[Brainlife] Newsletter, Vol.4 No.20

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BRAINLIFE NEWSLETTER

Volume 4, Number 20 - 3 May 2005	Volume 4 Archive

1: Am J Clin Oncol. 2004 Dec;27(6):638-9.

Solitary dural extramedullary plasmacytoma with inv(9)(p13q21).

Lee KS, Lee JA, Song HH, Byun J, Ahn JS, Zang DY, Park YI, Park SH, Park SW, Nam ES, Cho HC.

Department of Internal Medicine, Hallym University School of Medicine, Chunchon, Kangwon-do, Korea. LKSHMO@chollian.net

The authors report the case of a 24-year-old man who presented with a solitary dural extramedullary plasmacytoma (EMP) with inv(9)(p13q21). Chromosome 9 aberrations may be associated with the pathogenesis. This is the first reported case of solitary dural EMP associated with inv(9)(p13q21).

Publication Types:

Case Reports

PMID: 15577446 [PubMed - indexed for MEDLINE]..

2: Arch Pathol Lab Med. 2005 May;129(5):624-631.: Glioblastomas in the Older Old.

Kleinschmidt-Demasters BK, Lillehei KO, Varella-Garcia M.

From the Departments of Pathology (Dr Kleinschmidt-DeMasters), Neurology (Dr Kleinschmidt-DeMasters), Neurosurgery (Drs Kleinschmidt-DeMasters and Lillehei), and Medicine (Medical Oncology) (Dr Varella-Garcia), University of Colorado Health Sciences Center, Denver.

Context.-Recent studies have identified fundamental biological differences in the effects of epidermal growth factor receptor (EGFR) amplification on survival in older versus younger patients with glioblastoma multiforme (GBM). Cell cycle labeling indices have also been found to be inordinately high in older GBM patients and may contribute to the known adverse prognosis in this cohort. However, testing has not been conducted on significant numbers of patients of very advanced age, in whom these features might be expected to emerge as even more significant factors.Objective.-To assess EGFR amplification status and MIB-1 indices in patients with GBM who are older than 75 years.Design.-We identified 20 patients (female-male ratio, 11:9; 11 aged 75-79 years and 9 aged 80-87 years) and studied tumor tissue samples with immunohistochemistry for cell cycle labeling index and by fluorescence in situ hybridization for EGFR amplification. Survival data were obtained from the Colorado Tumor Registry.Results.-Mean MIB-1 index was high (24.8%), but individual indices did not correlate with survival. EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all but one of the remaining patients. Ninety-five percent of patients manifested EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found within a given tumor, with 10% to 60% of cells showing gain of chromosome 7. Overall patient survival was poor (mean, 4.6 months), but was significantly longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5 months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04).Conclusion.-The presence of EGFR amplification is a significant predictor of survival time in older old patients.

PMID: 15859633 [PubMed - as supplied by publisher]..

3: Cancer. 2005 Apr 28; [Epub ahead of print]: Temozolomide plus thalidomide in patients with brain metastases from melanoma.

Hwu WJ, Lis E, Menell JH, Panageas KS, Lamb LA, Merrell J, Williams LJ, Krown SE, Chapman PB, Livingston PO, Wolchok JD, Houghton AN.

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.

