Neuro-Oncology

Shaw, Edward, G.

doi: 10.1215/S1152851702200617pmid: 12838951

References Buckner, J.C., Gesme, D., Jr., O'Fallon, J.R., Hammack, J.E., Stafford, S., Brown, P.D., Hawkins, R., Scheithauer. B.W., Erickson, B.J., Levitt, R., Shaw, E.G., and Jenkins, R. ( 2003 ) Phase II trial of procarbazine, lomus tine, and vincristine as initial therapy for patients with low-grade oligo dendroglioma or oligoastrocytoma: Efficacy and associations with chromosomal abnormalities. J. Clin. Oncol. 21 , 251 -255. Google Scholar Cairncross, J.G., and Laperriere, N.J. ( 1989 ) Low-grade glioma. To treat or not to treat? Arch. Neurol. 46 , 1238 -1239. Google Scholar Gol, A. ( 1961 ) The relatively benign astrocytomas of the cerebrum. A clini cal study of 194 verified cases. J. Neurosurg. 18 , 501 -506. Google Scholar Horrax, G. ( 1954 ) Benign (favorable) types of brain tumor. The end results (up to twenty years), with statistics of mortality and useful survival. N. Engl. J. Med. 250 , 981 -984. Google Scholar Kleihues, P., and Cavenee, W.K. (Eds.) ( 2000 ) World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of the Nervous System . Lyon: IARC Press. Google Scholar Ling, C.C., Humm, J., Larson, S., Amols, H., Fuks, Z., Leibel, S., and Koutcher, J.A. ( 2000 ) Towards multidimensional radiotherapy: Biological imaging and biological conformality. Int. J. Radiat. Oncol. Biol. Phys. 47 , 551 -560. Google Scholar Louis, D., Holland, E.C., and Cairncross, J.G. ( 2001 ) Glioma classification. A molecular reappraisal. Am. J. Pathol. 159 , 779 -786. Google Scholar Morris, D.E., Bourland, J.D., Rosenman, J.G., and Shaw, E.G. ( 2001 ) Three-dimensional conformal radiation treatment planning and delivery for low- and intermediate-grade gliomas. Semin. Radiat. Oncol. 11 , 124 -137. Google Scholar Sanford, A., Kun, L., Sposto, R., Holmes, E., Wisoff, J.H., Heier, L., and McGuire-Cullen, P. ( 2002 ) Low-grade gliomas of childhood: Impact of surgical resection. A report from the Children's Oncology Group. J. Neurosurg. 96 , 427 -428 (abstract). Google Scholar Shaw, E.G. ( 1990 ) Low-grade gliomas: To treat or not to treat? A radiation oncologist's viewpoint. Arch. Neurol. 47 , 1138 -1140. Google Scholar Shaw, E.G., Daumas-Duport, C., Scheithauer, B.W., Gilbertson, D.T., O'Fallon, J.R., Earle, J.D., Laws, E.R, Jr., and Okazaki, H. ( 1989 ) Radiation therapy in the management of low-grade supratentorial astrocytomas. J. Neurosurg. 70 , 853 -861. Google Scholar Shaw, E., Arusell, R., Scheithauer, B., O'Fallon, J., O'Neill, B., Dianpoli, R., Nelson, D., Earle, J., Jones, C., Cascino, T., Nichols, D., Ivnik, R., Hell man, R., Curran, W., and Abrams, R. ( 2002a ) Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: Initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group Study. J. Clin. Oncol. 20 , 2267 -2276. Google Scholar Shaw, E., Stieber, V., Tatter, S., Ellis, E., Hinson, W., Kearns, W., Bourland, J.D., Munley, M., Lesser, G., and Stanton, C. ( 2002b ) Update of a phase I dose escalating study: Intensity modulated radiation therapy for glioblastoma multiforme (GBM). Neuro-Oncol. 4 , 359 (abstract). Google Scholar This content is only available as a PDF. © 2003 by the Society for Neuro-Oncology

Shaw, Edward, G.;Wisoff, Jeffrey, H.

