DOI QR코드

DOI QR Code

Retrospective Analysis of Cerebrospinal Fluid Profiles in 228 Patients with Leptomeningeal Carcinomatosis : Differences According to the Sampling Site, Symptoms, and Systemic Factors

  • Shim, Youngbo (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Gwak, Ho-Shin (Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center) ;
  • Kim, Sohee (Cancer Biostatistics Branch, National Cancer Center) ;
  • Joo, Jungnam (Cancer Biostatistics Branch, National Cancer Center) ;
  • Shin, Sang-Hoon (Neuro-Oncology Clinic, National Cancer Center) ;
  • Yoo, Heon (Neuro-Oncology Clinic, National Cancer Center)
  • Received : 2016.07.04
  • Accepted : 2016.08.02
  • Published : 2016.11.01

Abstract

Objective : Elevated cell counts and protein levels in cerebrospinal fluid (CSF) result from disease activity in patients with leptomeningeal carcinomatosis (LMC). Previous studies evaluated the use of CSF profiles to monitor a treatment response or predict prognosis. CSF profiles vary, however, according to the sampling site and the patient's systemic condition. We compared lumbar and ventricular CSF profiles collected before intraventricular chemotherapy for LMC and evaluated the association of these profiles with patients' systemic factors and LMC disease activity. Methods : CSF profiles were retrospectively collected from 228 patients who underwent Ommaya reservoir insertion for intraventricular chemotherapy after a diagnosis of LMC. Lumbar samples taken via lumbar puncture were used for the diagnosis, and ventricular samples were obtained later at the time of Ommaya reservoir insertion. LMC disease activity was defined as the presence of LMC-related symptoms such as increased intracranial pressure, hydrocephalus, cranial neuropathy, and cauda equina syndrome. Results : Cell counts (median : 8 vs. 1 cells/mL) and protein levels (median : 68 vs. 17 mg/dL) significantly higher in lumbar CSF than in ventricular CSF (p<0.001). Among the evaluated systemic factors, concomitant brain metastasis and previous radiation were significantly correlated with higher protein levels in the lumbar CSF (p=0.01 and <0.001, respectively). Among the LMC disease activity, patients presenting with hydrocephalus or cauda equina syndrome showed higher lumbar CSF protein level compared with that in patients without those symptoms (p=0.049 and p<0.001, respectively). The lumbar CSF cell count was significantly lower in patients with cranial neuropathy (p=0.046). The ventricular CSF cell counts and protein levels showed no correlation with LMC symptoms. Carcinoembryonic antigen (CEA), which was measured from ventricular CSF after the diagnosis in 109 patients, showed a significant association with the presence of hydrocephalus (p=0.01). Conclusion : The protein level in lumbar CSF indicated the localized disease activity of hydrocephalus and cauda equina syndrome. In the ventricular CSF, only the CEA level reflected the presence of hydrocephalus. We suggest using more specific biomarkers for the evaluation of ventricular CSF to monitor disease activity and treatment response.

