Biomedical subjects

R Soffietti

Publications and source records attributed to R Soffietti.

At least 19 recordsLinked to original sources

PubMed2006

EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force.

The objectives have been to establish evidence-based guidelines and identify controversies regarding the management of patients with brain metastases. The collection of scientific data was obtained by consulting the Cochrane Library, bibliographic databases, overview papers and previous guidelines from scientific societies and organizations. A tissue diagnosis is necessary when the primary tumor is unknown or the aspect on computed tomography/magnetic resonance imaging is atypical. Dexamethasone is the corticosteroid of choice for cerebral edema. Anticonvulsants should not be prescribed prophylactically. Surgery should be considered in patients with up to three brain metastases, being effective in prolonging survival when the systemic disease is absent/controlled and the performance status is high. Stereotactic radiosurgery should be considered in patients with metastases of 3-3.5 cm of maximum diameter. Whole-brain radiotherapy (WBRT) after surgery or radiosurgery is debated: in case of absent/controlled systemic cancer and Karnofsky Performance score of 70 or more, one can either withhold initial WBRT or deliver early WBRT with conventional fractionation to avoid late neurotoxicity. WBRT alone is the treatment of choice for patients with single or multiple brain metastases not amenable to surgery or radiosurgery. Chemotherapy may be the initial treatment for patients with brain metastases from chemosensitive tumors.

Advisory Committees↗

PubMed2006

Endocrine dysfunction in patients operated on for non-pituitary intracranial tumors.

OBJECTIVE: Hypopituitarism frequently follows pituitary neurosurgery (NS) and/or irradiation. However, the frequency of hypothalamic-pituitary dysfunction after NS of non-pituitary intracranial tumors is unclear. The aim of this study was to assess the presence of endocrine alterations in patients operated on for intracranial tumors. DESIGN: This is a retrospective study. METHODS: We studied 68 consecutive adult patients (28 female, 40 male, age 45.0 +/- 1.8 years; body mass index (BMI): 26.5 +/- 0.6) with intracranial tumors who underwent NS only (n = 17) or in combination with radiotherapy (RT) and/or chemotherapy (CT) (n = 51). In all subjects, basal endocrine parameters and the GH response to GHRH + arginine test (using BMI-dependent cut offs) were evaluated. RESULTS: In 20.6% of the patients, peripheral endocrinopathy related to CT and/or RT was present. Hypopituitarism was found in 38.2% of the patients. Total pituitary hormone, multiple pituitary hormone, and isolated pituitary hormone deficits were present in 16.2, 5.8, and 16.2% respectively. The most common pituitary deficits were, in decreasing order: LH/FSH 29.4%, GH 27.9%, ACTH 19.1%, TSH 17.7%, and diabetes insipidus 4.4%. Hyperprolactinemia was present in 13.2%. The prevalence of hypopituitarism was higher in patients who underwent NS only and with tumors located closely to the sella turcica, but a substantial proportion of patients with tumors not directly neighboring the sella also showed hypopituitarism. CONCLUSIONS: Hypopituitarism frequently occurs after NS for intracranial tumors. Also, exposure of these patients to CT and/or RT is frequently associated with peripheral endocrinopathies. Thus, endocrine evaluation and follow-up of patients treated for intracranial tumors should be performed on a regular basis.

Adult↗

PubMed2005

Radiotherapy and chemotherapy of brain metastases.

The authors have reviewed the results, the indications and the controversies regarding radiotherapy and chemotherapy of patients with newly diagnosed and recurrent brain metastases. Whole-brain radiotherapy, radiosurgery, hypofractionated stereotactic radiotherapy, brachytherapy and chemotherapy are the available options. New radiosensitizers and cytotoxic or cytostatic agents are being investigated. Adjuvant whole brain radiotherapy, either after surgery or radiosurgery, and prophylactic cranial irradiation in small-cell lung cancer are discussed, taking into account local control, survival, and risk of late neurotoxicity. Increasingly, the different treatments are tailored to the different prognostic subgroups, as defined by Radiation Therapy Oncology Group RPA Classes.

Antineoplastic Agents↗

PubMed2002

The position of the neurologist in neuro-oncology.

