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M Bonetti

Publications and source records attributed to M Bonetti.

At least 19 recordsLinked to original sources
PubMed2003

Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.

PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

Breast Neoplasms↗
PubMed2002

Multiscale clustering in granular surface flows.

We investigate steady granular surface flows in a rotating drum and demonstrate the existence of rigid clusters of grains embedded in the flowing layer. These clusters appear to be fractal and their size is power law distributed from the grain size scale up to the thickness of the flowing layer. The implications of the absence of a characteristic length scale on available theoretical models of dense granular flows are discussed. Finally, we suggest a possible explanation of the difference between velocity profiles observed in surface flows and in flows down a rough inclined plane.

Journal Article↗
PubMed2002

Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF.

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (+/-s.e.) were 54+/-2% for three cycles and 55+/-2% for six cycles (n=1024; risk ratio (risk ratio: CMFx3/CMFx6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation.

Adult↗
PubMed2002

Evaluation of Gd-enhancement in brain MR of multiple sclerosis: image subtraction with and without magnetization transfer.

The aim of our study was to test the possibility of using image subtraction in detecting enhancing lesions in brain MR scans with and without magnetization transfer (MT) in multiple sclerosis (MS). Ten MS patients underwent 1.5-T MR imaging of the brain with spin-echo T1-weighted sequences with and without MT, repeated after 0.1 mmol/kg of an usual two-compartment paramagnetic contrast agent (Gadoteridol, Gd-HP-DO3A). Precontrast images were subtracted from postcontrast. Enhancing lesions were counted on the postcontrast images only (post-Gd), comparing pre- and postcontrast images by direct visual control (pre/post-Gd), and on the subtracted images (SI) only. Without MT, 36 enhancing lesions were counted on post-Gd, 36 on pre/post-Gd, and 59 on SI; using MT, 69, 52, and 50, respectively. Significant differences were found for pre/post-Gd without MT vs SI without MT ( p=0.028) and vs pre/post-Gd with MT ( p=0.012) as well as for pre/post-Gd with MT vs post-Gd with MT ( p=0.028). With pre/post-Gd, MT allowed the detection of 1.6 enhancing lesions per patient more than without MT. Whereas the SI without MT allow the detection of an increased number of enhancing lesions, SI with MT do not. An off-site final assessment allowed calculation of sensitivity and positive predictive value as follows: without MT were 63 and 94% (post-Gd), 67 and 100% (pre/post-Gd), 96 and 88% (SI); and with MT were 93 and 73% (post-Gd), 96 and 100% (pre/post-Gd), 91 and 98% (SI), respectively. Thus, SI seem to increase the sensitivity without MT; moreover, they could be used to correct the pseudoenhancement that impair post-Gd images with MT.

Adult↗
PubMed2001

Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial.

PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P =.04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P =.03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P =.04). CONCLUSION: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.

Adolescent↗
PubMed2001

A nonparametric scoring algorithm for identifying informative genes from microarray data.

Microarray data routinely contain gene expression levels of thousands of genes. In the context of medical diagnostics, an important problem is to find the genes that are correlated with given phenotypes. These genes may reveal insights to biological processes and may be used to predict the phenotypes of new samples. In most cases, while the gene expression levels are available for a large number of genes, only a small fraction of these genes may be informative in classification with statistical significance. We introduce a nonparametric scoring algorithm that assigns a score to each gene based on samples with known classes. Based on these scores, we can find a small set of genes which are informative of their class, and subsequent analysis can be carried out with this set. This procedure is robust to outliers and different normalization schemes, and immediately reduces the size of the data with little loss of information. We study the properties of this algorithm and apply it to the data set from cancer patients. We quantify the information in a given set of genes by comparing its distribution of the score statistics to a set of distributions generated by permutations that preserve the correlation structure among the genes.

Algorithms↗
PubMed2000

Identifying breast cancer patients at high risk for bone metastases.

