Magnani E.,Azienda Ospedaliera ASMN |
Farnetti E.,Laboratory of Molecular Biology |
Nicoli D.,Laboratory of Molecular Biology |
Casali B.,Laboratory of Molecular Biology |
And 5 more authors.
Internal and Emergency Medicine | Year: 2013
Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of 5-fluorouracil (5-FU) and its derivatives (capecitabine and tegafur). Complete or partial deficiency of DPD activity has been demonstrated to induce severe toxicities in cancer patients treated with fluoropyrimidine therapy. We analyzed 180 individuals that were candidates for a treatment with 5-FU class drugs for the most common DPD mutation, IVS14+1G>A, and detected four heterozygous patients. We recorded the toxicities for all 180 individuals after the first two chemotherapy cycles and found that three of the four patients, although they were treated with a dose reduction in 50 % on the basis of the genetic analysis, all showed severe toxicities that resulted in hospitalization of patient and premature discontinuation of treatment. One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. Our data suggest that greater dose reductions or alternative therapies are needed for patients with DPD IVS14+1G>A mutations. © 2013 SIMI.
Catanoso M.G.,Servizio di Reumatologia |
Spaggiari L.,Azienda Ospedaliera ASMN |
Magnani L.,Servizio di Reumatologia |
Pipitone N.,Servizio di Reumatologia |
And 5 more authors.
Clinical and Experimental Rheumatology | Year: 2012
Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis (IRF). However, relapses are frequent upon tapering of the glucocorticoid dose. A variety of traditional immunosuppressants have been proposed as steroid-sparing agents, but some patients fail to adequately respond to combined glucocorticoid and immunosuppressive therapy. We report a patient with IRF refractory to combined glucocorticoid and methotrexate therapy treated with the anti-TNF-α monoclonal antibody infliximab. Infliximab was administered at 5 mglkglbodyweight at week 0,2, 6 and 8-weekly thereafter for 3 consecutive years. Drug efficacy and safety were assessed clinically and by laboratory tests at treatment onset and subsequently before each infusion. In addition, 18F-Fluorodeoxyglucose (FDG) positron emission computerised tomography (PET/CT) and abdominal CT scans were used to monitor disease activity and response to treatment. Infliximab therapy resulted in a satisfactory clinical and laboratory response paralleled by an improvement in imaging findings. No serious adverse events were noted. Infliximab may be an effective and safe treatment for refractory IRF. A controlled study is required to confirm our findings. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2012.
De Bari B.,University of Brescia |
Fiorentino A.,IRCCS |
Fiorentino A.,Sacro Cuore Don Calabria Hospital |
Greto D.,Radiotherapy Unit |
And 12 more authors.
Tumori | Year: 2013
Aims and background. The diagnostic and therapeutic approach to prostate cancer has evolved rapidly in last decades. Young professionals need an update about these recent developments in order to improve the care of patients treated in their daily clinical practice. Methods. On May 18, 2013, AIRO Giovani (the young section of the Italian Association of Radiation Oncology) organized a multidisciplinary meeting involving, as speakers, several young physicians from many parts of Italy actively involved in the diagnostic and therapeutic approach to prostate cancer. The meeting was specifically addressed to young physicians (radio-oncologists, urologists, medical oncologists) and presented the state-of-the-art of the diagnostic/therapeutic approach based on the latest evidence on the issue. Highlights of the congress are summarized and presented in this report. Results. The large participation in the meeting (more than 120 participants were present) confirmed the interest of young radiation oncologists in improving their skills in prostate cancer management. The contributions of the speakers confirmed the need for regular updates, considering the promising results of recently published studies and the many new ongoing trials, on the diagnostic and therapeutic approaches to prostate cancer. Conclusions. Multidisciplinary meetings are helpful to improve the skills of young professionals. Copyright - Il Pensiero Scientifico Editore.
Guarneri V.,University of Padua |
Guarneri V.,Instituto Oncologico Veneto IRCCS |
Dieci M.V.,University of Padua |
Dieci M.V.,Instituto Oncologico Veneto IRCCS |
And 8 more authors.
