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  1. Full text of "Public Accounts of the Province of Ontario for the year ended October 31 "
  2. San Bernardino Sun, Volume 72, 4 February 1966 — Page 41
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Volume 57 , Issue s1. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article.

Get access to the full version of this article. View access options below. You previously purchased this article through ReadCube. Institutional Login. Log in to Wiley Online Library. On term. Price, Terms, oeM-half cash, balance in six la beat tbat only aueh attendance a may know Oodapeed wo need the blmf acholar in political God Tha bond of'3. That depends npon tha acholar. Aa works ana a system of pi pea from a Ten acre of bearing orange tree, 1 nia is a great pargain. Thirty tract, acres and affection acre Fall reaped between the untrained Ignoramua who battery ot butlers for heating and aear Lo Angeles.

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A baru;tiin. Bearing, a loveiy none. The trees are of 6. Ao old ranch at Rlncon, ru. Price, t- lr tranaaotlon. Not a man who haa aeon lo carry ant any obhgationa made by to tha North weak 1 1, Iket sugar land, nono acre of fruits. Good cottage, Urge press figs, nectarines, apricots, peaches, pears, acre. Price, 10,, Ac. Tbe nursery stock consists of pelma and beard him but bnowi that ha la one Want A Trust, Wholesale Druggist, -rrsr- in trn tt lo auit at t. Fire acre tract,all In Navel orange, and all kind ol ornamental trees'.

There 7 Slock farm of M3J acres, t. A well known physician of New York iituateil adjacent the town ol CbJao, prune, ph. Pi Plum and fig tree at 12, to In property. JlU-So ha haa waa never ataroDed anon a rand. A 5 room cottage oq l l"g4,oo: sraicr pipcu into m nuuao, 8. Stock ranch of l. Now leat anma nail ,ivru vura mq iuwiiwii. I ho aufrar beet caUure it on premises. Ibis lias three f vutcr the streams ronninjf one who baa not aeen id maa, or nae acting dimrtly upon tha blood and moit proiitable anploymcnta in s.

Farts' act orchard. Twenty-four place feel aarfaoea of I bo arstem. MGMT methylation status was determined in 34 pts Grade 3—4 thrombocytopenia and neutropenia were observed in Conclusions : The findings of this present trial, the first to analyze second-line nitrosourea treatment in a homogeneous population following standard treatment, may represent a new benchmark of nitrosourea activity. However, as disease control was not long-standing, alternative doses, schedules, and drug-combinations should be evaluated in future studies.

This trial has been supported by an unrestricted grant of Italfarmaco Pharmaceuticals, Milan, Italy. Gerlach , E. Hattingen, K. Franz, T. Gasser, I. Kropf, A. Szelenyi, V. Methods : Data derived from a prospective series of 19 consecutive patients with newly diagnosed gliomas in the dominant hemisphere in close relation to anatomical language areas treated between November and November All patients underwent awake craniotomy for intraoperative language testing counting, naming, action naming and at least partial tumor resection according to intraoperative stimulation results.

Data of multimodal preoperative imaging were implemented in surgical navigation Brain Lab, Germany. In patients with extended tumors with limited surgical treatment option the intended surgical goal was to remove the suspected dedifferentiated tumor part defined by preoperative multimodal MR imaging. Results : According to standard preoperative MRI, 8 patients had signs suspicious of focal malignant tumor dedifferentiation. Although complete surgical resection of the tumors was deemed impossible due to intraoperative language test results, the dedifferentiated tumor part could be completely removed in all patients as proven by postoperative MRI.

In 13 of the patients with targeted resection, histology proved malignant transformation and therefore these patients underwent adjuvant treatment. Conclusions : Multimodal preoperative MR imaging is helpful to detect focal malignant transformation missed in standard diagnostic MRI in patients with presumed low-grade gliomas.