Neuro-oncology is a growing new subspeciality with a strong interdisciplinary character. This position paper explains the role of neurology in the multidisciplinary field of neurosurgeons, radiotherapists and general oncologists, dealing with neuro-oncological patients. The paper delineates the varied spectrum of the field of neuro-oncology which expands from primary brain tumours, to metastatic and non-metastatic effects of systemic cancer on the central and peripheral nervous system, neurotoxicity due to cancer treatment and issues of quality of life. It has been written by the scientific neuro-oncology panel of the European Federation of Neurological Societies (EFNS) to delineate the situation of neuro-oncology in Europe, and facilitate the understanding and implementation of this subspeciality in the future.

Brain Neoplasms↗

PubMed2001

Brain metastases from unknown primary tumour: a prospective study.

The best management of patients with brain metastases from an unknown primary tumour is still unclear, as data are scarce and studies are retrospective. We report 33 patients with biopsy-proven brain metastases from a primary tumour not found at the first investigations, who were treated by surgery and/or radiotherapy and followed with serial CT until death. Median survival time for all patients was 10 months and survival rates at 6 months, 1 year and 2 years were 76 %, 42 % and 15 % respectively. Patients with single brain metastasis treated by gross total resection and whole-brain radiotherapy (WBRT) had a median survival of 13 months with 76% alive at 6 months, 57 % at 1 year and 19% at 2 years. Patients with multiple brain metastases who underwent either WBRT alone or WBRT preceded by gross total resection of the symptomatic lesions had a poorer prognosis: median survival of 6-8 months with 50-100% alive at 6 months, 17-20% at 1 year and none alive at 2 years. In 85% of patients with a single brain metastasis a significant improvement in neurological functions was observed after surgical resection; among patients with multiple brain metastases a neurological improvement was observed in all patients who had a resection of symptomatic lesions and only in a half of patients who had WBRT alone. During the follow-up the primary tumour was found in 27/33 patients (82 %) and was located in the lung in 78%. Between 1987 and 1991 (with limited screening for the primary tumour in the follow-up) the unknown tumours were 6/15 (40%); in the more recent period (1992-1996) (CT-based screening for the primary tumour in the follow-up) no primary tumour remained unknown but overall survival has not significantly improved. The number of brain metastases was the only significant factor affecting survival after both univariate and multivariate analysis. This study suggests that, in patients with both single and multiple brain metastases from an undetected primary site when first studied, surgery and/or WBRT enable the control of the brain disease, partly because the systemic disease may be silent for a prolonged time. Only a few asymptomatic patients may benefit from an early detection and treatment of the primary tumour during the follow-up.

Adult↗

PubMed2001

Primitive cerebral melanoma: case report and review of the literature.

BACKGROUND: Central nervous system primary malignant melanoma accounts for approximately 1% of all the cases of melanoma; reports in the literature are relatively rare. CASE DESCRIPTION: A 74-year-old man was hospitalized because of an episode of aphasia. The neuroradiologic examinations demonstrated a round homogeneous lesion extending near the left sylvian fissure. He had no extracranial abnormalities. The patient underwent a neurosurgical procedure and the tumor was macroscopically totally excised. Pathological examination of the surgical specimen revealed a histological appearance similar to that of melanoma. A diagnosis of primary CNS melanoma was made after careful dermatologic and ophthalmologic examination, which ruled out presence of cutaneous or choroidal melanoma. The patient did not receive any further treatment and he is free of disease 2 years after diagnosis. CONCLUSIONS: We report a case of primary cerebral melanoma of the left temporal lobe; clinical, neuroradiological, and histological findings are discussed with review of the literature. Primary melanoma of the CNS may present either with localized intra/extra-axial mass lesions or with meningeal spread, which carries a worse prognosis. The prognosis of cerebral primitive melanoma is variable, although it is common opinion that primitive cerebral melanoma has a better prognosis than cutaneous melanoma, with two cases in the literature surviving 9 and 12 years.

Aphasia↗

PubMed2000

[Cerebral metastatis. Diagnostic and therapeutic features].

