Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme

The purpose of this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of glioblastoma multiforme in Aragon and La Rioja. An epidemiological survey

The aim of this work has been to evaluate the epidemiologic data in a series of 157 patients operated for glioblastoma multiforme in Aragón and La Rioja, during a period of 15 years. We haven't analyzed the cases that weren't operated on, because of the localization of the tumor or the bad situation of the patient. All the patients have an anatomopathologic confirmation. We have studied a total of 795 patients operated for a cerebral or cerebellar tumor. The glioblastoma multiforme was the third type of tumor in frequency, after the meningioma and the astrocytoma. In the different groups of age the peak incidence was between the 50 and 59 years old, followed the group between 60 to 69. 153 cases appeared in adults and only 4 cases were found below the age of 20. The right hemisphere was the most frequently affected. Males were more often affected than females, with 96 cases (61.14%) in males and 61 cases (38.85%) in females. We couldn't find a significative relation between the presence of the tumor and the profession or another personal antecedent of the patients.     

Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme

There has been considerable controversy over the concept of treating glioblastoma multiforme with cytoreductive surgery. Therefore, a retrospective study of cases treated between 1986 and 1991 was conducted to analyze and compare the results of stereotactic biopsy followed by radiation therapy performed in 58 patients with those of surgical resection plus radiation therapy in 57 patients. In both groups, conventionally fractionated radiation (1.7 to 2.0 Gy/day) was delivered, with a total dose of 50 to 60 Gy. Biopsy was performed only in patients with tumors judged to be inoperable. These patients carried a higher surgical risk and were in worse neurological condition than the patients in the resection group. The median survival time for the resection group was 39.5 weeks, as compared with 32 weeks for the biopsy group. This difference was not significant. The most important prognostic factor was the patient's age. The treatment variable biopsy versus resection did not reach prognostic relevance. In patients with midline shift who underwent biopsy, the Karnofsky Performance Scale score decreased in more patients during radiation therapy. The clinical status 6 weeks after surgery, however, showed no significant differences between the two groups. The comparable survival times for the two groups place doubt on the concept of treating glioblastoma multiforme with cytoreductive surgery. Presently, radiation therapy is the most effective treatment for patients with glioblastoma. There is no question that decompressive surgery followed by radiation therapy should be performed whenever necessary for sever space-occupying lesions and when it will not cause new neurological deficits.     

Survival and functional status after resection of recurrent glioblastoma multiforme

OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution.     

A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme

Pulmonary manifestations are the most common cause of death in patients with scleroderma. Consequently, the importance of treatment of both interstital lung disease and pulmonary hypertension has become increasingly evident. Until a placebo-controlled study of any drug has shown its beneficial effect on pulmonary dysfunction, cyclophosphamide may be useful for the treatment of scleroderma lung disease.     

Concordant methylation of the ER and N33 genes in glioblastoma multiforme

Methylation of promoter-associated CpG islands appears to be a potential way by which tumor suppressor genes are inactivated in cancer. Using Southern blot analysis, we have studied the methylation of several genes in glioblastoma multiforme (GBM), trying to determine their contribution to tumorigenesis. Genes studied included the estrogen receptor (ER), N33, the candidate tumor-suppressors P15, P16 and HIC1 and a control gene, c-abl. Hypermethylation of N33, ER, HIC1, P16, P15 and c-abl were found in 61%, 59%, 60%, 5%, 2% and 0% of GBM respectively. HIC1 methylation was detected in normal brain as well, but appeared to be more extensive in tumors. ER and N33 methylation were significantly more frequent in tumors from individuals over the age of 40 (70% and 88% vs 36% and 14%). In addition, there was a strong association between ER and N33 methylation, which were concordant in 81% of the cases (P<0.01). ER and N33 methylation in GBM may therefore appear as a result of shared etiologic factors, which may relate in part to aging cell populations in the brain.     

