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Biomedical subjects

L Gaspar

Publications and source records attributed to L Gaspar.

At least 19 recordsLinked to original sources
PubMed1996

A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis.

BACKGROUND: Cerebral metastasis is a common oncologic problem that occurs in 15-30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis. METHODS: A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions. RESULTS: Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3-11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9-7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was > or = 70% did not differ between the 2 groups. CONCLUSIONS: This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis.

Brain Neoplasms↗
PubMed1996

A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.

PURPOSE: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. METHODS AND MATERIALS: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. RESULTS: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study. CONCLUSION: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.

Adolescent↗
PubMed1996

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Adult↗
PubMed1996

Pre-radiation chemotherapy for malignant glioma in adults.

PURPOSE: To review our experience with pre-radiation chemotherapy for malignant glioma. METHODS: Consecutive adults with newly diagnosed glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic mixed glioma with a Karnofsky Performance Score of 60 or greater were treated with one cycle of procarbazine, lomustine and vincristine or lomustine alone, prior to radiation. Computed tomographic scans were obtained soon after surgery, eight weeks later, after radiation, and at regular intervals thereafter. The effects of chemotherapy and subsequent radiation and durations of tumor control and survival were assessed in this single arm, single center, prospective trial. RESULTS: Thirty-seven patients started chemotherapy, 36 were rescanned eight weeks after diagnosis. Five patients (16%) responded to the first cycle of chemotherapy, three had glioblastoma and two anaplastic oligodendroglioma. Seven (19%) progressed during the first cycle, 6 had glioblastoma; with the addition of radiation one progressive case responded, three stabilized, and three continued to progress. Median times to progression and median durations of survival were 26 weeks and 60 weeks for the entire group, 24 weeks and 44 weeks for glioblastoma, and greater than 104 weeks for anaplastic astrocytoma. CONCLUSIONS: Most patients with glioblastoma do not respond to one cycle of nitrosourea-based chemotherapy given prior to radiation, but patients with anaplastic oligodendroglioma sometimes do. Patients with anaplastic astrocytoma may not respond to one cycle of chemotherapy, but often respond to subsequent radiation. Judging by survival results, radiation can be delayed eight weeks without appearing to compromise patient outcome. IMPLICATIONS: Pre-radiation chemotherapy with newer agents can be evaluated more fully in the future knowing that brief delays in radiation are unlikely to yield substantially inferior results.

Adult↗
PubMed1995

Permanent iodine-125 implants in the up-front treatment of malignant gliomas.

Between July 1989 and July 1992, 58 patients with newly diagnosed, histologically confirmed malignant gliomas (40 anaplastic astrocytomas, 18 glioblastoma multiforme) underwent implantation with low-activity iodine-125 sources. Patients were considered appropriate candidates for brachytherapy if their Karnofsky scores were > or = 70 and their contrast-enhancing tumors were < 6 cm in maximum diameter. Tumor volumes ranged from 0.1 to 90 ml. Ten patients had implants only. The other 48 patients received additional external beam radiation; 38 patients received radiation 1 to 2 weeks after the implant, and 10 patients received radiation preceding the implant. Median survival has not been reached but is currently greater than 31 months for patients with anaplastic astrocytoma and greater than 23 months for patients with glioblastoma. The rate of second operation for this group of patients was 45% (26 patients). Brain necrosis requiring resection occurred in 11 patients (19%). Although further follow-up is required, we conclude that low-activity permanent iodine-125 implants provide patients who have newly diagnosed malignant gliomas long-term survival with an acceptable risk of late complications.

Adolescent↗
PubMed1993

A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. CNS Cancer Consortium.

PURPOSE: The object of this study was to ascertain the value of topical ascorbic acid in the prevention of radiation dermatitis. METHODS AND MATERIALS: Patients with primary or metastatic brain tumors were eligible. Patients applied a topical solution, twice per day prior to and throughout the course of radiotherapy, to the left and right sides of the head. The radiotherapist and the patient were blinded as to the contents of the solutions. The bottle for one side of the head contained topical ascorbic acid solution. The bottle for the other side of the head contained only vehicle. During and after the course of treatment the radiotherapist scored the skin reaction on both the left and right sides of the irradiated head using a skin reaction scale. The data were analyzed with a matched pair analysis. Since each patient received both treatments (ascorbic acid and control solutions) the statistical analysis concentrated on the paired difference in scores based on the probability of a "preference" for the treatment or control. RESULTS: Eighty-four patients entered the study. Sixty-five were suitable for analysis. In 10 patients there was a preference for ascorbic acid solution (15%), in 20 patients there was a preference for placebo (31%), and there was a preference for neither in 35 patients (54%). Ascorbic acid solution could be considered to have an effect if the percentage of preferences favoring ascorbic acid over placebo, among those subjects with a preference, significantly exceeded the 50% expected by chance. The observed percentage of preferences for ascorbic acid was only 33% (10 of 30 with a preference; p = .10, two-sided sign test). Patient age, race, sex, and total dose of irradiation had no detectable influence on the comparative skin toxicity scores. CONCLUSION: There is no discernible benefit to ascorbic acid lotion, in the manner in which we used it in this trial, for the prevention of radiation dermatitis.