doi: 10.1215/S1152851702000601pmid: 12816721

Abstract Over the last decade, the results of 5 prospective clinical trials of intracranial low-grade glioma (LGG) have been published, 4 in adults with supratentorial LGG and 1 in children with infra- and supratentorial LGG. The data from the more than 1600 patients treated on these studies are summarized herein. European Organization for Research and Treatment of Cancer study 22845 randomized 311 adults to postoperative observation or radiation therapy (RT). There was no difference in the 5-year overall survival (OS) rate between the 2 arms. Irradiated patients had a significantly improved 5-year progression-free survival (PFS) rate. European Organization for Research and Treatment of Cancer study 22844 randomized 379 adults to low-dose (45 Gy) versus high-dose (59.4 Gy) RT. Similarly, an intergroup study conducted by the North Central Cancer Treatment Group, Radiation Therapy Oncology Group, and Eastern Cooperative Group randomized 203 adults to low-dose (50.4 Gy) versus high-dose (64.8 Gy) RT. There was no difference in the 5-year OS or PFS rates between the 2 dose groups in either study. A Southwest Oncology Group study randomized 54 adults with incompletely resected LGG to RT alone or RT plus CCNU (lomustine) chemotherapy. There was no difference in outcome between the 2 treatment arms. Important prognostic factors for OS in these 4 adult trials included extent of surgical resection, histology, tumor size, and age. An intergroup study of the Children's Cancer Group and Pediatric Oncology Group enrolled 660 pediatric patients with management based on the extent of surgical resection: Children who underwent gross total tumor resection were observed postoperatively, whereas those who had subtotal resection or biopsy were either observed or administered RT at the discretion of their physician. Survival was most impacted by several prognostic factors, primarily extent of resection. Besides extent of resection, other prognostic factors that were consistent in predicting survival in these 5 clinical trials included patient age and tumor location, size, and histology. The data from these 5 studies indicate that for intracranial LGG in adults, postoperative RT is associated with improved 5-year PFS but not OS rates compared to postoperative observation. Radiation doses of 45 to 54 Gy result in 5-year OS and PFS rates that are similar to those for higher doses. The strategies of chemotherapy alone and RT plus chemotherapy are under investigation. For pediatric LGG, extent of surgical resection is the most important prognostic factor associated with favorable 5-year OS and PFS. Radiation therapy and chemotherapy are generally used in the settings of incomplete resection and recurrent disease, and these strategies are being investigated in prospective clinical trials. The schemata from recently completed and ongoing studies in both adult and pediatric intracranial LGG are reviewed. References Eyre, H.J., Crowley, J.J., Townsend, J.J., Eltringham, J.R., Morantz, R.A., Schulman, S.F., Quagliana, J.M., and al-Sarraf, M. ( 1993 ) A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected low-grade gliomas: A Southwest Oncology Group study. J. Neurosurg. 78 , 909 -914. Karim, A.B.M.F., Maat, B., Hatlevoll, R., Menten, J., Rutten, E.H., Thomas, D.G., Mascarenhas, F., Horiot, J.C., Parvinen, L.M., van Reijn, M., Jager, J.J., Fabrini, M.G., van Alphen, A.M., Hamers, H.P., Gaspar, L., Nooddman, E., Pierart, M., and van Glabbeke, M. ( 1996 ) A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer Study (EORTC) Study 22844. Int. J. Radiat. Oncol. Biol. Phys. 36 , 549 -556. Karim, A.B.M.F., Afra, D., Cornu, P., Bleehan, N., Schraub, S., De Witte, O., Darcel, F., Stenning, S., Pierart, M., and Van Glabbeke, M. ( 2002 ) Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council Study BR04: An interim analysis. Int. J. Radiat. Oncol. Biol. Phys. 52 , 316 -324. RTOG. Radiation Therapy Oncology Group, American College of Radiology ( 2002 ) RTOG 98–02, A phase II study of observation in favorable low-grade glioma and phase III study of radiation with or without PCV chemotherapy in unfavorable low-grade glioma. Online protocol accessed March 19, 2002 (http://www.rtog.org/members/protocols/98–02/main.html#a4). Sanford, A., Kun, L., Sposto, R., Holmes, E., Wisoff, J.H., Heier, L., and McGuire-Cullen, P. ( 2002 ) Low-grade gliomas of childhood: Impact of surgical resection. A report from the Children's Oncology Group. J. Neurosurg. 96 , 427 -428 (abstract). Shaw, E., Arusell, R., Scheithauer, B., O'Fallon, J., O'Neill, B., Dianpoli, R., Nelson, D., Earle, J., Jones, C., Cascino, T., Nichols, D., Ivnik, R., Hellman, R., Curran, W., and Abrams, R. ( 2002 ) Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: Initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J. Clin. Oncol. 20 , 2267 -2276. Author notes Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1030 (E.G.S.), andDivision of Pediatric Neurosurgery, New York University Medical Center, New York 10016 (J.H.W.); USA © 2003 by the Society for Neuro-Oncology