BACKGROUND: Temozolomide plus thalidomide is a promising oral combination regimen for the treatment of metastatic melanoma. The current Phase II study examined the efficacy and safety of this combination in chemotherapy-naive patients with brain metastases. METHODS: Patients with histologically confirmed metastatic melanoma and measurable brain metastases received temozolomide (75 mg/m(2) per day for 6 weeks with a 2-week break between cycles) plus concomitant thalidomide (200 mg/day escalating to 400 mg/day for patients < 70 years or 100 mg/day escalating to 250 mg/day for patients >/= 70 years). The primary end point was tumor response in the brain assessed every 8 weeks. RESULTS: Twenty-six patients with a median age of 60 years were treated. All patients had progressive brain metastases: 16 were symptomatic and 25 had extensive extracranial metastases. Eight patients had received whole-brain radiotherapy, 4 had received stereotactic radiotherapy, and 8 had received craniotomy with resection of hemorrhagic lesions. Fifteen patients completed >/= 1 cycle (median, 1 cycle; range, 0-4 cycles), and 11 discontinued treatment before completing 1 cycle (7 for intracranial hemorrhage, 2 for pulmonary embolism, 1 for deep vein thrombosis, and 1 for Grade 3 rash). Of 15 patients assessable for response, 3 had a complete or partial response (12% intent to treat) and 7 had minor response or stable disease in the brain. However, 5 of these 10 patients had disease progression at extracranial sites. The median survival period was 5 months for all 26 patients and 6 months for the 15 assessable patients. CONCLUSIONS: Temozolomide plus thalidomide was an active oral regimen for patients with brain metastases from malignant melanoma. Cancer 2005. (c) 2005 American Cancer Society.

PMID: 15861414 [PubMed - as supplied by publisher]..

4: Cancer. 2005 Apr 28; [Epub ahead of print]: Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction.

Lafay-Cousin L, Holm S, Qaddoumi I, Nicolin G, Bartels U, Tabori U, Huang A, Bouffet E.

Hospital for Sick Children, Toronto, Canada.

BACKGROUND: Carboplatin-based regimens have demonstrated activity in unresectable low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the use of these regimens has been limited by the development of carboplatin hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has been the recommended approach for HSR. However, no guidelines have existed to aid physicians when carboplatin desensitization techniques fail. METHODS: A pilot study of monotherapy with weekly vinblastine for LGG in 9 children who developed carboplatin HSR on a carboplatin and vincristine regimen was performed. RESULTS: Vinblastine toxicity was moderate and readily manageable. None of the 9 patients had disease progression on therapy. Magnetic resonance imaging evaluation of tumor size from diagnosis to the end of vinblastine treatment showed 1 complete response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable diseases (SD). CONCLUSIONS: This experience suggested that weekly vinblastine has a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable option for children who develop severe HSR. Cancer 2005. (c) 2005 American Cancer Society.

PMID: 15861409 [PubMed - as supplied by publisher]..

5: Int J Cancer. 2005 Apr 26; [Epub ahead of print]: Successful combination of local CpG-ODN and radiotherapy in malignant glioma.

Meng Y, Carpentier AF, Chen L, Boisserie G, Simon JM, Mazeron JJ, Delattre JY.

Federation de neurologie Mazarin and Institut National de la Sante et de la Recherche Medicale (INSERM) UMR-495,Hopital de la Salpetriere, Paris, France.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) display broad immunostimulating activity and are currently under clinical trial in various malignancies, including recurrent glioblastomas. Combining CpG-ODN with another therapy that could induce antigen release might enhance tumor-specific immune response. We investigated whether radiotherapy (RT) could be associated advantageously to intratumoral injections of CpG-ODN. Fisher rats bearing 9L glioma were treated with various combinations of RT and CpG-28, an oligonucleotide with good immunostimulating activity. RT and CpG-28 induced complete tumor remission in one-third of the animals. When both treatments were combined, complete tumor remission was achieved in two-thirds of the animals (p < 0.001 when compared to non-treated rats, p < 0.03 when compared to CpG-28 alone). Such efficacy was not observed in nude mice, underlying the role of T cells in antitumor effects. The combination of both treatments appeared optimal when the delay between RT and CpG-28 administration was <3 days (from 100% survival for a 3 days delay, to 57% survival for a 21 days delay, p < 0.05). Tumor infiltration by immune cells and expression within tumors of the CpG receptor, TLR9, were not modified by irradiation. These results support an attractive strategy of sequential radiotherapy and immunotherapy by CpG-ODN and have potential implications for future clinical trials with CpG-ODN. (c) 2005 Wiley-Liss, Inc.

PMID: 15856470 [PubMed - as supplied by publisher]..

6: Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):853-60.

Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol.

Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr.

