Romieu G.,Val dAurell Paul Lamarque Center |
Campone M.,West Cancer Institute |
Dieras V.,University Pierre and Marie Curie |
Cropet C.,Biostatistics and Treatment Evaluation Unit |
And 11 more authors.
The Lancet Oncology | Year: 2013
Background: Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer. Methods: In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive metastatic breast cancer with brain metastases not previously treated with WBRT, capecitabine, or lapatinib. Tretament was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m2, orally) from day 1 to day 14. The primary endpoint was the proportion of patients with an objective CNS response, defined as a 50% or greater volumetric reduction of CNS lesions in the absence of increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease. All responses had to be confirmed 4 weeks after initial response. Efficacy analyses included all patients who received the study drugs and were assessable for efficacy criteria. This trial is registered with ClinicalTrials.gov, number NCT00967031. Findings: Between April 15, 2009, to Aug 2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21·2 months (range 2·2-27·6). 29 patients had an objective CNS response (65·9%, 95% CI 50·1-79·5); all were partial responses. Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred. Interpretation: The combination of lapatinib and capecitabine is active as first-line treatment of brain metastases from HER2-positive breast cancer. A phase 3 trial is warranted. Funding: GlaxoSmithKline-France and UNICANCER. © 2013 Elsevier Ltd.
PubMed | Henri Mondor University Hospital, Cochin Hospital, j Service Onco Hematologie Hopital Saint Louis, q Center Hospitalier Lyon Sud and 10 more.
Type: Journal Article | Journal: Leukemia & lymphoma | Year: 2016
Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease.
PubMed | Bergonie Institute, Leon Berard Center, Paoli Calmettes Institute, Antoine Lacassagne Center and 7 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently.Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study.A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms.To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools.
PubMed | University of Nice Sophia Antipolis, Pasteur Hospital, Archet Hospital, Antoine Lacassagne Center and Paris-Sorbonne University
Type: Comparative Study | Journal: Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2016
Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment.We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP.IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples.The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively.This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.
Clough K.B.,Paris Breast Center |
Oden S.,Paris Breast Center |
Oden S.,University of Rouen |
Ihrai T.,Paris Breast Center |
And 4 more authors.
Annals of Surgical Oncology | Year: 2013
Background: Oncoplastic surgical techniques offer an option of breast conserving surgery for larger tumors with the use of glandular reshaping to prevent postoperative deformity. A technique for the excision of lower inner quadrant tumors via a V incision is described, the lower-inner quadrant-V (LIQ-V) mammoplasty, and the results of a pilot study are reported. Methods: Retrospective collection of pre- and postoperative data was collected from patients undergoing a LIQ-V mammoplasty for a LIQ tumor. Results: Twenty-two patients were operated on between 2004 and 2011 at a mean age of 58 years. The mean follow-up was 55 months. The mean resection weight was 101 g for tumors ranging in size from 4 to 31 mm. The margins were clear in 95 % of cases. There was one case of local recurrence and metastatic disease. The cosmetic outcome was judged as excellent in 68 % of cases, and no patient required further ipsilateral or contralateral symmetrizing surgery. Discussion: The deformity often associated with tumors of the LIQ is adequately addressed by this new technique. It has a complication rate comparable to other mammoplasty series and a high rate of clear resection margins. Many oncoplastic surgery techniques are based on inverted T mammoplasty, but these are not suited for all tumor locations. The LIQ-V mammoplasty is an adaptation of the standard techniques that best suit the LIQ. It is oncologically safe and provides disease-free margins, and although the resection volumes are large, the cosmetic outcome is not compromised. © 2013 Society of Surgical Oncology.
Cortot A.B.,Lyon University Hospital Center |
Cortot A.B.,International Agency for Research on Cancer |
Cortot A.B.,Dana-Farber Cancer Institute |
Italiano A.,French National Center for Scientific Research |
And 4 more authors.