In patients in which complete resection is precluded due to infiltration of functional language areas a targeted resection of the dedifferentiated tumor part s is a prerequisite for adequate histological diagnosis. However, long-term follow-up assessment is necessary to show, whether or not targeted resection of malignant tumor parts and adjuvant treatment prolongs survival in these patients. Bello 1 , A. Castellano 2 , G. Bertani 1 , A. Gambini 2 , A. Casarotti 1 , A.

Objective : to determine the uselfulness of the combined use of motor and language tract DTI FT and intraoperative subcortical mapping for surgical removal of gliomas. Methods : patients with gliomas 90 low and 20 high grade were submitted to surgery with the aid of motor and language mapping ISM. Data were transferred to the neuronavigational system. Functional subcortical sites identified during subcortical mapping were correlated with fiber tracts depicted by DTI-FT.

The impact of the combined use of DTI FT and subcortical mapping on duration and modalities of surgical procedures and on functional outcome of the patients was also evaluated. Results : In high-grade gliomas DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas fibers were frequently located inside the tumor mass.

For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest ROIs. When used in combination with subcortical mapping, DTI-FT offers the opportunity to quickly find the fibers associated with motor or language functions during surgery. The clinical relevance of this combined approach comes from the fact that it further enhances surgical safety maintaining a high rate of functional preservation. Rationale : For a long time, insular gliomas have been considered inoperable.

Here, the author details a 10 years personal consecutive experience of 52 patients operated on for a GIIG involving the insular lobe. On the basis of the functional and oncological results, both advances and limitations of this challenging surgery are discussed. Patients and Methods : Between and , 52 patients 31 men and 21 women, median age 36 years with an insular GIIG underwent surgery.

Five patients presented with mild language disorders, and one patient with a left hemiparesis. All surgeries were conducted under cortico-subcortical stimulation and in 16 patients while awake. In all cases, the resection was stopped according to functional boundaries. Results : There was neither operative nor postoperative mortality. Ten patients underwent a second or third surgery, with no additional deficit. The tumor was still a GIIG in 7 patients, whereas anaplastic transformation was diagnosed in 3 cases. A complementary treatment was given in 20 patients chemotherapy alone in 9 cases; chemotherapy and radiotherapy in 11 cases.

The better knowledge of the insular pathophysiology and the use of intraoperative functional mapping enable minimizing the risk of permanent deficit and even improving the quality of life while increasing the extent of resection and thus the impact on the natural history.

Full text of "Public Accounts of the Province of Ontario for the year ended October 31 "

Therefore, surgical removal has to systematically be considered for insular GIIG. However, this surgery remains challenging, especially within the anterior perforating substance and the posterior part of the dominant insula. Repeated operations can be suggested when the first resection was not complete. Stummer 1 , U. Pichlmeier 2 , G. Purpose : The benefit of cytoreductive surgery for glioblastoma multiforme GBM has not been demonstrated conclusively and selection bias in past series has been observed.

The ALA study investigated the influence of fluorescence-guided resections on outcome, generating an extensive database on GBM patients with a high frequency of complete resections. Patients and Methods : per protocol patients with newly diagnosed GBM were operated either with or without ALA and treated by radiotherapy. Early postoperative MRI was obtained in all patients. When stratified for complete vs. Differences in survival depending on resection status, especially in RPA classes IV and V, strongly support a causal influence of resection on survival.

Sato , T. Ito, M. Oikawa, H. Objective : For the patients with glioblastoma multiforme GBM involving pyramidal tracts, maximal resections are difficult to accomplish preserving their motor function. We use tractography-integrated functional neuronavigation and 5-aminolevulinic acid 5-ALA fluorescence-guided resection following the removal of GBM involving pyramidal tracts.

San Bernardino Sun, Volume 72, 4 February 1966 — Page 41

In this study we analyze the postoperative motor function and extent of resection in a series of patients who underwent surgery in our department. To preserve pyramidal tracts, we have used the tractography-integrated functional neuronavigation since We also developed a functional neuronavigation-guided fence-post procedure in to resolve the problem of brain shift, a disadvantage of the existing neuronavigation system. And we have attained precise resection on the tumor using 5-ALA fluorescence navigation. Intraoperatively, tumor fluoresence was visualized using a modified operating microscope.