Adolescent↗
PubMed1993

Predictors of survival following surgical resection of thymoma.

The aim of this study was to determine the predictors of long-term survival following surgical resection of thymoma. Forty-one patients with a histologically proven diagnosis of thymoma were evaluated and treated over a 30-year period (1961 to 1991) at our institution. Seven patients (Masaoka stage III or IV) were unresectable and were treated by radiotherapy and/or chemotherapy, with an overall 5 year survival of 50%. Thirty-four patients underwent primary surgical excision of the thymoma, most often through a median sternotomy, with 5- and 10-year survivals of 90%. Complete excision of the thymoma was achieved in 31 patients with a median survival of 54 months vs. 17 months if incomplete. Independent prognostic factors influencing survival were stage, histology, and patients judged to have a benign thymoma at surgery. Although the thymoma was associated with myasthenia gravis (8 patients) and second primary cancers (8 patients), neither factor was associated with overall survival. We conclude that the most significant predictors of long-term survival of thymoma include complete excision, Masaoka stage I disease, and lymphocytic histology. Multivariate analysis suggested that postoperative chemoradiotherapy may impact on survival.

Adolescent↗
PubMed1993

Radiation therapy in the unresectable cavernous hemangioma of the liver.

Hemangioma is the most common benign neoplasm of the liver, for which a 'wait and see' policy has been advised when it is small or without symptoms. Surgery is the treatment of choice of these tumors when marked symptomatology is present. However, some of these lesions cannot be excised due to their size, multiplicity, location or medical conditions. In these patients, radiotherapy has been reported to give good results with minor morbidity, suspending the tumor growth and decreasing the symptomatology. Seven symptomatic patients were treated with radiotherapy with a dose of 15-30 Gray in 15-22 fractions. Improvement of the quality of life was observed in all patients and the regression of the tumor volume was confirmed by computed tomography in five, with a follow-up ranging from 40 to 67 months.

Adult↗
PubMed1993

An analysis of radiotherapy data from the CNS cancer consortium's randomized prospective trial comparing AZQ to BCNU in the treatment of patients with primary malignant brain tumors. The CNS cancer consortium.

The CNS Cancer Consortium has conducted a phase III study comparing diaziquone (AZQ) with carmustine (BCNU) in the treatment of adults with primary anaplastic glial brain tumors. Patients eligible for this study were 18 years of age or older at the time of biopsy, subtotal resection, or gross total resection of an anaplastic glial brain tumor. Within 3 weeks of surgery, patients received whole brain radiotherapy at 1.7 to 2 Gy per fraction to a total whole brain dose of 42-48 Gy. This was followed by a boost to the tumor bed as ascertained by computed tomography (CT), angiography, and/or magnetic resonance imaging (MRI) of 1.7 to 2 Gy per fraction to a dose of 12-19 Gy. The recommended cumulative dose to the tumor bed was therefore 55-61 Gy. At 8 weeks following radiotherapy, patients were randomized to receive either AZQ at 15 mg/day for 3 days i.v. every 4 weeks or BCNU at 200 mg i.v. every 8 weeks. Chemotherapy was continued for at least 1 year unless death occurred, treatment failure was declared, or toxicity necessitated alteration of therapy. In the 249 randomized patients, there was no difference between the AZQ- and BCNU-treated patients in age, sex distribution, race, tumor histology, type of surgical resection, or Karnofsky performance status (KPS). Age and KPS at the initiation of therapy and tumor histology were the best overall predictors of survival. The type of chemotherapy (AZQ vs BCNU) was not predictive of survival. Two-year Kaplan-Meier survival was 22% in the AZQ-treated patients and 25% in BCNU-treated patients. In an analysis of radiotherapy administered we found that, within the range of doses required for this study, there was no influence of whole brain dose, boost dose, total dose, or size of the boost field on survival. The institution providing radiotherapy (teaching hospital vs nonteaching facility) did not influence survival.