Department of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada. luis.souhami@muhc.mcgill.ca

PURPOSE: Conventional treatment of glioblastoma multiforme (GBM) cures less than 5% of patients. We investigated the effect of stereotactic radiosurgery (SRS) added to conventional external beam radiation therapy (EBRT) with carmustine (BCNU) on the survival of patients with GBM. METHODS AND MATERIALS: A total of 203 patients with supratentorial GBM (tumor < or =40 mm) were randomly assigned either to postoperative SRS followed by EBRT (60 Gy) plus BCNU (80 mg/m(2) Days 1-3 every 8 weeks for six cycles) or to EBRT with BCNU alone. The dose of radiosurgery was tumor size-dependent and ranged from 15 Gy for largest to 24 Gy for smallest tumors. RT and BCNU were identical in both arms. RESULTS: At a median follow-up time of 61 months, the median survival in the radiosurgery group was 13.5 months (95% confidence interval, 11.0-14.8) as compared with 13.6 months (95% confidence interval, 11.2-15.2, p = 0.5711) for the standard treatment group. There were also no significant differences in 2- and 3-year survival rates and in patterns of failure between the two arms. Quality of life deterioration and cognitive decline at the end of therapy, compared with baseline, were comparable and there was no difference in quality-adjusted survival between the arms. CONCLUSIONS: Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.

Publication Types:

Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 15465203 [PubMed - indexed for MEDLINE]..

7: Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):20-31.: Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy.

Laprie A, Pirzkall A, Haas-Kogan DA, Cha S, Banerjee A, Le TP, Lu Y, Nelson S, McKnight TR.

Department of Radiology, University of California, San Francisco, San Francisco, CA, USA; Department of Radiation Oncology, Claudius Regaud Institute, Toulouse, France.

Background and Purpose: After radiotherapy (RT), children with diffuse intrinsic pontine gliomas (DIPG) are followed with sequential magnetic resonance imaging (MRI). However, MRI changes do not necessarily reflect tumor progression, and therefore additional noninvasive tools are needed to improve the definition of progression vs. treatment-related changes. In this study, we determined the feasibility and accuracy of multivoxel proton magnetic resonance spectroscopic imaging ((1)H-MRSI) for monitoring pediatric patients with DIPG. Methods and Patients: Twenty-four serial examinations of MRI/MRSI (7 2D-MRSI and 17 3D-MRSI) were performed on 8 patients with DIPG who received local RT. A total of 1635 voxels were categorized as "normal" or "abnormal" based on corresponding imaging findings on contrast-enhanced T1- and T2-weighted MRI. The choline to N-acetyl-aspartate ratio (Cho:NAA) and choline to creatine ratios (Cho:Cr) within each category of MRI abnormality were compared to their counterpart in normal surrounding tissues. The changes in these ratios corresponding to each type of abnormality were evaluated before RT, at response, and at recurrence, as determined by the clinical status of the patients. The presence or absence of lactate and lipid peaks was noted for each voxel. MRI/MRSI was performed on posterior fossa and supratentorial tissue of 3 volunteer pediatric patients. Results: The Cho:NAA and Cho:Cr values within the imaging abnormalities (3.8 +/- 0.93 and 3.55 +/- 1.37, respectively) were significantly higher than the mean values in normal-appearing regions (0.93 +/- 0.2 and 1.13 +/- 0.38, respectively) (p < 0.005). Cho:NAA values decreased from studies at diagnosis to the time of response to RT (3.12 +/- 0.5 and 2.08 +/- 0.73, respectively), followed by an increase at the time of relapse (from 1.83 +/- 0.92 to 4.29 +/- 1.08). Loss of lactate and lipid peaks correlated with response, and their presence and stability with relapse. In 3 patients, increased spectral abnormalities preceded the radiological and clinical deterioration by 2-5 months. Conclusion: Multivoxel MRSI is a feasible and reproducible noninvasive tool for assessing pediatric DIPG. Longitudinal multivoxel MRSI measurements have potential value in assessing response to radiation or other therapies, because they offer more coverage than single-voxel techniques and provide reliable spectral data.

PMID: 15850898 [PubMed - in process]..

8: J Clin Oncol. 2005 May 1;23(13):3155.: Treatment of brain metastases from melanoma.

