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Biomedical subjects

M Eoli

Publications and source records attributed to M Eoli.

At least 19 recordsLinked to original sources
PubMed2006

Methotrexate based chemotherapy and deferred radiotherapy for primary central nervous system lymphoma (PCNSL): single institution experience.

In the following study, we present our experience in the treatment of PCNSL patients using a multi-step schedule combining chemotherapy and deferred radiotherapy. Patients were treated with two modified M-BACOD cycles and then differently according to radiological response For PR, SD and PD patients, chemotherapy was interrupted and radiotherapy initiated immediately (45 Gy Whole-brain RT). With CR patients, chemotherapy was continued with a combination of HMTX, VCZ, PCB and HD Ara-C up to a total of nine cycles. In 36 patients suitable for evaluation (2 patients had undergone tumour resection): 69.4% (25 of 36) had a complete response (CR), 19.4% (7 of 36) had a partial response(PR), 8.3% (3 of 36) had stable disease(SD), and 2.7% (one of 36) had progressive disease (PD). The PR, SD and PD patients were immediately treated by radiotherapy. In this cohort of patients, we observed 6 CR, 4 PR and 2 PD, respectively, following radiotherapy. At first relapse, a total of 16 CR patients were treated by radiotherapy for a total dose of 45 Gy. The OS was 42.1 months for the entire group of patients. In CR patients treated at the moment of recurrence by salvage radiotherapy, the TTP (time lasting from histological diagnosis until recurrence of disease before RT) was 28.3 months, with a 43.4% of disease free patients observed at 2 years. The median disease-free time observed after complete response to radiotherapy was 10.5 months. In 16 patients (34%), further progression of disease was observed following radiotherapy. Two patients developed extra-CNS disease in the breast and testis. When taking into account the patients with radiotherapy delayed at recurrence, the OS was 48 months and the survival rates were 70% and 60% at 2 years and 5 years, respectively.

Adolescent↗
PubMed2006

Molecular markers of gliomas: a clinical approach.

Over the last decade, the knowledge on the molecular genetic background of gliomas has dramatically increased. This information provides the basis for the molecular target therapies and molecular tests serve to complement the subjective nature of histopathologic criteria and add useful data regarding response to treatments and prognosis. In particular, the use of loss of heterozygosity (LOH) and methylation specific polymerase chain reaction (PCR) (MSP) based testing of gliomas is already in place and used clinically in several centers. This paper provides a brief overview of these molecular genetic aberrations and discusses the clinical utility, as well as the advantages and disadvantages of such approach. Newly developed molecular techniques, such as LOH testing, fluorescence in situ hybridization (FISH), DNA sequencing and MSP, are currently being employed in assessment of gliomas in some laboratories. However, the clinical use of some markers and the context in which the information obtained should be used are still not entirely understood. Therefore, this paper will focus on validation and implementation of molecular testing in gliomas, with emphasis on LOH on chromosomes 1p, 19q, 17p and 10q and O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status.

Biomarkers, Tumor↗
PubMed2005

Local drug delivery in recurrent malignant gliomas.

In recurrent malignant gliomas, we scheduled a protocol by adding to systemic temozolomide a local treatment delivered through a reservoire positioned in the surgically created cavity, consisting of either mitoxantrone, liposome-loaded doxorubicine or nimustine (ACNU). The progression-free survival (PFS) and survival time (ST) of the whole group of 112 patients were 8.3 and 11 months, respectively, in GBM patients, and 14 and 18 months in AA patients. To limit the selection bias in recruitment we matched locally treated patients with the whole group of patients treated for 3 years and having undergone the same protocol with the exception of local drug delivery. Variables such as age, histology and local chemotherapy delivery were proved to be statistically significant independent factors on adjunctive PFS and ST. Another group of 12 recurrent malignant gliomas with further progression was locally managed according to convection-enhanced delivery (CED) of mitoxantrone; the preliminary results show good tolerability of the schedule.

Adolescent↗
PubMed2005

The role of the neurologist.

The contribution of the neurologist should focus on timely diagnosis with accurate differential diagnosis, indications for surgery and post-surgical treatment (in the setting of a multidisciplinary team), and follow-up of disease course/treatment-related complications.

Brain Neoplasms↗
PubMed2005

CXCL12 expression is predictive of a shorter time to tumor progression in low-grade glioma: a single-institution study in 50 patients.