Annals of Surgical Oncology | Year: 2015
Purpose: The phase II Ca.Pa.Be trial evaluated preoperative carboplatin–paclitaxel in combination with bevacizumab in triple-negative breast cancer patients with previously untreated stage II–III disease. The primary aim was the assessment of the rate of pathologic complete response (pCR). Secondary aims included safety, breast-conserving surgery rate, and early response assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: Patients with hormone receptor-negative, HER-2-negative stage II–III breast cancer were eligible. Treatment included paclitaxel 80 mg/mq + carboplatin area under the curve (AUC) 2 on days 1, 8, and 15, combined with bevacizumab 10 mg/kg on days 1 and 15 each 28 days, for 5 courses. At baseline, patients underwent breast DCE-MRI, followed by a single dose of bevacizumab 5 mg/kg (day −6). DCE-MRI was repeated before the initiation of chemotherapy. Results: Forty-four patients were enrolled. Forty-three patients underwent surgery, and 22 (50 %) received breast-conserving surgery (conversion rate from mastectomy indication at baseline, 34.4 %). A pCR in breast and axillary lymph nodes occurred in 22 patients (50 %). Bevacizumab-associated adverse events (AEs) were mild: G1–2 hypertension and bleeding occurred in 6 (13.6 %) and 12 (27 %) patients, respectively. No G4 nonhematologic AEs were recorded. More frequent G3 AEs were liver function test abnormalities (6.8 %), and diarrhea and fatigue (4.5 % each). The only G3–4 hematologic toxicity was neutropenia (G3, 25 %; G4, 9 %). Early assessed DCE-MRI response parameters failed to predict pCR. Conclusions: The neoadjuvant anthracycline-free combination of weekly paclitaxel and carboplatin plus bevacizumab is active and safe in triple-negative breast cancer, and the rate of pCR is comparable to that observed with more intensive carboplatin- and bevacizumab-containing regimens. Further investigation is warranted. © 2015, Society of Surgical Oncology.
Sini V.,Sacro Cuore Don Calabria Hospital |
Sini V.,SantAndrea Hospital |
Lunardi G.,Sacro Cuore Don Calabria Hospital |
Cirillo M.,Sacro Cuore Don Calabria Hospital |
And 16 more authors.
British Journal of Cancer | Year: 2014
Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m-2; 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m-2; 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m -2; and 43.3 (23.0-81.7, n=16) when ≥35.0 kg m-2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients. © 2014 Cancer Research UK.
Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer
Guarneri V.,University of Padua |
Guarneri V.,Instituto Oncologico Veneto Instituto Of Ricovero E Cura A Carattere Scientifico Irccs |
Dieci M.V.,University of Padua |
Frassoldati A.,University of Ferrara |
And 14 more authors.
Oncologist | Year: 2015
Background. The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete re- mission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers. Materials and Methods. Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastu- zumab, lapatinib, or both trastuzumab and lapatinib. Pre-and post-treatment samples were centrally evaluated for HER2, p95- HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses. Results. A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild- type and PIK3CA-mutated patients (33.3% vs. 22.7%; p 5.323). For patients receiving trastuzumab plus lapatinib, the probabil- ity of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p 5.06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade.The integrated analysis of gene expression and copy number data demonstrated that a 50- gene signature specifically predicted the lapatinib-induced pCR. Conclusion. PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib. © Alpha Med Press 2015.
PubMed | University of Udine, IRCSS AOU San Martino, Institute for Cancer Research and Treatment, Sacro Cuore Don Calabria Hospital and 2 more.
Type: Journal Article | Journal: British journal of cancer | Year: 2014
Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer.Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearmans rho) between the ES levels and BMI were assessed.Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m(-2); 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m(-2); 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m(-2); and 43.3 (23.0-81.7, n=16) when 35.0 kg m(-2). No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed.Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients.
PubMed | Gaetano Pini Institute, Instituto Giannina Gaslini, Carlo Poma Hospital, Azienda Ospedaliera ASMN and IRCCS Bambino Gesu Childrens Hospital
Type: Letter | Journal: Clinical and experimental rheumatology | Year: 2016
PubMed | Azienda Ospedaliera ASMN, Childrens Hospital of Pittsburgh and University of Bari
Type: Journal Article | Journal: Clinical and experimental rheumatology | Year: 2016
Dermatomyositis (DM) and polymyositis (PM) commonly cause weakness of the thigh muscles. However, it is debated whether DM and PM affect similar thigh muscles. Muscle oedema on fat-suppressed MRI sequences is thought to represent active inflammation. In this study, we aimed to assess which thigh muscle groups are preferentially inflamed in DM and PM, respectively, using short-tau inversion-recovery MRI sequences.We analysed 71 patients from 2 Rheumatology centres, 31 with DM and 40 with PM diagnosed according to the Bohan and Peter criteria. MRI oedema (1=present, 0=absent) was assessed bilaterally on fat-suppressed sequences in 17 pelvic floor and thigh muscles. An MRI oedema score (range 0-17) was calculated by adding the separate scores bilaterally and dividing them by two. Inter-rater variability was assessed by intraclass correlation coefficient. Fishers exact test was used to compare binomial data.Age and gender ratio were similar in patients with DM and PM. Disease duration (months, meanSD) was shorter (2031) in DM than in PM (5369) (p=0.02). The intraclass correlation coefficient between the radiologists involved was 0.78. Muscle oedema was more common in DM than in PM except in the posterior thigh muscles. In particular, 68% of patients with DM had involvement of at least one anterior thigh muscle versus 38% of patients with PM (p=0.02).Compared with PM, DM affects more thigh muscles, except those of the posterior compartment, which are equally involved in both disorders. These findings may be useful to target physiotherapy at the more frequently affected muscles.