All fluorescing tumor tissue was resected. Results : Motor function was preserved after appropriated tumor resection in all cases. Postoperatively, improvement of motor weakness was observed in six patients, whereas transient mild motor weakness occurred in two patients. Gross total removal was accomplished for four patients, subtotal removal was accomplished for two patients, and partial removal was accomplished for two patients.

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Conclusions : Combined use of tractography-integrated functional neuronavigation and 5-ALA fluorescence-guided resection contributes to maximal safe resection of GBM with pyramidal tract involvement. Diez Valle , S. Tejada Solis, M. Background : Gross total resection is increasingly recognized as an important first step and prognostic factor in the treatment of glioblastoma. In spite of this, most published papers lack an objective measurement of residual tumor after surgery. The removal of the entire MRI enhancing lesion is accepted as the gold standard of gross total resection.

Fluorescence guided resection of glioblastoma using 5 aminolevulinic acid 5-ala is a new technique developed by Dr. The European Medical Agency approved the marketing of 5-ala for this indication under the name Gliolan in January In an unusual agreement, the agency approved it to be used only by neurosurgeons who have done a specific training course. Methods : We report our initial experience with 10 glioblastoma cases.

The cases were consecutive patients in which surgery was indicated. There were three recurrent cases. We did volumetric MRI measurement pre- and postoperatively. For each case we took 6—8 biopsies of the borders of the lesion and the normal tissue, as shown by the fluorescence. Results : In all our cases, we could see under the fluorescence three different zones: pure tumor tissue in bright red; infiltrating tumor cells in the border of the lesion with the color gradually less intense, becoming shades of pink; and normal tissue in blue.

Interestingly, the pink areas always corresponded with tumor cells infiltrating brain tissue, never with solid tumor. Mean preoperative volume was 52 cc. There was no new neurological morbidity in the series. Conclusions : The fluorescence produced by 5-ala is a very efficient and safe method of achieving maximal safe resection of glioblastoma. This method allows the surgeon to see the solid tumor as well as the infiltrating border, which has a high tumor cell density. It could achieve greater resection than MRI guided surgery.

With this technique it's possible to obtain separate samples of the infiltrating border of the tumor during the surgery, and we think this could be useful for specific research on the diffuse part of the tumor. Grauer 1 , J. Molling 2 , R. Sutmuller 3 , S. Nierkens 2 , G. Introduction : Gliomas are aggressive brain tumors that actively suppress anti-tumor immune responses. In mice, we attempted to restore local T cell responses by intratumoral injection of various toll-like receptor TLR ligands.

Methods : Mice bearing intracerebral GL gliomas received a single intratumoral injection of various TLR ligands five days after tumor challenge and were monitored for survival. T cells were isolated at different time points from the tumor and cervical lymph nodes or spleen for functional characterization. Conclusion : In summary, this study underlines the potency of local TLR treatment in anti-glioma therapy and demonstrates that local CpG-ODN treatment most effectively restores anti-tumor immunity in a therapeutic murine glioma model.

Lamszus 1 , T. Martens 1 , Y. Laabs 1 , H. Witte 2 , M. Westphal 1 ; 1 Dept. Objective : A major shortcoming of traditional mouse models based on xenografted human glioblastoma cell lines is that tumor cells do not invade. Another deficit is that genetic alterations, such as amplification of the epidermal growth factor receptor EGFR , are typically not maintained in glioma cell lines and xenografts derived thereof. These models are therefore of limited value for preclinical therapeutic studies.