Cancer | Year: 2010
BACKGROUND: The objective of this study was to determine whether the mutation status of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) differed between primary tumors and matched distant metastases in nonsmall cell lung cancer (NSCLC). METHODS: Patientswho underwent resection for both primary NSCLC and matched distant metastases were included in the study. KRAS and EGFR mutation status were assessed by polymerase chain reaction (PCR) amplification and direct sequencing on both primary tumors and metastases. For KRAS analysis, mutant-enriched PCR (ME-PCR) was performed in case of discordance between a primary tumor and its matched metastasis. RESULTS: Twenty-one patients were included. No EGFR mutations were detected. KRAS mutationswere detected in 6 patients (28%). In all patients, themutations identified by direct sequencing were discordant between the primary tumor and the matched metastasis. The use of ME-PCR allowed a resolution of the discordance in 3 of the 6 cases by demonstrating the presence of low levels of mutant KRAS in lesions that were negative by direct sequencing. CONCLUSIONS: Highly sensitive tools are required to identify biomarkers. The KRAS mutation status mostly was concordant between primary tumors and matched distant metastases. In a few patients, KRAS mutation status differed between different tumor sites. © 2010 American Cancer Society.
Barriere J.,Antoine Lacassagne Center |
Hoch B.,Antoine Lacassagne Center |
Ferrero J.-M.,Antoine Lacassagne Center
Critical Reviews in Oncology/Hematology | Year: 2012
Since 2007, the advent of so-called " targeted" therapy has revolutionized the management of renal cell carcinoma (RCC), replacing interferon or interleukin-2 immunotherapy. The present article first reviews the fundamentals of current practice in the management of metastatic-phase RCC. It then goes on to consider the new perspectives opening up in terms of treatment strategy (sequential or combined treatments and new drugs) in what can be seen as a second phase in this ongoing revolution in treatment. In the years to come, the challenge will be to learn to optimize the use of the many drugs available, possibly in association with micro-invasive techniques, so as to achieve the third phase of the revolution: long-term remission in metastatic RCC. The search for factors predictive of response and greater knowledge of tumor biology will be essential steps, yet to be made, toward this goal. © 2011 Elsevier Ireland Ltd.
PubMed | Val Of Grace Military Hospital, Antoine Lacassagne Center, Lucien Neuwirth Cancer Institute, Porte Of Saint Cloud Clinical Center and Claude Bernard Private Hospital
Type: | Journal: Chinese journal of cancer | Year: 2016
No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6-76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.
PubMed | Antoine Lacassagne Center and Institut Universitaire de France
Type: Journal Article | Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery | Year: 2016
The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 6210.6years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22%, respectively. In multivariate analysis, ASA score (p=0.002), pathologic N-stage (p=0.01), and close surgical margins (p=0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83% of patients. 6.5% of patients remaining dependent on enteral nutrition 6months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.
Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first-line therapy for triple-negative, metastatic, or locally advanced breast cancer: Results from the GINECO A-TaXel phase 2 study
PubMed | Catherine of Sienne Center, Antoine Lacassagne Center, Armorican Radiology Clinic, William Morey Hospital and 6 more.
Type: Journal Article | Journal: Cancer | Year: 2016
The current study was performed to determine the efficacy and safety of first-line combination therapy with bevacizumab, paclitaxel, and capecitabine for triple-negative, locally advanced/metastatic breast cancer (LA/MBC).Patients with measurable triple-negative LA/MBC who had received no prior chemotherapy for their disease received 4-weekly cycles of paclitaxel (80 mg/mBetween April 2010 and March 2012, 62 eligible patients were enrolled. The median age of the patients was 57 years, 74% had received adjuvant chemotherapy, and 65% had visceral metastases. Patients received a median of 6 cycles (range, 1-45 cycles). The objective response rate was 77% (95% confidence interval [95% CI] 66%-88%), including complete response in 19% of patients. The median duration of response was 5.6 months (range, 1.3-27.6 months). The median progression-free survival was 7.6 months (95% CI, 6.3-9.0 months) and the median overall survival was 19.2 months (95% CI, 17.4-20.9 months). The most common grade 3 adverse events were hypertension (35% of patients) and neutropenia (23% of patients); 5% of patients experienced febrile neutropenia. Grade 2 hand-foot syndrome, alopecia, and nail toxicity each occurred in 40% of patients (adverse events were recorded before every cycle and graded according to Common Terminology Criteria for Adverse Events [version 4.0]). Treatment was interrupted because of toxicity in 22% of patients.A triplet regimen of paclitaxel, capecitabine, and bevacizumab followed by maintenance therapy with capecitabine and bevacizumab demonstrated high activity and manageable safety in this difficult-to-treat population. Cancer 2016;122:3119-26. 2016 American Cancer Society.