Brown, Paul, D.;Buckner, Jan, C.;Uhm, Joon, H.;Shaw, Edward, G.

doi: 10.1215/S1152851702000431pmid: 12816722

Abstract Radiotherapy is a component of the treatment regimen for the majority of patients with low-grade gliomas. Therefore, the effect of radiotherapy on the long-term cognitive performance of these patients is a major concern. This article reviews the neurocognitive effects of radiotherapy on patients with low-grade gliomas. The weight of evidence suggests only sporadic, limited neurocognitive damage from focal radiotherapy at the doses usually prescribed for low-grade gliomas. References Ahles, T.A., Saykin, A.J., Furstenberg, C.T., Cole, B., Mott, L.A., Skalla, K., Whedon, M.B., Bivens, S., Mitchell, T., Greenberg, E.R., and Silberfarb, P.M. ( 2002 ) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J. Clin. Oncol. 20 , 485 -493. Armstrong, C., Mollman, J., Corn, B.W., Alavi, J., and Grossman, M. ( 1993 ) Effects of radiation therapy on adult brain behavior: Evidence for a rebound phenomenon in a phase 1 trial. 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Perry,, Arie

doi: 10.1215/S1152851702000443pmid: 12816723

Abstract Although the term low-grade glioma (LGG) is useful for its connotation of a slow-growing, better prognosis CNS primary neoplasm typically occurring in a young patient, it also serves as a potential diagnostic wastebasket, occasionally leading to conceptual errors, therapeutic uncertainty, or misinterpretation of clinical data. For example, the LGG designation is occasionally invoked as a justification for lumping together biologically unrelated entities such as pilocytic astrocytoma and diffuse astrocytoma. Whereas the former represents a benign and potentially surgically curable neoplasm that virtually never undergoes malignant transformation, the latter is a surgically incurable low-grade malignancy, prone to further malignant progression and eventual fatality. Therefore, although rare cases lacking a clear distinction may be encountered, the term LGG should be abandoned for a more specific diagnosis whenever possible. 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Wu,, An-hua;Low, Walter, C.