We established a highly invasive orthotopic nude mouse model to evaluate the effects of monoclonal antibodies against EGFR cetuximab and vascular endothelial growth factor receptor-2 VEGFR-2, antibody DC Methods : Freshly resected glioblastoma tissue was minced and briefly cultured as spheroids in vitro. Spheroids were stereotactically injected into the striatum of nude mice. Animals were treated for 4 weeks with either interstitial infusion of cetuximab or intraperitoneal injections of DC Results : Highly invasive xenografts were obtained from 9 different glioblastomas.

Of 7 different xenograft-cases treated with cetuximab, 3 responded to treatment with significant tumor growth inhibition, whereas 4 did not. The proportion of apoptotic cells was increased in responding tumors, whereas the fraction of proliferating cells was decreased. None of 4 xenograft cases treated with DC responded to treatment, and quantification of intratumoral blood vessels showed that the diffusely invading tumors grew largely independent of angiogenesis.

Conclusions : This is the first study showing that inhibition of invasive glioblastoma growth can be achieved in vivo using interstitial delivery of an anti-EGFR antibody. In contrast, anti-angiogenic treatment was not effective against the diffusely invading tumors. Campos 1 , F. Zeppernick 1 , R. Ahmadi 1 , M.

Farhadi 1 , W. Roth 2 , P. Beckhove 3 , A. Unterberg 1 , B. Radlwimmer 4 , C. Background : Tumor stem cells TSCs are responsible for tumor initiation and therapy resistance in a variety of cancers, including leukemia, carcinomas of the breast and colon as well as several types of brain tumors. Differentiation of TSCs has been discussed as a possible approach to eradicate the tumor-driving cell population disrooting the actively proliferating tumor bulk.

Since all-trans retinoic acid ATRA is known as a modulator of differentiation and proliferation, we sought to elucidate whether ATRA induces differentiation of glioblastoma-derived TSCs, so-called brain tumor stem cells BTSCs , and if tumor-relevant properties of these cells are affected by differentiation. Impact of differentiation on the angiogenic capacity of BTSCs was measured by quantification of angiogenic cytokines and assessed in a HUVEC-based tube formation assay. Conclusion : Altogether, these results highlight the potential of differentiation treatment to target the tumor-driving compartment in glioblastoma and point out a potential therapeutic value in the eradication of TSCs.

Bello 1 , C. Verpelli 1 , G. Bertani 1 , G. Casaceli 1 , V. Lucini 2 , R. Galli 3 , C. Angiogenesis and invasion are strictly related phenomena involved in glioma genesis and progression. In vivo models based on the intracerebral injection of glioma cancer stem cells are well suited for studying the relationship between these two phenomena, because they both possess in these tumors features similar to those observed in the human setting.

In the first part of this work we analyzed the changes in tumor vasculature and cell infiltration during the various phases of tumor progression in a glioma nude mice model generated by the injection of glioma cancer stem cells isolated by a case of human anaplastic astrocytoma. Animals were sacrificed at various time points after glioma cancer stem cell injection. Sections were evaluated for vascular parameters vessel number, diameter, length, basal membrane, pericytic coverage, tumor hypoxia and pattern of tumor cell infiltration.

At early stage a small tumor mass, consisting of an agglomerate of dispersed elongated tumor cells, diffusely infiltrating the surrounding brain parenchyma, was evident. Most of the cells were co-opting preexisting tumor vasculature; in the tumor mass actively growing capillaries were present. At intermediate stage, larger tumors composed of a tumor core surrounded by a large area of infiltration were documented, in the context of which several foci of anaplasia were evident.

Angiogenesis was active, both in the tumor mass and particularly in the foci. At late stage, the tumors were large, densily and extensively infiltrating the brain parenchyma. Necrosis was also present. Angiogenesis was active and heterogeneous, with glomeruloid structures, mature and actively growing capillaries, co-opting vessels. This model strictly resembles human glioma, in terms of tumor cell and vasculature heterogeneity and tumor cell infiltration. It represents a good model of progression, which occurs at both the tumor cell and vasculature levels.