Brain metastases represent the most frequent intracranial neoplasms in adults: between 15 and 25% of patients with systemic tumors will face brain metastases along the clinical course of disease. Lung cancers, breast cancers and melanomas are the commonest causes of brain metastases (about 75%), while the primary site remains unknown inasmuch as 15% of cases. Headache, focal neurological deficits, epilepsy and intracranial hypertension are the most frequent initial symptoms and signs. Computerized Tomography and Magnetic Resonance represent the methods of choice for diagnosis. Supportive care is based on corticosteroids and antiepileptic drugs. Anticancer therapy planning must be based on prognostic factors: performance status, tumor activity and age. Surgical removal followed by external adjuvant radiotherapy is considered the best treatment in patients with single brain metastases and systemic disease under control or absent. Stereotactic radiosurgery is preferable in cases of unoperable metastatic lesions of the brain or progressive systemic disease. The usefulness of whole brain radiotherapy following surgery or radiosurgery is debated. In patients with multiple brain metastases, apart from radiotherapy, surgical excision of the symptomatic lesions, when feasible, seems advantageous. Chemotherapy is a valid option only in cases of metastases from chemosensitive neoplasms (small-cell lung tumors or breast tumors).

Brain Neoplasms↗

PubMed1998

PCV chemotherapy for recurrent oligodendrogliomas and oligoastrocytomas.

OBJECTIVE: The role of chemotherapy in the treatment of low-grade oligodendrogliomas and oligoastrocytomas is still unclear. A Phase II study was conducted to determine the benefits and toxicity of the procarbazine, lomustine, and vincristine (PCV) regimen in patients with low-grade oligodendrogliomas and oligoastrocytomas recurrent after surgery alone or surgery with radiotherapy. METHODS: Patients with both enhancing and nonenhancing tumors were treated with up to six cycles of standard PCV, and response was evaluated by conventional criteria based on computed tomography or magnetic resonance imaging. RESULTS: Sixteen of 26 patients (62%) responded to PCV: 3 (12%) experienced complete response, 13 (50%) experienced partial response, 8 (31%) had stable disease, and 2 (8%) had progressive disease. All symptomatic patients who responded and three with stable disease improved in seizure frequency, lateralizing signs, and symptoms of intracranial hypertension. The response rate for patients with enhancing lesions revealed by computed tomography or magnetic resonance imaging (74%) was significantly higher than that of patients with nonenhancing lesions (29%) (P < 0.05). Both oligodendrogliomas and oligoastrocytomas responded to PCV, with complete responses occurring in association with pure tumors only. The median time to tumor progression of all 26 patients was 24 months and was significantly longer for those with oligodendrogliomas compared with those with oligoastrocytomas (32 versus 12 mo) (P < 0.001). Chemotherapy was well tolerated, with mild hematological toxicity and rare skin rashes being the most frequent sequelae. CONCLUSION: These results suggest that chemotherapy with PCV is effective in the treatment of recurrent low-grade oligodendrogliomas and oligoastrocytomas.

Adult↗

PubMed1997

MRI diagnosis of intramedullary metastases from extra-CNS tumors.

The purpose of this study was to evaluate the topography, morphology and contrast enhancement of the intramedullary metastases (IM) from extra-CNS neoplasms. We report the results of a multicenter retrospective study on 18 patients with 26 IM examined with a 0.5T MR imaging system; intravenous injection of Gd-DTPA was performed in all cases. We found that the lesions are most frequently single, oval shaped, and small, with little or no deformation of the spinal cord (14 of 26 IM). They appear isointense on spin-echo T1-weighted images (24 of 26 IM), with a homogeneous and generally nodular high contrast enhancement after Gd-DTPA injection (21 of 26 IM), and present on T2- and proton-density-weighted sequences with a pronounced perilesional, pencil-shaped hyperintensity of the surrounding cord which is more evident in the cranial part of the cord referring to the IM.

Breast Neoplasms↗

PubMed1994

Proliferating cell nuclear antigen (PCNA) in low-grade astrocytomas: its prognostic significance.

AIMS AND BACKGROUND: A clear line cannot be drawn between well-differentiated and anaplastic astrocytomas, and a subset of low-grade tumors, histologically indistinguishable from the others, behaves similarly to anaplastic astrocytomas. The proliferative index could aid in the identification of this subgroup, for which a different therapeutic approach would be indicated. METHODS: We immunohistochemically evaluated the proliferating cell nuclear antigen (PCNA) expression in 77 well-differentiated astrocytomas, since PCNA has been considered a good proliferation marker. The prognostic significance of PCNA labeling index (LI) was assessed in univariate and multivariate analysis, taking into consideration some clinical and histologic factors known to affect prognosis. RESULTS: PCNA immunostaining identified a subgroup of tumors, characterized by a LI > 5%, with a median survival close to that observed in anaplastic astrocytomas. The survival table of such a group was significantly different from that of the group with a lower LI (p = 0.0009). Multivariate analysis confirmed that PCNA-LI is an independent prognostic factor (p = 0.001). CONCLUSION: These data suggest that PCNA immunostaining can be a useful tool to define the prognosis of low-grade astrocytomas on routine biopsy material.