Keywords

References

  1. An YJ, Cho HR, Kim TM, Keam B, Kim JW, Wen H, et al. : An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis in lung adenocarcinoma cancer patients. Int J Cancer 136 : 162- 171, 2015 https://doi.org/10.1002/ijc.28949
  2. Balm M, Hammack J : Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol 53 : 626-632, 1996 https://doi.org/10.1001/archneur.1996.00550070064013
  3. Boogerd W, Hart AA, van der Sande JJ, Engelsman E : Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer 67 : 1685-1695, 1991 https://doi.org/10.1002/1097-0142(19910315)67:6<1685::AID-CNCR2820670635>3.0.CO;2-M
  4. Bruna J, Gonzalez L, Miro J, Velasco R, Gil M, Tortosa A; Neuro-Oncology Unit of the Institute of Biomedical Investigation of Bellvitge : Leptomeningeal carcinomatosis : prognostic implications of clinical and cerebrospinal fluid features. Cancer 115 : 381-389, 2009 https://doi.org/10.1002/cncr.24041
  5. Chamberlain MC : Leptomeningeal metastasis. Curr Opin Oncol 22 : 627-635, 2010 https://doi.org/10.1097/CCO.0b013e32833de986
  6. Chamberlain MC : Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 38 : 135-140, 1998 https://doi.org/10.1023/A:1005982826121
  7. Chamberlain MC, Kormanik PA, Glantz MJ : A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases. Neuro Oncol 3 : 42-45, 2001 https://doi.org/10.1093/neuonc/3.1.42
  8. Clamon G, Doebbeling B : Meningeal carcinomatosis from breast cancer : spinal cord vs. brain involvement. Breast Cancer Res Treat 9 : 213-217, 1987 https://doi.org/10.1007/BF01806382
  9. Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, et al. : Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77 : 1315-1323, 1996 https://doi.org/10.1002/(SICI)1097-0142(19960401)77:7<1315::AID-CNCR14>3.0.CO;2-4
  10. Glantz MJ, Hall WA, Cole BF, Chozick BS, Shannon CM, Wahlberg L, et al. : Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer 75 : 2919-2931, 1995 https://doi.org/10.1002/1097-0142(19950615)75:12<2919::AID-CNCR2820751220>3.0.CO;2-9
  11. Glass JP, Melamed M, Chernik NL, Posner JB : Malignant cells in cerebrospinal fluid (CSF) : the meaning of a positive CSF cytology. Neurology 29 : 1369-1375, 1979 https://doi.org/10.1212/WNL.29.10.1369
  12. Grossman SA, Krabak MJ : Leptomeningeal carcinomatosis. Cancer Treat Rev 25 : 103-119, 1999 https://doi.org/10.1053/ctrv.1999.0119
  13. Gwak HS, Lee CH, Yang HS, Joo J, Shin SH, Yoo H, et al. : Chemoport with a non-collapsible chamber as a replacement for an Ommaya reservoir in the treatment of leptomeningeal carcinomatosis. Acta Neurochir (Wien) 153 : 1971-1978; discussion 1978, 2011 https://doi.org/10.1007/s00701-011-1086-2
  14. Herrlinger U, Forschler H, Kuker W, Meyermann R, Bamberg M, Dichgans J, et al. : Leptomeningeal metastasis : survival and prognostic factors in 155 patients. J Neurol Sci 223 : 167-178, 2004 https://doi.org/10.1016/j.jns.2004.05.008
  15. Hitchins RN, Bell DR, Woods RL, Levi JA : A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5 : 1655-1662, 1987 https://doi.org/10.1200/JCO.1987.5.10.1655
  16. Hladky SB, Barrand MA : Mechanisms of fluid movement into, through and out of the brain : evaluation of the evidence. Fluids Barriers CNS 11 : 26, 2014 https://doi.org/10.1186/2045-8118-11-26
  17. Jayson GC, Howell A : Carcinomatous meningitis in solid tumours. Ann Oncol 7 : 773-786, 1996 https://doi.org/10.1093/oxfordjournals.annonc.a010755
  18. Kaplan JG, DeSouza TG, Farkash A, Shafran B, Pack D, Rehman F, et al. : Leptomeningeal metastases : comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol 9 : 225-229, 1990 https://doi.org/10.1007/BF02341153
  19. Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, et al. : Response assessment criteria for brain metastases : proposal from the RANO group. Lancet Oncol 16 : e270-e278, 2015 https://doi.org/10.1016/S1470-2045(15)70057-4
  20. Nakagawa H, Kubo S, Murasawa A, Nakajima S, Nakajima Y, Izumoto S, et al. : Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors. J Neurooncol 12 : 111-120, 1992
  21. Park JH, Kim YJ, Lee JO, Lee KW, Kim JH, Bang SM, et al. : Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era. Lung Cancer 76 : 387-392, 2012 https://doi.org/10.1016/j.lungcan.2011.11.022
  22. Taillibert S, Laigle-Donadey F, Chodkiewicz C, Sanson M, Hoang-Xuan K, Delattre JY : Leptomeningeal metastases from solid malignancy : a review. J Neurooncol 75 : 85-99, 2005 https://doi.org/10.1007/s11060-004-8101-x
  23. Teplyuk NM, Mollenhauer B, Gabriely G, Giese A, Kim E, Smolsky M, et al : MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 14 : 689-700, 2012 https://doi.org/10.1093/neuonc/nos074
  24. Twijnstra A, Ongerboer de Visser BW, van Zanten AP : Diagnosis of leptomeningeal metastasis. Clin Neurol Neurosurg 89 : 79-85, 1987 https://doi.org/10.1016/0303-8467(87)90180-6
  25. Wasserstrom WR, Glass JP, Posner JB : Diagnosis and treatment of leptomeningeal metastases from solid tumors : experience with 90 patients. Cancer 49 : 759-772, 1982 https://doi.org/10.1002/1097-0142(19820215)49:4<759::AID-CNCR2820490427>3.0.CO;2-7
  26. Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR : Treatment for meningeal carcinomatosis in breast cancer. Cancer 50 : 219-222, 1982 https://doi.org/10.1002/1097-0142(19820715)50:2<219::AID-CNCR2820500209>3.0.CO;2-7

Cited by

  1. The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis vol.8, pp.None, 2016, https://doi.org/10.3389/fonc.2018.00509
  2. Meningeal carcinomatosis: three case-reports vol.16, pp.None, 2016, https://doi.org/10.1186/s12957-018-1376-8
  3. Causes of albuminocytological dissociation and the impact of age-adjusted cerebrospinal fluid protein reference intervals: a retrospective chart review of 2627 samples collected at tertiary care centr vol.9, pp.2, 2016, https://doi.org/10.1136/bmjopen-2018-025348
  4. 血清及脑脊液肿瘤标志物在非小细胞肺癌软脑膜转移辅助诊治中的价值 vol.23, pp.6, 2016, https://doi.org/10.3779/j.issn.1009-3419.2020.103.09
  5. Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses vol.10, pp.21, 2021, https://doi.org/10.3390/jcm10214860