Angiogenesis is striclty associated with invasion. In the second part of the work, we investigated if angiogenic treatment was able to inhibit the progression of the tumor toward more aggressive phenotype. Angiogenic inhibitors were administered alone or in combination to animals with early or intermediate stage tumors. Mice were sacrificed at various time points, and the infiltrative and angiogenic pattern of the tumors evaluated as previously described. In both settings, antiangiogenic treament reduced angiogenesis and tumor cell infiltration.

The effect was more prominent at early stage, where tumor progression was also inhibited. Bexell 1,2 , S.

Gunnarsson 1,2 , A. Tormin 2 , D. Gisselsson 3 , S. Scheding 2 , J. Bone-marrow derived mesenchymal stem cells MSCs have emerged as a promising cellular vehicle for delivery of anti-tumoral substances in glioma therapy. However, the capacity of MSCs to specifically migrate within an invasive GBM-like model has not been quantatively analyzed. Here we quantified the extent to which MSCs migrate to invasive tumor extensions and to distantly located tumor micro satellites.

MSC grafting was done intratumorally into established tumors in order to resemble a clinical scenario where MSCs are grafted following partial tumor resection. Importantly, MSC migration was largely restricted to tumor tissue and minimal numbers of MSCs were found in the normal brain parenchyma. Thus, we demonstrate proof-of-principle that one single MSC injection results in infiltration of the majority of invasive tumor extensions and of a significant fraction of tumor microsatellites.

Multiple intratumoral injections at different coordinates will likely increase the numbers of tumor satellites infiltrated by grafted MSCs. Thon 1 , H. Leske 1 , C. Schichor 1 , J. Tonn 1 , R. Goldbrunner 1 , A. Recently, it has been shown that VZV is suitable for tumor therapy in malignant melanomas. Focusing on a future oncolytic therapy for malignant gliomas, the aim of the following study was to asses permissive VZV replication in glioma cell lines and primary glioblastoma cell cultures in vitro. Methods : Three gliomas cell lines U87, U, U and six primary cell cultures from human glioblastoma specimens have been tested for permissive cellular VZV replication in vitro.

An established melanoma in vitro model has been used as positive control, and three normal brain cell cultures NBC have been used as negative controls. Since bone marrow derived human mesenchymal stem cells hMSC are regarded as potential carriers of oncolytic therapy, three hMSC cultures were included in this study. Infection rates have been qualitatively and quantitatively evaluated by cellular expression of early e. Oncolytic potency has been evaluated by cell counting and comparative morphometric culture analysis in simultaneously VZV infected glioma cells, hMSCs and normal brain derived cells in a time dependent protocol.

Interestingly, plaque formation and syncytial fusion, which are characteristic for melanoma VZV replication, rarely occurred within glioma cell lines. Interestingly, besides established VZV infected melanoma cells, permissive VZV replicating hMSCs have also been highly suitable for cellular vehicles in glioma cell infection. Conclusion : Wild-type VZV efficiently replicates within glioma cell cultures causing broad oncolytic cell death in vitro. The underlying mechanisms causing infections devoid of characteristic plaque formation are still unknown. Since hMSCs are known to have an intrinsic tumor cell tropism, autologous VZV-replicating hMSCs could be applicable as cellular vehicles for local oncolytic glioma cell infection.

Further investigations have to address sufficient glioma cell selectivity in VZV replication with respect to the normal brain parenchyma. Neyns 1 , J. Sadones 1 , E. Joosens 2 , F. Bouttens 3 , L. Verbeke 4 , J. Baurain 5 , L. Dhondt 6 , T. Strauven 7 , C. Chaskis 1 , A.

Augustinus, Antwerpen, Belgium. Pts were stratified in 2 treatment arms according to the amplification status of the EGFR gene of their high-grade glioma determined by fluorescence in situ hybridization on archival tumor material. Cetuximab was generally well tolerated. After a median follow-up of 17 months, 8 pts are alive 4 are still receiving cetuximab and 47 pts have died. The median PFS was 1. This subgroup consisted of 4 pts with de novo glioblastoma 3 without and 1 with EGFR amplification and 1 pt with an anaplastic astrocytoma with EGFR amplification.