PURPOSE: To identify patient populations at high risk for bone metastases at any time after diagnosis of operable breast cancer, because these patients are potential beneficiaries of treatment with bisphosphonates. PATIENTS AND METHODS: We evaluated data from 6,792 patients who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1993. Median follow-up was 10. 7 years. A total of 1,275 patients (18.7%) presented with node-negative disease, whereas 3,354 patients (49.4%) had one to three and 2,163 patients (31.9%) had four or more involved axillary lymph nodes. We also assessed the incidence of subsequent bone metastases in the cohort of 1,220 patients who had a first event in local or regional sites or soft tissue alone. Median follow-up for this cohort was 7.7 years from first recurrence. RESULTS: For the entire population with operable disease, the cumulative incidence of bone metastases at any time was 8.2% at 2 years from randomization and 27.3% at 10 years. The highest cumulative incidences of bone metastases at any time were among patients who had four or more involved axillary nodes at the time of diagnosis (14.9% at 2 years and 40.8% at 10 years) and among patients who had as their first event a local or regional recurrence or a recurrence in soft tissue, without any other overt metastases (21.1% at 2 years from first recurrence and 36.7% at 10 years). CONCLUSION: Treatments to prevent bone metastases may have a major impact on the course of breast cancer and may be most efficiently studied in populations with several involved axillary nodes at the time of presentation and in populations with local or regional recurrence or recurrence in soft tissue.

Aged↗
PubMed2000

A graphical method to assess treatment-covariate interactions using the Cox model on subsets of the data.

We introduce the subpopulation treatment effect pattern plot (STEPP) method, designed to facilitate the interpretation of estimates of treatment effect derived from different but potentially overlapping subsets of clinical trial data. In particular, we consider sequences of subpopulations defined with respect to a covariate, and obtain confidence bands for the collection of treatment effects (here obtained from the Cox proportional hazards model) associated with the sequences. The method is aimed at determining whether the magnitude of the treatment effect changes as a function of the values of the covariate. We apply STEPP to a breast cancer clinical trial data set to evaluate the treatment effect as a function of the oestrogen receptor content of the primary tumour.

Antineoplastic Agents, Hormonal↗
PubMed2000

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Adult↗
PubMed2000

Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: the International Breast Cancer Study Group Trial VII.

PURPOSE: Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII. PATIENTS AND METHODS: Postmenopausal women with operable, node-positive breast cancer were randomized to receive either tamoxifen alone for 5 years (306 patients) or tamoxifen plus three consecutive cycles of classical cyclophosphamide (100 mg/m(2) orally days 1 to 14), methotrexate (40 mg/m(2) intravenous days 1 and 8), and fluorouracil (600 mg/m(2) intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. RESULTS: Among the 299 patients who received at least one dose of CMF, women 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P =.004). More women in the older age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5%, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively). Older patients also received less than their expected CMF dose compared with younger postmenopausal women (P =.0008). The subjective burdens of treatment, however, were similar for younger and older patients based on quality-of-life measures (performance status, coping, physical well-being, mood, and appetite). For older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [CI], 0.65 to 1.52; P =.99). For younger patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% CI, 0.53 to 0.91; P =.008), but the test for heterogeneity of CMF effect according to age group was not statistically significant. The reduced effectiveness of CMF among older women could not be attributed to dose reductions according to dose received. CONCLUSION: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients.

Age Factors↗
PubMed2000

Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis.

We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.

Aged↗
PubMed1998

Quality of life assessment in the adjuvant setting: is it relevant? International Breast Cancer Study Group.

In the breast cancer adjuvant therapy setting, the critical issue to consider in treatment decision-making is the tradeoff between quality and quantity of life. The toxicities of adjuvant therapies, both acute and late, must be balanced against the potential benefits of delayed recurrence and improved survival. The question should be addressed concerning when quality-of-life assessment is relevant in the adjuvant setting. Such assessments can inform patients about what to expect from their treatment, describe quality-of-life differences between treatments, provide an additional baseline measure with potential prognostic significance, inform clinicians about their patients' experiences with toxicities, indicate situations in which psychosocial interventions might be useful, and document patient adaptation to diagnosis and treatment. The relevance of quality-of-life assessment in the adjuvant setting can be illustrated by investigating one of the most controversial questions of today: When should chemotherapy be added to tamoxifen for postmenopausal patients? Data from the International Breast Cancer Study Group (IBCSG) Trial VII showed that adding 3 months of CMF (cyclophosphamide 100 mg/m2 orally days 1-14; methotrexate 40 mg/m2 i.v. days 1, 8; fluorouracil 600 mg/m2 i.v. days 1, 8; repeated every 28 days) to tamoxifen significantly improved disease-free survival compared with tamoxifen alone. The Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment (QTWiST) method was used to compare the adjuvant therapies with respect to quality-adjusted survival. The analysis indicated that the decision to use adjuvant chemotherapy in this setting should be based on patient preferences concerning the relative importance of treatment toxicity versus disease recurrence.

