. Compared to the latter, patients who hid their intake were younger, more likely to be women and to be involved in a polygamist or in a non-cohabiting union. Viremia was observed in 4.4% of patients hiding ART intake and 9.4% of those taking it openly. By multivariate analysis, secret intake of ART was significantly associated with a lower risk of viremia (adjusted odds ratio 0.41, 95% confidence interval 0.22-0.76). The unexpected relation between secret intake of ART and viremia found in this study requires further investigations. Quantitative and qualitative studies need to be performed.


Subject(s)
Anti-Retroviral Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Medication Adherence/statistics & numerical data , Viral Load/drug effects , Viremia/drug therapy , Adolescent , Adult , Ambulatory Care Facilities , Anti-Retroviral Agents/therapeutic use , Burkina Faso , Cross-Sectional Studies , Female , HIV Infections/virology , Humans , Male , Middle Aged
14.
Antivir Ther ; 22(3): 195-203, 2017.
Article in English | MEDLINE | ID: mdl-27705950

ABSTRACT

BACKGROUND: To investigate change in renal function in African patients initiating second-line antiretroviral therapy (ART) including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). METHODS: HIV-1-positive adults, failing standard first-line ART were randomized to either TDF/emtricitabine (FTC)+LPV/r, abacavir + didanosine +LPV/r or TDF/FTC+ darunavir (DRV)/r and followed for 18 months. Patients with an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 at baseline were included in this analysis. RESULTS: Data from 438 out of 454 randomized patients were analysed. Median age was 38 years and 72% were women. Initiation of PI/r-based second-line regimen induced a marked eGFR decline of -10.5 ml/min/1.73 m2 at week 4 in all treatment groups with a greater decrease in TDF/FTC+LPV/r arm (-15.1 ml/min/1.73 m2). At month 18, mean eGFR in the non-TDF containing regimen recovered its baseline level and was significantly greater than eGFR 18-month levels in the TDF-containing regimens that experienced only partial recovery (difference: -10.7; CI -16.8, -4.6; P=0.001 in TDF/FTC+LPV/r and -6.4; CI -12.5, -0.3; P=0.04 in TDF/FTC+DRV/r). At 18 months, prevalence of stage 3 chronic kidney disease was low (<3%) and not associated with treatment. One treatment discontinuation and five TDF dosage reductions for renal toxicities were reported in TDF-containing arms. CONCLUSIONS: Overall, these results suggest a reasonable renal tolerance of a regimen associating TDF/FTC+PI/r in African patients with eGFR>60 ml/ml/1.73 m2 at baseline. They also support the recommendation of reassessing renal function 1 month after initiation of treatment including ritonavir to account for the ritonavir-related artefactual decrease of eGFR and determine the new reference baseline value.


Subject(s)
Anti-HIV Agents/adverse effects , Black People , HIV Infections/complications , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Adult , Aged , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/adverse effects , Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Kidney Function Tests , Male , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Retreatment , Treatment Outcome , Viral Load
15.
Cancer Radiother ; 20(6-7): 666-76, 2016 Oct.
Article in French | MEDLINE | ID: mdl-27614501

ABSTRACT

The standard treatment for extremity soft tissue sarcomas is based on the association of surgery and radiotherapy. This strategy allows local control improvement with the risk of increased toxicity. There is therefore a growing interest to identify those patients who will benefit from radiotherapy and those who will have the same local control with surgery alone. Furthermore, the development of toxicity has been correlated with the extension of the irradiated volume and the volume receiving high doses. Technological development as intensity modulated radiotherapy and image-guided radiotherapy allows limited irradiated volume improving the protection of the organs at risk leading to clinical benefit improvement. Moreover, efforts are being done to improve local control for the patients at high risk of local relapse. In this paper, we discuss all these mentioned aspects.


Subject(s)
Sarcoma/radiotherapy , Soft Tissue Neoplasms/radiotherapy , Edema/etiology , Fractures, Bone/etiology , Humans , Margins of Excision , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Patient Selection , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated/adverse effects , Sarcoma/surgery , Soft Tissue Neoplasms/surgery
16.
Ann Oncol ; 27(7): 1235-41, 2016 07.
Article in English | MEDLINE | ID: mdl-27029707

ABSTRACT

BACKGROUND: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. RESULTS: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. CONCLUSION: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. CLINICAL TRIAL NUMBER: NCT01480869.


Subject(s)
Breast Neoplasms/diet therapy , Dietary Supplements , Vitamin D Deficiency/diet therapy , Vitamin D/administration & dosage , Adult , Aged , Breast Neoplasms/blood , Breast Neoplasms/pathology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Quality of Life , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/pathology
17.
Sante ; 14(2): 75-9, 2004.
Article in French | MEDLINE | ID: mdl-15454364

ABSTRACT

In order to assess the action scheme of the National Program against Malaria, a study has been conducted in 25 pharmacies in Bouaké an area of high malaria transmission. The kind and quality of malaria treatments suggested by medical personnel, pharmacy sellers and used in automedication have been studied. The results proved that chloroquine is the molecule most delivered (25.7%) in private pharmacies. The parasitological diagnosis is scarcely requested by medical personnel. As in automedication, posological mistakes are relatively frequent with medical and pharmacy personnel (29.3%). The duration of the treatment is not specified in 14.2% of cases. Training and information actions must be reinforced for a better care of malaria.


Subject(s)
Antimalarials/therapeutic use , Chloroquine/therapeutic use , Malaria/drug therapy , Pharmaceutical Services/standards , Cote d'Ivoire , Drug Administration Schedule , Health Care Surveys , Humans , Malaria/prevention & control , Quality of Health Care
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