Conclusions : Cetuximab as a single agent was safe and well tolerated in this population of pretreated patients with recurrent HGG. Durable disease control was observed in a small subgroup of patients but was not predicted by EGFR amplification at initial diagnosis. Burzynski , R. Weaver, T. Janicki, B. Szymkowski, M. Walczak, G. For recurrent AA the overall survival is less than 2 years. ANP affects multiple targets, and its components have different mechanisms of action.

Twenty assessable adults, all diagnosed with AA, whose ages ranged from 20 to 51 years median age 41 years , were involved in this study. ANP was administered intravenously daily through a subclavian venous catheter via a double-channel infusion pump. The median duration of treatment was 6. The treatment was well tolerated with only one case of a serious toxicity of hypernatremia.

The median of progression-free survival based on K-M was These results compare favorably with the outcome of standard treatment. In conclusion, ANP is well tolerated and provides encouraging results in the treatment of recurrent AA and merits further investigation in a randomized phase III trial in comparison to standard treatment. Background : Nitrosourea-based chemotherapy NBC is a widely used treatment for patients pts with recurrent high-grade glioma HGG who have not received prior chemotherapy. We require deaths to detect HRs of 0. To observe deaths, a maximum of pts randomized over 4 years was anticipated, with a planned subgroup analysis in glioblastoma multiforme GBM pts.

Results : Accrual began in July and closed on January 31, We anticipate deaths by July , when the majority of patients will have completed treatment, and we will conduct the primary analysis at this time. Wick 1 , V. Puduvalli 2 , M. Chamberlain 3 , A. Carpentier 4 , L. Cher 5 , W. Mason 6 , M. Van den Bent 7 , S.

Hong 8 , D. Thornton 8 , H. Treatment continued until disease progression or unacceptable toxicity occurred. Secondary endpoints included overall survival OS , tumor response, safety, and patient-reported outcomes PROs. Pt characteristics were balanced between arms. Five 2. Median duration of therapy was 42 days on both arms. Four pts discontinued ENZ due to drug-related serious AEs erysipelas, aortic thrombosis, cerebral hemorrhage, and convulsion. Median TtD was 2.

Bogdahn 1 , A. Mahapatra 2 , V.

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Oliushine 3 , C. Mouli 4 , V. Parfenov 5 , G. Stockhammer 6 , S. Ludwig 7 , G. Wuerth 7 , H. Heinrichs 7 , K. Introduction and Objective : High-grade gliomas are very aggressive tumors, characterized by overexpression of transforming growth factor-beta 2 TGF-beta 2. TGF-beta 2 is one of the most potent immunosuppressors that induces escape from immunosurveillance. TGF-beta 2-specific phosphorothioate antisense oligodeoxynucleotide AP is targeted to suppress this protein and is used as monotherapy in this indication in clinical trials.

Methods : The international Phase IIb study with AP had an open-label, randomized, and active-control dose-finding design. AP was administered as monotherapy via intratumoral, convection-enhanced delivery CED using an external portable pump for 6 months with up to 11 treatment cycles 1 cycle: 7 days AP , 7 days isotonic saline. Even more encouraging results were obtained for AA patients. The current overall survival time in months is In both AP groups, the observed long-lasting tumor regression clearly exceeded the active treatment period. The follow-up period for the Phase IIb study has been extended.

Frappaz 1 , S. Dussart 1 , J. Pierga 2 , J. Fabbro 4 , L. Djafari 5 , M. Background : Despite improvements obtained with frontline treatments prognosis of recurrent HGG still remains dismal. HD chemotherapy suggested a dose-effect relationship in extra CNS lymphoma and germ cell tumors. Treatment was administered for one cycle. Results : 30 patients were eligible, but in 10 the phase I could not be performed 8 because sufficient number of PBSC could not be collected, and 2 for other reasons.