doi: 10.1215/S1152851702000510pmid: 12816724

Abstract The interleukin 13 alpha 2 receptor (IL-13Ra2) has been shown to be expressed in most malignant glioblastoma cells. Recent studies suggest that IL-13Ra2 serves as a dominant negative inhibitor or a decoy receptor for IL-13. To investigate the transcriptional regulation of this receptor, we cloned and characterized the promoter for the human IL-13Ra2 gene. Our results demonstrate that this promoter contains three TATA boxes and one CCAAT site. Several putative transcriptional factor binding sites for nuclear factor of activated T cells 1, AP1 (c-JUN and c-FOS), AP2, GABP, OCT1, GATA3, PRE, and C-ETS1 were predicted in the promoter region. Using the secreted alkaline phosphate reporter gene assay, we investigated the functional activity of the human IL-13Ra2 promoter by transient transfection in glioma cell lines U118, U87, and T98, which differ in their expression of the human IL-13Ra2 protein. The different secreted alkaline phosphate activities among these 3 cell lines suggest that the expression of human IL-13Ra2 is regulated at the transcriptional level. Methylation analysis showed that expression of IL-13Ra2 may not be the result of methylation of the CpG dinucleotides in the promoter region of the gene. Deletion analysis identified a 64 base pair (bp) region that is necessary for human IL-13Ra2 promoter activity. This 64-bp sequence contains cis-elements for AP1, nuclear factor of activated T cells, and AP2. The possible role of AP1 in the regulation of human IL-13Ra2 promoter activity was suggested by in vitro mutagenesis and c-JUN N-terminal kinase inhibition analysis. References Assimakopoulou, M., and Varakis, J. ( 2001 ) AP-1 and heat shock protein 27 expression in human astrocytomas. J. Cancer Res. Clin. Oncol. 127 , 727 -732. 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Author notes Department of Neurosurgery (A.W., W.C.L.) andGraduate Program in Neuroscience (W.C.L.), University of Minnesota Medical School, Minneapolis, MN 55455, USA, andDepartment of Neurosurgery, First Clinical College of China Medical University, Shenyang, China (A.W.) © 2003 by the Society for Neuro-Oncology

Hukin,, Juliette;Siffert,, Joao;Cohen,, Henry;Velasquez,, Linda;Zagzag,, David;Allen,, Jeffrey

doi: 10.1215/S1152851702000297pmid: 12816725

Abstract The goal of this study was to describe the demographic, histologic, and prognostic features of children with low-grade neuroepithelial tumors (LGN) of the CNS presenting with leptomeningeal metastases (LM) at diagnosis. We identified 528 newly diagnosed LGN children, 13 (3%) of whom had LM at diagnosis. LM was defined by neuroimaging, clinical evidence, and/or biopsy. The charts were reviewed and patients contacted to validate the demographic data, treatment, and clinical status. The distribution of LM patients by primary tumor site was diencephalon, 5; cerebrum, 2; spinal cord, 3; brainstem, 2; and cerebellum, 1. Six of 8 patients with LM had durable objective responses to chemotherapy. The 5-year progression-free survival of patients with LM at diagnosis was 17%, compared to 85% (95% CI, 80%-91%) for those with localized LGN who had a gross total resection and 51% (95% CI, 44%-52%) for those with localized LGN who had less aggressive surgery (P < 0.0001). Only 1 of these 13 LM patients died. The 5-year overall survival of the localized LGN group with a gross total resection was 97% (95% CI, 92%-99.9%), and that of the localized LGN group with less aggressive surgery was 88% (95% CI, 84%-95%) (P = 0.004). The 3% frequency of LM at diagnosis is likely an underestimate since patients with newly diagnosed LGN were not routinely staged. We suggest that staging be considered in the following circumstances: diencephalic primary site, unexplained hydrocephalus, clinical features suggestive of LM, and before adjuvant therapy is initiated. The prognosis for children with LM at diagnosis is favorable, and its identification alters therapeutic strategies. References Akar, Z., Tanriover, N., Kafadar, A.M., Gazioglu, N., Oz, B., and Kuday, C. ( 2000 ) Chiasmatic low-grade glioma presenting with sacral intradural spinal metastasis. Childs Nerv. Syst. 16 , 309 -311. Bauman, G., Pahapill, P., Macdonald, D., Fisher, B., Leighton, C., and Cairncross, G. 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Claffey, K.P., and Robinson, G.S. ( 1996 ) Regulation of VEGF/VPF expression in tumour cells: Consequences for tumor growth and metastasis. Cancer Metastasis Rev. 15 , 165 -176. De Vries, C., Escobedo, J.A., Ueno, H., Houck, K., Ferrara, N., and Williams, L.T. ( 1992 ) The fms-like tyrosine kinase, a receptor for vascular endothe lial growth factor. Science 255 , 989 -991. Di, X., Nishizaki, T., Harada, K., Kajiwara, K., Nakayama, H., and Ito, H. ( 1997 ) Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. J. Exp. Clin. Cancer Res. 16 , 153 -157. Doireau, V., Grill, J., Zerah, M., Lellouch-Tubiana, A., and Couanet, D. ( 1999 ) Chemotherapy for unresectable and recurrent intramedullary glial tumors in children. Brain Tumours Subcommittee of the French Society of Paediatric Oncology (SFOP). Br. J. Cancer 81 , 835 -840. Edvardsen, K., Brunner, N., Spang-Thomsen, M., Walsh, F.S., and Bock, E. 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Pollack, Ian, F.;Boyett, James, M.;Yates, Allan, J.;Burger, Peter, C.;Gilles, Floyd, H.;Davis, Richard, L.;Finlay, Jonathan, L.