The clinical course of 50 patients with low-grade glioma (31 male, 19 female) undergoing surgery at a single Institution from 1992 to 1996 was analyzed in relationship with known prognostic factors as far as time to tumor progression (TTP) and survival time (ST) are concerned. Moreover, microvessel density (MVD) and expression of the angiogenesis-related chemokine CXCL12 were investigated in surgical specimens. Age at diagnosis ranged from 1 to 68 years (median 30). Histology revealed 11 fibrillary, 6 protoplasmatic, 5 gemistocytic astrocytoma, 18 oligoastrocytoma and 10 oligodendroglioma. Mean follow-up was 86 months. Four patients were lost to follow-up. Of the remaining 46, twenty-four have shown disease progression and 14 have died. Median overall survival was not achieved; an estimated 75% percentage of survivors was found at 78 months. Complete gross tumor removal was associated to a longer TTP (P = 0.04 logrank). Of the investigated immunohistochemical parameters, while MVD was not predictive of subsequent TTP, expression of CXCL12 was associated with a significantly shorter TTP (P = 0.01 logrank): this predictive value remained significant (P = 0.02) at multivariate analysis. The data suggest the possible prognostic value for CXCL-12 (an angiogenesis- and tumor-growth-related chemokine) on TTP in low-grade gliomas.

Adult↗
PubMed2005

Systemic temozolomide combined with loco-regional mitoxantrone in treating recurrent glioblastoma.

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1-5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1-5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald's criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients' compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients' selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.

Adult↗
PubMed2004

Headache in brain tumours: a symptom to reappraise critically.

Headache can be either a late or early symptom of a brain tumour, depending on the location of the tumour. A constant, progressively increasing pain, or a change in the character of headache pain, may alert the physician to this occurrence. Fortunately most people with headache, even persistent or severe headaches, do not have a tumour. In this work we review the literature about prevalence of headache as an isolated/early symptom of brain tumour and report our experience.

Brain Neoplasms↗
PubMed2003

New approach in delivering chemotherapy: locoregional treatment for recurrent glioblastoma (rGBM).

The treatment of GBM tumor recurrence is generally a hopeless challenge, since recurred tumor is resistant to the most common therapeutic efforts. Some partial results can be achieved by targeting local disease control, in view of the fact that 95% of recurrences occur locally. We present results concerning three pilot studies, all performed in recurrent GBM patients who underwent second surgery and have been treated systemically with temozolomide and locally through an Ommaya reservoire according to the following schedules: a) in 20 rGBM, 4 mg novantrone was delivered day 1,5 every 30 days; in 26 rGBM, 4 mg novantrone was delivered every 20 days in association with locoregional radioimmunotherapy (RIT); in 12 rGBM pegylated liposomal doxorubicin 4 mg was delivered day 1,5,10,15,20 with 20 days interval. Results seem very promising since there is an extension of disease free and survival, both of more than 50 % if results are evaluated in relation with the most frequent data of the literature.

Antineoplastic Agents↗
PubMed2002

Intra-arterial ACNU and carboplatin versus intravenous chemotherapy with cisplatin and BCNU in newly diagnosed patients with glioblastoma.

Thirty glioblastoma patients treated at our institute between April 1998 and September 1999 were randomized in a two-arm study to receive carboplatin plus ACNU intraarterial (IA) chemotherapy (arm A) or cisplatin plus BCNU intravenous (IV) treatment (arm B). After the second course of chemotherapy and before the third cycle they also received concomitant radiotherapy, consisting of a median dose of 56.5 Gy. There were 3 (21.4%) partial responses and 11 (78.6%) disease stabilizations in group A. There were 5 (33%) partial responses and 10 disease stabilizations in group B. Time to tumor progression was 5.2 and 5.8 months for IA and IV treatment respectively. Median survival time was 18.3 months for arm A patients and 18.6 for arm B patients. Our IA chemotherapy schedule has produced no conclusive evidence of benefit compared with intravenous treatment. Moreover, its cost-benefit ratio is not good enough to justify its continued pursuit.

Adolescent↗
PubMed2001

Efficacy of intratumoral delivery of mitoxantrone in recurrent malignant glial tumours.

Ninety-nine patients bearing recurrent malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study. All patients were previously managed with radiotherapy 60 Gy total dose and chemotherapy with nitrosoureas and platinum compounds. At recurrence they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally by delivering 4mg of mitoxantrone every 20 days through the Ommaya reservoire, and 25 GBL (group C) treated with a second surgery and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoir after repeat surgery. A trend to different demographic features among subgroups (with locoregionally treated patients and patients undergoing repeat surgery being younger than the others) was seen in this non-randomized study, but this was not statistically significant. Median overall survival was 27, 26 and 15.5 months respectively for groups c, b and a (log-rank = 0.1). After tumor recurrence median survival was 16.8, 12 and 6.6 months respectively for groups c, b and a (log-rank = 0.001) For the 29 AA, overall survival was 48.5 and 100 months (log-rank = 0.03) if treated locally with second tumor debulking. Our results stress the opinion that a second operation could be indicated only if it is a part of a therapeutic protocol to allow a locoregional treatment. Moreover we can finally assume that local delivery of chemotherapy after tumor recurrence, possibly extends patients survival but certainly improves the number of long-survivors.