Legha SS.

PMID: 15860880 [PubMed - in process]..

9: J Clin Oncol. 2005 May 1;23(13):2955-61.: Time From Treatment to Subsequent Diagnosis of Brain Metastases in Stage III Non-Small-Cell Lung Cancer: A Retrospective Review by the Southwest Oncology Group.

Gaspar LE, Chansky K, Albain KS, Vallieres E, Rusch V, Crowley JJ, Livingston RB, Gandara DR.

MBA, University of Colorado Health Sciences Center, Department of Radiation Oncology, 1665 N Ursula St, Box F-706, Ste 1032, Aurora, CO 80010-0510; e-mail: laurie.gaspar@uchsc.edu.

PURPOSE A retrospective review of the Southwest Oncology Group (SWOG) database was undertaken to review the incidence and timing of diagnosis of brain metastases in patients undergoing combined-modality therapy for stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Four hundred twenty-two eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG protocols. Treatment varied with protocol but consisted of concurrent cisplatin-etoposide and radiation in all patients, with a surgery arm in two of the four protocols. Results Of the 422 total patients, 268 (64%) have experienced disease progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of the 268 patients with disease progression, progression in the brain only, in the brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of patients, respectively. Time from treatment to diagnosis of disease progression in the brain in 71 patients was as follows: during treatment, 16 relapses (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous histology and young patient age were the only significant predictors for increased risk of early relapse with brain metastases. CONCLUSION Brain metastases often develop early in the course of treatment for stage IIIA/B NSCLC. The statistical designs of ongoing trials of prophylactic cranial irradiation in stage III NSCLC have taken this into account.

PMID: 15860851 [PubMed - in process]..

10: J Neurochem. 2005 May;93(4):992-9.: Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo.

Eyupoglu IY, Hahnen E, Buslei R, Siebzehnrubl FA, Savaskan NE, Luders M, Trankle C, Wick W, Weller M, Fahlbusch R, Blumcke I.

Department of Neurosurgery, University of Erlangen, Germany.

Abstract Current treatment modalities for malignant gliomas do not allow long-term survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases (HDAC), as an effective experimental anti-glioma agent. Administration of SAHA to various glioma cell lines obtained from human, rat and mouse inhibited tumour cell growth in a range of 1-10 mum. This anti-glioma property is associated with up-regulation of the cell cycle control protein p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model using slice cultures of rat brain corroborated the anti-glioma properties of SAHA in the organotypic brain environment. In this model, glioma invasion compromised adjacent brain parenchyma, and this tumour-associated cytotoxicity could be inhibited by SAHA. In addition, a 10-fold dose escalation experiment did not challenge the viability of cultured brain slices. In vivo, a single intratumoural injection of SAHA 7 days after orthotopic implantation of glioma cells in syngeneic rats doubled their survival time. These observations identify chromatin-modifying enzymes as possible and promising targets for the pharmacotherapy of malignant gliomas.

PMID: 15857402 [PubMed - in process]..

11: Neurology. 2005 Apr 26;64(8):1444-5.: EGFR tyrosine kinase domain mutations in human gliomas.

Marie Y, Carpentier AF, Omuro AM, Sanson M, Thillet J, Hoang-Xuan K, Delattre JY.

Department of Neurology Mazarin and Institut National de la Sante et de la Recherche Medicale UMR-495, Paris, France.

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor effective in patients with lung cancer with mutations in exons 19 and 21 of the EGFR tyrosine kinase domain. In this study, the authors tested the presence of such mutations in 95 gliomas including glioblastomas, anaplastic oligodendrogliomas, and low-grade gliomas. No mutation was found, which suggests that the biology of EGFR in gliomas is different from lung cancer and that this may be a factor in the resistance of glioblastomas to gefitinib.

PMID: 15851741 [PubMed - in process]..

12: Neurosurgery. 2005 May;56(5):1021-34; discussion 1021-34.: Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques.

Paek SH, Audu PB, Sperling MR, Cho J, Andrews DW.