doi: 10.1215/S1152851703000097pmid: 12816726

Abstract To examine the influence of the pathology review mechanism on the results of analyses of therapeutic efficacy and biological prognostic correlates for pediatric high-grade gliomas, we evaluated the effects of using single-expert review or consensus review, as alternatives to institutional classification, in determining outcome results of a large randomized trial. The study group was the randomized cohort of Children's Cancer Group study 945, which compared efficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trial eligibility required institutional histopathologic diagnosis of high-grade glioma. Sections of study tumors also were centrally reviewed, initially by a study review neuropathologist and subsequently by 5 neuropathologists, including the review pathologist. Reviews were independent, and reviewers were masked to clinical factors and outcomes, and consensus diagnoses of the panel were then established. Among 172 eligible patients, 42 tumors were classified as discordant on single-expert review and 51 on consensus review. Progression-free survival probabilities calculated for patients with tumors classified as high-grade gliomas by either single-expert or consensus review were inferior to those for the overall, institutionally diagnosed cohort. However, conclusions of the study regarding relative efficacy of treatment and clinical and molecular outcome correlates were unaffected by diagnosis method. Resection extent, proliferation index, and p53 expression were associated strongly with outcome, regardless of diagnosis method. However, comparisons between arms in which inclusion was determined by different review criteria for each arm caused spurious conclusions about efficacy differences between treatments. We conclude that the pathology review mechanism had little effect on within-trial comparisons of therapeutic effects or prognostic correlates in this randomized study, but strongly influenced survival distributions that were calculated for each treatment arm. These results support the implementation of expedited central review in therapeutic studies involving childhood malignant gliomas as a way to prospectively identify and exclude cases with discordant diagnoses and indicate the need for additional measures, such as molecular assessments, to increase the reproducibility of neuro pathologic classification for these tumors. References Aldape, K., Simmons, M.L., Davis, R.L., Miike, R., Wiencke, J., Barger, G., Lee, M., Chen, P., and Wrensch, M. ( 2000 ) Discrepancies in diagnoses of neuroepithelial neoplasms: The San Francisco Bay Area Adult Glioma Study. Cancer 88 , 2342 -2349. 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Sanford, A., Kun, L., Sposto, R., Holmes, E., Wisoff, J.H., Heier, L., and McGuire-Cullen, P. ( 2002 ) Low-grade gliomas of childhood: Impact of surgical resection. A report from the Children's Oncology Group. J. Neurosurg. 96 , 427 -428. Schwartz, D., and Lellouch, J. ( 1967 ) Explanatory and pragmatic attitudes in therapeutical trials. J. Chronic Dis. 20 , 637 -648. Tsiatis, A. ( 1990 ) Analysis and interpretation of trial results: Intent-to-treat analysis. J. Acquir. Immune Defic. Syndr. 3 (Suppl. 2), S120 -S123. Wisoff, J.H., Boyett, J.M., Berger, M.S., Brant, C., Li, H., Yates, A.J., McGuire-Cullen, P., Turski, P.A., Sutton, L.N., Allen, J.C., Packer, R.J., and Finlay, J.L. ( 1998 ) Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: A report of the Children's Cancer Group trial no. CCG-945. J. Neurosurg. 89 , 52 -59. Yung, W.K., Prados, M.D., Yaya-Tur, R., Rosenfeld, S.S., Brada, M., Fried man, H.S., Albright, R., Olson, J., Chang, S.M., O'Neill, A.M., Friedman, A.H., Bruner, J., Yue, N., Dugan, M., Zaknoen, S., and Levin, V.A. ( 1999 ) Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group [erratum in J. Clin. Oncol. 17, 3693, 1999]. J. Clin. Oncol. 17 , 2762 -2771. Author notes Department of Neurosurgery, University of Pittsburgh School of Medicine and the Children's Hospital of Pittsburgh, Pittsburgh, PA 15213 (I.F.P.);Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105 (J.M.B.);Department of Pathology, Ohio State University, Columbus, OH 43210 (A.J.Y.);Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 (P.C.B);Department of Pathology, University of Southern California, Los Angeles, CA 90027 (F.H.G.);Department of Pathology, University of California, San Francisco, CA 94143 (R.L.D.);Department of Pediatrics, New York University Medical Center, New York 10016 (J.L.F.); USA © 2003 by the Society for Neuro-Oncology