Adult↗
PubMed1991

Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region).

The chromosomal localization of the genes coding for the pro-protein and pro-hormone convertases PC1, PC2, and Furin has been achieved by in situ hybridization. The genes for PC1 and PC2 were located on human chromosomes 5q15-21 and 20p11.1-11.2, respectively. The gene for Furin was assigned to the mouse chromosome 7D1-7E2 region. These data complete the chromosomal localization of these three convertases in both human and mouse. The results confirm the regional correspondence of the human chromosomes 15 and mouse chromosomes 7, as well as between human chromosome 20 and mouse chromosome 2. Furthermore, the identification of the NEC1 locus on human chromosome 5 and mouse chromosome 13 suggests a conservation of synthenic regions between these regions of the human and mouse genomes.

Animals↗
PubMed1991

Expression of endothelin-like peptide in the nervous system of the marine mollusk Aplysia.

The distribution of endothelin (ET)-like peptide immunoreactivity and mRNA in the nervous system of Aplysia californica was investigated by means of immunocytochemistry and in situ hybridization. Using specific antisera to human endothelin-1 (ET-1) and to the c-terminal peptide of human big endothelin-1 (22-38) (big ET-1), ET-like immunoreactivity was localized to various types of neurons. Immunoreactive nerve fibers for both antisera were prominent throughout the nervous system. Hybridization of radiolabeled complementary RNA probes for human ET-1 or rat endothelin (endothelin-3, ET-3) to paraformaldehyde-fixed, paraffin-embedded sections of various ganglia revealed the presence of a large number of labeled neurons. The number of labeled neurons was higher than those that were immunoreactive for the ET antisera. Preabsorption of the ET antisera with their respective synthetic peptide or hybridization of sections with the sense probes confirmed the specificity of the data. The present study shows that members of the endothelin family may be found in very distant phylogenetic organisms. This conservation suggests a possible role for this peptide as a neurotransmitter and/or neuromodulator in the central nervous systems of diverse species.

Animals↗
PubMed1991

ANF mRNA is detected by the polymerase chain reaction technique in the chorioidea and bodies but not in the retina of the rat eye.

Specific proANF mRNA was demonstrated by the polymerase chain reaction (PCR) technique in ciliary body and chorioidea tissue extracts but not in the retina of the rat eye. However, immunoreactive (IR) ANF was detected in all of these tissues by a specific and sensitive radioimmunoassay (RIA). Since ANF seems to be involved in the maintenance of intraocular pressure, the regulation of ANF gene expression in these distinct eye tissues could be an important factor in the pathogenesis of glaucoma.

Animals↗
PubMed1991

Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2.

Using a 796-basepair cDNA fragment obtained from a mouse pituitary library we have screened two mouse insulinoma libraries and isolated a full-length cDNA clone (2516 basepairs; 753 amino acids), designated mPC1. The cDNA sequence of mPC1 codes for a protein containing 753 amino acids and three potential N-glycosylation sites. This cDNA encodes a putative novel subtilisin-like proteinase, exhibiting within its presumed catalytic domain 64%, 55%, and 47% amino acid sequence identity to the recently characterized candidate prohormone convertases human Furin, mouse PC2, and yeast Kex2 gene products, respectively. An identical sequence to mPC1 was derived from a cDNA library of mouse corticotroph AtT-20 tumor cells. An ArgGlyAsp tripeptide identical to the recognition sequence of integrins was observed in the structures of the mammalian PC1, PC2, and Furin. In situ hybridization results demonstrated a distinct localization of the mPC1 and mPC2 transcripts in pituitary and brain. Thus, whereas both mPC1 and mPC2 are found in the intermediate lobe of the pituitary, only mPC1 is easily detected in the anterior lobe. In extrahypothalamic regions of the brain, including cortex, hippocampus, thalamus, and spinal cord, mPC2 transcripts predominate over mPC1. Both mRNAs are found in only a fraction of hypothalamic neurons, with greater abundance of mPC1 over mPC2 in the supraoptic nucleus. The genes coding for mPC1 and mPC2 map to the murine chromosomes 13 (band 13c) and 2 (2F3-2H2 region), respectively.

Amino Acid Sequence↗