Department of Neurosurgery, Seoul National University, Seoul, South Korea.

OBJECTIVE: Patients with brain metastases were analyzed retrospectively to assess the risks and benefits of surgery with modern neurosurgical techniques, including image guidance coupled as indicated with corticography. METHODS: We retrospectively analyzed charts of patients treated surgically for brain metastases. We identified patients with single or multiple brain metastases who underwent craniotomies to reverse associated neurological symptoms or establish a diagnosis. We assessed patients according to recursive partitioning analysis (RPA) prognostic groups as well as functional grades of tumor location (eloquent versus noneloquent, Grades I-III). Perioperative complications, neurological outcomes after surgery, survival, and prognostic factors were analyzed. Statistical analysis of survival was performed with the Kaplan-Meier method. A P value of <0.05 was considered statistically significant. RESULTS: Two hundred eight patients were treated between March 1995 and December 2002. Patient age ranged from 31 to 82 years (median, 59 yr). One lesion was resected in 191 patients, and of 76 patients with multiple lesions, two or more metastases were resected in 17 patients. Tumors were located in eloquent cortex in 27 patients and near eloquent cortex in 124 patients. Four patients died within 30 days after surgery for a mortality rate of 1.9%. Neurological deterioration was noted in 13 patients (6%) after surgery for Grade I and II tumors and in 5 patients (19%) of 27 patients with Grade III tumors. Karnofsky Performance Scale scores were improved (68 patients) or unchanged (124 patients) in 192 patients and worse in 16 patients after surgery. The median survival time (MST) from the date of surgery was 8 months for all patients and 9 months for 163 patients who did not undergo prior whole-brain radiation therapy. There was no difference in survival between patients operated for single metastasis (MST, 8 mo) versus patients with two or three metastases (MST, 9 mo; P = 0.9364). By both univariate and multivariate analysis, variables significantly affecting outcome included a high Karnofsky Performance Scale score and RPA Class I assignment. By univariate analysis, significant treatment variables included postoperative radiotherapy and postoperative chemotherapy. The MSTs of RPA Class I, II, and III patients were 16.1 months, 7.2 months, and 1.4 months, respectively (P < 0.001, log-rank test). These survival data compare favorably with the stereotactic radiosurgery boost arm of the recently published Radiation Therapy Oncology Group 9508 trial. CONCLUSION: In most patients with single or multiple brain metastases, surgical resection reversed or stabilized neurological symptoms with therapeutic benefit, conveying a notable survival advantage without apparent increased risk, particularly in RPA Class I patients. In patients with Grade III single metastasis or RPA Class II multiple metastasis, surgical judgment should be exercised, and stereotactic radiosurgery boost treatment may be preferable. An algorithm for treatment of brain metastases is proposed.

PMID: 15854250 [PubMed - in process]..

13: Neurosurgery. 2005 May;56(5):956-61; discussion 956-61.: Thirty-seven cases of intracranial meningiomas in the ninth decade of life: our experience and review of the literature.

D'Andrea G, Roperto R, Caroli E, Crispo F, Ferrante L.

Department of Neurosurgery, University of Rome La Sapienza, II Faculty of Medicine, S. Andrea Hospital, Rome, Italy. gdandrea2002@yahoo.it

OBJECTIVE: We report a series of 37 elderly patients who were surgically treated for intracranial meningioma in the ninth decade of life at our neurosurgical division between 1985 and 2002. METHODS: Our study included 37 patients ranging in age from 80 to 86 years (29 women, 8 men). The preoperative neurological status was evaluated according to Karnofsky Performance Scale (KPS) status. The patients' general health condition was evaluated according to the American Society of Anesthesiology (ASA) classification. RESULTS: Five patients (13.5%) experienced perioperative mortality. The risk of postoperative mortality was higher in patients graded as ASA Class III who had low preoperative KPS ratings (< 70), whereas it was lower in patients graded as ASA Classes I and II (P > 0.001). The postoperative mortality rate was significantly higher in patients graded as having a KPS score of less than 70 (P > 0.01). The risk of postoperative morbidity seems higher with larger maximum tumor diameters (P < 0.05). Surgical excision and the presence of a severe peritumoral edema seem to be associated with a higher risk of postoperative morbidity (P < 0.05). CONCLUSION: Surgical removal of a meningioma in the elderly is a safe procedure if the preoperative ASA classification is I or II and if the KPS rating is at least 70. Age seems not to be an insuperable obstacle when adequate management of all risk factors has been obtained.