Lee, Hoon, K.;Chang, Eric, L.;Fuller, Gregory, N.;Aldape, Kenneth, D.;Atkinson, George, J.;Levy, Lawrence, B.;McCutcheon, Ian, E.;Maor, Moshe, H.

doi: 10.1215/S1152851702000595pmid: 12816727

Abstract To assess the prognostic value of neurologic function (NF) in patients with astrocytic spinal cord glioma, we conducted a retrospective study of 25 patients who were treated at our institution between January 1970 and December 1999. The median age was 40 years, and the median follow-up was 54 months. Nineteen patients had a biopsy, 5 had a subtotal resection, and 1 had a gross total resection. Twenty-two patients received postoperative radiotherapy to a median dose of 45 Gy. NF ratings of 1 and 2 were considered favorable, and 3 and 4 were considered unfavorable, based on a scale of 1 to 4. Dual neuropathologic review confirmed the tumor to be low, intermediate, or high grade, based on the WHO grades I-II, III, or IV, respectively. Actuarial rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed. Our study results revealed that an improved 5-year OS rate was associated with favorable NF at diagnosis (73% vs. 22% for patients with unfavorable NF; P = 0.04) and favorable NF before radiation therapy (89% vs. 28% for patients with unfavorable NF; P = 0.049). There was a significant difference in OS based on tumor grade (P < 0.001) and age (risk ratio, 1.04; P = 0.027). PFS and LC were significantly better for young patients and those with lower tumor grade (P < 0.05). A multivariate analysis of age, NF at diagnosis, and postoperative NF for all patients showed postoperative NF and age to be independent prognostic factors for OS. We conclude that favorable NF may be associated with improved outcome in patients with astrocytic spinal cord glioma. References Bouffet, E., Pierre-Kahn, A., Marchal, J.C., Jouvet, A., Kalifa, C., Choux, M., Dhellemmes, P., Guerin, J., Tremoulet, M., and Mottolese, C. ( 1998 ) Prognostic factors in pediatric spinal cord astrocytomas. 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Biol. Phys. 48 , 837 -842. Shirato, H., Kamada, T., Hida, K., Koyanagi, I., Iwasaki, Y., Miyasaka, K., and Abe, H. ( 1995 ) The role of radiotherapy in the managment of spinal cord glioma. Int. J. Radiat. Oncol. Biol. Phys. 33 , 323 -328. Author notes Departments of Radiation Oncology (H.K.L., E.L.C., G.J.A., M.H.M.),Pathology (G.N.F., K.D.A.),Biomathematics (L.B.L.), andNeurosurgery (I.E.M.), The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA © 2003 by the Society for Neuro-Oncology