Adult↗

PubMed1992

Selective intra-arterial chemotherapy with BCNU in recurrent malignant gliomas.

Study of intra-arterial BCNU in 12 patients with recurrent glioblastoma multiforme and 5 patients with recurrent anaplastic astrocytoma already treated by surgery and radiotherapy indicates that the risk of BCNU toxicity can be reduced by the use of relatively low doses (160-180 mg/m2) of BCNU, the use of dextrose as solvent, selective injections of BCNU, and fast "bolus" injections of drug. No certain toxic effects of BCNU were observed in the 17 patients treated this way. Anaplastic astrocytomas, particularly in young patients, seem to respond relatively well to this treatment.

Adult↗

PubMed1991

Histologic prognostic factors in ependymoma.

The prognostic value of a series of histologic signs and clinical features was studied in a series of 298 ependymomas, collected from different institutions. The distribution of tumor sites varied in relation to patient age, with infratentorial cases prevailing under 4 years. Life table univariate analysis demonstrated as highly significant prognostic factors: (1) the number of mitoses; (2) endothelial hyperplasia; (3) necrosis; (4) intracranial site; (5) age less than 4 years. Multivariate analysis by tumor site revealed mitoses cell density, age greater than 16 years in supratentorial cases, and subependymoma in infratentorial cases to be prognostically important. Comparison of the anaplastic variant with the other tumor types in intracranial cases did not show a significant difference in survival even though the median survival time of anaplastic cases was shorter. The main conclusion is that the histological criteria employed to diagnose anaplasia in ependymomas. The number of mitoses is a very important prognostic factor in supratentorial cases, whereas endothelial proliferations and necroses are much less important as prognostic factors than in gliomas.

Adolescent↗

PubMed1991

Ependymoma: internal correlations among pathological signs: the anaplastic variant.

In a series of 298 cases of ependymoma, survival analysis identified some prognostic histological factors but failed to demonstrate a worse survival for the anaplastic variant diagnosed with the common criteria used for assessing anaplasia in primitive brain tumors. This finding suggests that either anaplastic ependymoma does not exist, or that the established criteria are not useful in its identification. To solve these problems, the association of histological, immunohistochemical, and ultrastructural signs in 173 intracranial cases was investigated and analyzed by means of contingency tables. Many signs had only focal distribution. Some signs, meaningful for anaplasia, such as very high cell density and number of mitoses, were found to be associated, whereas other signs usually considered indicative of anaplasia, such as endothelial hyperplasia, glomeruli, and necrosers, were not. In addition, pseudorosettes, mesodermic areas, and incomplete formation of perivascular pseudorosettes were signs associated with very high cell density and number of mitoses. Distribution of glial fibrillary acidic protein and vimentin, as well as other immunohistochemical and ultrastructural features, were not helpful, with the exception of microsettes found by electron microscopy. Our conclusion is that the anaplastic variant of ependymoma is recognizable only when some histological prognostic factors, such as cell density and number of mitoses, are maximally expressed.

Adolescent↗

PubMed1991

Lonidamine in malignant brain tumors.

Among new therapeutic modalities for both primary and secondary brain tumors, selective manipulation of metabolic pathways seems attractive. In human malignant gliomas and cell lines from a glioblastoma multiform, lonidamine has been shown to interfere with aerobic glycolysis with a decrease of lactate production by the inhibition of a mitochondrially-bound hexokinase; this selective reduction of the energetic capabilities of glioma cells would be a limiting factor for processes requiring energy, such as cell growth and recovery from potentially lethal damage after radiotherapy or chemotherapy. The activity of lonidamine in malignant gliomas after surgery in association with conventional radiotherapy is being investigated, while previous studies have suggested a limited, but clear therapeutic activity of the drug in recurrent malignant gliomas. In brain metastases lonidamine has not been effective as a radiation enhancer, but has been shown to potentiate systemic chemotherapy. Most common side effects were myalgias, testicular pain and ototoxicity with no serious organ toxicity or myelosuppression.