PMID: 15854243 [PubMed - in process]..

14: Neurosurgery. 2005 May;56(5):946-55; discussion 946-55.: Growth pattern changes of meningiomas: long-term analysis.

Nakasu S, Fukami T, Nakajima M, Watanabe K, Ichikawa M, Matsuda M.

Department of Neurosurgery, Shiga University of Medical Science, Ohtsu, Shiga, Japan. snakasu@belle.shiga-med.ac.jp

OBJECTIVE: Although tumors are generally expected to grow exponentially, it is not known whether meningiomas retain a constant growth rate or not because of the lack of long-term follow-up. We analyzed the long-term growth pattern of meningiomas. METHODS: Twenty patients with a total of 31 meningiomas were radiologically followed for 4.1 to 18.3 years (median, 10.1 yr). Seven patients (including two neurofibromatosis cases) had incidental tumors. Another 13 patients with symptomatic tumors were followed after surgery. Their volumes were measured, and their time-volume curves were plotted. RESULTS: The growth curves of four atypical meningiomas fitted better to an exponential curve (R > 0.95). Two calcified tumors did not grow. Although the other benign tumors grew exponentially or linearly, their tumor volume doubling times in the initial phase were shorter than those in the later phase in most cases. Meningiomas without calcification tended to grow exponentially, whereas those with calcification were likely to reveal a linear growth pattern (P = 0.002, chi2 test). This was supported by the observation that in two patients, the tumor growth pattern changed from exponential to linear and from linear to no growth with progression of calcification. CONCLUSION: Three growth patterns of meningiomas were demonstrated. Atypical meningiomas grew exponentially. Conversely, benign meningiomas revealed exponential, linear, or no growth. The growth pattern of the latter may change with the appearance of calcification.

PMID: 15854242 [PubMed - in process]..

15: Neurosurgery. 2005 May;56(5):936-45; discussion 936-45.: Outcome variation among "radioresistant" brain metastases treated with stereotactic radiosurgery.

Chang EL, Selek U, Hassenbusch SJ 3rd, Maor MH, Allen PK, Mahajan A, Sawaya R, Woo SY.

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. echang@mdanderson.org

OBJECTIVE: To determine the influence of histopathological diagnosis on the outcome of "radioresistant" brain metastases treated with stereotactic radiosurgery (SRS). METHODS: Patients (n = 189) with "radioresistant" brain metastases (n = 264) were consecutively treated with SRS between August 1991 and July 2002. The primary site of brain metastases was melanoma (n = 103), renal cell carcinoma (n = 77), and sarcoma (n = 9). The median age of the patients was 52 years, and the median Karnofsky Performance Scale score was 80. Initial brain metastasis presentation was single in 112 patients (59%). The median SRS dose was 18 Gy (range, 10-24 Gy). The median tumor volume was 1.6 cm3 (range, 0.06-27.5 cm3). The median follow-up of all patients was 7.4 months (range, 0.16-52 mo). RESULTS: The actuarial freedom from progression after 1 year was 64% for renal cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients (P < 0.001). The median survival time for all patients from time of SRS was 7.5 months. The rate of 1-year survival was 40% for renal cell carcinoma patients, 25% for melanoma patients, and 22% for sarcoma patients (P = 0.0354). The incidence of neurological death was lower among patients diagnosed with renal cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P = 0.001). CONCLUSION: Survival after SRS is significantly worse for patients with melanoma and sarcoma brain metastases compared with patients with renal cell carcinoma. Our data show that progressive brain metastases seem to cause most of the cancer-related deaths among patients with SRS-treated melanoma and sarcoma brain metastases. Future investigations using chemotherapy or novel agents to enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem warranted.