Landolfi, Joseph, C.;Nadkarni,, Mangala

doi: 10.1215/S1152851702000467pmid: 12816728

Abstract We describe a patient who presented with a clinical syndrome of limbic encephalitis, narcolepsy, and cataplexy. The anti-Ma2 antibody was positive. Although there was no mass on imaging, orchiectomy was performed in this patient, and testicular carcinoma was found. This is the first known case of limbic encephalitis and anti-Ma2 antibody to be associated with cataplexy and possible narcolepsy. Neurological symptoms precede the diagnosis of cancer in 50% of patients with paraneoplastic syndromes, and clinicians are therefore strongly advised to evaluate patients with neurological symptoms for this condition. References Barnett, M., Prosser, J., Sutton, I., Halmagyi, G.M., Davies, L., Harper, C., and Dalmau, J. ( 2001 ) Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J. Neurol. Neurosurg. Psychiatry 70 , 222 -225. Carskadon, M.A., Dement, W.C., Mitler, M.M., Roth, T., Westbrook, P.R., and Keenan, S. ( 1986 ) Guidelines for the multiple sleep latency test (MSLT): A standard measure of sleepiness. Sleep 9 , 519 -524. Dalmau, J., Gultekin, S.H., Voltz, R., Hoard, R., DesChamps, T., Balmaceda, C., Batchelor, T., Gerstner, E., Eichen, J., Frennier, J., Posner, J.B., and Rosenfeld, M.R. ( 1999 ) Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 122 , 27 -39. Dalmau, J., and Posner, J.B. ( 1997 ) Paraneoplastic syndromes affecting the nervous system. Semin. Oncol. 24 , 318 -328. Gultekin, S.H., Rosenfeld, M.R., Voltz, R., Eichen, J., Posner, J.B., and Dalmau, J. ( 2000 ) Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123 , 1481 -1494. Henson, R.A., and Urich, H. ( 1982 ) Cortical cerebellar degeneration. In: Henson, R.A., and Urich, H. (Eds.), Cancer and the Nervous System: The Neurological Manifestations of Systemic Malignant Disease. Oxford: Blackwell Scientific Publications, pp. 346 -367. Honda, Y., and Juji, T. (Eds.) ( 1988 ) HLA in Narcolepsy . Berlin: Springer-Verlag. Obermeyer, W.H., and Benca, R.M. ( 1996 ) Effects of drugs on sleep. Neurol. Clin. 14 , 827 -840. Overeem, S., Mignot, E., van Dijk, J.G., and Lammers, G.J. ( 2002 ) Narcolepsy: Clinical features, new pathophysiological insights, and future perspectives. J. Clin. Neurophysiol. 18 , 78 -105. Sammaritano, M., and Sherwin, A. ( 2000 ) Effect of anticonvulsants on sleep. Neurology 54 (Suppl. 1), S16 -S24. Sutton, I., Winer, J., Rowlands, D., and Dalmau, J. ( 2000 ) Limbic encephalitis and antibodies to Ma2: A paraneoplastic presentation of breast cancer. J. Neurol. Neurosurg. Psychiatr. 69 , 266 -268. Thorpy, M. ( 2001 ) Current concepts in the etiology, diagnosis and treatment of narcolepsy. Sleep Med. 2 , 5 -17. Voltz, R., Gultekin, S.H., Rosenfeld, M.R., Gerstner, E., Eichen, J., Posner, J.B., and Dalmau, J. ( 1999 ) A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N. Engl. J. Med. 340 , 1788 -1795. This content is only available as a PDF. © 2003 by the Society for Neuro-Oncology

Magtibay, Paul, M.;Friedman, Jonathan, A.;Rao, Ravi, D.;Buckner, Jan, C.;Cliby, William, A.