Antineoplastic Agents↗

PubMed1990

Vascular response to irradiation in malignant gliomas.

The vascular response to irradiation was studied in peritumoral cortex and tumor areas in 9 autopsied cases of glioblastoma multiforme and in 10 biopsies of reoperated cases. The study was carried out by histological, immunohistochemical and electron microscope procedures. Hyaline thickening of the vessel walls with deformation and impoverishment of endothelial nuclei are the most striking features. Formation of large PAS-positive areas from the confluence of thickened vessel walls and development of a fibroblastic proliferation follow. Fibroblastic areas may entrap tumor glial cells. In PAS-positive areas a special population resembles myofibroblasts of tissue scars. Electron microscope reveals the production of collagen fibrils in and outside vessel walls. The presence of collagen III and IV is in line with the present interpretation of the mesodermic component.

Adult↗

PubMed1989

Prognostic factors in well-differentiated cerebral astrocytomas in the adult.

Eighty-five "well-differentiated" astrocytomas in adults (age, greater than or equal to 18 years), operated on between 1950 and 1982, were retrospectively reviewed. The pilocytic variant was not included. Twenty-four clinical and 8 histological factors were analyzed to investigate their importance in predicting length of survival. Multivariate analysis showed that the following variables were correlated with survival time (P less than 0.01): extent of surgical removal, altered consciousness during preoperative examination, focal deficit as presenting symptom, performance status (Karnofsky rating) after surgery, and vessel size in the surgical specimen. Total removal of the tumor was related to a higher 5-year survival rate (51%) than subtotal removal (23.5%), and none of the patients with partial removal survived more than 5 years. Postoperative radiotherapy (40-55 Gy) improved only the 1- and 3-year survival rates. Based on the significant factors provided by multivariate analysis, a score was developed to detect subgroups with different prognoses. Median survival time ranged from 383 days for patients with a score greater than or equal to 2.5 to 1,533 days for those with a score less than 0.5; no patient with a score greater than or equal to 1.5 survived more than 10 years. The percentage of recurring astrocytomas that showed anaplastic areas in the second biopsy specimen was 79%. Total surgical removal is the most important factor in the management of well-differentiated astrocytomas, whereas the efficacy of postoperative radiotherapy still needs to be confirmed by prospective and randomized studies. The rationale for treating incompletely resected astrocytomas with radiation therapy could lie in the high incidence of malignant transformation.

Adolescent↗

PubMed1988

Prognostic value of histologic factors in adult cerebral astrocytoma.

Surgical specimens from 165 adults with cerebral astrocytoma were reviewed to establish the prognostic value of histologic factors when studied both individually and in combination. Glioblastomas were excluded. Nine morphologic parameters and 25 clinicotherapeutic factors were correlated with survival. Cell density, endothelial hyperplasia, number of mitoses X 10 high-power field (HPF), and vessel frequency appeared to be highly significant prognostic factors (P less than 0.001). Nuclear polymorphism, microcysts, and vessel size were significant moderately (P less than 0.01). Microcysts, vessel size, endothelial hyperplasia, and number of mitoses X 10 HPF remained significant statistically after a multivariate analysis that also included clinicotherapeutic factors. Survival was similar for astrocytomas with "extensive malignancy" and astrocytomas with only "slight and localized malignancy." Multivariate analysis showed that the presence or absence of malignancy was more important prognostically than the clinical variables (i.e., postoperative Karnofsky status or extent of surgical removal).

Adult↗

PubMed1987

Primary lymphomas of the brain: a clinico-pathologic review of 37 cases.

The clinico-pathologic data of 37 primary lymphomas of the brain were retrospectively reviewed. The tumors were classified according to the Kiel classification and the Working Formulation System. They represented 1.02% of all primary intracranial tumors of our series. The radiologic prediction appeared to be difficult: the suspicion was maximal when the absence of pathologic vessels at angiography occurred in a meningioma-like lesion at CT. Median survival was 4.53 months in the 16 cases who underwent surgery only versus 25.7 months in the 8 cases operated and irradiated with 40-60 Gy (p less than 0.01). The prognosis of lymphomas of the CNS, even if radioresponsive tumors, remains poor. Most patients relapse after treatment, most often locally in the brain, with a variable frequency of spinal or systemic localization.

Adolescent↗