Antineoplastic Agents, Hormonal↗
PubMed1997

Three-dimensional MR myelography of traumatic injuries of the brachial plexus.

PURPOSE: To determine the diagnostic accuracy of three-dimensional MR myelography in the evaluation of traumatic injuries of the brachial plexus. METHODS: Twenty patients with clinical and electromyographic evidence of traumatic brachial plexopathy were examined with three-dimensional MR myelography, conventional cervical myelography, and CT myelography 1 to 9 months after trauma. Three-dimensional MR myelography was performed on a 1.5-T MR unit with a constructive interference in steady state (CISS) technique. For each patient, maximum intensity myelographic projections and multiplanar reconstruction reformatted 1-mm axial sections were obtained from the same 3-D data set. Three-dimensional MR myelographic findings were compared with findings at cervical myelography and CT myelography. Surgical findings were available for comparison in 13 patients. RESULTS: Three-dimensional MR myelography enabled detection of meningoceles with avulsed or intact nerve roots, partial or complete radicular avulsions without disruption of the thecal sac, dural sleeve abnormalities, and dural scars. Assuming cervical myelography and CT myelography as the standards of reference, 3-D MR myelography showed 89% sensitivity, 95% specificity, and 92% diagnostic accuracy in the evaluation of nerve root integrity. CONCLUSION: Three-dimensional MR myelography can show the majority of traumatic lesions that involve the proximal portion of the brachial plexus in a single rapid examination. On the basis of our findings, we propose this technique as a screening examination for patients with traumatic brachial plexus palsy.

Adolescent↗
PubMed1996

Effect of different dialysis membranes on platelet function. A tool for biocompatibility evaluation.

Intradialytic coagulative and platelet activation, one of the main consequences of blood-membrane contact, was studied in a group of 5 RDT patients with a comparative evaluation of 3 different dialytic membranes: Cuprophan (CU), Polysulfone (PS) and Cellulose Triacetate (CT). Each patient underwent 5 consecutive dialysis sessions with the above mentioned membranes. Intradialytic platelet activation was studied through a morpho-functional evaluation between the mean platelet volume (MPV) and Serotonin (S), beta-Thromboglobulin (beta-TG) and Platelet Factor 4 (PF4) serum levels. These determinations were made before HD (time 0) and after 30', 120', and 240'. We also checked the intradialytic status of thrombogenesis and fibrinolysis determining aPTT, thrombin time, fibrinogen, antithrombin III (AT III), alpha-2 antiplasmin and plasminogen, at the same time intervals. All membranes tested (CU, PS, CT) caused appreciable intradialytic platelet activation, above all after 15' and at the end of dialysis sessions, more marked for CU than PS or CT. In particular MPV showed a decrease throughout the session (-5% at 30' and -9% at 240') while S, beta TG and PF4 peripheral blood levels showed a significant increase at the same intervals with CU membrane. Lastly coagulative and fibrinolytic parameters showed no significant differences among any of the membranes tested.

Adult↗
PubMed1994

[Modern imaging of maxillofacial deformities].

Facial malformations make a wide chapter of maxillofacial abnormalities whose treatment needs an accurate clinical-instrumental analysis to quantify malformation entity and to agree on precise lesion classification and subsequent management. Maxillofacial abnormalities are classified as congenital, growth-related and acquired. Congenital deformities include the alterations present at birth, i.e., craniofacial stenosis, oto-mandibular syndrome. Treacher-Collins and Goldenhar syndrome, facial clefts and lip-palate clefts. Growth-related malformations include the deformities appearing during growth and which are called maxillary dysmorphosis, e.g., hemimandibular hyperplasia, prognathism, maxillary hypoplasia, etc. Acquired malformations are those remaining after trauma or cancer surgery and those which are secondary to fibrous dysplasias of the craniofacial complex. May 1990 through May 1993, forty-two patients with different malformations were examined. The malformations secondary to cancer surgery were not included in our series. A radiologic study including conventional skull radiography, teleradiography and panoramic tomography had been performed for preliminary assessment before axial CT studies and 2D and 3D reconstructions. As for our series, in 20 patients coventional radiology was exhaustive to diagnose the disorder and to supply essential elements for treatment planning while axial CT and 3D reconstructions added no further piece of information. Only in the most complex malformations and in all cases of congenital malformations was axial CT needed to assess the type, extent and entity of the malformations allowing both the diagnosis and adequate surgical planning.

Adolescent↗