Isolation and characterization of a novel gene from human glioblastoma multiforme tumor tissue

The therapeutic application of high-dose interleukin (IL) 2 in human malignancy is limited by severe multiorgan toxicities that are mediated, in part, by tumor necrosis factor (TNF) and IL-1. CT1501R (lisofylline; LSF) is one of several methyl xanthine congeners that inhibit the effects of TNF by the interruption of specific signal transduction pathways. This randomized, placebo-controlled trial was designed to assess the activity of LSF in reducing the toxicities of high-dose IL-2 therapy. Fifty-three patients with metastatic renal cancer or malignant melanoma were treated with i.v. bolus IL-2, 600, 000 IU/kg every 8 h for 5 days (14 doses), followed by 9 days of rest and another 5-day course of IL-2. Patients were randomly assigned to LSF, 1.5 mg/kg i.v. bolus, or placebo every 6 h during IL-2 therapy. All patients were to be treated to individual maximum tolerance of IL-2 at the intensive care unit level of support. The end points for statistical analysis were the number of IL-2 doses administered during the first cycle of treatment (maximum, 28) and the toxicities experienced by each group after the first 8 planned IL-2 doses. There was no difference between the LSF and placebo groups in the mean number of IL-2 doses tolerated in the entire first cycle of therapy (19.6 +/- 5.4 versus 19.5 +/- 5.8, P = 0.86) or in the first or second 5-day course of IL-2. The only significant difference in toxicities occurring through the eighth dose of IL-2 was in the maximum elevation of serum creatinine (mean, 1.7 +/- 0.8 for placebo versus 1.5 +/- 0.6 mg/dl for LSF, P = 0.013). A Monte Carlo analysis of major toxicities over the first 14-dose course of therapy showed a statistically significant difference favoring the LSF-treated group (P = 0.025). LSF was well tolerated, associated only with mildly increased nausea (P = 0.006 after eight IL-2 doses, but not significant for the entire first cycle). The antitumor activity was comparable in both groups (objective responses, 2 of 28 with LSF versus 4 of 24 with placebo). The mean peak plasma concentrations of LSF on days 1, 5, and 19 were 6.24, 3.83, and 5.04 micromol/liter, respectively. In conclusion, with this dose and schedule, LSF did not alter the toxicities of high-dose i.v. IL-2 sufficiently to impact the overall dose intensity of IL-2. Successful IL-2 toxicity modulation may require the use of higher doses of LSF, the development of agents with more potent anti-TNF activity, and/or combined modulating agents that function via distinct mechanisms to interrupt cytokine-mediated signaling.     

Confidence intervals for the overall effect size in random-effects meta-analysis.

One of the main objectives in meta-analysis is to estimate the overall effect size by calculating a confidence interval (CI). The usual procedure consists of assuming a standard normal distribution and a sampling variance defined as the inverse of the sum of the estimated weights of the effect sizes. But this procedure does not take into account the uncertainty due to the fact that the heterogeneity variance (τ2) and the within-study variances have to be estimated, leading to CIs that are too narrow with the consequence that the actual coverage probability is smaller than the nominal confidence level. In this article, the performances of 3 alternatives to the standard CI procedure are examined under a random-effects model and 8 different τ2 estimators to estimate the weights: the t distribution CI, the weighted variance CI (with an improved variance), and the quantile approximation method (recently proposed). The results of a Monte Carlo simulation showed that the weighted variance CI outperformed the other methods regardless of the τ2 estimator, the value of τ2, the number of studies, and the sample size. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization

Comparative genomic hybridization (CGH) is a recent molecular cytogenetic method that detects and localizes gains or losses in DNA copy number across the entire tumor genome. We used CGH to examine 9 glioma cell lines and 20 primary and 10 recurrent glioblastoma tumors. More than 25% of the primary tumors had gains on chromosome 7; they also had frequent losses on 9p, 10, 13 and Y. The losses on chromosome 13 included several interstitial deletions, with a common area of loss of 13q21. The recurrent tumors not only had gains on chromosome 7 and losses on 9p, 10, 13 and Y but also frequent losses on 6 and 14. One recurrent tumor had a deletion of 10q22-26. Cell lines showed gains of 5p, 7 and Xp; frequent amplifications at 8q22-24.2, 7q21-32 and 3q26.2-29 and frequent losses on 4, 10, 13, 14 and Y. Because primary and recurrent tumors and cell lines showed abnormalities of DNA copy number on chromosomes 7, 10, 13 and Y, these regions may play a fundamental role in tumor initiation and/or progression. The propensity for losses on chromosomes 6 and 14 to occur in recurrent tumors suggests that these aberrations play a role in tumor recurrence, the development of resistance to therapy or both. Analysis of common areas of loss and gain in these tumors and cell lines provides a basis for future attempts to more finely map these genetic changes.     

Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme for use in boron neutron capture therapy

OBJECTIVE: The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed. METHODS: Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis. RESULTS: Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/- standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination. CONCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.     

钢铁渣处理和综合利用技术浅析

近年来,我国钢产量连续保持20%左右的高速增长。2006年中国钢产量达到4.2亿吨,已经连续11年居世界第一位。随着钢产量的迅速增长,钢铁企业产生的主要固体废弃物——钢铁渣总量也在急剧增加。对钢铁渣的回收利用已经成为制约钢铁生产与环境、社会和谐发展的重要因素。     

Sensitization of rat glioblastoma multiforme to cisplatin in vivo following restoration of wild-type p53 function

A panel of seven monoclonal antibodies (mAbs) raised against cardiac troponin-I (CdTnI) isolated from canine and human hearts, which have been shown to be cardiac-specific but cross-species reactive [Cummins, B., Aukland, M. L. & Cummins, P. (1987) Amer. Heart J. 113, 1333-1344], were used in this study. These mAbs were tested against recombinant wild-type and mutant human CdTnI proteins to assess their value as probes for the phosphorylation status of CdTnI. Four mAbs were found to react positively with the recombinant wild-type protein and their epitopes were contained in residues 31-210 of the human cardiac protein. Two of these mAbs appeared to be directed against the same epitope site within this region. The remaining three mAbs only reacted against the recombinant wild-type protein when it was phosphorylated, showing that these three antibodies were directed against the phosphate group(s) on Ser23 and/or Ser24. In order to investigate this further, a series of single and double mutants of CdTnI were used in which either Ala (to direct the enzymatic phosphorylation) or Asp (to mimic the phosphate group) replaced the Ser23 and/or Ser24. It was found the all three mAbs were able to react with the mono-phosphorylated form of the [Ala23]CdTnI single mutant but not the mono-phosphorylated form of the [Ala24]CdTnI single mutant, showing that they specifically required phosphorylation at Ser24. Experiments with a synthetic peptide composed of residues 1-29 of human CdTnI confirmed these data. Two of the three phosphorylation-specific mAbs were able to react with mutants containing either two Asp residues replacing Ser23 and Ser24 or one Asp residue instead of Ser24, indicating that a negative charge at position Ser24 is sufficient to invoke a reaction. The other mAb was more specific in that it would only react with CdTnI species with a phosphate group on Ser24.     

Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors

To characterize some of the genetic events underlying the development of glioblastoma multiforme, the authors analyzed 65 astrocytic tumors (seven pilocytic astrocytomas, eight astrocytomas, 16 anaplastic astrocytomas, and 34 glioblastomas multiforme) for loss of heterozygosity for chromosome 17p, loss of heterozygosity for chromosomes 10p and 10q, amplification of the epidermal growth factor receptor (EGFR) gene, and amplification of the oncogenes N-myc, c-myc, and N-ras using Southern blot analysis. Alterations of the p53 gene (positive immunostaining for p53 protein in tumors with or without p53 gene mutations) in these 65 tumors were analyzed previously. None of the 65 tumors showed amplification or rearrangement of N-myc, c-myc, or N-ras oncogenes. The molecular analysis presented here demonstrates distinct variants of astrocytic tumors, with at least three genetic pathways leading to glioblastoma multiforme. One pathway was characterized by 43 astrocytomas with alterations in p53. Glioblastomas with p53 alterations may represent tumors that progress from lower-grade astrocytomas. This variant was more likely to show loss of chromosome 17p than tumors without p53 alterations (p < 0.04). Seventy-five percent of tumors with loss of one 17p allele demonstrated mutations in the p53 gene. Loss of chromosome 10 was associated with progression from anaplastic astrocytoma (13%) to glioblastoma (38%) (p < 0.04). Amplification of the EGFR gene was a rare (7%) but late event in tumor progression (p < 0.03). A second pathway was characterized by six astrocytomas without p53 alterations and may represent clinically de novo high-grade tumors. These tumors were more likely to show amplification of the EGFR gene (83%) than tumors with p53 alterations. Sixty percent of tumors with EGFR amplification also showed loss of chromosome 10; loss of chromosome 17p was infrequent in this variant. One or more alternative pathways were characterized by 16 astrocytomas without p53 alterations and with none of the genetic changes analyzed in this study. Glioblastomas are a heterogeneous group of tumors that may arise via multiple genetic pathways.     

LSM particle size effect on the overall performance of IT-SOFC

In this paper, we reported the fuel cell performance with La0.8Sr0.2MnO3 (LSM)/Ce0.8Sm0.2O1.9 (SDC) composite cathode prepared from LSM powders of different particle sizes via the silk-printing technique. It was found that the change in particle size of LSM nanoparticle from 40 to 90 nm resulted in an increase in the maximum power density from 132 to 228 mW/cm2 at 650 ℃ with H2 as fuel and O2 as oxidant. And the polarization resistance of the electrode decreased from 2.547 to 1.034 Ω·cm2. Concerning the particle size of electrode materials, a higher activity was anticipated with smaller particles because a large number of TPB or electrode surface sites along with a higher porosity could be developed. However, this study showed that the electrode prepared with particles of larger diameter had fine and uniform micro-structure resulting in higher power density and lower overpotential, where homogeneous distribution of particles and pores was beneficial for increasing the electrochemical active area and the electronic conductivity of the electrodes as well as the gas diffusion for the reactants.     

烧结矿分级入炉在涟钢7号高炉的应用

涟钢7号高炉应用烧结矿分级入炉技术,经过一段时间的摸索后,取得了很好的效果,不仅优化了高炉操作,而且大大降低了烧结的返烧率,降低了成本.     

Radiotherapy in the multimodal treatment of esophageal carcinoma. A review

BACKGROUND: The curative potential of exclusively applied surgery or radiotherapy on esophageal carcinoma is exhausted. The 5-year survival rate of surgically treated esophageal carcinoma is stagnant at 20 to 30%, that for radiotherapeutically treated esophageal carcinoma at < or = 10%. The unchanged bad prognoses motivate the search for multimodal therapeutical concepts in order to improve the results of basic therapies. METHOD, RESULTS AND CONCLUSIONS: While neither perioperative radiotherapy nor perioperative chemotherapy were able to improve the treatment results significantly, a progress in the field of primary and preoperative radiochemotherapy emerges. On locally restricted tumors the latest findings show that a simultaneous radiochemotherapy with Cisplatin is more effective than radiotherapy alone. 20 to 30% histologically verified complete remissions can be reached through preoperative radiochemotherapy. These results will influence future treatment concepts. Brachytherapy can be taken into consideration in highly palliative situations as exclusive method of treatment or for support of laser treatment or bouginage for removal of stenosis. As the number of clinically controlled studies is not sufficient the importance of the brachytherapy boost for potentially curative intentions is not yet clear. Up to now the intraluminal hyperthermia is a underestimated method for improving the results of radiotherapy. Our overview summarizes all presently published randomized studies and relevant phase I/II-studies.     