Adolescent↗
PubMed2000

Embryonal tumors in the adult population: implications in therapeutic planning.

The natural history of neuroectodermal tumors is still debated as far as prognostic factors are concerned; the same uncertainty applies to the optimal radiotherapy schedule and even more to the presumptive additive effect of chemotherapy. The rarity of these tumors and the heterogeneity of management make interpretation of literature data also more difficult. We evaluated clinical course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8 with primitive neuroectodermal tumors (PNET). All patients were treated with radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27 patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8 years. Overall, PNET had a worse outcome as compared to MB: median survival times were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB patients are alive. No significant difference in disease-free period was found between patients of different age, desmoplastic variant, tumor localization, or extent of surgery. Patients considered to be "high risk" had a significantly shorter disease-free period as compared with low-risk patients (27 vs. 54.7 months, p = 0.04). Systemic or intrathecal chemotherapy did not influence progression-free survival (PFS). However, in the majority of chemotherapy-treated patients, a low-dose craniospinal radiotherapy was also delivered. This combination of treatments may have avoided the expected increased percentage of failure. Moreover, more than half of recurrent patients had a partial response to chemotherapy that extended survival for approximately 3 years. Repeated surgery and chemotherapy at recurrence favorably influenced survival time.

Adult↗
PubMed2000

Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: a clinical and molecular study of 30 families.

Spinal and bulbar muscular atrophy (Kennedy disease) is an adult form of X-linked motor neuron disease caused by the expansion of a polymorphic CAG-repeat sequence in the first exon of the androgen receptor gene. We studied clinical and molecular features of 36 patients and 19 heterozygous females. Phenotypic manifestations and disease severity broadly varied among our spinal and bulbar muscular atrophy patients. The size of CAG expansion significantly influences the age of disease onset, but neither clinical features nor disease severity. The majority of carrier women presented signs of chronic denervation at neurophysiological examination and, in three cases, low-amplitude sensory action potentials were recorded. Notably, a few women developed mild signs of bulbar motor neuron impairment later in life. The identification of a large number of patients by the use of the molecular test further supports the hypothesis that Kennedy disease had been previously underdiagnosed, probably because of the great variability of clinical presentation. Although an early diagnosis may not be crucial for treatment, given the lack of effective therapy, the molecular testing can be of great relevance for disease prognosis and genetic counseling.

Action Potentials↗
PubMed2000

Cisplatin and BCNU chemotherapy for anaplastic oligoastrocytomas.

In this study 32 newly diagnosed anaplastic oligoastrocytoma patients were enrolled (median age of 41 years, range 19-63; median Karnofsky performance status of 90, range 70-100). All patients were treated with Cisplatin (109 mg/m2) and BCNU (160 mg/m2). The chemotherapy started in the first week after surgery and it was administered every 6 weeks (5 scheduled cycles) for a total of 127 cycles. After the second cycle of chemotherapy all patients received radiotherapy (56.5 Gy). The median follow-up was 63.2 months (10-91). Nine patients were reoperated-on. The median time to tumor progression (TTP) and median survival time (ST) for the whole group of patients were 54.6 and 70.1 months, respectively. A proportional hazard model was used to look at potential prognostic factors for survival including lower age (< 40 years), extent of surgery (total/subtotal versus partial) and reoperation. When we analyzed the group of patients with total/subtotal surgery or age under 40 years the median ST could not be assessed due to the high number of surviving patients after a follow-up of 52 months. The median ST for the older patients or for patients partially operated-on was 54.1 and 42.2 months. In our study only total/subtotal surgery predicted for longer survival (p < 0.001). This schedule of treatment provides durable response in a selected group of anaplastic oligoastrocytoma patients.

Adult↗
PubMed1999

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and plasma thrombomodulin levels in glioblastoma patients.

Cellular adhesion molecules have been implicated in tumor progression and metastasis. Serum samples from 22 patients with glioblastoma (GBM), before surgery, and 19 sex and age matched healthy controls were analyzed for circulating levels of ICAM-1 and VCAM-1. At the same time also soluble plasma thrombomodulin, a marker of endothelial cell damage and activation, was detected. Soluble ICAM-1 and VCAM-1 levels were comparable in glioblastoma patients and healthy controls, while plasma thrombomodulin (TM) was significantly increased in cancer patients. There was no correlation between thrombomodulin levels and the presence of an intratumoral hemorrhage detected by CT scan, while entity of post-contrast enhacemement at CT correlated with higher TM levels. Further study with serial sampling of GBM patients and correlation with enhancement at CT will allow to ascertain the value of serum TM as a marker of disease recurrence or angiogenesis in those tumors.

Female↗
PubMed1999

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.

BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Activities of Daily Living↗