Masi G.,Instituto Toscano Tumori |
Salvatore L.,Instituto Toscano Tumori |
Boni L.,AOU Careggi Instituto Toscano Tumori |
Loupakis F.,Instituto Toscano Tumori |
And 14 more authors.
Annals of Oncology | Year: 2015
Background: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. Patients and methods: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on firstline regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. Results: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. Conclusions: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. Clinical Trials.gov number: NCT00720512. © The Author 2015.
PubMed | University of Barcelona, University of the Sea, University of Groningen, Roche Holding AG and 5 more.
Type: | Journal: Seminars in arthritis and rheumatism | Year: 2016
To report entry criteria and clinical features of patients with newly diagnosed and relapsing giant cell arteritis (GCA) enrolled in a randomized trial of tocilizumab, an interleukin-6 receptor-alpha inhibitor.Newly diagnosed GCA was defined as diagnosis 6 weeks before baseline. Relapsing GCA was defined as diagnosis >6 weeks before baseline with 2 consecutive weeks of prednisone 40mg/day. All patients had active GCA within 6 weeks of baseline. All statistical results are exploratory.Of 251 patients, 119 (47%) had newly diagnosed and 132 (53%) had relapsing GCA. Mean age was 69 years in both subsets; 75% were women. Relapsing patients were heavier [difference in means (95% CI): women, 4.18kg (0.49-7.87, P = 0.027); men, 8.25kg (1.42-15.09, P = 0.019)] and had higher mean body mass index [difference in means (95% CI): women, 1.72kg/mDemographics of the GiACTA population reflect the epidemiologic profile of GCA. Baseline comorbidities associated with glucocorticoids were more prevalent among relapsing patients than among those with newly diagnosed disease, highlighting the need for new GCA treatment options. More than one-third of patients were enrolled based on large-vessel imaging.
PubMed | University of Rome La Sapienza, cassagne Cancer Center, San Gerardo Hospital, University Hospital Maggiore della Carita and 6 more.
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2016
The quantitative assessment of Positron Emission Tomography (PET) scans using standardized uptake value and derived parameters proved to be superior to traditional qualitative assessment in several retrospective or mono-centric prospective reports. Since different scanners give different quantitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of quantitative PET in prospective multi-centre clinical trials and in every-day clinical life.We set up, under the auspices of Italian Foundation on Lymphoma (FIL), a CTQ program consisting of the PET/CT scan acquisition and analysis of (18)F and (68)Ge NEMA/IEC image quality phantoms for the reduction of inter-scanner variability. Variability was estimated on background activity concentration (BAC) and sphere to background ratio (SBR).The use of a (68)Ge phantom allowed reducing the inter-scanner variability among different scanners from 74.0% to 20.5% in BAC and from 63.3% to 17.4% in SBR compared to using the (18)F phantom. The CTQ criteria were fulfilled at first round in 100% and 28% of PET scanners with (68)Ge and (18)F respectively.The (68)Ge phantom proved a reliable tool for PET scanner qualification, able to significantly reduce the potential sources of error while increasing the reproducibility of PET derived quantitative parameter measurement.
PubMed | Arcispedale Santa Maria Nuova IRCCS, Skin Cancer Unit, The Second University of Naples and Aristotle University of Thessaloniki
Type: | Journal: OncoTargets and therapy | Year: 2016
Prior to 2011, the 1-year survival rates for patients suffering from advanced or metastatic melanoma was as low as 33%, with a median overall survival of about 9 months. Several chemotherapeutic regimens have been applied, either as monochemotherapy or as polychemotherapy, overall not resulting in an improvement of progression-free or overall survival. Novel insights into the epidemiology and biology of melanoma allowed the development of newer therapies. The discovery of mutations in BRAF, a part of the mitogen-activated protein kinase, allowed the development of two BRAF inhibitors, vemurafenib and dabrafenib, which significantly improved the outcome of metastatic melanoma treatment. This article reviews the mechanism of action, efficacy, and safety profile of dabrafenib. An in-depth knowledge of this medication will encourage clinicians to select the appropriate therapeutic strategy for each patient, as well as to prevent or adequately manage side effects, optimizing, thus, the drugs applicability.
PubMed | Arcispedale Santa Maria Nuova IRCCS, Anatomic Pathology Unit, Ghent University and Clinical Genetics Unit
Type: Journal Article | Journal: American journal of medical genetics. Part A | Year: 2016
Biallelic defects in the RIN2 gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with RIN2 mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition. 2016 Wiley Periodicals, Inc.
PubMed | Humanitas Research Hospital, Arcispedale Santa Maria Nuova IRCCS, University of Florence, University of Siena and University of Bari
Type: Journal Article | Journal: Clinical rheumatology | Year: 2016
The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behets disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (p<0.0001). Similarly, BCVA improved if compared to baseline (7.42.9 versus 8.52.1, p=0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.2742.8m at the end of follow-up (p<0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (p<0.0001 and p=0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
PubMed | Arcispedale Santa Maria Nuova IRCCS, University of Texas Health Science Center at Houston and University of Texas Medical Branch
Type: | Journal: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology | Year: 2016
To compare the effectiveness of customized versus population-based growth charts for prediction of adverse pregnancy outcomes.we searched MEDLINE, http://ClinicalTrials.gov and the Cochrane library up to May 31The search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined completely for eligibility. After excluding 7 records, 20 observational studies were included in a Bayesian meta-analysis. Customized-SGA had higher odds of IUFD (OR 7.8, 95% CI 4.2 -12.3), neonatal death (OR 3.5, 95% CI 1.1 - 8), perinatal death (OR 5.8, 95% CI 3.8 -7.8), and NICU admission (OR 3.6, 95% CI 2 - 5.5) than non-SGA. Population-SGA also had increased odds of adverse outcomes, albeit the point estimate of the pooled ORs were smaller: IUFD (OR 3.3, 95% CI 1.9 - 5), neonatal death (OR 2.9, 95% CI 1.2 - 4.5), perinatal death (OR 4, 95% CI 2.8 - 5.1), and NICU admission (OR 2.4, 95% CI 1.7 - 3.2). In the LGA versus non-LGA comparison, no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia, 3