PMID: 15854241 [PubMed - in process]..

16: Pediatr Neurol. 2005 Feb;32(2):127-30.

Visual disturbance associated with postoperative cerebellar mutism.

Daniels SR, Moores LE, DiFazio MP.

Department of Neurology, Walter Reed Army Medical Center, Washington, DC 20307, USA.

Cerebellar mutism is an uncommon complication of posterior fossa surgery. Manifestations include disturbances of articulation, prosody, and pitch, and, if severe, complete mutism. Symptoms are independent of recognizable cortical or brainstem injury, and recovery is variable, with permanent deficits frequently observed. Cerebellar dysfunction is commonly invoked as an etiology, although controversy remains concerning the mechanism. Visual impairment has been reported only once before in the setting of this disorder. We report a confirmatory case of sudden, severe visual loss in association with cerebellar mutism after resection of a midline medulloblastoma in a 7-year-old.

Publication Types:

Case Reports

PMID: 15664775 [PubMed - indexed for MEDLINE]..

17: Neurol India. 2005 Mar;53(1):112-4.: Does increased 18FDG uptake reflect malignant transformation of a low-grade glioma? A diagnostic dilemma.

Novak L, Molnar P, Lengyel Z, Tron L.

Department of Neurosurgery, University of Debrecen, Health and Life Sciences Center, Nagyerdei krt. 98, PO Box 31, 4012 Debrecen, Hungary. lnovak@jaguar.dote.hu

Benign gliomas of the brain show decreased uptake of 18F fluorodeoxyglucose (FDG) on positron emission tomography (PET). Malignant transformation is usually manifested by an increase of 18FDG uptake. A 45-year-old female has been followed up since 1987 by means of 18FDG-PET for a right hemispheric World Health Organization Grade II oligoastrocytoma. In 1996, increased epileptic activity was accompanied by increased 18FDG uptake within the temporal part of the tumor. After surgery, the epileptic seizures diminished. Histological examination of the resected tumor showed no change in the pathology when compared with the first biopsy. Localized temporal increase of 18FDG uptake was not associated with malignant progression. The decrease of seizure frequency might shed light on a putative connection of hyperglycolysis and epileptic discharges.

PMID: 15805670 [PubMed - in process]..

18: Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):643-50.: Prior hospitalization for epilepsy, diabetes, and stroke and subsequent glioma and meningioma risk.

Schwartzbaum J, Jonsson F, Ahlbom A, Preston-Martin S, Malmer B, Lonn S, Soderberg K, Feychting M.

Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Columbus, OH 43210, USA. schwartzbaum.1@osu.edu

We conducted a case-control study to evaluate the preclinical association between epilepsy, diabetes, and stroke and primary adult brain tumors. We first identified all 1,501 low-grade glioma, 4,587 high-grade glioma (HGG), and 4,193 meningioma cases reported to the Swedish Cancer Registry from 1987 to 1999. Next, controls (137,485) were randomly selected from the continuously updated Swedish Population Registry and matched to cases diagnosed that year on age and sex. Finally, cases and controls were linked to the Swedish Hospital Discharge Registry (1969-1999). We found that > or =8 years before HGG diagnosis (or control reference year) there was an elevated risk of HGG among people discharged with epilepsy [odds ratio (OR), 3.01; 95% confidence interval (95% CI), 1.73-5.22]. Two to 3 years before HGG diagnosis, this risk increased (OR, 5.33; 95% CI, 3.58-7.93) and was especially strong among people ages <55 years (OR, 13.49; 95% CI, 6.99-25.94). During this 2- to 3-year prediagnostic period, we also found an increased risk of HGG among people discharged with meningitis (OR, 3.02; 95% CI, 1.06-8.59) or viral encephalitis (OR, 12.64; 95% CI, 2.24-71.24). Results are similar for glioblastoma multiforme, low-grade glioma, and meningioma. In contrast, risk of HGG among people discharged with diabetes or stroke does not increase until year of brain tumor diagnosis. The occurrence of excess epilepsy > or =8 years before HGG diagnosis suggests a relatively long preclinical phase, but excess diabetes or stroke appear late in HGG development.

