A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.
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ABSTRACT:
SUBMITTER: Garzia L
PROVIDER: S-EPMC6346737 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.
Garzia Livia L Kijima Noriyuki N Morrissy A Sorana AS De Antonellis Pasqualino P Guerreiro-Stucklin Ana A Holgado Borja L BL Wu Xiaochong X Wang Xin X Parsons Michael M Zayne Kory K Manno Alex A Kuzan-Fischer Claudia C Nor Carolina C Donovan Laura K LK Liu Jessica J Qin Lei L Garancher Alexandra A Liu Kun-Wei KW Mansouri Sheila S Luu Betty B Thompson Yuan Yao YY Ramaswamy Vijay V Peacock John J Farooq Hamza H Skowron Patryk P Shih David J H DJH Li Angela A Ensan Sherine S Robbins Clinton S CS Cybulsky Myron M Mitra Siddhartha S Ma Yussanne Y Moore Richard R Mungall Andy A Cho Yoon-Jae YJ Weiss William A WA Chan Jennifer A JA Hawkins Cynthia E CE Massimino Maura M Jabado Nada N Zapotocky Michal M Sumerauer David D Bouffet Eric E Dirks Peter P Tabori Uri U Sorensen Poul H B PHB Brastianos Priscilla K PK Aldape Kenneth K Jones Steven J M SJM Marra Marco A MA Woodgett James R JR Wechsler-Reya Robert J RJ Fults Daniel W DW Taylor Michael D MD
Cell 20180201 5
While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninge ...[more]
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Project description:BackgroundDiagnosis of leptomeningeal metastasis (LM) has become increasingly frequent. The diagnostic gold standard has been CSF cytology, but MRI is now used routinely for diagnosis. Diagnosis and prognosis of LM has not been studied in the MRI era.MethodsPatients with LM from 2002 through 2004 were identified through a neurology database, as well as by reviewing all abnormal CSF cytologies from a pathology database. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LM were also included.ResultsA total of 187 patients with LM were analyzed in this retrospective review. Of these, 150 had solid and 37 had hematopoietic malignancies. Median age was 56.4 years, and median Karnofsky performance status (KPS) was 70. The most common types of solid tumor were breast (65 patients), lung (47), gastrointestinal (11), and melanoma (9). Of the hematopoietic tumors, 21 were lymphoma and 15 were leukemia. Fifty-three percent of patients were diagnosed by imaging, 23% by cytology, and 24% by both. Treatment included radiation therapy in 55%, intrathecal chemotherapy in 29%, and systemic chemotherapy in 18%; 21% received supportive care alone. Median overall survival was 2.4 (95% confidence interval 1.9-3.1) months. Median survival for patients with hematopoietic tumors was 4.7 months and for solid tumors was 2.3 months (p = 0.0006). In multivariate analysis, initial KPS and tumor type (solid vs hematopoietic) were significant predictors of survival.ConclusionsDespite enhanced diagnosis with MRI, prognosis remains poor in leptomeningeal metastasis. Those with hematopoietic tumors continue to fare better than those with solid tumors.
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Project description:The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease-related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for patients with breast cancer with newly diagnosed leptomeningeal metastasis. Safety and efficacy of intrathecal administration of new agents such as trastuzumab are under evaluation. Systemic therapy using targeted agents and immunotherapy has also improved outcome in patients with brain metastasis, and its emerging role in the management of leptomeningeal metastasis needs to better studied in prospective series. Focal radiotherapy is commonly indicated for the treatment of macroscopic disease such as meningeal nodules or clinically symptomatic central nervous system structures, for example, base of skull with cranial nerve involvement or cauda equine syndrome. The role of whole brain radiotherapy is decreasing. An individualised combination of different therapeutic options should be used considering the presentation of leptomeningeal metastasis, as well as the histological and molecular tumour characteristics, the presence of concomitant brain and systemic metastases, and prior cancer-directed treatments.
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