All but one had received previous RT, and 11 had received chemo, mainly nitrosourea. The association with other drugs that have no cross-resistance may then be explored further. Pfister 1 , W. Janzarik 2 , M. Remke 3 , A. Ernst 3 , A. Gnekow 4 , G. Reifenberger 5 , W. Scheurlen 6 , H. Omran 7 , A. Kulozik 1 , P. Pilocytic astrocytomas comprise the most frequent brain tumors in childhood.

However, the molecular mechanisms of pathogenesis and tumor recurrence are still poorly understood. Taken together, our findings implicate aberrant activation of the Mitogen-Activated Protein Kinase MAPK pathway due to gene duplication or activating mutation of BRAF as a common molecular pathomechanism in low-grade astrocytomas and provide a promising novel target for future treatment strategies. Eoli , A. Di Stefano, L. Valletta, S. Guzzetti, D. Bianchessi, B. Pollo, A. Silvani, M. Bruzzone, A. Boiardi, G. Broggi, G.

Finocchiaro; C. Besta, Milan, Italy. Recent data suggest that loss of MGMT expression due to promoter hypermethylation may occur in the pathway leading to secondary glioblastomas. Of the 34 patients with progressive disease, 22 had a second surgery: in most of them 17 out of 22 the second diagnosis was high-grade glioma 7 glioblastomas, 5 anaplastic astrocytomas, and 5 anaplastic oligoastrocytomas.

Three patients also had a third surgery: the last diagnosis was anapalstic astrocytomas in 1 and glioblastoma in 2. Both camparisons did not reach statistical significance due to the small number of cases. The findings indicate that in low-grade astrocytomas MGMT methylation is associated with tumor recurrence and is predictive of progression to a more malignant phenotype.

Trevisan 1 , E. Laguzzi 1 , D. Guarneri 1 , C. Bomprezzi 2 , M. Caroli 3 , B. Leoncini 1 , R. Soffietti 1 , R. Protracted administration of low doses of TMZ offers potential advantages over the standard TMZ schedule, leading to increased MGMT depletion, which may enhance the antitumor activity of alkylating agents. Few data are available on the efficacy and tolerability of protracted low-dose TMZ in patients with low-grade gliomas. Patients and Methods : Since September we enrolled in an ongoing multicenter phase II study 31 patients 25 evaluable for response , with a median age of 41 yrs and a median KPS of Patients underwent clinical and MRI assessment every 1 and 3 months, respectively, and monitoring by PET with methionine was performed in selected centers.

The primary endpoint was the response rate on MRI, and secondary endpoints were the progression free-survival PFS at 6 and 12 months, median PFS, quality of life, and toxicity. Median time to maximum radiographic response was 6 months. When patients develop cumulative lymphopenia, a conversion to standard dosing is feasible.

Rees 1,2 , J. Winston 1,2 , R. Jager 1,2 , C. Benton 1 , G. Brasil Caseiras 1,2 , P. Tofts 3 , D. Altmann 4 , D. Tozer 2 , A. Objective : To investigate the prognostic value of growth rate in adult patients with low-grade gliomas LGG. Methods : An observational cohort study was conducted on 50 adult patients with LGG. Patients received no treatment except anti-epileptic drugs until malignant transformation was suspected. Results : Growth rates measured over a 6-month period from study entry were highly variable between patients range: —4.

Cox regression analysis showed that faster growth rate was an independent prognostic factor allowing for confounding variables including tumor size, patient age and gender, tumor histology, and whether the tumor crossed the midline. Conclusions : Growth rate is a readily measured predictor of early transformation in LGG.

The data suggest that LGG growth is best considered a continuous variable, with higher growth rates associated with earlier transformation. Cruz , N. Perez, E. Rodriguez, M. Cusi, C.