Regional differences in bromodeoxyuridine uptake, expression of Ki-67 protein, and nucleolar organizer region counts in glioblastoma multiforme

To investigate intratumoral differences in indices of tumor cell proliferation, we measured the bromodeoxyuridine labeling index (BrdUrd LI), the Ki-67 protein proliferating cell indices (PCIs) determined by monoclonal antibody MIB 1 in microwave-processed paraffin sections (MIB 1 PCI) and in some cases by monoclonal antibody in frozen sections (Ki-67 PCI), and counts of argyrophilic nucleolar organizer regions (AgNORs) in 20 glioblastomas. In the most actively proliferating areas, MIB 1 and Ki-67 PCIs correlated well with the BrdUrd LI and with each other, while AgNOR counts correlated less strongly with these indices. In less active areas, the MIB 1 PCI and BrdUrd LI changed concomitantly from one area to another within a tumor except in areas of pseudopalisading with necrosis; in these areas the BrdUrd LI decreased significantly compared with neighboring tumor tissue, while the MIB 1 PCI did not. There was very little staining of gemistocytic nuclei with either anti-BrdUrd or MIB 1 monoclonal antibodies; this supports the concept that gemistocytes are mainly quiescent cells. AgNORs in all of the above-mentioned areas varied from tumor to tumor, which suggests that they may indicate some cellular activity other than proliferation. The close correlation between the BrdUrd LI and Ki-67 protein PCIs in corresponding regions of glioblastomas suggests that MIB 1 staining of microwave-processed paraffin sections can be used to evaluate the growth potential of individual glioblastomas and possibly of other gliomas as well.     

Hydroxyurea accelerates the loss of epidermal growth factor receptor genes amplified as double-minute chromosomes in human glioblastoma multiforme

OBJECTIVE: We sought to determine whether hydroxyurea could accelerate the loss of amplified epidermal growth factor receptor (EGFR) genes from glioblastoma multiforme (GBM). There is good reason to think that elimination of amplified EGFR genes from GBMs will negatively impact tumor growth. Hydroxyurea has previously been shown to induce the loss of amplified genes from extrachromosomal double minutes (dmin) but not from chromosomal homogeneously staining regions. METHODS: Pulsed-field gel electrophoresis and Southern blot hybridization were used to demonstrate EGFR genes amplified as dmin. Giemsa-stained metaphase spreads were prepared in an attempt to visualize dmin. A GBM cell line containing amplified EGFR genes was treated continuously in vitro with 0 to 150 mumol/L hydroxyurea, and slot blot analysis was used to show the loss of amplified EGFR genes. RESULTS: Amplified EGFR genes were found on dmin in 4 of 11 (36%) fresh human GBM biopsy specimens. None of the GBMs contained EGFR genes amplified as homogeneously staining regions. Amplified dmin were not microscopically visible when stained with Giemsa because of their small size. Slot blot analysis showed that these low doses of hydroxyurea accelerated the loss of amplified EGFR genes in a dose- and time-dependent fashion. Pulsed-field gel electrophoresis and Southern blot analysis confirmed that EGFR gene loss was accompanied by amplified dmin loss in a dose-dependent fashion. CONCLUSION: These studies suggest the potential use of low-dose hydroxyurea in the treatment of GBMs.     

Programmed heating of coke ovens for increased coke size

Abstract

Large, uniform sized coke is desirable for blast furnace use. It has previously been shown that the coke oven flue temperature in the first few hours of coking is a key determinant of coke size. In this paper, the authors present a new programmed heating approach, which is called pulsed heating, aiming to increase coke mean size at a given average flue temperature. The approach takes into account the charging sequence in coke oven batteries and the authors demonstrate how existing operating practice can be modified in batteries with suitable heating systems to achieve the desired heating programme. A mathematical model of fissure formation provides a prediction of the increase in coke mean size using pulsed heating, compared with standard heating. Pilot scale experiments have also been performed to validate the modelling approach. The results of the modelling indicate that the mean coke size can be increased by several millimetres in some cases, although results from the pilot scale show that pulsed heating increases coke size, but by a smaller amount than that predicted by the model. The potential advantages and limitations of pulsed heating are discussed, as well as opportunities for further investigation of the approach.