doi: 10.1215/S115285170200042Xpmid: 12816729

Abstract Patients with medulloblastoma uncommonly develop extracerebral metastases. We describe an adult patient with the unusual occurrence of intraperitoneal metastases associated with a ventriculoperitoneal (VP) shunt, as well as her subsequent treatment with high-dose chemotherapy and bone marrow transplantation. We review the literature regarding this rare presentation and association of metastatic spread via VP shunt devices. A 37-year-old woman presented with a rapidly enlarging pelvic mass. She had a history of medulloblastoma and had been treated with a combination of surgery, chemotherapy, and radiation 5 years previously, at which time a VP shunt had been placed for cerebrospinal fluid leakage. At laparotomy, she had unresectable intraperitoneal metastatic medulloblastoma. After an excellent response to cyclophosphamide, etoposide, and cisplatin, she underwent a resection of residual disease, followed by high-dose chemotherapy and a bone marrow transplant. We conclude that adult onset medulloblastoma with metastasis to the peritoneal cavity is rare and may be associated with a VP shunt. References Abraham, J., and Chandy, J. ( 1963 ) Ventriculo-atrial shunt in the management of posterior fossa tumors. Preliminary report. J. Neurosurg. 20 , 52 -53. Albright, A.L. ( 1983 ) The value of precraniotomy shunts in children with posterior fossa tumors. Clin. Neurosurg. 30 , 278 -285. Belza, M.G., Donaldson, S.S., Steinberg, G.K., Cox, R.S., and Cogen, P.H. ( 1991 ) Medulloblastoma: Freedom from relapse longer than 8 years—a therapeutic cure? J. Neurosurg. 75 , 575 -582. Berger, M.S., Baumeister, B., Geyer, J.R., Milstein, J., Kanev, P.M., and LeRoux, P.D. ( 1991 ) The risks of metastases from shunting in children with primary central nervous system tumors. J. Neurosurg. 74 , 872 -877. Carrie, C., Lasset, C., Alapetite, C., Haie-Meder, C., Hoffstetter, S., Demaille, M.C., Kerr, C., Wagner, J.P., Lagrange, J.-L., Maire, J.-P., Seng, S.-H., Man, Y.O., Murraciole, X., and Pinto, N. ( 1994 ) Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Retrospective study of 156 patients. Cancer 74 , 2352 -2360. Dunkel, I.J., Boyett, J.M., Yates, A., Rosenblum, M., Garvin, J.H., Jr., Bostrom, B.C., Goldman, S., Sender, L.S., Gardner, S.L., Li, H., Allen, J.C., and Finlay, J.L. ( 1998 ) High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group. J. Clin. Oncol. 16 , 222 -228. Hildebrand, J., Dewitte, O., Dietrich, P.Y., and de Tribolet, N. ( 1997 ) Management of malignant brain tumors. Eur. Neurol. 38 , 238 -253. Hoffman, H.J., Hendrick, E.B., and Humphreys, R.P. ( 1976 ) Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma. J. Neurosurg. 44 , 562 -566. Jamjoom, Z.A., Jamjoom, A.B., Sulaiman, A.H., Naim-Ur-Rahman, and al Rabiaa, A. ( 1993 ) Systemic metastasis of medulloblastoma through ventriculoperitoneal shunt: Report of a case and critical analysis of the literature. Surg. Neurol. 40 , 403 -410. Lewis, M.B., Nunes, L.B., Powell, D.E., and Shnider, B.I. ( 1973 ) Extra-axial spread of medulloblastoma. Cancer 31 , 1287 -1297. Nelson, A.A. ( 1936 ). Metastases of intracranial tumors. Am. J. Cancer 28 , 1 -12. Rochkind, S., Blatt, I., Sadeh, M., and Goldhammer, Y. ( 1991 ) Extracranial metastases of medulloblastoma in adults: Literature review. J. Neurol. Neurosurg. Psychiatr. 54 , 80 -86. Torres, C.F., Rebsamen, S., Silber, J.H., Sutton, L.N., Bilaniuk, L.T., Zimmerman, R.A., Goldwein, J.W., Phillips, P.C., and Lange, B.J. ( 1994 ) Surveillance scanning of children with medulloblastoma. N. Engl. J. Med. 330 , 892 -895. Author notes Divisions of Gynecologic Oncology (P.M.M., W.A.C.),Neurologic Surgery (J.A.F.), andMedical Oncology (R.D.R, J.C.B.), Mayo Clinic Rochester, Mayo Foundation, Rochester, MN 55905, USA © 2003 by the Society for Neuro-Oncology