PMID: 15767344 [PubMed - in process]..

19: Clin Radiol. 2005 Apr;60(4):493-502.: High-grade and low-grade gliomas: differentiation by using perfusion MR imaging.

Hakyemez B, Erdogan C, Ercan I, Ergin N, Uysal S, Atahan S.

Department of Radiology, BURTOM Radioimaging Center, Bursa, Turkey.

AIM: Relative cerebral blood volume (rCBV) is a commonly used perfusion magnetic resonance imaging (MRI) technique for the evaluation of tumour grade. Relative cerebral blood flow (rCBF) has been less studied. The goal of our study was to determine the usefulness of these parameters in evaluating the histopathological grade of the cerebral gliomas. METHODS: This study involved 33 patients (22 high-grade and 11 low-grade glioma cases). MRI was performed for all tumours by using a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence followed by conventional MRI. The rCBV and rCBF were calculated by deconvolution of an arterial input function. The rCBV and rCBF ratios of the lesions were obtained by dividing the values obtained from the normal white matter of the contralateral hemisphere. For statistical analysis Mann-Whitney testing was carried out. A p value of less than 0.05 indicated a statistically significant difference. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBV and rCBF ratios and grade of gliomas. Their cut-off value permitting discrimination was calculated. The correlation between rCBV and CBF ratios and glioma grade was assessed using Pearson correlation analysis. RESULTS: In high-grade gliomas, rCBV and rCBF ratios were measured as 6.50+/-4.29 and 3.32+/-1.87 (mean+/-SD), respectively. In low-grade gliomas, rCBV and rCBF ratios were 1.69+/-0.51 and 1.16+/-0.38, respectively. The rCBV and rCBF ratios for high-grade gliomas were statistically different from those of low-grade gliomas (p<0.001). The rCBV and CBF ratios were significantly matched with respect to grade, but difference between the two areas was not significant (ROC analysis, p>0.05). The cut-off value was taken as 1.98 in the rCBV ratio and 1.25 in the rCBF ratio. There was a strong correlation between the rCBV and CBF ratios (Pearson correlation=0.830, p<0.05). CONCLUSION: Perfusion MRI is useful in the preoperative assessment of the histopathologicalal grade of gliomas; the rCBF ratio in addition to the rCBV ratio can be incorporated in MR perfusion analysis for the evaluation.

PMID: 15767107 [PubMed - in process]..

20: J Clin Neurosci. 2005 Feb;12(2):166-168.: The effect of cyclin D expression on cell proliferation in human gliomas.

Zhang X, Zhao M, Huang AY, Fei Z, Zhang W, Wang XL.

Department of Neurosurgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, China.

The expression of three cyclin D subtypes was defined immunohistochemically with cyclin D1, D2 and D3 monoclonal antibodies in 52 human glioma biopsies and eight control samples of normal brain tissue. PCNA labeling indices (LI) were used to evaluate proliferation in the glioma biopsies. LI of cyclin D1, D2 and D3 were compared with histological grade and the proliferating cell nuclear antigen (PCNA) LI. Cyclin D1 expression only was observed in normal brain tissue, but marked overexpression of cyclin D1 and cyclin D3 was observed in glioma. Cyclin D1 LI increased with malignancy, in parallel with an increase in PCNA LI. Lower expression of cyclin D2 was found in a small fraction of the gliomas, but its LI did not vary significantly with grade. Cyclin D3 was mainly expressed by malignant gliomas and was rarely observed in low-grade glioma. Cyclin D2 and D3 expression correlated with PCNA LI, but not as strongly as for cyclin D1. Expression of cyclin D1 is closely related to both the oncogenesis and progression of glioma, while cyclin D3 is associated with transformation to a malignant phenotype. Cyclin D2 is weakly expressed and shows no marked relationship with any aspect of tumorigenesis. The exact contribution of cyclin D subtypes to cell cycle progression in neoplastic and reactive cells remains to be defined.

PMID: 15749420 [PubMed - as supplied by publisher]..